a
w CA 02268742 1999-04-19
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CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
MULTI-FUNCTIONAL CHIMERIC HEMATOPOIETIC
RECEPTOR AGONISTS
The present application claims priority under Title 35,
United States Code, ~119 of United States Provisional
application Serial No. 60/029,629, filed October 25,
1996.
Field of the Inyention
The present invention relates to multi-functional
chimeric hematopoietic receptor agonists. These multi-
functional chimeric hematopoietic receptor agonists
retain one or more activities of individual components
of the chimera molecule and may also show improved
hematopoietic cell-stimulating activity and/or an
improved activity profile which may include reduction of
undesirable biological activities associated with
individual hematopoietic growth factors and/or have
improved physical properties which may include increased
solubility, stability and refold efficiency.
Background of the Invention
Colony stimulating factors (CSFs) which stimulate
the differentiation and/or proliferation of bone marrow
cells have generated much interest because of their
therapeutic potential for restoring depressed levels of
hematopoietic stem cell-derived cells. CSFs in both
human and murine systems have been identified and
distinguished according to their activities. For
example, granulocyte-CSF (G-CSF) and macrophage-CSF (M-
CSF) stimulate the in vitro formation of neutrophilic
granulocyte and macrophage colonies, respectively, while
GM-CSF and interleukin-3 (IL-3) have broader activities
and stimulate the formation of both macrophage,
neutrophilic and eosinophilic granulocyte colonies. IL-
3 also stimulates the formation of mast, megakaryocyte
and pure and mixed erythroid colonies.
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z
U.S. 4,877,729 and U.S. 4,959,455 disclose a gibbon
IL-3 cDNA and a deduced human IL-3 DNA sequence and the
protein sequences for which they code. The hIL-3
disclosed has serine rather than proline at position 8
in the protein sequence.
International Patent Application (PCT) WO 88/00598
discloses gibbon- and human-like IL-3. The hIL-3
contains a Sere -> ProB replacement. Suggestions are
made to replace Cys by Ser, thereby breaking the
disulfide bridge, and to replace one or more amino acids
at the glycosylation sites.
U.S. 4,810,643 discloses a DNA sequence encoding
human G-CSF.
WO 91/02754 discloses a fusion protein comprised of
GM-CSF and IL-3 which has increased biological activity
compared to GM-CSF or IL-3 alone. Also disclosed are
nonglycosylated IL-3 and GM-CSF analog proteins as
components of the multi-functional chimeric
hematopoietic receptor agonist.
WO 92/04455 discloses fusion proteins composed of
IL-3 fused to a lymphokine selected from the group
consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-
CSF.
WO 95/21197 and WO 95/21254 disclose fusion
proteins capable of broad multi-functional hematopoietic
properties.
GB 2,285,446 relates to the c-mpl ligand
(thrombopoietin) and various forms of thrombopoietin
which are shown to influence the replication,
differentiation and maturation of megakaryocytes and
megakaryocytes progenitors which may be used for the
treatment of thrombocytopenia.
EP 675,201 A1 relates to the c-mpl ligand
(Megakaryocyte growth and development factor (MGDF),
allelic variations of c-mpl ligand and c-mpl ligand
attached to water soluble polymers such as polyethylene
glycol.
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3
WO 95/21920 provides the murine and human c-mpl
ligand and polypeptide fragments thereof. The proteins
are useful for in vivo and ex vivo therapy for
stimulating platelet production.
U.S. Patent No. 4,703,008 by Lin, F-K. discloses
the a cDNA sequence encoding erythropoietin, methods of
production and uses for erythropoietin.
WO 91/05867 discloses analogs of human
erythropoietin having a greater number of sites for
carbohydrate attachment than human erythropoietin, such
as EPO (Asn69 ) , EPO ( Asn125 , Serl2' ) , EPO ( Thrlzs ) , and EPO
( ProlZ' , ThrlzS ) .
WO 94 /24160 discloses erythropoietin muteins which
have enhanced activity, specifically amino acid
substitutions at positions 20, 49, 73, 140, 143, 146,
147 and 154.
WO 94/28391 discloses the native flt3 ligand
protein sequence and a cDNA sequence encoding the flt3
ligand, methods of expressing flt3 ligand in a host cell
transfected with the cDNA and methods of treating
patients with a hematopoietic disorder using flt3
ligand.
US Patent No. 5,554,512 is directed to human flt3
ligand as an isolated protein, DNA encoding the flt3
ligand, host cells transfected with cDNAs encoding flt3
ligand and methods for treating patients with flt3
ligand.
WO 94/26891 provides mammalianflt3 ligands,
including an isolate that has an insertion of 29 amino
acids, and fragments there of.
Rearrangement of Protein Seauences
In evolution, rearrangements of DNA sequences serve
an important role in generating a diversity of protein
CA 02268742 1999-04-19
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structure and function. Gene duplication and exon
shuffling provide an important mechanism to rapidly
generate diversity and thereby provide organisms with a
competitive advantage, especially since the basal
mutation rate is low (Doolittle, Protein Science 1:191-
200, 1992).
The development of recombinant DNA methods has made
it possible to study the effects of sequence
transposition on protein folding, structure and
function. The approach used in creating new sequences
resembles that of naturally occurring pairs of proteins
that are related by linear reorganization of their amino
acid sequences (Cunningham, et al., Proc. Natl. Acad.
Sci. U.S.A. 76:3218-3222, 1979; Teather & Erfle, J.
Bacteriol. 172: 3837-3841, 1990; Schimming et al., Eur.
J. Biochem. 204: 13-19, 1992; Yamiuchi and Minamikawa,
FEBS Lett. 260:127-130, 1991; MacGregor et al., FEBS
Lett. 378:263-266). The first in vitro application of
this type of rearrangement to proteins was described by
Goldenberg and Creighton (J. Mol. Biol. 165:407-413,
1983). A new N-terminus is selected at an internal site
(breakpoint) of the original sequence, the new sequence
having the same order of amino acids as the original
from the breakpoint until it reaches an amino acid that
is at or near the original C-terminus. At this point the
new sequence is joined, either directly or through an
additional portion of sequence (linker), to an amino
acid that is at or near the original N-terminus, and the
new sequence continues with the same sequence as the
original until it reaches a point that is at or near the
amino acid that was N-terminal to the breakpoint site of
the original sequence, this residue forming the new C-
terminus of the chain.
This approach has been applied to proteins which
range in size from 58 to 462 amino acids (Goldenberg &
Creighton, J. Mol. Biol. 165:407-413, 1983; Li &
Coffino, Mol. Cell. Biol. 13:2377-2383, 1993). The
proteins examined have represented a broad range of
CA 02268742 1999-04-19
WO 98117810 PCT/US97/20037
structural classes, including proteins that contain
predominantly a-helix (interleukin-4; Kreitman et al.,
Cytokine 7:311-318, 1995), b-sheet (interleukin-1;
Horlick et al., Protein Eng. 5:427-431, 1992), or
mixtures of the two (yeast phosphoribosyl anthranilate
isomerase; Luger et al., Science 243:206-210, 1989).
Broad categories of protein function are represented in
these sequence reorganization studies:
Enzymes
T4 lysozyme Zhang et al., Biochemistry
32:12311-12318, 1993; Zhang et
al., Nature Struct. Biol. 1:434-438
(1995)
dihydrofolate Buchwalder et al., Biochemistry
reductase 31:1621-1630, 1994; Protasova et
al., Prot. Eng. 7:1373-1377, 1995)
ribonuclease T1 Mullins et al., J. Am. Chem. Soc.
116:5529-5533, 1994; Garrett et al.,
Protein Science 5:204-211, 1996)
Bacillus b-glucanse Hahn et al., Proc. Natl. Acad. Sci.
U.S.A. 91:10417-10421, 1994)
aspartate Yang & Schachman, Proc. Natl. Acad.
transcarbamoylase Sci. U.S.A. 90:11980-11984, 1993)
phosphoribosyl Luger et al., Science 243:206-210
anthranilate (1989; Luger et al., Prot. Eng.
isomerase 3:249-258, 1990)
pepsin/pepsinogen Lin et al., Protein Science 4:159
166, 1995)
CA 02268742 1999-04-19
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glyceraldehyde-3- Vignais et al., Protein Science
phosphate dehydro- 4:994-1000, 1995)
genase
ornithine Li & Coffino, Mol. Cell. Biol.
decarboxylase 13:2377-2383, 1993)
yeast Ritco-Vonsovici et al., Biochemistry
phosphoglycerate 34:16543-16551, 1995)
dehydrogenase
Enzyme Inhibitor
basic pancreatic Goldenberg & Creighton, J. Mol.
trypsin inhibitor Biol. 165:407-413, 1983)
Cytokines
interleukin-1b Horlick et al., Protein Eng. 5:427-
431, 1992)
interleukin-4 Kreitman et al., Cytokine 7:311-
318, 1995)
Tyrosine Kinase
Recognition Domain
a-spectrin SH3 Viguera, et al., J.
domain Mol. Biol. 247:670-681, 1995)
Transmembrane
Protein
~omp A Koebnik & Kramer, J. Mol. Biol.
250:617-626, 1995)
Chimeric Protein
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WO 98/17810 PCT/US97/20037
interleukin-4- Kreitman et al., Proc. Natl. Acad.
Pseudomonas Sci. U.S.A. 91:6889-6893, 1994).
exotoxin
The results of these studies have been highly
variable. In many cases substantially lower activity,
solubility or thermodynamic stability were observed (E.
coli dihydrofolate reductase, aspartate
transcarbamoylase, phosphoribosyl anthranilate
isomerase, glyceraldehyde-3-phosphate dehydrogenase,
ornithine decarboxylase, omp A, yeast phosphoglycerate
dehydrogenase). In other cases, the sequence rearranged
protein appeared to have many nearly identical
properties as its natural counterpart (basic pancreatic
trypsin inhibitor, T4 lysozyme, ribonuclease T1,
Bacillus b-glucanase, interleukin-1b, a-spectrin SH3
domain, pepsinogen, interleukin-4). In exceptional
cases, an unexpected improvement over some properties of
the natural sequence was observed, e.g., the solubility
and refolding rate for rearranged a-spectrin SH3 domain
sequences, and the receptor affinity and anti-tumor
activity of transposed interleukin-4-Pseudomonas
exotoxin fusion molecule (Kreitman et al., Proc. Natl.
Acad. Sci. U.S.A. 91:6889-6893, 1994; Kreitman et al.,
Cancer Res. 55:3357-3363, 1995).
The primary motivation for these types of studies
has been to study the role of short-range and long-range
interactions in protein folding and stability. Sequence
rearrangements of this type convert a subset of
interactions that are long-range in the original
sequence into short-range interactions in the new
sequence, and vice versa. The fact that many of these
sequence rearrangements are able to attain a
conformation with at least some activity is persuasive
evidence that protein folding occurs by multiple folding
pathways (Viguera, et al., J. Mol. Biol. 247:570-681,
1995). In the case of the SH3 domain of a-spectrin,
CA 02268742 1999-04-19
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choosing new termini at locations that corresponded to
b-hairpin turns resulted in proteins with slightly less
stability, but which were nevertheless able to fold.
The positions of the internal breakpoints used in
the studies cited here are found exclusively on the
surface of proteins, and are distributed throughout the
linear sequence without any obvious bias towards the
ends or the middle (the variation in the relative
distance from the original N-terminus to the breakpoint
is ca. 10 to 80~ of the total sequence length). The
linkers connecting the original N- and C-termini in
these studies have ranged from 0 to 9 residues. In one
case (Yang & Schachman, Proc. Natl. Acad. Sci. U.S.A.
90:11980-11984, 1993), a portion of sequence has been
deleted from the original C-terminal segment, and the
connection made from the truncated C-terminus to the
original N-terminus. Flexible hydrophilic residues such
as Gly and Ser are frequently used in the linkers.
Viguera, et al.(J. Mod. Biol. 247:670-681, 1995)
compared joining the original N- and C- termini with 3-
or 4-residue linkers; the 3-residue linker was less
thermodynamically stable. Protasova et al. (Protein
Eng. 7:1373-1377, 1994) used 3- or 5-residue linkers in
connecting the original N-termini of E. coli
dihydrofolate reductase; only the 3-residue linker
produced protein in good yield.
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q
Summarv of the Invention
A hematopoietic protein comprising; an amino
acid sequence of the formula:
R1 L1-RZ, R2-L1-Ri. Ri-Ra, ~r R2-Ri
wherein Rland Rz are independently selected from
the group consisting of;
(I) A human EPO receptor agonist polypeptide,
comprising a modified EPO amino acid sequence of the
Formula:
1 5 AlaProProArgLeuIleCysAspSerArgValLeuGluArgTyrLeuLeuGluAlaLys
10 20
GluAlaGluAsnIleThrThrGlyCysAlaGluHisCysSerLeuAsnGluAsnIleThr
30 40
ValProAspThrLysValAsnPheTyrAlaTrpLysArgMetGluValGlyGlnGlnAla
50 60
ValGluValTrpGlnGlyLeuAlaLeuLeuSerGluAlaValLeuArgGlyGlnAlaLeu
~o so
LeuValAsnSerSerGlnProTrpGluProLeuGlnLeuHisValAspLysAlaValSer
90 100
3 0 GlyLeuArgSerLeuThrThrLeuLeuArgAlaLeuGlyAlaGlnLysGluAlaIleSer
110 120
ProProAspAlaAlaSerAlaAlaProLeuArgThrIleThrAlaAspThrPheArgLys
130 140
LeuPheArgValTyrSerAsnPheLeuArgGlyLysLeuLysLeuTyrThrGlyGluAla
150 160
CysArgThrGlyASpArg SEQ ID N0:464
166
wherein optionally 1-6 amino acids from the N-terminus
and 1-5 from the C-terminus can be deleted from said EPO
receptor agonist polypeptide;
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wherein the N-terminus is joined to the C-terminus
directly or through a linker (Lz) capable of joining the
N-terminus to the C-terminus and having new C- and N-
termini at amino acids;
23-24 47-48 109-110
24-25 48-49 110-111
25-26 49-50 111-112
26-27 50-51 112-113
27-28 51-52 113-114
28-29 52-53 114-115
29-30 53-54 115-116
30-31 54-55 116-117
31-32 55-56 117-118
32-33 56-57 118-119
33-34 57-58 119-120
34-35 77-78 120-121
35-36 78-79 121-122
36-37 79-80 122-123
37-38 80-81 123-124
38-39 81-82 124-125
39-40 82-83 125-126
40-41 84-85 126-127
41-42 85-86 127-128
42-43 86-87 128-129
43-44 87-88 129-130
44-45 88-89 130-131
45-46 108-109 131-132
46-47 respectively; and
(II) A human stem cell factor receptor agonist
polypeptide, comprising a modified stem cell factor
amino acid sequence of the Formula:
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I/
GluGlyIleCysArgAsnArgValThrAsnAsnValLysAspValThrLysLeuValAla
20
AsnLeuProLysAspTyrMetIleThrLeuLysTyrValProGlyMetASpValLeuPro
5 30 40
SerHisCysTrpIleSerGluMetValValGlnLeuSerAspSerLeuThrAspLeuLeu
50 60
1 0 AspLysPheSerAsnIleSerGluGlyLeuSerAsnTyrSerIleIleAspLysLeuVa1
70 80
AsnIleValAspAspLeuValGluCysValLysGluAsnSerSerLysAspLeuLysLys
90 100
SerPheLysSerProGluProArgLeuPheThrProGluGluPhePheArgIlePheAsn
110 120
ArgSerIleAspAlaPheLysAspPheValValAlaSerGluThrSerAspCysValVa1
2 0 130 140
SerSerThrLeuSerProGluLysAspSerArgValSerValThrLysProPheMetLeu
150 160
2 5 ProProValAlaAla SEQ ID N0:465
165
wherein optionally 1-23 amino acids can be deleted from
the C-terminus of said stem cell factor receptor agonist
30 polypeptide;
wherein the N-terminus is joined to the C-terminus
directly or through a linker (L2) capable of joining the
N-terminus to the C-terminus and having new C- and N-
35 termini at amino acids;
23-24 39-40 96-97
24-25 40-41 97-98
25-26 64-65 98-99
26-27 65-66 99-100
27-28 66-67 100-101
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28-29 67-68 101-102
29-30 68-69 102-103
30-31 69-70 103-104
31-32 70-71 104-105
32-33 89-90 105-106
33-34 90-91 106-107
34-35 91-92 107-108
35-36 92-93 108-109
36-37 93-94 109-110
37-38 94-95 110-111
38-39 95-96 respectively; and
(III) A human flt-3 receptor agonist
polypeptide, comprising a modified flt-3 ligand amino
acid sequence of the Formula:
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
20
1 0 GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAsp
30 40
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
50 60
LysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHis
70 80
PheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrASn
90 100
IleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThr
110 120
2 5 ArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
130 SEQ ID N0:466
wherein 1-7 amino acids are optionally deleted from the
C-terminus of said flt-3 receptor agonist polypeptide;
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~3
wherein the N-terminus is joined to the C-terminus
directly or through a linker (LZ) capable of joining the
N-terminus to the C-terminus and having new C- and N-
termini at amino acids;
28-29 42-43 93-94
29-30 64-65 94-95
30-31 65-66 95-96
31-32 66-67 96-g7
32-33 86-87 g7_9g
34-35 87-88 98-99
36-37 88-89 99-100
37-38 89-90 100-101
38-39 90-91 101-102
39-40 91-92 102-103
40-41 92-93 respectively; and
41-42
(IV) A polypeptide comprising; a modified human G-
CSF amino acid sequence of the formula:
1 10
Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
15 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
40
Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
20 50
Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80
Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100
3 0 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110
Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
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~u
120 130
Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140
Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
15
150 160
Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170
Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro SEQ zD No:858
wherein
Xaa atposition1 Thr,Ser, Tyr or Gly;
is Arg,
Xaa atposition2 s Pro
i or
Leu;
Xaa atposition3 s Leu,Arg, r Ser;
i Tyr
o
Xaa atposition13 isPhe,Ser, Thr or Pro;
His,
2 Xaa atposition16 isLys,Pro, Thr or His;
0 Ser,
Xaa atposition17 isCys,Ser, Ala, Ile, Tyr or Arg;
Gly,
Xaa atposition18 isLeu,Thr, His, Ile or Cys;
Pro,
Xaa atposition22 isArg,Tyr, Thr or Ala;
Ser,
Xaa atposition24 isIle,Pro, or Leu;
Tyr
2 Xaa atposition27 isAsp,or Gly;
5
Xaa atposition30 isAla,Ile, or Gly;
Leu
Xaa atposition34 isLys or Ser;
Xaa atposition36 isCys or Ser;
Xaa atposition42 isCys or Ser;
3 Xaa atposition43 isHis,Thr, Val, Lys, Trp, Ala, Arg,
0 Gly, Cys,
or Leu;
Xaa atposition44 isPro,Gly, Asp, Val, Ala, His, Trp,
Arg, Gln,
or Thr;
Xaa atposition46 isGlu,Arg, Arg, Ile or Ala;
Phe,
3 Xaa atposition47 isLeu or Thr;
5
Xaa atposition49 isLeu,Phe, or Ser;
Arg
Xaa atposition50 isLeu,Ile, Pro or Tyr;
His,
Xaa atposition54 isLeu or His;
Xaa atposition64 isCys or Ser;
4 Xaa atposition67 isGln,Lys, or Cys;
0 Leu
Xaa atposition70 isGln,Pro, Arg or Ser;
Leu,
Xaa atposition74 isCys or Ser;
Xaa atposition104i s , Gly al;
Asp or V
Xaa atposition108i s , Ala, , Arg, Trp, Gln or Gly;
Leu Val
45 Xaa atposition115i s , His, or Ala;
Thr Leu
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Xaa at position 120 is Gln, Gly, Arg, Lys or His
Xaa at position 123 is Glu, Arg, Phe or Thr
Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
Xaa at position 146 is Arg or Gln;
Xaa at position 147 is Arg or Gln;
Xaa at position 156 is His, Gly or Ser;
Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
Xaa at position 162 is Glu, Leu, Gly or Trp;
Xaa at position 163 is Val, Gly, Arg or Ala;
1 0 Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
Xaa at position 170 is His, Arg or Ser;
wherein optionally 1-11 amino acids from the N-terminus
and 1-5 from the C-terminus can optionally be deleted
from said modified human G-CSF amino acid sequence; and
wherein the N-terminus is joined to the C-terminus
directly or through a linker (Lz) capable of joining the
N-terminus to the C-terminus and having new C- and N-
termini at amino acids;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
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1b
60-61 98-99 140-141
61-62 99-100 141-142
or 142-143
respectively;
(V) A polypeptide comprising; a modified human IL-3
amino acid sequence of the formula:
Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn
1 5 10 15
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
25 30
15 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105
Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120
Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe SEQ ID No_859
125 130
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
4 0 Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn,
Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln,
Leu, Val or Gly;
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1
Xaa at position23 is Val,Ala,Gly,Trp,Lys,Phe,
Ile,
Leu, Ser, or Arg;
Xaa at position24 is Gly,Val,Arg,Ser,Phe,or Leu;
Ile,
Xaa at position25 is His,Gly,Gln,Arg,Pro,or Ala;
Thr,
Xaa at position26 is Thr,Phe,Gly,Arg,Ala,or Trp;
His,
Xaa at position27 is Gly,Arg,Thr,Ser,or
Leu, Ala;
Xaa at position28 is Arg,Leu,Gln,Gly,Pro,Val or Trp;
Lys,
Xaa at position29 is Asn,Leu,Pro,Arg,or
Gln, Val;
Xaa at position30 is His,Thr,Gly,Asp,Gln,Ser, Leu,
Pro, or
Lys ;
Xaa at position31 is Asp,Gly,Ala,Arg,Leu,or Gln;
Pro,
Xaa at position32 is Val,Arg,Gln,Asn,Gly,Ala, or
Leu, Glu;
Xaa at position33 is Leu,Gln,Ala,Thr,or
Pro, Glu;
Xaa at position34 is VaI,Gly,Ser,Lys,Glu,Gln, Thr,
Leu,
1 Arg, Ala, Phe, r
5 Ile Met;
o
Xaa at position35 is Ala,Gly,Asn,Pro,Gln,or Val;
Leu,
Xaa at position36 is Leu,or
Asp, Val;
Xaa at position37 is Ser,Pro,Trp,or
Phe, Ile;
Xaa at position38 is or
Asn, Ala;
2 Xaa at position40 is Trp,or
0 Leu, Arg;
Xaa at position41 is Cys,Arg,Leu,His,Met,or Pro;
Asn,
Xaa at position42 is Asp,Ser,Cys,Asn,Lys,Thr, Leu,
Gly,
Val, Glu, Phe, Ile,
Tyr, Met
or
Ala;
Xaa at position43 is Asn,Tyr,Leu,Phe,Asp,Ala, Cys,
Glu,
2 Gln, Arg, Thr, r
5 Gly Ser;
o
Xaa at position44 is Ser,Leu,Arg,Lys,Thr,Met, Trp,
Asp,
Glu, Asn, Gln, r
Ala Pro;
o
Xaa at position45 is Pro,Phe,Val,Met,Leu,Thr, Lys,
Gln,
Trp, Asp, Asn, Ser, le,
Arg, Ala, Glu
I or
His;
3 Xaa at position46 is Phe,Ser,Thr,Cys,Glu,Asn, Gln,
0 Asp,
Lys, His, Ala, Ile, Gly;
Tyr, Val
or
Xaa at position47 is Gly,Val,Ser,Arg,Pro,or His;
Ile,
Xaa at position48 is Ser,Cys,Arg,Ile,His,Phe, Glu,
Leu,
Lys, Thr, Ala,
Met,
Val
or
Asn;
3 Xaa at position49 is Arg,Ala,Gly,Pro,Asn,His, or
5 Met, Asp;
Xaa at position50 is Leu,Thr,Asp,Tyr,Lys,Asn, Ser,
Glu,
Ala, Ile, Val, His,Phe, Gln;
Met
or
Xaa at position51 is Arg,Met,Pro,Ser,Thr,or His;
Asn,
Xaa at position52 is His,Arg,Leu,Gly,Ser,or Thr;
Asn,
4 Xaa at position53 is Thr,Ala,Gly,Glu,Pro,Lys, Ser,
0 Leu, or
Met;
Xaa at position54 is Asp,Ile,Ser,Val,Thr,Gln, Asn,
Arg,
Lys, His, Alaor ;
Leu
Xaa at position55 is Thr,Val,Ser,Leu,or y;
Arg, Gl
4 Xaa at position56 is Gly,Cys,Ser,Gln,Glu,Arg, His,
5 Pro,
CA 02268742 1999-04-19
WO PCT/US97/20037
98!17810
18
Thr, Tyr, Phe,Leu,Val r
Ala, o Lys;
Xaa atposition57 isAsn or y;
Gl
Xaa atposition58 isLeu,Ser,Asp,Arg,Gln, Val,or
Cys;
Xaa atposition59 isGlu Tyr,His,Leu,Pro,
or
Arg;
Xaa atposition60 isAla,Ser,Pro,Tyr,Asn, or
Thr;
Xaa atposition61 isPhe,Asn,Glu,Pro,Lys, Arg,or
Ser;
Xaa atposition62 isAsn,His,Val,Arg,Pro, Thr,Asp,or
Ile;
Xaa atposition63 isArg,Tyr,Trp,Lys,Ser, His,Pro,or
Val;
Xaa atposition64 isAla,Asn,Pro,Ser,or
Lys;
Xaa atposition65 isVal,Thr,Pro,His,Leu, Phe,or
Ser;
Xaa atposition66 isLys,Ile,Arg,Val,Asn, Glu,or
Ser;
Xaa atposition67 isSer,Ala,Phe,Val,Gly, Asn,Ile,Pro,
or
His;
Xaa atposition68 isLeu,Val,Trp,Ser,Ile, Phe,Thr,or
His;
Xaa atposition69 isGln,Ala,Pro,Thr,Glu, Arg,Trp,Gly,
or
Leu;
Xaa atposition70 isAsn,Leu,Val,Trp,Pro, or a;
Al
Xaa atposition71 isAla,Met,Leu,Pro,Arg, Glu,Thr,Gln,
Trp,
or Asn;
Xaa atposition72 isSer,Glu,Met,Ala,His, Asn,Arg,or
Asp;
Xaa atposition73 isAla,Glu,Asp,Leu,Ser, Gly,Thr,or
Arg;
Xaa atposition74 isIle, , Gly,Ala;
Met, Pro,
Thr Arg,
Xaa atposition75 isGlu,Lys,Gly,Asp,Pro, Trp,Arg,Ser,
Gln,
or Leu;
Xaa atposition76 isSer,Val,Ala,Asn,Trp, Glu,Pro,Gly,
or
Asp;
Xaa atposition77 isIle,Ser,Arg,Thr,or
Leu;
Xaa atposition78 isLeu,Ala,Ser,Glu,Phe, Gly,or
Arg;
Xaa atposition79 isLys,Thr,Asn,Met,Arg, Ile,Gly,or
Asp;
3 Xaa atposition80 isAsn,Trp,Val,Gly,Thr, Leu,Glu,or
0 Arg;
Xaa atposition81 isLeu,Gln,Gly,Ala,Trp, Arg,Val,or
Lys;
Xaa atposition82 isLeu,Gln,Lys,Trp,Arg, Asp,Glu,Asn,
His, Ser, Tyr,Phe,Ile,Met Val;
Thr, Ala, or
Xaa atposition83 isPro,Ala,Thr,Trp,Arg, or
Met;
3 Xaa atposition84 isCys,Glu,Gly,Arg,Met, or
5 Val;
Xaa atposition85 isLeu,Asn,Val,or
Gln;
Xaa atposition86 isPro,Cys,Arg,Ala,or
Lys;
Xaa atposition87 isLeu,Ser,Trp,or
Gly;
Xaa atposition88 isAla,Lys,Arg,Val,or
Trp;
40 Xaa atposition89 isThr,Asp,Cys,Leu,Val, Glu,His,Asn,
or
Ser;
Xaa atposition90 isAla,Pro,Ser,Thr,Gly, Asp,Ile,or
Met;
Xaa atposition91 isAla,Pro,Ser,Thr,Phe, Leu,Asp,or
His;
Xaa atposition92 isPro,Phe,Arg,Ser,Lys, His,Ala,Gly,
Ile
45 or Leu;
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
Xaa atposition93 Asp,Ser, Asn,Pro,Ala,Leu,or Arg;
is
Thr,
Xaa atposition94 s Ile,Ser, Glu,Leu,Val,Gln,Lys,
i Arg, His,
Ala,
or Pro;
Xaa atposition95 Gln,Pro, Arg,Val,Leu,Gly,Thr,
is Asn,
His,
Lys, Ala,Trp,
Ser, Phe,
Ile,
or
Tyr;
Xaa atposition96 s Lys,Tyr, Gly,Ile,or
i Pro, Thr;
Xaa atposition97 s Val,Lys, Ala,or
i Ile, Asn;
Xaa atposition98 Ile,Asn, Leu,Asp,Ala,Thr,
is
His,
Glu, Ser,Phe, yr Pro;
Gln, Met, or
Val,
Lys,
Arg,
T
Xaa atposition99 s Leu,Arg, Asp,Val,Pro,Gln,
i Ile,
Gly, Phe,or ;
Ser, His
Xaa atposition100 is Tyr,Leu, His,Arg,Ile,Ser,Gln,
Lys, or
Pro;
Xaa atposition101 is Pro,Met, Lys,His,Thr,Val,
Asp,
Tyr, Asn,Ser, la, le, r
Glu, A Gly, Leu, Gln;
I o
Xaa atposition102 is Leu,Glu, Lys,Ser,Tyr,or
Gly, Pro;
Xaa atposition103 is or
Asp, Ser;
Xaa atposition104 is Val,Cys, Tyr,Thr,Met,Pro,Leu,
Trp,
Gln, Ala,Phe, r
Lys, o Gly;
2 Xaa atposition105 is Pro,Ala, Phe,Ser,Trp,Gln,Tyr,
0 Asn,
Leu, Ile,Asp, r ;
Lys, o His
Xaa atposition106 is Ser,Ala, Lys,Thr,Ile,Gly,or Pro;
Glu,
Xaa atposition108 is Lys,Asp, Leu,Thr,Ile,Gln,His,
Arg, Ser,
Ala or
Pro;
2 Xaa atposition109 is Thr,Pro, Glu,Tyr,Leu,Ser,or Gly;
5 Arg,
Xaa atposition110 is Ala,Asn, Thr,Leu,Arg,Gln,His,
Lys, Glu,
Ser,
or Trp;
Xaa atposition111 is Ile,Arg, Asp,or et;
Leu, M
Xaa atposition112 is Val,Gln, Tyr,Glu,His,Ser,or Phe;
Thr,
3 Xaa atposition113 is Ser,Cys, His,Gly,Trp,Tyr,Asp,
0 Phe,
Lys, Ile,Val Asn;
Leu, or
Xaa atposition114 is Cys,His, Ser,Trp,Arg,or eu;
Tyr, L
Xaa atposition115 is Asn,Val, Pro,Arg,Ala,His,Thr,
Leu,
Trp,
or Met;
3 Xaa atposition116 is Leu,Pro, Thr,Met,Asp,Val,Glu,
5 Lys,
Arg, Ser,Asn, is, ln, r ;
Trp, H Ala, o Ile
Tyr,
Phe,
G
Xaa atposition117 is Ser,Asn, Ile,Trp,Lys,or ro;
Thr, P
Xaa atposition118 is Ser,Pro, Ala,Glu,Cys,Asp,or Tyr;
Leu,
Xaa atposition119 is Ser,Lys, Pro,Leu,Thr,Tyr,or Arg;
Glu,
4 Xaa atposition120 is Ala,Pro, Leu,His,Val,or ln;
0 Asn, G
Xaa atposition121 is Ser,Ile, Asn,Pro,Lys,Asp,or Gly;
Ala,
Xaa atposition122 is Ser,Met, Trp,Arg,Phe,Pro,His,
Gln,
Ile, or
Tyr, Cys;
Xaa atposition123 is Met,Glu, His,Ser,Pro,Tyr,or Leu;
Ala,
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
.~O
wherein from 1 to 14 amino acids can optionally be
deleted from the N-terminus and/or from 1 to 15 amino
acids can optionally be deleted from the C-terminus of
said modified human IL-3 amino acid sequence; wherein
from 0 to 44 of the amino acids designated by Xaa are
different from the corresponding amino acids of native
(1-133) human interleukin-3; and
wherein the N-terminus is joined to the C-terminus
directly or through a linker (Lz), capable of joining
the N-terminus to the C-terminus and having new C- and
N-termini at amino acids;
26-27 49-50 83-84
27-28 50-51 84-85
28-29 51-52 85-86
29-30 52-53 86-87
30-31 53-54 87-88
31-32 54-55 88-89
32-33 64-65 89-90
33-34 65-66 90-92
34-35 66-67 91-92
35-36 67-68 92-93
36-37 68-69 97-98
37-38 69-70 98-99
38-39 70-71 99-100
39-40 71-72 100-101
40-41 72-73 101-102
41-42 82-83 102-103
or 103-104 respectively;
(VI) A polypeptide comprising; a modified human c-
mpl ligand amino acid sequence of the formula:
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer
2 0 1 5 10 15
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro
20 25 30 35
ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu
40 45 50 55
ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110
XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
115 120 125 130
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVa1
135 140 145 150
Arg SEQ ID No:860
153
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile,
Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val,
Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val,
Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr,
Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus
directly or through a linker (L2) capable of joining the
N-terminus to the C-terminus and having new C- and N-
termini at amino acids;
26-27 51-52 108-109
CA 02268742 1999-04-19
WO 98/17810 zz PCT/US97/20037
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-129
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 222-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 or 127-128
respectively;
(VII) A polypeptide comprising; a modified human
IL-3 amino acid sequence of the formula:
Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn
1 5 10 15
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~.3
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105
Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120
Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe SEQ ID No:859
125 130
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa atposition18is Asn,His, Leu,Ile, Phe,Arg,or Gln;
Xaa atposition19is Met,Phe, Ile,Arg, Gly,Ala,or Cys;
Xaa atposition20is Ile,Cys, Gln,Glu, Arg,Pro,or Ala;
Xaa atposition21is Asp,Phe, Lys,Arg, Ala,Gly,Glu, Gln,
Asn,
Thr, Val;
Ser
or
2 0 Xaa atposition22is Glu,Trp, Pro,Ser, Ala,His,Asp, Asn,
Gln,
Leu, Gly;
Val
or
Xaa atposition23is Ile,Val, Ala,Gly, Trp,Lys,Phe,
Leu, orArg;
Ser,
Xaa atposition24is Ile,Gly, Val,Arg, Ser,Phe,or Leu;
2 5 Xaa atposition25is Thr,His, Gly,Gln, Arg,Pro,or Ala;
Xaa atposition26is His,Thr, Phe,Gly, Arg,Ala,or Trp;
Xaa atposition27is Leu,Gly, Arg,Thr, Ser,or
Ala;
Xaa atposition28is Lys,Arg, Leu,Gln, Gly,Pro,Val or Trp;
Xaa atposition29is Gln,Asn, Leu,Pro, Arg,or
Val;
3 0 Xaa atposition30is Pro,His, Thr,Gly, Asp,Gln,Ser, Leu,
or
Lys;
Xaa atposition31is Pro,Asp, Gly,Ala, Arg,Leu,or Gln;
Xaa atposition32is Leu,Val, Arg,Gln, Asn,Gly,Ala, or Glu;
Xaa atposition33is Pro,Leu, Gln,Ala, Thr,or
Glu;
3 5 Xaa atposition34is Leu,Val, Gly,Ser, Lys,Glu,Gln, Thr,
Arg, Phe, r
Ala, Ile Met;
o
Xaa atposition35is Leu,Ala, Gly,Asn, Pro,Gln,or Val;
Xaa atposition36is Asp,Leu, or
Val;
Xaa atposition37is Phe,Ser, Pro,Trp, or
Ile;
4 0 Xaa atposition38is Asn,or a;
Al
Xaa atposition40is Leu,Trp, or
Arg;
Xaa atposition41is Asn,Cys, Arg,Leu, His,Met,or Pro;
Xaa atposition42is Gly,Asp, Ser,Cys, Asn,Lys,Thr, Leu,
Val, Phe, Ile,
Glu, Tyr, Met
or
Ala;
45 Xaa atposition43is Glu,Asn, Tyr,Leu, Phe,Asp,Ala, Cys,
CA 02268742 1999-04-19
WO 98/17810 PCT/ITS97/20037
Gln, Arg, Thr, Gly
or
Ser;
Xaa at position44isAsp,Ser,Leu,Arg, Lys,Thr,Met,Trp,
Glu, Asn, Gln, Ala
or
Pro;
Xaa at position45isGln,Pro,Phe,Val, Met,Leu,Thr,Lys,
Trp, Asp, Asn, Arg,Ser,Ala,Ile, ;
Glu
or
His
Xaa at position46isAsp,Phe,Ser,Thr, Cys,Glu,Asn,Gln,
Lys, His, Ala, Tyr,Ile,Val
or
Gly;
Xaa at position47isIle,Gly,Val,Ser, Arg,Pro,or is;
H
Xaa at position48isLeu,Ser,Cys,Arg, Ile,His,Phe,Glu,
Lys, Thr, Ala, Met,Val ;
or
Asn
Xaa at position49isMet,Arg,Ala,Gly, Pro,Asn,His,or
Asp;
Xaa at positionSOisGlu,Leu,Thr,Asp, Tyr,Lys,Asn,Ser,
Ala, Ile, Val, His,Phe,Met r
o Gln;
Xaa at position51isAsn,Arg,Met,Pro, Ser,Thr,or is;
H
Xaa at position52isAsn,His,Arg,Leu, Gly,Ser,or
Thr;
Xaa at position53isLeu,Thr,Ala,Gly, Glu,Pro,Lys,Ser,
or
Met;
Xaa at position54isArg,Asp,Ile,Ser, Val,Thr,Gln,Asn,
Lys, His, Alao r
Leu;
2 Xaa at position55isArg,Thr,Val,Ser, Leu,or
0 Gly;
Xaa at position56isPro,Gly,Cys,Ser, Gln,Glu,Arg,His,
Thr, Ala, Tyr, Phe,Leu,Val r
o Lys;
Xaa at position57isAsn or y;
Gl
Xaa at position58isLeu,Ser,Asp,Arg, Gln,Val,or
Cys;
2 Xaa at position59isGlu Tyr,His,Leu, or
5 Pro, Arg;
Xaa at position60isAla,Ser,Pro,Tyr, Asn,or
Thr;
Xaa at position61isPhe,Asn,Glu,Pro, Lys,Arg,or
Ser;
Xaa at position62isAsn,His,Val,Arg, Pro,Thr,Asp,or
Ile;
Xaa at position63isArg,Tyr,Trp,Lys, Ser,His,Pro,or
Val;
3 Xaa at position64isAla,Asn,Pro,Ser, or
0 Lys;
Xaa at position65isVal,Thr,Pro,His, Leu,Phe,or
Ser;
Xaa at position66isLys,Ile,Arg,Val, Asn,Glu,or
Ser;
Xaa at position67isSer,Ala,Phe,Val, Gly,Asn,Ile,Pro,
or
His;
3 Xaa at position68isLeu,Val,Trp,Ser, Ile,Phe,Thr,or
5 His;
Xaa at position69isGln,Ala,Pro,Thr, Glu,Arg,Trp,Gly,
or
Leu;
Xaa at position70isAsn,Leu,Val,Trp, Pro,or
Ala;
Xaa at position71isAla,Met,Leu,Pro, Arg,Glu,Thr,Gln,
4 Trp, or
0 Asn;
Xaa at position72isSer,Glu,Met,Ala, His,Asn,Arg,or
Asp;
Xaa at position73isAla,Glu,Asp,Leu, Ser,Gly,Thr,or
Arg;
Xaa at position74isIle,Met,Thr,Pro, Arg,Gly,Ala;
Xaa at position75isGlu,Lys,Gly,Asp, Pro,Trp,Arg,Ser,
45 Gln, or
Leu;
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
z5
Xaa at position76 is Val,Ala,Asn,Trp,Glu, Pro,Gly,
Ser, or
Asp;
Xaa at position77 is Ser,Arg,Thr,or eu;
Ile, L
Xaa at position78 is Ala,Ser,Glu,Phe,Gly, or
Leu, Arg;
Xaa at position79 is Thr,Asn,Met,Arg,Ile, Gly,or Asp;
Lys,
Xaa at position80 is Trp,Val,Gly,Thr,Leu, Glu,or Arg;
Asn,
Xaa at position81 is Gln,Gly,Ala,Trp,Arg, Val,or Lys;
Leu,
Xaa at position82 is Gln,Lys,Trp,Arg,Asp, Glu,Asn,
Leu,
His, Thr, Ser, Phe, ;
Ala, Ile,
Tyr, Met
or
Val
1 0 Xaa at position83 is Ala,Thr,Trp,Arg,or
Pro, Met;
Xaa at position84 is Glu,Gly,Arg,Met,or
Cys, Val;
Xaa at position85 is Asn,Val,or
Leu, Gln;
Xaa at position86 is Cys,Arg,Ala,or
Pro, Lys;
Xaa at position87 is Ser,Trp,or
Leu, Gly;
Xaa at position88 is Lys,Arg,Val,or
Ala, Trp;
Xaa at position89 is Asp,Cys,Leu,Val,Glu, His,Asn,
Thr, or
Ser;
Xaa at position90 is Pro,Ser,Thr,Gly,Asp, Ile,or Met;
Ala,
Xaa at position91 is Pro,Ser,Thr,Phe,Leu, Asp,or His;
Ala,
2 0 Xaa at position92 is Phe,Arg,Ser,Lys,His, Ala,Gly,
Pro, Ile
or Leu;
Xaa at position93 is Asp,Ser,Asn,Pro,Ala, Leu,or Arg;
Thr,
Xaa at position94 is Ile,Ser,Glu,Leu,Val, Gln,Lys,
Arg, His,
Ala, or
Pro;
2 5 Xaa at position95 is Gln,Pro,Arg,Val,Leu, Gly,Thr,
His, Asn,
Lys, Ser, Ala, Trp,
Phe,
Ile,
or
Tyr;
Xaa at position96 is Lys,Tyr,Gly,Ile,or
Pro, Thr;
Xaa at position97 is Val,Lys,Ala,or
Ile, Asn;
Xaa at position9$ is Ile,Asn,Leu,Asp,Ala, Thr,
His,
3 0 Glu, Gln, Ser, Phe, Pro;
Met,
Val,
Lys,
Arg,
Tyr
or
Xaa at position99 is Leu,Arg,Asp,Val,Pro, Gln,
Ile,
Gly, Ser, Phe, or
His;
Xaa at position100is Tyr,Leu,His,Arg,Ile, Ser,Gln,
Lys, or
Pro;
3 5 Xaa at position101is Pro,Met,Lys,His,Thr, Val,
Asp,
Tyr, Glu, Asn, Ser, le, ;
Ala, Leu,
Gly, or
I Gln
Xaa at position102is Leu,Glu,Lys,Ser,Tyr, or ro;
Gly, P
Xaa at position103is or
Asp, Ser;
Xaa at position104is Val,Cys,Tyr,Thr,Met, Pro,Leu,
Trp,
4 0 Gln, Lys, Ala, Phe,
or
Gly;
Xaa at position105is Pro,Ala,Phe,Ser,Trp, Gln,Tyr,
Asn,
Leu, Lys, Ile, Asp,r ;
o His
Xaa at position106is Ser,Ala,Lys,Thr,Ile, Gly,or Pro;
Glu,
Xaa at position108is Lys,Asp,Leu,Thr,Ile, Gln,His,
Arg, Ser,
4 5 Ala or
Pro;
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
2~
Xaa atposition109isArg,Thr,Pro, Glu,Tyr,Leu,Ser,or Gly;
Xaa atposition110isLys,Ala,Asn, Thr,Leu,Arg,Gln,His,
Glu,
Ser,
or Trp;
Xaa atposition111isLeu,Ile,Arg, Asp,or
Met;
Xaa atposition112isThr,Val,Gln, Tyr,Glu,His,Ser,or Phe;
Xaa atposition113isPhe,Ser,Cys, His,Gly,Trp,Tyr,Asp,
Lys, Ile,Val Asn;
Leu, or
Xaa atposition114isTyr,Cys,His, Ser,Trp,Arg,or
Leu;
Xaa atposition115isLeu,Asn,Val, Pro,Arg,Ala,His,Thr,
Trp,
or Met;
Xaa atposition116isLys,Leu,Pro, Thr,Met,Asp,Val,Glu,
Arg, Ser,Asn,
Trp, His,
Ala,
Tyr,
Phe,
Gln,
or
Ile;
Xaa atposition117isThr,Ser,Asn, Ile,Trp,Lys,or
Pro;
Xaa atposition118isLeu,Ser,Pro, Ala,Glu,Cys,Asp,or Tyr;
Xaa atposition119isGlu,Ser,Lys, Pro,Leu,Thr,Tyr,or Arg;
Xaa atposition120isAsn,Ala,Pro, Leu,His,Val,or n;
Gl
Xaa atposition121isAla,Ser,Ile, Asn,Pro,Lys,Asp,or Gly;
Xaa atposition122isGln,Ser,Met, Trp,Arg,Phe,Pro,His,
Ile, or ys;
Tyr, C
2 Xaa atposition123isAla,Met,Glu, His,Ser,Pro,Tyr,or Leu;
0
wherein from 1 to 14 amino acids can optionally be
deleted from the N-terminus and/or from 1 to 15 amino
acids can optionally be deleted from the C-terminus of
said modified human IL-3 amino acid sequence; and
wherein from 1 to 44 of the amino acids designated by
Xaa are different from the corresponding amino acids of
native (1-133) human interleukin-3; and
(VIII) a factor selected from the group consisting
of: a colony stimulating factor, a cytokine, a
lymphokine, an interleukin;.
and wherein L1 is a linker capable of linking Rlto Rz;
with the proviso that at least Rlor Rz is selected
from the polypeptide of formula (I) , (II), or (III);
and
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2~
said hematopoietic protein can optionally be
immediately preceded by (methionine-1 ) , ( alanine-1 ) or
(methionine-2, alanine-1} .
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(I) above are; 23-24, 24-25, 25-26, 27-28, 28-29, 29-30,
30-31, 31-32, 32-33, 33-34, 34-35, 35-36, 36-37, 37-38,
38-39, 40-41, 41-42, 42-43, 52-53, 53-54, 54-55, 55-56,
77-78, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85,
85-86, 86-87, 109-110, 110-111, 110-111, 111-112, 112
113, 113-114, 114-115, 115-116, 116-117, 117-118, 118
119, 119-120, 120-121, 121-122, 122-123, 123-124, 124
125, 125-126, 126-127, 127-128, 128-129, 129-130, 130
131, and 231-132.
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(I) above are; 23-24, 24-25, 31-32, 32-33, 37-38, 38-39,
82-83, 83-84, 85-86, 86-87, 87-88, 125-126, 126-127 and
131-132.
The EPO receptor agonists of the present invention
may contain amino acid substitutions, such as those
disclosed in WO 94/24160 or one or more of the
glycosylation sites at Asn24, Asn83, and Asnl2s are
changed to other amino acids such as but not limited to
Asp or Glu, deletions and/or insertions. It is also
intended that the EPO receptor agonists of the present
invention may also have amino acid deletions at
either/or both the N- and C- termini of the original
protein and or deletions from the new N- and/or C-
termini of the sequence rearranged proteins in the
formulas shown above.
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
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2~
(II) above are; 23-24, 24-25, 25-26, 33-34, 34-35, 35-
36, 36-37, 38-39, 39-40, 40-41, 64-65, 65-66, 66-67, 67-
68, 68-69, 69-70, 70-71, 89-90, 90-91, 91-92, 9-93, 93-
94, 94-95, 95-96, 96-97, 97-98, 98-99, 99-100, 100-101,
101-102, 102-103, 103-104, 104-105 and 105-106
respectively.
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
20 (II) above are; 64-65, 65-66, 92-93 and 93-94
respectively.
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(III) above are; 36-37, 37-38, 39-40, 41-42, 42-43, 64-
65, 65-66, 66-67, 86-87, 87-88, 88-89, 89-90, 90-91, 91-
92, 92-93, 93-94, 94-95, 95,-96, 96-97, 97-98, 98-99,
99-100 and 100-101
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(III) above are; 39-40, 65-66, 89-90, 99-100 and 100-
101.
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(IV) above are; 38-39, 39-40, 40-41, 41-42, 48-49, 53-
54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 60-61, 61-
62, 62-63, 64-65, 65-66, 66-67, 67-68, 68-69, 69-70, 96-
97, 125-126, 126-127, 127- 128, 128-129, 129-130, 130-
131, 131-132, 132-133, 133-134, 134-135, 135-136, 136-
137, 137-138, 138-139, 139-140, 140-141 and 141-142.
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(IV) above are; 38-39, 48-49, 96-97, 125-126, 132-133
and 141-142.
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x9
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(V) above are; 28-29, 29-30, 30-31, 31-32, 32-33, 33-34,
34-35, 35-36, 36-37, 37-38, 38-39, 39-40, 66-67, 67-68,
68-69, 69-70, 70-71, 84-85, 85-86, 86-87, 87-88, 88-89,
89-90, 90-91, 98-99, 99-100, 100-101 and 101-102.
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(V) above are; 34-35, 69-70 and 90-91.
The more preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(VI) above are; 80-81, 81-82, 82-83, 83-84, 84-85, 85-
86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113,
113-114, 114-115, 115-116, 116-117, 117-118, 118-119,
119-120, 120-121, 121-122, 122-123, 123-124, 124-125,
125-126 and 126-127.
The most preferred breakpoints at which new C-
terminus and N-terminus can be made in the polypeptide
(VI) above are; 81-82, 108-109, 115-116, 119-120, 122-
123 and 125-126.
