Note: Descriptions are shown in the official language in which they were submitted.
CA 02340616 2001-02-23
DEMANDES OU BREVETS VOI.UMINEUX
LA PRESENTS PARTIE DE CETTE DEMANDS OU CE BREVET
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CEC~ EST LF TOME _ ~"DE o~ _ -
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brevets
~ r.
JUMBO APPLlCATIONS/PATENTS
THIS SECTION OF THE APPLfCATIONIPATENT CONTAINS MORE ~'~
THAN ONE VOLUME
. THlS 1S VOLUME ~F
PIOTE:.Eor additional volumes please coniact'the Canadian Patent Ofiffice
CA 02340616 2001-02-23
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SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THElvvi
This application is a continuation-in-part of the following applications:
(1) provisional application Ser. No. 60/097,638 (GI 6908), filed August
24,1998;
(2) provisional application Ser. No. 60/097,659 (GI 6909), filed August
24,1998;
(3) provisional application Ser. No. 60/099,618 (GI 6910), filed September
9,1998;
{4) provisional application Ser. No. 60/102,092 (GI 6912), filed September
28,1998;
{5) provisional application Ser. No. 60/109,978 (GI 6914), filed November
25,1998;
(6) provisional application Ser. No. 60/113,645 (GI 6916), filed December
23,1998; and
(7) provisional application Ser. No. 60/113,646 (GI 6917), filed December
23,1998;
all of which are incorporated by reference herein.
FIELD OF THI~ INVENTION
The present invention provides novel polynucleotides and proteins encoded by
such polynucleotides, along with therapeutic, diagnostic and research
utilities for these
polynucleotides and proteins.
BACKGROUND OF THE INVENTION
Technology aimed at the discovery of protein factors (including e.g.,
cytokines,
such as lymphokines, interferons, CSFs and interleukins) has matured rapidly
over the
past decade. The now routine hybridization cloning and expression cloning
techniques
clone novel polynucleotides "directly" in the sense that they rely on
information directly
related to the discovered protein (i.e., partial DNA/amino acid sequence of
the protein
in the case of hybridization cloning; activity of the protein in the case of
expression
cloning). More recent "indirect" cloning techniques such as signal sequence
cloning, which
isolates DNA sequences based on the presence of a now well-recognized
secretory leader
3 0 sequence motif, as well as various PCR based or low stringency
hybridization cloning
techniques, have advanced the state of the art by making available large
numbers of
DNA/amino acid sequences for proteins that are known to have biological
activity by
virtue of their secreted nature in the case of leader sequence cloning, or by
virtue of the
cell or tissue source in the case of PCR-based techniques. It is to these
proteins and the
3 5 polynucleotides encoding them that the present invention is directed.
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SUMMARY OF THE TN~1FNTION
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:1;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 683 to nucleotide 934;
(c) a polynucieotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vbll 1 deposited with the ATCC under
accession number 98846;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vbll 1 deposited with the ATCC under accession number
98846;
(e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vbll 1 deposited with the ATCC under
accession number 98846;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vbll 1 deposited with the ATCC under accession number 98846;
(g) a polynucleotide encoding a protein comprising the amino acid
2 0 sequence of SEQ ID N0:2;
(h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:2 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:2;
(i) a polynucleotide which is an allelic variant of a polynucleotide of
2 5 (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-{h); and
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h) and that has a length that is
at least
25% of the length of SEQ ID NO:1.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:1 from nucleotide 683 to nucleotide 934; the nucleotide sequence of the
full-length
2
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protein coding sequence of clone vbll 1 deposited with the ATCC under
accession
number 98846; or the nucleotide sequence of a mature protein coding sequence
of clone
vbll_1 deposited with the ATCC under accession number 98846. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vbl l 1 deposited with the ATCC under accession
number 98846.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:2
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:2, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:2 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 37 to amino acid 46 of SEQ ID N0:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID NO:1.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
2 0 consisting of:
(aa) SEQ ID NO:1, but excluding the poly(A) tail at the
3' end of SEQ ID N0:1; and
(ab) the nucleotide sequence of the cDNA insert of clone
vbll 1 deposited with the ATCC under accession number 98846;
2 5 (ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
3 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
3
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(ba) SEQ ID NO:1, but excluding the poly(A) tail at the
3' end of SEQ ID NO:1; and
(bb) the nucleotide sequence of the cDNA insert of clone
vbll 1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:1 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:1 , but
excluding the
poly(A) tail at the 3' end of SEQ ID NO:1. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
1 S cDNA sequence of SEQ ID NO:1 from nucleotide 683 to nucleotide 934, and
extending
rnntiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID NO:1 from nucleotide 683 to nucleotide 934, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID NO:1 from nucleotide
683 to
nucleotide 934.
2 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:2;
(b) a fragment of the amino acid sequence of SEQ ID N0:2, the
2 5 fragment comprising eight contiguous amino acids of SEQ ID N0:2; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vbll 1 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:2. In further preferred
3 0 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:2 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:2, or a protein comprising a fragment of the amino acid sequence
of SEQ
4
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ID N0:2 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 37 to amino acid 46 of SEQ ID N0:2.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 63 to nucleotide 482;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 201 to nucleotide 482;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vbl2_1 deposited with the ATCC under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vbl2_1 deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vbl2_1 deposited with the ATCC under
accession number 98846;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vbl2_1 deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:4;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:4 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:4;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
3 0 of (h) or {i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
5
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:3.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:3 from nucleotide 63 to nucleotide 482; the nucleotide sequence of SEQ ID
N0:3 from
nucleotide 201 to nucleotide 482; the nucleotide sequence of the full-length
protein coding
sequence of clone vbl2_1 deposited with the ATCC under accession number 98846;
or the
nucleotide sequence of a mature protein coding sequence of clone vbl2_1
deposited with
the ATCC under accession number 98846. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vbl2_1 deposited with the ATCC under accession number 98846. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having
biological activity, the fragment preferably comprising eight {more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:4, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:4
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 65 to amino acid 74 of SEQ ID N0:4.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:3.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:3, but excluding the poly{A) tail at the
3' end of SEQ ID N0:3; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vbl2_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probe{s) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
6
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize.in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:3, but excluding the poly(A) tail at the
3' end of SEQ ID N0:3; and
(bb) the nucleotide sequence of the cDNA insert of clone
vbl2_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:3 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:3 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:3. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
2 0 cDNA sequence of SEQ ID N0:3 from nucleotide 63 to nucleotide 482, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:3 from nucleotide 63 to nucleotide 482, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 63
to
nucleotide 482. Also preferably the polynucleotide isolated according to the
above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:3 from nucleotide 20I to nucleotide 482, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:3 from
nucleotide 201 to nucleotide 482, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:3 from nucleotide 201 to nucleotide 482.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:4;
7
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(b) a fragment of the amino acid sequence of SEQ ID N0:4, the
fragment comprising eight contiguous amino acids of SEQ ID N0:4; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vbl2_1 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:4. In further preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:4 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:4, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:4 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 65 to amino acid 74 of SEQ ID N0:4.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 1195 to nucleotide 1527;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:5 from nucleotide 1468 to nucleotide 1527;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vbl4_1 deposited with the ATCC under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vbl4_1 deposited with the ATCC under accession number
98846;
(f) a poiynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vbl4_1 deposited with the ATCC under
accession number 98846;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vbl4_l deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:6;
8
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:6 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ TD N0:6;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(ar(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:5.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:5 from nucleotide 1195 to nucleotide 1527; the nucleotide sequence of SEQ
ID N0:5
from nucleotide 1468 to nucleotide 1527; the nucleotide sequence of the full-
length
protein coding sequence of clone vbl4_1 deposited with the ATCC under
accession
number 98846; or the nucleotide sequence of a mature protein coding sequence
of clone
vbl4_1 deposited with the ATCC under accession number 98846. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
2 0 the cDNA insert of clone vbl4_1 deposited with the ATCC under accession
number 98846.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:6
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:6, or a
2 5 polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:6 having biological activity, the fragment comprising the amino and
sequence
from amino acid 50 to amino acid 59 of SEQ ID N0:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:5.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:5, but excluding the poly(A) tail at the
3' end of SEQ ID N0:5; and
(ab) the nucleotide sequence of the cDNA insert of clone
vbl4_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:5, but excluding the poly(A) tail at the
3' end of SEQ ID N0:5; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vbl4_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b}(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:5 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:5 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:5. Also preferably the polynucleotide
isolated
3 0 according to the above process comprises a nucleotide sequence
corresponding to the
cDNA sequence of SEQ ID N0:5 from nucleotide 1195 to nucleotide 1527, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:5 from nucleotide 1195 to nucleotide 1527, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide
1195 to
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nucleotide 1527. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:5 from nucleotide 1468 to nucleotide 1527, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:5 from
nucleotide 1468 to nucleotide 1527, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:5 from nucleotide 1468 to nucleotide 1527.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:6;
(b) a fragment of the amino acid sequence of SEQ ID N0:6, the
fragment comprising eight contiguous amino acids of SEQ ID N0:6; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vbl4_1 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:6. In further preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:6 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:6, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:6 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 50 to amino acid 59 of SEQ ID N0:6.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucieotide comprising the nucleotide sequence of SEQ ID
N0:7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 82 to nucleotide 294;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:7 from nucleotide 109 to nucleotide 294;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vel I 1 deposited with the ATCC under
accession number 98846;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone yell 1 deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vell 1 deposited with the ATCC under
accession number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone yell 1 deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:8;
(i) a polynudeotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID NO:B having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:8;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:7.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:7 from nucleotide 82 to nucleotide 294; the nucleotide sequence of SEQ ID
N0:7 from
2 5 nucleotide 109 to nucleotide 294; the nucleotide sequence of the full-
length protein coding
sequence of clone vell_1 deposited with the ATCC under accession number 98846;
or the
nucleotide sequence of a mature protein coding sequence of clone yell 1
deposited with
the ATCC under accession number 98846. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone yell 1 deposited with the ATCC under accession number 98846. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:8, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:8
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 30 to amino acid 39 of SEQ ID N0:8.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:7.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:7, but excluding the poly{A) tail at the
3' end of SEQ ID N0:7; and
(ab) the nucleotide sequence of the cDNA insert of clone
vell_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:7, but excluding the poly{A) tail at the
3' end of SEQ ID N0:7; and
(bb) the nucleotide sequence of the cDNA insert of clone
vell_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7, and
extending
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contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:7 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:7 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:7. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:7 from nucleotide 82 to nucleotide 294, and
extending
rnntiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:7 from nucleotide 82 to nucleotide 294, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide 82
to
nucleotide 294. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:7 from nucleotide 109 to nucleotide 294, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:7 from
nucleotide 109 to nucleotide 294, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:7 from nucleotide 109 to nucleotide 294.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:8;
(b) a fragment of the amino acid sequence of SEQ ID N0:8, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:8; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vel l 1 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:8. In further preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:8 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:8, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:8 having biological activity, the fragment comprising the amino acid
sequence from
3 0 amino acid 30 to amino acid 39 of SEQ ID N0:8.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 22 to nucleotide 468;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 118 to nucleotide 468;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vf2_1 deposited with the ATCC under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vf2_1 deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vf2_1 deposited with the ATCC under accession
number 98846;
(g) a poiynucleotide encoding a mature protein encoded by the cDNA
insert of clone vf2_1 deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID NO:10;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID NO:10 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:10;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:9.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:9 from nucleotide 22 to nucleotide 468; the nucleotide sequence of SEQ ID
N0:9 from
nucleotide 118 to nucleotide 468; the nucleotide sequence of the full-length
protein coding
sequence of clone vf2_1 deposited with the ATCC under accession number 98846;
or the
nucleotide sequence of a mature protein coding sequence of clone vf2_1
deposited with
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the ATCC under accession number 98846. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vf2_1 deposited with the ATCC under accession number 98846. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID NO:10
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID NO:10, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
NO:10
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 69 to amino acid 78 of SEQ ID NO:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:9.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:9, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:9; and
(ab) the nucleotide sequence of the cDNA insert of clone
vf2_I deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:9, but excluding the poly(A) tail at the
3' end of SEQ ID N0:9; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vf2_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:9 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:9 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:9. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:9 from nucleotide 22 to nucleotide 468, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:9 from nucleotide 22 to nucleotide 468, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide 22
to
nucleotide 468. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:9 from nucleotide 118 to nucleotide 468, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:9 from
nucleotide I18 to nucleotide 468, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:9 from nucleotide 118 to nucleotide 468.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino and sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID NO:10, the
fragment comprising eight contiguous amino acids of SEQ ID N0:10; and
{c) the amino acid sequence encoded by the cDNA insert of clone vf2_1
3 0 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID NO:10. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID NO:10 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino ands
of SEQ ID NO:10, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID NO:10 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 69 to amino acid 78 of SEQ ID N0:10.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11 from nucleotide 124 to nucleotide 1641;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 262 to nucleotide 1641;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vg2_1 deposited with the ATCC under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vg2_1 deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vg2_1 deposited with the ATCC under
accession
number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vg2_1 deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:12;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:12 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ iD N0:12;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID NO:11.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:11 from nucleotide 124 to nucleotide 1641; the nucleotide sequence of SEQ
ID N0:11
from nucleotide 262 to nucleotide 1641; the nucleotide sequence of the full-
length protein
coding sequence of clone vg2_1 deposited with the ATCC under accession number
98846;
or the nucleotide sequence of a mature protein coding sequence of clone vg2_1
deposited
with the ATCC under accession number 98846. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vg2_1 deposited with the ATCC under accession number 98846. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:12
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:12, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:12
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 248 to amino acid 257 of SEQ ID N0:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:11.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID NO:11, but excluding the poly(A) tail at the
3' end of SEQ ID NO:11; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vg2_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) ~ isolating the DNA polynucleotides detected with the
probe{s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID NO:11, but excluding the poly(A) tail at the
3' end of SEQ ID NO:11; and
(bb) the nucleotide sequence of the cDNA insert of clone
vg2_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:11, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:11 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:11
, but
excluding the poly(A) tail at the 3' end of SEQ ID NO:11. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID NO:11 from nucleotide 124 to
nucleotide
1641, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID NO:11 from nucleotide 124 to nucleotide 1641, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID NO:11 from
nucleotide
124 to nucleotide 1641. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
NOal from nucleotide 262 to nucleotide 1641, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
NO:11 from
nucleotide 262 to nucleotide 1641, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID NO:11 from nucleotide 262 to nucleotide 1641.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:12;
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(b) a kagment of the amino acid sequence of SEQ ID N0:12, the
fragment comprising eight contiguous amino acids of SEQ ID N0:12; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vg2_1 deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:12. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:12 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino ands
of SEQ ID N0:12, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:12 having biological activity, the fragment comprising the amino acid
sequence
kom amino acid 248 to amino acid 257 of SEQ ID N0:12.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected kom the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13 kom nucleotide 380 to nucleotide 892;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:13 from nucleotide 416 to nucleotide 892;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vjl 1 deposited with the ATCC under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vjl_1 deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vjl 1 deposited with the ATCC under accession
number 98846;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vjl 1 deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:14;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID NO:I4 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:14;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
{a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(i) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i) and that has a length that is
at least
25% of the length of SEQ ID N0:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:13 from nucleotide 380 to nucleotide 892; the nucleotide sequence of SEQ ID
NO:13
from nucleotide 416 to nucleotide 892; the nucleotide sequence of the full-
length protein
coding sequence of clone vjl 1 deposited with the ATCC under accession number
98846;
or the nucleotide sequence of a mature protein coding sequence of clone vj1 1
deposited
with the ATCC under accession number 98846. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vj1 1 deposited with the ATCC under accession number 98846. in
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:14
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:14, or a
polynucleotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:14
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 80 to amino acid 89 of SEQ ID N0:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:13.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
{a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:13; and
(ab) the nucleotide sequence of the cDNA insert of clone
vjl_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:13; and
(bb) the nucleotide sequence of the cDNA insert of clone
vjl_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said primers) to human genomic DNA in
2 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:13 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:13
. Also
preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13 from
nucleotide 380 to nucleotide 892, and extending contiguously from a nucleotide
sequence
3 0 corresponding to the 5' end of said sequence of SEQ ID N0:13 from
nucleotide 380 to
nucleotide 892, to a nucleotide sequence corresponding to the 3' end of said
sequence of
SEQ ID N0:13 from nucleotide 380 to nucleotide 892. Also preferably the
polynucleotide
isolated according to the above process comprises a nucleotide sequence
corresponding
to the cDNA sequence of SEQ ID N0:13 from nucleotide 416 to nucleotide 892,
and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of said
sequence of SEQ ID N0:13 from nucleotide 416 to nucleotide 892, to a
nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:13 from nucleotide
416 to
nucleotide 892.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:14;
(b} a fragment of the amino acid sequence of SEQ ID N0:14, the
fragment comprising eight contiguous amino acids of SEQ ID N0:14; and
(c) the amino acid sequence encoded by the cDNA insert of clone vj1 1
deposited with the ATCC under accession number 98846;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:14. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:14 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:14, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:14 having biological activity, the fragment comprising the amino acid
sequence
2 0 from amino acid 80 to amino acid 89 of SEQ ID N0:14.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:15;
2 5 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 62 to nucleotide 1057;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 659 to nucleotide 1057;
(d) a polynucleotide comprising the nucleotide sequence of the full-
3 0 length protein coding sequence of clone vll 1 deposited with the ATCC
under
accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vl1 1 deposited with the ATCC under accession number
98846;
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vll 1 deposited with the ATCC under accession
number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vl1 1 deposited with the ATCC under accession number 98846;
{h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ TD N0:16;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:16 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:16;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:15.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:15 from nucleotide 62 to nucleotide 1057; the nucleotide sequence of SEQ ID
N0:15
from nucleotide 659 to nucleotide 1057; the nucleotide sequence of the full-
length protein
coding sequence of clone v1I 1 deposited with the ATCC under accession number
98846;
or the nucleotide sequence of a mature protein coding sequence of clone vll 1
deposited
2 5 with the ATCC under accession number 98846. In other preferred
embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vll 1 deposited with the ATCC under accession number 98846. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:16
having
3 0 biological activity, the fragment preferably comprising eight (more
preferably twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:16, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:16
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 161 to amino acid 170 of SEQ ID N0:16.
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Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:15.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:15, but excluding the poly(A) tail at the
3' end of SEQ ID N0:15; and
(ab) the nucleotide sequence of the cDNA insert of clone
v11 1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
2 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:15, but excluding the poly(A) tail at the
3' end of SEQ ID N0:15; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 5 vll_1 deposited with the ATCC under accession number 98846;
(ii) hybridizing said prixner(s) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
3 0 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:15 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:15
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:15. Also preferably the
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polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:15 from nucleotide 62 to
nucleotide
1057, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID NO:IS from nucleotide 62 to nucleotide 1057, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from
nucleotide
62 to nucleotide 1057. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:15 from nucleotide 659 to nucleotide 1057, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:15 from
nucleotide 659 to nucleotide 1057, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:15 from nucleotide 659 to nucleotide 1057.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:16;
(b) a fragment of the amino acid sequence of SEQ ID N0:16, the
fragment comprising eight contiguous amino acids of SEQ ID N0:16; and
(c) the amino acid sequence encoded by the cDNA insert of clone vlI 1
deposited with the ATCC under accession number 98846;
2 0 the protein being substantially free from other mammalian proteins.
Preferably such
protein comprises the amino acid sequence of SEQ ID N0:16. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:16 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 5 of SEQ ID NO:16, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:16 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 161 to amino acid 170 of SEQ ID N0:16.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
3 0 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 74 to nucleotide 529;
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(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 140 to nucleotide 529;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vk2_1 deposited with the ATCC under
accession number 98838;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vk2_1 deposited with the ATCC under accession number
98838;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vk2_1 deposited with the ATCC under accession
number 9883$;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vk2_1 deposited with the ATCC under accession number 98838;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:18;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:18 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:18;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
2 0 (a}-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 5 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:17 from nucleotide 74 to nucleotide 529; the nucleotide sequence of SEQ ID
N0:17
3 0 from nucleotide 140 to nucleotide 529; the nucleotide sequence of the full-
length protein
coding sequence of clone vk2_1 deposited with the ATCC under accession number
98838;
or the nucleotide sequence of a mature protein coding sequence of clone vk2_1
deposited
with the ATCC under accession number 98838. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
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of clone vlc2-1 deposited with the ATCC under accession number 98838. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:18
having
biological activity, the fragment preferably comprising eight {more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:18, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:18
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 71 to amino acid 80 of SEQ ID N0:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:17.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:17, but excluding the poly(A) tail at the
3' end of SEQ ID N0:17; and
(ab) the nucleotide sequence of the cDNA insert of clone
2 0 vk2_1 deposited with the ATCC under accession number 98838;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe{s);
2 5 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
3 0 (ba) SEQ ID N0:17, but excluding the poly(A) tail at the
3' end of SEQ ID N0:17; and
(bb) the nucleotide sequence of the cDNA insert of clone
v~ 1 deposited with the ATCC under accession number 98838;
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(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:17
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:17. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:17 from nucleotide 74 to
nucleotide
529, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:17 from nucleotide 74 to nucleotide 529, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from
nucleotide
74 to nucleotide 529. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:17 from nucleotide 140 to nucleotide 529, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:17 from
nucleotide 140 to nucleotide 529, to a nucleotide sequence corresponding to
the 3' end of
2 0 said sequence of SEQ ID N0:17 from nucleotide 140 to nucleotide 529.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:18;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:18, the
fragment comprising eight contiguous amino acids of SEQ ID N0:18; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vic2_1 deposited with the ATCC under accession number 98838;
the protein being substantially free from other mammalian proteins. Preferably
such
3 0 protein comprises the amino acid sequence of SEQ ID N0:18. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:18 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:18, or a protein comprising a fragment of the amino acid sequence
of SEQ
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ID N0:18 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 71 to amino acid 80 of SEQ ID N0:18.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 174 to nucleotide 3170;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 1098 to nucleotide 3170;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb21 1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb21_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb21 1 deposited with the ATCC under
accession number 98862;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb21_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:20;
(i) a polynudeotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:20 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:20;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
3 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ TD N0:19.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:19 from nucleotide 174 to nucleotide 3170; the nucleotide sequence of SEQ
ID N0:19
from nucleotide 1098 to nucleotide 3170; the nucleotide sequence of the full-
length
protein coding sequence of clone vb21_1 deposited with the ATCC under
accession
number 98862; or the nucleotide sequence of a mature protein coding sequence
of clone
vb21 1 deposited with the ATCC under accession number 98862. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vb21_1 deposited with the ATCC under accession number
98862.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N020
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:20, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:20 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 494 to amino acid 503 of SEQ ID N0:20.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:19.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:19, but excluding the poly(A) tail at the
3' end of SEQ ID N0:19; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vb21 1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:19, but excluding the poly{A) tail at the
3' end of SEQ ID N0:19; and
(bb} the nucleotide sequence of the cDNA insert of clone
vb21_I deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:19 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:19
, but
excluding the poly{A) tail at the 3' end of SEQ ID N0:19. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:19 from nucleotide 174 to
nucleotide
3170, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:19 from nucleotide 174 to nucleotide 3170, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:19 from
nucleotide
174 to nucleotide 3170. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:19 from nucleotide 1098 to nucleotide 3170, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:19 from
nucleotide 1098 to nucleotide 3170, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:19 from nucleotide 1098 to nucleotide 3170.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:20;
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(b) a fragment of the amino acid sequence of SEQ ID N0:20, the
fragment comprising eight contiguous amino acids of SEQ ID N0:20; and
{c) the amino acid sequence encoded by the cDNA insert of clone
vb21_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:20. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:20 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID NO~O, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:20 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 494 to amino acid 503 of SEQ ID N0:20.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 74 to nucleotide 1453;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:21 from nucleotide 224 to nucleotide 1453;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc35 1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
2 5 cDNA insert of clone vc35_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc35_1 deposited with the ATCC under
accession number 98862;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc35_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:22;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:22 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:22;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a~(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID NO:21.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:21 from nucleotide 74 to nucleotide 1453; the nucleotide sequence of SEQ ID
N0:21
from nucleotide 224 to nucleotide 1453; the nucleotide sequence of the full-
length protein
coding sequence of clone vc35_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc35_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc35_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:22
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:22, or a
polynucleotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:22
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 225 to amino acid 234 of SEQ ID N0:22.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:21.
3 0 Further embodiments of the invention provide isolated polynudeotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynudeotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:21, but excluding the poly(A) tail at the
3' end of SEQ ID N0:21; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc35_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynudeotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:21, but excluding the poly(A) tail at the
3' end of SEQ ID N0:21; and
(hb) the nucleotide sequence of the cDNA insert of done
2 0 vc35_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21, and
extending contiguously from a nucleotide sequence con:esponding to the 5' end
of SEQ
ID N0:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:21
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:21. Also preferably the
3 0 polynudeotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:21 from nucleotide 74 to
nucleotide
1453, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:21 from nucleotide 74 to nucleotide 1453, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from
nucleotide
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74 to nucleotide 1453. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:21 from nucleotide 224 to nucleotide 1453, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:21 from
nucleotide 224 to nucleotide 1453, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:21 from nucleotide 224 to nucleotide 1453.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino and sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:22;
(b) a fragment of the amino acid sequence of SEQ ID N0:22, the
fragment comprising eight contiguous amino acids of SEQ ID N0:22; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc35_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:22. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:22 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty} contiguous
amino acids
2 0 of SEQ ID N0:22, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:22 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 225 to amino acid 234 of SEQ ID N0:22.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 (a} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 135 to nucleotide 368;
(c} a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:23 from nucleotide 243 to nucleotide 368;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc36_1 deposited with the ATCC under
accession number 98862;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc36_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc36_1 deposited with the ATCC under
accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc36_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:24;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:24 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:24;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i) and that has a length that is
at least
25% of the length of SEQ ID N0:23.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:23 from nucleotide 135 to nucleotide 368; the nucleotide sequence of SEQ ID
N0:23
2 5 from nucleotide 243 to nucleotide 368; the nucleotide sequence of the full-
length protein
coding sequence of clone vc36_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone
.vc36_1 deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vc36_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:24
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:24, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:24
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 34 to amino acid 43 of SEQ ID N0:24.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:23.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:23, but excluding the poly(A) tail at the
3' end of SEQ ID N0:23; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc36_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:23, but excluding the poly(A) tail at the
3' end of SEQ ID N0:23; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc36_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b){iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:23 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:23
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:23. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:23 from nucleotide 135 to
nucleotide
368, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:23 from nucleotide 135 to nucleotide 368, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:23 from
nucleotide
135 to nucleotide 368. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:23 from nucleotide 243 to nucleotide 368, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:23 from
nucleotide 243 to nucleotide 368, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:23 from nucleotide 243 to nucleotide 368.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:24;
(b) a fragment of the amino acid sequence of SEQ ID N0:24, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:24; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc36_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:24. In further
preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino and sequence of SEQ ID N0:24 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:24, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:24 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 34 to amino acid 43 of SEQ ID N0:24.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 370 to nucleotide 1662;
(c) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc38_1 deposited with the ATCC under
accession number 98862;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc38_1 deposited with the ATCC under accession number
98862;
(e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc38_1 deposited with the ATCC under
accession number 98862;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc38_1 deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:26;
(h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:26 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:26;
(i) a polynucleotide which is an allelic variant of a polynucleotide of
2 0 (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in {a~(h); and
2 5 (1) a polynudeotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in {ar(h) and that has a length that is
at least
25% of the length of SEQ ID N0:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:25 from nucleotide 370 to nucleotide 1662; the nucleotide sequence of the
full-length
3 0 protein coding sequence of clone vc38_1 deposited with the ATCC under
accession
number 98862; or the nucleotide sequence of a mature protein coding sequence
of clone
vc38_1 deposited with the ATCC under accession number 98862. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc38_1 deposited with the ATCC under accession number
98862.