The multi-functional receptor agonist of the
present invention can also be represented by the
following formulas:
(T1)a-(L')b-X'-(L)~-Xz-(Lz)d-(T2)e
or
X1- ( L ) c-X2- ( L ) -Y~- ( L ) c-Yz
in which:
X' is a peptide comprising an amino acid sequence
corresponding to the sequence of residues n+1 through J
of the original protein having amino acids residues
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3~
numbered sequentially 1 through J with an amino terminus
at residue 1;
L is an optional linker;
X2 is a peptide comprising an amino acid sequence
of residues 1 through n of the original protein;
Y1 is a peptide comprising an amino acid sequence
corresponding to the sequence of residues n=1 through K
of the original protein having amino acids residues
numbered sequentially 1 through K with an amino terminus
at residue 1;
Yz is a peptide comprising an amino acid sequence
of residues 1 through n of the original protein;
L1 and L~ are optional peptide spacers:
n is an integer ranging from 1 to J-1;
b, c, and d are each independently 0 or 1;
a and a are either 0 or 1, provided that both a and
a cannot both be 0; and
T' and TZ are proteins .
The mufti-functional chimeric hematopoietic
receptor agonists of the present invention may contain
amino acid substitutions, deletions and/or insertions in
the individual protein components of the chimera
molecule. It is also intended that the mufti-functional
chimeric hematopoietic receptor agonists of the present
invention may also have amino acid deletions at
either/or both the N- and C- termini of the original
protein and or deletions from the new N- and/or C-
termini of the sequence rearranged proteins in the
formulas shown above.
A preferred embodiment of the present invention the
linker (L) , (L1) or (LZ) , of the above formulas, joining
the N-terminus to the C-terminus is a polypeptide
selected from the group consisting of:
Ser;
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Asn;
Gly;
Thr;
GlySer;
AlaAla;
GlySerGly;
GlyGlyGly;
GlyAsnGly;
GlyAlaGly;
GlyThrGly;
AlaSerAla;
AlaAlaAla;
GlyGlyGlySer SEQ ID N0:778;
GlyGlyGlySerGlyGlyGlySer SEQ ID N0:779;
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySer SEQ ID N0:780;
SerGlyGlySerGlyGlySer SEQ ID N0:781;
GluPheGlyAsnMet SEQ ID N0:782;
GluPheGlyGlyAsnMet SEQ ID N0:783;
GluPheGlyGlyAsnGlyGlyAsnMet SEQ ID N0:784;
GlyGlySerAspMetAlaGly SEQ ID N0:785;
SerGlyGlyAsnGly SEQ ID N0:786;
SerGlyGlyAsnGlySerGlyGlyAsnGly SEQ ID N0:787;
SerGlyGlyAsnGlySerGlyGlyAsnGlySerGlyGlyAsnGly
SEQ ID N0:788;
SerGlyGlySerGlySerGlyGlySerGly SEQ ID N0:789;
SerGlyGlySerGlySerGlyGlySerGlySerGlyGlySerGly
SEQ ID N0:790;
GlyGlyGlySerGlyGly SEQ ID N0:791;
GlyGlyGlySerGlyGlyGly SEQ ID N0:792;
GlyGlyGlySerGlyGlyGlySerGlyGly SEQ ID N0:793;
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
SEQ ID N0:794;
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SEQ ID N0:795;
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlySerGly SEQ ID N0:796;
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3~
ProProProTrpSerProArgProLeuGlyAlaThrAlaProThrAlaGly
GlnProProLeu SEQ ID N0:797;
ProProProTrpSerProArgProLeuGlyAlaThrAlaProThr
SEQ ID N0:798; and
ValGluThrValPheHisArgValSerGlnAspGlyLeuLeuThrSer
SEQ ID N0:799.
Additionally, the present invention relates to
recombinant expression vectors comprising nucleotide
sequences encoding the multi-functional chimeric
hematopoietic receptor agonists, related microbial
expression systems, and processes for making the multi-
functional chimeric hematopoietic receptor agonists. The
invention also relates to pharmaceutical compositions
containing the multi-functional chimeric hematopoietic
receptor agonists, and methods for using the multi-
functional chimeric hematopoietic receptor agonists.
In addition to the use of the multi-functional
chimeric hematopoietic receptor agonists of the present
invention in vivo, it is envisioned that in vitro uses
would include the ability to stimulate bone marrow and
blood cell activation and growth before infusion into
patients. Another intended use is for the production of
dendritic cells both in vivo and ex vivo.
It is believed that the reduced affinity of fusion
proteins is due, at least in part, to the inability of
the individual moieties to achieve their native
conformation when incorporated into a chimeric molecule
or to steric hindrance between the active site of the
individual moieties of the fusion protein. This
invention overcomes these limitations providing novel
multi-functional chimeric hematopoietic receptor
agonists that have a binding affinity comparable to or
greater than the individual components of the chimeric
molecule.
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33
PAGE INTENTIONALLY LEFT BLANK
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Brief Description of the Fiaures
Figure 1 schematically illustrates the sequence
rearrangement of a protein. The N-terminus (N) and the
C-terminus (C) of the native protein are joined through
a linker, or joined directly. The protein is opened at a
breakpoint creating a new N-terminus (new N) and a new
C-terminus (new-C) resulting in a protein with a new
linear amino acid sequence. A rearranged molecule may be
synthesized de novo as linear molecule and not go
through the steps of joining the original N-terminus and
the C-terminus and opening of the protein at the
breakpoint.
Figure 2 shows a schematic of Method I, for
creating new proteins in which the original N-terminus
and C-terminus of the native protein are joined with a
linker and different N-terminus and C-terminus of the
protein are created. In the example shown the sequence
rearrangement results in a new gene encoding a protein
with a new N-terminus created at amino acid 97 of the
original protein, the original C-terminus (a. a. 174)
joined to the amino acid 11 (a. a. 1- 10 are deleted)
through a linker region and a new C-terminus created at
amino acid 96 of the original sequence.
Figure 3 shows a schematic of Method II, for
creating new proteins in which the original N-terminus
and C-terminus of the native protein are joined without
a linker and different N-terminus and C-terminus of the
protein are created. In the example shown the sequence
rearrangement results in a new gene encoding a protein
with a new N-terminus created at amino acid 97 of the
original protein, the original C-terminus (a. a. 174)
joined to the original N-terminus and a new C-terminus
created at amino acid 96 of the original sequence.
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Figure 4 shows a schematic of Method III, for
creating new proteins in which the original N-terminus
and C-terminus of the native protein are joined with a
linker and different N-terminus and C-terminus of the
protein are created. In the example shown the sequence
rearrangement results in a new gene encoding a protein
- with a new N-terminus created at amino acid 97 of the
original protein, the original C-terminus (a. a. 174)
joined to amino acid 1 through a linker region and a new
C-terminus created at amino acid 96 of the original
sequence.
Figure 5 shows the bioactivity of the multi
functional receptor agonists comprising flt3 receptor
agonists pMON32332, pMON32333, pMON32334 and pMON32335
compared to recombinant native flt3 (Genzyme) in the
MUTZ-2 cell proliferation assay. MT = mock transfection
Figure 6 shows a DNA sequence encoding human mature
EPO based on the sequence of Lin et al. (PNAS 82:7580-
7584, 1985).
Figure 7a and 7b shows a DNA sequence encoding
native stem cell factor based on the sequence of Martin
et al. (Cell 63:203-211, 1990).
Figure 8 shows a DNA sequence encoding soluble stem
cell factor based on the sequence of Langley et al.
(Archives of Bichemistry and Biophysica 311:55-61,
1994).
Figure 9a and 9b shows the DNA sequence encoding
the 209 amino acid mature form of flt3 ligand from Lyman
et al. (Oncogene 11:1165-1172, 1995).
Figure 10 shows the DNA sequence encoding the 134
amino acid soluble form of flt3 ligand from Lyman et
al.(Oncogene 11:1165-1172, 1995).
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36
Detailed Description of the Invention
The present invention encompasses mufti-functional
chimeric hematopoietic receptor agonists formed from
covalently linked polypeptides, each of which may act
through a different and specific cell receptor to
initiate complementary biological activities.
Hematopoiesis requires a complex series of cellular
events in which stem cells generate continuously into
large populations of maturing cells in all major
lineages. There are currently at least 20 known
regulators with hematopoietic proliferative activity.
Most of these proliferative regulators can only
stimulate one or another type of colony formation in
vitro, the precise pattern of colony formation
stimulated by each regulator is quite distinctive. No
two regulators stimulate exactly the same pattern of
colony formation, as evaluated by colony numbers or,
more importantly, by the lineage and maturation pattern
of the cells making up the developing colonies.
Proliferative responses can most readily be analyzed in
simplified in vitro culture systems. Three quite
different parameters can be distinguished: alteration in
colony size, alteration in colony numbers and cell
lineage. Two or more factors may act on the progenitor
cell, inducing the formation of larger number of progeny
thereby increasing the colony size. Two or more factors
may allow increased number of progenitor cells to
proliferate either because distinct subsets of
progenitors cells exist that respond exclusively to one
factor or because some progenitors require stimulation
by two or more factors before being able to respond.
Activation of additional receptors on a cell by the use
of two or more factors is likely to enhance the mitotic
signal because of coalescence of initially differing
signal pathways into a common final pathway reaching the
nucleus (Metcalf, Nature 339:27, 1989). Other mechanisms
could explain synergy. For example, if one signaling
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3~
pathway is limited by an intermediate activation of an
additional signaling pathway which is caused by a second
factor, then this may result in a super additive
response. In some cases, activation of one receptor type
can induce an enhanced expression of other receptors
(Metcalf, Blood 82:3515-3523, 1993). Two or more factors
may result in a different pattern of cell lineages than
from a single factor. The use of multi-functional
chimeric hematopoietic receptor agonists may have a
potential clinical advantage resulting from a
proliferative response that is not possible by any
single factor.
The receptors of hematopoietic and other growth
factors can be grouped into two distinct families of
related proteins: (1) tyrosine kinase receptors,
including those for epidermal growth factor, M-CSF
(Sherr, Blood 75:1, 1990) and SCF (Yarden et al., EMBO
J. 6:3341, 1987): and (2) hematopoietic receptors, not
containing a tyrosine kinase domain, but exhibiting
obvious homology in their extracellular domain (Bazan,
PNAS USA 87:6934-6938, 1990). Included in this latter
group are erythropoietin (EPO) (D'Andrea et al., Cell
57:277, 1989), GM-CSF (Gearing et al., EMBO J. 8:3667,
1989), IL-3 (Kitamura et al., Cell 66:1165, 1991), G-CSF
(Fukunaga et al., J. Bio. Chem. 265:14008-15, 1990), IL-
4 (Harada et al., PNAS USA 87:857, 1990), IL-5 (Takaki
et al., EMBO J. 9:4367, 1990), IL-6 (Yamasaki et al.,
Science 241:825, 1988), IL-7 (Goodwin et al., Cell
60:941-51, 1990), LIF (Gearing et al., EMBO J. 10:2839,
1991) and IL-2 (Cosman et al., Mo1-Immunol. 23: 935-94,
1986). Most of the latter group of receptors exists in a
high-affinity form as heterodimers. After ligand
binding, the specific a-chains become associated with at
least one other receptor chain (b-chain, g-chain). Many
of these factors share a common receptor subunit. The a-
chains for GM-CSF, IL-3 and IL-5 share the same b-chain
(Kitamura et al., Cell 66:1165, 1991), Takaki et al.,
EMBO J. 10:2833-8, 1991) and receptor complexes for IL-
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38
6, LIF and IL-11. share a common b-chain (gp130) (Taga et
al., Cell 58:573-81, 1989; Gearing et al., Science
255:1434-7, 1992). The receptor complexes of IL-2, IL-
4, IL-7, IL-9 and IL-15 share a common g-chain (Kondo et
al., Science 262:1874, 1993; Russell et al., Science
266: 1042-1045, 1993; Noguchi et al., Science 262:1877,
1993; Giri et al., EMBO J. 13:2822-2830, 1994).
The use of a multiply acting hematopoietic factor
may also have a potential advantage by reducing the
demands placed on factor-producing cells and their
induction systems. If there are limitations in the
ability of a cell to produce a factor, then by lowering
the required concentrations of each of the factors, and
using them in combination may usefully reduce demands on
the factor-producing cells. The use of a multiply acting
hematopoietic factor may lower the amount of the factors
that would be needed, probably reducing the likelihood
of adverse side-effects.
Novel compounds of this invention are represented
by a formula selected from the group consisting of:
R1-L1-R2, R2-L1-R1, R1-R2, arid RZ-R~
Where R1 and RZ are as defined above.
Rz is preferably a colony stimulating factor with a
different but complementary activity than R1. By
complementary activity is meant activity which enhances
or changes the response to another cell modulator. The
R1 polypeptide is joined either directly or through a
linker segment to the Rz polypeptide. The term
"directly" defines multi-functional chimeric
hematopoietic receptor agonists in which the
polypeptides are joined without a peptide linker. Thus
L1 represents a chemical bond or polypeptide segment to
which both R1 and Rz are joined in frame, most commonly
L1 is a linear peptide to which R1 and Rz are joined by
amide bonds linking the carboxy terminus of R1 to the
amino terminus of L1 and carboxy terminus of L1 to the
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39
amino terminus of RZ. By "joined in frame" is meant that
there is no translation termination or disruption
between the reading frames of the DNA encoding R1 and Rz.
A non-exclusive list of other growth factors, i.e.
colony stimulating factors (CSFs), are cytokines,
lymphokines, interleukins, hematopoietic growth factors
which can be joined to (I), (II) or (III) include GM-
CSF, G-CSF, c-mpl ligand (also known as TPO or MGDF), M-
CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5,
IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-
15, LIF, flt3/flk2 ligand, human growth hormone, B-cell
growth factor, B-cell differentiation factor, eosinophil
differentiation factor and stem cell factor (SCF) also
known as steel factor or c-kit ligand. Additionally,
this invention encompasses the use of modified R1 or RZ
molecules or mutated or modified DNA sequences encoding
these Rl or Rz molecules. The present invention also
includes multi-functional chimeric hematopoietic
receptor agonists in which R1 or RZ is an hIL-3 variant,
c-mpl ligand variant, or G-CSF variant. A "hIL-3
variant" is defined as a hIL-3 molecule which has amino
acid substitutions and/or portions of hIL-3 deleted as
disclosed in WO 94/12638, WO 94/12639 and WO 95/00646,
as well as other variants known in the art. A "c-mpl
ligand variant" is defined an c-mpl ligand molecule
which has amino acid substitutions and/or portions of c-
mpl ligand deleted, disclosed in United States
Application Serial Number 08/383,035 as well as other
variants known in the art. A "G-CSF variant" is defined
an G-CSF molecule which has amino acid substitutions
and/or portions of G-CSF deleted, as disclosed herein,
as well as other variants known in the art. In addition
to the list above, IL-3 variants taught in WO 94/12639
and WO 94/12638, G-CSF receptor agonists disclosed in WO
97/12977, c-mpl receptor agonists disclosed in WO
97/12978, IL-3 receptor agonists disclosed in WO
97/12979 can be R1 or RZ of the present invention. As
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used herein "IL-3 variants" refer to IL-3 variants
taught in WO 94/12639 and WO 94/12638. As used herein
"fusion proteins" refer to fusion protein taught in WO
95/21197, and WO 95/21254. As used herein "G-CSF
receptor agonists" refer to G-CSF receptor agonists
disclosed in WO 97/12978. As used herein "c-mpl receptor
agonists" refer to c-mpl receptor agonists disclosed in
WO 97/12978. As used herein "IL-3 receptor agonists"
refer to IL-3 receptor agonists disclosed in WO
97/12979. As used herein "multi-functional receptor
agonists" refer to multi-functional receptor agonists
taught in WO 97/12985.
The linking group (L1) is generally a polypeptide
of between 1 and 500 amino acids in length. The linkers
joining the two molecules are preferably designed to (1)
allow the two molecules to fold and act independently of
each other, (2) not have a propensity for developing an
ordered secondary structure which could interfere with
the functional domains of the two proteins, (3) have
minimal hydrophobic characteristics which could interact
with the functional protein domains and (4) provide
steric separation of R1 and R2 such that R1 and Rz could
interact simultaneously with their corresponding
receptors on a single cell. Typically surface amino
acids in flexible protein regions include Gly, Asn and
Ser. Virtually any permutation of amino acid sequences
containing Gly, Asn and Ser would be expected to satisfy
the above criteria for a linker sequence. Other neutral
amino acids, such as Thr and Ala, may also be used in
the linker sequence. Additional amino acids may also be
included in the linkers due to the addition of unique
restriction sites in the linker sequence to facilitate
construction of the multi-functional chimeric
hematopoietic receptor agonists.
Preferred Lllinkers of the present invention
include sequences selected from the group of formulas:
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(Gly'Ser)° (SEQ ID N0:861) , (Gly°Ser)" (SEQ ID N0:862) ,
(GlySSer)° (SEQ ID N0:863), (Gly°Ser)° (SEQ ID N0:864) or
(AlaGlySer)" (SEQ ID N0:865).
One example of a highly-flexible linker is the
glycine and serine-rich spacer region present within the
pIII protein of the filamentous bacteriophages, e.g.
bacteriophages M13 or fd (Schaller et al., PNAS USA 72:
737-741, 1975). This region provides a long, flexible
spacer region between two domains of the pTII surface
protein. The spacer region consists of the amino acid
sequence:
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGlu
GlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGlyGlyGlySer
(SEQ ID N0:800).
The present invention also includes linkers in
which an endopeptidase recognition sequence is included.
Such a cleavage site may be valuable to separate the
individual components of the multi-functional chimeric
hematopoietic receptor agonist to determine if they are
properly folded and active in vitro. Examples of
various endopeptidases include, but are not limited to,
plasmin, enterokinase, kallikrein, urokinase, tissue
plasminogen activator, clostripain, chymosin,
collagenase, Russell's viper venom protease, postproline
cleavage enzyme, V8 protease, Thrombin and factor Xa.
Peptide linker segments from the hinge region of
heavy chain immunoglobulins IgG, IgA, IgM, IgD or IgE
provide an angular relationship between the attached
polypeptides. Especially useful are those hinge regions
where the cysteines are replaced with serines. Preferred
linkers of the present invention include sequences
derived from murine IgG gamma 2b hinge region in which
the cysteines have been changed to serines. These
linkers may also include an endopeptidase cleavage site.
Examples of such linkers include the following
sequences:
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h2
IleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLys
GluSerHisLysSerPro (SEQ ID N0:801) and
IleGluGlyArgIleSerGluProSerGlyProIleSerThrIleAsnProSer
ProProSerLysGluSerHisLysSerPro (SEQ ID N0:802).
The present invention is, however, not limited by
the form, size or number of linker sequences employed
and the only requirement of the linker is that
functionally it does not interfere with the folding and
function of the individual molecules of the multi-
functional chimeric hematopoietic receptor agonist.
Determination of the Linker LZ-
The length of the amino acid sequence of the
linker Lz to be used in R1 and/or RZ can be selected
empirically or with guidance from structural
information, or by using a combination of the two
approaches.
When no structural information is available, a
small series of linkers can be prepared for testing
using a design whose length is varied in order to span a
range from 0 to 50 A and whose sequence is chosen in
order to be consistent with surface exposure
(hydrophilicity, Hopp & Woods, Mol. Immunol. 20: 483-
489, 1983), Kyte & Doolittle, J. Mol. Biol. 157:105-132;
solvent exposed surface area, Lee & Richards, ~T. Mol.
Biol. 55:379-400, 1971) and the ability to adopt the
necessary conformation with out deranging the
conformation of R1 or R2(conformationally flexible;
Karplus & Schulz, Naturwissenschaften 72:212-213, 1985).
Assuming an average of translation of 2.0 to 3.8 A per
residue, this would mean the length to test would be
between 0 to 30 residues, with 0 to 15 residues being
the preferred range. Exemplary of such an empirical
series would be to construct linkers using a cassette
sequence such as "Gly-Gly-Gly-Ser" repeated n times,
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where n is 1, 2, 3 or 4. Those skilled in the art will
recognize that there are many such sequences that vary
in length or composition that can serve as linkers with
the primary consideration being that they be neither
S excessively long nor short (cf., Sandhu, Critical Rev.
Biotech. 12: 437-462, 1992); if they are too long,
entropy effects will likely destabilize the three-
dimensional fold, and may also make folding kinetically
impractical, and if they are too short, they will likely
destabilize the molecule because of torsional or steric
strain.
Those skilled in the analysis of protein structural
information will recognize that using the distance
between the chain ends, defined as the distance between
the c-alpha carbons, can be used to define the length of
the sequence to be used, or at least to limit the number
of possibilities that must be tested in an empirical
selection of linkers. They will also recognize that it
is sometimes the case that the positions of the ends of
the polypeptide chain are ill-defined in structural
models derived from x-ray diffraction or nuclear
magnetic resonance spectroscopy data, and that when
true, this situation will therefore need to be taken
into account in order to properly estimate the length of
the linker required. From those residues whose
positions are well defined are selected two residues
that are close in sequence to the chain ends, and the
distance between their c-alpha carbons is used to
calculate an approximate length for a linker between
them. Using the calculated length as a guide, linkers
with a range of number of residues (calculated using 2
to 3.8A per residue) are then selected. These linkers
may be composed of the original sequence, shortened or
lengthened as necessary, and when lengthened the
additional residues may be chosen to be flexible and
hydrophilic as described above; or optionally the
original sequence may be substituted for using a series
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of linkers, one example being the "Gly-Gly-Gly-Ser"
cassette approach mentioned above; or optionally a
combination of the original sequence and new sequence
having the appropriate total length may be used.
Determination of the Amino and Carboxyl Termini of R~
and R~
Sequences of R1 and Rz capable of folding to
biologically active states can be prepared by
appropriate selection of the beginning (amino terminus)
and ending (carboxyl terminus) positions from within the
original polypeptide chain while using the linker
sequence LZ as described above. Amino and carboxyl
termini are selected from within a common stretch of
sequence, referred to as a breakpoint region, using the
guidelines described below. A novel amino acid sequence
is thus generated by selecting amino and carboxyl
termini from within the same breakpoint region. In many
cases the selection of the new termini will be such that
the original position of the carboxyl terminus
immediately preceded that of the amino terminus.
However, those skilled in the art will recognize that
selections of termini anywhere within the region may
function, and that these will effectively lead to either
deletions or additions to the amino or carboxyl portions
of the new sequence.
It is a central tenet of molecular biology that the
primary amino acid sequence of a protein dictates
folding to the three-dimensional structure necessary for
expression of its biological function. Methods are
known to those skilled in the art to obtain and
interpret three-dimensional structural information using
x-ray diffraction of single protein crystals or nuclear
magnetic resonance spectroscopy of protein solutions.
Examples of structural information that are relevant to
the identification of breakpoint regions include the
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~5
location and type of protein secondary structure (alpha
and 3-10 helices, parallel and anti-parallel beta
sheets, chain reversals and turns, and loops; Kabsch &
Sander, Biopolymers 22: 2577-2637, 1983), the degree of
solvent exposure of amino acid residues, the extent and
type of interactions of residues with one another
(Chothia, Ann. Rev. Biochem. 53:537-572, 1984) and the
static and dynamic distribution of conformations along
the polypeptide chain (Alber & Mathews, Methods Enzymol.
154: 511-533, 1987). In some cases additional
information is known about solvent exposure of residues;
one example is a site of post-translational attachment
of carbohydrate which is necessarily on the surface of
the protein. When experimental structural information
25 is not available, or is not feasible to obtain, methods
are also available to analyze the primary amino acid
sequence in order to make predictions of protein
tertiary and secondary structure, solvent accessibility
and the occurrence of turns and loops. Biochemical
methods are also sometimes applicable for empirically
determining surface exposure when direct structural
methods are not feasible; for example, using the
identification of sites of chain scission following
limited proteolysis in order to infer surface exposure
(Gentile & Salvatore, Eur. J. Biochem. 218:603-621,
1993)
Thus using either the experimentally derived structural
information or predictive methods (e.g., Srinivisan &
Rose Proteins: Struct., Funct. & Genetics, 22: 81-99,
1995) the parental amino acid sequence is inspected to
classify regions according to whether or not they are
integral to the maintenance of secondary and tertiary
structure. The occurrence of sequences within regions
that are known to be involved in periodic secondary
structure (alpha and 3-10 helices, parallel and anti-
parallel beta sheets) are regions that should be
avoided. Similarly, regions of amino acid sequence that
are observed or predicted to have a low degree of
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solvent exposure are more likely to be part of the so-
called hydrophobic core of the protein and should also
be avoided for selection of amino and carboxyl termini.
In contrast, those regions that are known or predicted
to be in surface turns or loops, and especially those
regions that are known not to be required for biological
activity, are the preferred sites for location of the
extremes of the polypeptide chain. Continuous stretches
of amino acid sequence that are preferred based on the
above criteria are referred to as a breakpoint region.
Additional peptide sequences may also be added to
facilitate purification or identification of multi-
functional chimeric hematopoietic receptor agonist
proteins (e. g., poly-His). A highly antigenic peptide
may also be added that would enable rapid assay and
facile purification of the multi-functional chimeric
hematopoietic receptor agonist protein by a specific
monoclonal antibody.
"Mutant amino acid sequence," "mutant protein",
"variant protein", "mutein", or "mutant polypeptide"
refers to a polypeptide having an amino acid sequence
which varies from a native sequence due to amino acid
deletions, substitutions, or both, or is encoded by a
nucleotide sequence intentionally made variant from a
native sequence.. "Native sequence" refers to an amino
acid or nucleic acid sequence which is identical to a
wild-type or native form of a gene or protein.
Hematopoietic growth factors can be characterized
by their ability to stimulate colony formation by human
hematopoietic progenitor cells. The colonies formed
include erythroid, granulocyte, megakaryocyte,
granulocytic macrophages and mixtures thereof. Many of
the hematopoietic growth factors have demonstrated the
ability to restore bone marrow function and peripheral
blood cell populations to therapeutically beneficial
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levels in studies performed initially in primates and
subsequently in humans. Many or all of these biological
activities of hematopoietic growth factors involve
signal transduction and high affinity receptor binding.
Multi-functional chimeric hematopoietic receptor
agonists of the present invention may exhibit useful
properties such as having similar or greater biological
activity when compared to a single factor or by having
improved half-life or decreased adverse side effects, or
a combination of these properties.
Mufti-functional chimeric hematopoietic receptor
agonists which have little or no agonist activity maybe
useful as antagonists, as antigens for the production of
antibodies for use in immunology or immunotherapy, as
genetic probes or as intermediates used to construct
other useful hIL-3 muteins.
Biological activity of the mufti-functional
chimeric hematopoietic receptor agonist proteins of the
present invention can be determined by DNA synthesis in
factor-dependent cell lines or by counting the colony
forming units in an in vitro bone marrow assay.
The mufti-functional chimeric hematopoietic
receptor agonists of the present invention may have an
improved therapeutic profile as compared to single
acting hematopoietic agonists. For example, some
mufti-functional chimeric hematopoietic receptor
agonists of the present invention may have a similar or
more potent growth factor activity relative to other
hematopoietic agonists without having a similar or
corresponding increase in side-effects.
The present invention also includes the DNA
sequences which code for the mufti-functional chimeric
hematopoietic receptor agonist proteins, DNA sequences
which are substantially similar and perform
substantially the same function, and DNA sequences which
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differ from the DNAs encoding the multi-functional
chimeric hematopoietic receptor agonists of the
invention only due to the degeneracy of the genetic
code. Also included in the present invention are the
oligonucleotide intermediates used to construct the
mutant DNAs and the polypeptides coded for by these
oligonucleotides.
Genetic engineering techniques now standard in the
art (United States Patent 4,935,233 and Sambrook et al.,
"Molecular Cloning A Laboratory Manual", Cold Spring
Harbor Laboratory, 1989) may be used in the construction
of the DNA sequences of the present invention. One such
method is cassette mutagenesis (Wells et al., Gene
34:315-323, 1985) in which a portion of the coding
sequence in a plasmid is replaced with synthetic
oligonucleotides that encode the desired amino acid
substitutions in a portion of the gene between two
restriction sites.
Pairs of complementary synthetic oligonucleotides
encoding the desired gene can be made and annealed to
each other. The DNA sequence of the oligonucleotide
would encode sequence for amino acids of desired gene
with the exception of those substituted and/or deleted
from the sequence.
Plasmid DNA can be treated with the chosen
restriction endonucleases then ligated to the annealed
oligonucleotides. The ligated mixtures can be used to
transform competent JM101 cells to resistance to an
appropriate antibiotic. Single colonies can be picked
and the plasmid DNA examined by restriction analysis
and/or DNA sequencing to identify plasmids with the
desired genes.
Cloning of the DNA sequences of the novel multi-
functional hematopoietic agonists wherein at least one
of the with the DNA sequence of the other colony
stimulating factor may be accomplished by the use of
intermediate vectors. Alternatively one gene can be
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~9
cloned directly into a vector containing the other gene.
Linkers and adapters can be used for joining the DNA
sequences, as well as replacing lost sequences, where a
restriction site was internal to the region of interest.
Thus genetic material (DNA) encoding one polypeptide,
peptide linker, and the other polypeptide is inserted
into a suitable expression vector which is used to
transform bacteria, yeast, insect cells or mammalian
cells. The transformed organism is grown and the protein
isolated by standard techniques. The resulting product
is therefore a new protein which has a colony
stimulating factor joined by a linker region to a second
colony stimulating factor.
Another aspect of the present invention provides
plasmid DNA vectors for use in the expression of these
novel multi-functional chimeric hematopoietic receptor
agonists. These vectors contain the novel DNA sequences
described above which code for the novel polypeptides of
the invention. Appropriate vectors which can transform
microorganisms capable of expressing the multi-
functional chimeric hematopoietic receptor agonists
include expression vectors comprising nucleotide
sequences coding for the multi-functional chimeric
hematopoietic receptor agonists joined to
transcriptional and translational regulatory sequences
which are selected according to the host cells used.
Vectors incorporating modified sequences as
described above are included in the present invention
and are useful in the production of the multi-functional
chimeric hematopoietic receptor agonist polypeptides.
The vector employed in the method also contains selected
regulatory sequences in operative association with the
DNA coding sequences of the invention and which are
capable of directing the replication and expression
thereof in selected host cells.
As another aspect of the present invention, there
is provided a method for producing the novel multi-
functional chimeric hematopoietic receptor agonists.
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~l0
The method of the present invention involves culturing
suitable cells or cell line, which has been transformed
with a vector containing a DNA sequence coding for
expression of a novel multi-functional chimeric
hematopoietic receptor agonist. Suitable cells or cell
lines may be bacterial cells. For example, the various
strains of E. coli are well-known as host cells in the
field of biotechnology. Examples of such strains
include E. coli strains JM101 (Vanish-Perron et al. Gene
33: 103-119, 1985) and MON105 (Obukowicz et al., Applied
Environmental Microbiology 58: 1511-1523, 1992). Also
included in the present invention is the expression of
the multi-functional chimeric hematopoietic receptor
agonist protein utilizing a chromosomal expression
vector for E. coli based on the bacteriophage Mu
(Weinberg et al., Gene 126: 25-33, 1993). Various
strains of B. subtilis may also be employed in this
method. Many strains of yeast cells known to those
skilled in the art are also available as host cells for
expression of the polypeptides of the present invention.
When expressed in the E. coli cytoplasm, the gene
encoding the multi-functional chimeric hematopoietic
receptor agonists of the present invention may also be
constructed such that at the 5' end of the gene codons
are added to encode Met-2-Ala-1- or Met-1 at the N-terminus
of the protein. The N termini of proteins made in the
cytoplasm of E. coli are affected by post-translational
processing by methionine aminopeptidase (Ben Bassat et
al., J. Bac. 169:751-757, 1987) and possibly by other
peptidases so that upon expression the methionine is
cleaved off the N-terminus. The multi-functional
chimeric hematopoietic receptor agonists of the present
invention may include multi-functional chimeric
hematopoietic receptor agonist polypeptides having Met~l,
Ala-1 or Met-2-Ala-1 at the N-terminus . These mutant
multi-functional chimeric hematopoietic receptor
agonists may also be expressed in E. coli by fusing a
secretion signal peptide to the N-terminus. This signal
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S~
peptide is cleaved from the polypeptide as part of the
secretion process. Additional strategies for achieving
high-level expression of genes in E. coli can be found
in Sawas, C.M. (Microbiological Reviews 60;512-538,
1996).
Also suitable for use in the present invention are
mammalian cells, such as Chinese hamster ovary cells
(CHO). General methods for expression of foreign genes
in mammalian cells are reviewed in Kaufman, R. J., 1987)
Genetic Engineering, Principles and Methods, VoI. 9, J.
K. Setlow, editor, Plenum Press, New York. An
expression vector is constructed in which a strong
promoter capable of functioning in mammalian cells
drives transcription of a eukaryotic secretion signal
peptide coding region, which is translationally joined
to the coding region for the multi-functional chimeric
hematopoietic receptor agonist. For example, plasmids
such as pcDNA I/Neo, pRc/RSV, and pRc/CMV (obtained from
Invitrogen Corp., San Diego, California) can be used.
The eukaryotic secretion signal peptide coding region
can be from the gene itself or it can be from another
secreted mammalian protein (Bayne, M. L. et al., Proc.
Natl. Acad. Sci. USA 84: 2638-2642, 1987). After
construction of the vector containing the gene, the
vector DNA is transfected into mammalian cells. Such
cells can be, for example, the COS7, HeLa, BHK, CHO, or
mouse L lines. The cells can be cultured, for example,
in DMEM media (JRH Scientific). The polypeptide
secreted into the media can be recovered by standard
biochemical approaches following transient expression
for 24 - 72 hours after transfection of the cells or
after establishment of stable cell lines following
selection for antibiotic resistance. The selection of
suitable mammalian host cells and methods for
transformation, culture, amplification, screening and
product production and purification are known in the
art. See, e.g., Gething and Sambrook, Nature, 293:620-
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5z
625, 1981), or alternatively, Kaufman et al, Mol. Cell.
Biol., 5(7):1750-1759, 1985) or Howley et al., U.S. Pat.
No. 4,419,446. Another suitable mammalian cell line is
the monkey COS-1 cell line. A similarly useful
mammalian cell line is the CV-1 cell line.
Where desired, insect cells may be utilized as host
cells in the method of the present invention. See,
e.g., Miller et al., Genetic Engineering, 8:277-298
(Plenum Press 1986) and references cited therein. In
addition, general methods for expression of foreign
genes in insect cells using Baculovirus vectors are
described in: Summers, M. D. and Smith, G. E., 1987) - A
manual of methods for Baculovirus vectors and insect
cell culture procedures, Texas Agricultural Experiment
Station Bulletin No. 1555. An expression vector is
constructed comprising a Baculovirus transfer vector, in
which a strong Baculovirus promoter (such as the
polyhedron promoter) drives transcription of a
eukaryotic secretion signal peptide coding region, which
is translationally joined to the coding region for the
multi-functional chimeric hematopoietic receptor agonist
polypeptide. For example, the plasmid pVL1392 (obtained
from Invitrogen Corp., San Diego, California) can be
used. After construction of the vector carrying the
gene encoding the multi-functional chimeric
hematopoietic receptor agonist polypeptide, two
micrograms of this DNA is co-transfected with one
microgram of Baculovirus DNA (see Summers & Smith, 1987)
into insect cells, strain SF9. Pure recombinant
Baculovirus carrying the multi-functional chimeric
hematopoietic receptor agonist is used to infect cells
cultured, for example, in Excell 401 serum-free medium
(JRH Biosciences, Lenexa, Kansas). The mufti-functional
chimeric hematopoietic receptor agonist secreted into
the medium can be recovered by standard biochemical
approaches. Supernatants from mammalian or insect cells
expressing the mufti-functional chimeric hematopoietic
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receptor agonist protein can be first concentrated using
any of a number of commercial concentration units.
The multi-functional chimeric hematopoietic
receptor agonists of the present invention may be useful
in the treatment of diseases characterized by decreased
levels of either myeloid, erythroid, lymphoid, or
megakaryocyte cells of the hematopoietic system or
combinations thereof. In addition, they may be used to
activate mature myeloid and/or lymphoid cells. Among
conditions susceptible to treatment with the
polypeptides of the present invention is leukopenia, a
reduction in the number of circulating leukocytes (white
cells) in the peripheral blood. Leukopenia may be
induced by exposure to certain viruses or to radiation.
It is often a side effect of various forms of cancer
therapy, e.g., exposure to chemotherapeutic drugs,
radiation and of infection or hemorrhage. Therapeutic
treatment of leukopenia with these multi-functional
chimeric hematopoietic receptor agonists of the present
invention may avoid undesirable side effects caused by
treatment with presently available drugs.
The multi-functional chimeric hematopoietic
receptor agonists of the present invention may be useful
in the treatment of neutropenia and, for example, in the
treatment of such conditions as aplastic anemia, cyclic
neutropenia, idiopathic neutropenia, Chediak-Higashi
syndrome, systemic lupus erythematosus (SLE), leukemia,
myelodysplastic syndrome and myelofibrosis.
The multi-functional chimeric hematopoietic
receptor agonist of the present invention may be useful
in the treatment or prevention of thrombocytopenia.
Currently the only therapy for thrombocytopenia is
platelet transfusion which are costly and carry the
significant risks of infection (HIV, HBV) and
alloimunization. The multi-functional chimeric
hematopoietic receptor agonist may alleviate or diminish
the need for platelet transfusion. Severe
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thrombocytopenia may result from genetic defects such as
Fanconi's Anemia, Wiscott-Aldrich, or May Hegglin
syndromes. Acquired thrombocytopenia may result from
auto- or allo-antibodies as in Immune Thrombocytopenia
Purpura, Systemic Lupus Erythromatosis, hemolytic
anemia, or fetal maternal incompatibility. In addition,
splenomegaly, disseminated intravascular coagulation,
thrombotic thrombocytopenic purpura, infection or
prosthetic heart valves may result in thrombocytopenia.
Severe thrombocytopenia may also result from
chemotherapy and/or radiation therapy or cancer.
Thrombocytopenia may also result from marrow invasion by
carcinoma, lymphoma, leukemia or fibrosis.
The multi-functional chimeric hematopoietic
receptor agonists of the present invention may be useful
in the mobilization of hematopoietic progenitors and
stem cells in peripheral blood. Peripheral blood derived
progenitors have been shown to be effective in
reconstituting patients in the setting of autologous
marrow transplantation. Hematopoietic growth factors
including G-CSF and GM-CSF have been shown to enhance
the number of circulating progenitors and stem cells in
the peripheral blood. This has simplified the procedure
for peripheral stem cell collection and dramatically
decreased the cost of the procedure by decreasing the
number of pheresis required. The multi-functional
chimeric hematopoietic receptor agonist may be useful in
mobilization of stem cells and further enhance the
efficacy of peripheral stem cell transplantation.
The multi-functional chimeric hematopoietic
receptor agonists of the present invention may also be
useful in the ex vivo expansion of hematopoietic
progenitors and stem cells. Colony stimulating factors
(CSFs), such as hIL-3, have been administered alone, co-
administered with other CSFs, or in combination with
bone marrow transplants subsequent to high dose
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5~'
chemotherapy to treat the neutropenia and
thrombocytopenia which are often the result of such
treatment. However the period of severe neutropenia and
thrombocytopenia may not be totally eliminated. The
myeloid lineage, which is comprised of monocytes
(macrophages), granulocytes (including neutrophils) and
megakaryocytes, is critical in preventing infections and
bleeding which can be life-threatening. Neutropenia and
thrombocytopenia may also be the result of disease,
genetic disorders, drugs, toxins, radiation and many
therapeutic treatments such as conventional oncology
therapy.
Bone marrow transplants have been used to treat
this patient population. However, several problems are
associated with the use of bone marrow to reconstitute a
compromised hematopoietic system including: 1) the
number of stem cells in bone marrow, spleen, or
peripheral blood is limited, 2) Graft Versus Host
Disease, 3) graft rejection and 4) possible
contamination with tumor cells. Stem cells make up a
very small percentage of the nucleated cells in the bone
marrow, spleen and peripheral blood. It is clear that a
dose response exists such that a greater number of stem
cells will enhance hematopoietic recovery. Therefore,
the in vitro expansion of stem cells should enhance
hematopoietic recovery and patient survival. Bone marrow
from an allogeneic donor has been used to provide bone
marrow for transplant. However, Graft Versus Host
Disease and graft rejection limit bone marrow
transplantation even in recipients with HLA-matched
sibling donors. An alternative to allogeneic bone marrow
transplants is autologous bone marrow transplants. In
autologous bone marrow transplants, some of the
patient's own marrow is harvested prior to myeloablative
therapy, e.g. high dose chemotherapy, and is
transplanted back into the patient afterwards.
Autologous transplants eliminate the risk of Graft
Versus Host Disease and graft rejection. However,
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autologous bone marrow transplants still present
problems in terms of the limited number of stems cells
in the marrow and possible contamination with tumor
cells. The limited number of stem cells may be overcome
by ex-vivo expansion of the stem cells. In addition,
stem cells can be specifically isolated, based on the
presence of specific surface antigens such as CD34+ in
order to decrease tumor cell contamination of the marrow
graft.
The following patents contain further details on
separating stem cells, CD34+ cells, culturing the cells
with hematopoietic factors, the use of the cells for the
treatment of patients with hematopoietic disorders and
the use of hematopoietic factors for cell expansion and
gene therapy.
5,061,620 relates to compositions comprising human
hematopoietic stem cells provided by separating the stem
cells from dedicated cells.
5,199,942 describes a method for autologous
hematopoietic cell transplantation comprising: (1)
obtaining hematopoietic progenitor cells from a patient;
(2) ex-vivo expansion of cells with a growth factor
selected from the group consisting of IL-3, flt3 ligand,
c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein
and combinations thereof; (3) administering cellular
preparation to a patient.
5,240,856 relates to a cell separator that includes an
apparatus for automatically controlling the cell
separation process.
WO 91/16116 describes devices and methods for
selectively isolating and separating target cells from a
mixture of cells.
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WO 91/18972 describes methods for in vitro culturing of
bone marrow, by incubating suspension of bone marrow
cells, using a hollow fiber bioreactor.
WO 92/18615 relates to a process for maintaining and
expanding bone marrow cells, in a culture medium
containing specific mixtures of cytokines, for use in
transplants.
WO 93/08268 describes a method for selectively expanding
stem cells, comprising the steps of (a) separating CD34+
stem cells from other cells and (b) incubating the
separated cells in a selective medium, such that the
stem cells are selectively expanded.
WO 93/18136 describes a process for in vitro support of
mammalian cells derived from peripheral blood.
WO 93/18648 relates to a composition comprising human
neutrophil precursor cells with a high content of
myeloblasts and promyelocytes for treating genetic or
acquired neutropenia.
WO 94/08039 describes a method of enrichment for human
hematopoietic stem cells by selection for cells which
express c-kit protein.
WO 94/11493 describes a stem cell population that are
CD34+ and small in size, which are isolated using a
counterflow elutriation method.
WO 94/27698 relates to a method combining immunoaffinity
separation and continuous flow centrifugal separation
for the selective separation of a nucleated
heterogeneous cell population from a heterogeneous cell
mixture.
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WO 94/25848 describes a cell separation apparatus for
collection and manipulation of target cells.
The long term culturing of highly enriched CD34+
precursors of hematopoietic progenitor cells from human
bone marrow in cultures containing IL-1a, IL-3, IL-6 or
GM-CSF is discussed in Brandt et al J. Clin. Invest.
86:932-941, 1990).
One aspect of the present invention provides a method
for selective ex-vivo expansion of stem cells. The term
"stem cell" refers to the totipotent hematopoietic stem
cells as well as early precursors and progenitor cells
which can be isolated from bone marrow, spleen or
peripheral blood. The term "expansion" refers to the
differentiation and proliferation of the cells. The
present invention provides a method for selective ex-
vivo expansion of stem cells, comprising the steps of:
(a) separating stem cells from other cells, (b)
culturing said separated stem cells with a selective
media which contains multi-functional chimeric
hematopoietic receptor agonist proteins) and (c)
harvesting said stems cells. Stem cells, as well as
committed progenitor cells destined to become
neutrophils, erythrocytes, platelets, etc. may be
distinguished from most other cells by the presence or
absence of particular progenitor marker antigens, such
as CD34, that are present on the surface of these cells
and/or by morphological characteristics. The phenotype
for a highly enriched human stem cell fraction is
reported as CD34+, Thy-1+ and lin-, but it is to be
understood that the present invention is not limited to
the expansion of this stem cell population. The CD34+
enriched human stem cell fraction can be separated by a
number of reported methods, including affinity columns
or beads, magnetic beads or flow cytometry using
antibodies directed to surface antigens such as the
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CD34+. Further, physical separation methods such as
counterflow elutriation may be used to enrich
hematopoietic progenitors. The CD34+ progenitors are
heterogeneous, and may be divided into several sub-
s populations characterized by the presence or absence of
co-expression of different lineage associated cell
surface associated molecules. The most immature
progenitor cells do not express any known lineage
associated markers, such as HLA-DR or CD38, but they may
express CD90(thy-1). Other surface antigens such as
CD33, CD38, CD41, CD71, HLA-DR or c-kit can also be used
to selectively isolate hematopoietic progenitors. The
separated cells can be incubated in selected medium in a
culture flask, sterile bag or in hollow fibers. Various
colony stimulating factors may be utilized in order to
selectively expand cells. Representative factors that
have been utilized for ex-vivo expansion of bone marrow
include, c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6,
IL-11, flt-3 ligand or combinations thereof. The
proliferation of the stem cells can be monitored by
enumerating the number of stem cells and other cells, by
standard techniques (e.g. hemacytometer, CFU, LTCIC) or
by flow cytometry prior and subsequent to incubation.
Several methods for ex-vivo expansion of stem cells
have been reported utilizing a number of selection
methods and expansion using various colony stimulating
factors including c-kit ligand (Brandt et al., Blood
83:1507-1514 [1994], McKenna et al., Blood 86:3413-3420
[1995]), IL-3 (Brandt et al., Blood 83:1507-1514 [1994],
Sato et al., Blood 82:3600-3609 [1993]), G-CSF (Sato et
al., Blood 82:3600-3609 [1993]), GM-CSF (Sato et al.,
Blood 82:3600-3609 [1993]), IL-1 (Muench et al., Blood
81:3463-3473 [1993]), IL-6 (Sato et al., Blood 82:3600-
3609 [1993]), IL-11 (Lemoli et al., Exp. Hem. 21:1668-
1672 [1993], Sato et al., Blood 82:3600-3609 (1993]),
flt-3 ligand (McKenna et al., Blood 86:3413 3420 [1995])
and/or combinations thereof (Brandt et al., Blood
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83:1507 1514 [1994], Haylock et al., Blood 80:1405-1412
[1992], Koller et al., Biotechnology 11:358-363 [1993],
(Lemoli et al., Exp. Hem. 21:1668-1672 [1993]), McKenna
et al., Blood 86:3413-3420 [1995], Muench et al., Blood
81:3463-3473 [1993], Patchen et al., Biotherapy 7:13-26
[1994], Sato et al., Blood 82:3600-3609 [1993], Smith et
al., Exp. Hem. 21:870-877 [1993], Steen et al., Stem
Cells 12:214-224 [1994], Tsujino et al., Exp. Hem.
21:1379-1386 [1993]). Among the individual colony
stimulating factors, hIL-3 has been shown to be one of
the most potent in expanding peripheral blood CD34+
cells (Sato et al., Blood 82:3600-3609 [1993], Kobayashi
et al., Blood 73:1836-1841 [1989]). However, no single
factor has been shown to be as effective as the
combination of multiple factors. The present invention
provides methods for ex vivo expansion that utilize
multi-functional chimeric hematopoietic receptor
agonists that are more effective than a single factor
alone.
Another aspect of the invention provides methods of
sustaining and/or expanding hematopoietic precursor
cells which includes inoculating the cells into a
culture vessel which contains a culture medium that has
been conditioned by exposure to a stromal cell line such
as HS-5 (WO 96/02662, Roecklein and Torok-Strob, Blood
85:997-1105, 1995) that has been supplemented with a
multi-functional hematopoietic chimeric receptor agonist
of the present invention.
It is also envisioned that uses of mufti-functional
hematopoietic chimeric receptor agonists of the present
invention would include blood banking applications,
where the EPO receptor agonists are given to a patent to
increase the number of blood cells and blood products
are removed from the patient, prior to some medical
procedure. The blood products stored and transfused back
into the patient after the medical procedure.
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Additionally, it is envisioned that uses of multi-
functional hematopoietic chimeric receptor agonists
would include giving the multi-functional hematopoietic
chimeric receptor agonists to a blood donor prior to
blood donation to increase the number of blood cells,
thereby allowing the donor to safely give more blood.
Another projected clinical use of growth factors
has been in the in vitro activation of hematopoietic
progenitors and stem cells for gene therapy. Due to the
long life-span of hematopoietic progenitor cells and the
distribution of their daughter cells throughout the
entire body, hematopoietic progenitor cells are good
candidates for ex vivo gene transfection. In order to
have the gene of interest incorporated into the genome
of the hematopoietic progenitor or stem cell one needs
to stimulate cell division and DNA replication.
Hematopoietic stem cells cycle at a very low frequency
which means that growth factors may be useful to promote
gene transduction and thereby enhance the clinical
prospects for gene therapy. Potential applications of
gene therapy (review Crystal, Science 270:404-410
(1995]) include; 1) the treatment of many congenital
metabolic disorders and immunodeficiencies (Kay and Woo,
Trends Genet. 10:253-257 [1994]), 2) neurological
disorders (Friedmann, Trends Genet. 10:210-214 [1994]),
3) cancer (Culver and Blaese, Trends Genet. 10:174-178
[1994]) and 4) infectious diseases (Gilboa and Smith,
Trends Genet. 10:139-144 [1994]).
There are a variety of methods, known to those with
skill in the art, for introducing genetic material into
a host cell. A number of vectors, both viral and non-
viral have been developed for transferring therapeutic
genes into primary cells. Viral based vectors include;
1) replication deficient recombinant retrovirus (Boris-
Lawrie and Temin, Curr. Opin. Genet. Dev. 3:102-109
[1993], Boris-Lawrie and Temin, Annal. New York Acad.
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6~
Sci. 716:59-71 [1994], Miller, Current Top. Microbiol.
Immunol. 158:1-24 [1992]) and replication-deficient
recombinant adenovirus (Berkner, BioTechniques 6:616-629
[1988], Berkner, Current Top. Microbiol. Immunol.
158:39-66 [1992], Brody and Crystal, Annal. New York
Acad. Sci. 716:90-103 [1994]). Non-viral based vectors
include protein/DNA complexes (Cristiano et al., PNAS
USA. 90:2122-2126 [1993], Curiel et al., PNAS USA
88:8850-8854 [1991], Curiel, Annal. New York Acad. Sci.