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In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:26
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:26 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 210 to amino acid 219 of SEQ ID N0:26.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:25.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:25, but excluding the poly(A) tail at the
3' end of SEQ ID N0:25; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc38_1 deposited with the ATCC under accession number 98862;
2 0 (ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
{iii) isolating the DNA polynucleotides detected with the
probe(s);
and
2 5 (b) a process comprising the steps of:
{i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:25, but excluding the poly{A) tail at the
3 0 3' end of SEQ ID N0:25; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc38_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
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(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:25 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:25
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:25. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:25 from nucleotide 370 to
nucleotide
1662, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:25 from nucleotide 370 to nucleotide 1662, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from
nucleotide
370 to nucleotide 1662.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:26;
(b) a fragment of the amino acid sequence of SEQ ID N0:26, the
fragment comprising eight contiguous amino acids of SEQ ID N0:26; and
2 0 (c) the amino acid sequence encoded by the cDNA insert of clone
vc38_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:26. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
2 5 amino acid sequence of SEQ ID N0:26 having biological activity, the
fragment preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:26, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:26 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 210 to amino acid 219 of SEQ ID N0:26.
3 0 In one embodiment, the present invention provides a composition comprising
an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 105 to nucleotide 365;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 147 to nucleotide 365;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc39_1 deposited with the ATCC under
accession number 98862;
(e) a polynucleoHde encoding the full-length protein encoded by the
cDNA insert of clone vc39_1 deposited with the ATCC under accession number
98862;
(f) a polynucleoride comprising the nucleotide sequence of a mature
protein coding sequence of clone vc39_1 deposited with the ATCC under
accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc39_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:28;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:28 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:28;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:27.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:27 from nucleotide 105 to nucleotide 365; the nucleotide sequence of SEQ ID
N0:27
from nucleotide 147 to nucleotide 365; the nucleotide sequence of the full-
length protein
coding sequence of clone vc39_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc39_1
deposited
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with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc39_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:28
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID NO:28, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:28
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 38 to amino acid 47 of SEQ ID N0:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0~7.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:27, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:27; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc39_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:27, but excluding the poly(A) tail at the
3' end of SEQ ID N0:27; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vc39_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:27 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:27
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:27. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:27 from nucleotide 105 to
nucleotide
365, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:27 from nucleotide 105 to nucleotide 365, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:27 from
nucleotide
105 to nucleotide 365. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:27 from nucleotide 147 to nucleotide 365, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:27 from
nucleotide 147 to nucleotide 365, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:27 from nucleotide 147 to nucleotide 365.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:28;
(b) a fragment of the amino acid sequence of SEQ ID N0:28, the
fragment comprising eight contiguous amino acids of SEQ ID N0:28; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vc39_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:28. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:28 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:28, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:28 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 38 to amino acid 47 of SEQ ID N0:28.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 35 to nucleotide 1066;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 128 to nucleotide 1066;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc40_1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc40_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vc40_1 deposited with the ATCC under
accession number 98862;
(g} a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc40_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:30;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:30 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ TD N0:30;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-{i}; and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:29 from nucleotide 35 to nucleotide 1066; the nucleotide sequence of SEQ ID
N0:29
from nucleotide 128 to nucleotide 1066; the nucleotide sequence of the full-
length protein
coding sequence of clone vc40_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc40_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc40_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:30
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:30, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:30
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 167 to amino acid 176 of SEQ ID N0:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:29.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:29, but excluding the poly(A) tail at the
3' end of SEQ ID N0:29; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vc40_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:29, but excluding the poly(A) tail at the
3' end of SEQ ID N0:29; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc40_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:29 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:29
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:29. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:29 from nucleotide 35 to
nucleotide
1066, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:29 from nucleotide 35 to nucleotide 1066, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from
nucleotide
35 to nucleotide 1066. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:29 from nucleotide 128 to nucleotide 1066, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:29 from
nucleotide 128 to nucleotide 1066, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:29 from nucleotide 128 to nucleotide 1066.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:30;
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(b) a fragment of the amino acid sequence of SEQ ID N0:30, the
fragment comprising eight contiguous amino acids of SEQ ID N0:30; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc40_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:30. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:30 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:30, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:30 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 167 to amino acid 176 of SEQ ID N0:30.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 38 to nucleotide 553;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:31 from nucleotide 104 to nucleotide 553;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc46_1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc46_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc46_1 deposited with the ATCC under
accession number 98862;
3 0 (g) a polynucieotide encoding a mature protein encoded by the cDNA
insert of clone vc46_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:32;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:32 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:32;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynudeotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynudeotide that hybridizes under stringent conditions to any
one of the polynucieotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:31.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:31 from nucleotide 38 to nucleotide 553; the nucleotide sequence of SEQ ID
N0:31
from nucleotide 104 to nucleotide 553; the nucleotide sequence of the full-
length protein
coding sequence of clone vc46_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc46_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc46_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:32
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:32, or a
polynucleotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:32
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 81 to amino acid 90 of SEQ ID N0:32.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:31.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
{a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:31, but excluding the poly(A) tail at the
3' end of SEQ ID N0:31; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc46_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
. (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID NO:31, but excluding the poly(A) tail at the
3' end of SEQ ID N0:31; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vc46_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:31 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:31
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:31. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:31 from nucleotide 38 to
nucleotide
553, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:31 from nucleotide 38 to nucleotide 553, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from
nucleotide
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38 to nucleotide 553: Also preferably the polynudeotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:31 from nucleotide 104 to nucleotide 553, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:31 from
nucleotide 104 to nucleotide 553, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:31 from nucleotide 104 to nucleotide 553.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:32;
(b) a fragment of the amino acid sequence of SEQ ID N0:32, the
fragment comprising eight contiguous amino acids of SEQ ID N0:32; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc46_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:32. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:32 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:32, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:32 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 81 to amino acid 90 of SEQ ID N0:32.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 164 to nucleotide 2548;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:33 from nucleotide 242 to nucleotide 2548;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc49_1 deposited with the ATCC under
accession number 98862;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc49_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc49_1 deposited with the ATCC under
accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc49_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:34;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:34 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:34;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
{k) a polynudeotide which encodes a species homologue of the protein
of {h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:33 from nucleotide 164 to nucleotide 2548; the nucleotide sequence of SEQ
ID N0:33
2 5 from nucleotide 242 to nucleotide 2548; the nucleotide sequence of the
full-length protein
rnding sequence of clone vc49_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of done vc49_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vc49_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:34
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:34, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:34
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 392 to amino acid 401 of SEQ ID N0:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:33.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:33, but excluding the poly(A) tail at the
3' end of SEQ ID N0:33; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc49_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:33, but excluding the poly(A) tail at the
3' end of SEQ ID N0:33; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc49_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) . isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:33 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:33
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:33. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:33 from nucleotide 164 to
nucleotide
2548, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:33 from nucleotide 164 to nucleotide 2548, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from
nucleotide
164 to nucleotide 2548. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:33 from nucleotide 242 to nucleotide 2548, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:33 from
nucleotide 242 to nucleotide 2548, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:33 from nucleotide 242 to nucleotide 2548.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:34;
(b) a fragment of the amino acid sequence of SEQ ID N0:34, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:34; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc49_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:34. In further
preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:34 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:34, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:34 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 392 to amino acid 401 of SEQ ID N0:34.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35;
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(b). a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 150 to nucleotide 776;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:35 from nucleotide 246 to nucleotide 776;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc50_1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc50_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc50_1 deposited with the ATCC under
accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc50_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:36;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:36 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:36;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a poiynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 S (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:35.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:35 from nucleotide 150 to nucleotide 776; the nucleotide sequence of SEQ ID
N0:35
from nucleotide 246 to nucleotide 776; the nucleotide sequence of the full-
length protein
coding sequence of clone vc50_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc50_1
deposited
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with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc50_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:36
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:36, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:36
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 99 to amino acid 108 of SEQ ID N0:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:35.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
{aa) SEQ ID N0:35, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:35; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc50_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:35, but excluding the poly(A) tail at the
3' end of SEQ ID N0:35; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vc50_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
S (iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:35, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:35 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:35
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:35. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:35 from nucleotide 150 to
nucleotide
776, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:35 from nucleotide 150 to nucleotide 776, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from
nucleotide
150 to nucleotide 776. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:35 from nucleotide 246 to nucleotide 776, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:35 from
nucleotide 246 to nucleotide 776, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:35 from nucleotide 246 to nucleotide 776.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:36;
(b) a fragment of the amino acid sequence of SEQ ID N0:36, the
fragment comprising eight contiguous amino acids of SEQ ID NO:36; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vc50_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:36. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:36 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:36, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID NO:36 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 99 to amino acid 108 of SEQ ID N0:36.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 139 to nucleotide 1308;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 211 to nucleotide 1308;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vc51 1 deposited with the ATCC under
1 S accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc51 1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vc51 1 deposited with the ATCC under
accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc51 1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:38;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:38 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:38;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or {i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:37 from nucleotide 139 to nucleotide 1308; the nucleotide sequence of SEQ
ID N0:37
from nucleotide 211 to nucleotide 1308; the nucleotide sequence of the full-
length protein
coding sequence of clone vc51_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc51_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc51_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:38
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:38, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 190 to amino acid 199 of SEQ ID N0:38.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:37.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:37, but excluding the poly(A) tail at the
3' end of SEQ ID N0:37; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vc51 1 deposited with the ATCC under accession number 98862;
(ii) hybridi2ing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
S the group consisting of:
(ba) SEQ ID N0:37, but excluding the poly(A) tail at the
3' end of SEQ ID N0:37; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc51_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:37 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:37
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:37. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:37 from nucleotide 139 to
nucleotide
1308, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:37 from nucleotide 139 to nucleotide 1308, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from
nucleotide
139 to nucleotide 1308. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:37 from nucleotide 211 to nucleotide 1308, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:37 from
nucleotide 211 to nucleotide 1308, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:37 from nucleotide 211 to nucleotide 1308.
3 0 In other embodiments, the present invention provides a composirion
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:38;
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(b) a fragment of the amino acid sequence of SEQ ID N0:38, the
fragment comprising eight contiguous amino acids of SEQ ID N0:38; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc51_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:38. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:38 having biological ackivity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:38, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:38 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 190 to amino acid 199 of SEQ ID N0:38.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 21 to nucleotide 1142;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:39 from nucleotide 114 to nucleotide 1142;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc52_1 deposited with the ATCC under
accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc52_1 deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc52_1 deposited with the ATCC under
accession number 98862;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc52_1 deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:40;
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{i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:40 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:40;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a~(g) above;
(k) a polynudeotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:39.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:39 from nucleotide 21 to nucleotide 1142; the nucleotide sequence of SEQ ID
N0:39
from nucleotide 114 to nucleotide 1142; the nucleotide sequence of the full-
length protein
coding sequence of clone vc52_1 deposited with the ATCC under accession number
98862;
or the nucleotide sequence of a mature protein coding sequence of clone vc52_1
deposited
with the ATCC under accession number 98862. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc52_1 deposited with the ATCC under accession number 98862. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:40
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:40, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:40
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 182 to amino acid 191 of SEQ ID N0:40.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:39.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:39, but excluding the poly(A) tail at the
3' end of SEQ ID N0:39; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc52_1 deposited with the ATCC under accession number 98$62;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
{iii) isolating the DNA polynucleotides detected with the
probe{s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:39, but excluding the poly(A) tail at the
3' end of SEQ ID N0:39; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vc52_1 deposited with the ATCC under accession number 98862;
(ii) hybridizing said primers) tv human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:39 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:39
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:39. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:39 from nucleotide 21 to
nucleotide
1142, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:39 from nucleotide 21 to nucleotide 1142, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from
nucleotide
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21 to nucleotide 1142. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:39 from nucleotide 114 to nucleotide 1142, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
NO:39 from
nucleotide 114 to nucleotide 1142, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:39 from nucleotide 114 to nucleotide 1142.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:40;
(b) a fragment of the amino acid sequence of SEQ ID N0:40, the
fragment comprising eight contiguous amino acids of SEQ ID N0:40; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc52_1 deposited with the ATCC under accession number 98862;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:40. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino and sequence of SEQ ID N0:40 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:40, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:40 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 182 to amino acid 191 of SEQ ID N0:40.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41;
(b} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 13 to nucleotide 1416;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:41 from nucleotide 346 to nucleotide 1416;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc33_1 deposited with the ATCC under
accession number 98886;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc33_1 deposited with the ATCC under accession number
98886;
{f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc33_1 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc33_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:42;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:42 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:42;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:41 from nucleotide 13 to nucleotide 1416; the nucleotide sequence of SEQ ID
N0:41
2 5 from nucleotide 346 to nucleotide 1416; the nucleotide sequence of the
full-length protein
coding sequence of clone vc33_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vc33_1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vc33_1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:42
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:42, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:42
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 229 to amino acid 238 of SEQ ID N0:42.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:41.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:41, but excluding the poly(A) tail at the
3' end of SEQ ID N0:41; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc33_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:41, but excluding the poly(A) tail at the
3' end of SEQ ID N0:41; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc33_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:41 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:41
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:41. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:41 from nucleotide 13 to
nucleotide
1416, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:41 from nucleotide 13 to nucleotide 1416, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from
nucleotide
13 to nucleotide 1416. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:41 from nucleotide 346 to nucleotide 1416, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:41 from
nucleotide 346 to nucleotide 1416, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:41 from nucleotide 346 to nucleotide 1416.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:42;
(b) a fragment of the amino acid sequence of SEQ ID N0:42, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:42; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc33_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:42. In further
preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:42 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino ands
of SEQ ID N0:42, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:42 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 229 to amino acid 238 of SEQ ID N0:42.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:43;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ TD
N0:43 from nucleotide 232 to nucleotide 1461;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 280 to nucleotide 1461;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc34_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc34_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc34_1 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc34_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:44;
(i) a polynudeotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:44 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:44;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
{k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynudeotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:43.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:43 from nucleotide 232 to nucleotide 1461; the nucleotide sequence of SEQ
ID N0:43
from nucleotide 280 to nucleotide 1461; the nucleotide sequence of the full-
length protein
coding sequence of clone vc34_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vc34_1
deposited
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with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc34_1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:44
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:44, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:44
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 200 to amino acid 209 of SEQ ID N0:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:43.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:43, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:43; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc34_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at SO degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ 1D N0:43, but excluding the poly(A) tail at the
3' end of SEQ ID N0:43; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vc34_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:43, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:43 to a nucleotide sequence corresponding to the 3' end of SEQ TD N0:43
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:43. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:43 from nucleotide 232 to
nucleotide
1461, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:43 from nucleotide 232 to nucleotide 1461, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from
nucleotide
232 to nucleotide 1461. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:43 from nucleotide 280 to nucleotide 1461, and extending contiguously from
a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:43 from
nucleotide 280 to nucleotide 1461, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:43 from nucleotide 280 to nucleotide 1461.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:44;
(b) a fragment of the amino acid sequence of SEQ ID N0:44, the
fragment comprising eight contiguous amino acids of SEQ ID N0:44; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vc34_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:44. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:44 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:44, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:44 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 200 to amino acid 209 of SEQ ID N0:44.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 1922 to nucleotide 2350;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 2237 to nucleotide 2350;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc47 1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc47 1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vc47 1 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc47 1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:46;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:46 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:46;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:45.
Preferably, such .polynucleotide comprises the nucleotide sequence of SEQ ID
N0:45 from nucleotide 1922 to nucleotide 2350; the nucleotide sequence of SEQ
ID N0:45
from nucleotide 2237 to nucleotide 2350; the nucleotide sequence of the full-
length
protein coding sequence of clone vc47 1 deposited with the ATCC under
accession
number 98886; or the nucleotide sequence of a mature protein coding sequence
of clone
vc47 1 deposited with the ATCC under accession number 98886. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc47 1 deposited with the ATCC under accession number
98886.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:46
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:46, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:46 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 66 to amino acid 75 of SEQ ID N0:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:45.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:45, but excluding the poly(A) tail at the
3' end of SEQ ID N0:45; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vc47 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:45, but excluding the poly(A) tail at the
3' end of SEQ ID N0:45; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc47 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:45 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:45
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:45. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 1922 to
nucleotide
2350, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:45 from nucleotide 1922 to nucleotide 2350, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from
nucleotide
1922 to nucleotide 2350. Also preferably the polynucleotide isolated according
to the
2 5 above process comprises a nucleotide sequence corresponding to the cDNA
sequence of
SEQ ID N0:45 from nucleotide 2237 to nucleotide 2350, and extending
contiguously from
a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:45 from
nucleotide 2237 to nucleotide 2350, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:45 from nucleotide 2237 to nucleotide 2350.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:46;
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(b) a fragment of the amino acid sequence of SEQ ID N0:46, the
fragment comprising eight contiguous amino acids of SEQ ID N0:46; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc47 1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:46. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:46 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:46, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:46 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 66 to amino acid 75 of SEQ ID N0:46.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 111 to nucleotide 1337;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:47 from nucleotide 246 to nucleotide 1337;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc54_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc54_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc54_1 deposited with the ATCC under
accession number 98886;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone v~ 1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:48;
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(i) a polynudeotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:48 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:48;
(j) a polynudeotide which is an allelic variant of a polynudeotide of
(a)-{g) above;
(k) a polynudeotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any
one of the polynudeotides specified in (a)-(i); and
(m) a polynudeotide that hybridizes under stringent conditions to any
one of the polynudeotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:47.
Preferably, such polynudeotide comprises the nucleotide sequence of SEQ ID
N0:47 from nucleotide 111 to nucleotide 1337; the nucleotide sequence of SEQ
ID N0:47
from nucleotide 246 to nucleotide 1337; the nucleotide sequence of the full-
length protein
coding sequence of clone vc54_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of done v~ 1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynudeotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc54_1 deposited with the ATCC under accession number 98$86. In
further
preferred embodiments, the present invention provides a poiynudeotide encoding
a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:48
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:48, or a
polynudeotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:48
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 199 to amino acid 208 of SEQ ID N0:48.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:47.
3 0 Further embodiments of the invention provide isolated polynudeotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:47, but excluding the poly(A) tail at the
3' end of SEQ ID N0:47; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc54_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:47, but excluding the poly{A) tail at the
3' end of SEQ ID N0:47; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 v~ 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:47 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:47
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:47. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:47 from nucleotide 111 to
nucleotide
1337, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:47 from nucleotide 111 to nucleotide 1337, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from
nucleotide
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111 to nucleotide 1337. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:47 from nucleotide 246 to nucleotide 1337, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:47 from
nucleotide 246 to nucleotide 1337, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:47 from nucleotide 246 to nucleotide 1337.
1n other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:48;
(b) a fragment of the amino acid sequence of SEQ ID N0:48, the
fragment comprising eight contiguous amino acids of SEQ ID N0:48; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc54_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SBQ ID N0:48. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:48 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:48, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:48 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 199 to amino acid 208 of SEQ ID N0:48.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 189 to nucleotide 1637;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:49 from nucleotide 270 to nucleotide 1637;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc57_1 deposited with the ATCC under
accession number 98886;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc57_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc57 1 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc57 1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:50;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:50 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ TD N0:50;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:49 from nucleotide 189 to nucleotide 1637; the nucleotide sequence of SEQ
ID N0:49
2 5 from nucleotide 270 to nucleotide 1637; the nucleotide sequence of the
full-length protein
coding sequence of clone vc57 1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vc57 1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vc57 1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucieotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:50
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:50, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:50
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 236 to amino acid 245 of SEQ ID N0:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:49.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:49, but excluding the poly(A) tail at the
3' end of SEQ ID N0:49; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc57 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleoside sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:49, but excluding the poly(A) tail at the
3' end of SEQ ID N0:49; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc57 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:49, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:49 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:49
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:49. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 189 to
nucleotide
1637, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:49 from nucleotide 189 to nucleotide 1637, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from
nucleotide
189 to nucleotide 1637. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:49 from nucleotide 270 to nucleotide 1637, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:49 from
nucleotide 270 to nucleotide 1637, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:49 from nucleotide 270 to nucleotide 1637.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:50;
(b} a fragment of the amino acid sequence of SEQ ID N0:50, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:50; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc57 1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:50. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:50 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:50, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:50 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 236 to amino acid 245 of SEQ ID N0:50.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 15 to nucleotide 1934;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 1704 to nucleotide 2934;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vel3_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vel3_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vel3_1 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vel3_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:52;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:52 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:52;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:51.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:51 from nucleotide 15 to nucleotide 1934; the nucleotide sequence of SEQ ID
N0:51
from nucleotide 1704 to nucleotide 1934; the nucleotide sequence of the full-
length
protein coding sequence of clone vel3_1 deposited with the ATCC under
accession
number 98886; or the nucleotide sequence of a mature protein coding sequence
of clone
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vel3_1 deposited with the ATCC under accession number 98886. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vel3_1 deposited with the ATCC under accession number
98886.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:52
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:52, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:52 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 315 to amino acid 324 of SEQ ID N0:52.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:51.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:51, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:51; and
(ab) the nucleotide sequence of the cDNA insert of clone
vel3_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:51, but excluding the poly(A) tail at the
3' end of SEQ ID N0:51; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vel3_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:51 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:51
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:51. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:51 from nucleotide 15 to
nucleotide
1934, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:51 from nucleotide 15 to nucleotide 1934, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from
nucleotide
15 to nucleotide 1934. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:51 from nucleotide 1704 to nucleotide 1934, and extending contiguously from
a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:51 from
nucleotide 1704 to nucleotide 1934, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:51 from nucleotide 1704 to nucleotide 1934.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino arid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:52;
(b) a fragment of the amino acid sequence of SEQ ID N0:52, the
fragment comprising eight contiguous amino acids of SEQ ID N0:52; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vel3_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:52. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino and sequence of SEQ ID N0:52 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:52, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:52 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 315 to amino acid 324 of SEQ ID N0:52.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53 from nucleotide 240 to nucleotide 503;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53 from nucleotide 318 to nucleotide 503;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vel6_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vel6_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vel6_2 deposited with the ATCC under
accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vel6_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:54;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence,of SEQ ID N0:54 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:54;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:53 from nucleotide 240 to nucleotide 503; the nucleotide sequence of SEQ ID
N0:53
from nucleotide 318 to nucleotide 503; the nucleotide sequence of the full-
length protein
coding sequence of clone vel6_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vel6_1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vel6_1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:54
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:54, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:54
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 39 to amino acid 48 of SEQ ID N0:54.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:53.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:53, but excluding the poly(A) tail at the
3' end of SEQ ID N0:53; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vel6_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:53, but excluding the poly(A) tail at the
3' end of SEQ ID N0:53; and
(bb) the nucleotide sequence of the cDNA insert of clone
vel6_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b){iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:53 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:53
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:53. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0~3 from nucleotide 240 to
nucleotide
503, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:53 from nucleotide 240 to nucleotide 503, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from
nucleotide
240 to nucleotide 503. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:53 from nucleotide 318 to nucleotide 503, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:53 from
nucleotide 318 to nucleotide 503, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:53 from nucleotide 318 to nucleotide 503.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:54;
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(b) a fragment of the amino acid sequence of SEQ ID N0:54, the
fragment comprising eight contiguous amino acids of SEQ ID N0:54; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vel6_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:54. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:54 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:54, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:54 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 39 to amino acid 48 of SEQ ID N0:54.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55;
(b) a polynucleoHde comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 11 to nucleotide 1063;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:55 from nucleotide 71 to nucleotide 1063;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vf3_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
2 5 cDNA insert of clone vf3_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vf3_1 deposited with the ATCC under accession
number 98886;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vf3_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:56;
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(i) a polynucieotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:56 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:56;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a poiynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(I) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:55.
Preferably, such polynucieotide comprises the nucleotide sequence of SEQ ID
N0:55 from nucleotide I1 to nucleotide 1063; the nucleotide sequence of SEQ ID
N0:55
from nucleotide 71 to nucleotide 1063; the nucleotide sequence of the full-
length protein
coding sequence of clone vf3_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vf3_1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vf3_1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:56
having
biologicai activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:56, or a
poiynucieotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:56
having biological activity, the fragment comprising the amino acid sequence
fram amino
acid 170 to amino acid 179 of SEQ ID NO:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:55.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:55, but excluding the poly(A) tail at the
3' end of SEQ ID N0:55; and
(ab) the nucleotide sequence of the cDNA insert of clone
vf3_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe{s) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b} a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:55, but excluding the poly(A) tail at the
3' end of SEQ ID N0:55; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vf3_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:55 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:55
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:55. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:55 from nucleotide 11 to
nucleotide
1063, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:55 from nucleotide 11 to nucleotide 1063, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:55 from
nucleotide
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11 to nucleotide 1063. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:55 from nucleotide 71 to nucleotide 1063, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:55 from
nucleotide 71 to nucleotide 1063, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1063.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:56;
(b) a fragment of the amino acid sequence of SEQ ID N0:56, the
fragment comprising eight contiguous amino acids of SEQ ID N0:56; and
(c) the amino acid sequence encoded by the cDNA insert of clone vf3_1
deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:56. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:56 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:56, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:56 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 170 to amino acid 179 of SEQ ID N0:56.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 542 to nucleotide 886;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:57 from nucleotide 755 to nucleotide 886;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vj2_1 deposited with the ATCC under
accession number 98886;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vj2_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vj2_1 deposited with the ATCC under accession
number 98886;
(g) a polynucleofide encoding a mature protein encoded by the cDNA
insert of clone vj2_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:58;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:58 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:58;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a}-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i) and that has a length that is
at least
25% of the length of SEQ ID N0:57.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:57 from nucleotide 542 to nucleotide 886; the nucleotide sequence of SEQ ID
N0:57
from nucleotide 755 to nucleotide 886; the nucleotide sequence of the full-
length protein
coding sequence of clone vj2_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vj2_1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vj2_1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:58
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:58, or a
polynucleotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:58
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 52 to amino acid 61 of SEQ ID N0:58.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:57.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:57, but excluding the poly(A) tail at the
3' end of SEQ ID N0:57; and
(ab) the nucleotide sequence of the cDNA insert of clone
vj2_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:57, but excluding the poly(A) tail at the
3' end of SEQ ID N0:57; and
(bb) the nucleotide sequence of the cDNA insert of clone
vj2_1 deposited with the ATCC under accession number 98886;
{ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:57 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:57
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:57. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:57 from nucleotide 542 to
nucleotide
886, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:57 from nucleotide 542 to nucleotide 886, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from
nucleotide
542 to nucleotide 886. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:57 from nucleotide 755 to nucleotide 886, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ TD
N0:57 from
nucleotide 755 to nucleotide 886, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:57 from nucleotide 755 to nucleotide 886.