716:36-58 [1994]), electroporation and liposome
mediated delivery such as cationic liposomes (Farhood et
al., Annal. New York Acad. Sci. 716:23-35 [1994]).
The present invention provides an improvement to
the existing methods of expanding hematopoietic cells,
which new genetic material has been introduced, in that
it provides methods utilizing multi-functional chimeric
hematopoietic receptor agonist proteins that have
improved biological activity, including an activity not
seen by any single colony stimulation factor.
Many drugs may cause bone marrow suppression or
hematopoietic deficiencies. Examples of such drugs are
AZT, DDI, alkylating agents and anti-metabolites used in
chemotherapy, antibiotics such as chloramphenicol,
penicillin, gancyclovir, daunomycin and sulfa drugs,
phenothiazones, tranquilizers such as meprobamate,
analgesics such as aminopyrine and dipyrone, anti-
convulsants such as phenytoin or carbamazepine,
antithyroids such as propylthiouracil and methimazole
and diuretics. The multi-functional chimeric
hematopoietic receptor agonists of the present invention
may be useful in preventing or treating the bone marrow
suppression or hematopoietic deficiencies which often
occur in patients treated with these drugs.
Hematopoietic deficiencies may also occur as a
result of viral, microbial or parasitic infections,
burns and as a result of treatment for renal disease or
renal failure, e.g., dialysis. The multi-functional
chimeric hematopoietic receptor agonists of the present
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63
invention may be useful in treating such hematopoietic
deficiencies.
The treatment of hematopoietic deficiency may
include administration of a pharmaceutical composition
containing the mufti-functional chimeric hematopoietic
receptor agonists to a patient. The mufti-functional
chimeric hematopoietic receptor agonists of the present
invention may also be useful for the activation and
amplification of hematopoietic precursor cells by
treating these cells in vitro with the mufti-functional
chimeric hematopoietic receptor agonist proteins of the
present invention prior to injecting the cells into a
patient.
Various immunodeficiencies, e.g., in T and/or B
lymphocytes, or immune disorders, e.g., rheumatoid
arthritis, may also be beneficially affected by
treatment with the mufti-functional chimeric
hematopoietic receptor agonists of the present
invention. Immunodeficiencies may be the result of
viral infections, e.g., HTLVI, HTLVII, HTLVIII, severe
exposure to radiation, cancer therapy or the result of
other medical treatment. The mufti-functional chimeric
hematopoietic receptor agonists of the present invention
may also be employed, alone or in combination with other
colony stimulating factors, in the treatment of other
blood cell deficiencies, including thrombocytopenia
(platelet deficiency), or anemia. Other uses for these
novel polypeptides are the in vivo and ex vivo treatment
of patients recovering from bone marrow transplants, and
in the development of monoclonal and polyclonal
antibodies generated by standard methods for diagnostic
or therapeutic use.
Other aspects of the present invention are methods
and therapeutic compositions for treating the conditions
referred to above. Such compositions comprise a
therapeutically effective amount of one or more of the
mufti-functional chimeric hematopoietic receptor
agonists of the present invention in a mixture with a
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6~
pharmaceutically acceptable carrier. This composition
can be administered either parenterally, intravenously
or subcutaneously. When administered, the therapeutic
composition for use in this invention is preferably in
the form of a pyrogen-free, parenterally acceptable
aqueous solution. The preparation of such a
parenterally acceptable protein solution, having due
regard to pH, isotonicity, stability and the like, is
within the skill of the art.
Another intended use of the mufti-functional
chimeric hematopoietic receptor agonists of the present
invention is for the generation of larger numbers of
dendritic cells, from precursors, to be used as
adjuvants for immunization. Dendritic cells play a
crucial role in the immune system. They are the
professional antigen-presenting cells most efficient in
the activation of resting T cells and are the major
antigen-presenting cells for activation of naYve T cells
in vivo and, thus, for initiation of primary immune
responses. They efficiently internalize, process and
present soluble tumor-specific antigens (Ag). Dendritic
cells have the unique capacity to cluster naive T cells
and to respond to Ag encounter by rapid upregulation of
the expression of major histocompatability complex (MHC)
and co-stimulatory molecules, the production of
cytokines and migration towards lymphatic organs. Since
dendritic cells are of central importance for
sensitizing the host against a neoantigen for CD4-
dependent immune responses, they may also play a crucial
role in the generation and regulation of tumor immunity.
Dendritic cells originate from a bone marrow CD34+
precursor common to granulocytes and macrophages, and
the existence of a separate dendritic cell colony-
forming unit (CFU-DC) that give rise to pure dendritic
cell colonies has been established in humans. In
addition, a post-CFU CD14+ intermediate has been
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described with the potential to differentiate along the
dendritic cell or the macrophage pathway under distinct
cytokine conditions. This bipotential precursor is
present in the bone marrow, cord blood and peripheral
blood. Dendritic cells can be isolated based on specific
cell surface markers, such as CDla+, CD3-, CD4-, CD20-,
CD40+, CD80+, and CD83+, to delineate the maturation of
cultured dendritic cells.
Dendritic cells based strategies provide a method
for enhancing immune response against tumors and
infectious agents. AIDS is another disease for which
dendritic cell based therapies can be used, since
dendritic cells can play a major role in promoting HIV-
1 replication. An immunotherapy requires the generation
of dendritic cells from cancer patients, their in vitro
exposure to tumor Ag, derived from surgically removed
tumor masses, and reinjection of these cells into the
tumor patients. Relatively crude membrane preparations
of tumor cells will suffice as sources of tumor antigen,
avoiding the necessity for molecular identification of
the tumor antigen. The tumor antigen may also be
synthetic peptides, carbohydrates, or nucleic acid
sequences. In addition, concomitant administration of
cytokines such as the mufti-functional chimeric
hematopoietic receptor agonists of the present invention
may further facilitate the induction of tumor immunity.
It is foreseen that the immunotherapy can be in an in
vivo setting, wherein the mufti-functional chimeric
hematopoietic receptor agonists of the present invention
is administered to a patient, having a tumor, alone or
with other hematopoietic growth factors to increase the
number of dendritic cells and endogenous tumor antigen
is presented on the dendritic cells. It is also
envisioned that in vivo immunotherapy can be with
exogenous antigen. It is also envisioned that the
immunotherapy treatment may include the mobilization of
dendritic cell precursors or mature dendritic, by
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administering the multi-functional chimeric
hematopoietic receptor agonists of the present invention
alone or with other hematopoietic growth factors to the
patient, removing the dendritic cell precursors or
mature dendritic cells from the patient, exposing the
dendritic cells to antigen and returning the dendritic
cells to the patient. Furthermore, the dendritic cells
that have been removed can be cultured ex vivo with the
multi-functional chimeric hematopoietic receptor
agonists of the present invention alone or with other
hematopoietic growth factors to increase the number of
dendritic cells prior to exposure to antigen. Dendritic
cells based strategies also provide a method for
reducing the immune response in auto-immune diseases.
Studies on dendritic cells have been greatly
hampered by difficulties in preparing the cells in
sufficient numbers and in a reasonably pure form. In an
ex-vivo cell expansion setting, granulocyte-macrophage
colony-stimulating factor (GM-CSF) and tumor necrosis
factor-a (TNF-a ) cooperate in the ex vivo generation of
dendritic cells from hematopoietic progenitors (CD34+
cells) retrieved from bone marrow, cord blood, or
peripheral blood and flk-2/flt-3 ligand and c-kit ligand
(stem cell factor [SCF]) synergize to enhance the GM-CSF
plus TNF-a induced generation of dendritic cells (Siena,
S. et a1. Experimental Hematology 23:1463-1471, 1995).
Also provide is a method of ex vivo expansion of
dendritic cell precursors or mature dendritic cells
using the multi-functional chimeric hematopoietic
receptor agonists of the present invention to provide
sufficient quantities of dendritic cells for
immunotherapy .
The dosage regimen involved in a method for
treating the above-described conditions will be
determined by the attending physician considering
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various factors which modify the action of drugs, e.g.,
the condition, body weight, sex and diet of the patient,
the severity of any infection, time of administration
and other clinical factors. Generally, a daily regimen
may be in the range of 0.2 - 150 ug/kg of multi-
functional chimeric hematopoietic receptor agonist
protein per kilogram of body weight. Dosages would be
adjusted relative to the activity of a given multi-
functional chimeric hematopoietic receptor agonist
protein and it would not be unreasonable to note that
dosage regimens may include doses as low as 0.1
microgram and as high as 1 milligram per kilogram of
body weight per day. In addition, there may exist
specific circumstances where dosages of multi-functional
chimeric hematopoietic receptor agonist would be
adjusted higher or lower than the range of 0.2 - 150
micrograms per kilogram of body weight. These include
co-administration with other colony stimulating factors
or IL-3 variants or growth factors; co-administration
with chemotherapeutic drugs and/or radiation; the use of
glycosylated multi-functional chimeric hematopoietic
receptor agonist protein; and various patient-related
issues mentioned earlier in this section. As indicated
above, the therapeutic method and compositions may also
include co-administration with other human factors. A
non-exclusive list of other appropriate colony
stimulating factors (CSFs), cytokines, lymphokines,
hematopoietic growth factors and interleukins for
simultaneous or serial co-administration with the
polypeptides of the present invention includes GM-CSF,
G-CSF, c-mpl ligand (also known as TPO or MGDF), M-CSF,
erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL-
6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15,
.IL-16, LIF, flt3/flk2 ligand, B-cell growth factor, B-
cell differentiation factor and eosinophil
differentiation factor, stem cell factor (SCF) also
known as steel factor or c-kit ligand, or combinations
thereof. The dosage recited above would be adjusted to
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compensate for such additional components in the
therapeutic composition. Progress of the treated
patient can be monitored by periodic assessment of the
hematological profile, e.g., differential cell count and
the like.
MATERIALS AND METHODS
Unless noted otherwise, all specialty chemicals were
obtained from Sigma, Co. (St. Louis, MO). Restriction
endonucleases and T4 DNA lipase were obtained from New
England Biolabs (Beverly, MA) or Boehringer Mannheim
(Indianapolis, IN).
Transformation of E. coli strains
E. coli strains, such as DHSa''M (Life Technologies,
Gaithersburg, MD) and TG1 (Amersham Corp., Arlington
Heights, IL) are used for transformation of ligation
reactions and are the source of plasmid DNA for
transfecting mammalian cells. E. coli strains, such as
JM101 (Yanisch-Perron, et al., Gene, 33: 103-119, 1985)
and MON105 (Obukowicz, et al., Appl. and Envir. Mzcr.,
58: 1511-1523, 1992) can be used for expressing the
mufti-functional chimeric hematopoietic receptor agonist
of the present invention in the cytoplasm or periplasmic
space.
MON105 ATCC#55204: F-, lambda-,IN(rrnD, rrE)1, rpoD+,
rpoH358
DHSaTM: F-, phi80d1acZdeltaMlS, delta(lacZYA-argF)U169,
deoR, recAl, endAl, hsdRl7(rk-,mk+), phoA, supE441amda-,
thi-1, gyrA96, relA1
TG1: delta(lac-pro), supE, thi-1, hsdD5/F'(traD36,
proA+B+, lacIq, lacZdeltaMlS)
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6~
JM101 ATCC#33876: delta (pro lacy, supE, thi, F'(traD36,
proA+B+, lacIq, lacZdeltaMl5)
DHSaTM Subcloning efficiency cells are purchased as
competent cells and are ready for transformation using
the manufacturer's protocol, while both E. coli strains
TG1 and MON105 are rendered competent to take up DNA
using a CaClz method. Typically, 20 to 50 mL of cells
are grown in LB medium (1% Bacto-tryptone, 0.5% Bacto-
yeast extract, 150 mM NaCl) to a density of
approximately 1.0 optical density unit at 600 nanometers
(OD600) as measured by a Baush & Lomb Spectronic
spectrophotometer (Rochester, NY). The cells are
collected by centrifugation and resuspended in one-fifth
culture volume of CaCl2 solution (50 mM CaClz, 10 mM
Tris-C1, pH7.4) and are held at 4°C for 30 minutes. The
cells are again collected by centrifugation and
resuspended in one-tenth culture volume of CaClz
solution. Ligated DNA is added to 0.2 mL of these
cells, and the samples are held at 4°C for 30-60
minutes. The samples are shifted to 42°C for two
minutes and 1.0 mL of LB is added prior to shaking the
samples at 37°C for one hour. Cells from these samples
are spread on plates (LB medium plus 1.5o Bacto-agar)
containing either ampicillin (100 micrograms/mL, ug/mL)
when selecting for ampicillin-resistant transformants,
or spectinomycin (75 ug/mL) when selecting for
spectinomycin-resistant transformants. The plates are
incubated overnight at 37°C. Colonies are picked and
inoculated into LB plus appropriate antibiotic (100
ug/mL ampicillin or 75 ug/mL spectinomycin) and are
grown at 37°C while shaking.
Methods for creation of Genes with new N-terminus/C-
terminus
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Method I. Creation of genes with new N-terminus/C-
terminus which contain a linker region (LZ).
5 Genes with new N-terminus/C-terminus which contain
a linker region (Lz) separating the original C-terminus
and N-terminus can be made essentially following the
method described in L. S. Mullins, et al (J. Am. Chem.
Soc. 115, 5529-5533, 1994). Multiple steps of
10 polymerase chain reaction (PCR) amplifications are used
to rearrange the DNA sequence encoding the primary amino
acid sequence of the protein. The steps are illustrated
in Figure 2.
In the first step, the first primer set ("new
15 start" and "linker start") is used to create and
amplify, from the original gene sequence, the DNA
fragment ("Fragment Start") that contains the sequence
encoding the new N-terminal portion of the new protein
followed by the linker (Lz) that connects the C-terminal
20 and N-terminal ends of the original protein. In the
second step, the second primer set ("new stop" and
"linker stop") is used to create and amplify, from the
original gene sequence, the DNA fragment ("Fragment
Stop") that encodes the same linker as used above,
25 followed by the new C-terminal portion of the new
protein. The "new start" and "new stop" primers are
designed to include the appropriate restriction sites
which allow cloning of the new gene into expression
plasmids. Typical PCR conditions are one cycle 95°C
30 melting for two minutes; 25 cycles 94°C denaturation for
one minute, 50°C annealing for one minute and 72°C
extension for one minute; plus one cycle 72°C extension
for seven minutes. A Perkin Elmer GeneAmp PCR Core
Reagents kit is used. A 100 ul reaction contains 100
35 pmole of each primer and one ug of template DNA; and lx
PCR buffer, 200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200
uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM
CA 02268742 1999-04-19
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MgCl2. PCR reactions are performed in a Model 480 DNA
thermal cycler (Perkin Elmer Corporation, Norwalk, CT).
"Fragment Start" and "Fragment Stop", which have
complementary sequence in the linker region and the
coding sequence for the two amino acids on both sides of
the linker, are joined together in a third PCR step to
make the full-length gene encoding the new protein. The
DNA fragments "Fragment Start" and "Fragment Stop" are
resolved on a 1o TAE gel, stained with ethidium bromide
and isolated using a Qiaex Gel Extraction kit (Qiagen).
These fragments are combined in equimolar quantities,
heated at 70°C for ten minutes and slow coo~.ed to allow
annealing through their shared sequence in "linker
start" and "linker stop". In the third PCR step,
primers "new start" and "new stop" are added to the
annealed fragments to create and amplify the full-length
new N-terminus/C-terminus gene. Typical PCR conditions
are one cycle 95°C melting for two minutes; 25 cycles
94°C denaturation for one minute, 60°C annealing for one
minute and 72°C extension for one minute; plus one cycle
72°C extension for seven minutes. A Perkin Elmer
GeneAmp PCR Core Reagents kit is used. A 100 ul
reaction contains 100 pmole of each primer and
approximately 0.5 ug of DNA; and 1x PCR buffer, 200 uM
dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units
AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions
are purified using a Wizard PCR Preps kit (Promega).
Method II. Creation of genes with new N-terminus/C-
terminus without a linker region.
New N-terminus/C-terminus genes without a linker
joining the original N-terminus and C-terminus can be
made using two steps of PCR amplification and a blunt
end ligation. The steps are illustrated in Figure 3.
In the first step, the primer set ("new start" and "P-bl
CA 02268742 1999-04-19
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start") is used to create and amplify, from the original
gene sequence, the DNA fragment ("Fragment Start") that
contains the sequence encoding the new N-terminal
portion of the new protein. In the second step, the
primer set ("new stop" and "P-bl stop") is used to
create and amplify, from gene sequence, the DNA fragment
("Fragment Stop") that contains the sequence encoding
the new C-terminal portion of the new protein. The "new
start" and "new stop" primers are designed to include
appropriate restriction sites which allow cloning of the
new gene into expression vectors. Typical PCR conditions
are one cycle 95°C melting for two minutes; 25 cycles
94°C denaturation for one minute, 50°C annealing for 45
seconds and 72°C extension for 45 seconds. Deep Vent
polymerase (New England Biolabs) is used to reduce the
occurrence of overhangs in conditions recommended by the
manufacturer. The "P-bl start" and "P-bl stop" primers
are phosphorylated at the 5' end to aid in the
subsequent blunt end ligation of "Fragment Start" and
"Fragment Stop" to each other. A 100 ul reaction
contained 150 pmole of each primer and one ug of
template DNA; and 1x Vent buffer (New England Biolabs),
300 uM dGTP, 300 uM dATP, 300 uM dTTP, 300 uM dCTP, and
1 unit Deep Vent polymerase. PCR reactions are
performed in a Model 480 DNA thermal cycler (Perkin
Elmer Corporation, Norwalk, CT). PCR reaction products
are purified using a Wizard PCR Preps kit (Promega).
The primers are designed to include appropriate
restriction sites which allow for the cloning of the new
gene into expression vectors. Typically "Fragment Start"
is designed to create NcoI restriction site , and
"Fragment Stop" is designed to create a HindIII
restriction site. Restriction digest reactions are
purified using a Magic DNA Clean-up System kit
(Promega). Fragments Start and Stop are resolved on a
1~ TAE gel, stained with ethidium bromide and isolated
using a Qiaex Gel Extraction kit (Qiagen). These
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73
fragments are combined with and annealed to the ends of
the ~ 3800 base pair NcoI/HindIII vector fragment of
pMON3934 by heating at 50°C for ten minutes and allowed
to slow cool. The three fragments are ligated together
using T4 DNA ligase (Boehringer Mannheim). The result is
a plasmid containing the full-length new N-terminus/C-
terminus gene. A portion of the ligation reaction is
used to transform E. coli strain DHSa cells (Life
Technologies, Gaithersburg, MD). Plasmid DNA is
purified and sequence confirmed as below.
Method III. Creation of new N-terminus/C-terminus genes
by tandem-duplication method
New N-terminus/C-terminus genes can be made based
on the method described in R. A. Horlick, et al Protein
Eng. 5:427-431, 1992). Polymerase chain reaction (PCR)
amplification of the new N-terminus/C-terminus genes is
performed using a tandemly duplicated template DNA. The
steps are illustrated in Figure 3.
The tandemly-duplicated template DNA is created by
cloning and contains two copies of the gene separated by
DNA sequence encoding a linker connecting the original
C- and N-terminal ends of the two copies of the gene.
Specific primer sets are used to create and amplify a
full-length new N terminus/C-terminus gene from the
tandemly-duplicated template DNA. These primers are
designed to include appropriate restriction sites which
allow for the cloning of the new gene into expression
vectors. Typical PCR conditions are one cycle 95°C
melting for two minutes; 25 cycles 94°C denaturation for
one minute, 50°C annealing for one minute and 72°C
extension for one minute; plus one cycle 72°C extension
for seven minutes. A Perkin Elmer GeneAmp PCR Core
Reagents kit (Perkin Elmer Corporation, Norwalk, CT). is
used. A 100 ul reaction contains 100 pmole of each
CA 02268742 1999-04-19
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primer and one ug of template DNA; and lx PCR buffer,
200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5
units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR
reactions are performed in a Model 480 DNA thermal
cycler (Perkin Elmer Corporation, Norwalk, CT). PCR
reactions are purified using a Wizard PCR Preps kit
(Promega).
Cloning of new N-terminus/C-terminus Genes into multi-
functional recet~tor aaonist expression vectors.
The new N-terminus/C-terminus gene is digested with
restriction endonucleases to create ends that are
compatible to insertion into an expression vector
containing another colony stimulating factor gene. This
expression vector is likewise digested with restriction
endonucleases to form compatible ends. After
purification, the gene and the vector DNAs are combined
and ligated using T4 DNA lipase. A portion of the
ligation reaction is used to transform E. coli. Plasmid
DNA is purified and sequenced to confirm the correct
insert. The correct clones are grown for protein
expression.
DNA isolation and characterization
Plasmid DNA can be isolated by a number of
different methods and using commercially available kits
known to those skilled in the art. A few such methods
are shown herein. Plasmid DNA is isolated using the
Promega WizardT"' Miniprep kit {Madison, WI), the Qiagen
QIAwell Plasmid isolation kits (Chatsworth, CA) or
Qiagen Plasmid Midi kit. These kits follow the same
general procedure for plasmid DNA isolation. Briefly,
cells are pelleted by centrifugation (5000 x g), plasmid
DNA released with sequential NaOH/acid treatment, and
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cellular debris is removed by centrifugation (10000 x
g). The supernatant (containing the plasmid DNA) is
loaded onto a column containing a DNA-binding resin, the
column is washed, and plasmid DNA eluted with TE. After
screening for the colonies with the plasmid of interest,
the E. coli cells are inoculated into 50-100 mLs of LB
plus appropriate antibiotic for overnight growth at 37°C
in an air incubator while shaking. The purified plasmid
DNA is used for DNA sequencing, further restriction
enzyme digestion, additional subcloning of DNA fragments
and transfection into mammalian, E. coli or other cells.
Seauence confirmation.
Purified plasmid DNA is resuspended in dHzO and
quantitated by measuring the absorbance at 260/280 nm in
a Bausch and Lomb Spectronic 601 UV spectrometer. DNA
samples are sequenced using ABI PRISMTM DyeDeox~'M
terminator sequencing chemistry (Applied Biosystems
Division of Perkin Elmer Corporation, Lincoln City, CA)
kits (Part Number 401388 or 402078) according to the
manufacturers suggested protocol usually modified by the
addition of 5~ DMSO to the sequencing mixture.
Sequencing reactions are performed in a Model 480 DNA
thermal cycler (Perkin Elmer Corporation, Norwalk, CT)
following the recommended amplification conditions.
Samples are purified to remove excess dye terminators
with Centri-Sep'~'° spin columns (Princeton Separations,
Adelphia, NJ) and lyophilized. Fluorescent dye labeled
sequencing reactions are resuspended in deionized
formamide, and sequenced on denaturing 4.75
polyacrylamide-8M urea gels using an ABI Model 373A
automated DNA sequencer. Overlapping DNA sequence
fragments are analyzed and assembled into master DNA
contigs using Sequencher DNA analysis software (Gene
Codes Corporation, Ann Arbor, MI).
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~6
Ext~ression of multi-functional receptor aaonists in
mammalian cells
Mammalian Cell Transfection/Production of Conditioned
Media
The BHK-21 cell line can be obtained from the ATCC
(Rockville, MD). The cells are cultured in Dulbecco's
modified Eagle media (DMEM/high-glucose), supplemented
to 2 mM (mM) L-glutamine and 10o fetal bovine serum
(FBS). This formulation is designated BHK growth media.
Selective media is BHK growth media supplemented with
453 units/mL hygromycin B (Calbiochem, San Diego, CA).
The BHK-21 cell line was previously stably transfected
with the HSV transactivating protein VP16, which
transactivates the IE110 promoter found on the plasmid
pMON3359 (See Hippenmeyer et al., Bio/Technology,
pp.1037-1041, 1993). The VP16 protein drives expression
of genes inserted behind the IE110 promoter. BHK-21
cells expressing the transactivating protein VP16 are
designated BHK-VP16. The plasmid pMON1118 (See Highkin
et al., Poultry Sci., 70: 970-981, 1991) expresses the
hygromycin resistance gene from the SV40 promoter. A
similar plasmid is available from ATCC, pSV2-hph.
BHK-VP16 cells are seeded into a 60 millimeter (mm)
tissue culture dish at 3 X 105 cells per dish 24 hours
prior to transfection. Cells are transfected for 16
hours in 3 mL of "OPTIMEM"''''"' (Gibco-BRL, Gaithersburg,
MD) containing 10 ug of plasmid DNA containing the gene
of interest, 3 ug hygromycin resistance plasmid,
pMONl118, and 80 ug of Gibco-BRL "LIPOFECTAMINE"'1'"~ per
dish. The media is subsequently aspirated and replaced
with 3 mL of growth media. At 48 hours post-
transfection, media from each dish is collected and
assayed for activity (transient conditioned media). The
cells are removed from the dish by trypsin-EDTA, diluted
1:10 and transferred to 100 mm tissue culture dishes
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containing 10 mL of selective media. After approximately
7 days in selective media, resistant cells grow into
colonies several millimeters in diameter. The colonies
are removed from the dish with filter paper (cut to
approximately the same size as the colonies and soaked
in trypsin/EDTA) and transferred to individual wells of
a 24 well plate containing 1 mL of selective media.
After the clones are grown to confluence, the
conditioned media is re-assayed, and positive clones are
expanded into growth media.
Expression of mufti-functional recet~tor aaonists in E
coli
E. coli strain MON105 or JM101 harboring the
plasmid of interest are grown at 37°C in M9 plus
casamino acids medium with shaking in a air incubator
Model G25 from New Brunswick Scientific (Edison, New
Jersey). Growth is monitored at OD600 until it reaches
a value of 1.0 at which time Nalidixic acid (10
milligrams/mL) in 0.1 N NaOH is added to a final
concentration of 50 ug/mL. The cultures are then shaken
at 37°C for three to four additional hours. A high
degree of aeration is maintained throughout culture
period in order to achieve maximal production of the
desired gene product. The cells are examined under a
light microscope for the presence of inclusion bodies
(IB). One mL aliquots of the culture are removed for
analysis of protein content by boiling the pelleted
cells, treating them with reducing buffer and
electrophoresis via SDS-PAGE (see Maniatis et al.
Molecular Cloning: A Laboratory Manual, 1982). The
culture is centrifuged (5000 x g) to pellet the cells.
Inclusion Body pret~aration. Extraction Refolding
Dialysis, DEAE Chromatography and Characterization of
the mufti-functional chimeric hematot~oietic receptor
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78
acronists which accumulate as inclusion bodies in E
coli.
Isolation of Inclusion Bodies:
The cell pellet from a 330 mL E. coli culture is
resuspended in 15 mL of sonication buffer (10 mM 2-
amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride
(Tris-HC1), pH 8.0 + 1 mM ethylenediaminetetraacetic
acid (EDTA). These resuspended cells are sonicated
using the microtip probe of a Sonicator Cell Disruptor
(Model W-375, Heat Systems-Ultrasonics, Inc.,
Farmingdale, New York). Three rounds of sonication in
sonication buffer followed by centrifugation are
employed to disrupt the cells and wash the inclusion
bodies (IB). The first round of sonication is a 3
minute burst followed by a 1 minute burst, and the final
two rounds of sonication are for 1 minute each.
Extraction and refolding of proteins from inclusion body
pellets:
Following the final centrifugation step, the IB
pellet is resuspended in 10 mL of 50 mM Tris-HC1, pH
9.5, 8 M urea and 5 mM dithiothreitol (DTT) and stirred
at room temperature for approximately 45 minutes to
allow for denaturation of the expressed protein.
The extraction solution is transferred to a beaker
containing 70 mL of 5 mM Tris-HC1, pH 9.5 and 2.3 M urea
and gently stirred while exposed to air at 4°C for 18 to
48 hours to allow the proteins to refold. Refolding is
monitored by analysis on a Vydac (Hesperia, Ca.) C18
reversed phase high pressure liquid chromatography (RP-
HPLC) column (0.46x25 cm). A linear gradient of 40o to
65~ acetonitrile, containing 0.1~ trifluoroacetic acid
(TFA), is employed to monitor the refold. This gradient
is developed over 30 minutes at a flow rate of 1.5 mL
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?9
per minute. Denatured proteins generally elute later in
the gradient than the refolded proteins.
Purification:
Following the refold, contaminating E. coli
proteins are removed by acid precipitation. The pH of
the refold solution is titrated to between pH 5.0 and pH
5.2 using 15~ (v/v) acetic acid (HOAc). This solution
is stirred at 4°C for 2 hours and then centrifuged for
minutes at 12,000 x g to pellet any insoluble
protein.
The supernatant from the acid precipitation step is
dialyzed using a Spectra/Por 3 membrane with a molecular
15 weight cut off (MWCO) of 3,500 daltons. The dialysis is
against 2 changes of 4 liters (a 50-fold excess) of 10
mM Tris-HC1, pH 8.0 for a total of 18 hours. Dialysis
lowers the sample conductivity and removes urea prior to
DEAF chromatography. The sample is then centrifuged (20
20 minutes at 12,000 x g) to pellet any insoluble protein
following dialysis.
A Bio-Rad Bio-Scale DEAE2 column (7 x 52 mm) is
used for ion exchange chromatography. The column is
equilibrated in a buffer containing 10 mM Tris-HC1, pH
8.0, and a 0-to-500 mM sodium chloride (NaCl) gradient,
in equilibration buffer, over 45 column volumes is used
to elute the protein. A flow rate of 1.0 mL per minute
is used throughout the run. Column fractions (2.0 mL
per fraction) are collected across the gradient and
analyzed by RP HPLC on a Vydac (Hesperia, Ca.) C18
column (0.46 x 25 cm). A linear gradient of 40o to 65~
acetonitrile, containing 0.1~ trifluoroacetic acid
(TFA), is employed. This gradient is developed over 30
minutes at a flow rate of 1.5 mL per minute. Pooled
fractions are then dialyzed against 2 changes of 4
liters (50-to-500-fold excess) of 10 mM ammonium acetate
(NH4Ac), pH 4.0 for a total of 18 hours. Dialysis is
performed using a Spectra/Por 3 membrane with a MWCO of
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3,500 daltons. Finally, the sample is sterile filtered
using a 0.22~un syringe filter (uStar LB syringe filter,
Costar, Cambridge, Ma.), and stored at 4°C.
In some cases the folded proteins can be affinity
purified using affinity reagents such as mAbs or
receptor subunits attached to a suitable matrix.
Alternatively, (or in addition) purification can be
accomplished using any of a variety of chromatographic
methods such as: ion exchange, gel filtration or
hydrophobic chromatography or reversed phase HPLC.
These and other protein purification methods are
described in detail in Methods in Enzymology, Volume 182
'Guide to Protein Purification' edited by Murray
Deutscher, Academic Press, San Diego, CA (1990).
Protein Characterization:
The purified protein is analyzed by RP-HPLC,
electrospray mass spectrometry, and SDS-PAGE. The
protein quantitation is done by amino acid composition,
RP-HPLC, and Bradford protein determination. In some
cases tryptic peptide mapping is performed in
conjunction with electrospray mass spectrometry to
confirm the identity of the protein.
AML Proliferation Assay for Bioactive Human Interleukin-
3
The factor-dependent cell line AML 193 was obtained
from the American Type Culture Collection (ATCC,
Rockville, MD). This cell line, established from a
patient with acute myelogenous leukemia, is a growth
factor dependent cell line which displayed enhanced
growth in GM-CSF supplemented medium (Lange, B., et al.,
Blood 70: 192, 1987; Valtieri, M., et al., J. Immunol.
138:4042, 1987). The ability of AML 193 cells to
proliferate in the presence of human IL-3 has also been
documented. (Santoli, D., et al., J. Intmunol. 139: 348,
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1987). A cell line variant was used, AML 193 1.3, which
was adapted for long term growth in IL-3 by washing out
the growth factors and starving the cytokine dependent
AML 193 cells for growth factors for 24 hours. The
cells are then replated at 1x105 cells/well in a 24 well
plate in media containing 100 U/mL IL-3. It took
approximately 2 months for the cells to grow rapidly in
IL-3. These cells are maintained as AML 193 1.3
thereafter by supplementing tissue culture medium (see
below) with human IL-3.
AML 193 1.3 cells are washed 6 times in cold Hanks
balanced salt solution (HBSS, Gibco, Grand Island, NY)
by centrifuging cell suspensions at 250 x g for 10
minutes followed by decantation of the supernatant.
Pelleted cells are resuspended in HBSS and the procedure
is repeated until six wash cycles are completed. Cells
washed six times by this procedure are resuspended in
tissue culture medium at a density ranging from 2 x 10s
5
to 5 x 10 viable cells/mL. This medium is prepared by
supplementing Iscove's modified Dulbecco's Medium (IMDM,
Hazelton, Lenexa, KS) with albumin, transferrin, lipids
and 2-mercaptoethanol. Bovine albumin (Boehringer-
Mannheim, Indianapolis, IN) is added at 500 ug/mL; human
transferrin (Boehringer-Mannheim, Indianapolis, IN) is
added at 100 ug/mL; soybean lipid (Boehringer-Mannheim,
Indianapolis, IN) is added at 50 ug/mL; and 2-
mercaptoethanol (Sigma, St. Louis, MO) is added at 5 x
-s
10 M.
Serial dilutions of human interleukin-3 or multi-
functional chimeric hematopoietic receptor agonist
proteins are made in triplicate series in tissue culture
medium supplemented as stated above in 96 well Costar
3596 tissue culture plates. Each well contained 50 ul
of medium containing interleukin-3 or mufti-functional
chimeric hematopoietic receptor agonist proteins once
serial dilutions are completed. Control wells contained
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8~
tissue culture medium alone (negative control). AML 193
1.3 cell suspensions prepared as above are added to each
well by pipetting 50 ~1 (2.5 x 104 cells) into each
well. Tissue culture plates are incubated at 37°C with
5o COz in humidified air for 3 days. On day 3, 0.5 uCi
'H-thymidine (2 Ci/mM, New England Nuclear, Boston, MA)
is added in 50 ul of tissue culture medium. Cultures
are incubated at 37°C with 5% COz in humidified air for
18-24 hours. Cellular DNA is harvested onto glass
filter mats (Pharmacia LKB, Gaithersburg, MD) using a
TOMTEC cell harvester (TOMTEC, Orange, CT) which
utilized a water wash cycle followed by a 70o ethanol
wash cycle. Filter mats are allowed to air dry and then
placed into sample bags to which scintillation fluid
(Scintiverse II, Fisher Scientific, St. Louis, MO or
BetaPlate Scintillation Fluid, Pharmacia LKB,
Gaithersburg, MD) is added. Beta emissions of samples
from individual tissue culture wells are counted in a
LKB BetaPlate model 1205 scintillation counter
(Pharmacia LKB, Gaithersburg, MD) and data is expressed
as counts per minute of 'H-thymidine incorporated into
cells from each tissue culture well. Activity of each
human interleukin-3 preparation or multi-functional
chimeric hematopoietic receptor agonist protein
preparation is quantitated by measuring cell
proliferation ('H-thymidine incorporation) induced by
graded concentrations of interleukin-3 or multi-
functional chimeric hematopoietic receptor agonist.
5
Typically, concentration ranges from 0.05 pM - 10 pM
are quantitated in these assays. Activity is determined
by measuring the dose of interleukin-3 or multi-
functional chimeric hematopoietic receptor agonist
protein which provides 500 of maximal proliferation (ECso
- 0.5 x (maximum average counts per minute of 'H-
thymidine incorporated per well among triplicate
cultures of all concentrations of interleukin-3 tested -
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83
background proliferation measured by 'H-thymidine
incorporation observed in triplicate cultures lacking
interleukin-3). This ECso value is also equivalent to 1
unit of bioactivity. Every assay is performed with
native interleukin-3 as a reference standard so that
relative activity levels could be assigned.
Typically, the multi-functional chimeric
hematopoietic receptor agonist proteins were tested in a
concentration range of 2000 pM to 0.06 pM titrated in
serial 2 fold dilutions.
Activity for each sample was determined by the
concentration which gave 50°s of the maximal response by
fitting a four-parameter logistic model to the data. It
was observed that the upper plateau (maximal response)
for the sample and the standard with which it was
compared did not differ. Therefore relative potency
calculation for each sample was determined from EC50
estimations for the sample and the standard as
indicated above. AML 193.1.3 cells proliferate in
response to hIL-3, hGM-CSF and hG-CSF. Therefore the
following additional assays were performed for some
samples to demonstrate that the G-CSF receptor agonist
portion of the multi-functional chimeric hematopoietic
receptor agonist proteins was active. The proliferation
assay was performed with the multi-functional chimeric
hematopoietic receptor agonist plus and minus
neutralizing monoclonal antibodies to the hIL-3 receptor
agonist portion. In addition, a fusion molecule with the
factor Xa cleavage site was cleaved then purified and
the halves of the molecule were assayed for
proliferative activity. These experiments showed that
both components of the multi-functional chimeric
hematopoietic receptor agonist proteins were active.
TF1 c-mpl liaand dependent proliferation assay
The c-mpl ligand proliferative activity can be
assayed using a subclone of the pluripotential human
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cell line TF1 (Kitamura et al., J. Cell Physiol 140:323-
334. [1989]). TF1 cells are maintained in h-IL3 (100
U/mL). To establish a sub-clone responsive to c-mpl
ligand, cells are maintained in passage media containing
10~ supernatant from BHK cells transfected with the gene
expressing the 1-153 form of c-mpl ligand {pMON26448).
Most of the cells die, but a subset of cells survive.
After dilution cloning, a c-mpl ligand responsive clone
is selected, and these cells are split into passage
media to a density of 0.3 x 106 cells/mL the day prior
to assay set-up. Passage media for these cells is the
following: RPMI 1640 (Gibco), 10o FBS (Harlan, Lot
#91206), 10% c-mpl ligand supernatant from transfected
BHK cells, 1 mM sodium pyruvate {Gibco), 2 mM glutamine
(Gibco), and 100 ug/mL penicillin-streptomycin (Gibco).
The next day, cells are harvested and washed twice in
RPMI or IMDM media with a final wash in the ATL, or
assay media. ATL medium consists of the following: IMDM
(Gibco), 500 ug/mL of bovine serum albumin, 100 ug/mL of
human transferrin, 50 ug/mL soybean lipids, 4 x 10-8M
beta-mercaptoethanol and 2 mL of A9909 (Sigma,
antibiotic solution) per 1000 mL of ATL. Cells are
diluted in assay media to a final density of 0.25 x 106
cells/mL in a 96-well low evaporation plate {Costar) to
a final volume of 50 ul. Transient supernatants
(conditioned media) from transfected clones are added at
a volume of 50 ul as duplicate samples at a final
concentration of 50~ and diluted three-fold to a final
dilution of 1.80. Triplicate samples of a dose curve of
IL-3 variant pMON13288 starting at 1 ng/mL and diluted
using three-fold dilutions to 0.0014ng/mL is included as
a positive control. Plates are incubated at 5~ COz and
37° C. At day six of culture, the plate is pulsed with
0.5 Ci of 3H/well (NEN) in a volume of 20 ul/well and
allowed to incubate at 5o COz and 37° C for four hours.
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The plate is harvested and counted on a Betaplate
counter.
MUTZ-2 Cell Proliferation Assay
A cell line such as MUTZ-2, which is a human myeloid
leukemia cell line (German Collection of Microorganisms
and Cell Cultures, DSM ACC 271), can be used to
determine the cell proliferative activity of flt3
receptor agonists. MUTZ-2 cultures are maintained with
recombinant native flt3 ligand (20-100ng/mL) in the
growth medium. Eighteen hours prior to assay set-up,
MUTZ-2 cells are washed in IMDM medium (Gibco) three
times and are resuspended in IMDM medium alone at a
concentration of 0.5-0.7 x 10E6 cells/mL and incubated
at 37°C and 5~C02 to starve the cells of flt3 ligand.
The day of the assay, standards and flt3 receptor
agonists are diluted to two fold above desired final
concentration in assay media in sterile tissue culture
treated 96 well plates. Flt3 receptor agonists and
standards are tested in triplicate. 50u1 of assay media
is loaded into all wells except row A. 75u1 of the flt3
receptor agonists or standards are added to row A and
25u1 taken from that row and serial dilutions (1:3)
performed on the rest of the plate (rows B through G).
Row H remains as a media only control. The starved
MUTZ-2 cells are washed two times in IMDM medium and
resuspended in 50u1 assay media. 50u1 of cells are
added to each well resulting in a final concentration of
0.25 x 10E6cells/mL. Assay plates containing cells are
incubated at 37°C and 5~C02 for 44hrs. Each well is
then pulsed with luCi/well of tritiated thymidine in a
volume of 20u1 for four hours. Plates are then
harvested and counted.
Other in vitro cell based proliferation assays
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gw
Other in vitro cell based assays, known to those
skilled in the art, may also be useful to determine the
activity of the multi-functional chimeric hematopoietic
receptor agonists depending on the factors that comprise
the molecule in a similar manner as described in the AML
193.1.3 cell proliferation assay. The following are
examples of other useful assays.
TF1 proliferation assay: TF1 is a pluripotential human
cell line (Kitamura et al., J. Cell Physiol 140:323-334.
[1989]) that responds to hIL-3.
32D proliferation assay: 32D is a murine IL-3 dependent
cell line which does not respond to human IL-3 but does
respond to human G-CSF which is not species restricted.
Baf/3 proliferation assay: Baf/3 is a murine IL-3
dependent cell line which does not respond to human IL-3
or human c-mpl ligand but does respond to human G-CSF
which is not species restricted.
T1165 proliferation assay: T1165 cells are a IL-6
dependent murine cell line (Nordan et al., 1986) which
respond to IL-6 and IL-11.
Human Plasma Clot meg-CSF Assay: Used to assay
megakaryocyte colony formation activity (Mazur et al.,
1981).
Transfected cell lines:
Cell lines such as the murine Baf/3 cell line can
be transfected with a colony stimulating factor
receptor, such as the human G-CSF receptor or human c-
mpl receptor, which the cell line does not have. These
transfected cell lines can be used to determine the
activity of the ligand for which the receptor has been
transfected into the cell line.
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g7
One such transfected Baf/3 cell line was made
by cloning the cDNA encoding c-mpl from a library made
from a c-mpl responsive cell line and cloned into the
multiple cloning site of the plasmid pcDNA3 (Invitrogen,
San Diego Ca.). Baf/3 cells were transfected with the
plasmid via electroporation. The cells were grown under
6418 selection in the presence of mouse IL-3 in Wehi
conditioned media. Clones were established through
limited dilution.
In a similar manner the human G-CSF receptor can be
transfected into the Baf/3 cell line and used to
determine the bioactivity of the multi-functional
chimeric hematopoietic receptor agonists.
Analvsis of c-mpl liaand proliferative activity
Methods
1. Bone marrow proliferation assay
a. CD34+ Cell Purification:
Bone marrow aspirates (15-20 mL) were obtained from
normal allogeneic marrow donors after informed consent.
Cells were diluted 1:3 in phosphate buffered saline
(PBS, Gibco-BRL), 30 mL were layered over 15 mL
Histopaque-1077 (Sigma) and centrifuged for 30 minutes
at 300 RCF. The mononuclear interface layer was
collected and washed in PBS. CD34+ cells were enriched
from the mononuclear cell preparation using an affinity
column per manufacturers instructions (CellPro, Inc.,
Bothell WA). After enrichment, the purity of CD34+
cells was 70~ on average as determined by using flow
cytometric analysis using anti-CD34 monoclonal antibody
conjugated to fluorescein and anti-CD38 conjugated to
phycoerythrin (Becton Dickinson, San Jose CA).
Cells were resuspended at 40,000 cells/mL in X-vivo
10 media (Bio-Whittaker, Walkersville, MD) and 1 mL was
plated in 12-well tissue culture plates (Costar). The
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growth factor rhlL-3 was added at 100 ng/mL (pMON5873)
was added to some wells. hIL3 variants were used at 10
ng/mL to 100 ng/mL. Conditioned media from BHK cells
transfected with plasmid encoding c-mpl ligand or multi-
functional chimeric hematopoietic receptor agonists were
tested by addition of 100 jtl of supernatant added to 1
mL cultures (approximately a 10% dilution). Cells were
incubated at 37°C for 8-14 days at 5% COZ in a 37°C
humidified incubator.
b. Cell Harvest and Analysis:
At the end of the culture period a total cell count
was obtained for each condition. For fluorescence
analysis and ploidy determination cells were washed in
megakaryocyte buffer (MK buffer, 13.6 mM sodium citrate,
1 mM theophylline, 2.2 um PGE1, 11 mM glucose, 3% w/v
BSA, in PBS, pH 7.4,) (Tourer et al., Blood 70: 1735-
1742, 1987) resuspended in 500 ul of MK buffer
containing anti-CD4la FITC antibody (1:200, AMAC,
Westbrook, ME) and washed in MK buffer. For DNA
analysis cells were permeablized in MK buffer containing
0.5% Tween 20 (Fisher, Fair Lawn NJ)for 20 min. on ice
followed by fixation in 0.5% Tween-20 and 1%
paraformaldehyde (Fisher Chemical) for 30 minutes
followed by incubation in propidium iodide (Calbiochem ,
La Jolla Ca) (50 ug/mL) with RNA-ase (400 U/mL) in 55%
v/v MK buffer (200mOsm) for 1-2 hours on ice. Cells
were analyzed on a FACScan or Vantage flow cytometer
(Becton Dickinson, San Jose, CA). Green fluorescence
(CD4la-FITC) was collected along with linear and log
signals for red fluorescence (PI) to determine DNA
ploidy. All cells were collected to determine the
percent of cells that were CD41+, Data analysis was
performed using software by LYSIS (Becton Dickinson, San
Jose, CA). Percent of cells expressing the CD41 antigen
was obtained from flow cytometry analysis(Percent).
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~g
Absolute (Abs) number of CD41+ cells/mL was calculated
by: (Abs)=(Cell Count}*(Percent)/100.
2. Megakaryocyte fibrin clot assay.
CD34+ enriched population were isolated as described
above. Cells were suspended at 25,000 cells/mL with or
without cytokine(s) in a media consisting of a base
Iscoves IMDM media supplemented with 0.3~ BSA, 0.4mg/mL
apo-transferrin, 6.67~zM FeClz, 25ug/mL CaClz, 25ug/mL L-
asparagine, 500ug/mL e-amino-n-caproic acid and
penicillin/streptomycin. Prior to plating into 35mm
plates, thrombin was added (0.25 Units/mL) to initiate
clot formation. Cells were incubated at 37°C for 13
days at 5% COZ in a 37°C humidified incubator.
At the end of the culture period plates were fixed with
methanol: acetone (1:3), air dried and stored at -200C
until staining. A peroxidase immunocytochemistry
staining procedure was used (Zymed, Histostain-SP. San
Francisco, CA) using a cocktail of primary monoclonal
antibodies consisting of anti-CD4la, CD42 and CD61.
Colonies were counted after staining and classified as
negative, CFU-MK (small colonies, 1-2 foci and less that
approx. 25 cells), BFU-MK (large, multi-foci colonies
with > 25 cells) or mixed colonies (mixture of both
positive and negative cells.
Methylcellulose Assav
This assay reflects the ability of colony stimulating
factors to stimulate normal bone marrow cells to produce
different types of hematopoietic colonies in vitro
(Bradley et al., Aust. Exp Bzol. Sci. 44:287-300,
1966), Pluznik et al., J. Cell Comp. Physio 66:319-324,
1965).
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Methods 90
Approximately 30 mL of fresh, normal, healthy bone
marrow aspirate are obtained from individuals following
informed consent. Under sterile conditions samples are
diluted 1:5 with a 1X PBS (#14040.059 Life Technologies,
Gaithersburg, MD.) solution in a 50 mL conical tube
(#25339-50 Corning, Corning MD). Ficoll (Histopaque
1077 Sigma H-8889) is layered under the diluted sample
and centrifuged, 300 x g for 30 min. The mononuclear
cell band is removed and washed two times in 1X PBS and
once with 1% BSA PBS (CellPro Co., Bothel, WA).
Mononuclear cells are counted and CD34+ cells are
selected using the Ceprate LC (CD34) Kit (CellPro Co.,
Bothel, WA) column. This fractionation is performed
since all stem and progenitor cells within the bone
marrow display CD34 surface antigen.
Cultures are set up in triplicate with a final volume of
1.0 mL in a 35 X 10 mm petri dish (Nunc#174926).
Culture medium is purchased from Terry Fox Labs. (HCC-
4230 medium (Terry Fox Labs, Vancouver, B.C., Canada)
and erythropoietin (Amgen, Thousand Oaks, CA.) is added
to the culture media. 3,000-10,000 CD34+ cells are
added per dish. Recombinant IL-3, purified from
mammalian cells or E. coli, and mufti-functional
chimeric hematopoietic receptor agonist proteins, in
conditioned media from transfected mammalian cells or
purified from conditioned media from transfected
mammalian cells or E. coli, are added to give final
concentrations ranging from .001 nM to 10 nM.
Recombinant hIL-3, GM-CSF, c-mpl ligand and multi-
functional chimeric hematopoietic receptor agonist are
supplied in house. G-CSF (Neupogen) is from Amgen
(Thousand Oaks Calf.). Cultures are resuspended using a
3cc syringe and 1.0 mL is dispensed per dish. Control
(baseline response) cultures received no colony
stimulating factors. Positive control cultures received
conditioned media (PHA stimulated human cells: Terry Fox
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~1
Lab. H2400). Cultures are incubated at 37°C, 5% COz in
humidified air.
Hematopoietic colonies which are defined as greater than
50 cells are counted on the day of peak response (days
10-11) using a Nikon inverted phase microscope with a
40x objective combination. Groups of cells containing
fewer than 50 cells are referred to as clusters.
Alternatively colonies can be identified by spreading
the colonies on a slide and stained or they can be
picked, resuspended and spun onto cytospin slides for
staining.
Human Cord Blood Hemopoietic Growth Factor Assays
Bone marrow cells are traditionally used for in vitro
assays of hematopoietic colony stimulating factor (CSF)
activity. However, human bone marrow is not always
available, and there is considerable variability between
donors. Umbilical cord blood is comparable to bone
marrow as a source of hematopoietic stem cells and
progenitors (Broxmeyer et al., PNAS USA 89:4109-113,
1992; Mayani et al., Blood 81:3252-3258, 1993). In
contrast to bone marrow, cord blood is more readily
available on a regular basis. There is also a potential
to reduce assay variability by pooling cells obtained
fresh from several donors, or to create a bank of
cryopreserved cells for this purpose. By modifying the
culture conditions, and/or analyzing for lineage
specific markers, it is be possible to assay
specifically for granulocyte / macrophage colonies (CFU-
GM), for megakaryocyte CSF activity, or for high
proliferative potential colony forming cell (HPP-CFC)
activity.
Methods
Mononuclear .cells (MNC) are isolated from cord blood
within 24 hr. of collection, using a standard density
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gradient (1.077 g/mL Histopaque). Cord blood MNC have
been further enriched for stem cells and progenitors by
several procedures, including immunomagnetic selection
for CD14-, CD34+ cells; panning for SBA-, CD34+
fraction using coated flasks from Applied Immune Science
(Santa Clara, CA); and CD34+ selection using a CellPro
(Bothell, WA) avidin column. Either freshly isolated or
cryopreserved CD34+ cell enriched fractions are used for
the assay. Duplicate cultures for each serial dilution
of sample (concentration range from 1 pM to 1204 pM) are
prepared with 1x104 cells in 1ml of 0.9% methylcellulose
containing medium without additional growth factors
(Methocult H4230 from Stem Cell Technologies, Vancouver,
BC.). In some experiments, Methocult H4330 containing
erythropoietin (EPO) was used instead of Methocult
H4230, or Stem Cell Factor (SCF), 50 ng/mL (Biosource
International, Camarillo, CA) was added. After culturing
for 7-9 days, colonies containing >30 cells are counted.
In order to rule out subjective bias in scoring, assays
are scored blind.
Additional details about recombinant DNA methods
which may be used to create the variants, express them
in bacteria, mammalian cells or insect cells,
purification and refold of the desired proteins and
assays for determining the bioactvity of the proteins
may be found in co-filed Applications WO 95/00646, WO
94/12639, WO 94/12638, wo 95/20976, wo 95/21197, wo
95/20977, WO 95/21254 and US 08/383,035 which are hereby
incorporated by reference in their entirety.
Further details known to those skilled in the art
may be found in T. Maniatis, et al., Molecular Cloninor
A Laboratory Manual, Cold Spring Harbor Laboratory,
1982) and references cited therein, incorporated herein
by reference; and in J. Sambrook, et al., Molecular
Cloning, A Laboratory Manual, 2nd edition, Cold Spring
Harbor Laboratory, 1989) and references. cited therein,
incorporated herein by reference.
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93
TABLE 1
OLIGONUCLEOTIDES
S c-mplNcoI ACGTCCATGGCNTCNCCNGCNCCNCCTGCTTGTGCACTCCGAGTC
SEQ ID N0:317
N=A,C,G
or T
Ecompl ATGCACGAATTCCCTGACGCAGAGGGTGGA SEQ ID N0:318
10c-mplHindIIITGACAAGCTTACCTGACGCAGAGGGTGGACCCT SEQ ID
N0:319
4L-5' AATTCGGCAA SEQ ID N0:320
4L-3' CATGTTGCCG SEQ ID N0:321
1S
5L-5' AATTCGGCGGCAA SEQ ID N0:322
5L-3' CATGTTGCCGCCG SEQ ID N0:323
208L-5' AATTCGGCGGCAACGGCGGCAA SEQ ID N0:324
8L-3' CATGTTGCCGCCGTTGCCGCCG SEQ ID N0:325
31-5' CGATCCATGGAGGTTCACCCTTTGCCT SEQ ID N0:326
2S
31-3' GATCAAGCTTATGGGCACTGGCTCAGTCT SEQ ID N0:327
35-5' CGATACATGTTGCCTACACCTGTCCTG SEQ ID N0:328
3035-3' GATCAAGCTTAAGGGTGAACCTCTGGGCA SEQ ID N0:329
39-5' CGATCCATGGTCCTGCTGCCTGCTGTG SEQ ID N0:330
39-3' GATCAAGCTTAAGGTGTAGGCAAAGGGTG SEQ ID N0:331
35
43-5' CGATCCATGGCTGTGGACTTTAGCTTGGGA SEQ ID N0:332
43-3' GATCAAGCTTAAGGCAGCAGGACAGGTGT SEQ ID N0:333
4045-5' CGATCCATGGACTTTAGCTTGGGAGAA SEQ ID N0:334
45-3' GATCAAGCTTACACAGCAGGCAGCAGGAC SEQ ID N0:335
49-5' CGATCCATGGGAGAATGGAAAACCCAG SEQ ID N0:336
4S
49-3' GATCAAGCTTACAAGCTAAAGTCCACAGC SEQ ID N0:337
82-5' CGATCCATGGGACCCACTTGCCTCTCA SEQ ID N0:338
SO82-3' GATCAAGCTTACAGTTGTCCCCGTGCTGC SEQ ID N0:339
109-5' CAGTCCATGGGAACCCAGCTTCCTCCA SEQ ID N0:340
109-3' GATCAAGCTTAAAGGAGGCTCTGCAGGGC SEQ ID N0:341
SS
116-5' CGATCCATGGGCAGGACCACAGCTCAC SEQ ID N0:342
116-3' GATCAAGCTTACTGTGGAGGAAGCTGGGTT SEQ ID N0:343
6O120-5' CGATCCATGGCTCACAAGGATCCCAATGCC SEQ ID N0:344
120-3' GATCAAGCTTATGTGGTCCTGCCCTGTGG SEQ ID N0:345
123-5' CGATCCATGGATCCCAATGCCATCTTCCTG SEQ ID N0:346
6S
123-3' GATCAAGCTTACTTGTGAGCTGTGGTCCT SEQ ID N0:347
126-5' CGATCCATGGCCATCTTCCTGAGCTTCCAA SEQ ID N0:348
7O126-3' GATCAAGCTTAATTGGGATCCTTGTGAGCTGT SEQ ID N0:349
SYNNOXA1.REQAATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA
GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC
TCC SEQ ID N0:350
7S
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9~
SYNNOXA2.REQ CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG
CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA
CGG SEQ ID N0:351
Llsyn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT
CTAACTGCTC TATAATGAT SEQ ID N0:352
Llsyn.rev CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC
CTGCGCTTGC TCAAGG SEQ ID N0:353
L3syn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT
CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT GAT
SEQ ID No:354
L3syn.rev CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC
GCCAGAGCCA CCACCCTGTT GTTCCTGCGC TTGCTCAAGG SEQ ID N0:355
35start.seq GATCGACCAT GGCTCTGGAC CCGAACAACC TC SEQ ID N0:356
39rev.seq CTCGATTACG TACAAAGGTG CAGGTGGT SEQ ID N0:357
70start.seq GATCGACCAT GGCTAATGCA TCAGGTATTG AG SEQ ID N0:358
69rev.seq CTCGATTACG TATTCTAAGT TCTTGACA SEQ ID N0:359
9lstart.seq GATCGACCAT GGCTGCACCC TCTCGACATC CA SEQ ID N0:360
90rev.seq CTCGATTACG TAGGCCGTGG CAGAGGGC SEQ ID N0:361
101start.seq GATCGACCAT GGCTGCAGGT GACTGGCAAG AA SEQ ID N0:362
100rev.seq CTCGATTACG TACTTGATGA TGATTGGA SEQ ID N0:363
L-llstart.seq GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG
CTGCGCAAGG TGGCGTAGAA CGCG SEQ ID N0:364
L-llstop.seq CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG
AGCTTCCTGC TCAAGTCTTT AGAG SEQ ID N0:365
P-blstart.seq GGGCTGCGCA AGGTGGCG SEQ ID N0:366
P-blstop.seq ACACCATTGG GCCCTGCCAG C SEQ ID N0:367
39start.seq GATCGACCAT GGCTTACAAG CTGTGCCACC CC SEQ ID N0:368
38stop.Seq CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT SEQ ID N0:369
97start.seq GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC SEQ ID N0:370
96stop.Seq CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT SEQ ID N0:371
126start.seq GATCGACCAT GGCTATGGCC CCTGCCCTGC AG SEQ ID N0:372
125stop.Seq CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT SEQ ID N0:373
133start.seq GATCGACCAT GGCTACCCAG GGTGCCATGC CG SEQ ID N0:374
132stop.seq CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA SEQ ID N0:375
142start.seq GATCGACCAT GGCTTCTGCT TTCCAGCGCC GG SEQ ID N0:376
141stop.Seq CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC SEQ ID N0:377
GLYXA1 GTAGAGGGCG GTGGAGGCTC C SEQ ID N0:378
GLYXA2 CCGGGGAGCC TCCACCGCCC TCTAC SEQ ID N0:379
~1GGGSfor TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT
GTCTACACCA TTG SEQ ID N0:380
1GGGSrev CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA
AGGTGGCGTA GAA SEQ ID N0:381
NCOFLT CTGACCATGGCNACCCAGGACTGCTCCTTCCAA SEQ ID N0:807
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98/17810
HIND160 ACTGAAGCTTAGGGCTGACACTGCAGCTCCAG SEQ ID NO:B08
HIND165 ACTGAAGCTTACAGGGTTGAGGAGTCGGGCTG SEQ ID N0:809
FL23For GACTGCCATGGCNACYCAGGAYTGYTCYTTYCAACACAGCCCCATC
SEQ ID NO:810
FH3AFor GACTGCCATGGCNACYCAGGAYTGYTCYTTYCAACACAGCCCCATC
SEQ ID NO:811
SCF.REV TGTCCARACTCATCAATGTATC SEQ ID NO:B12
39FOR CATGGCCATGGCCGACGAGGAGCTCTGCGGGGGCCTCT SEQ
ID N0:813
39REV GCTAGAAGCTTACTGCAGGTTGGAGGCCACGGTGAC SEQ ID
N0:814
65FOR CATGGCCATGGCCTCCAAGATGCAAGGCTTGCTGGAGC SEQ
ID N0:815
65REV GCTAGAAGCTTACCCAGCGACAGTCTTGAGCCGCTC SEQ ID
N0:816
89FOR CATGGCCATGGCCCCCCCCAGCTGTCTTCGCTTCGT SEQ ID
N0:817
89REV GCTAGAAGCTTAGGGCTGAAAGGCACATTTGGTGACA SEQ ID
N0:818
L5A CCCTGTCTGGCGGCAACGGCACCCAGGACTGCTCCTTCCAAC
SEQ ID N0:819
L10A GCGGTAACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTTCCAAC
SEQ ID
N0:820
L15A ACGGCAGTGGTGGCAATGGGAGCGGCGGAAATGGAACCCAGGACT
GCTCCTTCCAAC SEQ ID N0:821
L5B GTGCCGTTGCCGCCAGACAGGGTTGAGGAGTCGGGCTG SEQ
ID N0:822
L10B ATTACCTCCACTGCCGTTACCGCCTGACAGGGTTGAGGAGTCGGG
CTG SEQ ID
No:823
L15B GCTCCCATTGCCACCACTGCCGTTACCTCCAGACAGGGTTGAGGA
GTCGGGCTG SEQ ID N0:824
L15C GATGAGGATCCGGTGGCAATGGGAGCGGCGGAAATGGAACCCAGG
ACTGCTCCTTCCACC SEQ ID N0:825
L15D GATGACGGATCCGTTACCTCCAGACAGGGTTGAGGAGTCGGGCTG
SEQ ID N0:826
L15E GATGACGGATCCGGAGGTAATGGCACCCAGGACTGCTCCTTCCAAC
SEQ ID N0:827
339FOR2 GACTGCCATGGCCGACGAGGAGCTCTGCG SEQ ID N0:828
339REV2 GACTCAAGCTTACTGCAGGTTGGAGGCC SEQ ID N0:829
339-lOFOR3GACTCGGGATCCGGAGGTTCTGGCACCCAGGACTGCTCC SEQ
ID N0:830
339-15FOR2GACTGGGATCCGGTGGCAGTGGGAGCGGCGGATCTGGAACC SEQ
ID N0:831
339REV3 GACTTGGGATCCACTACCTCCAGACAGGGTTGAGGA GTC SEQ
ID N0:832
FLN3 ACTGACGGATCCACCGCCCAGGGTTGAGGAGTCGGGCTG SEQ
ID N0:833
FLN7 ACTGACGGATCCACCTCCTGACCCACCGCCCAGGGTTGAGGAGTCGGGCTG
SEQ ID
N0:834
FLN11 ACTGACGGATCCACCTCCTGACCCACCTCCTGACCCACCGCCCAG
GGTTGAGGAGTCGGGCTG SEQ ID N0:835
C-term ACGTAAAGCTTACAGGGTTGAGGAGTCG SEQ ID N0:836
FLC3 GTCAGTGGATCCGGAGGTACCCAGGACTGCTCCTTCCAA C SEQ
ID N0:837
FLC4 GTCAGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAAC
SEQ ID N0:838
FLC10 TCAGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAAC
SEQ ID N0:839
N-term TAGTCCATGGCCACCCAGGACTGCTCC SEQ ID N0:840
134.rev GCATTACGTAGGGCTGACACTGCAGCTCCAG SEQ ID N0:841
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96
139.rev GCATTACGTACAGGGTTGAGGAGTCGGGCTG SEQ ID
N0:842
F129for GTCAGACCATGGCCGATTACCCAGTCACCGTGGCCTC SEQ
ID N0:843;
FL29rev TCTGACAAGCTTATTGAAGCAGGTAGTCAGACAGCTCAC
SEQ ID N0:844;
FL35for GTCAGCCCATGGCCGCCTCCAACCTGCAGGACGAGGA SEQ
ID N0:845;
FL35rev TCTGACAAGCTTACACGGTGACTGGGTAACTTGAAGC SEQ
ID N0:846;
FL63for GTCAGACCATGGCCGTCGCTGGGTCCAAGATGCAAGGC
SEQ ID N0:847;
FL63rev TCTGACAAGCTTAAGTCTTGAGCCGCTCCATCCAGCG SEQ
ID N0:848;
FL95for GTCAGACCATGGCCCGCTTCGTCCAGACCAACATCTCC
SEQ ID N0:849;
FL95rev TCTGACAAGCTTAAAGACAGCTGGGGGGGGGCTGAA SEQ
ID N0:850;
FL99for GTCAGACCATGGCCACCAACATCTCCCGCCTCCTGCAG
SEQ ID N0:851;
FL99rev CTCGACAAGCTTACTGGACGAAGCGAAGACAGCTGGG SEQ
ID N0:852;
FLTAFLS1 GATCACATGTCTACAAATCAAGATCTGCCTGTG SEQ ID
N0:853
2S
FLTR1N GATCGAATTCGTTGTCTTGGATGAAAGGGA SEQ ID N0:854
HGCFOR ACTTGAATTCATCATCCTGGGCCTGTTCGGGC SEQ ID
N0:855
HGCREV ACTCAAGCTTAGAAGCTCCCCAGCGCCTCC SEQ ID N0:856
FL29FOR GTCAGACCATGGCCGATTACCCAGTCACCGTGGCCTC SEQ
ID N0:382
FL35FOR GTCAGCCCATGGCCGCCTCCAACCTGCAGGACGAGGA SEQ ID N0:383
FL63FOR GTCAGACCATGGCCGTCGCTGGGTCCAAGATGCAAGGC SEQ ID No:384
FL95FOR GTCAGACCATGGCCCGCTTCGTCCAGACCAACATCTCC SEQ ID N0:385
FL99FOR GTCAGACCATGGCCACCAACATCTCCCGCCTCCTGCAG SEQ ID N0:3B6
FL29REV TCTGACAAGCTTATTGAAGCAGGTAGTCAGACAGCTCAC SEQ ID
N0:387
FL35REV TCTGACAAGCTTACACGGTGACTGGGTAATCTTGAAGC SEQ ID N0:388
FL63REV TCTGACAAGCTTAAGTCTTGAGCCGCTCCATCCAGCG SEQ ID N0:389
89 REVSTOP GTCAAGAAGCTTACGGCTGAAAGGCACATTTG SEQ ID No:390
FL95REV TCTGACAAGCTTAAAGACAGCTGGGGGGGGGCTGAA SEQ ID N0:391
FL99REV CTCGACAAGCTTACTGGACGAAGCGAAGACAGCTGGG SEQ ID N0:392
F1t36 GTTGCCATGGCNTCNAAYCTGCARGAYGARGARCTGT
GCGGGGGCCTCTGGCGGCTG SEQ ID No:393
F1t37 GTTGCCATGGCNAAYCTGCARGAYGARGARCTGTGYG
GGGGCCTCTGGCGGCTGGTC SEQ ID No:394
F1t38 GTTGCCATGGCNCTGCARGAYGARGARCTGTGYGGYG
GCCTCTGGCGGCTGGTCCTG SEQ ID N0:395
F1t39 GTTGCCATGGCNCARGAYGARGARCTGTGYGGYGGYC
CA 02268742 1999-04-19
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TCTGGCGGCTGGTCCTGGCA SEQ ID No:396
F1t40 GTTGCCATGGCNGAYGARGARCTGTGYGGYGGYCTCT
GGCGGCTGGTCCTGGCACAG SEQ ID N0:397
F1t41 GTTGCCATGGCNGARGARCTGTGYGGYGGYCTCTGGC
GGCTGGTCCTGGCACAGCGC SEQ ID No:398
F1t42 GTTGCCATGGCNGARCTGTGYGGYGGYCTGTGGCGYC
TGGTCCTGGCACAGCGCTGG SEQ ID N0:399
F1t43 GTTGCCATGGCNCTGTGYGGYGGYCTGTGGCGYCTGG
TCCTGGCACAGCGCTGGATG SEQ ID N0:400
40 COLI GTTGCCATGGCWGATGAAGAACTGTGTGGNGGNCTGTGGCGG
SEQ
ID N0:401
36REV TATGCAAGCTTAGGCCACGGTGACTGGGTA SEQ ID N0:402
37REV TATGCAAGCTTAGGAGGCCACGGTGACTGG SEQ ID No:403
38REV TATGCAAGCTTAGTTGGAGGCCACGGTGAC SEQ ID No:404
39REV TATGCAAGCTTACAGGTTGGAGGCCACGGT SEQ ID N0:405
41REV TATGCAAGCTTAGTCCAGGTTGGAGGCCAC SEQ ID No:406
42REV TATGCAAGCTTACTCGTCCAGGTTGGAGGC SEQ ID N0:407
43REV TATGCAAGCTTACTCCTCGTCCAGGTTGGA SEQ ID No:408
39N TERM-2 GACTAGCCATGGCNGAYGARGARCTGTGYGGTGGCCTCTGGCGG SEQ
ID No:409
SNA B1CTERM GACTAGTACGTACTGCAGGTTGGAGGCCACGG SEQ ID N0:410
29SMB1 GCAGGTTACGTATTGAAGCAGGTAGTCAGACAGCTC SEQ ID
N0:411
34SNAB1 GCAGGTTACGTACACGGTGACTGGGTAATCTTGAAG SEQ ID
N0:412
63SNAB1 GCAGGTTACGTAAGTCTTGAGCCGCTCCATCCAGC SEQ ID N0:413
66SNAB1 GCAGGTTACGTAGCCAGCGACAGTCTTGAGCCGCTC SEQ ID
No:414
CA 02268742 1999-04-19
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89N-TERMCSLI GTCAAGCCATGGCNCCRCCRAGCTGTCTRCGCT
TCGTTCAGACCAACTC SEQ ID N0:415
89SNAB1 GCAGGTTACGTACGGCTGAAAGGCACATTTGGTGACAA SEQ ID
No:416
945 SMB1 GCAGGTTACGTAAAGACAGCTGGGGGGGGG SEQ ID N0:417
98SUAB1 GCAGGTTACGTACTGGACGAAGCGAAGACAGCTG SEQ
ID No:418
BAM FOR 1 TCAGTTGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTA
SEQ ID N0:426
BAM REV TCAGTTGGATCCTCCGCCAGAACCACCGCCTGACCCACCTCCTGACCC
1
SEQ ID N0:427
NAVREV L GTCTGAGGCGCCACCGCACCGACCGCTGGACAACCGCCTCTGACCC
AGGACTGCTCCTTC SEQ ID N0:428
NAVREV S GTCTGAGGCGCCACCGCACCGACCACCCAGGACTGCTCCTTCCAAC
SEQ ID N0:429
NAVFOR GTCTGAGGCGCCGAGTGGACGCGGGCTCCACGGTGGCGGCAGGGT
TGAGGAGTCGGGCTG SEQ ID N0:430
XBAFOR1 GCTACGTCTAGATCTCCTGACCTCGACCCAGGACTGCTCCTTCCAAC
SEQ ID N0:447
XBAREV1 GCTAGTTCTAGACCATCCTGGCTGACACGGTGAAACACCGTCTCTACG
GGCTGACACTGCAGCTCCAG SEQ ID No:448
LNK1FOR GTCAGTACTAGTATGGGTGTCCGGGCTCTTCGGCTCCTGCAGG
TTGGAGGCCACGG SEQ ID N0:449
LNK1REV GTCAGTACTAGTCCGCCATCTCCGACACCATTAGGCCCTGCCAGC
SEQ ID N0:450
LNK2FOR GTCAGTTCCGGAGATTTCGGTTCTGCAGAGGGCTGCGCAAGG
TGGCGTA SEQ ID No:451
LNK2REV GTCAGTTCCGGATACTCATACCAGCCCGCCATCCCCGGGTTCTA
ATCTGCAAGATGAAGAGCTG 5EQ ID N0:452
LNK7FOR GTCAGTACTAGTATGGGTGTCCGGGCTCTTCGGAAAGGCACATTT
GGTGACAAAGTGTATC SEQ ID N0:453
LNK7REV GTCAGTACTAGTCCGCCATCTCCGGGTACACCATTAGGCCCTG
CCAGC SEQ ID N0:454
LNK8REV GTCAGTTCCGGATACTCATACCAGCCCGCCATCCCCGGGTAAGGCC
TTTCAGCCCCCCCCCAG SEQ ID No:455
C1FOR GTCAGACCATGGCCACTCAGGACTCCTCTTTTC SEQ
ID N0:456
CA 02268742 1999-04-19
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C3FOR CACTTTGTCACCAAATCTGCCTTTCAG SEQ ID No:457
C3REV CTGAAAGGCAGATTTGGTGACAAAGTG SEQ ID N0:458
CSFOR GCCCCCCCCCAGCTCTCTTCG SEQ ID N0:459
CSREV CGAAGAGAGCTGGGGGGGGGC SEQ ID N0:460
C6REV GTCAGTTACGTACAGGGTTGAAGGAGTCGGGCTGAGACTGC
SEQ ID
N0:461
GPFOR1 GTCAGTCCATGGCTACTCAAGGTGCTATGC SEQ ID
NO:462
GPREV2 GTAGCATACGTAGGGCTGCAGGGCAGGGGCC SEQ ID
No:463
CA 02268742 1999-04-19
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loo
TABLE 2
GENE SEQUENCES
pMON30304
S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGT SEQ ID
NO:1
1S pMON26458
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
TGCGTCAGGGAATTC SEQ ID N0:2
2S pMON28548
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
3O GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
TGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG
CTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG
3S CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGA
GCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTG
GGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACA
GCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT
GTAGGAGGGTCCACCCTCTGCGTCAGG SEQ ID N0:3
pMON28500
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
4S TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
TGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT
SO CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA
GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGG
CAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC
AGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTC
SS CTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG SEQ ID N0:4
pMON2850I
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
60 CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
6S TGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG
CTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG
CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGA
GCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTG
GGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG
7O GGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT
TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG SEQ ID N0:5
pMON28502
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~0(
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
S CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
TGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTC
AGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACA
CCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC
ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCA
TCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTT
CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGA
AAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG
SEQ ID N0:6
1S
Syntanl
1 CATGGCTAACTGCTCTATAA CACTTAAAGA
TGATCGATGA
AATTATACAT
51 GACCACCTGCACCTTTGCTGGACCCGAACA ACCTCAATGACGAAGACGTC
101 TCTATCCTGATGGACCGAAACCTTCGACTT CCAAACCTGGAGAGCTTCGT
151 AAGGGCTGTCAAGAACTTAGAAAATGCATC AGGTATTGAGGCAATTCTTC
201 GTAATCTCCAACCATGTCTGCCCTCTGCCA CGGCCGCACCCTCTCGACAT
251 CCAATCATCATCAAGGCAGGTGACTGGCAA GAATTCCGGGAAAAACTGAC
ZS 301 GTTCTATCTGGTTACCCTTGAGCAAGCGCA GGAACAACAGGGTGGTGGCT
351 CTAACTGCTCTATAATGATCGATGAAATTA TACATCACTTAAAGAGACCA
401 CCTGCACCTTTGCTGGACCCGAACAACCTC AATGACGAAGACGTCTCTAT
451 CCTGATGGACCGAAACCTTCGACTTCCAAA CCTGGAGAGCTTCGTAAGGG
501 CTGTCAAGAACTTAGAAAATGCATCAGGTA TTGAGGCAATTCTTCGTAAT
3O 551 CTCCAACCATGTCTGCCCTCTGCCACGGCC GCACCCTCTCGACATCCAAT
601 CATCATCAAGGCAGGTGACTGGCAAGAATT CCGGGAAAAACTGACGTTCT
651 ATCTGGTTACCCTTGAGCAAGCGCAGGAAC AACAGTAC
SEQ ID 7
N0:
3S
Syntan3
1 CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA
51 GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC
40 101 TCTATCCTGATGGACCGAAA CCAAACCTGGAGAGCTTCGT
CCTTCGACTT
151 AAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTC
201 GTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACAT
251 CCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGAC
301 GTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCT
4S 351 CTGGCGGTGGCAGCGGCGGCGGTTCTAACTGCTCTATAATGATCGATGAA
401 ATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAA
451 CCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTC
501 CAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCA
551 GGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCAC
.
SO 601 GGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAG
651 AATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAG
701 GAACAACAGTAC SEQ
ID N0:8
SS pMON31104
1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT
51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA
101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA
CO 151 CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCAT
201 CAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGG
251 TTACCCTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCTCTAACTGCTCT
301 ATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
351 GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCT
6S 401 CTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAAC
451 ATGGCTACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCG
501 GGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGT
551 CGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGC
601 TCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGG
70 651 CGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCC
701 ACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCT
751 CCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAG
801 CCRACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGG
851 AAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
7S 901 GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAAT
CA 02268742 1999-04-19
WO 98/17810 PCT/CTS97/20037
951 GGCCCCTGCC CTGCAGCCCT AATAA SEQ ID N0:9
pMON31105
1 ATGGCTAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATG
51 TCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGG
101 CAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACC
151 CTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCTCTAACTGCTCTATAAT
lO 201 GATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG
251 ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAAC
301 CTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGA
351 ATACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCT
401 CTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAAC
IS 451 ATGGCTACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCG
501 GGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGT
551 CGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGC
601 TCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGG
651 CGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCC
20 701 ACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCT
751 CCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAG
801 CCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGG
851 AAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
901 GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAAT
2$ 951 GGCCCCTGCCCTGCAGCCCTAATAA D NO:10
SEQ
I
pMON31106
30 1 ATGGCTGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCA
51 AGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGC
101 AGGAACAACAGGGTGGTGGCTCTAACTGCTCTATAATGATCGATGAAATT
151 ATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCT
201 CAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAA
3S 251 ACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT
301 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGC
351 CTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCT
401 CTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAAC
451 ATGGCTACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCG
40 501 GGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGT
551 CGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGC
601 TCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGG
651 CGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCC
701 ACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCT
4S 751 CCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAG
801 CCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGG
851 AAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
901 GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAAT
951 GGCCCCTGCCCTGCAGCCCTAATAA
SEQ
ID N0:11
50
pMON31107
1 ATGGCTGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGA CGTTCTATCT
SS 51 GGTTACCCTTGAGCAAGCGCAGGAACAACAGGGTGGTGGC TCTAACTGCT
101 CTATAATGATCGATGAAATTATACATCACTTAAAGAGACC ACCTGCACCT
151 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA TCCTGATGGA
201 CCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG GCTGTCAAGA
251 ACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA TCTCCAACCA
60 301 TGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA TCATCATCAA
351 GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT GGTCCAATCT
401 CTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAA ATCTCCAAAC
451 ATGGCTACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTT TCCAGCGCCG
501 GGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTC CTGGAGGTGT
65 551 CGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGG CTCTGGCGGC
601 TCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAA AGATCCAGGG
651 CGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTAC AAGCTGTGCC
701 ACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCAT CCCCTGGGCT
751 CCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAG GCTGCTTGAG
7O 801 CCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTG CAGGCCCTGG
851 AAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACT GCAGCTGGAC
901 GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAG AACTGGGAAT
951 GGCCCCTGCCCTGCAGCCCTAATAA
SEQ
ID N0:12
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~~3
pMON31108
1 ATGGCTCTGGACCCGAACAA GAAGACGTCTCTATCCTGAT
CCTCAATGAC
51 GGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCA
S 101 AGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
151 CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCAT
201 CAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGG
251 TTACCCTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCTCTGGCGGTGGC
301 AGCGGCGGCGGTTCTAACTGCTCTATAATGATCGATGAAATTATACATCA
351 CTTAAAGAGACCACCTGCACCTTTGTACGTAGAGGGCGGTGGAGGCTCCC
401 CGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
451 AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGGTGCCATGCCGGC
501 CTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCC
551 ATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
1S 601 CAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTT
651 AGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGC
701 TGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGA
751 CACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGC
801 CCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCT
851 ACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCC
901 ACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTG
951 GCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTAATAA
SEQ ID :13
N0
2S pMON31109
1 ATGGCTAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATG
51 TCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGG
101 CAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACC
151 CTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCTCTGGCGGTGGCAGCGG
201 CGGCGGTTCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAA
251 AGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGAC
301 GTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTT
351 CGTAAGGGCTGTCAAGAACTTAGAATACGTAGAGGGCGGTGGAGGCTCCC
3S 401 CGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
451 AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGGTGCCATGCCGGC
501 CTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCC
551 ATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
601 CAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTT
651 AGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGC
701 TGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGA
751 CACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGC
801 CCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCT
851 ACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCC
4S 901 ACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTG
951 GCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTAATAA
SEQ ID
N0:14
pMON31110
SO
1 ATGGCTGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCA
51 AGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGC
101 AGGAACAACAGGGTGGTGGCTCTGGCGGTGGCAGCGGCGGCGGTTCTAAC
151 TGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGC
SS 201 ACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGA
251 TGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTC
301 AAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCA
351 ACCATGTCTGCCCTCTGCCACGGCCTACGTAGAGGGCGGTGGAGGCTCCC
401 CGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
60 451 AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGGTGCCATGCCGGC
501 CTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCC
551 ATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
601 CAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTT
651 AGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGC
6S 701 TGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGA
751 CACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGC
801 CCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCT
851 ACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCC
901 ACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTG
70 951 GCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTAATAA
SEQ ID :15
N0
pMON31111
7S 1 ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~O~t
51 GGTTACCCTTGAGCAAGCGCAGGAACAACAGGGTGGTGGCTCTGGCGGTG
101 GCAGCGGCGGCGGTTCTAACTGCTCTATAATGATCGATGAAATTATACAT
151 CACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGA
201 CGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGG
S 251 AGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
301 GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACC
351 CTCTCGACATCCAATCATCATCAAGTACGTAGAGGGCGGTGGAGGCTCCC
401 CGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
451 AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGGTGCCATGCCGGC
501 CTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCC
551 ATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
601 CAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTT
651 AGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGC
701 TGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGA
1S 751 CACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGC
801 CCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCT
851 ACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCC
901 ACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTG
951 GCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTAATAA
SEQ ID :16
N0
pMON131B2
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
2S S1 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTT
401 ACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGC
451 ATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGC
501 AGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCC
3S 551 TGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
601 CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGA
651 AGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGG
701 CCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGC
751 CATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGC
801 GCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTT
851 TAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAG
901 CTGTGTGCCACCTAATAA
SEQ
ID N0:17
4S pMON13183
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
SO 151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
SS 401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTACAAG
451 CTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCC
501 CTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCT
551 GCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
601 GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCA
60 651 GCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAAC
701 TGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
751 GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCT
801 GCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGC
851 CCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAG
6S 901 CAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTG
951 TGCCACCTAATAA SEQ N0:18
ID
pMON13184
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG
7S 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
251 CAATCATCATCAAGGCAGGTGACTGGCAAG
AATTCCGGGA
AAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTC
401 CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
451 GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCT
501 GCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCC
551 GGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTG
601 TCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGG
651 CTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGG
701 GCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGC
751 CACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGC
801 TCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGA
851 GCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTG
901 GAAGGGATATCCTAATAA
SEQ
ID N0:19
pMON13185
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
2O 51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCCCGAG
452 TTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCAC
501 CACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGC
551 CCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
601 GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTA
651 CCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGCTCTC
701 AGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGAT
751 GGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCC
801 CGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCC
851 TGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAA
901 CTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGG
951 GATATCCTAATAA SEQ N0:20
ID
pMON13186
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
4S 101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
SO 351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTA
401 TGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCT
451 GCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAG
501 CTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTG
551 GCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
SS 601 AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCAC
651 CTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGG
701 GCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTG
751 GCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCT
801 CCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACA
60 851 CACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATG
901 GAAGAACTGGGATAATAA
SEQ
ID N0:21
pMON13187
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG
201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC
251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG
301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG
351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC
401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC
7S 451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC
551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC
601 TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA
651 GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA
S 701 AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC
751 CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG
801 CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC
851 AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG
901 CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA
951 ACTGGGATAA TAA SEQ ID N0:22
pMON13188
1S 1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
ZO 251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTA
401 CCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
451 GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCG
ZS 501 CGTTCTACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGA
551 GCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGC
601 GCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGA
651 GGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGA
701 GCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTC
3O 751 CATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGAT
801 ATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCG
B51 ACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCT
901 GCCCTGCAGCCCTAATAA
SEQ
ID N0:23
3S
pMON13189
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
4O 101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
4S 351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
551 TACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTC
SO 601 CTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGC
651 GCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGC
701 TGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCC
751 TGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAG
801 CGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCC
SS 851 CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
901 GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCT
951 GCAGCCCTAATAA SEQ N0:24
ID
60 pMON13190
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
f>S151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTT
70 401 CTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAG
451 AGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTC
501 TGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAG
551 TGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCC
601 ACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCT
75 651 GGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGC
CA 02268742 1999-04-19
WO 98/17810 PCT/LTS97/20037
r~~
701 TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG
751 CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA
801 CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA
851 TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG
901 CCGGCCTTCG CCTAATAA SEQ ID N0:25
pMON13191
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
1J 251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTCTGCT
451 TTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTT
501 CCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGGCG
551 GCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGA
601 AAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTA
651 CAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCA
701 TCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCA
751 GGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCT
801 GCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACAC
851 TGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAA
901 GAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGC
951 CTTCGCCTAATAA SEQ N0:26
ID
pMON13192
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTT
401 ACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGC
451 ATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGC
501 AGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCC
551 TGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
601 CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGA
651 AGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGG
701 CCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGC
751 CATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGC
801 GCAGCCCACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGC
851 TCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTC
901 CAGGAGAAGCTGTGTGCCACCTAATAA
SEQ ID
N0:27
pMON13193
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGA GGTATTGAGGCAATTCTTCG
AAATGCATCA
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTACAAG
451 CTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCC
501 CTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCT
551 GCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
601 GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCA
7O 651 GCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAAC
701 TGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
751 GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCT
801 GCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGC
851 CCACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
901 TCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGA
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
Io8
951 GAAGCTGTGT GCCACCTAAT AA SEQ ID N0:28
pMON25190
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTC
401 CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
1S 451 GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCT
501 GCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCC
551 GGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTG
601 TCGTACCGCGTTCTACGCCACCTTGCGCAGCCCACACCATTGGGCCCTGC
651 CAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAA
2O 701 AGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTAC
751 AAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCAT
801 CCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAG
851 GCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTG
901 CAGGCCCTGGAAGGGATATCCTAATAA ID N0:29
SEQ
2S
pMON25191
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
30 51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
3S 301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCCCGAG
451 TTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCAC
501 CACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGC
4O 551 CCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
601 GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTA
651 CCGCGTTCTACGCCACCTTGCGCAGCCCACACCATTGGGCCCTGCCAGCT
701 CCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATC
751 CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCT
45 801 GTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCT
851 GGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
901 TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGC
951 CCTGGAAGGGATATCCTAATAA SEQ
ID N0:30
SO
pMON13194
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
SS 101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
6O 351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTA
401 TGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCT
451 GCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAG
501 CTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCACAC
551 CATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTA
6S 601 GAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCT
651 GTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGAC
701 ACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
751 CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTA
801 CCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCA
70 851 CCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
901 CAGCAGATGGAAGAACTGGGATAATAA ID N0:31
SEQ
pMON13195
7S
CA 02268742 1999-04-19
WO 98117810 PCT/US97/20037
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
S 201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTATGGCC
451 CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTT
501 CCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCC
551 TGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCACACCATTG
601 GGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCA
651 AGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTG
IS 701 CCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCT
751 CTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCA
801 GCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGG
851 GGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTG
901 GACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCA
951 GATGGAAGAACTGGGATAATAA SEQ
ID N0:32
pMON13196
2S 1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
20i TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTA
401 CCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
451 GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCG
3S 501 CGTTCTACGCCACCTTGCGCAGCCCACACCATTGGGCCCTGCCAGCTCCC
551 TGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAG
601 GGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTG
651 CCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGG
701 CTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTG
751 AGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCT
BO1 GGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGG
B51 ACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGA
901 ATGGCCCCTGCCCTGCAGCCCTAATAA
SEQ
ID N0:33
4S
pMON13197
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
SO 101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
S5 351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
551 TACGCCACCTTGCGCAGCCCACACCATTGGGCCCTGCCAGCTCCCTGCCC
GO 601 CAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGA
651 TGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACC
701 CCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
751 CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCA
801 ACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAG
65 851 GGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTC
901 GCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGC
951 CCCTGCCCTGCAGCCCTAATAA SEQ
ID N0:34
70 pMON13198
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
7S 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
l10
201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC
251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG
301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG
351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT
S 401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG
451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCAC
501 ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT
551 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG
601 CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG
651 ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG
701 CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC
751 TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC
801 CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT
851 GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG
1S 901 GGTGCCATGC CGGCCTTCGC CTAATAA SEQ ID N0:35
pMON13199
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
2S 251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTCTGCT
451 TTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTT
501 CCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCACACCAT
551 TGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAG
601 CAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTG
651 TGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACT
701 CTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTG
3S 751 CAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCA
801 GGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCT
851 TGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAG
901 CAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGC
951 CATGCCGGCCTTCGCCTAATAA SEQ
ID N0:36
pMON31112
1 ATGGCTAACTGCTCTAACATGATCGATGAA ACCTGAAGCA
ATCATCACCC
51 GCCACCGCTGCCGCTGCTGGACTTCAACAACCTCAATGGTGAAGACCAAG
4S 101 ATATCCTAATGGACAATAACCTTCGTCGTCCAAACCTCGAGGCATTCAAC
151 CGTGCTGTCAAGTCTCTGCAGAATGCATCAGCAATTGAGAGCATTCTTAA
201 AAATCTCCTGCCATGTCTGCCGCTAGCCACGGCCGCACCCACGCGACATC
251 CAATCCATATCAAGGACGGTGACTGGAATGAATTCCGTCGTAAACTGACC
301 TTCTATCTGAAAACCTTGGAGAACGCGCAGGCTCAACAGTACGTAGAGGG
SO 351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
551 TACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTC
SS 601 CTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGC
651 GCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGC
701 TGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCC
751 TGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAG
801 CGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCC
GO 851 CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
901 GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCT
951 GCAGCCCTAATAA SEQ N0:37
ID
pMON31113
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA
51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG
101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC
151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA
201 AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC
251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC
301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG
351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC
401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG
7S 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC
551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC
601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA
651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC
701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC
751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA
801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG
851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC
901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC
951 CCCTGCCCTG CAGCCCTAAT AA SEQ ID N0:38
pMON31114
1 ATGGCTAACTGCTCTAACATGATCGATGAA ACCTGAAGCA
ATCATCACCC
1S 51 GCCACCGCTGCCGCTGCTGGACTTCAACAACCTCAATGGTGAAGACCAAG
101 ATATCCTGATGGAAAATAACCTTCGTCGTCCAAACCTCGAGGCATTCAAC
151 CGTGCTGTCAAGTCTCTGCAGAATGCATCAGCAATTGAGAGCATTCTTAA
201 AAATCTCCTGCCATGTCTGCCCCTGGCCACGGCCGCACCCACGCGACATC
251 CAATCATCATCCGTGACGGTGACTGGAATGAATTCCGTCGTAAACTGACC
301 TTCTATCTGAAAACCTTGGAGAACGCGCAGGCTCAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
2S 551 TACGCCACCTTGCGCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTC
601 CTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGC
651 GCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGC
701 TGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCC
751 TGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAG
3O 801 CGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCC
851 CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
901 GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCT
951 GCAGCCCTAATAA SEQ N0:39
ID
3S
pMON31115
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA
51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG
40 101 ATATCCTAATGGACAATAACCTTCGTCGTCCAAACCTCGAGGCATTCAAC
151 CGTGCTGTCAAGTCTCTGCAGAATGCATCAGCAATTGAGAGCATTCTTAA
201 AAATCTCCTGCCATGTCTGCCGCTAGCCACGGCCGCACCCACGCGACATC
251 CAATCCATATCAAGGACGGTGACTGGAATGAATTCCGTCGTAAACTGACC
301 TTCTATCTGAAAACCTTGGAGAACGCGCAGGCTCAACAGTACGTAGAGGG
4S 351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
551 TACGCCACCTTGCGCAGCCCACACCATTGGGCCCTGCCAGCTCCCTGCCC
SO 601 CAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGA
651 TGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACC
701 CCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
751 CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCA
801 ACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAG
SS B51 GGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTC
901 GCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGC
951 CCCTGCCCTGCAGCCCTAATAA SEQ
ID N0:40
60 pMON28505
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
6S ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCT
TTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG
GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT
70 TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA
ACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATG
GCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGC
AGACTGAGCCAGTGCCCA SEQ ID N0:41
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
pMON28506
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
S GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCT
GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT
CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT
CCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG
GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCT
CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAG
1S TGCCCAGAGGTTCACCCT SEQ ID N0:42
pMON28507
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
2O AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCT
ZS GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG
CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG
ACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG
ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGT
3O GACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTT
CACCCTTTGCCTACACCT SEQ ID N0:43
pMON28508
3S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
40 GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTT
AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTG
GAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG
GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC
AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGA
4S GGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTC
CTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT
ACACCTGTCCTGCTGCCT SEQ ID N0:44
pMON28509
SO
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
S5 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTG
GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA
GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT
CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGAT
6O CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGT
AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT
GTCCTGCTGCCTGCTGTG SEQ ID N0:45
6S pMON28510
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
7O ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGGAACCGTCTGG
TCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAACTCCAAACATGGGAGAATGGAAAACC
CAGATGGAGGAGACCAAGGCACAGGACATTCTGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGG
GACAACTGGGACCCACTTGCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCT
7S GCAGGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCATCTTCCTGA
CA 02268742 1999-04-19
WO 98/17810 ~ ~ ~ PCT/US97/20037
GCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGGGGTCCACCCTCTGCGTCAGGGAATT
CGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT
GTCCTTCACAGCAGACTGACCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACT
TTAGTTG SEQ ID N0:46
S
pMON28511
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGC
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC
1S CAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC
CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCG
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTG SEQ ID N0:47
pMON28512
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
ZS AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTT
CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGA
AAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCC
GCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGC
CAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA
ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA
3S CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG
GCCCTGCAGAGCCTCCTT SEQ ID N0:48
pMON28513
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACA
GCTCACAAGGATCCCRATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT
GTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTC
CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT
TTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG
SO GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT
TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA
ACCCAGCTTCCTCCACAG SEQ ID N0:49
pMON28514
SS
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
60 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGAT
CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGT
AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT
65 GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT
CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT
CCACAGGGCAGGACCACA SEQ ID N0:50
70 pMON28515
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
7S ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCC
ATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGC
GTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT
S CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA
GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGG
CAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC
AGGACCACAGCTCACAAG SEQ ID N0:51
pMON28516
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
IS GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTG
AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAA
TTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC
CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG
GACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTT
CTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCT
GGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA
2S GCTCACAAGGATCCCAAT SEQ ID N0:52
pMON28519
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCT
3S TTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG
GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT
TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA
ACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCG
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCA SEQ ID N0:53
pMON28520
4S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
SO GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCT
GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT
CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT
CCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG
S5 GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCG
CCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC
CCAGAGGTTCACCCT SEQ ID N0:54
pMON28521
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
6S TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCT
GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG
CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG
ACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG
ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGAC
CTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC
CCTTTGCCTACACCT SEQ ID N0:55
7S pMON28522
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTT
AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTG
GAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG
IO GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC
AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGA
GGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTC
AGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACA
CCTGTCCTGCTGCCT SEQ ID N0:56
1S
pMON28523
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
2O GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTG
GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA
25 GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT
CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGAT
CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA
CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC
30 CTGCTGCCTGCTGTG SEQ ID N0:57
pMON28524
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
35 AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAA
4O ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA
CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG
GCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATC
TTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC
AGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGAC
4S TCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCT
GTGGACTTTAGCTTG SEQ ID N0:58
pMON28525
SO GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
SS GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGC
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC
CAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC
CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCT
CCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTG
60 AGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGG
AAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA
GCACGGGGACAACTG SEQ ID N0:59
pMON28526
6S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
70 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTT
CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGA
AAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCT
CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAG
75 TGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG
GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCC
CTGCAGAGCCTCCTT SEQ ID N0:60
pMON28527
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACA
GCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT
GTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGA
GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTG
CCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA
CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGC
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC
CAGCTTCCTCCACAG SEQ ID N0:61
pMON28528
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
2S GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGAT
CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA
CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC
CTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTG
GGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC
CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCA
3S CAGGGCAGGACCACA SEQ ID N0:62
pMON28529
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCC
4S ATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGC
GTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT
GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT
GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG
SO CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG
ACCACAGCTCACAAG SEQ ID N0:63
pMON2B530
SS GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
E>O
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTG
AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAA
TTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT
GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGAC
TTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTG
65 CTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGA
CAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT
CACAAGGATCCCAAT SEQ ID N0:64
pMON28533
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTGACTTCCAAACCTGGAGAGCTTCGTAAGGG
CTGTCAAGAACTTAGAAAATGCATCAGGTATGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCAC
GGCCGCACCCTCTCGCATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTAT
7S TGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGTAACCGTCTGGTCCA
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCT
ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTZjGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAG
GACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTC
TCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAG
S CTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA
GGAAAGGTGCGTTTCCTGATGC'I'TGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAAC
ATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCAC
AGCAGACTGAGCCAGTGCCCA SEQ ID N0:65
pMON28534
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
1S ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCT
GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT
CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT
CCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG
GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCG
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
CTGAGCCAGTGCCCAGAGGTTCACCCT SEQ ID N0:66
2S
pMON28535
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCT
GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG
3S ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG
CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG
ACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG
ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCG
CCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC
CCAGAGGTTCACCCTTTGCCTACACCT SEQ ID N0:67
pMON28536
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
4S AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTT
SO AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTG
GAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG
GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC
AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGA
GGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGAC
SS CTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC
CCTTTGCCTACACCTGTCCTGCTGCCT SEQ ID N0:68
pMON28537
60 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GS GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTG
GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA
GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT
CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGAT
CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
70 ACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGA
GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTG
CCTACACCTGTCCTGCTGCCTGCTGTG SEQ ID N0:69
pMON28538
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ltd
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAA
ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA
CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG
GCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATC
TTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC
AGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA
CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC
CTGCTGCCTGCTGTGGACTTTAGCTTG SEQ ID N0:70
1S pMON28539
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGC
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC
CAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC
2S CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGC
AACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTT
CACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGC
TTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG
GGAGTGATGGCAGCACGGGGACAACTG SEQ ID N0:71
pMON28540
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
3S GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTT
CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGA
4O AAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATG
GCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGC
AGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGA
GAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTG
ATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC
4S CTCCTTGGGGCCCTGCAGAGCCTCCTT SEQ ID N0:72
pMON28541
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
SO AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACA
SS GCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT
GTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCT
TGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAG
GTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG
GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG
f)O
GGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGC
CTCCTTGGAACCCAGCTTCCTCCACAG SEQ ID N0:73
pMON28542
6S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
70 GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGAT
CCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGA
GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTG
CCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA
7S CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
Ilq
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC
CAGCTTCCTCCACAGGGCAGGACCACA SEQ ID N0:74
pMON28543
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCC
ATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGC
GTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT
AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT
1S GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT
CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT
CCACAGGGCAGGACCACAGCTCACAAG SEQ ID N0:75
pMON28544
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
2S ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTG
AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAA
TTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT
CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA
GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGG
CAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC
AGGACCACAGCTCACAAGGATCCCAAT SEQ ID N0:76
3S
pMON28545
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAAC
AACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCT
GGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCC
ATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGC
4S GTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT
CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA
GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGG
CAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCT
CACAAG SEQ ID N0:77
pMON15981
SS 1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGATCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
GO 251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAA.~CATGTCTTACAAG
451 CTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCC
E>S501 CTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCT
551 GCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
601 GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCA
651 GCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAAC
701 TGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
7O 751 GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCT
801 GCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGC
851 CCGGCGGCGGCTCTGACATGGCTACACCATTAGGCCCTGCCAGCTCCCTG
901 CCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGGAAGATCCAGGG
951 CGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTAATAA; SEQ ID
N0:78
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
l~
pMON15982
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
S 101 CTATCCTGATGGATCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
IO 351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTCTCCCGAG
451 TTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCAC
501 CACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGC
551 CCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
IS 602 GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTA
651 CCGCGTTCTACGCCACCTTGCGCAGCCCGGCGGCGGCTCTGACATGGCTA
701 CACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
751 TTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAA
801 GCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCG
20 851 GACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAG
901 GCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCT
951 CTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCTAATAA; SEQ ID
N0:79
pMON15965
25
1 ATGGCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAG
51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGATCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
30 201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTCTTCTGCT
3S 451 TTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTT
501 CCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCGGCGGCG
551 GCTCTGACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGC
601 TTCCTGCTCAAGTCTTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGC
651 AGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGG
40 701 AGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGC
751 TCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCA
801 TAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATAT
851 CCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
901 TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGC
4S 951 CCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTAATAA SEQ ID
N0:80
pMON15966
1 ATGGCTAACTGCTCTATAATGATCGATGAA ACTTAAAGAG
ATTATACATC
SO 51 ACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCT
101 CTATCCTGATGGATCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTA
151 AGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCG
201 TAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
SS 301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTCTATGGCC
451 CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTT
501 CCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCC
EO 551 TGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCGGCGGCGGC
601 TCTGACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTT
651 CCTGCTCAAGTCTTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAG
701 CGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
751 CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTC
6S 801 CTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATA
851 GCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
901 CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTT
951 TGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGATAATAA SEQ ID
N0:81
70 pMON15967
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT
101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
7S 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
t~~
201 TAATCTCCAA CCTCTGCCACGGCCGCACCCTCTCGACATC
CCATGTCTGC
251 CAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACG
301 TTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGG
351 CGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACC
401 CGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTCTACCCAG
451 GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGT
501 CCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTC
551 TACGCCACCTTGCGCAGCCCGGCGGCGGCTCTGACATGGCTACACCATTA
601 GGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCA
AGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTG
651
701 CCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCT
751 CTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCA
801 GCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGG
851 GGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTG
1S GACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCA
901
951 GATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTAATAA SEQ ID
N0:82
pMON15960
2O 1 ATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCT
51 CAAGTCTTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCC
101 AGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTG
151 CTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCC
201 CAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCC
2S 251 TTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAG
301 TTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCAC
351 CACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGC
401 CCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
451 GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTA
30 501 CCGCGTTCTACGCCACCTTGCGCAGCCCGGCGGCGGCTCTGACATGGCTA
551 CACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
601 TTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAA
651 GCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCG
701 GACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAG
3S 751 GCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCT
801 CTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTC
851 CCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATC
901 TGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCA
1001TCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTT
4O 1051CTACGCCACCTTGCGCAGCCCTGATAA
SEQ
ID N0:83
PMON32132
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
4S CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
SO TGCGTCAGG SEQ ID N0:84
PMON32133
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
SS CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG
AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG
6O SEQ ID N0:85
pMON32134
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA
6S CTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA
TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC
CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT
GCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTC
70 TGCGTCAGG SEQ ID N0:86
Pmon13181
1 CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG
7S 51 AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
i zz,
102 CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG
151 TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT
201 CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA
251 TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA
S 301 CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag
351 ggcggtggag gctcCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA
401 CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGTAAGGTA
451 CCGCATGCAA GCTT SEQ ID N0:87
Pmon13180.Seg
1 CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG
51 AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT
101 CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG
151 TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT
201 CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA
251 TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA
301 CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag
351 ggcggtggag gctcCCCGGG TGGTGGTTCT GGCGGCGGCT CCAACATGTA
401 AGGTACCGCA TGCAAGCTT SEQ ID N0:88
pMON30237.seq
GCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGCGCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCC SEQ ID N0:89
pMON30238.seq
GCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCGACTCCTCAACCCTG SEQ ID N0:90
pMON30239.seq
SO GCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCGACTCCTCAACCCTG SEQ ID N0:91
pMON32329.seq
GGAACTCAGGATTGTTCTTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCC SEQ ID N0:92
pMON32330.seq
7$ GGTACCCAGGATTGTTCTTTCCAACACAGCCCCATCTCCTCCGACTTCGC
CA 02268742 1999-04-19
WO 98/17810 ~z 3 PCT/US97/20037
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCGACTCCTCAACCCTG SEQ ID N0:93
pMON32341.seq
GCCACTCAGGACTGTTCTTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
1S CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCC SEQ ID N0:94
pMON32342.seq
GCCACTCAGGACTGCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCGACTCCTCAACCCTG SEQ ID N0:95
pMON32320.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
4$ CTGTCTGGAGGTAACGGATCCGGTGGCAATGGGAGCGGCGGAAATGGAAC
CCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCA
AAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAG SEQ ID N0:96
pMON32321.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
SS TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCAGGCGGTAACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTT
CCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGT
CTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
SEQ ID N0:97
pMON32322.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCTGGCGGCAACGGCACCCAGGACTGCTCCTTCCAACACAGCCCCAT
CTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTC
AAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:98
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
pMON32323.seq
S GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGTAACGGATCCGGTGGCA
ATGGGAGCGGCGGAAATGGAACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCT
TCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCT
GCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGG SEQ ID N0:99
I5
pMON32324.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGTAACGGATCCGGAGGTA
ATGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTC
2S GCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGT
CACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGC
GGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
SEQ ID N0:200
pMON32325.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
3S CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGTCTGGCGGCAACGGCACGCAGGACT
GCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAA
CCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCAC
AGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:101
pMON32326.seq
4S GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCTGGAGGTAACGGCAGTGGTGGCAATGGGAGCGGTGGAAATGGAAC
CCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCA
SO AAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGT
CCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGA
TGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAA
TGTGCCTTTCAGCCC SEQ ID N0:202
SS
pMON32327.seq
60 GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCAGGCGGTAACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTT
CCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGT
65 CTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
GACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTG
GATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGG
AGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
SEQ ID N0:103
pMON32328.seq
GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
7S GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
CA 02268742 1999-04-19
WO 98117810 ~zs PCT/US97/20037
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCTGGCGGCAACGGCACGCAGGACTGCTCCTTCCAACACAGCCCCAT
CTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTC
AAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGC
GGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAA
GACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGG
AGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:104
pMON32348.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
1S CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCTGGAGGTAGTGGATCCGGAGGTTCTGGCAACCCAGGACTGCTCCT
TCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
ZO TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
SEQ ID N0:105
pMON32350.seq
2S GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
30 AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGTCTGGAGGTAGTGGATCCGGTGGCAGTGGGAGCGGCGGATCTGGAAC
CCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCA
AAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAG SEQ ID N0:106
FLT3N.seq
CCATGGCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCC SEQ ID N0:107
SO
FLT3C.seq
GGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTC
CGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATT
SS ACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGC
CTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGT
CGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATAC
ACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTC
GTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGT
GO GGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGC
TGCAGTGTCAGCCCGACTCCTCAACCCTGTAAGCTT SEQ ID N0:108
6S FLT7N.seq
CCATGGCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
70 GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
~5 GTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCC
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/ITS97/20037
SEQ ID N0:109
S FLT4C.seq
GGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTC
CTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAG
ATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGG
GGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGAC
TGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGA
TACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGC
TTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCT
GGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGG
IS AGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTAAGCTT
SEQ ID N0:110
FLTIIN.seq
CCATGGCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
2$ GGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTT
TGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCC
AGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAG
GAGGTGGATCC SEQ ID N0:111
FLTIOC.seq
3S GGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTT
CCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGT
CTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
GACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTG
GATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGG
AGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
CCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCA
GGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGA
ACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG
TAAGCTT SEQ ID N0:112
4S
pMON32365.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
SO CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
SS CTGGGCGGTGGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:113
60 pMON32366.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
6S CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAG
CCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACC
7O TGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:114
pMON32367.seq
7S GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
S AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAGGACTGCTCCTT
CCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGT
CTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
SEQ ID N0:115
pMON32368.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGA
CTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCC
GTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCC
AACCTGCAG SEQ ID N0:116
2S pMON32369.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
3O CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCAC
CCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCA
3$ AAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAG SEQ ID N0:117
pMON32370.seq
GCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCCCCCCCCAGCTGCCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCT
4$ GCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTC
AGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCT
CCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA
GATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:118
pMON30247.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
SS ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCCAGGAC
TGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCG
TGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCA
ACCTGCAGGACGAGGAGCTCTGCGGGGCGCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGG
CTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCT
TTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCAC
TCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCC SEQ ID N0:119
pMON30248.seq
7S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
CA 02268742 1999-04-19
WO 98/17810 PCTNS97/20037
~zg
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
S TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCCAGGAC
TGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCG
lO TGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCA
ACCTGCAGGACGAGGAGCTCTGCGGGGCGCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGG
CTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCT
TTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
IS CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCAC
TCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCT
CAACCCTG SEQ ID N0:120
20 pMON32332.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
2S GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
30 CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
3S CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCAGGCGGT
AACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0;121
pMON32333.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
4S ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
SO TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
SS ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
AACGGATCCGGTGGCAATGGGAGCGGCGGAAATGGAACCCAGGACTGCTC
60 CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAG SEQ ID N0:122
6S pMON32334.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
70 GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
~S CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CA 02268742 1999-04-19
WO 98!17810 ~~ PCTItTS97l20037
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGTCTGGCGGCAACGGCACGCAGGACTGCTCCTTCCAAC
ACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGA
GGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGG
AGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:123
pMON32335.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
1S ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
2S CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGTCTGGAGGTAACGGATCCGGAGGTAATGGCACCCAGG
ACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTC
CAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGG
CACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:124
pMON32336.seq
3S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
4S CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGTCTGGAGGTAACGGATCCGGTGGCAATGGGAGCGGCG
SO GAAATGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGG SEQ ID N0:125
pMON32337.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
6S TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
~TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGCGGC
AACGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTT
CGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAG
TCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGG
CGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGG
~S GTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTG
CA 02268742 1999-04-19
WO 98/17810 PCT/I1S97/20037
X130
TCACCAAATGTGCCTTTCAGCCC SEQ ID N0:126
S pMON32338.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
lO TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
1S TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCAGGCGGT
AACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
20 TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCT
CAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACA
CGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:127
2S
pMON32339.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTA
3O TCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGG
GCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
3S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
40 AACGGCAGTGGTGGTAATGGGAGCGGCGGAAATGGAACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
4S TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCC SEQ ID N0:128
$0 pMON32364.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
5S TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCGACTCAGGAC
60 TGTTCTTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCG
TGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCA
ACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGG
CTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCT
6S TTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCAC
TCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCC SEQ ID N0:129
70 pMON32377.seq
GCTAACTGCTC.TATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
7S GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
A3~
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCAACCCAGGAC
TGCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCG
TGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCA
ACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGG
CTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCT
TTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCAC
TCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCT
CAACCCTG SEQ ID N0:130
1S
pMON32392.seq
GCCACTCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
2S AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCC
AAACATGGCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAA
AGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATT
CGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTC
TTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGA
CATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACT
3S GACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:131
pMON32352.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCCAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
SO GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCAGGCGGT
SS AACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:132
60 pMON32353.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
6S GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
70 CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
7S CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/Z0037
~3~
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
AACGGATCCGGTGGCAATGGGAGCGGCGGAAATGGAACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
S CAG SEQ ID N0:133
pMON32354.seq
IO GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
15 TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
2O TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGTCTGGCGGCAACGGCACGCAGGACTGCTCCTTCCAAC
ACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
25 TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGA
GGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGG
AGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:134
30 pMON32355.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
3S GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
40 CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
4S CTCCTCAACCCTGTCTGGAGGTAACGGATCCGGAGGTAATGGCACCCAGG
ACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTC
CAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGG
CACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:135
pMON32356.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
$5 ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGTCTGGAGGTAACGGATCCGGTGGCAATGGGAGCGGCG
' GAAATGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGG SEQ ID N0:136
pMON32357.seq
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~ 33
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGCGGC
AACGGCACGCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTT
1S CGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAG
TCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGG
CGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGG
GTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTG
TCACCAAATGTGCCTTTCAGCCC SEQ ID N0:137
pMON32358.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
3$ GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCAGGCGGT
AACGGCAGTGGAGGTAATGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCT
CAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACA
CGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:138
pMON32359.seq
4S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
SO TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
55 TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
AACGGCAGTGGTGGCAATGGGAGCGGCGGAAATGGAACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
60 TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCC SEQ ID N0:139
6S
pMON32360.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
70 ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
7S TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
CA 02268742 1999-04-19
WO 98/17810 ~,~~ PC'T/US97/20037
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCCAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
AGTGGATCCGGAGGTTCTGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:140
pMON32352.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTCTGGAGGT
AGTGGATCCGGTGGCAGTGGGAGCGGCGGATCTGGAACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAG SEQ ID N0:141
pMON32393.seq
GCCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAA
GCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTC
AGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGT
GAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGA
ATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAAA
SO TTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAAC
CTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCC
AAACCTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAG
GTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACG
GCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGA
SS ATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGG
AACAACAG SEQ ID N0:142
pMON32371.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
6S TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
75 GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
,t35
TCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGA
CTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACC
CAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:143
pMON32372.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
1S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
TCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTC
CGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATT
ZS ACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:144
pMON32373.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
3S TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
4S TCAGGAGGTGGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:145
SO pMON32374.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
SS GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
60 CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
G5 CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
TCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCA
ACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTG
ACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:146
pMON32375.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
7S ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
CA 02268742 1999-04-19
WO 98/17810 ~3~ PCT/US97/20037
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
S TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
TCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTC
1S CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAG SEQ ID N0:147
pMON32376.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
2S GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCG
GCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGA
ACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
3S CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
TCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAG
TGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCG
CTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
4O ACCGTGGCCTCCAACCTGCAG SEQ ID N0:148
pMON32378.seq
4S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
SO TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
SS TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGATCCGGAGGTACCCAGGACTGCTCCTTCC
AACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCT
6O GACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGA
CGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGA
TGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:149
6S pMON32379.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
70 GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
75 CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CA 02268742 1999-04-19
WO 98/17810 ,/3~ PCT/US97120037
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCT
TCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCA
GGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCT
GGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:150
pMON323B0.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
2S CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAGG
ACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTC
CAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGG
CACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:151
pMON32381.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTG
GTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCAC
CGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGC
TGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG SEQ ID N0:152
pMON32382.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
f>O TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCG
GAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCC
AGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCT
7S GGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
CA 02268742 1999-04-19
WO 981I78I0 ~ 3~ PCT/US97l20037
GGG SEQ ID N0:153
pMON32383.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCTCCAAGATG
1S CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATG
TGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCT
CCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGA
CTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCG
GAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACAC
AGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTA
CCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGG
AGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAG
CGGCTCAAGACTGTCGCTGGG SEQ ID N0:154
pMON32384.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
TCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGA
CTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACC
CAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTC
TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGC
4S TGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACT
TTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:155
pMON32385.seq
SO
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
55 TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
60 TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
TCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTC
CGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATT
65 ACCCAGTCACCGTGGCCTCCAACCTGCAGGATGAGGAGCTCTGCGGGGGC
CTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGT
CGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATAC
ACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:156
pMON32386.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
~S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/Z0037
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
TCAGGAGGTGGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCT
CAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACA
IS CGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:157
pMON32387.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
2S TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGA
TCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCA
ACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTG
ACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGAC
3S GAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGAT
GGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGC
GCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID N0:158
pMON32388.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
SO CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
TCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTC
S5 CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCG
CTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGC
TGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
60 CCC SEQ ID N0:159
pMON32389.seq
6S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
70 TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGC
TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
7S CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCC
CA 02268742 1999-04-19
WO 98/17810 ~~ O PCT/US97/20037
GGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGG
TCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAG
TGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCG
CTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
S ACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCG
GCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGT
CCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCC SEQ ID N0:160
hflt3-28291ink10.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
1$ TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGG
AGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCG
CTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:161
hflt3-28291ink15.seq
3$ GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
4O TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
45 GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
50 TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGG
AGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCA
TCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
CAA SEQ ID N0:162
hflt3-34351ink10.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
6$ TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGC
TGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG SEQ ID N0:163
CA 02268742 1999-04-19
WO 98/17810 PCT/ITS97/20t137
hflt3-34351ink15.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAAGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
1S GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGG
CACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTG
TCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
GTG SEQ ID N0:164
2S
hflt3-62631ink10.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
3S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
TCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAG
GTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCAC
CGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGC
4S TGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:165
hflt3-62631ink15.seq
SO GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
SS TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
60 CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
TCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAG
GTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATC
6S TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCA
AGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCG
GGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACT SEQ ID N0:166
hflt3-94951ink10.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
7S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCC
lO GGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTT
CGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAG
TCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGG
CGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGG
GTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTG
1S TCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0:167
hflt3-94951ink15.seq
ZO GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
ZS TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
3O GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCC
CATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGC
TTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
3S TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCT
CAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACA
CGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTT SEQ ID N0:168
hflt3-98991ink10.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
4S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
SO TGGAAGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
ACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAG
SS GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAAT
CCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCT
CCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTG
GCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCA
AGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTG
60 CCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:169
hflt3-98991ink15.seq
E)S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
70 TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
7S GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
CA 02268742 1999-04-19
WO 98/17810 ~~ 3 PCT/US97/20037
ACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGA
CTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACC
CAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTC
S TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGC
TGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACT
TTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTC
CAG SEQ ID N0:170
hflt3-28291ink6.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
1S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
2S GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTACCCAGGA
CTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCC
GTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:171
hflt3-28291ink7.seq
3S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
4S GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCACCCA
GGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAA
TCCGTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:172
SS hflt3-28291ink13.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
6S CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCTCAGG
GGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCT
CCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:173
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
hflt3-28291ink21.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
S ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTG
GCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTG
1S GGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCA
GACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGC
TGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGG
AGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCT
CCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAA SEQ ID N0:174
2S hflt3-34351ink6.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
3S CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGATCCGGAGGTACTGCTCCTTCCAACACAGCCCCATC
TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCA
AGATTACCCAGTCACCGTG SEQ ID N0:175
4S
hflt3-34351ink7.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
SS TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGATCCGGAGGTGGCACTGCTCCTTCCAACACAGCCCC
CS ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCT
TCAAGATTACCCAGTCACCGTG SEQ ID N0:176
hflt3-34351ink13.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
CA 02268742 1999-04-19
WO 98/17810 ~~ 5 PCT/I1S97/20037
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
S CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACTGC
TCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGA
GCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG SEQ ID N0:177
1S
hflt3-34351ink21.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
2S TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAAC
CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCT
CCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTC
GCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGG
CTCAGGGGGAGGTAGTGGTAGGACTGCTCCTTCCAACACAGCCCCATCTC
CTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAG
ATTACCCAGTCACCGTG SEQ ID N0:178
hflt3-62631ink6.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
SO TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
TCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTACCCAGGACT
SS GCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAA
CCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCAC
AGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:179
hflt3-62631ink7.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
6S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
7S AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
CA 02268742 1999-04-19
WO 98/17810 ~~ ~ PCT/US97/20037
TCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCACCCAGG
ACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTC
CAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGG
S CACAGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:180
hflt3-62631ink13.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
IS TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
TCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCTCAGGGG
GAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
2S GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTA
CCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCC
TCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:181
hflt3-62631ink21.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
3S GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGT
CACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGA
CCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTG
4S TCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAG
GTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCT
GTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGC
AGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGC
SO TGGATGGAGCGGCTCAAGACT SEQ ID N0:182
hflt3-94951ink6.seq
SS GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
60 TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
f)S GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAAT
CCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCT
CCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTG
70 GCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCA
AGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTG
CCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0.:183
hflt3-94951ink7.seq
7S
CA 02268742 1999-04-19
WO 98/17810 ~~,~ PCTIUS97/20037
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
S TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
lO CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCACC
CAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAA
AATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGG
1S CCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTC
CTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGAT
GCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAAT
GTGCCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0:184
hflt3-94951ink13.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
2S TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCTCA
3S GGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTC
CTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAG
ATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGG
GGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGAC
TGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGA
TACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0:185
hflt3-99951ink21.seq
4S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
SO TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGC
SS GCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGC
AGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTG
CTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTG
AGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAAC
GO CTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACA
GCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCT
TGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTT SEQ ID N0:186
6S
hflt3-98991ink6.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
7O TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
7S TGGAAGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
~t~ 8
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
ACTCCTCAACCCTGGGCGGTGGATCCGGAGGTACCCAGGACTGCTCCTTC
CAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTC
TGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGG
ACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGA
GCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCC
CCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:187
hflt3-98991ink7.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAAGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
ACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCT
GTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGC
AGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGC
TGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCT
GGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGC
CCCCCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:188
hflt3-98991ink13.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAAGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
ACTCCTCAACCCTGGGCGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGC
SO TGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCA
CCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTC
CAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCA
CCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:189
hflt3-98991ink21.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACC
ACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATA
TCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGG
GCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAA
TCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAA
TCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
6S TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGG
TGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGT
CTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTG
GATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCG
ACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACA
CAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACT
ACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAG
GAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGA
7S GCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCG
CA 02268742 1999-04-19
WO 98117810 ~~ PCT/US97/20037
TGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAG SEQ ID N0:190
pMON32390
GGATCCACCATGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGT
CCGCCCCGCCATGTCTACAAATCAAGATCTGCCTGTGATCAAGTGTGTTT
TAATCAATCATAAGAACAATGATTCATCAGTGGGGAAGTCATCATCATAT
IO CCCATGGTATCAGAATCCCCGGAAGACCTCGGGTGTGCGTTGAGACCCCA
GAGCTCAGGGACAGTGTACGAAGCTGCCGCTGTGGAAGTGGATGTATCTG
CTTCCATCACACTGCAAGTGCTGGTCGATGCCCCAGGGAACATTTCCTGT
CTCTGGGTCTTTAAGCACAGCTCCCTGAATTGCCAGCCACATTTTGATTT
ACAAAACAGAGGAGTTGTTTCCATGGTCATTTTGAAAATGACAGAAACCC
AAGCTGGAGAATACCTACTTTTTATTCAGAGTGAAGCTACCAATTACACA
ATATTGTTTACAGTGAGTATAAGAAATACCCTGCTTTACACATTAAGAAG
ACCTTACTTTAGAAAAATGGAAAACCAGGACGCCCTGGTCTGCATATCTG
AGAGCGTTCCAGAGCCGATCGTGGAATGGGTGCTTTGCGATTCACAGGGG
GAAAGCTGTAAAGAAGAAAGTCCAGCTGTTGTTAAAAAGGAGGAAAAAGT
GCTTCATGAATTATTTGGGATGGACATAAGGTGCTGTGCCAGAAATGAAC
TGGGCAGGGAATGCACCAGGCTGTTCACAATAGATCTAAATCAAACTCCT
CAGACCACATTGCCACAATTATTTCTTAAAGTAGGGGAACCCTTATGGAT
AAGGTGCAAAGCTGTTCATGTGAACCATGGATTCGGGCTCACCTGGGAAT
TAGAAAACAAAGCACTCGAGGAGGGCAACTACTTTGAGATGAGTACCTAT
2S TCAACAAACAGAACTATGATACGGATTCTGTTTGCTTTTGTATCATCAGT
GGCAAGAAACGACACCGGATACTACACTTGTTCCTCTTCAAAGCATCCCA
GTCAATCAGCTTTGGTTACCATCGTAGAAAAGGGATTTATAAATGCTACC
AATTCAAGTGAAGATTATGAAATTGACCAATATGAAGAGTTTTGTTTTTC
TGTCAGGTTTAAAGCCTACCCACAAATCAGATGTACGTGGACCTTCTCTC
GAAAATCATTTCCTTGTGAGCAAAAGGGTCTTGATAACGGATACAGCATA
TCCAAGTTTTGCAATCATAAGCACCAGCCAGGAGAATATATATTCCATGC
AGARAATGATGATGCCCAATTTACCAAAATGTTCACGCTGAATATAAGAA
GGAAACCTCAAGTGCTCGCAGAAGCATCGGCAAGTCAGGCGTCCTGTTTC
TCGGATGGATACCCATTACCATCTTGGACCTGGAAGAAGTGTTCAGACAA
GTCTCCCAACTGCACAGAAGAGATCACAGAAGGAGTCTGGAATAGAAAGG
CTAACAGAAAAGTGTTTGGACAGTGGGTGTCGAGCAGTACTCTAAACATG
AGTGAAGCCATAAAAGGGTTCCTGGTCAAGTGCTGTGCATACAATTCCCT
TGGCACATCTTGTGAGACGATCCTTTTAAACTCTCCAGGCCCCTTCCCTT
TCATCCAAGACAACGAATTCATCATCCTGGGCCTGTTCGGCCTCCTGCTG
TTGCTCACCTGCCTCTGTGGAACTGCCTGGCTCTGTTGCAGCCCCAACAG
GAAGAATCCCCTCTGGCCAAGTGTCCCAGACCCAGCTCACAGCAGCCTGG
GCTCCTGGGTGCCCACAATCATGGAGGAGGATGCCTTCCAGCTGCCCGGC
CTTGGCACGCCACCCATCACCAAGCTCACAGTGCTGGAGGAGGATGAAAA
GAAGCCGGTGCCCTGGGAGTCCCATAACAGCTCAGAGACCTGTGGCCTCC
CCACTCTGGTCCAGACCTATGTGCTCCAGGGGGACCCAAGAGCAGTTTCC
ACCCAGCCCCAATCCCAGTCTGGCACCAGCGATCAGGTCCTTTATGGGCA
GCTGCTGGGCAGCCCCACAAGCCCAGGGCCAGGGCACTATCTCCGCTGTG
ACTCCACTCAGCCCCTCTTGGCGGGCCTCACCCCCAGCCCCAAGTCCTAT
GAGAACCTCTGGTTCCAGGCCAGCCCCTTGGGGACCCTGGTAACCCCAGC
SO CCCAAGCCAGGAGGACGACTGTGTCTTTGGGCCACTGCTCAACTTCCCCC
TCCTGCAGGGGATCCGGGTCCATGGGATGGAGGCGCTGGGGAGCTTC SEQ ID N0:191
pMON30329.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAG
CGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAAC
ACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAG
ACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACT
CGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID
N0:1.92
pMON32173.seq
7S
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
GCCACTCAGGACTGCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
S CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGT
CCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACC
CAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCT
GACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGG
GGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAG
ATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
CCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAG
CTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAG
IS CCCGACTCCTCAACCCTG SEQ ID N0:193
pMON32175.seq
GCCACCCAGGACTGCTCCTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCATGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
2S TGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGT
CCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACA
CCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAG
ATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAG
GAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAG
GCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTG
CAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCC
GACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACC
CAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGC
CATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTTTACGCCACCTTGCGCAGCCC SEQ ID
3S No:194
pMON32204.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACTCAGGACTGCTCTTTTCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAG
CGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAAC
ACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAG
ACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACT
CGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTACGTAGAG
SS GGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCC
TCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAG
ATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAAC
ATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAG
AACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID N0:195
pMON32205.seq
6S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTG
GACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAAC
CTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACTCAGGACTGCTCTTTTCAA
CACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGAT
TACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTC
75 CTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAG
CA 02268742 1999-04-19
WO 98!17810 ~~~ PCT/US97/20037
CGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGC
TTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCC
TGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG
TACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT
S CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTG
AACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTC
CAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATC
ACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ
ID N0:196
pMON32208.seq
GCCACTCAGGACTGCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGT
CCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACA
CCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAG
ATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAG
GAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAG
GCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTG
CAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCC
GACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACC
CAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGC
CATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTACGTAGAG
GGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCT
AAAGAATCTCATAAATCTCCAAACATGGCTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCC
TCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
3S GCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAG
ATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAAC
ATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAG
AACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID N0:197
pMON35767.seq/pMON32191.seq
GGCCACTCAGGACTGCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGA
GCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCT
4S CTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGG
GTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTT
TCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTC
CGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCA
GTGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGG
SO CGGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAA
GTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCAC
CTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCC
CCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCT
TTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGA
SS CACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAAT
GGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGC
AGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCA
CCTTGCGCAGCCG SEQ ID N0:198
pMON32397.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
6S CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97I20037
,t5~r
GGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAA
ATCCGTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:199
pMON32398.seq
S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
1S CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
GGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA SEQ ID N0:200
pMON32399.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
2S CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAACCTGCAGGACGAG
GAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTG SEQ ID N0:201
pMON35700.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
4S GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAAGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGCCTCCAACCTGCAGGACGAG
GAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
SO GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG SEQ ID N0:202
SS
pMON35701.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
60 CTGCTCGCRTTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGGTCCAAGATGCAA
f)S GGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTG
GCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGAC
TCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTACCCAGGACTGCTCCTTCCAACAC
AGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTAC
70 CCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTG
GCACAGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:203
pMON35702.seq
CA 02268742 1999-04-19
WO 98/17810 X53 PCT/US97/20037
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
S GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGTCGCTGGGTCCAAGATGCAA
GGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTG
GCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGAC
TCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGAC
TGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTAC
CTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTC
TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACT SEQ ID N0:204
IS
pMON35703.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTCCAGACCAACATC
2S TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
GGATCCGGAGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAA
ATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGAC
GAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACT
GTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAA
TGTGCCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0:205
pMON35704.seq
3S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
GGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
4S GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTT SEQ ID N0:206
SO pMON35705.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
S5 AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAHACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAAGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATCTCCCGCCTCCTG
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
6O CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGT
ACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGC
GGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCC
AAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
6S CCCCCCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:207
pMON35706.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
70 GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
75 CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCACCAACATCTCCCGCCTCCTG
CA 02268742 1999-04-19
WO 98117810 PCT/US97/20037
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGT
GGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
S GACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACC
AAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAG SEQ ID N0:208
pMON35733.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
1S GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTCTAATCTGCAAGATGAAGAG
CTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
TTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
ZS SEQ ID N0:209
pMON35734.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
3S CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCAACCTGCAAGATGAAGAGCTG
TGTGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGT
GGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTC
GCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCC
SEQ ID N0:210
4S pMON35735.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
SO AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCTGCAGGATGAGGAACTGTGC
GGCGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCC
S5 AAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCTTTTCAG
CCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAG
CAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGT
CAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGC
TCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
60 GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAAC
SEQ ID N0:211
pMON35736.seq
6S GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
70 CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCAAGATGAAGAGCTGTGTGGT
GGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAG
ATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
CCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAG
7S CTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAG
CA 02268742 1999-04-19
WO 98/17810 X55 PCT/US97/20037
CCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCA
GGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
SEQ ID N0:212
S
pMON35738.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGAAGAACTGTGTGGTGGTCTG
1S TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAA
GGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTG
GCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGAC
TCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGA
GGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGAC
SEQ ID N0:213
pMON35739.seq
2S
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGAGCTGTGTGGTGGCCTGTGG
CGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGC
TTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
3$ TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAAAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCC
TCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGT
AGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAG
SEQ ID N0:214
pMON35740.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
SO CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCTGTGCGGTGGTCTGTGGCGT
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
SS ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
SEQ ID N0:215
60 pMON35741.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
GS AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTTCTAATCTGCAAGATGAAGAG
CTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
70 GGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGAC
CA 02268742 1999-04-19
WO 98/17810 PCTNS97/20037
TCCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
SEQ ID N0:216
pMON35742.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCAAGATGAAGAACTGTGCGGT
GGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAG
1S ATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
CCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCGGGAGACCTCCGAGCAG
CCGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAG
CCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCA
GGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
SEQ ID N0:217
pMON35743.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTG
GACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAAC
CTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCTGTGCGGTGGTCTGTGGCGT
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
3S AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCGGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAGATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
SEQ ID N0:218
pMON32179.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
4S AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
SO ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGAT
GAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAA
GACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTC
SS AAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCT
GCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAA
AAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:219
pMON35707.seq
GCGGATGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAGGCCCTGGATCACTCGCCAGAACTTCTCCCGG
6S TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGA
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
. CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGC
GGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAA
GAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTA
AAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATG
GAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCA
TCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTG
GTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:220
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
pMON35708.seq
GCCGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
S ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
1S ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:221
pMON35709.seq
GCAGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
ZS GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
3O AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID No:222
3S
pMON35710.seq
GCGGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCCTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
40 ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCCTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
4S CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
SO ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:223
pMON35711.seq
SS GCGGATGAGGAGCTGTGTGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGGGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
6O GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
f)S AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:224
pMON35719.seq
GGCCGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCG
GCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTT
7S GCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTG
CA 02268742 1999-04-19
WO 98/17810 ~5~ PCT/US97/20037
TCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCT
GAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTC
AACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTC
CTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCT
S TCAATACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCC
GTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGA
AATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGA
CATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAA
GCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGC
IO CACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAA
ACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:225
pMON35720.seq
IS GCCGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGC
TGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACG
GAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGC
CAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCA
ZO GGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATC
TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
GTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
2S ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:226
30 pMON35721.seq
GCCGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACC
AAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTG
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
3S CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGT
GGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAGGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
GACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACTTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
4O TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
'ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGP,TGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
4S CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:227
pMON35722.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
SO TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
SS CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
60 CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:22B
pMON35723.seq
6S
GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAG
CAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGT
CAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGC
ACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
70 TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGC
GGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCC
AAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
7S ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/CTS97I20037
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:229
S
pMON35725.seq
GCCACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATC
ACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGT
GGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTYGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTG
AACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTC
1S CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:230
pMON35726.seq
2S GCCCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
CAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAACGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
TTTTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
3S ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:231
pMON35744.seq
GCTTCAAATCTGCAGGATGAAGAGCTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAG
ATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAAC
4S ATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAG
AACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGA
GGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTC
CAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA
GATTACCCAGTCACCGTGGCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
SO ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
SS CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:232
pMON35745.seq
GO GCTAATCTGCAAGATGAGGAGCTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
E>S GGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAA
CACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGAT
TACCCAGTCACCGTGGCCTCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
70 AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:233
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
/110
pMON35746.seq
GCGCTGCAGGATGAAGAGCTGTGTGGCGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTTGATGGAG
CGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACAC
TTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCC
CGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTC
TCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGG
TCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACAC
AGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTAC
CCAGTCACCGTGGCCTCCAACTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
1S CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:234
pMON35747.seq
GCGCAAGATGAGGAACTGTGTGGTGGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
2S CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCCCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:235
pMON35748.seq
GCTGAAGAACTG'PGTGGTGGCCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACC
AAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTG
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGT
GGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATC
4S TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
GTGGCCTCCAACCTGCAGGACTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
SO TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:236
SS pMON35749.seq
GCTCTGTGCGGTGGCCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
6O ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
6S ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
70 CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:237
pMON35750.seq
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/20037
GCACTGTGTGGTGGTCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
S CTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
1S SEQ ID N0:238
pMON35769.seq
GCTCTGTGTGGCGGTCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
ZO GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTGCAGTGTCGGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
2S GACTTCGCTGTCAAGATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
30 TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:239
3S pMON35771.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
40 CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
4S TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
SO CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:240
pMON35774.seq
GCTCAAGATGATGAGCTGTGTGGTGGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
55 CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGCGGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTAGTGGTACC
6O CAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCT
GACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCAT
AAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCA
CCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAAC
6S CTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATT
GAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCA
ATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTT
GAGCAAGCGCAGGAACAACAG SEQ ID N0:241
70 pMON35775.seq
GCCCAAGATGAAGAACTGTGTGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
7S CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
X162
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCA
CTCGGCGCCACCGCACCGACCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTC
GCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAAC
CTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
S TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
lO CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG SEQ ID N0:242
pMON35776.seq
GCCCAAGATGAAGAACTGTGTGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
IS CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCA
CTCGGCGCCACCGCACCGACCGCTGGACAACCGCCTCTGACCCAGGACTGCTCCTTCCAACACAGC
ZO CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGC
TCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAAC
AACCTCAATTCTGAAGACATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCA
2S TTCGTAAGGGCTGTCAAGCACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAA
CCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGG
CAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAG
SEQ ID N0:243
pMON32169.seq/pMON40000.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
3S CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
4S CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID
SO N0:244
pMON32188.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
SS AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
GO CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCAAATCTGCAAGACGAGGAGCTGTGCGGGGGC
CTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATG
ES CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCC
CCCAGCTGTCTTCGCTTCGTCCAGATCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTG
GTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCC
GACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGG
GGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAA
70 ATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCC SEQ ID
N0:245
pMON32273.seq
CA 02268742 1999-04-19
WO 98/17810 X63 PCTlUS97/20037
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
S CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGC
CAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCA
GGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
1S CAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC SEQ ID
N0:246
pMON35795.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
2S AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCTGCAGGATGAGGAACTGTGCGGCGGCCTC
TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAA
GGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTG
3S GCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGAC
TCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGA
GGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATC
CGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAAC SEQ ID
N0:247
pMON35796.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
4S CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
SO GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCAAGATGAAGAGCTGTGTGGTGGTCTCTGG
CGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGC
TTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGC
SS TGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCG
CTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCC
TCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGT
AGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG SEQ ID
60 No:248
pMON35797.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
6S AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
70 CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATGTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGAAGAACTGTGTGGTGGTCTGTGGCGGCTG
GTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTG
7S GAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~t~4
CGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAG
CCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACC
CTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGT
ACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
S TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGAC SEQ ID
N0:249
pMON35798.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
1S GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGAGCTGTGTGGTGGCCTGTGGCGTCTGGTC
CTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAG
CGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGC
TTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCC
TGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG
GGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACC
CAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCT
GACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAG SEQ ID
N0:250
pMON35799.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
3$ CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCTGTGCGGTGGTCTGTGGCGTCTGGTCCTG
GCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGC
GTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTC
GTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGC
4$ GGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG SEQ ID
N0:251
SO pMON39914.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
SS AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
6O GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGGCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
E>S AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGCCGCCACCGTGGAGCCCGCGTCCACTCGGCGCCACCGCACCGACCACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
CAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:252
70 pMON39915.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCC.CAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
7S AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~~5
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGGCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGCGGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGC
GGAGGTGGCTCTGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAG SEQ ID N0:253
pMON39916.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
2S GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGGCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGCCGCCACCGTGGAGCCCGCGTCCACTCGGCGCCACCGCACCGACCGCTGGACAACCGCCT
CTGACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID
3$ N0:254
pMON35712.seq
GCCGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
4S ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
CAA SEQ ID N0:255
SO pMON35713.seq
GCCGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGC
TGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACG
GAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGC
SS CAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCA
GGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATC
TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
GTG SEQ ID N0:256
60 pMON35714.seq
GCCGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACC
AAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTG
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
6$ CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGT
GGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
'GACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACT SEQ ID N0:257
pMON35715.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
7S TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~1 lv<p
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
S GGG SEQ ID N0:25B
pMON35716.seq
GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAG
CAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGT
CAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGC
ACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGC
GGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCC
AAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCC SEQ ID N0:259
pMON35717.seq
GCCCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCC
TTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTT
CAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGG
2S CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTT SEQ ID N0:260
pMON35718.seq
GCCACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATC
ACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGT
GGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
3S GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTG
AACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTC
CAG SEQ ID N0:261
pMON32170.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
4S ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
SO ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
SS CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
60 N0:262
pMON32187.seq
6S GCAGATGAAGAACTGTGTGGGGGACTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
70 GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
7S CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CA 02268742 1999-04-19
WO 98/17810 ~6~ PCT/US97J20037
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
S GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:263
pMON32271.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
1S TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCACTC
GGCGCCACCGCACCGACCGCTGGACAACCGCCTCTGACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGC
TCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTA
2O GAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAG
CTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGC
TCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTC
TACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTG
CAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCT
2$ GCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGG
GTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
CAGCCG SEQ ID N0:264
pMON32272.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
3$ TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGC
GGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTG
CCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTC
CAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCT
CTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTG
AGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCC
GAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAG
CAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCC
TCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTG
TCGTACCGCGTTCTACGCCACCTTGCGCAGCCG SEQ ID N0:265
pMON32274.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
SS TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCACTC
GGCGCCACCGCACCGACCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
TACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTACACCA
TTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGRAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
CS GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCG SEQ ID
N0:266
pMON35751.seq
GCGGATGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAGGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGA
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/20037
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGC
GGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAA
GAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTC
S CTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTG
TGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCC
TGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCAT
AGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCC
ACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAA
CTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAG
CGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTT
CTACGCCACCTTGCGCAGCCC SEQ ID N0:267
pMON35752.seq
1S
GCCGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
2S CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
3O CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:268
pMON35753.seq
3S
GCAGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
4O TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
4S TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
SO TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTGTACGCCACCTTGCGCAGCCC SEQ ID
N0:269
SS pMON35754.seq
GCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAG
CAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGT
CAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGC
C)O ACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTG
TCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGC
GGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCC
AAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAG
CCGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
f)S TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
GTGCCCCAGAGCTTCCTGCTCARGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
70 CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTATACGCCACCTTGCGCAGCCC SEQ ID N0:270
7S pMON35755.seq
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCTTCAAATCTGCAGGATGAAGAGCTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAG
ATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAAC
S ATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAG
AACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGA
GGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTC
CAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA
GATTACCCAGTCACCGTGGCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCATCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
1S GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:271
pMON35756.seq
GCTAATCTGCAAGATGAGGAGCTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
2S CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGT
GGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAA
CACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGAT
TACCCAGTCACCGTGGCCTCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTATACGCCACCTTGCGCAGCCC SEQ ID
No:272
pMON35757.seq
GCGCTGCAGGATGAAGAGCTGTGTGGCGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTTGATGGAG
4S CGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACAC
TTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCC
CGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTC
TCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGG
TCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACAC
SO AGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTAC
CCAGTCACCGTGGCCTCCAACTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
SS CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
60 CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:273
pMON35758.seq
E>S GCACTGTGCGGTGGTCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTACAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
70 GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
7S CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
~!'~D
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
S GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:274
pMON35759.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
2S CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:275
pMON35760.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTG
CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
4S CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:276
pMON35761.seq
GCGCTGTGTGGTGGTCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
SS CTGCAGTGTCGGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCC
GGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
AACTTCGCTGTCAAGATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
TCCAACCTGCAGGACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATTTTTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
6O TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
6S TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:277
70 pMON35762.seq
GCTGAACTGTGTGGTGGTCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACT
GTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAA
TGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAG
7S GAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGA
TCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCC
TCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTG
GCCTCCAACCTGCAGGACGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
S ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:278
1S
pMON35763.seq
GCTGAAGAACTGTGTGGTGGCCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAG
ACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACC
AAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTG
CAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGC
CTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGT
GGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATC
TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
2S GTGGCCTCCAACCTGCAGGACTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
3S N0:279
pMON35764.seq
GCTCAGGACGAGGAACTGTGTGGTGGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGC
4S CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
SO CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
SS CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:280
pMON35765.seq
60 GCCACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATC
ACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGT
GGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTTGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCA
6S CAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTG
AACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTC
CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
70 CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:281
pMON35766.seq/pMON32190.seq/pMON40001.seq
S
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
1S TTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTAC
AAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTG
AGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTC
CTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCC
CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTT
GCGCAGCCG SEQ ID N0:282
pMON35768.seq
2S
GCTCAAGATGAAGAACTGTGCGGTGGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
3O CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGAGGCGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTCCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
35 TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
40 TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
No:283
4S pMON35770.seq
GCGCTGTGTGGTGGCCTGTGGCGTCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTC
GCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATAT
GCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAG
SO ACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAG
CTGCAGTGTCGGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCA
GGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAGATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
GACGAGGAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATC
SS AACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCC
AGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGC
GCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTC
GGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCA
GGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGG
6O ATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACC
ATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCG
GCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTC
CTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:284
6S pMON35772.seq
GCCTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCC
TTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACC
TCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTTCCGGTGCCTGGAGCTG
70 CAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGA
GGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGT
GAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAG
CTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCT
GGCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
7S TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~~3
CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:285
pMON35773.seq
GCTCAAGACGAAGAACTGTGTGGTGGTCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
IS CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCA
GGCGGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTAGTGGTACC
CAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCT
GACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCAT
AAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACC
TACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
2S TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCC SEQ ID N0:286
pMON35777.seq
GCCCAAGATGAAGAACTGTGTGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCA
CTCGGCGCCACCGCACCGACCACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTC
GCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAAC
CTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCC
CTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCG
CTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACAC
TCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGC
TTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCC
CCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGG
CAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTC
GCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAG
GTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID N0:287
pMON35778.seq
GCCCAAGATGAAGAACTGTGTGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGG
CTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTT
SS GTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGC
CTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCC
CGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCA
CTCGGCGCCACCGCACCGACCGCTGGACAACCGCCTCTGACCCAGGACTGCTCCTTCCAACACAGC
CCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCA
GTCACCGTGGCCTCCAACCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
E)S CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:288
pMON35779.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGC
GGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCAT
AAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACC
TACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCQTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCC SEQ ID N0:289
pMON35780.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCCC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGC
GGTGGTTCTGGCGGAGGATCCGGCGGCGGAAGCGGAGGTGGCTCTGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCAT
AAATCTCCAAACATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TGCTTAGAGCAAGTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACC
TACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCC SEQ ID N0:290
pMON35782.seq
GCGGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGCCGCCACCGTGGAGCCCGCGTCCACTC
GGCGCCACCGCACCGACCGCTGGACAACCGCCTCTGACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCACCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACACCA
TTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAAGTGAGGAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
SS TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC SEQ ID
N0:291
pMON39908.seq
GCTGATGAGGAGCTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGTAGAGACGGTGTTTCACCGTGTCAGCCAGGATGGTCTAGAT
CTCCTGACCTCGACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAA
ATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTACACCATTG
7O GGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAG
GGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACTAACAAGCTGTGCCACCCCGAGGAGCTG
GTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTG
CAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCC
CTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTT
GCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGT
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTG
CAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCG SEQ ID N0:292
S pMON32275.seq
GCTGATGAAGAACTGTGTGGTGGGCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCG
GGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCT
CCAAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTA
GAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAG
CTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGC
TCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTC
TACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTG
CAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCT
GCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGG
GTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCG
CAGCCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCAACCCAGGACTGCTCTTTTCAA
CACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGAT
TACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:293
2S
pMON35781.seq
GCCACCCAGGACTGCTCCTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGAGCCGAAGAGC
CCGGACACCCATACTAGTCCGCCATCTCCGACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGC
TTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAG
CTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATC
CCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTC
3S CATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGC
CCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAA
GAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTC
CAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGC
GTTCTACGCCACCTTGCGCAGCCCTCTGCAGAACCGAAATCTCCGGATACTCATACCAGCCCGCCA
TCCCCGGGTTCTAATCTGCAAGATGAAGAGCTGTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAG
CGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAAC
ACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGCCTTCGCTTCGTCCAG
ACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACT
CGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID
N0:294
pMON35783.seq
GCCACCCAGGACTGCTCCTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
SO CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTGGCAGGGGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CCGAAGAGCCCGGACACCCATACTAGTCCGCCATCTCCGGGTACACCATTGGGCCCTGCCAGCTCC
CTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCG
SS CTCCAGGAGAAGCTGTGTGCCACTACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACT
CTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCT
TGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCC
CCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGC
AGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCG
60 CCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGG
TGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCTGCAGAACCGAAATCTCCGGATACTCATA
CCAGCCCGCCATCCCCGGGTAAGGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCA
ACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCC
AGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID
65 No:295
pMON32276.seq
7O GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATCTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
7S GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTCCTCCTTCCAACACAGCCCC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
TTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACTAAC
S AAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTG
AGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTC
CTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCC
CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTT
GCGCAGCCG SEQ ID N0:296
pMON32277.seq
1S GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATCTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTCCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGCGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID
N0:297
pMON32278.seq
3S
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTCTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTAGAGCTGCAGTCTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
4S TTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACTAAC
AAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTG
AGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTC
CTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCC
SO CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTT
GCGCAGCCG SEQ ID N0:298
pMON32279.seq
SS
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
60 CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
65 CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCAGATGAAGAACTGTGTGGGGGCCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTCT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTCTCAGCCCGACTCCTCA
7O ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACTCAGGACTGTTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID
N0:299
75 pMON35790.seq
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
GCCACTCAGGACTCCTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
S TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATCTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGC
GGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACT
AACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
1S GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCG SEQ ID N0:300
pMON35791.seq
GCCACTCAGGACTGTTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
2S CAGCCCCCCCCCAGCTCTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TCTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGC
GGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACC
TACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
3S GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCG SEQ ID N0:301
pMON35792.seq
GCCACTCAGGACTGTTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGCGGCTCCAACATGGCTACACCA
TTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATC
CAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACTAACAAGCTGTGCCACCCCGAGGAG
CTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCC
SO CTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAG
GCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGAC
TTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCACCCAG
GGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTTGCTAGCCAT
CTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCG SEQ ID
SS No:3oz
pMON39905.seq
GCCACTCAGGACTGTTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
GO CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
6S TCTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGC
GGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACC
TACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
7O TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCG SEQ ID N0:303
7S
CA 02268742 1999-04-19
WO 98/17810 ~ ~,8 PCT/US97/20037
pMON39906.seq
GCCACTCAGGACTGTTCTTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
S TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGCGCCTGGAGCTGCAG
TCTCAGCCCGACTCCTCAACCCTGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGC
GGCGGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAG
TCTTTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACT
AACAAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCC
CTGAGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTT
TTCCTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGAC
ACACTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATG
GCCCCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCA
GGAGGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCAC
CTTGCGCAGCCG SEQ ID N0:304
pMON39909.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTACTCAAGGTGCTATGCCAGCTTTTGCTTCTGCTTTTCAACGTCGTGCAGGT
GGTGTTCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTT
GCGCAGCCCTCTGGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGA
AAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCC
GAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGC
CAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTC
CTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTC
GCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCC
SEQ ID N0:305
pMON39910.seq
GCTACTCAAGGTGCTATGCCAGCTTTTGCTTCTGCTTTTCAACGTCGTGCAGGTGGTGTTCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTCT
GGCGGCTCTGGCGGCTCTCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTGAGAAAGATCCAGGGC
4S GATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCACCCCGAGGAGCTGGTG
CTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCCAGCCAGGCCCTGCAG
CTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGGCTCCTGCAGGCCCTG
GAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGACGTCGCCGACTTTGCC
ACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAGCCCTACGTAGAGGGC
SO GGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAA
GAATCTCATAAATCTCCAAACATGGCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTG
GCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGC
GTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTC
GTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
55 ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGC
GGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:306
pMON35727.seq
GCCGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCGACGAGGAGCTCTGCGGGGGCCTC
TGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAA
GGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCC
AGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTG
7S GCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGAC
CA 02268742 1999-04-19
WO 98/17810 ~ ~ PCT/US97/20037
TCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGAC
TGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTAC
CTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:307
pMON32168.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCA
ATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAAATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTCTGCGGGGGC
CTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCC
CCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTG
GTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCC
GACTCCTCAACCCTG SEQ ID N0:308
pMON32195.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCT
TTAGAGCAAGTGAGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTAC
AAGCTGTGCCACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTG
AGCTCCTGCCCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTC
CTCTACCAGGGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACA
CTGCAGCTGGACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCC
CCTGCCCTGCAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGA
GGGGTCCTGGTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTT
GCGCAGCCCTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATC
AACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGT
GGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAG
ATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCC
CCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAG
CTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAG
CCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCA
SO GGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTC
AAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG
SEQ ID N0:309
pMON32196.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
E)S CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
' CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGC
GGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAA
GAATCTCATAAATCTCCAAACATGGCTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCC
GACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
TCCAACCTGCAGGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATG
GAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATA
CACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATC
TCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAAC
S TTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTG SEQ ID N0:310
pMON32197.seq
GCTACACCATTGGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTCTTTAGAGCAAGTG
AGAAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGCCAC
CCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGCCCC
AGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAGGGG
CTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTGGAC
GTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTGCAG
1S CCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTGGTT
GCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCCTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
2S CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGC
GGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAA
GAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTG
GCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGC
GTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTC
GTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGG
ATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGC
GGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAG
GACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGAC
TACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID N0:311
3S
pMON32206.seq
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTG
GACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAAC
CTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGT
AATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCA
GGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAA
CAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAAC
CCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGT
4$ CTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATG
CAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCC
CCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTG
GTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCC
GACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGG
SO GGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAA
ATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGTAC
GTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCT
CCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGG
CTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTG
SS CTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGT
CTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTG
AAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCA
ACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGT
GGTACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
60 CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAG SEQ ID
N0:312
pMON32207.seq
6S GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
70 GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGGTGGTTCTGGCGGC
GGCTCCAACATGGCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGG
ATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAG
7S ATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAAC
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAG
AACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGA
GGTGGGTCAGGAGGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTC
CAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAA
GATTACCCAGTCACCGTGGCCTCCAACCTGCAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAA
CCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAAC
ATGGCTACACCATTAGGCCCTGCCAGCTCCCTGCCCCAGAGCTTCCTGCTCAAGTGCTTAGAGCAA
GTGAGGAAGATCCAGGGCGATGGCGCAGCGCTCCAGGAGAAGCTGTGTGCCACCTACAAGCTGTGC
CACCCCGAGGAGCTGGTGCTGCTCGGACACTCTCTGGGCATCCCCTGGGCTCCCCTGAGCTCCTGC
CCCAGCCAGGCCCTGCAGCTGGCAGGCTGCTTGAGCCAACTCCATAGCGGCCTTTTCCTCTACCAG
GGGCTCCTGCAGGCCCTGGAAGGGATATCCCCCGAGTTGGGTCCCACCTTGGACACACTGCAGCTG
GACGTCGCCGACTTTGCCACCACCATCTGGCAGCAGATGGAAGAACTGGGAATGGCCCCTGCCCTG
CAGCCCACCCAGGGTGCCATGCCGGCCTTCGCCTCTGCTTTCCAGCGCCGGGCAGGAGGGGTCCTG
GTTGCTAGCCATCTGCAGAGCTTCCTGGAGGTGTCGTACCGCGTTCTACGCCACCTTGCGCAGCCC
TGATAAGGATCCGAATTCGGCAGC SEQ ID N0:313
pMON35728.seq
GCCGACGAGGAGCTGTGCGGTGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGAACCCAGGACTGCTCCTTCCAACACAGCCCCATCTCCTCCGACTTCGCT
GTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTG
CAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCG
TCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTAACTGCTCTATAATGATCGATGAA
ATTATACATCACTTAAAGAGACCACCTAACCCTTTGCTGGACCCGAACAACCTCAATTCTGAAGAC
ATGGATATCCTGATGGAACGAAACCTTCGAACTCCAAACCTGCTCGCATTCGTAAGGGCTGTCAAG
CACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCC
ACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAA
CTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGC
TCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCAT
AAATCTCCAAACATGGCCGACGAGGAGCTCTGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGC
3S TGGATGGAGCGGCTCAAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACG
GAGATACACTTTGTCACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACC
AACATCTCCCGCCTCCTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGC
CAGAACTTCTCCCGGTGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCA
GGAGGTGGGTCAGGAGGTGGATCCGGAGGTGGCACCCAGGACTGCTCCTTCCAACACAGCCCCATC
TCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTCACC
GTGGCCTCCAACCTGCAG SEQ ID N0:314
pMON32183.seq
GCTGATGAAGAACTGTGTGGTGGTCTGTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTC
AAGACTGTCGCTGGGTCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTC
ACCAAATGTGCCTTTCAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTC
CTGCAGGAGACCTCCGAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGG
SO TGCCTGGAGCTGCAGTGTCAGCCCGACTCCTCAACCCTGGGCGGTGGGTCAGGAGGTGGGTCAGGA
GGTGGATCCGGAGGTGGCTCAGGGGGAGGTAGTGGTACCCAGGACTGCTCCTTCCAACACAGCCCC
ATCTCCTCCGACTTCGCTGTCAAAATCCGTGAGCTGTCTGACTACCTGCTTCAAGATTACCCAGTC
ACCGTGGCCTCCAACCTGCAGGAATTCAAGCTTGAGCCCAGAGGGCCCACAATCAAGCCCTGTCCT
CCATGCAAATGCCCAGCACCTAACCTCTTGGGTGGACCATCCGTCTTCATCTTCCCTCCAAAGATC
5$ AAGGATGTACTCATGATCTCCCTGAGCCCCATAGTCACATGTGTGGTGGTGGATGTGAGCGAGGAT
GACCCAGATGTCCAGATCAGCTGGTTTGTGAACAACGTGGAAGTACACACAGCTCAGACACAAACC
CATAGAGAGGATTACAACAGTACTCTCCGGGCGGTCAGTGCCCTCCCCATCCAGCACCAGGACTGG
ATGAGTGGCAAGGAGTTCAAATGCAAGGTCAACAACAAAGACCTCCCAGCGCCCATCGAGAGAACC
ATCTCAAAACCCAAAGGGTCAGTAAGAGCTCCACAGGTATATGTCTTGCCTCCACCAGAAGAAGAG
60 ATGACTAAGAAACAGGTCACTCTGACCTGCATGGTCACAGACTTCATGCCTGAAGACATTTACGTG
GAGTGGACCAACAACGGGAAAACAGAGCTAAACTACAAGAACACTGAACCAGTCCTGGACTCTGAT
GGTTCTTACTTCATGTACAGCAAGCTGAGAGTGGAAAAGAAGAACTGGGTGGAAAGAAATAGCTAC
TCCTGTTCAGTGGTCCACGAGGGTCTGCACAATCACCACACGACTAAGAGCTTCTCCCGGACTCCG
GGTAAA SEQ ID N0:315
pMON32184.seq
GCCACCCAGGACTGCTCCTTTCAACACAGCCCCATCTCCTCCGACTTCGCTGTCAAAATCCGTGAG
CTGTCTGACTACCTGCTTCAAGATTACCCAGTCACCGTGGCCTCCAACCTGCAGGACGAGGAGCTC
TGCGGGGGCCTCTGGCGGCTGGTCCTGGCACAGCGCTGGATGGAGCGGCTCAAGACTGTCGCTGGG
TCCAAGATGCAAGGCTTGCTGGAGCGCGTGAACACGGAGATACACTTTGTCACCAAATGTGCCTTT
CAGCCCCCCCCCAGCTGTCTTCGCTTCGTCCAGACCAACATCTCCCGCCTCCTGCAGGAGACCTCC
GAGCAGCTGGTGGCGCTGAAGCCCTGGATCACTCGCCAGAACTTCTCCCGGTGCCTGGAGCTGCAG
TGTCAGCCCGACTCCTCAACCCTGGAATTCAAGCTTGAGCCCAGAGGGCCCACAATCAAGCCCTGT
CCTCCATGCAAATGCCCAGCACCTAACCTCTTGGGTGGACCATCCGTCTTCATCTTCCCTCCAAAG
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
Z
ATCAAGGATGTACTCATGATCTCCCTGAGCCCCATAGTCACATGTGTGGTGGTGGATGTGAGCGAG
GATGACCCAGATGTCCAGATCAGCTGGTTTGTGAACAACGTGGAAGTACACACAGCTCAGACACAA
ACCCATAGAGAGGATTACAACAGTACTCTCCGGGCGGTCAGTGCCCTCCCCATCCAGCACCAGGAC
TGGATGAGTGGCAAGGAGTTCAAATGCAAGGTCAACAACAAAGACCTCCCAGCGCCCATCGAGAGA
S ACCATCTCAAAACCCAAAGGGTCAGTAAGAGCTCCACAGGTATATGTCTTGCCTCCACCAGAAGAA
GAGATGACTAAGAAACAGGTCACTCTGACCTGCATGGTCACAGACTTCATGCCTGAAGACATTTAC
GTGGAGTGGACCAACAACGGGAAAACAGAGCTAAACTACAAGAACACTGAACCAGTCCTGGACTCT
GATGGTTCTTACTTCATGTACAGCAAGCTGAGAGTGGAAAAGAAGAACTGGGTGGAAAGAAATAGC
TACTCCTGTTCAGTGGTCCACGAGGGTCTGCACAATCACCACACGACTAAGAGCTTCTCCCGGACT
CCGGGTAAA SEQ ID N0:316
CA 02268742 1999-04-19
WO 98117810 ~~~ PCT/US97/20037
TABLE 3
PROTEIN SEQUENCES
pMON26458pep
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgASpSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyVaIMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe SEQ ID N0:467
pMON28548pep
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProASnAlaIlePheLeuSerPheGlnHisLeuLeuArgGIyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu
ValGlyGlySerThrLeuCysValArg SEQ ID N0:468
pMON28500
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValASpPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSer
ProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisVa1
LeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeu
ProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGln
AspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu
GlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeu
GlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHis
LysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPhe
LeuMetLeuValGlyGlySerThrLeuCysValArg SEQ ID N0:469
pMON28501
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValASpPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnASpIleLeuGlyAIaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProASnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArg SEQ ID N0:470
pMON28502
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
CA 02268742 1999-04-19
WO 98117810 ~~~ PCT/US97/20037
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGly
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr
ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu
ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla
ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVa1
ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg
ThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGly
LysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg SEQ ID N0:471
13182.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
20Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
25Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaTyrLysLeuCys
His ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro
Trp AlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
Gly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
30Leu LeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThr
Leu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle
Trp GlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
35Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
Ala ThrSEQID
N0:472
13183.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
45Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
50Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaTyrLysLeuCys
His ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro
Trp AlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
55Gly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
Leu LeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThr
Leu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle
Trp GlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
60Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
Ala ThrSEQID
N0:473
65
13184.Pept
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
70 Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser.Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
75 Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
,r 85
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
G1y Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser SEQ ID N0:474
IS
13185.Pept
AsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArg
ProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
ValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
SerPheValArgA1aValLysAsnLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
AlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
2$ GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
GlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
GlyGluProSerGlyProIleSerThrIleAsnProSerProPro
SerLysGluSerHisLysSerProAsnMetAlaProGluLeuGly
ProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetG1uGluLeuGlyMetAlaProAlaLeu
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGln
ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSer
GlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGlu
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLys
LeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCys
ProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerSEQID
N0:475
13186.Pept
AsnCysSerIleMetIleAspGluIleI1eHisHisLeuLysArg
ProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
ValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
SerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
AlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
GlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
GlyGlyGlySerGlyGlyGlySerAsnMetAlaMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSer
PheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
SerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeu
GluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuVal
LeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer
CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeu5erGlnLeu
HisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeu
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
LeuGlySEQID
N0:476
13187.Pept
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
CA 02268742 1999-04-19
WO 98/17810 ~ ~~ PCT/US97/20037
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaMetAlaProAla
Leu GlnProThrGlnGlyAlaMetProAlaPheA1aSerAlaPhe
Gln ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSer
Phe LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
Ser GlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeu
Glu GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
Lys LeuCysAlaThrTyrLysLeuCysHisProGluGluLeuVal
Leu LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer
Cys ProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeu
His SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
Gly IleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeu
Asp ValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
Leu GlySEQID
N0:477
13188.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaThrGlnGlyAla
Met ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVal
Leu ValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArg
Val LeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySer
Gln SerPheLeuLeuLysSerLeuGluGlnValArgLysIleGln
Gly AspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLys
Leu CysHisProGluGluLeuValLeuLeuGlyHisSerLeuGly
Ile ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
Leu AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
Gln GlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGly
Pro ThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
Thr IleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
Gln ProSEQID
N0:478
13189.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla
Met ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVal
Leu ValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArg
Val LeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySer
Gln SerPheLeuLeuLysSerLeuGluGlnValArgLysIleGln
Gly AspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLys
Leu CysHisProGluGluLeuValLeuLeuGlyHisSerLeuGly
Ile ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
Leu AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
Gln GlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGly
Pro ThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
Thr IleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
Gln ProSEQID
N0:479
13190.Pept
Asn Cys Ser Ile Met Ile Asp Glu.Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
CA 02268742 1999-04-19
WO 98/17810 ~$~ PCT/(JS97/20037
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
S Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Sex His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
Phe Ala SEQ ID N0:480
13191.Pept
AsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArg
ProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
ValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
2S SerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
AlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
GlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
GlyGluProSerGlyProIleSerThrIleAsnProSerProPro
SerLysGluSerHisLysSerProAsnMetAlaSerAlaPheGln
ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSer
GlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGlu
3S GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLys
LeuCysAlaThrTyrLysLeuCysHisProGluGluLeuVaILeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCys
ProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAsp
ValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAla
PheAlaSEQID
N0:481
4S
13192.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
SS Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaTyrLysLeuCys
His ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro
Trp AlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
Gly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
Leu LeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThr
Leu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle
Trp GlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
6S Val SerTyrArgValLeuArgHisLeuAlaGlnProThrProLeu
Gly ProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeu
Glu GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
Lys LeuCysAlaThrSEQID
N0:482
13193.Pept
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
7S Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaTyrLysLeuCys
His ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro
Trp AlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
Gly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
Leu LeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThr
Leu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle
Trp GlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProThrProLeu
Gly ProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeu
Glu GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
Lys LeuCysAlaThrSEQID
N0:483
25190.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaProGluLeuGly
Pro ThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
Thr IleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
Gln ProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGln
Arg ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
Leu GluValSerTyrArgValLeuArgHisLeuAlaGlnProThr
Pro LeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
Ser LeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeu
Gln GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
Leu ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeu
Ser SerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
Gln LeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAla
Leu GluGlyIleSerSEQID
N0:484
pMON25191.Pep
AsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArg
ProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
ValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
SerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
AlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
GlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
GlyGluProSerGlyProIleSerThrIleAsnProSerProPro
SerLysGluSerHisLysSerProAsnMetAlaProGluLeuGly
ProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGln
ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThr
ProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeu
GlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeu
SerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAla
LeuGluGlyIleSerSEQID
N0:485
13194.Pept
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
CA 02268742 1999-04-19
WO ~ PCT/US97/20037
98/17810 ~9
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaMetAlaProAla
Leu GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
Gln ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSer
Phe LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
Thr ProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
Lys SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
Leu GlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGlu
Glu LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
Leu SerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeu
Ser GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
Ala LeuGluGlyIleSerProGluLeuGlyProThrLeuAspThr
Leu GlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGln
Met GluGluLeuGlySEQID
N0:486
13195.Pept
25Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
30Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly G1uProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaMetAlaProAla
35Leu GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
Gln ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSer
Phe LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
Thr ProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
Lys SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
40Leu GlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGlu
Glu LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
Leu SerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeu
Ser GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
Ala LeuGluGlyIleSerProGluLeuGlyProThrLeuAspThr
45Leu GlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGln
Met GluGluLeuGlySEQID
N0:487
13196.Pept
50
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
55Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GlyGlySerGlyGlyGlySerAsnMetAlaThrGlnGlyAla
60Met ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVal
Leu ValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArg
Val LeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSer
Ser LeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArg
Lys IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAla
65Thr TyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
Ser LeuGlyIleProTrpAlaProLeuSerSerCysProSerGln
Ala LeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeu
Phe LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerPro
Glu LeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp
70Phe AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAla
Pro AlaLeuGlnProSEQID
N0:488
13197.Pept
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/ITS97/20037
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
S Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProP
ro
Ser LysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla
Met ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVal
Leu ValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArg
Val LeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSer
Ser LeuProGlnSerPheLeuLeuLysSerLeuGluGlnValAr
g
1S Lys IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAla
Thr TyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
Ser LeuGlyIleProTrpAlaProLeuSerSerCysProSerGln
Ala LeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeu
Phe LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerPro
Glu LeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp
Phe AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAla
Pro AiaLeuGlnProSEQID 0:489
N
2S 13198.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
3S Gly GlyGlySerGlyGlyGlySerAsnMetAlaSerAlaPheGln
Arg ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
Leu GluValSerTyrArgValLeuArgHisLeuAlaGlnProThr
Pro LeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
Ser LeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeu
Gln GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
Leu ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeu
Ser SerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
Gln LeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAla
Leu GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeu
4S Gln LeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMet
Glu GluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAla
Met ProAlaPheAlaSEQID 0
N0:49
SO
13199.Pept
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
Pro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
5S Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIle
Glu AlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThr
Ala AlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
Gln GluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
60 Gln AlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerPro
Gly GluProSerGlyProIleSerThrIleAsnProSerProPro
Ser LysGluSerHisLysSerProAsnMetAlaSerAlaPheGln
Arg ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
Leu GluValSerTyrArgValLeuArgHisLeuAlaGlnProThr
65 Pro LeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
Ser LeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeu
Gln GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
Leu ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeu
Ser SerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
70 Gln LeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAla
Leu GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeu
Gln LeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMet
Glu GluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAla
Met ProAlaPheAlaSEQID
N0:491
7S
CA 02268742 1999-04-19
WO 98117810 ~ ~ ~ PCT/US97120037
31104.Pep
Leu AspProAsnAsnLeuAsnAspGluAspValSerIleLeuMet
S Asp ArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAla
Val LysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArg
Asn LeuGlnProCysLeuProSerAlaThrAlaAlaProSerArg
His ProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGlu
Lys LeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
10Gln GlyGlyGlySerAsnCysSerIleMetIleAspGluIleIle
His HisLeuLysArgProProAlaProLeuTyrValGluGlyGly
Gly GlySerProGlyGluProSerGlyProIleSerThrIleAsn
Pro SerProProSerLysGluSerHisLysSerProAsnMetAla
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
1SAla GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
Ala ThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGly
20His SerLeuGlyIleProTrpAlaProLeuSerSerCysProSer
Gln AlaLeuG1nLeuAlaGlyCysLeuSerGlnLeuHisSerGly
Leu PheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
Pro GluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAla
Asp PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMet
2SAla ProAlaLeuGlnProSEQID
N0:492
31105.Pep
30Asn AlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCys
Leu ProSerAlaThrAlaAlaProSerArgHisProIleIleIle
Lys AlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyr
Leu ValThrLeuGluGlnAlaGlnGluGlnGlnGlyGlyGlySer
Asn CysSerIleMetIleAspGluIleIleHisHisLeuLysArg
3SPro ProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAsp
Val SerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGlu
Ser PheValArgAlaValLysAsnLeuGluTyrValGluGlyGly
Gly GlySerProGlyGluProSerGlyProIleSerThrIleAsn
Pro SerProProSerLysGluSerHisLysSerProAsnMetAla
40Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
4SAla ThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGly
His SerLeuGlyIleProTrpAlaProLeuSerSerCysProSer
Gln AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGly
Leu PheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
Pro GluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAla
SOAsp PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMet
Ala ProAlaLeuGlnProSEQID
N0:493
31106.Pep
SS
Ala ProSerArgHisProIleIleIleLysAlaGlyAspTrpGln
Glu PheArgGluLysLeuThrPheTyrLeuValThrLeuGluGln
Ala GlnGluGlnGlnGlyGlyGlySerAsnCysSerIleMetIle
Asp GluIleIleHisHisLeuLysArgProProAlaProLeuLeu
60Asp ProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAsp
Arg AsnLeuArgLeuProAsnLeuGluSerPheValArgAlaVal
Lys AsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsn
Leu GlnProCysLeuProSerAlaThrAlaTyrValGluGlyGly
Gly GlySerProGlyGluProSerGlyProIleSerThrIleAsn
6SPro SerProProSerLysGluSerHisLysSerProAsnMetAla
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
70Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
Ala ThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGly
His SerLeuGlyIleProTrpAlaProLeuSerSerCysProSer
Gln AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGly
Leu PheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
7SPro GluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAla
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/20037
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
Ala Pro Ala Leu Gln Pro SEQ ID N0:494
31107.Pep
Ala GlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeu
Val ThrLeuGluGlnAlaGlnGluGlnGlnGlyGlyGlySerAsn
Cys SerIleMetIleAspGluIleIleHisHisLeuLysArgPro
10Pro AlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspVal
Ser IleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSer
Phe ValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGlu
Ala IleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAla
Ala ProSerArgHisProIleIleIleLysTyrValGluGlyGly
15Gly GlySerProGlyGluProSerGlyProIleSerThrIleAsn
Pro SerProProSerLysGluSerHisLysSerProAsnMetAla
Thr GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArg
Ala GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGlu
Val SerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGly
20Ser GlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnVal
Arg LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
Ala ThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGly
His SerLeuGlyIleProTrpAlaProLeuSerSerCysProSer
Gln AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGly
25Leu PheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
Pro GluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAla
Asp PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMet
Ala ProAlaLeuGlnProSEQID
N0:495
31208.Pep
Leu AspProAsnAsnLeuAsnAspGluAspValSerIle LeuMet
Asp ArgAsnLeuArgLeuProAsnLeuGluSerPheVal ArgAla
35Val LysAsnLeuGluAsnAlaSerGlyIleGluAlaIle LeuArg
Asn LeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArg
His ProIleIleIleLysAlaGlyAspTrpGlnGluPhe ArgGlu
Lys LeuThrPheTyrLeuValThrLeuGluGlnAlaGln GluGln
Gln GlyGlyGlySerGlyGlyGlySerGlyGlyGlySer AsnCys
40Ser IleMetIleAspGluIleIleHisHisLeuLysArg ProPro
Ala ProLeuTyrValGluGlyGlyGlyGlySerProGly GluPro
Ser GlyProIleSerThrIleAsnProSerProProSer LysGlu
Ser HisLysSerProAsnMetAlaThrGlnGlyAlaMet ProAla
Phe AlaSerAlaPheGlnArgArgAlaGlyGlyValLeu ValAla
45Ser HisLeuGlnSerPheLeuGluValSerTyrArgVal LeuArg
His LeuAlaGlnProSerGlyGlySerGlyGlySerGln SerPhe
Leu LeuLysSerLeuGluGlnValArgLysIleGlnGly AspGly
Ala AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeu CysHis
Pro GluGluLeuValLeuLeuGlyHisSerLeuGlyIle ProTrp
50Ala ProLeuSerSerCysProSerGlnAlaLeuGlnLeu AlaGly
Cys LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGln GlyLeu
Leu GlnAlaLeuGluGlyIleSerProGluLeuGlyPro ThrLeu
Asp ThrLeuGlnLeuAspValAlaAspPheAlaThrThr IleTrp
Gln GlnMetGluGluLeuGlyMetAlaProAlaLeuGln ProSEQ ID
N0:496
55
31109.Pep
Asn AlaSerGlyIleGluAlaIleLeuArgAsnLeuGln ProCys
Leu ProSerAlaThrAlaAlaProSerArgHisProIle IleIle
60Lys AlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyr
Leu ValThrLeuGluGlnAlaGlnGluGlnGlnGlyGly GlySer
Gly GlyGlySerGlyGlyGlySerAsnCysSerIleMet IleAsp
Glu IleIleHisHisLeuLysArgProProAlaProLeu LeuAsp
Pro AsnAsnLeuAsnAspGluAspValSerIleLeuMet AspArg
65Asn LeuArgLeuProAsnLeuGluSerPheValArgAla ValLys
Asn LeuGluTyrValGluGlyGlyGlyGlySerProGly GluPro
Ser GlyProIleSerThrIleAsnProSerProProSer LysGlu
Ser HisLysSerProAsnMetAlaThrGlnGlyAlaMet ProAla
Phe AlaSerAlaPheGlnArgArgAlaGlyGlyValLeu ValAla
70Ser HisLeuGlnSerPheLeuGluValSerTyrArgVal LeuArg
His LeuAlaGlnProSerGlyGlySerGlyGlySerGln SerPhe
Leu LeuLysSerLeuGluGlnValArgLysIleGlnGly AspGly
Ala AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeu CysHis
Pro GluGluLeuValLeuLeuGlyHisSerLeuGlyIle ProTrp
75Ala ProLeuSerSerCysProSerGlnAlaLeuGlnLeu AlaGly
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97l20037
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
SEQ ID N0:497
31110.Pep
Ala ProSerArgHisProIleIleIleLysAlaGlyAspTrpGln
10Glu PheArgGluLysLeuThrPheTyrLeuValThrLeuGluGln
Ala GlnGluGlnGlnGlyGlyGlySerGlyGlyGlySerGlyGly
Gly SerAsnCysSerIleMetIleAspGluIleIleHisHisLeu
Lys ArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAsp
Glu AspValSerIleLeuMetAspArgAsnLeuArgLeuProAsn
15Leu GluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
Gly IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSer
Ala ThrAlaTyrValGluGlyGlyGlyGlySerProGlyGluPro
Ser GlyProIleSerThrIleAsnProSerProProSerLysGlu
Ser HisLysSerProAsnMetAlaThrGlnGlyAlaMetProAla
20Phe AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
Ser HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
His LeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
Leu LeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGly
Ala AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis
2SPro GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrp
Ala ProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
Cys LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeu
Leu GlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu
Asp ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrp
30Gln GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
SEQ N0:498
ID
31111.Pep
35Ala GlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeu
Val ThrLeuGluGlnAlaGlnGluGlnGlnGlyGlyGlySerGly
Gly GlySerGlyGlyGlySerAsnCysSerIleMetIleAspGlu
Ile IleHisHisLeuLysArgProProAlaProLeuLeuAspPro
Asn AsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
40Leu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsn
Leu GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGln
Pro CysLeuProSerAlaThrAlaAlaProSerArgHisProIle
Ile IleLysTyrValGluGlyGlyGlyGlySerProGlyGluPro
Ser GlyProIleSerThrIleAsnProSerProProSerLysGlu
45Ser HisLysSerProAsnMetAlaThrGlnGlyAlaMetProAla
Phe AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
Ser HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
His LeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
Leu LeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGly
50Ala AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis
Pro GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrp
AIa ProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
Cys LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeu
Leu GlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu
5$Asp ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrp
Gln GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
SEQ ID N0:499
pMON15981
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgASn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaASpPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis
LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu
CA 02268742 1999-04-19
WO 98/17810 ~9 ~ PCT/US97/20037
ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThr SEQ ID N0:500
pMON159B2
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaPro
IS AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu
ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer
SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp
GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu
ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGln
AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
LeuLeuGlnAlaLeuGluGlyIleSer SEQ ID N0:501
pMON15965
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuASpProAsnASnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVa1
AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln
ProGlyGlyGlySerASpMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer
PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln
GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu
GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp
PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
ThrGlnGlyAlaMetProAlaPheAla SEQ ID N0:502
pMON15966
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProASnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet
ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu
$S GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly
SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
SerLeuGluGlnValArgLysIleGlnGlyASpGlyAlaAlaLeuGlnGluLysLeuCys
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIle
ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr
IleTrpGlnGlnMetGluGluLeuGly SEQ ID N0:503
pMON15967
MetAlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuASpProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
~LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu
CA 02268742 1999-04-19
WO 98117810 ~9 ~ PCT/US97/20037
GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis
ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer
CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe
S LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu
AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
LeuGlyMetAlaProAlaLeuGlnPro SEQ ID N0:504
pMON31112.pep
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnASn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleHisIleLysAspGlyASpTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
SEQ ID N0:505
pMON31113.pep
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn
3S LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleIleIleArgAspGlyASpTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProASnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnPro SEQ ID N0:506
pMON31114.pep
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
SS ProLeuLeuAspPheAsnASnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysASnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
6S LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
SEQ ID N0:507
pMON31115.pep
MetAlaASnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
75 ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnASpIleLeuMetAspAsnAsn
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~r96
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnPro SEQ ID N0:508
pMON28505
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVa1
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu
GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu
ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaPro
ProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSer
ArgLeuSerGlnCysPro SEQ ID N0:509
pMON28506
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuASpProAsnASnLeuASnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe
LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer
ThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAsp
LeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGln
CysProGluValHisPro SEQ ID N0:510
pMON28507
AlaASnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnASnLeuAsnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu
ProProGlnGlyArgThrThrAlaHisLysAspProASnAlaIlePheLeuSerPheGln
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVa1
ArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu
SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVa1
HisProLeuProThrPro SEQ ID N0:511
pMON28508
CA 02268742 1999-04-19
WO 98/17810 PCT/L1S97I20037
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuPro SEQ ID N0:512
pMON28509
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr
LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr
ThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyASn
MetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAsp
SerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro
ValLeuLeuProAlaVa1 SEQ ID N0:513
pMON28510
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerPro
AlaProProAlaCysASpLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu
HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro
AlaValAspPheSerLeu SEQ ID N0:514
pMON28511
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe
GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu
LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu
ProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMet
GluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMet
AlaAlaArgGlyGlnLeu SEQ ID N0:515
CA 02268742 1999-04-19
WO 98/17810 ~~ ~ PCT/US97/20037
pMON28512
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProASnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerPro
AlaProProAlaCysASpLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu
HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro
AlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly
AlaLeuGlnSerLeuLeu SEQ ID N0:516
pMON28513
AlaASnCysSerIleMetIleAspGluIleIleHisIiisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr
LeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysASpLeu
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys
ProGluValHisProLeuProThrProValLeuLeuProAlaValASpPheSerLeuGly
GluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeu
LeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeu
LeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGly
ThrGlnLeuProProGln SEQ ID N0:517
pMON28514
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro
ProGlnGlyArgThrThr SEQ ID N0:518
pMON28515
f)~ AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnASpGluAspValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluASnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnfiisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyASnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgASpSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLys SEQ ID N0:519
CA 02268742 1999-04-19
WO 98/17810 ~ ~~ PCT/US97/20037
pMON28516
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnASnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVa1
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMet
AlaSerProAlaProProAlaCysASpLeuArgValLeuSerLysLeuLeuArgAspSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVa1
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly
GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr
AlaHisLysAspProAsn SEQ ID N0:520
pMON28519
AlaAsnCysSerIleMetIieAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVa1
AspPheSerLeuGlyGluTrpLysThrGlnI?etGluGluThrLysAlaGlnAspIleLeu
GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu
ValGlyGlySerThrLeuCysValArgGluPheGlyASnMetAlaSerProAlaProPro
AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg
LeuSerGlnCysPro SEQ ID N0:521
pMON28520
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerL2uLeu
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe
LeuSerPheGlnFiisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer
ThrLeuCysValArgGluPheGlyASnMetAlaSerProAlaProProAlaCysAspLeu
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys
ProGluValHisPro SEQ ID N0:522
pMON28521
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuASpProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetValLeuLeuProAlaValASpPheSerLeuGlyGluTrpLys
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu
ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVa1
ArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer
LysLeuLeuArgAspSerHisValLeuHisSerArgLeu5erGlnCysProGluValHis
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
ProLeuProThrPro SEQ ID N0:523
pMON28522
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
IS ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLysASpProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr
ProValLeuLeuPro SEQ ID N0:529
pMON28523
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluASnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr
LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr
ThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMet
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVa1
LeuLeuProAlaVal SEQ ID N0:525
pMON28529
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnASnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProASnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
SO HisLysSerProASnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAIa
ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis
SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla
ValAspPheSerLeu SEQ ID N0:526
pMON28525
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuASpProAsnAsnLeuAsnAspGluASpValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
CA 02268742 1999-04-19
WO 98/17810 ~ ~ PCT/US97/20037
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeu SEQ ID N0:527
pMON28526
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla
ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis
SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla
ValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIle
LeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro
ThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAla
LeuGlnSerLeuLeu SEQ ID N0:528
pMON28527
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr
LeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg
ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro
GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu
TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu
LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu
GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr
GlnLeuProProGln SEQ ID N0:529
pMON28528
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnASnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg
GluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLys
LeuLeuArgAspSerHisValLeuI-IisSerArgLeuSerGlnCysProGluValHisPro
LeuProThrProValLeuLeuProAlaValASpPheSerLeuGlyGluTrpLysThrGln
MetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyVa1
MetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSer
GlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProPro
GlnGlyArgThrThr SEQ ID N0:530
pMON28529
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnASnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProASnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr
ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu
ThrLysAlaGlnASpIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVa1
ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg
ThrThrAlaHisLys SEQ ID N0:531
pMON28530
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVa1
1S ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAla
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysASpProAsn SEQ ID N0:532
pMON28533
2S
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVa1
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu
3S GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu
ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSer
ProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisVal
LeuHisSerArgLeuSerGlnCysPro SEQ ID N0:533
pMON28534
4S AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
SO TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer
SS LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe
LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer
ThrLeuCysValArgGluPheGlyGIyAsnGlyGlyAsnMetAlaSerProAlaProPro
AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg
60 LeuSerGlnCysProGluValHisPro SEQ ID N0:534
pMON28535
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
6S LeuLeuAspProAsnAsnLeuAsnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
70 ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu
7S ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln
CA 02268742 1999-04-19
WO 98/17810 ~ ~ PCT/US97/20037
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVa1
ArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeu
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys
ProGluValHisProLeuProThrPro SEQ ID N0:535
pMON28536
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuASpProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis
ProLeuProThrProValLeuLeuPro SEQ ID N0:536
pMON28537
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProASnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr
LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr
ThrAlaHisLysAspProASnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsn
GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu
LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu
ProThrProValLeuLeuProAlaVal SEQ ID N0:537
pMON28538
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgASnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly
5$ ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVa1
LeuLeuProAlaValAspPheSerLeu SEQ ID N0:538
pMON28539
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuASpProAsnAsnLeuASnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln
GlyArgThrThrAlaHisLysAspProASnAlaIlePheLeuSerPheGlnHisLeuLeu
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe
CA 02268742 1999-04-19
wo 9sn7s><o rcT~s9~izoo37
204
GlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu
SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVa1
HisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu
GlyValMetAlaAlaArgGlyGlnLeu SEQ ID N0:539
pMON28540
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgASpSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVa1
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly
GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu
LeuLeuGlyAlaLeuGlnSerLeuLeu SEQ ID N0:540
pMON28541
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr
LeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAla
CysASpLeuArgValLeuSerLysLeuLeuArgAspSerFiisValLeuHisSerArgLeu
SerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPhe
SerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAla
ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeu
SerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSer
LeuLeuGlyThrGlnLeuProProGln SEQ ID N0:541
pMON28542
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg
GluPheGlyGlyAsnGlyGlyASnMetAlaSerProAlaProProAlaCysAspLeuArg
ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro
GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu
TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu
LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu
GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr
GlnLeuProProGlnGlyArgThrThr SEQ ID N0:542
pMON28543
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluASpValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProASnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer
CA 02268742 1999-04-19
WO 98/17810 ~5 PCT/US97/20037
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro
ProGlnGlyArgThrThrAlaHisLys SEQ ID N0:543
pMON28544
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetRlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVa1
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGly
GlyAsnMetAlaSerProRlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgASpSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLysAspProAsn SEQ ID N0:544
pMON28545
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysRrgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnMetAlaSerProAlaProProRlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnRSpIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAla
HisLys SEQ ID N0:545
pMON32132
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArg SEQ ID N0:546
PMON32133
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaRrgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu
ValGlyGlySerThrLeuCysValArg SEQ ID N0:547
PMON32134
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu
LeuProAlaValRspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
GlnASpIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg
PheLeuMetLeuValGlyGlySerThrLeuCysValArg SEQ ID N0:548
pMON30237.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln
AspGluGluLeuCysGlyAlaLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
IS ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnPro
SEQ ID N0:549
pMON30238.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerASpTyrLeuLeuGlnASpTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
SEQ ID N0:550
pMON30239.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnGluThrSerGluGlnLeuValAlaLeuLysPro
TrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeu SEQ ID N0:551
pMON32329.pep
GlyThrGlnASpCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnPro
SEQ ID N0:552
pMON32330.pep
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
SEQ ID N0:553
pMON32341.pep
AlaThrGlnASpCysSerPheGlnHisSerProIleSerSerASpPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnPro
SEQ ID N0:554
pMON32342.pep
CA 02268742 1999-04-19
WO 98/17810 ~ PCT/US97/20037
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
SEQ ID N0:555
pMON32320.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlyAsnGlySerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:556
pMON32321.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGln SEQ ID N0:557
pMON32322.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlyASnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGln SEQ ID N0:55B
pMON32323.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGly
SerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyr
ProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeu
ValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:559
pMON32324.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGly
SerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
TrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:560
pMON32325.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThr5erG1uGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
CA 02268742 1999-04-19
WO 98117810 ~ ~ PCT/US97/20037
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGly
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAsp
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGly SEQ ID N0:561
pMON32326.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeu
GluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyAsn
GlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:562
pMON32327.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeu
GluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyAsn
GlyThrGlnASpCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnPro SEQ ID N0:563
pMON32328.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
3S SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeu
GluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGlyAsnGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCys
GlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnPro SEQ ID N0:564
pMON32348.pep
4S
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
SO IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlySerGlySerGlyGlySerGlySerGlyGlySerGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:565
SS
pMON32350.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
60 IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlySerGlySerGlyGlySerGlyThrGlnASpCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
6S TyrProValThrValAlaSerAsnLeuGln SEQ ID N0:566
FLT3N.pep
70 MetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerASpTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpAzgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
7S ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
CA 02268742 1999-04-19
WO 98117810 ~g PCT/L1S97/20037
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySer SEQ ID N0:567
FLT3C.pep
GlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer
AsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrp
MetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsn
ThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPhe
ValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSer
SerThrLeu SEQ ID N0:568
FLT7N.pep
MetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySer SEQ ID N0:569
FLT4C.pep
GlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
TrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeu SEQ ID N0:570
FLTIIN.pep
MetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer SEQ ID N0:571
FLTIOC.pep
GlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGln
GlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSer
GluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeu SEQ ID N0:572
pMON32365.pep
AlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGln SEQ ID N0:573
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
pMON32366.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSer
SerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVa1
ThrValAlaSerAsnLeuGln SEQ ID N0:574
pMON32367.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGln SEQ ID N0:575
pMON32368.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGly5erG1yG1yGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:576
pMON32369.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:577
pMON32370.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerASpPheAlaValLys
IleArgGluLeuSerASpTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
Gln SEQ ID N0:578
pMON30247.pep
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuASnAspGluAspValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyAlaLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
CA 02268742 1999-04-19
WO 98/17810 2~~ PCT/US97/20037
LeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
Pro SEQ ID N0:579
pMON30248.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuASnAspGluAspValSerIleLeuMetAspArgASnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaThrGlnASpCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyAlaLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLystSetGlnGlyLeuLeuGlu
ArgValASnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
ProAspSerSerThrLeu SEQ ID N0:580
pMON32332.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID
No:581
pMON32333.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluASpValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID
N0:582
pMON32334.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgASnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
CA 02268742 1999-04-19
WO 98/17810 PCT/I1S97/20037
2~Z
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGInLeuValAlaLeuLysProTrp
IleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuSerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
S AlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:583
pMON32335.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnASpGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuSerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID
No:584
pMON32336.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuASnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyASnGlySerGlyGly
AsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
Gln SEQ ID N0:585
pMON32337.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuAsnAspGluASpValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:586
pMON32338.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProAsnAsnLeuASnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysASnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
CA 02268742 1999-04-19
WO 98/i7810 2 ~ 3 PCT/US97/20037
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlySerGlyGiyAsnGlyThrGlnASpCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID
N0:587
pMON32339.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
LeuLeuAspProASnAsnLeuASnAspGluAspValSerIleLeuMetASpArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlySerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHis
SerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrp
ArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
Pro SEQ ID N0:588
pMON32369.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
Pro SEQ ID N0:589
pMON32377.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValASnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
ProAspSerSerThrLeu SEQ ID N0:590
pMON32352.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProASnPro
LeuLeuAspProAsnAsnLeuAsnSerGluASpMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
2 ~I~
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlyASnGlySerGlyGlyAsnGlyThrGlnASp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID
N0:591
pMON32353.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlyAsnGlySerGlyGlyAsnGlySerGlyGly
AsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
Gln SEQ ID N0:592
pMON32354.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuSerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:593
pMON32355.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProASnPro
LeuLeuAspProASnASnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnASpCysSerPheGlnHisSer
ProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID
N0:594
pMON32356.pep
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
z,~ 5
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuSerGlyGlyAsnGlySerGlyGlyASnGlySerGlyGlyAsnGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCys
GlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
Gly SEQ ID N0:595
pMON32357.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:596
pMON32358.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID
N0:597
pMON32359.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuSerGlyGly
AsnGlySerGlyGlyAsnGlySerGlyGlyAsnGlyThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrp
ArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
Pro SEQ ID N0:598
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
pMON32360.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
1$ CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlySerGlySerGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID
N0:599
pMON32362.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuSerGlyGlySerGlySerGlyGlySerGlySerGlyGly
SerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeu
Gln SEQ ID N0:600
pMON32392.pep
AlaThrGlnAspCysSerPheGlnFiisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProTyrValGluGlyGly
GlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuASnSerGluAsp
MetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAla
ValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCys
LeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:601
pMON32393.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMet
IleASpGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsn
LeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProASnLeuLeu
AlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArg
CA 02268742 1999-04-19
WO 98/17810 z ~ ~ PCT/IJS97/20037
AsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGlu
GlnAlaGlnGluGlnGln SEQ ID N0:602
pMON32396.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ProHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
1S HisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeu SEQ ID N0:603
pMON32371.pep
2S
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
3S GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:604
pMON32372.pep
4S AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluASpMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
SO TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuVaiLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
SS CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:605
pMON32373.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
7S ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/20037
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln SEQ ID
N0:606
pMON32374.pep
AlaASnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnASnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
SEQ ID N0:607
pMON32375.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuVaiThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
Gln SEQ ID N0:608
pMON32376.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlySerGlyGlyGlySerGlyThrGlnASpCysSerPheGlnHisSerProIleSer
SerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProVa1
ThrValAlaSerAsnLeuGln SEQ ID N0:609
pMON32378.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyThrGlnASpCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:610
pMON32379.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSer
SerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVa1
ThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID N0:611
pMON32380.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly SEQ ID
N0:612
pMON32381.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetASpIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGly5erG1yG1yGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGly
LeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SEQ ID N0:613
pMON32382.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IieGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
2.20
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
S IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCys
GlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
Gly SEQ ID N0:614
1S pMON32383.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
2S IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
ThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGly SEQ ID N0:615