In other embodim~ts, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:58;
(b) a fragment of the amino acid sequence of SEQ ID N0:58, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:58; and
(c) the amino acid sequence encoded by the cDNA insert of clone vj2_1
deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:58. In further
preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:58 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:58, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:58 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 52 to amino acid 61 of SEQ ID N0:58.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ TD
N0:59;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 30 to nucleotide 344;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 84 to nucleotide 344;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vp7 1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp7 1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of done vp7 1 deposited with the ATCC under accession
number 98886;
{g} a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp7 1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:60;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID NO:60 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID NO:60;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 {1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:59.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:59 from nucleotide 30 to nucleotide 344; the nucleotide sequence of SEQ ID
N0:59
from nucleotide 84 to nucleotide 344; the nucleotide sequence of the full-
length protein
coding sequence of clone vp7 1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vp7 1
deposited
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with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vp7 1 deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:60
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:60, or a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:60
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 47 to amino acid 56 of SEQ ID N0:60.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:59.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:59, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID N0:59; and
(ab) the nucleotide sequence of the cDNA insert of clone
vp7 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human øenntr,;r nnra ;.,
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:59, but excluding the poly(A) tail at the
3' end of SEQ ID N0:59; and
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(bb) the nucleotide sequence of the cDNA insert of done
vp7 1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynudeotide products of step (b)(iii).
Preferably the polynudeotide isolated according to the above process comprises
a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:59 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:59
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:59. Also preferably the
polynudeotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:59 from nucleotide 30 to
nucleotide
344, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:59 from nucleotide 30 to nucleotide 344, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from
nucleotide
30 to nucleotide 344. Also preferably the polynudeotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:59 from nucleotide 84 to nucleotide 344, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:59 from
nucleotide 84 to nucleotide 344, to a nucleotide sequence corresponding to the
3' end of
said sequence of SEQ ID N0:59 from nucleotide 84 to nucleotide 344.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino add sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:60;
(b) a fragment of the amino acid sequence of SEQ ID N0:60, the
fragment comprising eight contiguous amino acids of SEQ ID N0:60; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vp7 1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:60. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:60 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:60, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:60 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 47 to amino acid 56 of SEQ ID N0:60.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:61;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 23 to nucleotide 757;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 119 to nucleotide 757;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vp8_1 deposited with the ATCC under
accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp8_1 deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 0 protein coding sequence of clone vp8_1 deposited with the ATCC under
accession
number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp8_1 deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid
2 5 sequence of SEQ ID N0:62;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:62 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:62;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
3 0 (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleodde that hybridizes under stringent conditions to any
one of the polynucleotides specified in {a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:61 from nucleotide 23 to nucleotide 757; the nucleotide sequence of SEQ ID
N0:61
from nucleotide 119 to nucleotide 757; the nucleotide sequence of the full-
length protein
coding sequence of clone vp8_1 deposited with the ATCC under accession number
98886;
or the nucleotide sequence of a mature protein coding sequence of clone vp8_1
deposited
with the ATCC under accession number 98886. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vp8_I deposited with the ATCC under accession number 98886. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:62
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:62, or a
polynucleotide
encoding a protein comprising a fragment of the amino and sequence of SEQ ID
N0:62
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 117 to amino acid 126 of SEQ ID N0:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:61.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:61, but excluding the poly(A) tail at the
3' end of SEQ ID N0:61; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vp8_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:61, but excluding the poly(A) tail at the
3' end of SEQ ID N0:61; and
(bb) the nucleotide sequence of the cDNA insert of clone
vp8_1 deposited with the ATCC under accession number 98886;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:61 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:61
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:61. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:61 from nucleotide 23 to
nucleotide
757, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:61 from nucleotide 23 to nucleotide 757, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from
nucleotide
23 to nucleotide 757. Also preferably the polynucleotide isolated according to
the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:61 from nucleotide 119 to nucleotide 757, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:61 from
nucleotide 119 to nucleotide 757, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:61 from nucleotide 119 to nucleotide 757.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:62;
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(b) a fragment of the amino acid sequence of SEQ ID N0:62, the
fragment comprising eight contiguous amino acids of SEQ ID N0:62; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vp8_1 deposited with the ATCC under accession number 98886;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:62. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:62 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:62, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:62 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 117 to amino acid 126 of SEQ ID N0:62.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 1048 to nucleotide 3726;
(c) a polynucleotide comprising the nucleotide sequence of the full
2 0 length protein coding sequence of clone vb22_1 deposited with the ATCC
under
accession number 98933;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb22_1 deposited with the ATCC under accession number
98933;
2 5 (e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb22_1 deposited with the ATCC under
accession number 98933;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb22_1 deposited with the ATCC under accession number 98933;
3 0 (g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:64;
(h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:64 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:64;
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(i) a polynucleotide which is an allelic variant of a polvnucleotide of
(a)-(f) above;
(j) a polynucieotide which encodes a species homologue of the protein
of (g) or (h) above.;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h) and that has a length that is
at least
25% of the length of SEQ ID N0:63.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:63 from nucleotide 1048 to nucleotide 3726; the nucleotide sequence of the
full-length
protein coding sequence of clone vb22_1 deposited with the ATCC under
accession
number 98933; or the nucleotide sequence of a mature protein coding sequence
of clone
vb22_1 deposited with the ATCC under accession number 98933. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vb22_1 deposited with the ATCC under accession number
98933.
In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:64
having biological activity, the fragment preferably comprising eight (more
preferably
2 0 twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:64, or
a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:64 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 441 to amino acid 450 of SEQ ID N0:64.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 5 ID N0:63.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
3 0 in 6X SSC at 65 degrees C to a nucleofide sequence selected from the group
consisting of:
(aa) SEQ ID N0:63, but excluding the poly(A) tail at the
3' end of SEQ ID N0:63; and
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(ab) the nucleotide sequence of the cDNA insert of clone
vb22_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:63, but excluding the poly(A) tail at the
3' end of SEQ ID N0:63; and
(bb) the nucleotide sequence of the cDNA insert of done
vb22_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:63 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:63
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:63. Also preferably the
2 5 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:63 from nucleotide 1048 to
nucleotide
3726, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:63 from nucleotide 1048 to nucleotide 3726, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from
nucleotide
3 0 1048 to nucleotide 3726.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:64;
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(b) a fragment of the amino acid sequence of SEQ ID N0:64, the
fragment comprising eight contiguous amino acids of SEQ ID N0:64; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb22_1 deposited with the ATCC under accession number 98933;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:64. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino and sequence of SEQ ID N0:64 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:64, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:64 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 441 to amino acid 450 of SEQ ID N0:64.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:65;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:65 from nucleotide 134 to nucleotide 667;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:65 from nucleotide 191 to nucleotide 667;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc48_1 deposited with the ATCC under
accession number 98933;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc48_1 deposited with the ATCC under accession number
98933;
a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc48_1 deposited with the ATCC under
accession number 98933;
3 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc48_1 deposited with the ATCC under accession number 98933;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:66;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:66 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:66;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in {a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:65.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:65 from nucleotide 234 to nucleotide 667; the nucleotide sequence of SEQ ID
N0:65
from nucleotide 191 to nucleotide 667; the nucleotide sequence of the full-
length protein
coding sequence of clone vc48_1 deposited with the ATCC under accession number
98933;
or the nucleotide sequence of a mature protein coding sequence of clone vc48_1
deposited
with the ATCC under accession number 98933. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc48_1 deposited with the ATCC under accession number 98933. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:66
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:66, or a
polynucleotide
2 5 encoding a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:66
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 84 to amino acid 93 of SEQ ID N0:66.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:65.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID NO:65, but excluding the poly{A) tail at the
3' end of SEQ ID N0:65; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc48_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:65, but excluding the poly(A) tail at the
3' end of SEQ ID N0:65; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vc48_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:65, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:65 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:65
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:65. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:65 from nucleotide 134 to
nucleotide
667, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:65 from nucleotide 134 to nucleotide 667, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:65 from
nucleotide
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134 to nucleotide 667. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:65 from nucleotide 191 to nucleotide 667, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:65 from
nucleotide 191 to nucleotide 667, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:65 from nucleotide 191 to nucleotide 667.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:66;
(b) a fragment of the amino acid sequence of SEQ ID N0:66, the
fragment comprising eight contiguous amino acids of SEQ ID N0:66; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc48_1 deposited with the ATCC under accession number 98933;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:66. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:66 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:66, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:66 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 84 to amino acid 93 of SEQ ID N0:66.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:67;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:67 from nucleotide 65 to nucleotide 457;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:67 from nucleotide 158 to nucleotide 457;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vp3_1 deposited with the ATCC under
accession number 98933;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp3_1 deposited with the ATCC under accession number
98933;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vp3_1 deposited with the ATCC under accession
number 98933;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp3_1 deposited with the ATCC under accession number 98933;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:68;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:68 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:68;
{j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
2 0 (m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:67.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:67 from nucleotide 65 to nucleotide 457; the nucleotide sequence of SEQ ID
N0:67
2 5 from nucleotide 158 to nucleotide 457; the nucleotide sequence of the full-
length protein
coding sequence of clone vp3_1 deposited with the ATCC under accession number
98933;
or the nucleotide sequence of a mature protein coding sequence of clone vp3_1
deposited
with the ATCC under accession number 98933. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
3 0 of clone vp3_1 deposited with the ATCC under accession number 98933. In
further
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising a fragment of the amino acid sequence of SEQ ID N0:68
having
biological activity, the fragment preferably comprising eight (more preferably
twenty,
most preferably thirty) contiguous amino acids of SEQ ID N0:68, or a
polynucieotide
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encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:68
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 60 to amino acid 69 of SEQ ID N0:68.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:67.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:67, but excluding the poly(A) tail at the
3' end of SEQ ID N0:67; and
(ab) the nucleotide sequence of the cDNA insert of clone
vp3_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
2 0 and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 5 (ba) SEQ ID N0:67, but excluding the poly(A) tail at the
3' end of SEQ ID N0:67; and
(bb) the nucleotide sequence of the cDNA insert of clone
vp3_1 deposited with the ATCC under accession number 98933;
(ii) hybridizing said primers) to human genomic DNA in
3 0 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:67, and
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extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:67 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:67
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:67. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:67 from nucleotide 65 to
nucleotide
457, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:67 from nucleotide 65 to nucleotide 457, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:67 from
nucleotide
65 to nucleotide 457. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:67 from nucleotide 158 to nucleotide 457, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:67 from
nucleotide 158 to nucleotide 457, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:67 from nucleotide 158 to nucleotide 457.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:68;
(b) a fragment of the amino acid sequence of SEQ ID N0:68, the
2 0 fragment comprising eight contiguous amino acids of SEQ ID N0:68; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vp3_1 deposited with the ATCC under accession number 98933;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:68. In further
preferred
2 5 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:68 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:68, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:68 having biological activity, the fragment comprising the amino acid
sequence
3 0 from amino acid 60 to amino acid 69 of SEQ ID N0:68.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:69;
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{b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:69 from nucleotide 29 to nucleotide 1387;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:69 from nucleotide 113 to nucleotide 1387;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc61 1 deposited with the ATCC under
accession number 207012;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc61 1 deposited with the ATCC under accession number
207012;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc61_1 deposited with the ATCC under
accession number 207012;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc61_1 deposited with the ATCC under accession number 207012;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:70;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:70 having biological activity, the fragment
2 0 comprising eight contiguous amino acids of SEQ ID N0:70;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 5 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-{i) and that has a length that is
at least
25% of the length of SEQ ID N0:69.
3 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:69 from nucleotide 29 to nucleotide 1387; the nucleotide sequence of SEQ ID
N0:69
from nucleotide 113 to nucleotide 1387; the nucleotide sequence of the full-
length protein
coding sequence of clone vc61 1 deposited with the ATCC under accession number
207012; or the nucleotide sequence of a mature protein coding sequence of
clone vc61_1
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deposited with the ATCC under accession number 207012. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc61_1 deposited with the ATCC under accession number
207012. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:70 having biological activity, the fragment preferably comprising
eight (more
preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:70, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
of SEQ ID N0:70 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 221 to amino acid 230 of SEQ ID N0:70.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:69.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a} a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:69, but excluding the poly(A) tail at the
2 0 3' end of SEQ ID NO:69; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc61_1 deposited with the ATCC under accession number 207012;
(ii} hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 5 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b} a process comprising the steps of:
{i) preparing one or more polynucleotide primers that
3 0 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
{ba) SEQ ID N0:69, but excluding the poly(A) tail at the
3' end of SEQ ID N0:69; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vc61 1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:69, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:69 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:69
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:69. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:69 from nucleotide 29 to
nucleotide
1387, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:69 from nucleotide 29 to nucleotide 1387, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:69 from
nucleotide
29 to nucleotide 1387. Also preferably the poIynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:69 from nucleotide 113 to nucleotide 1387, and extending contiguously from
a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:69 from
nucleotide 113 to nucleotide 1387, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:69 from nucleotide 113 to nucleotide 1387.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:70;
(b) a fragment of the amino acid sequence of SEQ ID N0:70, the
fragment comprising eight contiguous amino acids of SEQ ID N0:70; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vc61_1 deposited with the ATCC under accession number 207012;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:70. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:70 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino ands
of SEQ ID N0:70, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:70 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 221 to amino acid 230 of SEQ ID N0:70.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:71;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:71 from nucleotide 44 to nucleotide 1513;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:71 from nucleotide 92 to nucleotide 1513;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:71 from nucleotide 1 to nucleotide 458;
(e) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vpl5_1 deposited with the ATCC under
accession number 207012;
(f) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vpl5_1 deposited with the ATCC under accession number
2 0 207012;
(g) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vpl5_1 deposited with the ATCC under
accession number 207012;
(h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vpl5_1 deposited with the ATCC under accession number 207012;
(i) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:72;
(j) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:72 having biological activity, the fragment
3 0 comprising eight contiguous amino acids of SEQ ID N0:72;
(k) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein
of (i) or (j) above ;
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~~); and
(n) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in {a)-(j) and that has a length that is
at least
25% of the Length of SEQ ID N0:71.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:71 from nucleotide 44 to nucleotide 1513; the nucleotide sequence of SEQ ID
N0:71
from nucleotide 92 to nucleotide 1513; the nucleotide sequence of SEQ ID N0:71
from
nucleotide 1 to nucleotide 458; the nucleotide sequence of the full-length
protein coding
sequence of clone vpl5_1 deposited with the ATCC under accession number
207012; or
the nucleotide sequence of a mature protein coding sequence of clone vpl5_1
deposited
with the ATCC under accession number 207012. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vpl5_1 deposited with the ATCC under accession number 207012. In yet
other
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising the amino acid sequence of SEQ ID N0:72 from amino acid 1
to amino
acid 139. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:72 having biological activity, the fragment preferably comprising
eight (more
2 0 preferably twenty, most preferably thirty) contiguous amino acids of SEQ
ID N0:72, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
of SEQ ID N0:72 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 240 to amino acid 249 of SEQ ID N0:72.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:71.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
{a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
3 0 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID NO:71, but excluding the poly(A) tail at the
3' end of SEQ ID N0:71; and
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(ab) the nucleotide sequence of the cDNA insert of clone
vpl5_1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:71, but excluding the poly(A) tail at the
3' end of SEQ ID N0:71; and
(bb) the nucleotide sequence of the cDNA insert of clone
vpl5_1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ TD N0:71, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:71 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:71
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:71. Also preferably the
2 5 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:71 from nucleotide 44 to
nucleotide
1513, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:71 from nucleotide 44 to nucleotide 1513, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:71 from
nucleotide
3 0 44 to nucleotide 1513. Also preferably the polynucleotide isolated
according to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:71 from nucleotide 92 to nucleotide 1513, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:71 from
nucleotide 92 to nucleotide 1513, to a nucleotide sequence corresponding to
the 3' end of
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said sequence of SEQ ID N0:71 from nucleotide 92 to nucleotide 1513. Also
preferably
the ,polynucleotide isolated according to the above process comprises a
nucleotide
sequence corresponding to the cDNA sequence of SEQ ID N0:71 from nucleotide 1
to
nucleotide 458, and extending contiguously from a nucleotide sequence
corresponding
to the 5' end of said sequence of SEQ ID N0:71 from nucleotide 1 to nucleotide
458, to a
nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:71 from
nucleotide 1 to nucleotide 458.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:72;
(b) the amino acid sequence of SEQ ID N0:72 from amino acid I to
amino acid 139;
(c) a fragment of the amino acid sequence of SEQ ID N0:72, the
fragment comprising eight contiguous amino acids of SEQ ID N0:72; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vpl5_1 deposited with the ATCC under accession number 207012;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino and sequence of SEQ ID N0:72 or the amino acid
sequence
2 0 of SEQ ID N0:72 from amino and 1 to amino acid 139. In further preferred
embodiments,
the present invention provides a protein comprising a fragment of the amino
acid
sequence of SEQ ID N0:72 having biological activity, the fragment preferably
comprising
eight (more preferably twenty, most preferably thirty) contiguous amino acids
of SEQ ID
N0:72, or a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:72
2 5 having biological activity, the fragment comprising the amino acid
sequence from amino
acid 240 to amino acid 249 of SEQ ID N0:72.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:73;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:73 from nucleotide 348 to nucleotide 743;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:73 from nucleotide 414 to nucleotide 743;
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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vpl7 1 deposited with the ATCC under
accession number 207012;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vpl7 1 deposited with the ATCC under accession number
207012;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vpl7_1 deposited with the ATCC under
accession number 207012;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vpl7 1 deposited with the ATCC under accession number 207012;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ TD N0:74;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:74 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:74;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynudeotide which encodes a species homologue of the protein
2 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
2 5 25% of the length of SEQ ID N0:73.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:73 from nucleotide 348 to nucleotide 743; the nucleotide sequence of SEQ TD
N0:73
from nucleotide 414 to nucleotide 743; the nucleotide sequence of the full-
length protein
coding sequence of clone vpl7 1 deposited with the ATCC under accession number
3 0 207012; or the nucleotide sequence of a mature protein coding sequence of
clone vpl7 1
deposited with the ATCC under accession number 207012. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vpl7 1 deposited with the ATCC under accession number
207012. In further preferred embodiments, the present invention provides a
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polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:74 having biological activity, the fragment preferably comprising
eight (more
preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:74, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
of SEQ ID N0:74 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 61 to amino acid 70 of SEQ ID N0:74.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:73.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:73, but excluding the poly(A) tail at the
3' end of SEQ ID N0:73; and
(ab) the nucleotide sequence of the cDNA insert of clone
vpl7 1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said probes) to human genomic DNA in
2 0 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
2 5 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:73, but excluding the poly(A) tail at the
3' end of SEQ ID N0:73; and
3 0 (bb) the nucleotide sequence of the cDNA insert of clone
vpl7 1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
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(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:73, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:73 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:73
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:73. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:73 from nucleotide 348 to
nucleotide
743, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:73 from nucleotide 348 to nucleotide 743, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:73 from
nucleotide
348 to nucleotide 743. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:73 from nucleotide 414 to nucleotide 743, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:73 from
nucleotide 414 to nucleotide 743, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:73 from nucieotide 414 to nucleotide 743.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:74;
(b) a fragment of the amino acid sequence of SEQ ID N0:74, the
fragment comprising eight contiguous amino acids of SEQ ID N0:74; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vpl7_1 deposited with the ATCC under accession number 207012;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:74. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:74 having biological activity, the fragment
preferably
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:74, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:74 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 61 to amino acid 70 of SEQ ID N0:74.
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In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:75;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:75 from nucleotide 144 to nucleotide 461;
(c) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vpl9_1 deposited with the ATCC under
accession number 207012;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vpl9_1 deposited with the ATCC under accession number
207012;
(e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vpl9_1 deposited with the ATCC under
accession number 207012;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vpl9_1 deposited with the ATCC under accession number 207012;
(g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:76;
2 0 (h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:76 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:76;
(i) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(f) above;
2 5 (j) a polynucleotide which encodes a speaes homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any
3 0 one of the polynucleotides specified in (a~(h) and that has a length that
is at least
25% of the length of SEQ ID N0:75.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:75 from nucleotide 144 to nucleotide 461; the nucleotide sequence of the
full-length
protein coding sequence of clone vpl9_1 deposited with the ATCC under
accession
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number 207012; or the nucleotide sequence of a mature protein coding sequence
of clone
vpl9_1 deposited with the ATCC under accession number 207012. In other
preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vpl9_1 deposited with the ATCC under accession number
207012. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:76 having biological activity, the fragment preferably comprising
eight (more
preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:76, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
of SEQ ID N0:76 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 48 to amino acid 57 of SEQ ID N0:76.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:75.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
2 0 (aa) SEQ ID N0:75, but excluding the poly(A) tail at the
3' end of SEQ ID N0:75; and
(ab) the nucleotide sequence of the cDNA insert of clone
vpl9_I deposited with the ATCC under accession number 207012;
(ii) hybridizing said probes) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:75, but excluding the poly(A) tail at the
3' end of SEQ ID N0:75; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vpl9_1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:75, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:75 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:75
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:75. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:75 from nucleotide 144 to
nucleotide
461, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:75 from nucleotide 144 to nucleotide 461, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:75 from
nucleotide
144 to nucleotide 461.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:76;
(b) a fragment of the amino acid sequence of SEQ ID N0:76, the
fragment comprising eight contiguous amino acids of SEQ ID N0:76; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vpl9_1 deposited with the ATCC under accession number 207012;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:76. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:76 having biological activity, the fragment
preferably
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:76, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:76 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 48 to amino acid 57 of SEQ ID N0:76.
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In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:77;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:77 from nucleotide 54 to nucleotide 368;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:77 from nucleotide 141 to nucleotide 368;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:77 from nucleotide 51 to nucleotide 332;
(e) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vql 1 deposited with the ATCC under
accession number 207012;
(f) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql_1 deposited with the ATCC under accession number
207012;
(g) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vq1_1 deposited with the ATCC under accession
number 207012;
2 0 (h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vql 1 deposited with the ATCC under accession number 207012;
(i) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:78;
(j) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:78 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:78;
(k) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein
3 0 of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(j); and
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(n) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(j) and that has a length that is
at least
25% of the length of SEQ ID N0:77.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:77 from nucleotide 54 to nucleotide 368; the nucleotide sequence of SEQ ID
N0:77
from nucleotide 141 to nucleotide 368; the nucleotide sequence of SEQ ID N0:77
from
nucleotide 51 to nucleotide 332; the nucleotide sequence of the full-length
protein coding
sequence of clone vql 1 deposited with the ATCC under accession number 207012;
or the
nucleotide sequence of a mature protein coding sequence of clone vq1 1
deposited with
the ATCC under accession number 207012. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vql_1 deposited with the ATCC under accession number 207012. In yet
other
preferred embodiments, the present invention provides a polynucleotide
encoding a
protein comprising the amino acid sequence of SEQ ID N0:78 from amino acid 1
to amino
acid 93. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:78 having biological activity, the fragment preferably comprising
eight (more
preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:78, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
2 0 of SEQ ID N0:78 having biological activity, the fragment comprising the
amino acid
sequence from amino acid 47 to amino acid 56 of SEQ ID N0:78.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:77.
Further embodiments of the invention provide isolated polynucleotides produced
2 5 according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
3 0 (aa) SEQ ID N0:77, but excluding the poly(A) tail at the
3' end of SEQ ID N0:77; and
(ab) the nucleotide sequence of the cDNA insert of clone
vql_1 deposited with the ATCC under accession number 207012;
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(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
{ba) SEQ ID N0:77, but excluding the poly(A) tail at the
3' end of SEQ ID N0:77; and
(bb) the nucleotide sequence of the cDNA insert of clone
vql 1 deposited with the ATCC under accession number 207012;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:77, and
2 0 extending contiguously from a nucleotide sequence corresponding to the 5'
end of SEQ
ID N0:77 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:77
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:77. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:77 from nucleotide 54 to
nucleotide
2 5 368, and extending contiguously from a nucleotide sequence corresponding
to the 5' end
of said sequence of SEQ ID N0:77 from nucleotide 54 to nucleotide 368, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:77 from
nucleotide
54 to nucleotide 368. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
3 0 N0:77 from nucleotide 141 to nucleotide 368, and extending contiguously
from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:77 from
nucleotide 141 to nucleotide 368, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:77 from nucleotide 141 to nucleotide 368. Also
preferably
the polynucleotide isolated according to the above process comprises a
nucleotide
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sequence corresponding to the cDNA sequence of SEQ ID N0:77 from nucleotide 51
to
nucleotide 332, and extending contiguously from a nucleotide sequence
corresponding
to the 5' end of said sequence of SEQ ID N0:77 from nucleotide 51 to
nucleotide 332, to
a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:77 from
nucleotide 51 to nucleotide 332.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:78;
(b) the amino acid sequence of SEQ ID N0:78 from amino acid 1 to
amino acid 93;
(c) a fragment of the amino acid sequence of SEQ ID N0:78, the
fragment comprising eight contiguous amino acids of SEQ ID N0:78; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vq1_1 deposited with the ATCC under accession number 207012;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:78 or the amino acid
sequence
of SEQ ID N0:78 from amino acid 1 to amino acid 93. In further preferred
embodiments,
the present invention provides a protein comprising a fragment of the amino
acid
2 0 sequence of SEQ ID N0:78 having biological activity, the fragment
preferably comprising
eight (more preferably twenty, most preferably thirty) contiguous amino acids
of SEQ ID
N0:78, or a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:78
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 47 to amino acid 56 of SEQ ID N0:78.
2 5 In one embodiment, the present invention provides a composition comprising
an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:79;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:79 from nucleotide 2 to nucleotide 1018;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:79 from nucleotide 53 to nucleotide 1018;
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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vpl4_1 deposited with the ATCC under
accession number 207011;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vpl4_1 deposited with the ATCC under accession number
207011;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vpl4_1 deposited with the ATCC under
accession number 207011;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vpl4_1 deposited with the ATCC under accession number 207011;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:80;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:80 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:80;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a~(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
2 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i} and that has a length that is
at least
2 5 25% of the length of SEQ ID N0:79.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:79 from nucleotide 2 to nucleotide 1018; the nucleotide sequence of SEQ ID
N0:79
from nucleotide 53 to nucleotide 1018; the nucleotide sequence of the full-
length protein
coding sequence of clone vpl4_1 deposited with the ATCC under accession number
3 0 207011; or the nucleotide sequence of a mature protein coding sequence of
clone vpl4_1
deposited with the ATCC under accession number 207011. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vpl4_1 deposited with the-ATCC under accession number
207011. In further preferred embodiments, the present invention provides a
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polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:80 having biological activity, the fragment preferably comprising
eight (more
preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:80, or
a polynucleotide encoding a protein comprising a fragment of the amino acid
sequence
of SEQ ID N0:80 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 164 to amino acid 173 of SEQ ID N0:80.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:79.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:79, but excluding the poly(A) tail at the
3' end of SEQ ID N0:79; and
(ab) the nucleotide sequence of the cDNA insert of clone
vpl4_1 deposited with the ATCC under accession number 207011;
(ii) hybridizing said probes) to human genomic DNA in
2 0 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
2 5 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:79, but excluding the poly(A) tail at the
3' end of SEQ ID N0:79; and
3 0 {bb) the nucleotide sequence of the cDNA insert of clone
vpl4_1 deposited with the ATCC under accession number 207011;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
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(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:79, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:79 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:79
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:79. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:79 from nucleotide 2 to
nucleotide
1018, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:79 from nucleotide 2 to nucleotide 101$, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:79 from
nucleotide
2 to nucleotide 1018. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:79 from nucleotide 53 to nucleotide 1018, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:79 from
nucleotide 53 to nucleotide 1018, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:79 from nucleotide 53 to nucleotide 1018.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:80;
(b) a fragment of the amino acid sequence of SEQ ID N0:80, the
fragment comprising eight contiguous amino acids of SEQ ID N0:80; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vpl4_1 deposited with the ATCC under accession number 207011;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:80. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:80 having biological activity, the fragment
preferably
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:80, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:80 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 164 to amino acid 173 of SEQ ID N0:80.
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In certain preferred embodiments, the polynucleotide is operably linked to an
expression control sequence. The invention also provides a host cell,
including bacterial,
yeast, insect and mammalian cells, transformed with such polynucleotide
compositions.
Also provided by the present invention are organisms that have enhanced,
reduced, or
modified expression of the genes) corresponding to the polynucleotide
sequences
disclosed herein.
Processes are also provided for producing a protein, which comprise:
(a) growing a culture of the host cell transformed with such
polynucleotide compositions in a suitable culture medium; and
(b) purifying the protein from the culture.
The protein produced according to such methods is also provided by the present
invention.
Protein compositions of the present invention may further comprise a
pharmaceutically acceptable carrier. Compositions comprising an antibody which
specifically reacts with such protein are also provided by the present
invention.
Methods are also provided for preventing, treating or ameliorating a medical
condition which comprises administering to a mammalian subject a
therapeutically
effective amount of a composition comprising a protein of the present
invention and a
pharmaceutically acceptable carrier.
BR_1~F DESCRIP'TTON OF THE DRAWIN~C;S
Figures 1A and 18 are schematic representations of the pED6 and pNOTs vectors,
respectively, used for deposit of clones disclosed herein.
2 5 DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
Nucleotide and amino acid sequences, as presently determined, are reported
below for each clone and protein disclosed in the present application. The
nucleotide
sequence of each clone can readily be determined by sequencing of the
deposited clone
3 0 in accordance with known methods. The predicted amino acid sequence {both
full-length
and mature forms) can then be determined from such nucleotide sequence. The
amino
acid sequence of the protein encoded by a particular clone can also be
determined by
expression of the clone in a suitable host cell, collecting the protein and
determining its
sequence. For each disclosed protein applicants have identified what they have
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determined to be the reading frame best identifiable with sequence information
available
at the time of filing.
As used herein a "secreted" protein is one which, when expressed in a suitable
host
cell, is transported across or through a membrane, including transport as a
result of signal
sequences in its amino acid sequence. "Secreted" proteins include without
limitation
proteins secreted wholly (e.g., soluble proteins) or partially (e.g. ,
receptors) from the cell
in which they are expressed. "Secreted" proteins also include without
limitation proteins
which are transported across the membrane of the endoplasmic reticulum.
Clone "vbll 1"
A polynucleotide of the present invention has been identified as clone "vbll
l".
vbll_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vbll_1 is a full-length clone,
including the
entire coding sequence of a secreted protein {also referred to herein as "vbll
1 protein").
The nucleotide sequence of vbll 1 as presently determined is reported in SEQ
ID
N0:1, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vbll 1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:2.
Another
2 0 potential vbl l_1 reading frame and predicted amino acid sequence that
could be encoded
by basepairs 84 to 236 of SEQ ID NO:1 is reported in SEQ ID N0:121. Amino
acids 13 to
of SEQ ID N0:121 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 26 of SEQ ID N0:121. Due to the
hydrophobic nature of the predicted leader/signal sequence, it is likely to
act as a
25 transmembrane domain should the predicted leader/signal sequence not be
separated
from the remainder of the protein of SEQ ID N0:121.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vbll 1 should be approximately 1751 bp.
The nucleotide sequence disclosed herein for vbll 1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vbll 1 demonstrated at least some similarity with
sequences
identified as N94870 (yy63bO5.r1 Homo sapiens cDNA clone 278193 5'). Based
upon
sequence similarity, vbl l 1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts a potential
transmembrane
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domain within the vbll 1 protein sequence centered around amino acid 27 of SEQ
ID
N0:2.
Clone"vbl2 1"
A polynucleotide of the present invention has been identified as clone "vbl2
1".
vbl2_I was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vbl2_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vbl2_1 protein').
The nucleotide sequence of vbl2_1 as presently determined is reported in SEQ
ID
N0:3, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vbl2_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:4.
Amino
acids 34 to 46 of SEQ ID N0:4 are a predicted leader/signal sequence, with the
predicted
mature amino acid sequence beginning at amino acid 47. Due to the hydrophobic
nature
of the predicted leader/signal sequence, it is likely to act as a
transmembrane domain
should the predicted leader/signal sequence not be separated from the
remainder of the
vbl2_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 0 vbl2_1 should be approximately 2289 bp.
The nucleotide sequence disclosed herein for vbl2_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vbl2_1 demonstrated at least S(1n'1P Cimilarifcr wi~A
~o""e.,..,...
identified as AA426009 (zw49e1 l.sl Soares total fetus Nb2HF8 9w Homo sapiens
cDNA
2 5 clone 773420 3', mRNA sequence). Based upon sequence similarity, vbl2_1
proteins and
each similar protein or peptide may share at least some activity. The
TopPredII computer
program predicts three additional potential transmembrane domains within the
vbl2 1
protein sequence, centered around amino acids 11, 60, and 104 of SEQ ID N0:4,
respectively. The nucleotide sequence of vbl2_1 indicates that it may contain
a THE1B
3 0 repeat sequence.
vbl2_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 17 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
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Clone "vbl4 1"
A polynucleotide of the present invention has been identified as clone
"vbl4_1".
vbl4_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vbl4_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vbl4_1 protein").
The nucleotide sequence of vbl4_1 as presently determined is reported in SEQ
ID
N0:5, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vbl4_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:6.
Amino
acids 79 to 91 of SEQ ID N0:6 are a predicted leader/signal sequence, with the
predicted
mature amino acid sequence beginning at amino acid 92. Due to the hydrophobic
nature
of the predicted leader/signal sequence, it is likely to act as a
transmembrane domain
should the predicted leader/signal sequence not be separated from the
remainder of the
vbl4_1 protein. Another potential vbl4_1 reading frame and predicted amino
acid
sequence that could be encoded by basepairs 182 to 484 of SEQ ID N0:5 is
reported in
SEQ ID N0:122.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vbl4_1 should be approximately 2377 bp.
2 0 The nucleotide sequence disclosed herein for vbl4_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vbl4_1 demonstrated at least some similarity with
sequences
identified as AF007149 (Homo Sapiens clone 23568, 23621, 23795, 23873 and
23874
mRNA sequences), AF0706I2 (Homo sapiens clone 24771 mRNA sequence), T23635
2 5 (Human gene signature HUMGS05495; standard; cDNA to mRNA), and W02197
(za57e04.r1 Soares fetal liver spleen INFI,S Homo sapiens cDNA clone 296670
5', mRNA
sequence). Based upon sequence similarity, vbl4_1 proteins and each similar
protein or
peptide may share at least some activity.
3 0 Clone "yell 1"
A polynucleotide of the present invention has been identified as clone "vell
1".
vel l_1 was isolated from a human adult brain (Alzheimer s hippocampus level
7) cDNA
library and was identified as encoding a secreted or transmembrane protein on
the basis
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of computer analysis of the amino acid sequence of the encoded protein. yell 1
is a full-
length clone, including the entire coding sequence of a secreted protein (also
referred to
herein as "yell 1 protein").
The nucleotide sequence of vel l_1 as presently determined is reported in SEQ
ID
N0:7, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the yel l 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:8. Amino acids 1
to 9 of
SEQ ID N0:8 are a predicted leader/signal sequence, with the predicted mature
amino
acid sequence beginning at amino and 10. Due to the hydrophobic nature of the
predicted
leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
leader/signal sequence not be separated from the remainder of the vell_1
protein.
The EcolZI/NotI restriction fragment obtainable from the deposit containing
clone
vell_1 should be approximately 984 bp.
The nucleotide sequence disclosed herein for vell_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vell_1 demonstrated at least some similarity with
sequences
identified as F22745 (H.sapiens EST sequence (LL,45/C09) from skeletal muscle,
mRNA
sequence) and Q60824 (Human brain Expressed Sequence Tag EST00928; standard;
DNA). Based upon sequence similarity, yell 1 proteins and each similar protein
or
2 0 peptide may share at least some activity. The TopPredII computer program
predicts a
potential transmembrane domain within the yell 1 protein sequence centered
around
amino acid 35 of SEQ ID N0:8.
Clone "vf2 1"
2 5 A polynucleotide of the present invention has been identified as clone
"vf2 1".
vf2_1 was isolated from a human adult heart cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vf2_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vf2_1 protein").
3 0 The nucleotide sequence of vf2_1 as presently determined is reported in
SEQ ID
N0:9, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vf2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID NO:10. Amino acids
20 to 32
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of SEQ ID NO:10 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 33. Due to the hydrophobic nature
of the
predicted Ieader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vf2_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
~ 1 should be approximately 1162 bp.
The nucleotide sequence disclosed herein for vf2_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vf2_1 demonstrated at least some similarity with
sequences
identified as AA605037 (no68h 10.s 1 NCI_CGAP_AA 1 Homo sapiens cDNA clone
IMAGE:1112035 similar to contains Alu repetitive element;contains element THR
repetitive element; mRNA sequence). Based upon sequence similarity, vf2_1
proteins and
each similar protein or peptide may share at least some activity. The
TopPredlI computer
program predicts two potential transmembrane domains within the vf2_1 protein
sequence, one centered around amino acid 30 and another around amino acid 70
of SEQ
ID NO:10. The nucleotide sequence of vf2_1 indicates that it may contain an
Alu
repetitive element.
2 0 Clone "vg2 1"
A polynucleotide of the present invention has been identified as clone
"vg2_1".
vg2_1 was isolated from a human adult brain cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vg2_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vg2_1 protein").
The nucleotide sequence of vg2_1 as presently determined is reported in SEQ ID
N0:11, and includes a poIy(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vg2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:12. Amino acids
34 to 4b
3 0 of SEQ ID N0:12 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 47. Due to the hydrophobic nature
of the
predicted Ieader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vg2_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vg2_1 should be approximately 1993 bp.
The nucleotide sequence disclosed herein for vg2_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLAST7C and
FASTA search protocols. vg2_1 demonstrated at least some similarity with
sequences
identified as AA830272 (oc45gll.sl NCI CGAP_GCB1 Homo sapiens cDNA clone
TMAGE 1352708 3' similar to TR Q92853 Q92853 HU-K4; mRNA sequence) and D31740
(Homo sapiens DNA, CpG island). The predicted amino acid sequence disclosed
herein
for vg2_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vg2_1 protein demonstrated at
least
some similarity to sequences identified as AF026124 (schwannoma-associated
protein
[Mus musculus]) and U60644 (HU-K4 [Homo sapiens]). Based upon sequence
similarity,
vg2_1 proteins and each similar protein or peptide may share at least some
activity.
Profile hidden markov model analysis (Eddy, S. R., 1996, Curr. Opin. Struct.
Biol. 6(3):
361-365; incorporated by reference herein) of the predicted vg2_1 protein
revealed two
phospholipase D active sites (amino acid residues 209 to 236 and 423 to 449 of
SEQ ID
N0:12). Phospholipase D (PLD) genes are members of a superfamily that is
defined by
2 0 several highly conserved motifs. In mammals, it has been proposed that
phospholipase D
plays a role in membrane vesicular trafficking and in signal transduction.
Using
site-directed mutagenesis, twenty-five point mutants have been made in human
PLD1
(hPLDl) and then characterized (Sung et al., 1997, EMBO J. 16(15): 4519-4530;
which is
incorporated by reference herein). Sung et al. found that a motif (HxKxxxxD;
see for
2 5 example amino acids 214-221 of SEQ ID N0:12) and a serine/threorune
conserved in all
members of the PLD superfamily are critical for PLD biochemical activity,
suggesting a
possible catalytic mechanism. The vg2_1 clone appears to encode a membrane
protein
that may be a phospholipase related to the phospholipase D family. The
TopPredII
computer program predicts four potential transmembrane domains within the
vg2_1
3 0 protein sequence, centered around amino acids 40, 305, 330, and 455 of SEQ
ID N0:12,
respectively.
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Clone "vjl 1"
A polynudeotide of the present invention has been identified as clone "vjl 1".
vjl 1 was isolated from a human fetal brain cDNA library (enriched for
Gprotein-coupled
receptors) and was identified as encoding a secreted or transmembrane protein
on the
basis of computer analysis of the amino acid sequence of the encoded protein.
vjl 1 is a
full-length done, including the entire coding sequence of a secreted protein
(also referred
to herein as "vjl_1 protein").
The nucleotide sequence of vjl 1 as presently determined is reported in SEQ ID
N0:13. What applicants presently believe to be the proper reading frame and
the
predicted amino add sequence of the vjl 1 protein corresponding to the
foregoing
nucleotide sequence is reported in SEQ ID N0:14. Amino acids 1 to 12 of SEQ ID
N0:14
are a predicted leader/signal sequence, with the predicted mature amino acid
sequence
beginning at amino acid 13. Due to the hydrophobic nature of the predicted
leader/signal
sequence, it is likely to act as a transmembrane domain should the predicted
leader/signal
sequence not be separated from the remainder of the vjl 1 protein. Another
potential
vjl_1 reading frame and predicted amino acid sequence that could be encoded by
basepairs 1795 to 2064 of SEQ ID N0:13 is reported in SEQ ID N0:123.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vjl_1 should be approximately 2895 bp.
2 0 The nucleotide sequence disclosed herein for vj1 1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/B1..ASTX and
FASTA search protocols. vjl_1 demonstrated at least some similarity with
sequences
identified as AA410352 (zvllfOl.r1 Soares NhHMPu S1 Homo sapiens cDNA clone
753337 5', mRNA sequence). Based upon sequence similarity, vj2 1 proteins and
each
2 5 similar protein or peptide may share at least some activity. The TopPredII
computer
program predicts a potential transmembrane domain within the vj1 1 protein
sequence
centered around amino acid 70 of SEQ ID N0:14. The nucleotide sequence of vjl
1
indicates that it may contain repetitive elements.
3 0 Clone "vll 1"
A polynudeotide of the present invention has been identified as clone "v11 I".
vll_1 was isolated from a human fetal cartilage cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
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amino acid sequence of the encoded protein. v11_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vll
1 protein").
The nucleotide sequence of vll 1 as presently determined is reported in SEQ ID
NOaS, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vll 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:16. Amino acids
187 to
199 of SEQ ID N0:16 are a predicted Ieader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 200. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vll_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
v11 1 should be approximately 1936 bp.
The nucleotide sequence disclosed herein for vll 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vll_1 demonstrated at least some similarity with
sequences
identified as AA464362 (zx81b12.r1 Soares ovary tumor NbHOT Homo Sapiens cDNA
clone 810143 5', mRNA sequence), M90089 (Mouse inositol 1,4,5-triphosphate
receptor
mRNA sequence), and T21689 (Human gene signature HUMGS03131; standard; cDNA
2 0 to mRNA). The predicted amino acid sequence disclosed herein for vll_1 was
searched
against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vh_1 protein demonstrated at least some
similarity to the
sequence identified as U80846 (partial CDS jCaenorhabditis elegansJ). Based
upon
sequence similarity, vll_1 proteins and each similar protein or peptide may
share at least
2 5 some activity. The TopPredII computer program predicts two additional
potential
transmembrane domains within the vll_1 protein sequence, one centered around
amino
acid 192 and another around amino acid 234 of SEQ ID N0:16.
vll_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 37 kDa was detected in membrane fractions using
SDS
3 0 polyacrylamide gel electrophoresis.
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Clone "vk2 1"
A polynucleotide of the present invention has been identified as clone "vk2
1".
vk2_1 was isolated from a human adult brain cDNA library (enriched for G-
protein-
coupled receptors) and was identified as encoding a secreted or transmembrane
protein
on the basis of computer analysis of the amino acid sequence of the encoded
protein.
vk2_1 is a full-length clone, including the entire coding sequence of a
secreted protein
(also referred to herein as "vk2_1 protein').
The nucleotide sequence of vk2_1 as presently determined is reported in SEQ ID
N0:17, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vk2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:18. Amino acids
10 to 22
of SEQ ID N0:18 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signai sequence not be separated from the remainder of
the vk2_1
protein. Basepairs 416 to 418 of SEQ ID N0:17 may represent the site of an
alternatively
spliced exon that is not present in clone vk2_1.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vk2_1 should be approximately 1284 bp.
2 0 The nucleotide sequence disclosed herein for vk2_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vk2_1 demonstrated at least some similarity with
sequences
identified as AA152101 (z149f09.s1 Soares pregnant uterus NbHPU Homo sapiens
cDNA
clone 505289 3', mRNA sequence) and Q78696 (Sequence encoding therapeutic
2 5 polypeptide from glioblastoma cell line; standard; cDNA to mRNA). The
predicted amino
acid sequence disclosed herein for vk2_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vk2_1
protein demonstrated at least some similarity to the sequence identified as
866278
(Therapeutic polypeptide from glioblastoma cell line). Based upon sequence
similarity,
3 0 vk2_1 proteins and each similar protein or peptide may share at least some
activity. The
TopPredII computer program predicts two additional potential transmembrane
domains
within the vk2_1 protein sequence, one centered around amino acid 61 and
another
around amino acid 97 of SEQ ID N0:18.
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Clone"vb21 1"
A polynucleotide of the present invention has been identified as clone "vb2l
1".
vb21 1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vb21 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vb21
1 protein").
The nucleotide sequence of vb21 1 as presently determined is reported in SEQ
ID
N0:19, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vb21_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:20. Amino
acids 296 to 308 of SEQ ID N0:20 are a predicted leader/signal sequence, with
the
predicted mature amino acid sequence beginning at amino acid 309. Due to the
hydrophobic nature of the predicted leader/signal sequence, it is likely to
act as a
transmembrane domain should the predicted leader/signal sequence not be
separated
from the remainder of the vb21_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vb21 1 should be approximately 4159 bp.
The nucleotide sequence disclosed herein for vb21 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
2 0 FASTA search protocols. vb21 1 demonstrated at least some similarity with
sequences
identified as AA026150 (zj99c10.s1 Soares pregnant uterus NbHPU Homo sapiens
cDNA
clone 469170 3', mlZIVA sequence), T72108 (Human semaphorin Z gene; standard;
cDNA
to mRNA), U52840 (Human semaphorin F homology, X97817 (M. musculus mRNA for
semaphorin F}, and X97818 (M. musculus mRNA for semaphorin G). The predicted
2 5 amino acid sequence disclosed herein for vb21 1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
predicted vb21_1 protein demonstrated at least some similarity to sequences
identified
as W19857 (Human semaphorin Z) and X97818 (samaphorin G [Mus musculus]).
Semaphorins are important membrane proteins involved in axonal guidance in the
3 0 embryonic stage, and may also have a role in nerve regeneration after
injury. Based upon
sequence similarity, vb21_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts four additional
potential
transmembrane domains within the vb21 1 protein sequence, centered around
amino
acids 237, 523, 769, and 895 of SEQ ID N0:20, respectively.
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'lone "vc35 1"
A polynucleotide of the present invention has been identified as clone "vc35
1".
vc35_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc35_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc35_I protein").
The nucleotide sequence of vc35_1 as presently determined is reported in SEQ
ID
N0:21, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc35_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:22. Amino acids
38 to 50
of SEQ ID N0:22 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 51. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc35_1
1 5 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc35_1 should be approximately 3042 bp.
The nucleotide sequence disclosed herein for vc35_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BIrASTN/BLASTX and
2 0 FASTA search protocols. vc35_1 demonstrated at least some similarity with
sequences
identified as AA532364 (nj12a08.s1 NCI_CGAP_Pr22 Homo Sapiens cDNA clone
IMAGE:986102, mltNA sequence), AF029343 (human protocadherin 68), and T22263
(Human gene signature HUMGS03835; standard; cDNA to mIZNA). The predicted
amino
acid sequence disclosed herein for vc35_1 was searched against the GenPept and
GeneSeq
2 5 amino acid sequence databases using the B1.ASTX search protocol. The
predicted vc35_1
protein demonstrated at least some similarity to sequences identified as
Y08715
(protocadherin-4 [Mus musculus)). Based upon sequence similarity, vc35_1
proteins and
each similar protein or peptide may share at least some activity.
3 0 Clone "vc36 1"
A polynucleotide of the present invention has been identified as clone
"vc36_1".
vc36_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
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amino acid sequence of the encoded protein. vc36_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc36_1 protein").
The nucleotide sequence of vc36_1 as presently determined is reported in SEQ
ID
N0:23, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc36_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:24. Amino acids
24 to 36
of SEQ ID N0:24 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 37. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc36 1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc36_1 should be approximately 1395 bp.
The nucleotide sequence disclosed herein for vc36_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc36_1 demonstrated at least some similarity with
sequences
identified as AA259070 (zs33c04.r1 NCI_CGAP_GCBl Homo sapiens cDNA clone IMAGE
686982 5', mRNA sequence) and W67508 (zd40f11.s1 Soares fetal heart NbHHI9W
Homo
sapiens cDNA clone 343149 3', mRNA sequence). Based upon sequence similarity,
vc36_1
2 0 proteins and each similar protein or peptide may share at least some
activity. The
nucleotide sequence of vc36_1 indicates that it may contain repetitive
elements.
Clone "vc38 1"
A polynucleotide of the present invention has been identified as clone "vc38
1".
2 5 vc38_1 was isolated from a human fetal brain cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc38_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc38_1 protein").
The nucleotide sequence of vc38_1 as presently determined is reported in SEQ
ID
3 0 N0:25, and includes a poly(A) tail. What applicants presently believe to
be the proper
reading frame and the predicted amino acid sequence of the vc38_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:26.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc38_1 should be approximately 2468 bp.
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The nucleotide sequence disclosed herein for vc38_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc38_1 demonstrated at least some similarity with
sequences
identified as AF03740t? (neuropeptide Y/peptide YY receptor Ya [Danio rerioJ).
Motifs
analysis and profile hidden markov model analysis of the predicted vc38_1
protein both
reveal the presence of the G-protein-coupled receptor signature. G-protein-
coupled
receptors (also called R7G) are an extensive group of hormones,
neurotransmitters,
odorants, and light receptors which transduce extracellular signals by
interaction with
guanine nucleotide-binding (G) proteins. Most G-protein-coupled receptors lack
a signal
peptide, as does the predicted vc38_1 protein. Based upon sequence similarity,
vc38_1
proteins and each similar protein or peptide may share at least some activity.
The
TopPredII computer program predicts seven potential transmembrane domains
within
the vc38_1 protein sequence, centered around amino acids 60, 90,130, 170, 225,
280, and
318 of SEQ ID N0:26, respectively.
vc3S_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 71 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
Clone "vc39 1"
2 0 A polynucleotide of the present invention has been identified as clone
"vc39_i".
vc39_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc39_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc39_1 protein").
2 5 The nucleotide sequence of vc39_1 as presently determined is reported in
SEQ ID
N0:27, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc39_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:28. Amino acids
2 to 14
of SEQ ID N0:28 are a predicted leader/signal sequence, with the predicted
mature
3 0 amino acid sequence beginning at amino acid 15. Due to the hydrophobic
nature of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc39_1
protein.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc39_1 should be approximately 2048 bp.
The nucleotide sequence disclosed herein for vc39_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc39_1 demonstrated at least some similarity with
sequences
identified as AA631722 (np79d04.s1 NCI_CGAP_Pr2 Homo Sapiens cDNA clone
IMAGE:1132519 similar to gb:M21121 T-CELL SPECIFIC RANTES PROTEIN
PRECURSOR (I-iIJMAN); contains Alu repetitive element; mRNA sequence). Based
upon
sequence similarity, vc39_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts an additional potential
transmembrane domain within the vc39_1 protein sequence centered around amino
acid
40 of SEQ ID N0:28. The nucleotide sequence of vc39_1 indicates that it may
contain an
Alu/SVA repetitive element.
Clone "vc40 1"
A polynucleotide of the present invention has been identified as clone "vc40
1".
vc40_I was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc40_1 is a full-length clone,
including the
2 0 entire coding sequence of a secreted protein (also referred to herein as
"vc40_1 protein").
The nucleotide sequence of vc40_1 as presently determined is reported in SEQ
ID
N0:29, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc40_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:30. Amino acids
19 to 31
2 5 of SEQ ID N0:30 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc40_1
protein.
3 0 The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc40_1 should be approximately 2297 bp.