pMON32384.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaVa1
LysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsn
LeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgVaIAsnThr
GluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:616
pMON32385.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
6S AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer
AsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrp
MetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsn
ThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:617
pMON32386.pep
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
2?.~
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
S ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
1S ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID
N0:618
pMON32387.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProASnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
2S ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyr
ProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeu
ValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGly
3S LeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
SEQ ID N0:619
pMON32388.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
4S ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrASnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
SO AsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGlyGly
SerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrp
ArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
SS GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
Pro SEQ ID N0:620
pMON32389.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluASpMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
6S ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGlu
LeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
222
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheVa1
ThrLysCysAlaPheGlnPro SEQ ID N0:621
hfit3-28291ink10.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArg
GlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSer
SerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln SEQ ID
N0:622
hflt3-28291ink15.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArg
GlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnASpCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeu
Gln SEQ ID N0:623
hflt3-34351ink10.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
$0 IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1 SEQ ID
N0:624
hflt3-34351ink15.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
CA 02268742 1999-04-19
WO 98117810 PCT/L1S97/20037
2z3
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
S GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
Val SEQ ID N0:625
hflt3-62631ink10.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
1S IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeu
2S LeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGly
LeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr SEQ ID
N0:626
hflt3-62631ink15.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
3S IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGinAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThr
GlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGlu
4S LeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
Thr SEQ ID N0:627
SO hflt3-94951ink10.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuAsnSerGluAspMetASpIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
SS IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
60 ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyThrGlnASpCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
6S ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeu SEQ ID
N0:628
70 hflt3-94951ink15.pep
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProASnLeuLeuAIaPheValArgAlaValLysHisLeuGluASnAlaSerGly
7S IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThr
ValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
Leu SEQ ID N0:629
hflt3-98991ink10.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlySerSer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGiuLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerASpTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGlu
LeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheVa1
ThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln SEQ ID
No:630
hflt3-98991ink15.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrAsnIleSerArgLeuLeuGlnGIuThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlyThrGlnASpCysSerPheGlnHisSerProIleSerSerAspPheAlaVa1
LysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsn
LeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThr
GluIleHisPheVaIThrLysCysAlaPheGlnProProProSerCysLeuArgPheVa1
Gln SEQ ID N0:631
hflt3-28291ink6.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuASpProAsnAsnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspTyrProValThrValAlaSerASnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrASnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArg
GlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGln SEQ ID N0:632
hflt3-28291ink7.pep
CA 02268742 1999-04-19
WO 98/17810 2z5 PCT/US97/20037
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
S ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArg
GlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
1$ AlaValLysIleArgGluLeuSerAspTyrLeuLeuGln SEQ ID N0:633
hflt3-28291ink13.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspTyrProValThrValAlaSerASnLeuGlnASpGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArg
GlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
3S SEQ ID N0:634
hflt3-28291ink21.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
4S TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrTleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
SO LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
55 TrpMetGluArgLeuLysThr SEQ ID N0:635
hflt3-34351ink6.pep
60 AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
6S TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
70 GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrVa1 SEQ ID N0:636
7S
CA 02268742 1999-04-19
WO 98/17810 PCT/IJS97/20037
2,ZCP
hflt3-34351ink7.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProASnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlyThr
GlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGlu
LeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1 SEQ ID N0:637
hflt3-34351inkl3.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetASpIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgASnLeuGInProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
SEQ ID N0:638
hflt3-34351ink21.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnASpTyrProValThrVa1 SEQ ID N0:639
hflt3-62631ink6.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGIuAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerPro
7J IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyr
CA 02268742 1999-04-19
WO 98/17810 2~~ PCT/US97/20037
ProValThrValAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeuTrpArgLeu
ValLeuAlaGlnArgTrpMetGluArgLeuLysThr SEQ ID N0:640
hflt3-62631ink7.pep
AlaASnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlyThrGlnASpCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr SEQ ID N0:641
hflt3-62631ink13.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProASnAsnLeuAsn5erGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProASp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
SEQ ID No:642
hflt3-62631ink21.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProASnMetAlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
TrpMetGluArgLeuLysThr SEQ ID N0:643
hflt3-94951ink6.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyThrGln
CA 02268742 1999-04-19
WO 98!17810 PCT/US97/20037
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGlu
LeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheVa1
ThrLysCysAlaPheGlnProProProSerCysLeu SEQ ID N0:644
hflt3-94951ink7.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProASnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlyThr
GlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGlu
LeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeu SEQ ID N0:645
hflt3-94951ink13.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuAsnSerGluAspMetASpIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
TrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeu
SEQ ID N0:646
hflt3-94951ink21.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProASnAsnLeuAsn5erGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeu SEQ ID N0:647
hflt3-98991ink6.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlySerSer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
CA 02268742 1999-04-19
WO 98/17810 ~~~ PCT/US97/20037
HisLysSerProAsnMetAlaThrASnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGly
LeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAla
PheGlnProProProSerCysLeuArgPheValGln SEQ ID N0:648
hflt3-98991ink7.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProASnAsnLeuASnSerGluAspMetASpIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlySerSer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlyThrGlnAspCysSer
PheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyr
LeuLeuGlnASpTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGly
GlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCys
AlaPheGlnProProProSerCysLeuArgPheValGln SEQ ID N0:649
hflt3-98991ink13.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlySerSer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln
SEQ ID N0:650
hflt3-98991ink21.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnPro
LeuLeuAspProAsnASnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeu
ArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIle
SerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuVa1
LeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeu
LeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGln SEQ ID N0:651
GlySerThrMetSerArgLeuProValLeuLeuLeuLeuGlnLeuLeuValArgProAlaMetSerThrAsnGln
AspLeuProValIleLysCysValLeuIleAsnHisLysAsnAsnAspSerSerValGlyLysSerSerSerTyr
ProMetValSerGluSerProGluAspLeuGlyCysAlaLeuArgProGlnSerSerGlyThrValTyrGluAla
AlaAlaValGluValAspValSerAlaSerIleThrLeuGlnValLeuValAspAlaProGlyAsnIleSerCys
LeuTrpValPheLysHisSerSerLeuAsnCysGlnProHisPheAspLeuGlnAsnArgGlyValValSerMet
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
230
ValIleLeuLysMetThrGluThrGlnAlaGlyGluTyrLeuLeuPheIleGlnSerGluAlaThrAsnTyrThr
IleLeuPheThrValSerIleArgAsnThrLeuLeuTyrThrLeuArgArgProTyrPheArgLysMetGluAsn
GlnAspAlaLeuValCysIleSerGluSerValProGluProIleValGluTrpValLeuCysAspSerGlnGly
GluSerCysLysGluGluSerProAlaValValLysLysGluGluLysValLeuHisGluLeuPheGlyMetAsp
IleArgCysCysAlaArgAsnGluLeuGlyArgGluCysThrArgLeuPheThrIleAspLeuAsnGlnThrPro
GlnThrThrLeuProGlnLeuPheLeuLysValGlyGluProLeuTrpIleArgCysLysAlaValHisValASn
HisGlyPheGlyLeuThrTrpGluLeuGluAsnLysAlaLeuGluGluGlyAsnTyrPheGluMetSerThrTyr
SerThrAsnArgThrMetIleArgIleLeuPheAlaPheValSerSerValAlaArgAsnAspThrGlyTyrTyr
ThrCysSerSerSerLysHisProSerGlnSerAlaLeuValThrIleValGluLysGlyPheIleASnAlaThr
AsnSerSerGluAspTyrGluIleAspGlnTyrGluGluPheCysPheSerValArgPheLysAlaTyrProGln
IleArgCysThrTrpThrPheSerArgLysSerPheProCysGluGlnLysGlyLeuAspAsnGlyTyrSerIle
SerLysPheCysAsnHisLysHisGlnProGlyGluTyrIlePheHisAlaGluAsnAspAspAlaGlnPheThr
LysMetPheThrLeuAsnIleArgArgLysProGlnValLeuAlaGluAlaSerAlaSerGlnAlaSerCysPhe
SerAspGlyTyrProLeuProSerTrpThrTrpLysLysCysSerAspLysSerProAsnCysThrGluGluIle
ThrGluGlyValTrpAsnArgLysAlaAsnArgLysValPheGlyGlnTrpValSerSerSerThrLeuAsnMet
SerGluAlaIleLysGlyPheLeuValLysCysCysAlaTyrAsnSerLeuGlyThrSerCysGluThrIleLeu
LeuAsnSerProGlyProPheProPheIleGlnAspAsnGluPheIleIleLeuGlyLeuPheGlyLeuLeuLeu
LeuLeuThrCysLeuCysGlyThrAlaTrpLeuCysCysSerProAsnArgLysAsnProLeuTrpProSerVal
ProAspProAlaHisSerSerLeuGlySerTrpValProThrIleMetGluGluAspAlaPheGlnLeuProGly
LeuGlyThrProProIleThrLysLeuThrValLeuGluGluAspGluLysLysProValProTrpGluSerHis
AsnSerSerGluThrCysGlyLeuProThrLeuValGlnThrTyrValLeuGlnGlyAspProArgAlaValSer
ThrGlnProGlnSerGlnSerGlyThrSerAspGlnValLeuTyrGlyGlnLeuLeuGlySerProThrSerPro
GlyProGlyHisTyrLeuArgCysAspSerThrGlnProLeuLeuAlaGlyLeuThrProSerProLysSerTyr
GluAsnLeuTrpPheGlnAlaSerProLeuGlyThrLeuValThrProAlaProSerGlnGluAspAspCysVal
PheGlyProLeuLeuAsnPheProLeuLeuGlnGlyIleArgValHisGlyMetGluAlaLeuGlySerPhe
SEQ ID N0:652
pMON30329.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuASpThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaThrGlnASpCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAsp
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
SEQ iD N0:653
pMON32173.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAla
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyr
LeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeu
ValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgVa1
AsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsn
IleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSer
ArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu SEQ ID N0:654
pMON32175.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAla
ThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGln
GlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeu
SerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGly
ProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGly
CA 02268742 1999-04-19
WO 98/17810 PCT/I1S97/20037
~3~I
MetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
SEQ ID N0:655
pMON32209.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnI?etGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPhe
AlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAsp
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyr
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLys
GluSerHisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerASpPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu SEQ
ID N0:656
pMON32205.pep
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsn
AsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArg
AlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnASp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArg
LeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeu
GluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAIaLeu~ysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeu SEQ ID N0:657
pMON32208.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAla
ThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGln
GlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeu
SerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGly
ProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGly
MetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly
ValLeuValAiaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProTyr
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLys
GluSerHisLysSerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu SEQ
ID No:658
CA 02268742 1999-04-19
WO 98!17810 PCT/ETS97/20037
2 32
pMON35767.pep/pMON32191.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
1$ ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:659
pMON32397.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluASpMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaASpTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrp
MetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGln
GluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln SEQ ID
N0:660
pMON32398.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrp
MetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGln
GluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
Gln SEQ ID N0:661
pMON32399.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnProLeuLeuASpProAsn
AsnLeuASnSerGluAspMetASpIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaAlaSerAsn
LeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSer
fi5 AspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1 SEQ ID
N0:662
pMON35700.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProASnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaAlaSerAsn
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
233
LeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThr
Val SEQ ID N0:663
pMON35701.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProASn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGly
GlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr SEQ ID
N0:664
pMON35702.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGly
GlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIle
SerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer
AsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLys
Thr SEQ ID N0:665
pMON35703.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaArgPheVa1
GlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeuTrp
ArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGlu
ArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeu SEQ ID
N0:666
pMON35704.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluASnAlaSerGlyIleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaArgPheVa1
GlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerASpTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnASpGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
Leu SEQ ID N0:667
pMON35705.pep
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~ 34
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuASpProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlySerSerProGlyGluProSer
GlyProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArg
CysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThr
GluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGln SEQ ID
N0:668
pMON35706.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProASnProLeuLeuAspProASn
AsnLeuASnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArg
CysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheVal
Gln SEQ ID N0:669
pMON35733.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaSerAsnLeu
GlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAla SEQ ID N0:670
pMON35734.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgASnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSer SEQ ID N0:671
pMON35735.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysFiisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaLeuGlnAsp
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGly
GlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSer
CA 02268742 1999-04-19
WO 98/17810 ~ 35 PCT/US97/20037
PheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyr
ProValThrValAlaSerAsn SEQ ID N0:672
pMON35736.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeu SEQ ID N0:673
pMON35738.pep
AlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuGlnAsp SEQ ID N0:674
pMON35739.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaGluLeuCys
GlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGln
GlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeu
ArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIle
ThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGly
GlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVal
AlaSerAsnLeuGlnAspGlu SEQ ID N0:675
pMON35740.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaLeuCysGly
GlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGly
LeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThr
ArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerPro
fi5
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGlu SEQ ID N0:676
pMON35741.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaSerAsnLeu
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
z3~
GlnASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspSerAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
Asp'FyrProValThrValAla SEQ ID N0:677
pMON35742.pep
AlaAsnCysSerIleMetIleASpGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaGlnAspGlu
GluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuArgGluThrSerGluGlnProValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrPro
ValThrValAlaSerASnLeu SEQ ID N0:678
pMON35743.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsn
AsnLeuAsnSerGluAspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArg
AlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaLeuCysGly
GlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGly
LeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThr
ArgGlnAsnPheSerArgCysLeuGluLeuGlnCysArgProAspSerSerThrLeuGlyGlyGlySerGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGlu SEQ ID N0:679
pMON32179.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIle
AsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleASpGluIle
IleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnASnLeuAsnSerGluAspMetAspIleLeu
MetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluASnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIle
IleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGlu
GlnGln SEQ ID N0:680
pMON35707.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuArgProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaASnCysSerIleMetIleAspGluIleIleHisHisLeuLysArg
ProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetASpIleLeuMetGluArgAsnLeuArg
ThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArg
AsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrp
GlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGln SEQ ID
No:681
pMON35708.pep
CA 02268742 1999-04-19
WO 98/17810 ~3~ PCT/US97/20037
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:682
pMON35709.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:683
pMON35710.pep
AlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgLeuValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThrVa1
AlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetASpIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:684
pMON35711.pep
AlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlyArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleF-IisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuASnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:685
pMON35719.pep
MetAlaAspTyrProValThrValAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeuTrpArgLeuVa1
LeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsn
ThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArg
CysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIle
AsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIleMetIleAspGluIle
IleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuASnSerGluAspMetAspIleLeu
MetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIle
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
23~
IleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGlu
GlnGln SEQ ID N0:686
pMON35720.pep
AlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGInGlyLeuLeuGluArgValAsnThrGluIleHisPheValThr
LysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
ProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValTyrValGluGlyGlyGlyGIySerProGlyGluProSerGlyProIIeSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMet
1S GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGiuAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:687
pMON35721.pep
AlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAla
PheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSer
2S SerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVa1
ThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThrTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuASnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:688
3S
pMON35722.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVaIThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlyTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
4S ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluASpMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIIeLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGInGluGln
SO Gln SEQ ID N0:689
pMON35723.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVal
SS AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
60 CysAlaPheGlnProTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGInProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
6S LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:690
pMON35725.pep
70 AlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
7S GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
LeuArgPheValGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnASnLeuAsnSerGluAspMetAspIleLeuMet
GluArgASnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:691
pMON35726.pep
AlaArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysPheTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuASnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:692
pMON35744.pep
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSer
GluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnPro
AspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetASpIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:693
pMON35745.pep
AlaAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCys
AlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGlu
GlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyr
LeuLeuGlnAspTyrProValThrValAlaSerTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:694
pMON35746.pep
AlaLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgLeuMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAla
PheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuVaiAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSer
SerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThr
GlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgASnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:695
pMON35747.pep
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerFiisLysSerProASnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProASnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:696
I$ pMON35748.pep
AlaGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisI-IisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:697
pMON35749.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnASpCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProASnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgASnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:698
pMON35750.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGly5erG1yG1yGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:699
pMON35769.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysArgProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrTleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgASnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:700
pMON35771.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlyTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProASnMetAlaAsnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluASpMetAspIleLeuMet
IS GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
Gln SEQ ID N0:701
pMON35774.pep
AlaGlnAspAspGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGinGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
2$ ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGly
GlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSerLysGluSerHisLysSer
ProAsnMetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAsnProLeuLeu
AspProAsnASnLeuAsnSerGluASpMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAla
PheValArgAlaValLysHisLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeu
ProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLys
LeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGln SEQ ID N0:702
pMON35775.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaASnCysSerIleMetIleAspGluIleIle
HisHisLeuLysArgProProAsnProLeuLeuAspProAsnAsnLeuAsnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
SO Gln SEQ ID N0:703
pMON35776.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSer
ThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrAlaGlyGlnProProLeuThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIle
MetIleASpGluIleIleHisHisLeuLysArgProProAsnProLeuLeuAspProASnAsnLeuAsnSerGlu
AspMetAspIleLeuMetGluArgAsnLeuArgThrProAsnLeuLeuAlaPheValArgAlaValLysHisLeu
GluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeu
GluGlnAlaGlnGluGlnGln SEQ ID N0:704
pMON32169.pep/pMON40000.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~Z
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluPro5erGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln SEQ ID N0:705
pMON32188.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuVa1
LeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsn
ThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnIleAsnIle
SerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArg
CysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAla
ValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer SEQ ID N0:706
pMON32273.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGlu
LeuGlnCysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCys
GlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGln
GlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro SEQ ID N0:707
pMON35795.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
SS GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThr
GluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaVa1
LysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsn SEQ ID N0:708
pMON35796.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSer
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~,3
LysGluSerHisLysSerProAsnMetAlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArg
LeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeu
$ GluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGly
GlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeu SEQ ID N0:709
pMON35797.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArg
TrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHis
PheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeu
GlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeu
GlnCysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
2$ GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAsp SEQ ID N0:710
pMON35798.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuASpValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrp
MetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPhe
ValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGln
GluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGln
CysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGlu
LeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGlu SEQ ID N0:711
4$ pMON35799.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuASpValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheVa1
ThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGly
GlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGlu SEQ ID N0:712
pMON39914.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuASpValAlaASpPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeu
CA 02268742 1999-04-19
WO 98!17810 PCT/US97/20037
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProASpSerSerThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThr
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyr
LeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:713
pMON39915.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIle
SerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer
AsnLeuGln SEQ ID N0:714
pMON39916.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgI-iisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThr
AlaGlyGlnProProLeuThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln SEQ ID N0:715
pMON35712.pep
AlaAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeu
AlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThr
GluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSer
ArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCys
LeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
GlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGln SEQ ID N0:716
pMON35713.pep
AlaAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThr
LysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGln
ProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsp
TyrProValThrVa1 SEQ ID N0:717
pMON35714.pep
AlaValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAla
PheGlnProProProSerCysLeuArgPheValGInThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSer
SerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVa1
ThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThr SEQ ID N0:718
pMON35715.pep
CA 02268742 1999-04-19
WO 98/17810 PCTIUS97/20037
~r5
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGly SEQ ID N0:719
pMON35716.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnPro SEQ ID N0:720
pMON35717.pep
AlaArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrp
IleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
AspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeu SEQ ID N0:721
pMON35718.pep
AlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGln SEQ ID N0:722
pMON32170.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:723
pMON32187.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspserSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnASp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:724
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
2u ~
pMON32271.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVal
AlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGln
S ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr5erG1uGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrAlaGlyGlnProProLeuThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGlyGly
GlySerASnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGln
ValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGlu
GluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIle
SerProGluLeuGlyProThrLeuAspThrLeuGlnLeuASpValAlaAspPheAlaThrThrIleTrpGlnGln
1S MetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGln
ArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis
LeuAlaGlnPro SEQ ID N0:725
pMON32272.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
2S LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGly
GlySerProGlyGlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGln
SerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeu
SerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGln
GlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAla
AspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAla
MetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeu
3S GluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:726
pMON32274.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrThrGlnAspCysSerPheGlnHisSer
4S ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGlyGlyGlySerAsnMetAlaThr
ProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGly
AspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGly
HisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
SO GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyPro
ThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMet
AlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVa1
LeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ
ID N0:727
SS
pMON35751.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
60 ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuArgProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
65 LysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysCysLeuGluGlnValArgLysIleGlnGlyASpGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuASpThrLeuGlnLeuAspValAlaAspPheAlaThr
70 ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:728
7$ pMON35752.pep
CA 02268742 1999-04-19
WO 98/17810 ~ ~ ~ PCT/US97120037
AlaASpGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVal
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:729
pMON35753.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgVaIValArgHisLeuAlaGlnPro SEQ ID N0:730
pMON35754.pep
AlaProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerValPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValIleArgHisLeuAlaGlnPro SEQ ID N0:731
pMON35755.pep
AlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSer
GluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnPro
AspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerHisProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuASp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:732
pMON35756.pep
AlaAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCys
AlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGlu
CA 02268742 1999-04-19
WO 98/17810 ~ $ PCT/US97/20037
GlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAsp
SerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGly
ThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyr
LeuLeuGlnAspTyrProValThrValAlaSerTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
S ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValIleArgHisLeuAlaGlnPro SEQ ID N0:733
pMON35757.pep
AlaLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgLeuMetGluArgLeuLys
ThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAla
PheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGln
LeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSer
SerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThr
GlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeu
LeuGlnAspTyrProValThrValAlaSerAsnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuASpValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:734
pMON35758.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:735
pMON35759.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGly5erG1yG1yGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlyTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyASpGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:736
pMON35760.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnASpCysSerPheGlnHisSerPro
IleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
~9
LysThrValAlaGlyTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:737
pMON35761.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysArgProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPhe
GlnHisSerProIleSerSerAsnPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrPro
ValThrValAlaSerAsnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIlePheThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:73B
pMON35762.pep
AlaGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGly
GlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGiyGlySerGlyThrGlnAspCysSer
PheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyr
ProValThrValAlaSerAsnLeuGlnAspGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:739
pMON35763.pep
AlaGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAla
GlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAsp
TyrProValThrValAlaSerAsnLeuGlnAspTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:740
pMON35764.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaASpPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
S LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVaiLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:741
pMON35765.pep
AlaThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLys
IleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeu
CysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMet
IS GlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCys
LeuArgPheValGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:742
2S
pMON35766.pep/pMON32190.pep/pMON40001.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVal
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
3S GlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisPro
GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeu
GlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerProGluLeuGlyProThrLeuASpThrLeuGlnLeuAspValAlaASpPheAlaThrThrIleTrpGln
GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
HisLeuAlaGlnPro SEQ ID N0:743
pMON35768.pep
4S
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
SO ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGln
AspCysSerPheGlnHisSerProIleSerSerAspSerAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
SS AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
60 SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:744
pMON35770.pep
AlaLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySer
6S LysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysTyrAlaPheGlnProProPro
SerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLys
ProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysArgProAspSerSerThrLeuGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
70 SerASnLeuGlnAspGluGluTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThr
IleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSer
LeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrp
AlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe
7S LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeu
CA 02268742 1999-04-19
WO 98/17810 25 ~ PCT/US97/20037
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThr
GlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGln
SerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:745
pMON35772.pep
AlaSerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnPro
ProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAla
LeuLysProTrpIleThrArgGlnAsnPhePheArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerPro
IleSerSerAspPheAlaValLysTleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAla
SerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeu
LysThrValAlaGlyTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:746
pMON35773.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGly
GlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSer
ProAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnVa1
ArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeu
AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaASpPheAlaThrThrIleTrpGlnGlnMet
GluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArg
ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeu
AlaGlnPro SEQ ID N0:747
pMON35777.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrThrGlnAspCysSerPheGlnHis
SerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThr
ValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGly
AlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPhe
LeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:748
pMON35778.pep
AlaGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThr
ValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPhe
GlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeu
ValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSer
ThrLeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrAlaGlyGlnProProLeuThrGln
AspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeu
GlnAspTyrProValThrValAlaSerAsnLeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuASp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
25Z
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:749
pMON35779.pep
$
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVal
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGly
GlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSer
ProAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnVa1
I$ ArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeu
AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaASpPheAlaThrThrIleTrpGlnGlnMet
GluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArg
ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeu
AlaGlnPro SEQ ID N0:750
pMON35780.pep
2$ AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgProLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGly
GlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSer
ProAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnVa1
ArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
3$ LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeu
AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuASpThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMet
GluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArg
ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeu
AlaGlnPro SEQ ID N0:751
pMON35782.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
4$ AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuProProProTrpSerProArgProLeuGlyAlaThrAlaProThrAlaGlyGlnProProLeuThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
$0 AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlyThrProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrProLeuGly
ProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIleGlnGlyASpGlyAla
AlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeu
GlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAiaGlyCysLeuSerGlnLeuHis
$$ SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAsp
ThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAla
LeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAla
SerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:752
60 pMON39908.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
6$ AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProValGluThrVa1
PheHisArgValSerGlnAspGlyLeuAspLeuLeuThrSerThrGlnAspCysSerPheGlnHisSerProIle
SerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSer
AsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGlyGlyGlySerASnMetAlaThrPro
LeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp
70 GlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGln
LeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThr
LeuAspThrLeuGlnLeuAspValAlaASpPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAla
ProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeu
CA 02268742 1999-04-19
WO 98/17810 252 PCT/US97/20037
ValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro SEQ ID
NO:753
pMON32275.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProPro
SerLysGluSerHisLysSerProAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeu
LeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyr
LysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCys
ProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeu
GlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAla
ThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAla
PheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyPro
IleSerThrIleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnAspCysSer
PheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGlnAspTyr
ProValThrValAlaSerAsnLeuGln SEQ ID N0:754
pMON35781.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnGluProLysSerProAspThrHisThrSer
ProProSerProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnVa1
ArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGlu
LeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeu
AlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMet
GluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArg
ArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeu
AlaGlnProSerAlaGluProLysSerProAspThrHisThrSerProProSerProGlySerAsnLeuGlnAsp
GluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGly
SerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProPro
ProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeu
LysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu
SEQ ID N0:755
pMON35783.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyTrpGlnGlyArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheProLysSerProASpThrHisThrSerProProSer
ProGlyThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
SerAlaGluProLysSerProAspThrHisThrSerProProSerProGlyLysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysPro
TrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu SEQ ID
N0:756
pMON32276.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGiuArgValAsnThrGluIleHisPheValThrLysSerAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
~SerSerPheGlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
GlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLysLeuCysHisPro
GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeu
GlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGln
GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
25~
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
HisLeuAlaGlnPro SEQ ID N0:757
pMON32277.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysSerAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGinProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspSerSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:75B
pMON32278.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
2$ AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerSerLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnSerGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerASnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
GlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLysLeuCysHisPro
GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeu
GlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGln
GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
HisLeuAlaGlnPro SEQ ID N0:759
pMON32279.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuVaILeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGinProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerSerLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnSerGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerASnLeuGln SEQ ID N0:760
pMON35790.pep
AlaThrGlnAspSerSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysSerAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysSerLeuGluGlnValArgLysIleGlnGlyASpGlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:761
pMON35791.pep
CA 02268742 1999-04-19
WO 98117810 PCT/US97/20037
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValASnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerSerLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnSerGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:762
pMON35792.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGlyGlyGlySerAsn
MetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrAsnLysLeuCysHisProGluGluLeuVal
LeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGlu
LeuGlyProThrLeuASpThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
LeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln
Pro SEQ ID N0:763
pMON39905.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnASpGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnSerGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAiaAlaLeuGlnGluLysLeuCysAlaThrTyrLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuASpThrLeuGlnLeuAspValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPro SEQ ID N0:764
pMON39906.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgArgLeuGluLeuGlnSerGlnProAspSerSerThrLeuTyrValGluGlyGlyGlyGlySerProGly
GlyGlySerGlyGlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeu
LysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrASnLys
LeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysPro
SerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuASpValAlaAspPheAlaThr
ThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPhe
AlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerFiisLeuGlnSerPheLeuGluValSerTyr
ArgValLeuArgHisLeuAlaGlnPr SEQ ID N0:765
pMON39909.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArg.ValASnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnASp
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
z5~
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
GlyGlySerASnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyVa1
LeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGly
GlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGly
IleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSer
GlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThr
LeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnPro SEQ ID N0:766
pMON39910.pep
AlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHis
LeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySer
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeu
CysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyr
GlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProTyrVaIGlu
GlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMet
GluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheVa1
ThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGlu
ThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCys
GlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGly
GlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeu
SerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:767
pMON35727.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVal
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnASpCysSerPheGlnHisSer
ProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnASpTyrProValThrVa1
AlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGly
GlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnASpTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:76B
pMON32168.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProASpSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerASpTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGly
ProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProASnMetAlaThrGlnAspCys
SerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAsn
TyrProValThrValAlaSerASnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrASnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProASpSerSerThrLeu SEQ ID N0:769
pMON32195.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
GlyGlySerAsnMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu
CA 02268742 1999-04-19
WO 98/17810 PCT1US97/20037
25~'
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisPro
GluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeu
GlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGly
IleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGln
GlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArg
HisLeuAlaGlnProTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGly
GlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAsp
PheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln
SEQ ID N0:770
pMON32196.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGly
GlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLys
SerProAsnMetAlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArg
GluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGly
GlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGly
LeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArg
PheValGlnThrASnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVaIAlaLeuLysProTrpIleThr
ArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeu SEQ ID N0:771
pMON32197.pep
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
TyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSer
LysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGln
ArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValASnThrGluIle
HisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeu
LeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGlu
LeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIle
ArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGly
GlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLys
SerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArg
LeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLys
CysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSer
GluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGlnPro
AspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySer
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGln SEQ ID N0:772
pMON32206.pep
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsn
AsnLeuAsnAspGluASpValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArg
AlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAla
ThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyASpTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSer
GlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAspGluGlu
CA 02268742 1999-04-19
WO 98/17810 ~5~ PCT/US97/20037
LeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLys
MetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSer
CysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysPro
TrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGly
SerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGln
HisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProVa1
ThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThr
IleASnProSerProProSerLysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeu
TrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeu
GluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheVa1
GlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGln
AsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySer
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAspCysSerPheGlnHisSerProIleSer
SerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsn
LeuGln SEQ ID N0:773
pMON32207.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnASp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGlyGlySerGly
GlyGlySerAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGlu
ArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThr
LysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThr
SerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPheSerArgCysLeuGluLeuGlnCysGln
ProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGly
SerGlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSer
AspTyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerPro
GlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMet
AlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysCysLeuGluGlnValArgLysIle
GlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeu
LeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCys
LeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeu
GlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeu
GlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGly
GlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro
STPSTPGIySerGluPheGlySer SEQ ID N0:774
pMON35728.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlyThrGlnAspCysSerPheGlnHisSer
ProIleSerSerASpPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGlnAspTyrProValThrVa1
AlaSerAsnLeuGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleASn
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaAsnCysSerIleMetIleAspGluIlelle
HisHisLeuLysArgProProAsnProLeuLeuASpProAsnAsnLeuAsnSerGluAspMetAspIleLeuMet
GluArgAsnLeuArgThrProASnLeuLeuAlaPheValArgAlaValLysHisLeuGluAsnAlaSerGlyIle
GluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIle
LysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGln
GlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProPro
SerLysGluSerHisLysSerProAsnMetAlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAla
GlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGlu
IleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThrAsnIleSerArg
LeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeu
GluLeuGlnCysGlnProAspSerSerThrLeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGly
GlyThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAIaSerAsnLeuGln SEQ ID N0:775
pMON32183.pep
AlaAspGluGluLeuCysGlyGlyLeuTrpArgLeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrVa1
AlaGlySerLysMetGlnGlyLeuLeuGluArgValAsnThrGluIleHisPheValThrLysCysAlaPheGln
ProProProSerCysLeuArgPheValGlnThrAsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuVa1
AlaLeuLysProTrpIleThrArgGlnAsnPheSerArgCysLeuGluLeuGlnCysGlnProAspSerSerThr
LeuGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGlyThrGlnAsp
CysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAspTyrLeuLeuGln
AspTyrProValThrValAlaSerAsnLeuGlnGluPheLysLeuGluProArgGlyProThrIleLysProCys
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ProProCysLysCysProAlaProAsnLeuLeuGlyGlyProSerValPheIlePheProProLysIleLysAsp
ValLeuMetIleSerLeuSerProIleValThrCysValValValAspValSerGluAspAspProAspValGln
IleSerTrpPheValAsnAsnValGluValHisThrAlaGlnThrGlnThrHisArgGluAspTyrAsnSerThr
LeuArgAlaValSerAlaLeuProIleGlnHisGlnAspTrpMetSerGlyLysGluPheLysCysLysValAsn
S AsnLysAspLeuProAlaProIIeGluArgThrIleSerLysProLysGlySerValArgAlaProGlnValTyr
ValLeuProProProGluGluGluMetThrLysLysGlnValThrLeuThrCysMetValThrAspPheMetPro
GluAspIleTyrValGluTrpThrAsnASnGlyLysThrGluLeuAsnTyrLysAsnThrGluProValLeuAsp
SerAspGlySerTyrPheMetTyrSerLysLeuArgValGluLysLysAsnTrpValGluArgAsnSerTyrSer
CysSerValValHisGluGlyLeuHisAsnHisHisThrThrLysSerPheSerArgThrProGlyLys SEQ
ID N0:776
pMON32184.pep
AlaThrGlnAspCysSerPheGlnHisSerProIleSerSerAspPheAlaValLysIleArgGluLeuSerAsp
TyrLeuLeuGlnAspTyrProValThrValAlaSerAsnLeuGlnAspGluGluLeuCysGlyGlyLeuTrpArg
LeuValLeuAlaGlnArgTrpMetGluArgLeuLysThrValAlaGlySerLysMetGlnGlyLeuLeuGluArg
ValAsnThrGluIleHisPheValThrLysCysAlaPheGlnProProProSerCysLeuArgPheValGlnThr
AsnIleSerArgLeuLeuGlnGluThrSerGluGlnLeuValAlaLeuLysProTrpIleThrArgGlnASnPhe
SerArgCysLeuGluLeuGlnCysGlnProAspSerSerThrLeuGluPheLysLeuGluProArgGlyProThr
IleLysProCysProProCysLysCysProAlaProAsnLeuLeuGlyGlyProSerValPheIlePheProPro
LysIleLysAspValLeuMetIleSerLeuSerProIleValThrCysValValValAspValSerGluAspAsp
ProAspValGlnIleSerTrpPheValAsnAsnValGluValHisThrAlaGlnThrGlnThrHisArgGluAsp
TyrAsnSerThrLeuArgAlaValSerAlaLeuProIleGlnHisGlnAspTrpMetSerGlyLysGluPheLys
CysLysValAsnAsnLysAspLeuProAlaProIleGluArgThrIleSerLysProLysGlySerValArgAla
ProGlnValTyrValLeuProProProGluGluGluMetThrLysLysGlnValThrLeuThrCysMetValThr
AspPheMetProGluASpIleTyrValGluTrpThrAsnAsnGlyLysThrGluLeuAsnTyrLysAsnThrGlu
ProValLeuAspSerAspGlySerTyrPheMetTyrSerLysLeuArgValGluLysLysAsnTrpValGluArg
AsnSerTyrSerCysSerValValHisGluGlyLeuHisAsnHisHisThrThrLysSerPheSerArgThrPro
GlyLys SEQ ID N0:777
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The following examples will illustrate the invention in
greater detail although it will be understood that the
invention is not limited to these specific examples.
EXAMPLE 1
Construction of parental BHK expression vector
A. Removal of AfIIII site from mammalian expression
plasmid.
A new mammalian expression vector was constructed
to accept NcoI-HindIII or AflIII-HindIII gene fragments
in-frame and 3' to the hIL-3 receptor agonist pMON13146
(WO 94/12638) gene and a mouse IgG2b linker fragment.
First, the single AflIII site was removed from pMON3934,
which is a derivative of pMON3359. pMON3359 is a pUCl8-
based vector containing a mammalian expression cassette.
The cassette includes a herpes simplex viral promoter
IE110 (-800 to +120) followed by a modified human IL-3
signal peptide sequence and an SV40 late poly-
adenylation (poly-A) signal which has been subcloned
into the pUCl8 polylinker (See Hippenmeyer et al.,
Bio/Technology, 1993, pp.1037-1041). The modified human
IL-3 signal sequence, which facilitates secretion of
gene products outside of the cell, is flanked by a BamHI
site on the 5' end and a unique NcoI site on the 3' end.
A unique HindIII site is 3' to the NcoI site and 5' to
the poly-A sequence. The DNA sequence encoding the
signal peptide is shown below (restriction enzyme sites
are indicated above). The ATG (methionine) codon within
the NcoI site is in-frame with the initiator ATG of the
signal peptide (underlined);
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BamHI NcoI
5'GGATCCACCATGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGCCATGG
(SEQ ID N0:857)
The single AfIIII site was removed from pMON3934 by
digestion with AflIII followed by filling in the
overhangs by addition of a DNA polymerase and
nucleotides. The digested DNA fragment was purified via
Magic PCR Clean up kit (Promega) and ligated with T4 DNA
ligase. The ligation reaction was transformed into DHSa
=M and the cells were plated onto LB-agar plus
ampicillin. Individual colonies were screened for the
loss of the AfIIII site by restriction analysis with
AflIII and HindIII which results in a single fragment if
the AfIIII site was removed. The resulting plasmid was
designated pMON30275.
B. Transfer of hIL-3 receptor agonist pMON13416/IgG2b
cassette into pMON30275.
The NcoI-HindIII fragment (ca. 425 bp) from
pMON30245 was ligated to the NcoI-HindIII fragment (ca.
3800 bp) of the pMON30275. pMON30245 (WO 94/12638)
contains the gene coding for hIL-3 receptor agonist
pMON13416 joined to a mouse IgG2b hinge fragment.
Immediately 3' to the IgG2b hinge and 5' to the HindIII
site is an AfIIII site. Genes can be cloned into the
AfIIII-HindIII sites as NcoI-HindIII or AfIIII-HindIII
fragments in frame with the hIL-3 variant
pMON13416/IgG2b hinge to create novel chimeras. The Ncol
site and the AfIIII site have compatible overhangs and
will ligate but both recognition sites are lost. The
plasmid, pMON30304 containing the DNA sequence of (SEQ
ID N0:1), coding for hIL-3 variant pMON13416 joined with
a mouse IgG2b hinge region, was a result of this
cloning.
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EXAMPLE 2
Construction of an intermediate lasmid containin one
copy of the c-mpl liaand (1-153) aene of the dimer
temt~late
In order to generate a plasmid DNA with the coding
sequence of c-mpl (1-153) ligand followed by a unique
EcoRI restriction site, the gene is isolated via reverse
transcriptase/polymerase chain reaction (RT/PCR). Human
fetal (lot #38130) and adult liver (lot #46018) A+ RNA
are obtained from Clontech (Palo Alto, CA) for source of
c-mpl ligand messenger RNA (mRNA). The first strand
cDNA reactions are carried out using a cDNA Cycle'1'M Kit
obtained from Invitrogen (San Diego, CA). In the RT
reaction, random primers and oligo dT primer are used to
generate cDNA from a combination of human and fetal
liver mRNA. For amplification of c-mpl ligand gene
fragment encoding amino acids 1-153, the RT product
serves as the template for PCR with a combination of the
primers, Forward primer: c-mplNcoI (SEQ ID N0:317) and
Reverse primer: Ecompl. The c-mplNcoI primer anneals to
the c-mpl ligand gene (bases #279-311 based on c-mpl
ligand sequence from Gene bank accession #L33410 or de
Sauvage et al., Nature 369: 533-538 (1994)) and encodes
a NcoI restriction enzyme site immediately 5' to the
first colon (Ser+1) of c-mpl ligand. The NcoI
restriction enzyme site codes for methionine and alanine
colons prior to Ser+1 and includes colon degeneracy for
the Ala colon and the first four colons (Ser, Pro, Ala,
& Pro) of c-mpl ligand. The Ecompl primer anneals to
bases #720-737 of c-mpl ligand and encodes an EcoRI site
(GAATTC) in-frame with the c-mpl ligand gene immediately
following Arg-153. The EcoRI site creates Glu and Phe
colons following Arg-153. The ca. 480 by PCR product
was purified, digested with NcoI and EcoRI and ligated
to the NcoI-EcoRI vector fragment of pMON3993 (ca. 4550
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bp.). pMON3993 was a derivative of pMON3359 (described
in Example 1). The human IL-3 signal peptide sequence,
which had been subcloned as a BamHI fragment into the
unique BamHI site between the IE110 promoter and poly-A
signal, contains an NcoI site at its 3' end and is
followed by a unique EcoRI site. The plasmid, pMON26458
containing the DNA sequence of (SEQ ID N0:2), coding for
c-mpl ligand amino acids 1-153 (SEQ ID N0:467), was the
result of this cloning.
EXAMPLE 3
Construction of the parental plasmids containing the
second genes of the dimer templates
For amplification of c-mpl ligand gene fragments
starting at amino acid 1 (Ser) with a termination codon
following amino acid 153 (Arg), the RT reaction from
Example 2 serves as the template for PCR with a
combination of the following primers; c-mplNcoI (SEQ ID
N0:317) (forward primer) and c-mplHindIII (SEQ ID
N0:319) (reverse primer). The c-mplNcoI (SEQ ID N0:317)
primer is described in Example 2. The c-mplHindIII (SEQ
ID N0:319) primer, which anneals to bases #716-737 of c-
mpl ligand, adds both a termination codon and a HindIII
restriction enzyme site immediately following the final
codon, Argls' .
Two types of PCR products are generated from the RT
cDNA samples, one with a deletion of the codons for
amino acids 112-115 and one without the deletion of
these codons. The c-mpl ligand PCR products (ca. 480
bp) are digested with NcoI and HindIII restriction
enzymes for transfer to a mammalian expression vector,
pMON3934. pMON3934 is digested with NcoI and HindIII
(ca. 3800 bp) and will accept the PCR products.
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Plasmid, pMON32132 (SEQ ID N0:84), coding for c-mpI
ligand amino acids 1-153 (SEQ ID N0:546) was a result of
this cloning. Plasmid, pMON32134 (SEQ ID N0:86), coding
for c-mpl ligand amino acids 1-153 (SEQ ID N0:548) was a
result of this cloning. Plasmid, pMON32133 (SEQ ID
N0:85), coding for c-mpl ligand amino acids 1-153 with a
deletion of codons 112-115 (0112-115) (SEQ ID N0:547)
was also a result of this cloning.
EXAMPLE 4
Generation of PCR dimer template 5L with a 112-115
deletion in the second c-mpl liaand Gene
A PCR template for generating novel forms of c-mpl
ligand is constructed by ligating the 3.7 Kbp
BstXI/EcoRI fragment of pMON26458 to the 1 Kbp
NcoI/BstXI fragment from pMON32133 (containing a
deletion of amino acids 112-115) along with the
EcoRI/AfIIII 5L synthetic oligonucleotide linker 5L-5'
(SEQ ID N0:322) and 5L-3' (SEQ ID N0:323).
The EcoRI end of the linker will ligate to the
EcoRI end of pMON26458. The AfIIII end of the linker
will ligate to the NcoI site of pMON32133, and neither
restriction site will be retained upon ligation. The
BstXI sites of pMON26458 and pMON32133 will ligate as
well. Plasmid, pMON28548, is a result of the cloning
and contains the DNA sequence of (SEQ ID N0:3) which
encodes amino acids 1-153 c-mpl ligand fused via a
GluPheGlyGlyAsnMet (SEQ ID N0:783) linker to amino acids
1-153 c-mpl ligand that contains a deletion of amino
acids 112-115 (SEQ ID N0:468).
EXAMPLE 5
Generation of PCR dimer temt~late 4L
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A PCR template for generating novel forms of c-mpl
ligand is constructed by ligating the 3.7 Kbp
BstXI/EcoRI fragment of pMON26458 to the 1 Kbp
NcoI/BstXI fragment from pMON32132 along with the
EcoRI/AfIIII 4L synthetic oligonucleotide linker 4L-5'
(SEQ ID N0:320) and 4L-3' (SEQ ID N0:321).
The EcoRI end of the linker will ligate to the
EcoRI end of pMON26458. The AfIIII end of the linker
will ligate to the NcoI site of pMON32132, and neither
restriction site will be retained upon ligation. The
BstXI sites of pMON26458 and pMON32132 will ligate as
well. The plasmid, pMON28500, is a result of the
cloning and contains the DNA sequence of (SEQ ID N0:4)
which encodes amino acids 1-153 c-mpl ligand fused via a
GluPheGlyAsnMetAla (SEQ ID N0:223) linker (4L) to amino
acids 1-153 c-mpl ligand (SEQ ID N0:469).
EXAMPLE 6
Generation of PCR dimer template 5L
A PCR template for generating novel forms of c-mpl
ligand is constructed by ligating the 3.7 Kbp
BstXI/EcoRI fragment of pMON26458 to the 1 Kbp
NcoI/BstXI fragment from pMON32132 along with the
EcoRI/AflIII 5L synthetic oligonucleotide linker 5L-5'
(SEQ ID N0:322) and 5L-3' (SEQ ID N0:323).
The EcoRI end of the linker will ligate to the
EcoRI end of pMON26458. The AfIIII end of the linker
will ligate to the NcoI site of pMON32132, and neither
restriction site will be retained upon ligation. The
BstXI sites of pMON26458 and pMON32132 will ligate as
well. Plasmid, pMON28501 is a result of the cloning and
contains the DNA sequence of (SEQ ID N0:4) which encodes
amino acids 1-153 c-mp1 ligand fused via a
GluPheGlyGlyAsnMet (SEQ ID N0:783) linker (5L) to amino
acids 1-153 c-mpl ligand (SEQ ID N0:470).
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EXAMPLE 7
Generation of PCR dimer templates 8L
A PCR template for generating novel forms of c-mpl
ligand is constructed by Iigating the 3.7 Kbp
BstXI/EcoRI fragment of pMON26458 to the 1 Kbp
NcoI/BstXI fragment from pMON32134 along with the
EcoRI/AfIIII 8L synthetic oligonucleotide linker 8L-5'
(SEQ ID N0:324} and 8L-3' (SEQ ID N0:325).
The EcoRI end of the linker will ligate to the
EcoRI end of pMON26458. The AfIIII end of the linker
will ligate to the Ncol site of pMON32134, and neither
restriction site will be retained upon ligation. The
BstXI sites of pMON26458 and pMON32134 will ligate as
well. Plasmid, pMON28502 is a result of the cloning
which contains the DNA sequence of (SEQ ID N0:6) and
encodes amino acids 1-153 c-mpl ligand fused via a
GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID N0:224) linker
(8L) to amino acids 1-153 c-mpl ligand (SEQ ID N0:471).
EXAMPLES 8-44
Generation of novel c-mpl liaand aenes with new N
terminus and C-terminus
A. PCR generation of genes encoding novel c-mpl ligand
receptor agonists.
Genes encoding novel c-mpl ligand receptor agonists
were generated using Method III (Horlick et al., Prot.
Eng. 5:427-433, 1992 ). The PCR reactions were carried
out using dimer templates, pMONs 28500, 28501, 28502 or
28548 and one of the sets of synthetic primer sets below
(The first number refers to the position of the first
amino acid in the original sequence. For example, the
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31-5' and 31-3' refers to the 5' and 3' oligo primers,
receptively, for the sequence beginning at the codon
corresponding to residue 31 of the original sequence.).
31-5' (SEQ ID N0:326) and 31-3' (SEQ ID N0:327), 35-5'
(SEQ ID N0:328) and 35-3' (SEQ ID N0:329), 39-5' (SEQ ID
N0:330) and 39-3' (SEQ ID N0:331), 43-5' (SEQ ID N0:332)
and 43-3' (SEQ ID N0:333), 45-5' (SEQ ID N0:334) and 45-
3' (SEQ ID N0:335), 49-5' (SEQ ID N0:336) and 49-3' (SEQ
ID N0:337), 82-5' (SEQ ID N0:338) and 82-3' (SEQ ID
N0:339), 109-5' (SEQ ID N0:340) and 109-3' (SEQ ID
N0:341}, 115-5' (SEQ ID N0:342) and 115-3' (SEQ ID
N0:343), 120-5' (SEQ ID N0:344) and 120-3' (SEQ ID
N0:345), 123-5' (SEQ ID N0:346) and 123-3' (SEQ ID
N0:347), 126-S' (SEQ ID N0:348) and 126-3' (SEQ ID
N0:349).
The templates and oligonucleotide sets used in the PCR
reactions are shown in Table 4. The products that were
generated were about 480 by and were purified via Magic
PCR Clean up kits (Promega).
B. Subcloning of novel c-mpl receptor agonist gene
products into mammalian expression vector for generation
of chimeras.
The c-mpl receptor agonist gene PCR products were
digested with NcoI and HindIII or AfIIII and HindIII
restriction enzymes (ca. 470 bp) for transfer to a
mammalian expression vector. The expression vector,
pMON30304, was digested with NcoI and HindIII (ca. 4200
bp) and accepts the PCR products as NcoI-HindIII or
AflIII-HindIII fragments. The restriction digest of the
PCR product and the resulting plasmids are shown in
Table 4.
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TABLE 4
PCR PCR Product ResultingBreakpoint
Example# PCR ProductRestrictionLinkerPlasmid in c-mpl
template PrimerDigest
pMON ligand
set
Example8 pMON2850131 NcoI/HindIII5L 28505 30-31
Example9 pMON2850135 AfIIII/Hindl5L 28506 34-35
II
Example10pMON2850139 NcoI/HindIII5L 28507 38-39
Example11pMON2850143 NcoI/HindIII5L 28508 42-43
Example12pMON2850145 NcoI/HindIII5L 28509 44-45
Example13pMON2850149 NcoI/HindIII5L 28510 48-49
Example14pMON2850182 NcoI/HindIII5L 28511 B1-82
Example15pMON28501109 NcoI/HindIII5L 28512 108-109
Example16pMON28501116 NcoI/HindIII5L 28513 115-116
Example17pMON28501120 NcoI/HindIII5L 28514 119-120
Example18pMON28501123 NcoI/HindIII5L 28515 122-123
Example19pMON28501126 NcoI/HindIII5L 28516 125-126
Example20pMON2850031 NcoI/HindIII4L 28519 30-31
Example21pMON2850035 AfIIII/HindI4L 28520 34-35
II
Example22pMON2850039 NcoI/HindIII4L 28521 38-39
Example23pMON2850043 Ncol/HindIII4L 28522 42-43
Example24pMON2850045 NcoI/HindIII4L 28523 44-45
Example25pMON2850049 NcoI/HindIII4L 28524 48-49
Example26pMON2850082 NcoI/HindIII4L 28525 81-82
Example27pMON28500109 NcoI/HindIII4L 28526 108-109
Example28pMON28500116 NcoI/HindIII4L 28527 115-116
Example29pMON28500120 Ncol/HindIII4L 28528 119-220
Example30pMON28500123 NcoI/HindIII4L 28529 122-123
Example31pMON28500126 NcoI/HindIII4L 28530 125-126
Example32pMON2850231 NcoI/HindIIIBL 28533 30-31
Example33pMON2850235 AfIIII/HindI8L 28534 34-35
II
Example34pMON2850239 NcoI/HindIIIBL 28535 38-39
Example35pMON2850243 NcoI/HindIII8L 28536 42-43
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10
TABLE 4 cont.
PCR PCR Product ResultingBreakpoint
Example# PCR ProductRestrictionLinkerPlasmid in c-mpl
templatePrimerDigest pMON ligand
set
Example36 pMON2850245 NcoI/HindIII8L 28537 44-45
Example37 pMON2850249 NcoI/HindIIIBL 28538 48-49
Example38 pMON2850282 Ncol/HindIII8L 28539 81-82
Example39 pMON28502109 NcoI/HindIII8L 28540 108-109
Example40 pMON28502116 NcoI/HindIII8L 28541 115-116
EXAMPLE41 pMON28502120 NcoI/HindIIiBL 28542 119-120
Example42 pMON28502123 NcoI/HindIII8L 28543 122-123
Example43 pMON28502126 NcoI/HindIII8L 28544 125-126
Example44 pMON28548123 NcoI/HindIII5L 28545 122-123
EXAMPLE 45
Construction of pMON15960
Construction of pMON15960, an intermediate plasmid used
for constructing plasmids containing DNA sequences
encoding G-CSF Serl' with a new N-terminus and C-
terminus. Plasmid pACYC177 (Chang, A.C.Y. and Cohen,
S.N. J. Bacteriol. 134:1141-1156, 1978) DNA was
digested with restriction enzymes HindIII and BamHI,
resulting in a 3092 base pair HindIII, BamHI fragment.
Plasmid, pMON13037 (WO 95/21254), DNA was digested with
BglII and FspI, resulting in a 616 base pair BglII,
FspI fragment. A second sample of plasmid, pMON13037,
DNA was digested with NcoI and HindIII, resulting in a
556 base pair NcoT, HindIII fragment. The synthetic DNA
" oligonucleotides 1GGGSfor (SEQ ID N0:380) and 1GGGSrev
(SEQ ID N0:381) were annealed to each other, and then
digested with AfIIII and FspI, resulting in a 21 base
pair AfIIII, FspI fragment. The restriction fragments
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were ligated, and the ligation reaction mixture was used
to transform E. coli K-12 strain JM101. Transformant
bacteria were selected on ampicillin-containing plates.
Plasmid DNA was isolated and analyzed by restriction
analysis to confirm the correct insert.
EXAMPLE 46
Construction of pMON15981
Construction of pMON15981, a plasmid containing DNA
sequences encoding a multi-functional hematopoietic
receptor agonist. Plasmid, pMON15960, DNA was digested
with restriction enzyme SmaI and used as template in a
PCR reaction using synthetic DNA oligonucleotides 38
stop (SEQ ID N0:369) and 39 start (SEQ ID N0:368) as
primers, resulting in the amplification of a DNA
fragment of 576 base pairs. The amplified fragment was
digested with restriction enzymes HindIII and NcoI,
resulting in a HindIII, NcoI fragment of 558 base pairs.
Plasmid, pMON13181, DNA was digested with HindIII and
AfIIII, resulting in a HindIII, AflIII fragment of 4068
base pairs. The restriction fragments were ligated, and
the ligation reaction mixture was used to transform E.
coli K-12 strain JM101. Transformant bacteria were
selected on ampicillin-containing plates. Plasmid DNA
was isolated, analyzed by restriction analysis, and
sequenced to confirm the correct insert. The plasmid,
pMON15981, contains the DNA sequence of (SEQ ID N0:78)
which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAIaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
3 5 SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVa1
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AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis
LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu
ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThr (SEQ ID N0:500)
EXAMPLE 47
Construction of~MON15982
Construction of pMON15982, a plasmid containing DNA
sequences encoding a multi-functional hematopoietic
receptor agonist. Plasmid, pMON15960, DNA was digested
with restriction enzyme SmaI and used as template in a
PCR reaction using synthetic DNA oligonucleotides 96
stop {SEQ ID N0:371) and 97 start {SEQ ID N0:370) as
primers, resulting in the amplification of a DNA
fragment of 576 base pairs. The amplified fragment was
digested with restriction enzymes HindIII and NcoI,
resulting in a HindIII, NcoI fragment of 558 base pairs.