The nucleotide sequence disclosed herein for vc40_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc40_1 demonstrated at least some similarity with
sequences
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identified as AA143014 {z148g04.r1 Scares pregnant uterus NbHPtJ Homo sapiens
cDNA
clone 505206 5', mRNA sequence) and T20006 (Human gene signature HUMGS01143;
standard; cDNA to mRNA). Based upon sequence similarity, vc40_1 proteins and
each
similar protein or peptide may share at least some activity. The TopPredII
computer
program predicts three additional potential transmembrane domains within the
vc40_1
protein sequence, centered around amino acids 101, 136, and 182 of SEQ ID
N0:30,
respectively.
Clone "vc46 1"
A polynucleotide of the present invention has been identified as clone
"vc46_1".
vc46_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino and sequence of the encoded protein. vc46_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc46_1 protein").
The nucleotide sequence of vc4b_1 as presently determined is reported in SEQ
ID
N0:31, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc46_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:32. Amino acids
10 to 22
of SEQ ID N0:32 are a predicted leader/signal sequence, with the predicted
mature
2 0 amino acid sequence beginning at amino acid 23. Due to the hydrophobic
nature of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc46 1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 5 vc46_1 should be approximately 2938 bp.
The nucleotide sequence disclosed herein for vc46_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc46_1 demonstrated at least some similarity with
sequences
identified as AA029404 (ze94e06.r1 Scares fetal heart NbHHI9W Homo sapiens
cDNA
3 0 clone 366658 5', mRNA sequence) and AQ071029 (human genomic fragment).
Based upon
sequence similarity, vc46_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts two additional
potential
transmembrane domains within the vc46_1 protein sequence, one centered around
amino
acid 70 and another around amino acid 130 of SEQ ID N0:32.
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vc46_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 19 kDa was detected in conditioned medium and
membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone"vc49 1"
A polynucleotide of the present invention has been identified as clone "vc49
1".
vc49_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc49_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc49_1 protein").
The nucleotide sequence of vc49_1 as presently determined is reported in SEQ
ID
N0:33, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc49_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:34. Amino acids
14 to 26
of SEQ ID N0:34 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 27. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc49_1
protein.
2 0 The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc49_1 should be approximately 3471 bp.
The nucleotide sequence disclosed herein for vc49_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc49_1 demonstrated at least some similarity with
sequences
2 5 identified as AI075929 (ov46h11.x1 Soares_testis_NHT Homo sapiens cDNA
clone IMAGE
16404213' similar to TR Q63418 Q63418 PROTOCADHERIN-3; mRNA sequence), I79964
(Sequence 109 from patent US 5708143), and T03572 (Human protocadherin pc3
coding
sequence; standard; cDNA). The predicted amino acid sequence disclosed herein
for
vc49_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
3 0 using the BLASTX search protocol. The predicted vc49_1 protein
demonstrated at least
some similarity to sequences identified as L43592 (protocadherin-3 [Rattus
norvegicus])
and 886865 (Human protocadherin pc3). Based upon sequence similarity, vc49_1
proteins
and each similar protein or peptide may share at least some activity. The
TopPredlT
computer program predicts two potential transmembrane domains within the vc49
1
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protein sequence, one definite transmembrane domain centered around amino acid
700
and another possible transmembrane domain centered around amino acid 260 of
SEQ ID
N0:34. Profile hidden markov model and motifs analyses of the predicted vc49_1
protein
sequence have revealed it to contain five cadherin extracellular repeated
domain
signatures at amino acids 142 to 242, 251 to 347, 356 to 451, 460 to 561, and
576 to 67I of
SEQ ID N0:34. Cadherins are a family of animal glyco-proteins responsible for
calcium-dependent cell-cell adhesion. Cadherins preferentially interact with
themselves
in a homophilic manner in connecting cells; thus acting as both receptor and
ligand.
Structurally, cadherins are built of the following domains: a signal sequence,
followed by
a propeptide of about 130 residues, then an extracellular domain of around 600
residues,
then a transmembrane region, and finally a C-terminal cytoplasmic domain of
about 150
residues. The predicted vc49_1 protein sequence almost exactly follows this
structure (its
cytoplasmic domain being approximately 100 amino acids). Clearly, vc49_1
protein
appears to represent a novel member of the cadherin superfamily.
Clone "vc50 1"
A polynucleotide of the present invention has been identified as clone "vc50
I".
vc50_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
2 0 amino acid sequence of the encoded protein. vc50_l is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc50_1 protein").
The nucleotide sequence of vc50_1 as presently determined is reported in SEQ
ID
N0:35, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc50_I protein
corresponding
2 5 to the foregoing nucleotide sequence is reported in SEQ ID N0:36. Amino
acids 20 to 32
of SEQ ID N0:36 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 33. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc50_1
3 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc50_1 should be approximately 3819 bp.
The nucleotide sequence disclosed herein for vc50_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
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FASTA search protocols. v~ 1 demonstrated at least some similarity with
sequences
identified as AA193122 (zr39d05.r1 Soares NhHMPu Sl Homo Sapiens cDNA clone
665769 5', mRNA sequence), T26031 (Human gene signature HIJMGS08267; standard;
cDNA to mRNA), 231718 (H.sapiens gene for myelin protein zero), and 299943
(Human
DNA sequence from PAC 313L4 on chromosome 1q24). The predicted amino acid
sequence disclosed herein for vc50_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
v~ 1
protein demonstrated at least some similarity to the sequence identified as
K03242 (rat PO
myelin prepeptide), L24893 (myelin protein zero [Homo sapiensJ), and M62860
(mouse
peripheral myelin protein) . Based upon sequence similarity, vc50_1 proteins
and each
similar protein or peptide may share at least some activity. The TopPredII
computer
program predicts an additional potential transmembrane domain within the
vc50_1
protein sequence centered around amino acid 181 of SEQ ID N0:36.
vc50_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 26 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vc51 1"
A polynucleotide of the present invention has been identified as clone "vc5l
I".
2 0 vc51_1 was isolated from a human fetal brain cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc51 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vc51
I protein").
The nucleotide sequence of vc51 1 as presently determined is reported in SEQ
ID
2 5 N0:37, and includes a poly(A) tail. What applicants presently believe to
be the proper
reading frame and the predicted amino acid sequence of the vc51_1 protein
corresponding
to the foregoing nucleoside sequence is reported in SEQ ID N0:38. Amino acids
12 to 24
of SEQ ID N0:38 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 25. Due to the hydrophobic nature
of the
3 0 predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc51 1
protein. If the "G" residue at position 388 of SEQ ID N0:37 were deleted, two
alternative
potential vc51_1 reading frames and predicted amino acid sequences that could
be
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encoded by basepairs 333 to 1310 of SEQ ID N0:37 and by basepairs 139 to 522
of SEQ ID
N0:37 are reported in SEQ ID N0:124 and SEQ ID N0:125, respectively.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc51_1 should be approximately 1992 bp.
The nucleotide sequence disclosed herein for vc51 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc51 1 demonstrated at least some similarity with
sequences
identified as T21514 (Human gene signature HUMGS02887; standard; cDNA to
mRIVA)
and W52782 (zd13h06.r1 Soares fetal heart NbHHI9W Homo sapiens cDNA clone
340571
5', mRNA sequence). The predicted amino acid sequence disclosed herein for
vc51_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
BLASTX search protocol. The predicted vc51_1 protein demonstrated at least
some
similarity to sequences identified as U90716 (human cell surface protein
HCAR), Y07593
(coxsackie and adenovirus receptor protein [Homo sapiens]), Y10320 (mouse
coxsackie
and adenovirus receptor homology, and W 14146 (Human A33 antigen). Based upon
sequence similarity, vc51 1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts four additional
potential
transmembrane domains within the vc51 1 protein sequence centered around amino
acids
17, 216, 260, and 373 of SEQ ID NO:38, respectively.
Clone"vc52 1"
A polynucleotide of the present invention has been identified as clone "vc52
1".
vc52_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
2 5 amino acid sequence of the encoded protein. vc52_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc52_1 protein").
The nucleotide sequence of vc52_1 as presently determined is reported in SEQ
ID
N0:39, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc52_1 protein
corresponding
3 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:40. Amino
acids 19 to 31
of SEQ ID N0:40 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vc52_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc52_1 should be approximately 2018 bp.
The nucleotide sequence disclosed herein for vc52_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc52_1 demonstrated at least some similarity with
sequences
identified as AA075627 (zm89a01.s1 Stratagene ovarian cancer (#937219) Homo
Sapiens
cDNA clone 545064 3', mRNA sequence) and T24879 (Human gene signature
HUMGS06985; standard; cDNA to mRNA). The predicted amino acid sequence
disclosed
herein for vc52_1 was searched against the GenPept and GeneSeq amino acid
sequence
databases using the BLASTX search protocol. The predicted vc52_1 protein
demonstrated
at least some similarity to sequences identified as AL021890 (putative protein
[Arabidopsis thaliana]), L47993 (ORF YJR072c [Saccharomyces cerevisiaej), and
U10402
(undefined protein (Caenorhabditis elegans]). Based upon sequence similarity,
vc52_1
proteins and each similar protein or peptide may share at least some activity.
The
TopPredII computer program predicts a potential transmembrane domain within
the
vc52_1 protein sequence centered around amino acid 145 of SEQ ID N0:40.
vc52_1 protein was expressed in a COS cell expression system, and an expressed
2 0 protein band of approximately 44 kDa was detected in conditioned medium
and
membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc33 1"
A polynucleotide of the present invention has been identified as clone "vc33
1".
2 5 vc33_1 was isolated from a human fetal brain cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc33_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc33_1 protein").
The nucleotide sequence of vc33_1 as presently determined is reported in SEQ
ID
3 0 N0:41, and includes a poly(A) tail. What applicants presently believe to
be the proper
reading frame and the predicted amino acid sequence of the vc33_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:42. Amino acids
99 to 111
of SEQ ID N0:42 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 112. Due to the hydrophobic nature
of the
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predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc33_I
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc33_1 should be approximately 2877 bp.
The nucleotide sequence disclosed herein for vc33_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLAST7C and
FASTA search protocols. vc33_1 demonstrated at least some similarity with
sequences
identified as AA846599 (aj97g02.s1 Soares parathyroid tumor NbHPA Homo Sapiens
cDNA clone IMAGE:1404434 3' similar to gb:M95549 SODIUM/GLUCOSE
COTRANSPORTER-LIKE (HUMAN); mRNA sequence), M95549 (Homo sapiens
sodium/glucose cotransporter-like protein mRNA, complete cds), and Q89779
(Cotransporter protein SNSTl cDNA; standard; cDNA). The predicted amino acid
sequence disclosed herein for vc33_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vc33_1
protein demonstrated at least some similarity to sequences identified as
M95549
(sodium/glucose cotransporter-like protein [Homo sapiens]) and 873593
(Cotransporter
protein SNST1). Based upon sequence similarity, vc33_1 proteins and each
similar protein
or peptide may share at least some activity. The TopPredII computer program
predicts
2 0 three additional potential transmembrane domains within the vc33_1 protein
sequence,
centered around amino acids 186, 260, and 324 of SEQ ID N0:42, respectively.
vc33_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 45 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vc34 1"
A polynucleotide of the present invention has been identified as clone
"vc34_1".
vc34_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
3 0 amino acid sequence of the encoded protein. vc34_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc34_1 protein").
The nucleotide sequence of vc34_1 as presently determined is reported in SEQ
ID
N0:43, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc34_1 protein
corresponding
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to the foregoing nucleotide sequence is reported in SEQ ID N0:44. Amino acids
4 to 16
of SEQ ID N0:44 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 17. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc34_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc34_1 should be approximately 3062 bp.
The nucleotide sequence disclosed herein for vc34_Z was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc34_1 demonstrated at least some similarity with
sequences
identified as AA927558 (om71e04.s1 NCI CGAP_GC4 Homo sapiens cDNA clone IMAGE
1552638 3', ml2NA sequence) and U79281 (Human clone 23588 mRNA sequence).
Based
upon sequence similarity, vc34_1 proteins and each similar protein or peptide
rilay share
at least some activity. The TopPredII computer program predicts two additional
potential
transmembrane domains within the vc34_1 protein sequence, one centered around
amino
acid 251 and another around amino acid 283 of SEQ ID N0:44.
vc34_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 72 kDa was detected in conditioned medium using
SDS
2 0 polyacrylamide gel electrophoresis.
Clone"vc47 1"
A polynucleotide of the present invention has been identified as clone "vc47
1".
vc47 1 was isolated from a human fetal brain cDNA library and was identified
as
2 5 encoding a secreted or transmembrane protein on the basis of computer
analysis of the
amino acid sequence of the encoded protein. vc47 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc47_1 protein').
The nucleotide sequence of vc47 1 as presently determixied is reported in SEQ
ID
N0:45, and includes a poly(A) tail. What applicants presently believe to be
the proper
3 0 reading frame and the predicted amino acid sequence of the vc47 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:46. Amino acids
93 to 105
of SEQ ID N0:46 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 106. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vc47 1
protein.
Another potential vc47 1 reading frame and predicted amino acid sequence that
could be encoded by basepairs 1047 to 1322 of SEQ ID N0:45 is reported in SEQ
ID
N0:126. Amino acids 11 to 23 of SEQ ID N0:126 are a predicted leader/signal
sequence,
with the predicted mature amino acid sequence beginning at amino acid 24. Due
to the
hydrophobic nature of this predicted leader/signal sequence, it is likely to
act as a
transmembrane domain should the predicted leader/signal sequence not be
separated
from the remainder of the protein of SEQ ID N0:126.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc47_1 should be approximately 3676 bp.
The nucleotide sequence disclosed herein for vc47_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc47_1 demonstrated at least some similarity with
sequences
identified as AA339320 (EST44392 Fetal brain I Homo sapiens cDNA 5' end, mRNA
sequence) and 802462 (ye82h04.r1 Homo sapiens cDNA clone 124279 5'). Based
upon
sequence similarity, vc47 1 proteins and each similar protein or peptide may
share at least
some activity. The nucleotide sequence of vc47 1 indicates that it may contain
one or
more of the following repetitive elements: Alu, L1MB7.
Clone "vc54 1"
A polynucleotide of the present invention has been identified as clone
"vc54_1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc54_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc54_1 protein").
The nucleotide sequence of vc54_1 as presently determined is reported in SEQ
ID
N0:47, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the v~ 1 protein
corresponding
3 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:48. Amino
acids 33 to 45
of SEQ ID N0:48 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 46. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vc54_1
protein.
The EcolZI/NotI restriction fragment obtainable from the deposit containing
clone
v~ 1 should be approximately 2083 bp.
The nucleotide sequence disclosed herein for vc54_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. v~ 1 demonstrated at least some similarity with
sequences
identified as AF007152 (Homo Sapiens clone 23649 and 23755 unknown mRNA,
partial
cds), Q76901 (Human genome fragment (Preferred); standard; DNA), and T46905
(EST014
BL29 Burkitt's lymphoma, Pascalis Sideras Homo sapiens cDNA clone BL29-14 5',
mlZIVA
sequence). The predicted amino acid sequence disclosed herein for vc54_1 was
searched
against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vc54_1 protein demonstrated at least some
similarity to
the sequence identified as AF007152 (unknown (Homo sapiens]). Based upon
sequence
similarity, vc54_1 proteins and each similar protein or peptide may share at
least some
activity. The TopPredII computer program predicts two additional potential
transmembrane domains within the vc54_1 protein sequence, one centered around
amino
acid 220 and another around amino acid 247 of SEQ ID N0:48.
v~ 1 protein was expressed in a COS cell expression system, and an expressed
2 0 protein band of approximately 44 kDa was detected in membrane fractions
using SDS
polyacrylamide gel electrophoresis.
Clone"vc57 1"
A polynucleotide of the present invention has been identified as clone "vc57
1".
2 5 vc57 1 was isolated from a human fetal brain cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc57_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vc57
1 protein").
The nucleotide sequence of vc57 1 as presently determined is reported in SEQ
ID
3 0 N0:49, and includes a poly(A) tail. What applicants presently believe to
be the proper
reading frame and the predicted amino acid sequence of the vc57 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ TD N0:50. Amino acids
15 to 27
of SEQ ID N0:50 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature
of the
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predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc57_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc57 1 should be approximately- 2564 bp.
The nucleotide sequence disclosed herein for vc57 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc57 1 demonstrated at least some similarity with
sequences
identified as AA156231 (z150a11.s1 Scares pregnant uterus NbHPU Homo sapiens
cDNA
clone 505340 3', mRNA sequence). The predicted amino acid sequence disclosed
herein
for vc57 1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vc57 1 protein demonstrated at
least
some similarity to the sequence identified as U41635 (OS-9 precursor [Homo
Sapiens]).
Based upon sequence similarity, vc57 1 proteins and each similar protein or
peptide may
share at least some activity.
vc57 1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 51 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
2 0 Clone "vela 1"
A polynucleotide of the present invention has been identified as clone "vela 1
".
vel3_1 was isolated from a human adult brain (Alzheimer's hippocampus level 7)
cDNA
library and was identified as encoding a secreted or transmembrane protein on
the basis
of computer analysis of the amino acid sequence of the encoded protein. vel3_1
is a full-
2 5 length clone, including the entire coding sequence of a secreted protein
(also referred to
herein as "vel3_1 protein").
The nucleotide sequence of vel3_1 as presently determined is reported in SEQ
ID
N0:51, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vel3_1 protein
corresponding
3 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:52. Amino
acids 551 to
563 of SEQ ID N0:52 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 564. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vela 1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vel3_1 should be approximately 3046 bp.
The nucleotide sequence disclosed herein for vel3_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vel3_1 demonstrated at least some similarity with
sequences
identified as AA587395 (nn82h06.s1 NCI_CGAP Co9 Homo Sapiens cDNA clone
IMAGE:1090427 similar to contains element THR repetitive element; mltNA
sequence)
and Q76778 (Human genome fragment (Preferred); standard; DNA). The predicted
amino
acid sequence disclosed herein for vel3_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vel3_1
protein demonstrated at least some similarity to the sequence identified as
U50828 (sel-1
gene product [Caenorhabditis elegans]). Based upon sequence similarity, vel3_1
proteins
and each similar protein or peptide may share at least some activity.
Clone "ve 6 1"
A polynucleotide of the present invention has been identified as clone
"vel6_1".
vel6_1 was isolated from a human adult brain (Alzheimer's hippocampus level 7)
cDNA
2 0 library and was identified as encoding a secreted or transmembrane protein
on the basis
of rnmputer analysis of the amino acid sequence of the encoded protein. vel6_1
is a full-
length clone, including the entire coding sequence of a secreted protein (also
referred to
herein as "vel6_1 protein").
The nucleotide sequence of vel6_1 as presently determined is reported in SEQ
ID
N0:53, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vel6_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:54. Amino acids
14 to 26
of SEQ ID N0:54 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 27. Due to the hydrophobic nature
of the
3 0 predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vel6 1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vel6_1 should be approximately 2033 bp.
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The nucleotide sequence disclosed herein for vel6_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. No hits were found in the databases. The nucleotide
sequence
of vel6_1 indicates that it may contain one or more of the following
repetitive elements:
Alu, MER.
Clone "vf3 1"
A polynucleotide of the present invention has been identified as clone "vf3
1".
vf3_1 was isolated from a human adult heart cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vf3_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vf3_1 protein").
The nucleotide sequence of vf3_1 as presently determined is reported in SEQ ID
N0:55, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vf3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:56. Amino acids
8 to 20
of SEQ ID N0:56 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 0 the predicted leader/signal sequence not be separated from the remainder
of the vf3_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vf3_1 should be approximately 2987 bp.
The nucleotide sequence disclosed herein for vf3_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vf3_1 demonstrated at least some similarity with
sequences
identified as 278394 (H.sapiens mRNA, expressed sequence tag ICRFp507K11187
(5'),
mRNA sequence). The predicted amino acid sequence disclosed herein for vf3_1
was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
3 0 BLASTX search protocol. The predicted vf3_1 protein demonstrated at least
some
similarity to the sequence identified as U41558 (K02B2.3 gene product
[Caenorhabditis
elegans]). Based upon sequence similarity, vf3_1 proteins and each similar
protein or
peptide may share at least some activity. The TopPredII computer program
predicts two
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additional potential transmembrane domains within the vf3_1 protein sequence,
one
centered around amino acid 242 and another around amino acid 275 of SEQ ID
N0:56.
vf3_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 39 kDa was detected in membrane fractions using
SDS
S polyacrylamide gel electrophoresis.
Clone "~~ 1"
A polynucleotide of the present invention has been identified as clone
"vj2_I".
vj2_1 was isolated from a human fetal brain (whole brain, enriched for
Gprotein-coupled
I O receptors) cDNA library and was identified as encoding a secreted or
transmembrane
protein on the basis of computer analysis of the amino acid sequence of the
encoded
protein. vj2_1 is a full-length clone, including the entire coding sequence of
a secreted
protein (also referred to herein as "vj2_1 protein").
The nucleotide sequence of vj2_1 as presently determined is reported in SEQ ID
15 N0:57, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vj2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:58. Amino acids
59 to 71
of SEQ ID N0:58 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 72. Due to the hydrophobic nature
of the
2 0 predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vj2_1
protein.
Another potential vj2_1 reading frame and predicted amino acid sequence that
could be encoded by basepairs 146 to 400 of SEQ ID N0:57 is reported in SEQ ID
N0:127.
2 5 The TopPredlT computer program predicts two potential transmembrane
domains within
the amino acid sequence of SEQ ID N0:127.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vj2_1 should be approximately 1762 bp.
The nucleotide sequence disclosed herein for vj2_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
PASTA search protocols. vj2_1 demonstrated at least some similarity with
sequences
identified as N36445 (yx83c04.r1 Homo Sapiens cDNA clone 268326 5'). Based
upon
sequence similarity, vj2_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts three potential
transmembrane
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domains within the vj2_1 protein sequence, centered around amino acids 30, 67,
and 90
of SEQ ID N0:58, respectively. The nucleotide sequence of vj2_1 indicates that
it may
contain one or more repetitive elements.
Clone "vp7 1"
A polynucleotide of the present invention has been identified as done "vp7 1".
vp7 1 was isolated from a human adult prostate cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vp7_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vp7
1 protein").
The nucleotide sequence of vp7_1 as presently determined is reported in SEQ ID
N0:59, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vp7 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:60. Amino acids
6 to 18
of SEQ ID N0:60 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vp7 1
protein. Another potential vp7 1 reading frame and predicted amino acid
sequence that
2 0 could be encoded by basepairs 2071 to 2430 of SEQ ID N0:59 is reported in
SEQ ID
N0:128.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vp7 1 should be approximately 2638 bp.
The nucleotide sequence disclosed herein for vp7_1 was searched against the
2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vp7 1 demonstrated at least some similarity with
sequences
identified as N49433 (yv21e12.r1 Homo sapiens cDNA clone 243406 5') and Q63862
(AP2
sequence obtained by PCR for tumour specific DNA; standard; cDNA). Based upon
sequence similarity, vp7 1 proteins and each similar protein or peptide may
share at least
3 0 some activity. The TopPredlT computer program predicts an additional
potential
transmembrane domain within the vp7_1 protein sequence centered around amino
acid
75 of SEQ ID N0:60. The nucleotide sequence of vp7 1 indicates that it may
contain one
or more Alu repeat sequences.
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Clone "vn8 1 "
A polynucleotide of the present invention has been identified as clone
"vp8_1".
vp8_1 was isolated from a human adult prostate cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vp8_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vp8_1 protein").
The nucleotide sequence of vp8_1 as presently determined is reported in SEQ ID
N0:61, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vp8_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:62. Amino acids
20 to 32
of SEQ ID N0:62 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 33. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vp8_1
protein. If two insertions of "C" residues were made in the nucleotide
sequence of SEQ
ID N0:61, one after the "A" at position 380 and another after the "G" at
position 382, the
resulting nucleotide sequence would be predicted to encode the amino acid
sequence
reported in SEQ ID N0:129.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 0 vp8_1 should be approximately 1513 bp.
The nucleotide sequence disclosed herein for vp8_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vp8_1 demonstrated at least some similarity with
sequences
identified as AA284421 (zs59c10.r1 NCI_CGAP_GCBl Homo sapiens cDNA clone IMAGE
2 5 701778 5' similar to contains AIu repetitive element; mltNA sequence) and
AC002086
(Human PAC clone DJ525N14 from Xq23, complete sequence). Based upon sequence
similarity, vp8_1 proteins and each similar protein or peptide may share at
least some
activity. Profile hidden markov model analysis reveals the presence of an SH2
domain in
the predicted vp8_1 protein (SEQ ID N0:62). SH2 domains function as regulatory
3 0 modulators of infra-cellular signalling cascades by interacting with high
affinity to
phosphotyrosine-containing target peptides in a sequence-specific and strictly
phosphoryiation-dependent manner. The nucleotide sequence of vp8_1 indicates
that it
may contain one or more AIu repeat sequences.
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vp8_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 34 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis. '
Clone"vb22 1"
A polynucleotide of the present invention has been identified as clone
"vb22_1".
vb22_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vb22_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vb22_1 protein").
The nucleotide sequence of vb22_1 as presently determined is reported in SEQ
ID
N0:63, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vb22_I protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:64.
Another potential vb22_1 reading frame and predicted amino acid sequence is
encoded
by basepairs 152 to 1006 of SEQ ID N0:63 and is reported in SEQ ID N0:130.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb22_1 should be approximately 4176 bp.
The nucleotide sequence disclosed herein for vb22_1 was searched against the
2 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb22_1 demonstrated at least some similarity with
sequences
identified as L10335 (Homo sapiens neuroendocrine-specific protein C (NSP)
mRNA,
complete cds), N21304 (yx53f07.s1 Homo sapiens cDNA clone 265477 3' similar to
SP:A60021 A60021 TROPOMYOSIN-RELATED PROTEIN, NEURONAL), and V23695
2 5 (Human NSPLP protein A coding sequence; standard; cDNA). The predicted
amino acid
sequence disclosed herein for vb22_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vb22_1
protein demonstrated at least some similarity to sequences identified as
L10333
(nueroendocrine-speciEc protein A [Homo sapiens]) and W53947 {Human NSPLP
protein
3 0 A). Based upon sequence similarity, vb22_1 proteins and each similar
protein or peptide
may share at least some activity. The TopPredII computer program predicts two
potential
transmembrane domains within the vb22_1 protein sequence, one centered around
amino
acid 730 and another around amino acid 846 of SEQ ID N0:64. The nucleotide
sequence
of vb22_1 appears to contain a short simple nucleotide repeat ("GGA") region.
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Clone "vc48 1"
A polynucleotide of the present invention has been identified as clone
"vc48_I".
vc48_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc48_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc48_I protein").
The nucleotide sequence of vc48_1 as presently determined is reported in SEQ
ID
N0:65, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc48_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:66. Amino acids
7 to 19
of SEQ ID N0:66 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 20. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc48_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc48_1 should be approximately 3096 bp.
The nucleotide sequence disclosed herein for vc48_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
2 0 FASTA search protocols. vc48_1 demonstrated at least some similarity with
sequences
identified as AA292779 (zt56c06.s1 Soares ovary tumor NbHOT Homo sapiens cDNA
clone 726346 3', mRNA sequence). The predicted amino acid sequence disclosed
herein
for vc48_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vc48_1 protein demonstrated at
least
2 5 some sirrularity to sequences identified as AL031765 (Drosophila genomic
product 22E5.z)
and 281058 {F11E6.e [Caenorhabditis elegans]). Based upon sequence similarity,
vc48_1
proteins and each similar protein or peptide may share at least some activity.
The
TopPredII computer program predicts four potential transmembrane domains
within the
vc48_1 protein sequence, one centered around amino acid 39 and others around
amino
3 0 acids 69,107 and 134 of SEQ ID N0:66, respectively. The nucleotide
sequence of vc48_1
appears to contain a simple nucleotide repeat ("AC") and one or more of the
following
repetitive elements: Alu and MIR.
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Clone "vp3 1"
A polynucleotide of the present invention has been identified as clone
"vp3_1".
vp3_1 was isolated from a human adult prostate cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vp3_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vp3_1 protein").
The nucleotide sequence of vp3_1 as presently determined is reported in SEQ ID
N0:67, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vp3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:68. Amino acids
19 to 32
of SEQ ID N0:68 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vp3_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vp3_1 should be approximately 552 bp.
The nucleotide sequence disclosed herein for vp3_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
2 0 FASTA search protocols. vp3_1 demonstrated at least some similarity with
sequences
identified as AA225045 (nc34c06.r1 NCI_CGAP_Pr2 Homo Sapiens cDNA clone IMAGE
1010026, mRNA sequence), M18157 (Human glandular kallikrein gene, complete
cds), and
T35868 (Prostate-specific antigen gene partial sequence; standard; DNA). Based
upon
sequence similarity, vp3_1 proteins and each similar protein or peptide may
share at least
2 5 some activity.
Clone "vc61 1"
A polynucleotide of the present invention has been identified as clone "vc61
1".
vc61_1 was isolated from a human fetal brain cDNA library and was identified
as
3 0 encoding a secreted or transmembrane protein on the basis of computer
analysis of the
amino acid sequence of the encoded protein. vc61 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vc61
1 protein").
The nucleotide sequence of vc61 1 as presently determined is reported in SEQ
ID
N0:69, and includes a poly(A) tail. What applicants presently believe to be
the proper
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reading frame and the predicted amino acid sequence of the vc61_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:70. Amino acids
16 to 28
of SEQ ID N0:70 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 29. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc61 1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc61_1 should be approximately 3199 bp.
The nucleotide sequence disclosed herein for vc61 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc61 1 demonstrated at least some similarity with
sequences
identified as AI028115 (ow51d09.x1 Soares_parathyroid tumor_NbHPA Homo Sapiens
cDNA clone IMAGE 1650353 3' similar to gb S67859 TRANSCRIPT ION I1VTTIA'I'ION
FACTOR IIE-ALPHA CHAIN (HUMAN); m,~A), V20913 (Human induced tumour
protein cDNA), and 299129 (Human DNA sequence from clone 425C14 on chromosome
6q22 Contains the HSF2 gene for Heat Shock Factor 2 (Heat Shock Transcription
Factor
2, HST'F 2) and an unknown gene similar to the placental protein D1FF33 gene;
Contains
ESTs, ST'Ss and GSSs, complete sequence). Tie predicted amino acid sequence
disclosed
2 0 herein for vc61 1 was searched against the GenPept and GeneSeq amino acid
sequence
databases using the BLAST7C search protocol. The predicted vc62_1 protein
demonstrated
at least some similarity to sequences identified as W52812 (Human induced
tumour
protein) and 299129 (dJ425C14.2 (Placental protein D1FF33 LIKE) [Homo
sapiens]). The
deduced vc61 1 protein has amino acid similarity to human and mouse diff33
protein.
2 5 Diff33 is a transmembrane protein which is overexpressed in testicular
tumors from
polyomavirus large T-antigen transgenic mice. Based upon sequence similarity,
vc61_1
proteins and each similar protein or peptide may share at least some activity.
The
TopPredII computer program predicts nine additional potential transmembrane
domains
within the vc61_1 protein sequence, centered around amino acids 50,100,150,
210, 240,
3 0 270, 320, 390, and 430 of SEQ ID N0:70, respectively. The nucleotide
sequence of vc61_1
indicates that it may contain an Alu repetitive element.
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Clone "vpl5 1"
A polynucleotide of the present invention has been identified as clone
"vpl5_1".
vpl5_1 was isolated from a human adult prostate cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vpl5_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vpl5_1 protein").
The nucleotide sequence of vpl5_1 as presently determined is reported in SEQ
ID
N0:71, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vpl5_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:72. Amino
acids 4 to 16 of SEQ ID N0:72 are a predicted leader/signal sequence, with the
predicted
mature amino acid sequence beginning at amino acid 17. Due to the hydrophobic
nature
of the predicted Ieader/signal sequence, it is likely to act as a
transmembrane domain
should the predicted leader/signal sequence not be separated from the
remainder of the
vpl5_1 protein. If a "C" residue were inserted between nucleotides 458 and 459
of SEQ
ID N0:71, nucleotides 44 to 568 of the resulting nucleotide sequence would
encode a
protein having an amino acid sequence reported as SEQ ID N0:131.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vpl5_1 should be approximately 2033 bp.
2 0 The nucleotide sequence disclosed herein for vpl5_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vpl5_1 demonstrated at least some similarity with
sequences
identified as AI033082 (ow97g04.s1 Soares_fetal_Iiver_spleen_1NFLS Sl Homo
Sapiens
cDNA clone IMAGE 1654806 3', mRNA sequence) and T21877 (Human gene signature
HUMGS03418). The predicted amino acid sequence disclosed herein for vpl5_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
BLASTX search protocol. The predicted vpl5_1 protein demonstrated at least
some
similarity to sequences identified as 845335 (Thrombomodulin analogue Q336N,
Q365E)
and U94333 (ClqR(p) (Homo sapiens]). The predicted vpl5_1 protein shows some
amino
3 0 acid similarity to multiple thrombomodulin analogues (such as GeneSeq
accession
number 845335), and shows some end-to-end similairity to GenPept accession
number
U94333, which is described as a "... human Clq/MBL/SPA receptor that mediates
enhanced phagocytosis in vitro" (Nepomuceno et al., 1997, Immunity 6(2):119-
129, which
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is incorporated by reference herein). Based upon sequence similarity, vpl5_1
proteins
and each similar protein or peptide may share at least some activity.
vpl5_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 24 kDa was detected in conditioned medium and
membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vol7 1"
A polynucleotide of the present invention has been identified as clone "vpl7
1".
vpl7 1 was isolated from a human adult prostate cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vpl7 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vpl7
1 protein").
The nucleotide sequence of vpl7 1 as presently determined is reported in SEQ
ID
N0:73, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vpl7 1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:74. Amino
ands 10 to 22 of SEQ ID N0:74 are a predicted leader/signal sequence, with the
predicted
mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic
nature
of the predicted leader/signal sequence, it is likely to act as a
transmembrane domain
2 0 should the predicted leader/signal sequence not be separated from the
remainder of the
vpl7 1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vpl7 1 should be approximately 3150 bp.
The nucleotide sequence disclosed herein for vpl7 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vpl7 1 demonstrated at least some similarity with
sequences
identified as AI056890 (oz03g07.x1 Soares_fetal_Iiver_spleen_1NFLS_Sl Homo
sapiens
cDNA clone IMAGE 1674300 3', mRNA sequence) and T64815 (Tumour suppressor
activated pathway gene TSAP6). Based upon sequence similarity, vpl7_1 proteins
and
3 0 each similar protein or peptide may share at least some activity. The
TopPredII computer
program predicts two additional potential transmembrane domains within the
vpl7 1
protein sequence, one centered around amino acid 50 and another around amino
acid 80
of SEQ ID N0:74.
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Clone "vnl9 1 "
A polynucleotide of the present invention has been identified as clone
"vpl9_1".
vpl9_1 was isolated from a human adult prostate cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vpl9_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vpl9_1 protein').
The nucleotide sequence of vpl9_1 as presently determined is reported in SEQ
ID
N0:75, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vpl9_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:76.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vpl9_1 should be approximately 971 bp.
The nucleotide sequence disclosed herein for vpl9_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
PASTA search protocols. vpl9_1 demonstrated at least some similarity with
sequences
identified as AA716408 (Zg64b02.s1 Soares fetal heart NbHHI9W Homo sapiens
cDNA
clone 398091 3', mRNA sequence) and T20711 (Human gene signature HUMGS01928).
Based upon sequence similarity, vpl9_1 proteins and each similar protein or
peptide may
share at least some activity. The TopPredII computer program predicts a
potential
2 0 transmembrane domain within the vpl9_1 protein sequence centered around
amino acid
23 of SEQ ID N0:76; due to its hydrophobic nature, this region (amino acids 20
to 32)
could also be a leader/signal sequence, with the mature protein beginning at
amino acid
33 of SEQ ID N0:76.
Clone "val 1"
A polynucleotide of the present invention has been identified as clone "vql
1".
vql 1 was isolated from a human adult lung cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vql_1 is a full-length clone,
including the
3 0 entire coding sequence of a secreted protein (also referred to herein as
"vql 1 protein").
The nucleotide sequence of vql 1 as presently determined is reported in SEQ ID
N0:77, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vq1_I protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:78. Amino acids
17 to 29
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of SEQ ID N0:78 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 30. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vql_1
protein. If a "T" residue were inserted between nucleotides 332 and 333 of SEQ
ID
N0:77, nucleotides 54 to 496 of the resulting nucleotide sequence would encode
a protein
having an amino acid sequence reported as SEQ ID N0:132.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vql 1 should be approximately 873 bp.
The nucleotide sequence disclosed herein for vql_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/gL~~ ~d
FASTA search protocols. vql_1 demonstrated at least some similarity with
sequences
identified as No hits were found in the databases. The TopPredII computer
program
predicts an additional potential transmembrane domain within the vq1_1 protein
sequence, extending from about amino acid 36 to about amino acid 76 of SEQ ID
N0:78.
The nucleotide sequence of vq1 1 indicates that it may contain an Alu
repetitive element.
Clone "vul4 1"
2 0 A polynucleotide of the present invention has been identified as clone
"vpl4_1".
vpl4_1 was isolated from a human adult prostate cDNA library and was
identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vpl4_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vpl4_I protein").
The nucleotide sequence of vpl4_1 as presently determined is reported in SEQ
ID
N0:79, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vpl4_1 protein
corresponding to the foregoing nucleotide sequence is reported in SEQ ID
N0:80. Amino
acids 5 to 17 of SEQ ID N0:80 are a predicted leader/signal sequence, with the
predicted
3 0 mature amino acid sequence beginning at amino acid 18. Due to the
hydrophobic nature
of the predicted leader/signal sequence, it is likely to act as a
transmembrane domain
should the predicted leader/signal sequence not be separated from the
remainder of the
vpl4_1 protein.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vpl4_1 should be approximately 1355 bp.
The nucleotide sequence disclosed herein for vpl4_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vpl4_1 demonstrated at least some similarity with
sequences
identified as AI052724 (oz27a12.x1 Soares total_fetus Nb2HF8 9w Homo Sapiens
cDNA clone IMAGE:1676542 3' similar to SW:yQIQ_BACSU P54554
HYPOTHETICAL OXIDOREDUCTASE IN GLNQ-ANSR INTERGENIC REGION;
mRNA sequence) and T20001 (Human gene signature HUMGS01138). The predicted
amino acid sequence disclosed herein for vpl4_1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
predicted vpl4_1 protein demonstrated at least some similarity to sequences
identified
as 861477 (Clavulanic acid dehydrogenase sequence) and 299116 (similar to
ketoacyI
reductase [Bacillus subtilis]). The predicted vpl4_1 protein shows some amino
acid
similarity to various dehydrogenases due to the presence of a short-chain
alcohol
dehydrogenase family signature at amino acids 51 to 240 of SEQ 1D NO:80, as
detected
by motifs and hidden markov model analysis. Based upon sequence similarity,
vpl4_1
proteins and each similar protein or peptide may share at least some activity.
The
TopPredII computer program predicts four additional potential transmembrane
domains
within the vpl4_1 protein sequence, centered around amino acids 55, 195, 230,
and 300
of SEQ ll~ N0:80, respectively.
Deposit of Clones
Clones vbll_l, vbl2_1, vbl4_l, yell 1, vf2_l, vg2_l, vjl_l, and vll_1 were
2 5 deposited on August 20,1998 with the ATCC (American Type Culture
Collection,10801
University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original
deposit under
the Budapest Treaty and were given the accession number 98846, from which each
clone
comprising a particul~. polynucleotide is obtainable.
Clone vk2_1 was deposited on August 20,1998 with the ATCC (American Type
3 0 Culture Collection, 10801 University Boulevard, Manassas, Virginia 20110-
2209 U.S.A.)
as an original deposit under the Budapest Treaty and was given the accession
number
98838, from which the vk2_1 clone comprising a particular polynucleotide is
obtainable.
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Clones vb21_l, vc35_l, vc36_l, vc38_l, vc39_1, vc40_l, vc46_1, vc49_l, vc50 1,
vc51 1, and vc52_1 were deposited on September 2,1998 with the ATCC (American
Type
Culture Collection,10801 University Boulevard, Mantissas, Virginia 20110-2209
U.S.A.)
as an original deposit under the Budapest Treaty and were given the accession
number
98862, from which each clone comprising a particular polynucleotide is
obtainable.
Clones vc33_l, vc34_l, vc47 1,, vc54_l, vc57 1, vel3_1, vel6_I, vf3_1, vj2_l,
vp7 1, and vp8_1 were deposited on September 22,1998 with the ATCC (.American
Type
Culture Collection, 10801 University Boulevard, Mantissas, Virginia 20110-2209
U.S.A.)
as an original deposit under the Budapest Treaty and were given the accession
number
98886, from which each clone comprising a particular polynucleotide is
obtainable.
Clones vb22_l, vc48_l, and vp3_1 were deposited on October 16,1998 with the
ATCC (American Type Culture Collection, 10801 University Boulevard, Mantissas,
Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty
and were
given the accession number 98933, from which each clone comprising a
particular
polynucleotide is obtainable.
Clones vc61_l, vpl5_l, vpl7 1, vpl9_1, and vql_1 were deposited on December
23,1998 with the ATCC (American Type Culture Collection,10801 University
Boulevard,
Mantissas, Virginia 20110-2209 U.S.A.) as an original deposit under the
Budapest Treaty
and were given the accession number 207012, from which each clone comprising a
2 0 particular polynucleotide is obtainable.
Clone vpl4_1 was deposited on December 23, 1998 with the ATCC (American
Type Culture Collection, 10801 University Boulevard, Mantissas, Virginia 20110-
2209
U.S.A.) as an original deposit under the Budapest Treaty and was given the
accession
number 207011, from which the vpl4_1 clone comprising a particular
polynucleotide is
2 5 obtainable.
All restrictions on the availability to the public of the deposited material
will be
irrevocably removed upon the granting of the patent, except for the
requirements
specified in 37 C.F.R. ~ L808(b), and the term of the deposit will comply with
37 C.F.R.
~ 1.806.
3 0 Each clone has been transfected into separate bacterial cells (E. colt' in
this
composite deposit. Each clone can be removed from the vector in which it was
deposited
by performing an EcoRI/NotI digestion (5' site, EcoRI; 3' site, NotI) to
produce the
appropriate fragment for such clone. Each clone was deposited in either the
pED6 or
pNOTs vector depicted in Figures 1A and 1B, respectively. The pED6dpc2 vector
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CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
("pED6") was derived from pED6dpc1 by insertion of a new polylinker to
facilitate
cDNA cloning (Kaufman et al., 1991, Nucleic Acids Res.19: 4485-4490); the
pNOTs vector
was derived from pMT2 (Kaufman et al.,1989, Mol. Cell. Biol. 9: 946-958) by
deletion of
the DHFR sequences, insertion of a new polylinker, and insertion of the M13
origin of
replication in the CIaI site. In some instances, the deposited clone can
become "flipped"
(i.e., in the reverse orientation) in the deposited isolate. In such
instances, the cDNA insert
can still be isolated by digestion with EcoRI and NotI. However, NotI will
then produce
the 5' site and EcoRI will produce the 3' site for placement of the cDNA in
proper
orientation for expression in a suitable vector. The cDNA may also be
expressed from the
vectors in which they were deposited.
Bacterial cells containing a particular clone can be obtained from the
composite
deposit as follows:
An oligonucleotide probe or probes should be designed to the sequence that is
known for that particular clone. This sequence can be derived from the
sequences
provided herein, or from a combination of those sequences. The sequence of an
oligonucleotide probe that was used to isolate or to sequence each full-length
clone is
identified below, and should be most reliable in isolating the clone of
interest.
Cl-ne Probe SeduellCP
2 0 vbl l_1 SEQ ID N0:81
vbl2_1 SEQ ID N0:82
vbl4_1 SEQ ID N0:83
vell_1 SEQ ID N0:84
vf2_1 SEQ ID N0:85
2 5 vg2_1 SEQ ID N0:86
vj1 1 SEQ ID N0:87
vll_1 SEQ ID N0:88
vk2_1 SEQ ID N0:89
vb21_1 SEQ ID N0:90
3 0 vc35_1 SEQ ID N0:91
vc36_1 SEQ ID N0:92
vc38_1 SEQ ID N0:93
vc39_1 S EQ ID N0:94
vc40_1 SEQ ID N0:95
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vc46_1 SEQ ID N0:96
vc49_1 SEQ ID N0:97
vc5t1_1 SEQ ID N0:98
vc51_1 SEQ ID N0:99
vc52_1 SEQ ID N0:100
vc33_1 SEQ ID N0:101
vc34_1 SEQ ID N0:102
vc47 1 SEQ ID N0:103
vc54_1 SEQ ID N0:104
vc57 1 S EQ ID N0:105
vel3_1 SEQ ID N0:106
vel6_1 SEQ ID N0:107
vf3_1 SEQ ID N0:108
vj2_1 SEQ ID N0:109
vp7 1 SEQ ID N0:110
~'8 1 SEQ ID NO:111
vb22_1 SEQ ID N0:112
vc48_1 SEQ ID N0:113
vp3_1 SEQ ID N0:114
2 0 vc61_1 SEQ ID N0:115
vpl5_1 SEQ ID N0:116
vpl7 1 SEQ ID NO:I17
vpl9_1 SEQ ID N0:118
vql_1 SEQ ID N0:119
vpl4_i SEQ ID N0:120
In the sequences listed above which include an N at position 2, that position
is occupied
in preferred probes/primers by a biotinylated phosphoaramidite residue rather
than a
nucleotide (such as, for example, that produced by use of biotin
phosphoramidite (1-
3 0 dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl)-
(N,N-
diisopropyl)-phosphoramadite) (Glen Research, cat. no.10-1953)).
The design of the oligonucleotide probe should preferably follow these
parameters:
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WO 00/11015 PCT/US99/19351
(a) It should be designed to an area of the sequence which has the fewest
ambiguous bases ("N's"), if any;
(b) It should be designed to have a T°, of approx. 80 ° C
(assuming 2° for each
A or T and 4 degrees for each G or C).
The oligonucleotide should preferably be labeled with y 32P ATP (specific
activity 6000
Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for
labeling oligonucleotides. Other labeling techniques can also be used.
Unincorporated
label should preferably be removed by gel filtration chromatography or other
established
methods. The amount of radioactivity incorporated into the probe should be
quantitated
by measurement in a scintillation counter. Preferably, specific activity of
the resulting
probe should be approximately 4e+6 dpm/pmole.
The bacterial culture containing the pool of full-length clones should
preferably
be thawed and 100 lzl of the stock used to inoculate a sterile culture flask
containing 25 m1
of sterile L-broth containing ampicillin at 100 ug/ml. The culture should
preferably be
grown to saturation at 37°C, and the saturated culture should
preferably be diluted in
fresh L-broth. Aliquots of these dilutions should preferably be plated to
determine the
dilution and volume which will yield approximately 5000 distinct and well-
separated
colonies on solid bacteriological media containing L-broth containing
ampicillin at 100
ug/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at
37°C. Other
2 0 known methods of obtaining distinct, well-separated colonies can also be
employed.
Standard colony hybridization procedures should then be used to transfer the
colonies to nitrocellulose filters and lyse, denature and bake them.
The filter is then preferably incubated at 65°C for 1 hour with gentle
agitation in
6X SSC (20X stock is 175.3 g NaCI/liter, 88.2 g Na citrate/liter, adjusted to
pH 7.0 with
2 5 NaOH) containing 0.5% SDS,100 ug/ml of yeast RNA, and 10 mM EDTA
(approximately
10 mL per 150 mm filter). Preferably, the probe is then added to the
hybridization mix at
a concentration greater than or equal to le+6 dprn/mL. The filter is then
preferably
incubated at 65°C with gentle agitation overnight. The filter is then
preferably washed in
500 mL of 2X SSC/0.5% SDS at room temperature without agitation, preferably
followed
3 0 by 500 mL of 2X SSC/0.1% SDS at room temperature with gentle shaking for
15 minutes.
A third wash with 0.1X SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is
optional. The
filter is then preferably dried and subjected to autoradiography for
sufficient time to
visualize the positives on the X-ray film. Other known hybridization methods
can also
be employed.
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The positive colonies are picked, grown in culture, and plasmid DNA isolated
using standard procedures. The clones can then be verified by restriction
analysis,
hybridization analysis, or DNA sequencing.
Fragments of the proteins of the present invention which are capable of
exhibiting
biological activity are also encompassed by the present invention. Fragments
of the
protein may be in linear form or they may be cyclized using known methods, for
example,
as described in H.U. Saragovi, et al., Bio/Technology ,~Q, 773-778 (1992) and
in R.S.
McDowell, et al., J. Amer. Chem. Soc. ,1~4, 9245-9253 (1992), both of which
are incorporated
herein by reference. Such fragments may be fused to carrier molecules such as
immunoglobulins for many purposes, including increasing the valency of protein
binding
sites. For example, fragments of the protein may be fused through "linker"
sequences to
the Fc portion of an immunoglobulin. For a bivalent form of the protein, such
a fusion
could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes
may also
be used to generate such fusions. For example, a protein - IgM fusion would
generate a
decavalent form of the protein of the invention.
The present invention also provides both full-length and mature forms of the
disclosed proteins. The full-length form of the such proteins is identified in
the sequence
listing by translation of the nucleotide sequence of each disclosed clone. The
mature
forms) of such protein may be obtained by expression of the disclosed full-
length
2 0 polynucleotide (preferably those deposited with the ATCC) in a suitable
mammalian cell
or other host cell. The sequences) of the mature forms) of the protein may
also be
determinable from the amino acid sequence of the full-length form.
The present invention also provides genes corresponding to the polynucleotide
sequences disclosed herein. "Corresponding genes" are the regions of the
genome that
2 5 are transcribed to produce the mRNAs from which cDNA polynucleotide
sequences are
derived and may include contiguous regions of the genome necessary for the
regulated
expression of such genes. Corresponding genes may therefore include but are
not limited
to coding sequences, 5' and 3' untranslated regions, alternatively spliced
exons, introns,
promoters, enhancers, and silencer or suppressor elements. The corresponding
genes can
3 0 be isolated in accordance with known methods using the sequence
information disclosed
herein. Such methods include the preparation of probes or primers from the
disclosed
sequence information for identification and/or amplification of genes in
appropriate
genomic libraries or other sources of genomic materials. An "isolated gene" is
a gene that
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WO 00/11015 PCT/US99/19351
has been separated from the adjacent coding sequences, if any, present in the
genome of
the organism from which the gene was isolated.
The chromosomal location corresponding to the polynucleotide sequences
disclosed herein may also be determined, for example by hybridizing
appropriately
labeled polynucleotides of the present invention to chromosomes in situ. It
may also be
possible to determine the corresponding chromosomal location for a disclosed
polynucleotide by identifying significantly similar nucleotide sequences in
public
databases, such as expressed sequence tags (ESTs), that have already been
mapped to
particular chromosomal locations. For at least some of the polynucleotide
sequences
disclosed herein, public database sequences having at least some similarity to
the
polynucleotide of the present invention have been listed by database accession
number.
Searches using the GenBank accession numbers of these public database
sequences can
then be performed at an Internet site provided by the National Center for
Biotechnology
Information having the address http://www.ncbi.nlm.nih.gov/UruGene/, in order
to
identify "UniGene clusters" of overlapping sequences. Many of the "UruGene
clusters"
so identified will already have been mapped to particular chromosomal sites.
Organisms that have enhanced, reduced, or modified expression of the genes)
corresponding to the polynucleotide sequences disclosed herein are provided.
The
desired change in gene expression can be achieved through the use of antisense
polynucleotides or ribozymes that bind and/or cleave the mRNA transcribed from
the
gene (Albert and Morris,1994, Trends Phurma~col. Sci.15(7): 250-254; Lavarosky
et al.,1997,
Biochem. Mol. Med. 62(1):11-22; and Hampel,1998, Prog. Nucleic Acid Res. Mol.
Biol. 58: 1-
39; all of which are incorporated by reference herein). The desired change in
gene
expression can also be achieved through the use of double-stranded
ribonucleotide
molecules having some complementarity to the mRNA transcribed from the gene,
and
which interfere with the transcription, stability, or expression of the mRNA
("RNA
intereference" or "RNAi"; Fire et al.,1998, Nature 391 (6669): 806-811;
Montgomery et al.,
1998, Proc. Natl. Acad. Sci. LISA 95 (26): 15502-15507; and Sharp,1999, Genes
Dev.13 (2):
139-141; all of which are incorporated by reference herein). Transgenic
animals that have
3 0 multiple copies of the genes) corresponding to the polynucleotide
sequences disclosed
herein, preferably produced by transformation of cells with genetic constructs
that are
stably maintained within the transformed cells and their progeny, are
provided.
Transgenic animals that have modified genetic control regions that increase or
reduce
gene expression levels, or that change temporal or spatial patterns of gene
expression, are
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WO 00/11015 PCT/US99/19351
also provided (see European Patent No. 0 649 464 $1, incorporated by reference
herein).