Plasmid, pMON13181, DNA was digested with HindIII and
AfIIII, resulting in a HindIII, AfIIII fragment of 406$
base pairs. The restriction fragments were ligated, and
the ligation reaction mixture was used to transform E.
coli K-12 strain JM101. Transformant bacteria were
selected on ampicillin-containing plates. Plasmid DNA
was isolated, analyzed by restriction analysis, and
sequenced to confirm the correct insert. The plasmid,
pMON15982, contains the DNA sequence of {SEQ ID N0:79)
which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
3 5 GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
' SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu
4 0 AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaPro
AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu
ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer
SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp
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GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu
ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGln
AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
LeuLeuGlnAlaLeuGluGlyIleSer (SEQ ID N0:501)
EXAMPLE 48
Construction of t~MON15965
Construction of pMON15965, a plasmid containing DNA
sequences encoding a multi-functional hematopoietic
receptor agonist. Plasmid, pMON15960, DNA was digested
with restriction enzyme SmaI and used as template in a
PCR reaction using synthetic DNA oligonucleotides 142
stop (SEQ ID N0:377) and 141 start (SEQ ID N0:376) as
primers, resulting in the amplification of a DNA
fragment of 576 base pairs. The amplified fragment was
digested with restriction enzymes HindIII and NcoI,
resulting in a HindIII, NcoI fragment of 558 base pairs.
Plasmid, pMON13181, DNA was digested with HindIII and
AfIIII, resulting in a HindIII, AfIIII fragment of 4068
base pairs. The restriction fragments were ligated, and
the ligation reaction mixture was used to transform E.
coli K-12 strain JM101. Transformant bacteria were
selected on ampicillin-containing plates. Plasmid DNA
was isolated, analyzed by restriction analysis, and
sequenced to confirm the correct insert. The plasmid,
pMON15965, contains the DNA sequence of (SEQ ID N0:80)
which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
3 5 SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVa1
AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln
4 0 ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer
PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln
GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
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GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu
GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp
PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
ThrGlnGlyAlaMetProAlaPheAla (SEQ ID N0:502)
EXAMPLE 49
Construction of pMON15966
Construction of pMON15966, a plasmid containing DNA
sequences encoding a multi-functional hematopoietic
receptor agonist. Plasmid, pMON15960, DNA was digested
with restriction enzyme Smal and used as template in a
PCR reaction using synthetic DNA oligonucleotides 126
stop (SEQ ID N0:372) and 125 start (SEQ ID N0:373) as
primers, resulting in the amplification of a DNA
fragment of 576 base pairs. The amplified fragment was
digested with restriction enzymes HindIII and NcoI,
resulting in a HindIII, NcoI fragment of 558 base pairs.
Plasmid, pMON13181, DNA was digested with HindIII and
AfIIII, resulting in a HindIII, AfIIII fragment of 4068
base pairs. The restriction fragments were ligated, and
the ligation reaction mixture was used to transform E.
coli K-12 strain JM101. Transformant bacteria were
selected on ampicillin-containing plates. Plasmid DNA
was isolated, analyzed by restriction analysis, and
sequenced to confirm the correct insert. The plasmid,
pMON15966, contains the DNA sequence of (SEQ ID N0:81)
which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
3 5 SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet
ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu
GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly
SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIle
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ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr
IleTrpGlnGlnMetGluGluLeuGly (SEQ ID N0:503)
EXAMPLE 50
Construction of pMON15967
Construction of pMON15967, a plasmid containing DNA
sequences encoding a multi-functional hematopoietic
receptor agonist. Plasmid, pMON15960, DNA was digested
with restriction enzyme SmaI and used as template in a
PCR reaction using synthetic DNA oligonucleotides 132
stop (SEQ ID N0:375) and 133 start (SEQ ID N0:374) as
primers, resulting in the amplification of a DNA
fragment of 576 base pairs. The amplified fragment was
digested with restriction enzymes HindIII and NcoI,
resulting in a HindIII, NcoI fragment of 558 base pairs.
Plasmid, pMON13181, DNA was digested with HindIII and
AfIIII, resulting in a HindIII, AflIII fragment of 4068
base pairs. The restriction fragments were ligated, and
the ligation reaction mixture was used to transform E.
coli K-12 strain JM101. Transformant bacteria were
selected on ampicillin-containing plates. Plasmid DNA
was isolated, analyzed by restriction analysis, and
sequenced to confirm the correct insert. The plasmid,
pMON15967, contains the DNA sequence of (SEQ ID NO: 82)
which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
3 5 SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGiyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu
GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis
ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer
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CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe
LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu
AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
LeuGlyMetAlaProAlaLeuGlnPro SEQ ID N0:504
EXAMPLE 51
Construction of t~MON13180, an intermediate t~lasmid used
for constructina t~lasmids that contain DNA sequence
encodina multi-functional hematopoietic receptor
aaonists.
Plasmid, pMON13046 (WO 95/21254), DNA was digested
with restriction endonucleases XmaI and SnaBI, resulting
in a 4018 base pair vector fragment. The 4018 base pair
XmaI-SnaBI fragment was purified using a Magic DNA
Clean-up System kit (Promega, Madison, WI) in which the
base pair XmaI-SnaBI insert fragment is not retained.
The complimentary pair of synthetic oligonucleotides,
20 glyxal (SEQ ID N0:378) and glyxa2 (SEQ ID N0:379), were
designed to remove sequence encoding a factor Xa
cleavage site. When properly assembled these
oligonucleotides also result in XmaI and SnaBI ends.
The primers, Glyxal and glyxa2, were annealed in
25 annealing buffer (20mM Tris-HC1 pH7.5, 10 mM MgClz, 50
mM NaCl) by heating at 70°C for ten minutes and allowed
to slow cool. The 4018 base pair XmaI-SnaBI fragment
from pMON13046 was ligated with the assembled
oligonucleotides using T4 DNA lipase (Boehringer
Mannheim, Indianapolis, IN). A portion of the ligation
reaction was used to transform E. coli strain DHSa cells
(Life Technologies, Gaithersburg, MD). Transformant
bacteria were selected on ampicillin-containing plates.
Plasmid DNA was isolated from the transformants and
analyzed using a PCR based assay: Plasmid DNA from
selected transformants was sequenced to confirm the
correct insertion of the oligonucleotides. The
resulting plasmid was designated pMON13180 (SEQ ID
N0:88).
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
2~
EXAMPLE 52
Construction of t~MON13181 an intermediate t~lasmid used
for constructing plasmids that contain DNA seauences
encoding multi-functional hematot~oietic recet~tor
aaonists.
Plasmid, pMON13047 (WO 95/21254), DNA was digested
with restriction endonucleases Xmal and SnaBI, resulting
in a 4063 base pair vector fragment. The 4063 base pair
XmaI-SnaBI fragment was purified using a Magic DNA
Clean-up System kit (Promega, Madison, WI) in which the
25 base pair XmaI-SnaBI insert fragment is not retained.
The complimentary pair of synthetic oligonucleotides,
glyxal (SEQ ID N0:378) and glyxa2 (SEQ ID N0:379), were
designed to remove sequence encoding the factor Xa
cleavage site. When properly assembled these
oligonucleotides also result in XmaI and SnaBI ends.
Glyxal and glyxa2 were annealed in annealing buffer by
heating at 70°C for ten minutes and allowed to slow
cool. The 4063 base pair XmaI-SnaBI fragment from
pMON13047 was ligated with the assembled
oligonucleotides using T4 DNA ligase (Boehringer
Mannheim, Indianapolis, IN). A portion of the ligation
reaction was used to transform E. coli strain DH5a, cells
(Life Technologies, Gaithersburg, MD). Transformant
bacteria were selected on ampicillin-containing plates.
Plasmid DNA was isolated from the transformants and
analyzed using a PCR based assay. Plasmid DNA from
selected transformants was sequenced to confirm the
correct insertion of the oligonucleotides. The
resulting plasmid was designated pMON13181 (SEQ ID
N0:87).
EXAMPLE 53
CA 02268742 1999-04-19
WO 98/17810 2~~ PCT/US97/20037
Construction of pMON13182
The new N-terminus/C-terminus gene in pMON13182 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
39 start (SEQ ID N0:368) and L-11 start (SEQ ID N0:364).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 38 stop (SEQ
ID N0:369) and L-11 stop (SEQ ID N0:365). The full-
length new N terminus/C-terminus G-CSF Serl' gene was
created and amplified from the annealed Fragments Start
and Stop using primers 39 start and 38 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13180, was digested with restriction
endonucleases HindIII and AfIIII, resulting in a 4023
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase {Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DH5oc cells {Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13182.
E. coli strain JM101 was transformed with pMON13182
for protein expression and protein isolation from
inclusion bodies.
' The plasmid, pMON13182, contains the DNA sequence
. 35 of (SEQ ID N0:17) which encodes the following amino acid
sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
CA 02268742 1999-04-19
WO ~ ~g PCT/US97/20037
98/17810
Pro Pro AlaProLeuLeu AspProAsn AsnLeuAsnAsp GluAsp
Val Ser IleLeuMetAsp ArgAsnLeu ArgLeuProAsn LeuGIu
Ser Phe ValArgAlaVal LysAsnLeu GluAsnAlaSer GlyIle
Glu Ala IleLeuArgAsn LeuGlnPro CysLeuProSer AlaThr
Ala Ala ProSerArgHis ProIleIle IleLysAlaGly AspTrp
Gln Glu PheArgGluLys LeuThrPhe TyrLeuValThr LeuGlu
Gln Ala GlnGluGlnGln TyrValGlu GlyGlyGlyGly SerPro
Gly Gly GlySerGlyGly GlySerAsn MetAlaTyrLys LeuCys
His Pro GluGluLeuVal LeuLeuGly HisSerLeuGly IlePro
Trp Ala ProLeuSerSer CysProSer GlnAlaLeuGln LeuAla
Gly Cys LeuSerGlnLeu HisSerGly LeuPheLeuTyr GlnGly
Leu Leu GlnAlaLeuGlu GlyIleSer ProGluLeuGly ProThr
Leu Asp ThrLeuGlnLeu AspValAla AspPheAlaThr ThrIle
Trp Gln GlnMetGluGlu LeuGlyMet AlaProAlaLeu GlnPro
1 Thr Gln GlyAlaMetPro AlaPheAla SerAlaPheGln ArgArg
5
Ala Gly GlyValLeuVal AlaSerHis LeuGlnSerPhe LeuGlu
Val Ser TyrArgValLeu ArgHisLeu AlaGlnProSer GlyGly
Ser Gly GlySerGlnSer PheLeuLeu LysSerLeuGlu GlnVal
Arg Lys IleGlnGlyAsp GlyAlaAla LeuGlnGluLys LeuCys
2 Ala Thr (SEQID N0:472)
0
EXAMPLE 54
Construction of nMON13183
The new N-terminus/C-terminus gene in
pMON13183 was created using Method I as described in
Materials and Methods. "Fragment Start" was created and
amplified from G-CSF Serl' sequence in pMON13037 using
the primer set, 39 start (SEQ ID N0:368) and L-11 start
(SEQ ID N0:364). Fragment Stop was created and
amplified from G-CSF Serl' sequence in pMON13037 using
the primer set, 38 stop (SEQ ID N0:369) and L-11 stop
(SEQ ID N0:365). The full-length new N terminus/C-
terminus G-CSF Serl' gene was created and amplified from
the annealed Fragments Start and Stop using 39 start and
38 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13181, was digested with restriction
endonucleases HindIII and AfIIII, resulting in a 4068
base pair vector fragment, and purified using a Magic
CA 02268742 1999-04-19
WO 98/17810 ~~ PCT/US97/20037
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DHSa cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13183.
E. coli strain JM101 was transformed with pMON13183
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13183, contains the DNA sequence
of (SEQ ID N0:18) which encodes the following amino
acid sequence:
Asn CysSerIle MetIleAsp GluIleIleHis HisLeuLysArg
Pro ProAlaPro LeuLeuAsp ProAsnAsnLeu AsnAspGluAsp
Val SerIleLeu MetAspArg AsnLeuArgLeu ProAsnLeuGlu
2 Ser PheValArg AlaValLys AsnLeuGluAsn AlaSerGlyIle
0
Glu AlaIleLeu ArgAsnLeu GlnProCysLeu ProSerAlaThr
Ala AlaProSer ArgHisPro IleIleIleLys AlaGlyAspTrp
Gln GluPheArg GluLysLeu ThrPheTyrLeu ValThrLeuGlu
Gln AlaGlnGlu GlnGlnTyr ValGluGlyGly GlyGlySerPro
2 Gly GluProSer GlyProIle SerThrIleAsn ProSerProPro
5
Ser LysGluSer HisLysSer ProAsnMetAla TyrLysLeuCys
His ProGluGlu LeuValLeu LeuGlyHisSer LeuGlyIlePro
Trp AlaProLeu SerSerCys ProSerGlnAla LeuGlnLeuAla
Gly CysLeuSer GlnLeuHis SerGlyLeuPhe LeuTyrGlnGly
3 Leu LeuGlnAla LeuGluGly IleSerProGlu LeuGlyProThr
0
Leu AspThrLeu GlnLeuAsp ValAlaAspPhe AlaThrThrIle
Trp GlnGlnMet GluGluLeu GlyMetAlaPro AlaLeuGlnPro
Thr GlnGlyAla MetProAla PheAlaSerAla PheGlnArgArg
Ala GlyGlyVal LeuValAla SerHisLeuGln SerPheLeuGlu
3 Val SerTyrArg ValLeuArg HisLeuAlaGln ProSerGlyGly
5
Ser GlyGlySer GlnSerPhe LeuLeuLysSer LeuGluGlnVal
Arg LysIleGln GlyAspGly AlaAlaLeuGln GluLysLeuCys
Ala Thr(SEQ
ID
N0:473)
40 EXAMPLE 55
Construction of t~MON13184
The new N-terminus/C-terminus gene in pMON13184 was
45 created using Method I as described in Materials and
CA 02268742 1999-04-19
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Methods. Fragment Start was created and amplified from
G-CSF Serf' sequence in pMON13037 using the primer set,
97 start (SEQ ID N0:370) and L-11 start (SEQ ID N0:364).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 96 stop (SEQ
ID N0:371) and L-11 stop (SEQ ID N0:365). The full-
length new N terminus/C-terminus G-CSF Serl' gene was
created and amplified from the annealed Fragments Start
and Stop using 97 start and 96 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucl.eases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13180, was digested with restriction
endonucleases HindIII and AflIII, resulting in a 4023
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DH5oc cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13184.
E. coli strain JM101 was transformed with pMON13184
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13184, contains the DNA sequence
of (SEQ ID N0:19) which encodes the following amino
acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
3 5 Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
4 0 Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
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Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
1 0 Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser (SEQ ID N0:474)
EXAMPLE 56
Construction of pMON13185
The new N-terminus/C-terminus gene in pMON13185 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
97 start (SEQ ID N0:370) and L-11 start (SEQ ID N0:364).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 96 stop (SEQ
ID N0:371) and L-11 stop (SEQ ID N0:365). The full-
length new N terminus/C-terminus G-CSF Sere' gene was
created and amplified from the annealed Fragments Start
and Stop using 97 start and 96 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13181, was digested with restriction
endonucleases HindIII and AfIIII, resulting in a 4068
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DHSa cells (Life Technologies,
CA 02268742 1999-04-19
WO 98/17810 28~ PCT/ITS97/20037
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13185.
E. coli strain JM101 was transformed with pMON13185
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13185, contains the DNA sequence
of (SEQ ID N0:20) which encodes the following amino
acid sequence:
Asn CysSerIleMet IleAspGluIle IleHisHis LeuLysArg
Pro ProAlaProLeu LeuAspProAsn AsnLeuAsn AspGluAsp
Val SerIleLeuMet AspArgAsnLeu ArgLeuPro AsnLeuGlu
Ser PheValArgAla ValLysAsnLeu GluAsnAla SerGlyIle
Glu AlaIleLeuArg AsnLeuGlnPro CysLeuPro SerAlaThr
Ala AlaProSerArg HisProIleIle IleLysAla GlyAspTrp
Gln GluPheArgGlu LysLeuThrPhe TyrLeuVal ThrLeuGlu
2 Gln AlaGlnGluGln GlnTyrValGlu GlyGlyGly GlySerPro
0
Gly GluProSerGly ProIleSerThr IleAsnPro SerProPro
Ser LysGluSerHis LysSerProAsn MetAlaPro GluLeuGly
Pro ThrLeuAspThr LeuGlnLeuAsp ValAlaAsp PheAlaThr
Thr IleTrpGlnGln MetGluGluLeu GlyMetAla ProAlaLeu
2 Gln ProThrGlnGly AlaMetProAla PheAlaSer AlaPheGln
5
Arg ArgAlaGlyGly ValLeuValAla SerHisLeu GlnSerPhe
Leu GluValSerTyr ArgValLeuArg HisLeuAla GlnProSer
Gly GlySerGlyGly SerGlnSerPhe LeuLeuLys SerLeuGlu
Gln ValArgLysIle GlnGlyAspGly AlaAlaLeu GlnGluLys
3 Leu CysAlaThrTyr LysLeuCysHis ProGluGlu LeuValLeu
0
Leu GlyHisSerLeu GlyIleProTrp AlaProLeu SerSerCys
Pro SerGlnAlaLeu GlnLeuAlaGly CysLeuSer GlnLeuHis
Ser GlyLeuPheLeu TyrGlnGlyLeu LeuGlnAla LeuGluGly
Ile Ser(SEQID N0:475)
EXAMPLE 57
Construction of t~MON13186
The new N-terminus/C-terminus gene in pMON13186 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
126 start (SEQ ID N0:372) and L-11 start (SEQ ID
N0:364). Fragment Stop was created and amplified from
CA 02268742 1999-04-19
WO 98/17810 ~ 8~ PCT/L1S97/20037
G-CSF Serl' sequence in pMON13037 using the primer set,
125 stop (SEQ ID N0:373) and L-11 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
Fragments Start and Stop using 126 start and 125 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases Ncol
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13180, was digested with restriction
endonucleases HindIII and AfIIII, resulting in a 4023
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DH5oc cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13186.
E. coli strain JM101 was transformed with pMON13186
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13186, contains the DNA sequence
of (SEQ ID N0:21) which encodes the following amino
acid sequence:
3 Asn Cys SerIleMetIle AspGluIleIle HisHisLeu LysArg
0
Pro Pro AlaProLeuLeu AspProAsnAsn LeuAsnAsp GluAsp
Val Ser IleLeuMetAsp ArgAsnLeuArg LeuProAsn LeuGlu
Ser Phe ValArgAlaVal LysAsnLeuGlu AsnAlaSer GlyIle
Glu Ala IleLeuArgAsn LeuGlnProCys LeuProSer AlaThr
3 Ala Ala ProSerArgHis ProIleIleIle LysAlaGly AspTrp
5
Gln Glu PheArgGluLys LeuThrPheTyr LeuValThr LeuGlu
Gln Ala GlnGluGlnGln TyrValGluGly GlyGlyGly SerPro
Gly Gly GlySerGlyGly GlySerAsnMet AlaMetAla ProAla
Leu Gln ProThrGlnGly AlaMetProAla PheAlaSer AlaPhe
4 Gln Arg ArgAlaGlyGly ValLeuValAla SerHisLeu GlnSer
0
Phe Leu GluValSerTyr ArgValLeuArg HisLeuAla GlnPro
Ser Gly GlySerGlyGly SerGlnSerPhe LeuLeuLys SerLeu
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Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
Leu Gly (SEQ ID N0:476)
EXAMPLE 58
Construction of pMON13187
The new N-terminus/C-terminus gene in pMON13187 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
126 start (SEQ ID N0:372) and L-11 start (SEQ ID
N0:364). Fragment Stop was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
125 stop (SEQ ID N0:373) and L-12 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
Fragments Start and Stop using 126 start and 125 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13181, was digested with restriction
endonucleases HindIII and AflIII, resulting in a 4068
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DHSa cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13187.
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E. coli strain JM101 was transformed with pMON13187
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13187, contains the DNA sequence
of (SEQ ID N0:22) which encodes the following amino
acid sequence:
Asn Cys SerIleMetIle AspGluIle IleHisHisLeu LysArg
Pro Pro AlaProLeuLeu AspProAsn AsnLeuAsnAsp GluAsp
Val Ser IleLeuMetAsp ArgAsnLeu ArgLeuProAsn LeuGlu
Ser Phe ValArgAlaVal LysAsnLeu GluAsnAlaSer GlyIle
Glu Ala IleLeuArgAsn LeuGlnPro CysLeuProSer AlaThr
Ala Ala ProSerArgHis ProIleIle IleLysAlaGly AspTrp
Gln Glu PheArgGluLys LeuThrPhe TyrLeuValThr LeuGlu
Gln Ala GlnGluGlnGln TyrValGlu GlyGlyGlyGly SerPro
Gly Glu ProSerGlyPro IleSerThr IleAsnProSer ProPro
Ser Lys GluSerHisLys SerProAsn MetAlaMetAla ProAla
Leu Gln ProThrGlnGly AlaMetPro AlaPheAlaSer AlaPhe
2 Gln Arg ArgAlaGlyGly ValLeuVal AlaSerHisLeu GlnSer
0
Phe Leu GluValSerTyr ArgValLeu ArgHisLeuAla GlnPro
Ser Gly GlySerGlyGly SerGlnSer PheLeuLeuLys SerLeu
Glu Gln ValArgLysIle GlnGlyAsp GlyAlaAlaLeu GlnGlu
Lys Leu CysAlaThrTyr LysLeuCys HisProGluGlu LeuVal
2 Leu Leu GlyHisSerLeu GlyIlePro TrpAlaProLeu SerSer
5
Cys Pro SerGlnAlaLeu GlnLeuAla GlyCysLeuSer GlnLeu
His Ser GlyLeuPheLeu TyrGlnGly LeuLeuGlnAla LeuGlu
Gly Ile SerProGluLeu GlyProThr LeuAspThrLeu GlnLeu
Asp Val AlaAspPheAla ThrThrIle TrpGlnGlnMet GluGlu
30 Leu Gly (SEQ N0:477)
ID
EXAMPLE 59
Construction of bMON13188
35 The new N-terminus/C-terminus gene in pMON13188 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
133 start (SEQ ID N0:374) and L-11 start (SEQ ID
40 N0:364). Fragment Stop was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
132 stop (SEQ ID N0:375) and L-11 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
45 Fragments Start and Stop using 133 start and 132 stop.
CA 02268742 1999-04-19
WO 98/17810 2 g(p PCT/US97/20037
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13180, was digested with restriction
endonucleases HindIII and AflIII, resulting in a 4023
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DHSa cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13188.
E. coli strain JNI101 was transformed with pMON13188
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13188, contains the DNA sequence
of (SEQ ID N0:23) which encodes the following amino
acid sequence:
2 Asn Cys SerIleMetIle AspGluIleIle HisHisLeu LysArg
5
Pro Pro AlaProLeuLeu AspProAsnAsn LeuAsnAsp GluAsp
Val Ser IleLeuMetAsp ArgAsnLeuArg LeuProAsn LeuGlu
Ser Phe ValArgAlaVal LysAsnLeuGlu AsnAlaSer GlyIle
Glu Ala IleLeuArgAsn LeuGlnProCys LeuProSer AlaThr
3 Ala Ala ProSerArgHis ProIleIleIle LysAlaGly AspTrp
0
Gln Glu PheArgGluLys LeuThrPheTyr LeuValThr LeuGlu
Gln Ala GlnGluGlnGln TyrValGluGly GlyGlyGly SerPro
Gly Gly GlySerGlyGly GlySerAsnMet AlaThrGln GlyAla
Met Pro AlaPheAlaSer AlaPheGlnArg ArgAlaGly GlyVal
3 Leu Val AlaSerHisLeu GlnSerPheLeu GluValSer TyrArg
5
Val Leu ArgHisLeuAla GlnProSerGly GlySerGly GlySer
Gln Ser PheLeuLeuLys SerLeuGluGln ValArgLys IleGln
Gly Asp GlyAlaAlaLeu GlnGluLysLeu CysAlaThr TyrLys
Leu Cys HisProGluGlu LeuValLeuLeu GlyHisSer LeuGly
4 Ile Pro TrpAlaProLeu SerSerCysPro SerGlnAla LeuGln
0
Leu Ala GlyCysLeuSer GlnLeuHisSer GlyLeuPhe LeuTyr
Gln Gly LeuLeuGlnAla LeuGluGlyIle SerProGlu LeuGly
Pro Thr LeuAspThrLeu GlnLeuAspVal AlaAspPhe AlaThr
Thr Ile TrpGlnGlnMet GluGluLeuGly MetAlaPro AlaLeu
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Gln Pro (SEQ ID N0:478)
EXAMPLE 60
Construction of pMON13189
The new N-terminus/C-terminus gene in pMON13189 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
133 start (SEQ ID N0:374) and L-11 start (SEQ ID
N0:364). Fragment Stop was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
132 stop (SEQ ID N0:375) and L-11 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
Fragments Start and Stop using 133 start and 132 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13181, was digested with restriction
endonucleases HindIII and AfIIII, resulting in a 4068
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA lipase {Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DH5ot cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13189.
E. coli strain JM101 was transformed with pMON13189
for protein expression and protein isolation from
inclusion bodies.
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The plasmid, pMON13189, contains the DNA sequence
of (SEQ ID N0:24) which encodes the following amino
acid sequence:
Asn CysSerIleMet IleAspGluIle IleHisHis LeuLysArg
Pro ProAlaProLeu LeuAspProAsn AsnLeuAsn AspGluAsp
Val SerIleLeuMet AspArgAsnLeu ArgLeuPro AsnLeuGlu
Ser PheValArgAla ValLysAsnLeu GluAsnAla SerGlyIle
Glu AlaIleLeuArg AsnLeuGlnPro CysLeuPro SerAlaThr
Ala AlaProSerArg HisProIleIle IleLysAla GlyAspTrp
Gln GluPheArgGlu LysLeuThrPhe TyrLeuVal ThrLeuGlu
Gln AlaGlnGluGln GlnTyrValGlu GlyGlyGly GlySerPro
Gly GluProSerGly ProIleSerThr IleAsnPro SerProPro
Ser LysGluSerHis LysSerProAsn MetAlaThr GlnGlyAla
Met ProAlaPheAla SerAlaPheGln ArgArgAla GlyGlyVal
Leu ValAlaSerHis LeuGlnSerPhe LeuGluVal SerTyrArg
Val LeuArgHisLeu AlaGlnProSer GlyGlySer GlyGlySer
Gln SerPheLeuLeu LysSerLeuGlu GlnValArg LysIleGln
Gly AspGlyAlaAla LeuGlnGluLys LeuCysAla ThrTyrLys
2 Leu CysHisProGlu GluLeuValLeu LeuGlyHis SerLeuGly
0
Ile ProTrpAlaPro LeuSerSerCys ProSerGln AlaLeuGln
Leu AlaGlyCysLeu SerGlnLeuHis SerGlyLeu PheLeuTyr
Gln GlyLeuLeuGln AlaLeuGluGly IleSerPro GluLeuGly
Pro ThrLeuAspThr LeuGlnLeuAsp ValAlaAsp PheAlaThr
2 Thr IleTrpGlnGln MetGluGluLeu GlyMetAla ProAlaLeu
5
Gln Pro(SEQ 479)
ID
N0:
EXAMPLE 61
Construction of pMON13190
The new N-terminus/C-terminus gene in pMON13190 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
142 start (SEQ ID N0:376) and L-11 start (SEQ ID
N0:364). Fragment Stop was created and amplified from
G-CSF Ser~' sequence in pMON13037 using the primer set,
141 stop (SEQ ID N0:377) and L-11 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
Fragments Start and Stop using 142 start and 141 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
CA 02268742 1999-04-19
WO 98/17810 ~ g~ PCT/US97/20037
plasmid, pMON13180, was digested with restriction
endonucleases HindIII and AflIII, resulting in a 4023
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DHSot, cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13190.
E. coli strain JM101 was transformed with pMON13190
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13190, contains the DNA sequence
of (SEQ ID N0:25) which encodes the following amino
acid sequence:
Asn Cys SerIleMet IleAspGluIleIle HisHisLeu LysArg
Pro Pro AlaProLeu LeuAspProAsnAsn LeuAsnAsp GluAsp
Val Ser IleLeuMet AspArgAsnLeuArg LeuProAsn LeuGlu
Ser Phe ValArgAla ValLysAsnLeuGlu AsnAlaSer GlyIle
2 Glu Ala IleLeuArg AsnLeuGlnProCys LeuProSer AlaThr
5
Ala Ala ProSerArg HisProIleIleIle LysAlaGly AspTrp
Gln Glu PheArgGlu LysLeuThrPheTyr LeuValThr LeuGlu
Gln Ala GlnGluGln GlnTyrValGluGly GlyGlyGly SerPro
Gly Gly GlySerGly GlyGlySerAsnMet AlaSerAla PheGln
3 Arg Arg AlaGlyGly ValLeuValAlaSer HisLeuGln SerPhe
0
Leu Glu ValSerTyr ArgValLeuArgHis LeuAlaGln ProSer
Gly Gly SerGlyGly SerGlnSerPheLeu LeuLysSer LeuGlu
Gln Val ArgLysIle GlnGlyAspGlyAla AlaLeuGln GluLys
Leu Cys AlaThrTyr LysLeuCysHisPro GluGluLeu ValLeu
3 Leu Gly HisSerLeu GlyIleProTrpAla ProLeuSer SerCys
5
Pro Ser GlnAlaLeu GlnLeuAlaGlyCys LeuSerGln LeuHis
Ser Gly LeuPheLeu TyrGlnGlyLeuLeu GlnAlaLeu GluGly
Ile Ser ProGluLeu GlyProThrLeuAsp ThrLeuGln LeuAsp
Val Ala AspPheAla ThrThrIleTrpGln GlnMetGlu GluLeu
4 Gly Met AlaProAla LeuGlnProThrGln GlyAlaMet ProAla
0
Phe Ala (SEQ N0:480)
ID
EXAMPLE 62
CA 02268742 1999-04-19
WO 98/17810 2~~ PCT/US97/20037
Construction of pMON13191
The new N-terminus/C-terminus gene in pMON13191 was
created using Method I as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
142 start (SEQ ID N0:376) and L-12 start (SEQ ID
N0:364). Fragment Stop was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
141 stop (SEQ ID N0:377) and L-11 stop (SEQ ID N0:365).
The full-length new N terminus/C-terminus G-CSF Serl'
gene was created and amplified from the annealed
Fragments Start and Stop using 142 start and 141 stop.
The resulting DNA fragment which contains the new
gene was digested with restriction endonucleases NcoI
and HindIII and purified using a Magic DNA Clean-up
System kit (Promega, Madison, WI). The intermediate
plasmid, pMON13181, was digested with restriction
endonucleases HindIII and AflIII, resulting in a 4068
base pair vector fragment, and purified using a Magic
DNA Clean-up System kit (Promega, Madison, WI). The
purified restriction fragments were combined and ligated
using T4 DNA ligase (Boehringer Mannheim, Indianapolis,
IN). A portion of the ligation reaction was used to
transform E. coli strain DH5ot cells (Life Technologies,
Gaithersburg, MD). Transformant bacteria were selected
on ampicillin-containing plates. Plasmid DNA was
isolated and sequenced to confirm the correct insert.
The resulting plasmid was designated pMON13191.
E. coli strain JM101 was transformed with pMON13191
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13191, contains the DNA sequence
of (SEQ ID N0:26) which encodes the following amino
acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
CA 02268742 1999-04-19
WO 98/17810 2g~ PCT/US97/20037
Pro ProAlaPro LeuLeuAspPro AsnAsnLeuAsn AspGluAsp
Val SerIleLeu MetAspArgAsn LeuArgLeuPro AsnLeuGlu
Ser PheValArg AlaValLysAsn LeuGluAsnAla SerGlyIle
Glu AlaIleLeu ArgAsnLeuGln ProCysLeuPro SerAlaThr
Ala AlaProSer ArgHisProIle IleIleLysAla GlyAspTrp
Gln GluPheArg GluLysLeuThr PheTyrLeuVal ThrLeuGlu
Gln AlaGlnGlu GlnGlnTyrVal GluGlyGlyGly GlySerPro
Gly GluProSer GlyProIleSer ThrIleAsnPro SerProPro
Ser LysGluSer HisLysSerPro AsnMetAlaSer AlaPheGln
Arg ArgAlaGly GlyValLeuVal AlaSerHisLeu GlnSerPhe
Leu GluValSer TyrArgValLeu ArgHisLeuAla GlnProSer
Gly GlySerGly GlySerGlnSer PheLeuLeuLys SerLeuGlu
Gln ValArgLys IleGlnGlyAsp GlyAlaAlaLeu GlnGluLys
Leu CysAlaThr TyrLysLeuCys HisProGluGlu LeuValLeu
Leu GlyHisSer LeuGlyIlePro TrpAlaProLeu SerSerCys
Pro SerGlnAla LeuGlnLeuAla GlyCysLeuSer GlnLeuHis
Ser GlyLeuPhe LeuTyrGlnGly LeuLeuGlnAla LeuGluGly
Ile SerProGlu LeuGlyProThr LeuAspThrLeu GlnLeuAsp
Val AlaAspPhe AlaThrThrIle TrpGlnGlnMet GluGluLeu
2 Gly MetAlaPro AlaLeuGlnPro ThrGlnGlyAla MetProAla
0
Phe Ala(SEQ N0:481)
ID
EXAMPLE 63
Construction of pMON13192
The new N-terminus/C-terminus gene in pMON13192 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF sequence in pMON13037 using the primer set, 39
start (SEQ ID N0:368) and P-bl start (SEQ ID N0:366).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 38 stop (SEQ
ID N0:369) and P-bl stop (SEQ ID N0:367). Fragment
Start was digested with restriction endonuclease NcoI,
and Fragment Stop was digested with restriction
endonuclease HindIII. After purification, the digested
Fragments Start and Stop were combined with and ligated
to the approximately 3800 base pair NcoI-HindIII vector
fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Serl'
gene and was digested with restriction endonucleases
NcoI and HindIII. The digested DNA was resolved on a 1~
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
Z9z
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA). The
intermediate plasmid, pMON13180, was digested with
restriction endonucleases HindIII and AfIIII, resulting
in a 4023 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit (Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA ligase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DH5oc cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
insertion of the new gene. The resulting plasmid was
designated pMON13192.
E. coli strain ,7M101 was transformed with pMON13192
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13192, contains the DNA sequence
of (SEQ ID N0:27) which encodes the following amino
acid sequence:
13192.Pept
Asn Cys SerIleMetIle AspGluIleIle HisHisLeu LysArg
Pro Pro AlaProLeuLeu AspProAsnAsn LeuAsnAsp GluAsp
Val Ser IleLeuMetAsp ArgAsnLeuArg LeuProAsn LeuGlu
Ser Phe ValArgAlaVal LysAsnLeuGlu AsnAlaSer GlyIle
3 Glu Ala IleLeuArgAsn LeuGlnProCys LeuProSer AlaThr
0
Ala Ala ProSerArgHis ProIleIleIle LysAlaGly AspTrp
Gln Glu PheArgGluLys LeuThrPheTyr LeuValThr LeuGlu
Gln Ala GlnGluGlnGln TyrValGluGly GlyGlyGly SerPro
Gly Gly GlySerGlyGly GlySerAsnMet AlaTyrLys LeuCys
3 His Pro GluGluLeuVal LeuLeuGlyHis SerLeuGly IlePro
5
Trp Ala ProLeuSerSer CysProSerGln AlaLeuGln LeuAla
Gly Cys LeuSerGlnLeu HisSerGlyLeu PheLeuTyr GlnGly
Leu Leu GlnAlaLeuGlu GlyIleSerPro GluLeuGly ProThr
Leu Asp ThrLeuGlnLeu AspValAlaAsp PheAlaThr ThrIle
40 Trp Gln GlnMetGluGlu LeuGlyMetAla ProAlaLeu GlnPro
Thr Gln GlyAlaMetPro AlaPheAlaSer AlaPheGln ArgArg
Ala Gly GlyValLeuVal AlaSerHisLeu GlnSerPhe LeuGlu
Val Ser TyrArgValLeu ArgHisLeuAla GlnProThr ProLeu
Gly Pro AlaSerSerLeu ProGlnSerPhe LeuLeuLys SerLeu
45 Glu Gln ValArgLysIle GlnGlyAspGly AlaAlaLeu GlnGlu
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
z93
Lys Leu Cys Ala Thr (SEQ ID N0:482)
EXAMPLE 64
Construction of pMON13193
The new N-terminus/C-terminus gene in pMON13193 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
39 start (SEQ ID N0:368) and P-bl start (SEQ ID N0:366).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 38 stop (SEQ
ID N0:369) and P-bl stop (SEQ ID N0:367). Fragment
Start was digested with restriction endonuclease NcoI,
and Fragment Stop was digested with restriction
endonuclease HindIII. After purification, the digested
Fragments Start and Stop were combined with and ligated
to the approximately 3800 base pair NcoI-HindIII vector
fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Serl'
gene and was digested with restriction endonucleases
NcoI and HindIII. The digested DNA was resolved on a 10
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA). The
intermediate plasmid, pMON13181, was digested with
restriction endonucleases HindIII and AflIII, resulting
in a 4068 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit (Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA ligase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DHSa cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
CA 02268742 1999-04-19
WO 98/17810 PCT/US97120037
2g4
insertion of the new gene. The resulting plasmid was
designated pMON13193.
E. coli strain JM101 was transformed with pMON13193
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13193, contains the DNA sequence
of (SEQ ID N0:28) encodes the following amino acid
sequence:
Asn Cys SerIleMet IleAspGluIle IleHisHisLeu LysArg
Pro Pro AlaProLeu LeuAspProAsn AsnLeuAsnAsp GluAsp
Val Ser IleLeuMet AspArgAsnLeu ArgLeuProAsn LeuGlu
Ser Phe ValArgAla ValLysAsnLeu GluAsnAlaSer GlyIle
Glu Ala IleLeuArg AsnLeuGlnPro CysLeuProSer AlaThr
Ala Ala ProSerArg HisProIleIle IleLysAlaGly AspTrp
Gln Glu PheArgGlu LysLeuThrPhe TyrLeuValThr LeuGlu
Gln Ala GlnGluGln GlnTyrValGlu GlyGlyGlyGly SerPro
Gly Glu ProSerGly ProIleSerThr IleAsnProSer ProPro
2 Ser Lys GluSerHis LysSerProAsn MetAlaTyrLys LeuCys
0
His Pro GluGluLeu ValLeuLeuGly HisSerLeuGly IlePro
Trp Ala ProLeuSer SerCysProSer GlnAlaLeuGln LeuAla
Gly Cys LeuSerGln LeuHisSerGly LeuPheLeuTyr GlnGly
Leu Leu GlnAlaLeu GluGlyIleSer ProGluLeuGly ProThr
2 Leu Asp ThrLeuGln LeuAspValAla AspPheAlaThr ThrIle
5
Trp Gln GlnMetGlu GluLeuGlyMet AlaProAlaLeu GlnPro
Thr Gln GlyAlaMet ProAlaPheAla SerAlaPheGln ArgArg
Ala Gly GlyValLeu ValAlaSerHis LeuGlnSerPhe LeuGlu
Val Ser TyrArgVal LeuArgHisLeu AlaGlnProThr ProLeu
3 Gly Pro AlaSerSer LeuProGlnSer PheLeuLeuLys SerLeu
0
Glu Gln ValArgLys IleGlnGlyAsp GlyAlaAlaLeu GlnGlu
Lys Leu CysAlaThr (SEQ N0:483)
ID
EXAMPLE 65
Construction of t~MON25190
The new N-terminus/C-terminus gene in pMON25190 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF sequence in pMON13037 using the primer set, 97
start (SEQ ID N0:370) and P-bl start (SEQ ID N0:366).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 96 stop (SEQ
ID N0:371) and P-bl stop (SEQ ID N0:367). Fragment
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
295
Start was digested with restriction endonuclease NcoI,
and Fragment Stop was digested with restriction
endonuclease HindIII. After purification, the digested
Fragments Start and Stop were combined with and ligated
to the approximately 3800 base pair NcoI-HindIII vector
fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Serl'
gene and was digested with restriction endonucleases
Ncol and HindIII. The digested DNA was resolved on a 10
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA). The
intermediate plasmid, pMON13180, was digested with
restriction endonucleases HindIII and AfIIII, resulting
in a 4023 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit (Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA ligase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DHSoc cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
insertion of the new gene. The resulting plasmid was
designated pMON25190.
E. coli strain JM101 was transformed with pMON25190
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON25190, contains the DNA sequence
- of (SEQ ID N0:29) which encodes the following amino
acid sequence:
3 5 Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
CA 02268742 1999-04-19
WO 98/17810 2g~ PCTIUS97/20037
Ala AlaPro SerArgHisPro IleIleIleLys AlaGlyAsp Trp
Gln GluPhe ArgGluLysLeu ThrPheTyrLeu ValThrLeu Glu
Gln AlaGln GluGlnGlnTyr ValGluGlyGly GlyGlySer Pro
Gly GlyGly SerGlyGlyGly SerAsnMetAla ProGluLeu Gly
Pro ThrLeu AspThrLeuGln LeuAspValAla AspPheAla Thr
Thr IleTrp GlnGlnMetGlu GluLeuGlyMet AlaProAla Leu
Gln ProThr GlnGlyAlaMet ProAlaPheAla SerAlaPhe Gln
Arg ArgAla GlyGlyValLeu ValAlaSerHis LeuGlnSer Phe
Leu GluVal SerTyrArgVal LeuArgHisLeu AlaGlnPro Thr
Pro LeuGly ProAlaSerSer LeuProGlnSer PheLeuLeu Lys
Ser LeuGlu GlnValArgLys IleGlnGlyAsp GlyAlaAla Leu
Gln GluLys LeuCysAlaThr TyrLysLeuCys HisProGlu Glu
Leu ValLeu LeuGlyHisSer LeuGlyIlePro TrpAlaPro Leu
Ser SerCys ProSerGlnAla LeuGlnLeuAla GlyCysLeu Ser
Gln LeuHis SerGlyLeuPhe LeuTyrGlnGly LeuLeuGln Ala
Leu GluGly IleSer(SEQ
ID
N0:484)
EXAMPLE 66
Construction of pMON25191
The new N-terminus/C-terminus gene in pMON25191 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
97 start (SEQ ID N0:370} and P-bl start (SEQ ID N0:366).
Fragment Stop was created and amplified from G-CSF Ser"
sequence in pMON13037 using the primer set, 96 stop (SEQ
ID N0:371) and P-bl stop (SEQ ID N0:367). Fragment
Start was digested with restriction endonuclease NcoI,
and Fragment Stop was digested with restriction
endonuclease HindIII. After purification, the digested
Fragments Start and Stop were combined with and ligated
to the approximately 3800 base pair NcoI-HindIII vector
fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Serl'
gene and was digested with restriction endonucleases
NcoI and HindIII. The digested DNA was resolved on a 1o
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA}. The
CA 02268742 1999-04-19
WO 98/17810 PCT/US97/20037
2 g~
intermediate plasmid, pMON13181, was digested with
restriction endonucleases HindIII and AflIII, resulting
in a 4068 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit (Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA lipase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DHSa cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
insertion of the new gene. The resulting plasmid was
designated pMON25191.
E. coli strain JM101 was transformed with pMON25191
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON25191, contains the DNA sequence
of (SEQ ID N0:30) which encodes the following amino
acid sequence:
Asn CysSer IleMetIleAsp GluIleIleHis HisLeuLysArg
Pro ProAla ProLeuLeuAsp ProAsnAsnLeu AsnAspGluAsp
Val SerIle LeuMetAspArg AsnLeuArgLeu ProAsnLeuGlu
2 5 Ser PheVal ArgAlaValLys AsnLeuGluAsn AlaSerGlyIle
Glu AlaIle LeuArgAsnLeu GlnProCysLeu ProSerAlaThr
Ala AlaPro SerArgHisPro IleIleIleLys AlaGlyAspTrp
Gln GluPhe ArgGluLysLeu ThrPheTyrLeu ValThrLeuGlu
Gln AlaGln GluGlnGlnTyr ValGluGlyGly GlyGlySerPro
3 0 Gly GluPro SerGlyProIle SerThrIleAsn ProSerProPro
Ser LysGlu SerHisLysSer ProAsnMetAla ProGluLeuGly
Pro ThrLeu AspThrLeuGln LeuAspValAla AspPheAlaThr
Thr IleTrp GlnGlnMetGlu GluLeuGlyMet AlaProAlaLeu
Gln ProThr GlnGlyAlaMet ProAlaPheAla SerAlaPheGln
3 5 Arg ArgAla GlyGlyValLeu ValAlaSerHis LeuGlnSerPhe
Leu GluVal SerTyrArgVal LeuArgHisLeu AlaGlnProThr
Pro LeuGly ProAlaSerSer LeuProGlnSer PheLeuLeuLys
Ser LeuGlu GlnValArgLys IleGlnGlyAsp GlyAlaAlaLeu
Gln GluLys LeuCysAlaThr TyrLysLeuCys HisProGluGlu
40 Leu ValLeu LeuGlyHisSer LeuGlyIlePro TrpAlaProLeu
Ser SerCys ProSerGlnAla LeuGlnLeuAla GlyCysLeuSer
Gln LeuHis SerGlyLeuPhe LeuTyrGlnGly LeuLeuGlnAla
Leu GluGly IleSer(SEQ N0:485)
ID
CA 02268742 1999-04-19
WO 98/17810 ~ g g PCT/US97/20037
EXAMPLE 67
Construction of t~MON13194
The new N-terminus/C-terminus gene in pMON13194 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
126 start (SEQ ID N0:372) and P-bl start (SEQ ID
N0:366). Fragment Stop was created and amplified from
G-CSF Serl' sequence in pMON13037 using the primer set,
125 stop (SEQ ID N0:371) and P-bl stop (SEQ ID N0:367).
Fragment Start was digested with restriction
endonuclease NcoI, and Fragment Stop was digested with
restriction endonuclease HindIII. After purification,
the digested Fragments Start and Stop were combined with
and ligated to the approximately 3800 base pair Ncol-
HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Ser"
gene and was digested with restriction endonucleases
NcoI and HindIII. The digested DNA was resolved on a 10
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA). The
intermediate plasmid, pMON13180, was digested with
restriction endonucleases HindIII and AflIII, resulting
in a 4023 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit {Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA ligase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DHSa cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
CA 02268742 1999-04-19
WO 98/17810 Zg9 PCT/US97/20037
insertion of the new gene. The resulting plasmid was
designated pMON13194.
E. coli strain JM101 was transformed with pMON13194
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13194, contains the DNA sequence
of (SEQ ID N0:31) which encodes the following amino
acid sequence:
Asn CysSerIle MetIle AspGluIleIleHis HisLeuLysArg
Pro ProAlaPro LeuLeu AspProAsnAsnLeu AsnAspGluAsp
Val SerIleLeu MetAsp ArgAsnLeuArgLeu ProAsnLeuGlu
Ser PheValArg AlaVal LysAsnLeuGluAsn AlaSerGlyIle
1 Glu AlaIleLeu ArgAsn LeuGlnProCysLeu ProSerAlaThr
5
Ala AlaProSer ArgHis ProIleIleIleLys AlaGlyAspTrp
Gln GluPheArg GluLys LeuThrPheTyrLeu ValThrLeuGlu
Gln AlaGlnGlu GlnGln TyrValGluGlyGly GlyGlySerPro
Gly GlyGlySer GlyGly GlySerAsnMetAla MetAlaProAla
2 Leu GlnProThr GlnGly AlaMetProAlaPhe AlaSerAlaPhe
0
Gln ArgArgAla GlyGly ValLeuValAlaSer HisLeuGlnSer
Phe LeuGluVal SerTyr ArgValLeuArgHis LeuAlaGlnPro
Thr ProLeuGly ProAla SerSerLeuProGln SerPheLeuLeu
Lys SerLeuGlu GlnVal ArgLysIleGlnGly AspGlyAlaAla
2 Leu GlnGluLys LeuCys AlaThrTyrLysLeu CysHisProGlu
5
Glu LeuValLeu LeuGly HisSerLeuGlyIle ProTrpAlaPro
Leu SerSerCys ProSer G1nAlaLeuGlnLeu AlaGlyCysLeu
Ser GlnLeuHis SerGly LeuPheLeuTyrGln GlyLeuLeuGln
Ala LeuGluGly IleSer ProGluLeuGlyPro ThrLeuAspThr
3 Leu GlnLeuAsp ValAla AspPheAlaThrThr IleTrpGlnGln
0
Met GluGluLeu Gly(SEQID N0:486)
EXAMPLE 68
35 Construction of pMON13195
The new N-terminus/C-terminus gene in pMON13195 was
created using Method II as described in Materials and
Methods. Fragment Start was created and amplified from
40 G-CSF Serl' sequence in pMON13037 using the primer set,
126 start (SEQ ID N0:372 and P-bl start (SEQ ID N0:366).
Fragment Stop was created and amplified from G-CSF Serl'
sequence in pMON13037 using the primer set, 125 stop
(SEQ ID N0:373) and P-bl stop (SEQ ID N0:367). Fragment
CA 02268742 1999-04-19
WO 98/17810 3~ PCT/US97/20037
Start was digested with restriction endonuclease NcoI,
and Fragment Stop was digested with restriction
endonuclease HindIII. After purification, the digested
Fragments Start and Stop were combined with and ligated
to the approximately 3800 base pair NcoI-HindIII vector
fragment of pMON3934.
The intermediate plasmid described above contained
the full length new N-terminus/C-terminus G-CSF Serl'
gene and was digested with restriction endonucleases
NcoI and HindIII. The digested DNA was resolved on a 10
TAE gel, stained with ethidium bromide and the full-
length new N-terminus/C-terminus G-CSF Serl' gene was
isolated using Geneclean (Bio101, Vista, CA). The
intermediate plasmid, pMON13181, was digested with
restriction endonucleases HindIII and AflIII, resulting
in a 4068 base pair vector fragment, and purified using
a Magic DNA Clean-up System kit (Promega, Madison, WI).
The purified restriction fragments were combined and
ligated using T4 DNA ligase (Boehringer Mannheim,
Indianapolis, IN). A portion of the ligation reaction
was used to transform E. coli strain DH5oc cells (Life
Technologies, Gaithersburg, MD). Transformant bacteria
were selected on ampicillin-containing plates. Plasmid
DNA was isolated and sequenced to confirm the correct
insertion of the new gene. The resulting plasmid was
designated pMON13195.
E. coli strain JM101 was transformed with pMON13195
for protein expression and protein isolation from
inclusion bodies.
The plasmid, pMON13195, contains the DNA sequence
of (SEQ ID N0:32) which encodes the following amino
acid sequence:
3 5 Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile.Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
CA 02268742 1999-04-19 -
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