In addition, organisms are provided in which the genes) corresponding to the
polynucleotide sequences disclosed herein have been partially or completely
inactivated,
through insertion of extraneous sequences into the corresponding genes) or
through
deletion of all or part of the corresponding gene(s). Partial or complete gene
inactivation
can be accomplished through insertion, preferably followed by imprecise
excision, of
transposable elements (Plasterk,1992, Bioessays 14(9): 629-633; Zwaal et
al.,1993, Proc. Natl.
Acad. Sci. LISA 90(16): 7431-7435; Clark ef al.,1994, Proc. Natl. Acad. Sci.
LISA 91(2): 719-722;
all of which are incorporated by reference herein), or through homologous
recombination,
preferably detected by positive/negative genetic selection strategies (Mansour
et al.,1988,
Nature 336: 348-352; U.S. Patent Nos. 5,464,764; 5,487,992; 5,627,059;
5,631,153; 5,614, 396;
5,616,491; and 5,679,523; all of which are incorporated by reference herein).
These
organisms with altered gene expression are preferably eukaryotes and more
preferably
are mammals. Such organisms are useful for the development of non-human models
for
the study of disorders involving the corresponding gene(s), and for the
development of
assay systems for the identification of molecules that interact with the
protein products)
of the corresponding gene(s).
Where the protein of the present invention is membrane-bound (e.g., is a
receptor),
the present invention also provides for soluble forms of such protein. In such
forms, part
2 0 or all of the intracellular and transmembrane domains of the protein are
deleted such that
the protein is fully secreted from the cell in which it is expressed. The
intracellular and
transmembrane domains of proteins of the invention can be identified in
accordance with
known techniques for determination of such domains from sequence information.
For
example, the TopPredII computer program can be used to predict the location of
2 5 transmembrane domains in an amino acid sequence, domains which are
described by the
location of the center of the transmsmbrane domain, with at least ten
transmembrane
amino acids on each side of the reported central residue{s).
Proteins and protein fragments of the present invention include proteins with
amino acid sequence lengths that are at least 25%(more preferably at least
50%, and most
3 0 preferably at least 75%) of the length of a disclosed protein and have at
least 60% sequence
identity {more preferably, at least 75% identity; mast preferably at least 90%
or 95%
identity) with that disclosed protein, where sequence identity is determined
by comparing
the amino acid sequences of the proteins when aligned so as to maximize
overlap and
identity while minimizing sequence gaps. Also included in the present
invention are
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WO 00/11015 PCTNS99/19351
proteins and protein fragments that contain a segment preferably comprising 8
or more
(more preferably 20 or more, most preferably 30 or more) contiguous amino
acids that
shares at least 75% sequence identity (more preferably, at least 85% identity;
most
preferably at least 95% identity) with any such segment of any of the
disclosed proteins.
In particular, sequence identity may be determined using WU-BLAST
(Washington University BLAST) version 2.0 software, which builds upon WU-BLAST
version 1.4, which in turn is based on the public domain NCBI-BLAST version
1.4
(Altschul and Gish, 1996, Local alignment statistics, Doolittle ed., Methods
in Enzymology
266: 460-480; Altschul et al., 1990, Basic local alignment search tool,
Journal of
Molecular Biology 215: 403-410; Gish and States, 1993, Identification of
protein coding
regions by database similarity search, Nature Genetics 3: 266-272; Karlin and
Altschul,
1993, Applications and statistics for multiple high-scoring segments in
molecular
sequences, Proc. Natl. Acad Sci. USA 90: 5873-5877; all of which are
incorporaxed by
reference herein). WU-BLAST version 2.0 executable programs for several UNIX
platforms can be downloaded from ftp://blast.wustl.edu/blast/executables. The
complete
suite of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is
provided at that site, in addition to several support programs. WU-BLAST 2.0
is
copyrighted and may not be sold or redistributed in any forrn or manner
without the
express written consent of the author; hut the posted executables may
otherwise be freely
2 0 used for commercial, nonprofit, or academic purposes. In all search
programs in the suite
-- BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX -- the gapped alignment
routines are integral to the database search itself, and thus yield much
better sensitivity and
selectivity while producing the more easily interpreted output. Gapping can
optionally be
turned off in all of these programs, if desired. The default penalty (Q) for a
gap of length
2 5 one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be
changed to any
integer value including zero, one through eight, nine, ten, eleven, twelve
through twenty,
twenty-one through fifty, fifty-one through one hundred, etc. The default per-
residue
penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=10 for
BLASTN,
but may be changed to any integer value including zero, one, two, three, four,
five, six,
3 0 seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through
fifty, fifty-one
through one hundred, etc. Any combination of values for Q and R can be used in
order to
align sequences so as to maximize overlap and identity while minimizing
sequence gaps.
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T'he default amino acid comparison matrix is BLOSUM62, but other amino acid
comparison matrices such as PAM can be utilized.
Species homologues of the disclosed polynucleotides and proteins are also
provided by the present invention. As used herein, a "species homologue" is a
protein or
polynucleotide with a different species of origin from that of a given protein
or
polynucleotide, but with significant sequence similarity to the given protein
or
polynucleotide. Preferably, polynucleotide species homologues have at least
60% sequence
identity {more preferably, at least 75% identity; most preferably at least 90%
identity) with
the given polynucleotide, and protein species homologues have at least 30%
sequence
identity (more preferably, at least 45% identity; most preferably at least 60%
identity} with
the given protein, where sequence identity is determined by comparing the
nucleotide
sequences of the polynucleotides or the amino acid sequences of the proteins
when
aligned so as to maximize overlap and identity while rrunimizing sequence
gaps. Species
homologues may be isolated and identified by making suitable probes or primers
from
the sequences provided herein and screening a suitable nucleic acid source
from the
desired species. Preferably, species homologues are those isolated from
mammalian
speties. Most preferably, species homologues are those isolated from certain
mammalian
species such as, for example, Pan troglodytes, Gorilla gorilla, Pongo
pygmaeus, Hylobates
concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus
aethiops, Cebus capucinus,
2 0 Aotus trivirgatus, Sanguinus Oedipus, Microcebus murinus, Mus musculus,
Rattus norvegicus,
Cricetulus griseus, Fells catus, Mustela vison, Canis familuxris, Oryctolagus
cuniculus, Bos taurus,
Ovis cries, Sus scrofa, and Eguus caballus, for which genetic maps have been
created
allowing the identification of synteruc relationships between the genomic
organization of
genes in one species and the genomic organization of the related genes in
another species
2 5 (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al.,
1993, Nature
Genetics 3:103-112; Johansson et al.,1995, Genomics 25: 682-690; Lyons et
al.,1997, Nature
Genetics 15: 47-56; O'Brien et al.,1997, Trends in Genetics 13(10): 393-399;
Carver and Stubbs,
1997, Genome Research 7:1123-1137; all of which are incorporated by reference
herein).
The invention also encompasses allelic variants of the disclosed
polynucleotides
3 0 or proteins; that is, naturally-occurring alternative forms of the
isolated polynucleotides
which also encode proteins which are identical or have significantly similar
sequences to
those encoded by the disclosed polynucleotides. Preferably, allelic variants
have at least
60% sequence identity (more preferably, at least 75% identity; most preferably
at least 90%
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identity) with the given polynucleotide, where sequence identity is determined
by
comparing the nucleotide sequences of the polynucleotides when aligned so as
to maximize
overlap and identity while minimizing sequence gaps. Allelic variants may be
isolated and
identified by making suitable probes or primers from the sequences provided
herein and
screening a suitable nucleic acid source from individuals of the appropriate
species.
The invention also includes polynucleotides with sequences complementary to
those of the polynucleotides disclosed herein.
The present invention also includes polynucleotides that hybridize under
reduced
stringency conditions, more preferably stringent conditions, and most
preferably highly
stringent conditions, to polynucleotides described herein. Examples of
stringency
conditions are shown in the table below: highly stringent conditions are those
that are at
least as stringent as, for example, conditions A-F; stringent conditions are
at least as
stringent as, for example, conditions G-L; and reduced stringency conditions
are at least
as stringent as, for example, conditions M-R.
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StringencyPolynucleotideHybridHybridization TemperatureWash
and
ConditionHybrid LengthBuffer' T~p~~re
t
and Buffer'
A DNA:DNA x 50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC, 50% formamide
B DNA:DNA <50 TB*; lxSSC TB*; lxSSC
C DNA:RNA x 50 67C; lxSSC -or- 67C; 0.3xSSC
45C; lxSSC, 50% formamide
D DNA:RNA <50 Tp*; lxSSC TD*; lxSSC
E RNA:RNA x 50 70C; lxSSC -or- 70C; 0.3xSSC
50C; lxSSC, 50% formamide
F RNA:RNA <50 TF*; lxSSC TF*; lxSSC
G DNA:DNA x 50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC, 50% formamide
H DNA:DNA <50 TH*; 4xSSC *
T
;
H
I DNA:RNA x 50 67C; 4xSSC -or- 67'C; lxSSC
45C; 4xSSC, 50% formamide
1 DNA:RNA <50 T~*; 4xSSC T~'; 4xSSC
RNA:RNA x 50 70C; 4xSSC -or- 67C; lxSSC
50C; 4xSSC, 50% formamide
L RNA:RNA <50 T~*; ~ T~*; ~
M DNA:DNA x 50 50C; 4xSSC -or- 50C; 2xSSC
40C; 6xSSC, 50% formamide
N DNA:DNA <50 TN*; 6xSSC TN*; 6xSSC
DNA:RNA x 50 55C; 4xSSC -or- 55C; 2xSSC
42C; 6xSSC, 50% formamide
P DNA:RNA <50 Tp*; 6xSSC Tp*; 6xSSC
C2 RNA:RNA x 50 60C; 4xSSC -or- 6p
45C; 6xSSC, 50% formamide
2 R RNA:RNA <50 TR*; 4xSSC Ts*; 4xSSC
0
;: The hybrid length is that anticipated for the hybridized regions) of the
hybridizing polynudeotides. When
hybridizing a polynucleotide to a target polynucleotide of unknown sequence,
the hybrid length is assumed
to be that of the hybridizing polynucleotide. When polynucleotides of known
sequence are hybridized, the
2 5 hybrid length can be determined by aligning the sequences of the
polynucleotides and identifying the region
or regions of optimal sequence complementarity.
': SSPE (ixSSPE is 0.15M NaCI, lOmM NaHZPO" and 1.25mM EDTA, pH 7.4) can be
substituted for SSC
(lxSSC is 0.15M NaCI and lSmM sodium citrate) in the hybridization and wash
buffers; washes are
performed for 15 minutes after hybridization is complete.
3 0 "TB - TR: The hybridization temperature for hybrids anticipated to be less
than 50 base pairs in length should
be 5-10°C less than the melting temperature (Tm) of the hybrid, where
Tm is determined according to the
following equations. For hybrids less than 18 base pairs in length,
T°,(°C) = 2(# of A + T bases) + 4(# of G +
C bases). For hybrids between 18 and 49 base pairs in length, Tm(°C) =
81.5 + 16.6(log~o[Na']) + 0.41(%G+C)
(600/N), where N is the number of bases in the hybrid, and [Na'] is the
concentration of sodium ions in the
3 5 hybridization buffer ([Na'] for lxSSC = 0.165 M).
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Additional examples of stringency conditions for polynucleotide hybridization
are
provided in Sambrook, J., E.F. Fritsch, and T. Maniatis, 1989, Molecular
Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor,
NY,
chapters 9 and 11, and Current Protocols in Molecular Biology,1995, F.M.
Ausubel et al., eds.,
John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by
reference.
Preferably, each such hybridizing polynucleotide has a length that is at least
25%(more preferably at least 50%, and most preferably at least 75%) of the
length of the
polynucleotide of the present invention to which it hybridizes, and has at
least 60%
sequence identity (more preferably, at least 75% identity; most preferably at
least 90% or
95% identity) with the polynucleotide of the present invention to which it
hybridizes,
where sequence identity is determined by comparing the sequences of the
hybridizing
polynucleotides when aligned so as to maximize overlap and identity while
minimizing
sequence gaps.
The isolated polynucleotide endcoing the protein of the invention may be
operably
linked to an expression control sequence such as the pMT2 or pED expression
vectors
disclosed in Kaufman et al., Nucleic Acids Res. 9 4485-4490 (1991), in order
to produce
the protein recombinantly. Many suitable expression control sequences are
known in the
art. General methods of expressing recombinant proteins are also known and are
exemplified in R. Kaufman, Methods in Enzymology 1~5, 537-566 (1990). As
defined
2 0 herein "operably linked" means that the isolated polynucleotide of the
invention and an
expression control sequence are situated within a vector or cell in such a way
that the
protein is expressed by a host cell which has been transformed (transfected)
with the
ligated polynucleotide/expression control sequence.
A number of types of cells may act as suitable host cells for expression of
the
2 5 protein. Mammalian host cells include, for example, monkey COS cells,
Chinese Hamster
Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human
Co1o205
cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal
diploid cells, cell
strains derived from in vi o culture of primary tissue, primary explants, HeLa
cells,
mouse L cells, BHK, HL-60, U937, HaK or Jurkat cells.
3 0 Alternatively, it may be possible to produce the protein in lower
eukaryotes such
as yeast or in prokaryotes such as bacteria. Potentially suitable yeast
strains include
Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains,
Candida, or any
yeast strain capable of expressing heterologous proteins. Potentially suitable
bacterial
strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium,
or any bacterial
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strain capable of expressing heterologous proteins. If the protein is made in
yeast or
bacteria, it may be necessary to modify the protein produced therein, for
example by
phosphorylation or glycosylation of the appropriate sites, in order to obtain
the functional
protein. Such covalent attachments may be accomplished using known chemical or
enzymatic methods.
The protein may also be produced by operably linking the isolated
polynucleotide
of the invention to suitable control sequences in one or more insect
expression vectors,
and employing an insect expression system. Materials and methods for
baculovirus/insect cell expression systems are commercially available in kit
form from,
e.g., Invitrogen, San Diego, California, U.S.A. (the MaxBac RO kit), and such
methods are
well known in the art, as described in Summers and Smith, Texas A~~ricultural
Experiment
Station Bulletin No 15.55 (L9871 incorporated herein by reference. As used
herein, an
insect cell capable of expressing a polynucleotide of the present invention is
"transformed."
The protein of the invention may be prepared by culturing transformed host
cells
under culture conditions suitable to express the recombinant protein. The
resulting
expressed protein may then be purified from such culture (i.e., from culture
medium or
cell extracts) using known purification processes, such as gel filtration and
ion exchange
chromatography. The purification of the protein may also include an affinity
column
2 0 containing agents which will bind to the protein; one or more column steps
over such
affinity resins as concanavalin A-agarose, heparin-toyopearl~ or Cibacrom blue
3GA
Sepharose~; one or more steps involving hydrophobic interaction chromatography
using
such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity
chromatography.
2 5 Alternatively, the protein of the invention may also be expressed in a
form which
will facilitate purification. For example, it may be expressed as a fusion
protein, such as
those of maltose binding protein (MBP), glutathione-S-transferase (GST) or
thioredoxin
(T1ZX). Kits for expression and purification of such fusion proteins are
commercially
available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, NJ)
and
3 0 lnvitrogen Corporation (Carlsbad, CA), respectively. The protein can also
be tagged with
an epitope and subsequently purified by using a specific antibody directed to
such
epitope. One such epitope ("Flag") is commercially available from the Eastman
Kodak
Company (New Haven, CT).
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Finally, one or more reverse-phase high performance liquid chromatography (RP-
HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having
pendant
methyl or other aliphatic groups, can be employed to further purify the
protein. Some or
all of the foregoing purification steps, in various combinations, can also be
employed to
provide a substantially homogeneous isolated recombinant protein. The protein
thus
purified is substantially free of other mammalian proteins and is defined in
accordance
with the present invention as an "isolated protein."
The protein of the invention rnay also be expressed as a product of transgenic
animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or
sheep which
are characterized by somatic or germ cells containing a nucleotide sequence
encoding the
protein.
The protein may also be produced by known conventional chemical synthesis.
Methods for constructing the proteins of the present invention by synthetic
means are
known to those skilled in the art. The synthetically-constructed protein
sequences, by
virtue of sharing primary, secondary or tertiary structural and/or
conformational
characteristics with proteins may possess biological properties in common
therewith,
including protein activity. Thus, they may be employed as biologically active
or
immunological substitutes for natural, purified proteins in screening of
therapeutic
compounds and in immunological processes for the development of antibodies.
2 0 The proteins provided herein also include proteins characterized by amino
acid
sequences similar to those of purified proteins but into which modification
are naturally
provided or deliberately engineered. For example, modifications in the peptide
or DNA
sequences can be made by those skilled in the art using known techniques.
Modifications
of interest in the protein sequences may include the alteration, substitution,
replacement,
2 5 insertion or deletion of a selected amino acid residue in the coding
sequence. For
example, one or more of the cysteine residues may be deleted or replaced with
another
amino acid to alter the conformation of the molecule. Techniques for such
alteration,
substitution, replacement, insertion or deletion are well known to those
skilled in the art
(see, e.g., U.S. Patent No. 4,518,584). Preferably, such alteration,
substitution, replacement,
3 0 insertion or deletion retains the desired activity of the protein.
Other fragments and derivatives of the sequences of proteins which would be
expected to retain protein activity in whole or in part and may thus be useful
for screening
or other immunological methodologies may also be easily made by those skilled
in the art
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WO 00/11015 PCT/US99/19351
given the disclosures herein. Such modifications are believed to be
encompassed by the
presentinvention.
USES AND BIOLOGI~ai. A~y~y
The polynucleotides and proteins of the present invention are expected to
exhibit
one or more of the uses or biological activities (including those associated
with assays
cited herein) identified below. Uses or activities described for proteins of
the present
invention may be provided by administration or use of such proteins or by
administration
or use of polynucleotides encoding such proteins (such as, for example, in
gene therapies
or vectors suitable for introduction of DNA).
Research Uses and Utilities
The polynucleotides provided by the present invention can be used by the
research
community for various purposes. The polynucleotides can be used to express
recombinant protein for analysis, characterization or therapeutic use; as
markers for
tissues in which the corresponding protein is preferentially expressed (either
constitutively or at a particular stage of tissue differentiation or
development or in disease
states); as molecular weight markers on Southern gels; as chromosome markers
or tags
(when labeled) to identify chromosomes or to map related gene positions; to
compare
2 0 with endogenous DNA sequences in patients to identify potential genetic
disorders; as
probes to hybridize and thus discover novel, related DNA sequences; as a
source of
information to derive I'CR primers for genetic fingerprinting; as a probe to
"subtract-out"
known sequences in the process of discovering other novel polynucleotides; for
selecting
and making oligomers for attachment to a "gene chip" or other support,
including for
2 5 examination of expression patterns; to raise anti-protein antibodies using
DNA
immunization techniques; and as an antigen to raise anti-DNA antibodies or
elicit another
immune response. Where the polynucleotide encodes a protein which binds or
potentially
binds to another protein (such as, for example, in a receptor-ligand
interaction), the
polynucleotide can also be used in interaction trap assays (such as, for
example, those
3 0 described in Gyuris et al.,1993, Cell 75: 791-803 and in Rossi et
al.,1997, Proc. Natl. Acad.
Sci. USA 94: 8405-8410, all of which are incorporated by reference herein) to
identify
polynucleotides encoding the other protein with which binding occurs or to
identify
inhibitors of the binding interaction.
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The proteins provided by the present invention can similarly be used in assay
to
determine biological activity, including in a panel of multiple proteins for
high-
throughput screening; to raise antibodies or to elicit another immune
response; as a
reagent (including the labeled reagent) in assays designed to quantitatively
determine
levels of the protein (or its receptor) in biological fluids; as markers for
tissues in which
the corresponding protein is preferentially expressed (either constitutively
or at a
particular stage of tissue differentiation or development or in a disease
state); and, of
course, to isolate correlative receptors or ligands. Where the protein binds
or potentially
binds to another protein (such as, for example, in a receptor-ligand
interaction), the
protein can be used to identify the other protein with which binding occurs or
to identify
inhibitors of the binding interaction. Proteins involved in these binding
interactions can
also be used to screen for peptide or small molecule inhibitors or agonists of
the binding
interaction.
Any or all of these research utilities are capable of being developed into
reagent
grade or kit format for commercialization as research products.
Methods for performing the uses listed above are well known to those skilled
in
the art. References disclosing such methods include without limitation
"Molecular
Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press,
Sambrook,
J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide
to
2 0 Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R.
Kimmel eds.,1987.
Nutrition 1 Uses
Polynucleotides and proteins of the present invention can also be used as
nutritional sources or supplements. Such uses include without limitation use
as a protein
2 5 or amino acid supplement, use as a carbon source, use as a nitrogen source
and use as a
source of carbohydrate. In such cases the protein or polynucleotide of the
invention can
be added to the feed of a particular organism or can be administered as a
separate solid
or liquid preparation, such as in the form of powder, pills, solutions,
suspensions or
capsules. In the case of microorganisms, the protein or polynucleotide of the
invention
3 0 can be added to the medium in or on which the microorganism is cultured.
Cvtokine and Cell Proliferation/Differentiation Activity
A protein of the present invention may exhibit cytokine, cell proliferation
(either
inducing or inhibiting) or cell differentiation (either inducing or
inhibiting) activity or may
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induce production of other cytokines in certain cell populations. Many protein
factors
discovered to date, including all known cytokines, have exhibited activity in
one or more
factor-dependent cell proliferation assays, and hence the assays serve as a
convenient
confirmation of cytokine activity. The activity of a protein of the present
invention is
evidenced by any one of a number of routine factor dependent cell
proliferation assays
for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11,
BaF3,
MC9/G, M+ (preB M+), 2E8, RBS, DA1,123, T1165, HT2, CTLL2, TF-1, Mo7e and CMK.
The activity of a protein of the invention may, among other means, be measured
by the following methods:
Assays for T-cell or thymocyte proliferation include without limitation those
described in: Current Protocols in Immunology, Ed by j. E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and
Wiley-
Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-
3.19; Chapter
7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500,
1986;
Bertagnolli et al., J. lmmunol.145:1706-1712, 1990; Bertagnolli et al.,
Cellular Immunology
133:327 341, 1991; Bertagnolli, et al., J. Immunol. 149:3778-3783, 1992;
Bowman et al., J.
Immunol. 152: 1756-1761, 1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph
node
cells or thymocytes include, without limitation, those described in:
Polyclonal T cell
2 0 stimulation, Kruisbeek, A.M, and Shevach, E.M. In Current Protocols in
Immunology. J.E.e.a.
Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and
Measurement of mouse and human Interferon y, Schreiber, R.D. In Current
Protocols in
Immunology, j.E.e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons,
Toronto.1994.
Assays for proliferation and differentiation of hematopoietic and
lymphopoietic
2 5 cells include, without limitation, those described in: Measurement of
Human and Murine
InterIeukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In
Current
Protocols in Immunology. j.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John
Wiley and Sons,
Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et
al., Nature
336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-
2938, 1983;
3 0 Measurement of mouse and human interleukin 6 - Nordan, R. In Current
ProEocols in
Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Whey and Sons,
Toronto.1991;
Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of
human
Interleukin 11- Bennett, F., Giannotti, J., Clark, S.C. and Turner, K. J. In
Current Protocols
in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons,
Toronto. 1991;
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Measurement of mouse and human Interleukin 9 - Ciarletta, A., Giannotti, J.,
Clark, S.C.
and Turner, K.J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol
1 pp. 6.13.1,
John Wiley and Sons, Toronto. 1991.
Assays for T-cell clone responses to antigens (which will identify, among
others,
proteins that affect APC-T cell interactions as well as direct T-cell effects
by measuring
proliferation and cytokine production) include, without limitation, those
described in:
Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H.
Margulies,
E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-
Interscience
(Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6,
Cytokines and
their cellular receptors; Chapter 7, Lmmunologic studies in Humans);
Weinberger et al.,
Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. j.
Immun.
11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al.,
J. Immunol.
140:508-512, 1988.
Immune Stimulatin ~r SunnreSS,'n_~ Activity
A protein of the present invention may also exhibit immune stimulating or
immune suppressing activity, including without limitation the activities for
which assays
are described herein. A protein may ho "~ac,.~ :.- ~L.. ~__~__ _ . ~ . _
deficiencies and disorders (including severe combined immunodeficiency
(SCID)), e.g.,
2 0 in regulating (up or down) growth and proliferation of T and/or B
lymphocytes, as well
as effecting the cytolytic activity of NK cells and other cell populations.
These immune
deficiencies may be genetic or be caused by viral (e.g., HIV) as well as
bacterial or fungal
infections, or may result from autoimmune disorders. More specifically,
infectious
diseases causes by viral, bacterial, fungal or other infection may be
treatable using a
2 5 protein of the present invention, including infections by HIV, hepatitis
viruses,
herpesviruses, mycobacteria, Leishmania spp., malaria spp. and various fungal
infections
such as candidiasis. Of course, in this regard, a protein of the present
invention may also
be useful where a boost to the immune system generally may be desirable, i.e.,
in the
treatment of cancer.
3 0 Autoimmune disorders which may be treated using a protein of the present
invention include, for example, connective tissue disease, multiple sclerosis,
systemic
lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation,
Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes
mellitis,
myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye
disease.
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Such a protein of the present invention may also to be useful in the treatment
of allergic
reactions and conditions, such as asthma (particularly allergic asthma) or
other respiratory
problems. Other conditions, in which immune suppression is desired (including,
for
example, organ transplantation), may also be treatable using a protein of the
present
invention.
Using the proteins of the invention it may also be possible to regulate immune
responses in a number of ways. Down regulation may be in the form of
inhibiting or
blocking an immune response already in progress or may involve preventing the
induction of an immune response. The functions of activated T cells may be
inhibited by
suppressing T cell responses or by inducing specific tolerance in T cells, or
both.
Immunosuppression of T cell responses is generally an active, non-antigen-
specific,
process which requires continuous exposure of the T cells to the suppressive
agent.
Tolerance, which involves inducing non-responsiveness or anergy in T cells, is
distinguishable from immunosuppression in that it is generally antigen-
specific and
persists after exposure to the tolerizing agent has ceased. Operationally,
tolerance can be
demonstrated by the lack of a T cell response upon reexposure to specific
antigen in the
absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without
limitation B lymphocyte antigen functions (such as , for example, B~), eg.,
preventing
2 0 high level lymphokine synthesis by activated T cells, will be useful in
situations of tissue,
skin and organ transplantation and in graft-versus-host disease (GVHD). For
example,
blockage of T cell function should result in reduced tissue destruction in
tissue
transplantation. Typically, in tissue transplants, rejection of the transplant
is initiated
through its recognition as foreign by T cells, followed by an immune reaction
that destroys
2 5 the transplant. The administration of a molecule which inhibits or blocks
interaction of
a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a
soluble,
monomeric form of a peptide having B7-2 activity alone or in conjunction with
a
monomeric form of a peptide having an activity of another B lymphocyte antigen
(eg., B7
1, B7-3) or blocking antibody), prior to transplantation can lead to the
binding of the
3 0 molecule to the natural ligand(s) on the immune cells without transmitting
the
corresponding costimulatory signal. Blocking B lymphocyte antigen function in
this
matter prevents cytokine synthesis by immune cells, such as T cells, and thus
acts as an
immunosuppressant. Moreover, the lack of costimulation may also be sufficient
to
anergize the T cells, thereby inducing tolerance in a subject. Induction of
long-term
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tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of
repeated
administration of these blocking reagents. To achieve sufficient
immunosuppression or
tolerance in a subject, it may also be necessary to block the function of a
combination of
B lymphocyte antigens.
The efficacy of particular blocking reagents in preventing organ transplant
rejection or GVHD can be assessed using animal models that are predictive of
efficacy in
humans. Examples of appropriate systems which can be used include allogeneic
cardiac
grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of
which have been
used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in
vivo as
described in Lenschow et al., Science 257:789-792 (1992) and Turka et al.,
Proc. Natl. Acad.
Sci USA, 89:11102-11105 (1992). In addition, marine models of GVHD (see Paul
ed.,
Fundamental Immunology, Raven Press, New York, 1989, pp. $46-847) can be used
to
determine the effect of blocking B lymphocyte antigen function in vivo on the
development
of that disease.
Blocking antigen function may also be therapeutically useful for treating
autoimmune diseases. Many autoimmune disorders are the result of inappropriate
activation of T cells that are reactive against self tissue and which promote
the production
of cytokines and autoantibodies involved in the pathology of the diseases.
Preventing the
activation of autoreactive T cells may reduce or eliminate disease symptoms.
2 0 Administration of reagents which block costimulation of T cells by
disrupting
receptor:ligand interactions of B lymphocyte antigens can be used to inhibit T
cell
activation and prevent production of autoantibodies or T cell-derived
cytokines which
may be involved in the disease process. Additionally, blocking reagents may
induce
antigen-specific tolerance of autoreactive T cells which could lead to long-
term relief from
the disease. The efficacy of blocking reagents in preventing or alleviating
autoimmune
disorders can be determined using a number of well-characterized animal models
of
human autoimmune diseases. Examples include marine experimental autoimmune
encephalitis, systemic lupus erythmatosis in MRL/Ipr/Ipr mice or NZB hybrid
mice,
marine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB
rats, and
3 0 marine experimental myasthenia gravis (see Paul ed., Fundamental
Immunology, Raven
Press, New York,1989, pp. 840-856).
Upregulation of an antigen function (preferably a B lymphocyte antigen
function),
as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing
immune
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response or eliciting an initial immune response. For example, enhancing an
immune
response through stimulating B lymphocyte antigen function may be useful in
cases of
viral infection. In addition, systemic viral diseases such as influenza, the
common cold,
and encephalitis might be alleviated by the administration of stimulatory
forms of B
lymphocyte antigens systemically.
Alternatively, anti-viral immune responses may be enhanced in an infected
patient
by removing T cells from the patient, costimulating the T cells in vitro with
viral antigen-
pulsed APCs either expressing a peptide of the present invention or together
with a
stimulatory form of a soluble peptide of the present invention and
reintroducing the in
vitro activated T cells into the patient. Another method of enhancing anti-
viral immune
responses would be to isolate infected cells from a patient, transfect them
with a nucleic
acid encoding a protein of the present invention as described herein such that
the cells
express all or a portion of the protein on their surface, and reintroduce the
transfected
cells into the patient. The infected cells would now be capable of delivering
a
costimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of antigen function
(preferably B lymphocyte antigen function) may be useful in the induction of
tumor
immunity. Tumor cells (e.g., sarcoma, melanoma, lymphoma, leukemia,
neuroblastoma,
carcinoma) transfected with a nucleic acid encoding at least one peptide of
the present
2 0 invention can be administered to a subject to overcome tumor-specific
tolerance in the
subject. If desired, the tumor cell can be transfected to express a
combination of peptides.
For example, tumor cells obtained from a patient can be transfected ex vivo
with an
expression vector directing the expression of a peptide having B7 2-like
activity alone, or
in conjunction with a peptide having B7-1-like activity and/or B7 3-like
activity. The
2 5 transfected tumor cells are returned to the patient to result in
expression of the peptides
on the surface of the transfected cell. Alten~atively, gene therapy techniques
can be used
to target a tumor cell for transfection in vivo.
The presence of the peptide of the present invention having the activity of a
B
lymphocyte antigens) on the surface of the tumor cell provides the necessary
3 0 costimulation signal to T cells to induce a T cell mediated immune
response against the
transfected tumor cells. In addition, tumor cells which lack MHC class I or
MHC class II
molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC
class II
molecules, can be transfected with nucleic acid encoding all or a portion of
(e.g., a
cytoplasmic-domain truncated portion) of an MHC class I a chain protein and
(3Z
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microglobulin protein or an MHC class II a chain protein and an MHC class II
~i chain
protein to thereby express MHC class I or MHC class II proteins on the cell
surface.
Expression of the appropriate class I or class II MHC in conjunction with a
peptide having
the activity of a B lymphocyte antigen (eg., B7-1, B7-2, B7-3) induces a T
cell mediated
immune response against the transfected tumor cell. Optionally, a gene
encoding an
antisense construct which blocks expression of an MHC class II associated
protein, such
as the invariant chain, can also be cotransfected with a DNA encoding a
peptide having
the activity of a B lymphocyte antigen to promote presentation of tumor
associated
antigens and induce tumor specific immunity. Thus, the induction of a T cell
mediated
1.0 immune response in a human subject may be sufficient to overcome tumor-
specific
tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured
by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without
limitation, those described in: Current Protocols in Immunology, Ed by J. E.
Coligan, A.M.
Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing
Associates
and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte
Function 3.1
3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl.
Acad. Sci.
USA 78:2488-2492,1981; Herrmann et al., J. Immunol.128:1968-1974,1982; Handa
et aL,
2 0 J. Immunol.135:1564-1572,1985; Takai et al., J. Immunol.137:3494-
3500,1986; Takai et al.,
J. lmmunol.140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA
78:2488-2492,
1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J.
Immunol.
135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet
al., J.
Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988;
Bertagnolli et al.,
2 5 Cellular Immunology 133:327 341,1991; Brown et al., J. Immunol. 153:3079-
3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching
(which will identify, among others, proteins that modulate T-cell dependent
antibody
responses and that affect Th1/Th2 profiles) include, without limitation, those
described
in: Maliszewski, J. Immunol. 144:3028-3033,1990; and Assays for B cell
function: In vitro
3 0 antibody production, Mond, J.j. and Brunswick, M. In Current Protocols in
Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons,
Toronto.1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others,
proteins that generate predominantly Thl and CTL responses) include, without
limitation,
those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
ICruisbeek,
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D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and
Wiley-
Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-
3.19; Chapter
7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-
3500,1986; Takai
et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol.
149:3778-3783,1992.
Dendritic cell-dependent assays (which will identify, among others, proteins
expressed by dendritic cells that activate naive T-cells) include, without
limitation, those
described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al.,
Journal of
Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of
Immunology
154:5071-5079,1995; Porgador et al., Journal of Experimental Medicine 182:255-
260,1995;
Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science
264:961-965,
1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264,1989;
Bhardwaj
et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al.,
Journal of
Experimental Medicine 172:631-640,1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others,
proteins that prevent apoptosis after superantigen induction and proteins that
regulate
lymphocyte homeostasis) include, without limitation, those described in:
Darzynkiewicz
et al., Cytometry 13:795-808,1992; Gorczyca et al., Leukemia 7:659-670,1993;
Gorczyca et
al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991;
Zacharchuk,
Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897,
1993;
2 0 Gorczyca et al., International Journal of Oncology 1:639-648,1992.
Assays for proteins that influence early steps of T-cell commitment and
development include, without limitation, those described in: Antica et al.,
Blood
84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et
al., Blood
85:2770-2778,1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551,1991.
HematopoieSis Re lating Achvit~r
A protein of the present invention may be useful in regulation of
hematopoiesis
and, consequently, in the treatment of myeloid or lymphoid cell deficiencies.
Even
marginal biological activity in support of colony forming cells or of factor-
dependent cell
3 0 lines indicates involvement in regulating hematopoiesis, e.g. in
supporting the growth and
proliferation of erythroid progenitor cells alone or in combination with other
cytokines,
thereby indicating utility, for example, in treating various anemias or for
use in
conjunction with irradiation/chemotherapy to stimulate the production of
erythroid
precursors and/or erythroid cells; in supporting the growth and proliferation
of myeloid
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cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF
activity)
useful, for example, in conjunction with chemotherapy to prevent or treat
consequent
myelo-suppression; in supporting the growth and proliferation of
megakaryocytes and
consequently of platelets thereby allowing prevention or treatment of various
platelet
disorders such as thrombocytopenia, and generally for use in place of or
complimentary
to platelet transfusions; and/or in supporting the growth and proliferation of
hematopoietic stem cells which are capable of maturing to any and all of the
above-
mentioned hematopoietic cells and therefore find therapeutic utility in
various stem cell
disorders (such as those usually treated with transplantation, including,
without
limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well
as in
repopulating the stem cell compartment post irradiation/chemotherapy, either
in-vivo or
ex-vivo (i.e., in conjunction with bone marrow transplantation or with
peripheral
progenitor cell transplantation (homologous or heterologous)) as normal cells
or
genetically manipulated for gene therapy.
The activity of a protein of the invention may, among other means, be measured
by the following methods:
Suitable assays for proliferation and differentiation of various hematopoietic
lines
are cited above.
Assays for embryonic stem cell differentiation (which will identify, among
others,
2 0 proteins that influence embryonic differentiation hematopoiesis) include,
without
limitation, those described in: Johansson et al. Cellular Biology 15:141-
151,1995; Keller et
al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood
81:2903-2915,1993.
Assays for stem cell survival and differentiation (which will identify, among
2 5 others, proteins that regulate lympho-hematopoiesis) include, without
limitation, those
described in: Methylcellulose colony forming assays, Freshney, M.G. In Culture
of
Hematapoietic Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss,
Inc., New York,
NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992;
Primitive
hematopoietic colony forming cells with high proliferative potential, McNiece,
i.K. and
3 0 Briddell, R.A. In Culture of Hematopoietic Cells. R.I. Freshney, et al.
eds. Vol pp. 23-39,
Wiley-Liss, Inc., New York, NY.1994; Neben et al., Experimental Hematology
22:353-359,
1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of
Hematopoietic
Cells. R.I. Freshney, et al. eds. Vol pp. l-21, Wiley-Liss, Inc.., New York,
NY.1994; Long
term bone marrow cultures in the presence of stromal cells, Spooncer, E.,
Dexter, M. and
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Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol
pp. 163-179,
Wiley-Liss, Inc., New York, NY.1994; Long term culture initiating cell assay,
Sutherland,
H.j. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 139-
162, Wiley-Liss,
Inc., New York, NY. 1994.
T~sue Growth Activity
A protein of the present invention also may have utility in compositions used
for
bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration,
as well as
for wound healing and tissue repair and replacement, and in the treatment of
burns,
incisions and ulcers.
A protein of the present invention, which induces cartilage and/or bone growth
in circumstances where bone is not normally formed, has application in the
healing of
bone fractures and cartilage damage or defects in humans and other animals.
Such a
preparation employing a protein of the invention may have prophylactic use in
closed as
well as open fracture reduction and also in the improved fixation of
artificial joints. De
novo bone formation induced by an osteogeruc agent contributes to the repair
of
congenital, trauma induced, or oncologic resection induced craniofacial
defects, and also
is useful in cosmetic plastic surgery.
A protein of this invention may also be used in the treatment of periodontal
2 0 disease, and in other tooth repair processes. Such agents may provide an
environment
to attract bone-forming cells, stimulate growth of bone-forming cells or
induce
differentiation of progenitors of bone-forming cells. A protein of the
invention may also
be useful in the treatment of osteoporosis or osteoarthritis, such as through
stimulation
of bone and/or cartilage repair or by blocking inflammation or processes of
tissue
2 5 destruction (collagenase activity, osteoclast activity, etc.) mediated by
inflammatory
processes.
Another category of tissue regeneration activity that may be attributable to
the
protein of the present invention is tendon/Iigament formation. A protein of
the present
invention, which induces tendon/ligament-like tissue or other tissue formation
in
3 0 circumstances where such tissue is not normally formed, has application in
the healing of
tendon or ligament tears, deformities and other tendon or ligament defects in
humans and
other animals. Such a preparation employing a tendon/ligament-like tissue
inducing
protein may have prophylactic use in preventing damage to tendon or ligament
tissue, as
well as use in the improved fixation of tendon or ligament to bone or other
tissues, and
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WO 00/11015 PCT/US99/19351
in repairing defects to tendon or ligament tissue. De novo tendon/ligament-
like tissue
formation induced by a composition of the present invention contributes to the
repair of
congenital, trauma induced, or other tendon or ligament defects of other
origin, and is also
useful in cosmetic plastic surgery for attachment or repair of tendons or
ligaments. The
compositions of the present invention may provide an environment to attract
tendon- or
ligament-forming cells, stimulate growth of tendon- or ligament-forming cells,
induce
differentiation of progenitors of tendon- or ligament-forming cells, or induce
growth of
tendon/ligament cells or progenitors ex vivo for return in vivo to effect
tissue repair. The
compositions of the invention may also be useful in the treatment of
tendinitis, carpal
tunnel syndrome and other tendon or ligament defects. The compositions may
also
include an appropriate matrix and/or sequestering agent as a carrier as is
well known in
the art.
The protein of the present invention may also be useful for proliferation of
neural
cells and for regeneration of nerve and brain tissue, i.e. for the treatment
of central and
peripheral nervous system diseases and neuropathies, as well as mechanical and
traumatic disorders, which involve degeneration, death or trauma to neural
cells or nerve
tissue. More specifically, a protein may be used in the treatment of diseases
of the
peripheral nervous system, such as peripheral nerve injuries, peripheral
neuropathy and
localized neuropathies, and central nervous system diseases, such as
Alzheimer's,
2 0 Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis,
and Shy-Drager
syndrome. Further conditions which may be treated in accordance with the
present
invention include mechanical and traumatic disorders, such as spinal cord
disorders, head
trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies
resulting
from chemotherapy or other medical therapies may also be treatable using a
protein of the
2 5 invention.
Proteins of the invention may also be useful to promote better or faster
closure of
non-healing wounds, including without limitation pressure ulcers, ulcers
associated with
vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit
activity for
3 0 generation or regeneration of other tissues, such as organs (including,
for example,
pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth,
skeletal or cardiac)
and vascular (including vascular endothelium) tissue, or for promoting the
growth of cells
comprising such tissues. Part of the desired effects may be by inhibition or
modulation
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of fiibrotic scarring to allow normal tissue to regenerate. A protein of the
invention may
also exhibit angiogenic activity.
A protein of the present invention may also be useful for gut protection or
regeneration and treatment of lung or liver fibrosis, reperfusion injury in
various tissues,
and conditions resulting from systemic cytokine damage.
A protein of the present invention may also be useful for promoting or
inhibiting
differentiation of tissues described above from precursor tissues or cells; or
for inhibiting
the growth of tissues described above.
The activity of a protein of the invention may, among other means, be measured
by the following methods:
Assays for tissue generation activity include, without limitation, those
described
in: International Patent Publication No. W095/16035 (bone, cartilage, tendon);
International Patent Publication No. W095/05846 (nerve, neuronal);
International Patent
Publication No. W091 /07491 (skin, endothelium ).
Assays for wound healing activity include, without limitation, those described
in:
Winter, Epidermal Wound Hea ,n pps. 71-112 (Maibach, HI and Rovee, DT, eds.),
Year
Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J.
Invest.
Dermatol 71:382-84 (1978).
Activin/Inhibin Activity
A protein of the present invention may also exhibit activin- or inhibin-
related
activities. Inhibins are characterized by their ability to inhibit the release
of follicle
stimulating hormone (FSH), while activins and are characterized by their
ability to
stimulate the release of follicle stimulating hormone (FSH). Thus, a protein
of the present
2 5 invention, alone or in heterodimers with a member of the inhibin a family,
may be useful
as a contraceptive based on the ability of inhibins to decrease fertility in
female mammals
and decrease spermatogenesis in male mammals. Administration of sufficient
amounts
of other inhibins can induce infertility in these mammals. Alternatively, the
protein of the
invention, as a homodimer or as a heterodimer with other protein subunits of
the inhibin-
3 0 p group, may be useful as a fertility inducing therapeutic, based upon the
ability of activin
molecules in stimulating FSH release from cells of the anterior pituitary.
See, for example,
United States Patent 4,798,885. A protein of the invention may also be useful
for
advancement of the onset of fertility in sexually immature mammals, so as to
increase the
lifetime reproductive performance of domestic animals such as cows, sheep and
pigs.
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The activity of a protein of the invention may, among other means, be measured
by the following methods:
Assays for activin/inhibin activity include, without limitation, those
described in:
Vale et al., Endocrinology 91:562-572,1972; Ling et al., Nature 321:779-
782,1986; Vale et
al., Nature 321:776-779,1986; Mason et al., Nature 318:659-663, 1985; Forage
et al., Proc.
Natl. Acad. Sci. USA 83:3091-3095,1986.
Chemotactic/Chemokin t~'c Activity
A protein of the present invention may have chemotactic or chemokinetic
activity
(e.g., act as a chemokine) for mammalian cells, including, for example,
monocytes,
fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or
endothelial cells.
Chemotactic and chemokinetic proteins can be used to mobilize or attract a
desired cell
population to a desired site of action. Chemotactic or chemokinetic proteins
provide
particular advantages in treatment of wounds and other trauma to tissues, as
well as in
treatment of localized infections. For example, attraction of lymphocytes,
monocytes or
neutrophils to tumors or sites of infection may result in improved immune
responses
against the tumor or infecting agent.
A protein or peptide has chemotactic activity for a particular cell population
if it
can stimulate, directly or indirectly, the directed orientation or movement of
such cell
2 0 population. Preferably, the protein or peptide has the ability to directly
stimulate directed
movement of cells. Whether a particular protein has chemotactic activity for a
population
of cells can be readily determined by employing such protein or peptide in any
known
assay for cell chemotaxis.
The activity of a protein of the invention may, among other means, be measured
2 5 by the following methods:
Assays for chemotactic activity (which will identify proteins that induce or
prevent
chemotaxis) consist of assays that measure the ability of a protein to induce
the migration
of cells across a membrane as well as the ability of a protein to induce the
adhesion of one
cell population to another cell population. Suitable assays for movement and
adhesion
3 0 include, without limitation, those described in: Current Protocols in
Immunology, Ed by
J.E. Coligan, A.M. ICruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub.
Greene
Publishing Associates and Wiley-lnterscience (Chapter 6.12, Measurement of
alpha and
beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-
1376,1995; Lied et al.
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APMIS 103:140-146,1995; Muller et al Eur. J. Immunol. 25: 174ø1748; Gruber et
al. J. of
Immunol. 152:5860-5867,1994; Johnston et al. J. of Immunol. 153:1762-
1768,1994.
Hemostatic and Thrombol r~tnc
A protein of the invention may also exhibit hemostatic or thrombolytic
activity.
As a result, such a protein is expected to be useful in treatment of various
coagulation
disorders (including hereditary disorders, such as hemophilias) or to enhance
coagulation
and other hemostatic events in treating wounds resulting from trauma, surgery
or other
causes. A protein of the invention may also be useful for dissolving or
inhibiting
formation of thromboses and for treatment and prevention of conditions
resulting
therefrom (such as, for example, infarction of cardiac and central nervous
system vessels
(e.g., stroke).
The activity of a protein of the invention may, among other means, be measured
by the following methods:
Assay for hemostatic and thrombolytic activity include, without limitation,
those
described in: Linet et al., J. Olin. Pharmacol. 26:131-140,1986; Burdick et
al., Thrombosis
Res. 45:413-419,1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub,
Prostaglandins
35:467-474,1988.
Recgp or/Ligand Ac~vi~
A protein of the present invention may also demonstrate activity as receptors,
receptor ligands or inhibitors or agonists of receptor/ligand interactions.
Examples of
such receptors and ligands include, without limitation, cytokine receptors and
their
ligands, receptor kinases and their ligands, receptor phosphatases and their
ligands,
2 5 receptors involved in cell-cell interactions and their ligands (including
without limitation,
cellular adhesion molecules (such as selectins, integrins and their ligands)
and
receptor/ligand pairs involved in antigen presentation, antigen recognition
and
development of cellular and humoral immune responses). Receptors and ligands
are also
useful for screening of potential peptide or small molecule inhibitors of the
relevant
3 0 receptor/ligand interaction. A protein of the present invention
(including, without
limitation, fragments of receptors and ligands) may themselves be useful as
inhibitors of
receptor/ligand interactions.
The activity of a protein of the invention may, among other means, be measured
by the following methods:
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Suitable assays for receptor-ligand activity include without limitation those
described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and
Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under
static
conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-
6868, 1987;
Bierer et al., J. Exp. Med.168:1145-1156, 1988; Rosenstein et al., J. Exp.
Med.169:149-160
1989; Stoltenborg et al., J. Immunol. Methods 175:59-68,1994; Stitt et al.,
Cell 80:661-670,
1995.
Anti-Inflammator3r Activi
Proteins of the present invention may also exhibit anti-inflammatory activity.
The
anti-inflammatory activity may be achieved by providing a stimulus to cells
involved in
the inflammatory response, by inhibiting or promoting cell-cell interactions
(such as, for
example, cell adhesion), by inhibiting or promoting chemotaxis of cells
involved in the
inflammatory process, inhibiting or promoting cell extravasation, or by
stimulating or
suppressing production of other factors which more directly inhibit or promote
an
inflammatory response. Proteins exhibiting such activities can be used to
treat
inflammatory conditions including chronic or acute conditions}, including
without
limitation inflammation associated with infection (such as septic shock,
sepsis or systemic
2 0 inflammatory response syndrome (SIRS)), ischemia-reperfusion injury,
endotoxin
lethality, arthritis, complement-mediated hyperacute rejection, nephritis,
cytokine or
chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or
resulting
from over production of cytokines such as TNF or IL-1. Proteins of the
invention may also
be useful to treat anaphylaxis and hypersensitivity to an antigenic substance
or material.
Cadherin/Tumor Invasion Suvpressor Activity
Cadherins are calcium-dependent adhesion molecules that appear to play major
roles during development, particularly in defining specific cell types. Loss
or alteration
of normal cadherin expression can lead to changes in cell adhesion properties
linked to
3 0 tumor growth and metastasis. Cadherin malfunction is also implicated in
other human
diseases, such as pemphigus vulgaris and pemphigus foliaceus (auto-immune
blistering
skin diseases), Crohn's disease, and some developmental abnormalities.
The cadherin superfamily includes well over forty members, each with a
distinct
pattern of expression. All members of the superfamily have in common conserved
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extracellular repeats (cadherin domains), but structural differences are found
in other
parts of the molecule. The cadherin domains bind calcium to form their
tertiary structure
and thus calcium is required to mediate their adhesion. Only a few amino acids
in the
first cadherin domain provide the basis for homophilic adhesion; modification
of this
recognition site can change the specificity of a cadherin so that instead of
recognizing only
itself; the mutant molecule can now also bind to a different cadherin. In
addition, some
cadherins engage in heterophilic adhesion with other cadherins.
E-cadherin, one member of the cadherin superfamily, is expressed in epithelial
cell
types. Pathologically, if E-cadherin expression is lost in a tumor, the
malignant cells
become invasive and the cancer metastasizes. Transfection of cancer cell lines
with
polynucleotides expressing E-cadherin has reversed cancer-associated changes
by
returning altered cell shapes to normal, restoring cells' adhesiveness to each
other and to
their substrate, decreasing the cell growth rate, and drastically reducing
anchorage-
independent cell growth. Thus, reintroducing E-cadherin expression reverts
carcinomas
to a less advanced stage. It is likely that other cadherins have the same
invasion
suppressor role in carcinomas derived from other tissue types. Therefore,
proteins of the
present invention with cadherin activity, and polynucleotides of the present
invention
encoding such proteins, can be used to treat cancer. Introducing such proteins
or
polynucleotides into cancer cells can reduce or eliminate the cancerous
changes observed
2 0 in these cells by providing normal cadherin expression.
Cancer cells have also been shown to express cadherins of a different tissue
type
than their origin, thus allowing these cells to invade and metastasize in a
different tissue
in the body. Proteins of the present invention with cadherin activity, and
polynucleotides
of the present invention encoding such proteins, can be substituted in these
cells for the
2 5 inappropriately expressed cadherins, restoring normal cell adhesive
properties and
reducing or eliminating the tendency of the cells to metastasize.
Additionally, proteins of the present invention with cadherin activity, and
polynucleotides of the present invention encoding such proteins, can used to
generate
antibodies recognizing and binding to cadherins. Such antibodies can be used
to block
3 0 the adhesion of inappropriately expressed tumor-cell cadherins, preventing
the cells from
forming a tumor elsewhere. Such an anti-cadherin antibody can also be used as
a marker
for the grade, pathological type, and prognosis of a cancer, i.e. the more
progressed the
cancer, the less cadherin expression there will be, and this decrease in
cadherin expression
can be detected by the use of a cadherirt-binding antibody.
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Fragments of proteins of the present invention with cadherin activity,
preferably
a polypeptide comprising a decapeptide of the cadherin recognition site, and
poly-
nucleotides of the present invention encoding such protein fragments, can also
be used
to block cadherin function by binding to cadherins and preventing them from
binding in
ways that produce undesirable effects. Additionally, fragments of proteins of
the present
invention with cadherin activity, preferably truncated soluble cadherin
fragments which
have been found to be stable in the circulation of cancer patients, and
polynucleotides
encoding such protein fragments, can be used to disturb proper cell-cell
adhesion.
Assays for cadherin adhesive and invasive suppressor activity include, without
limitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-
18817, 1995;
Miyaki et al. Oncogene 11: 2547-2552,1995; Ozawa et al. Cell 63: 1033-
1038,1990.
Tumor Inhibition Activit~"~
In addition to the activities described above for immunological treatment or
prevention of tumors, a protein of the invention may exhibit other anti-tumor
activities.
A protein may inhibit tumor growth directly or indirectly (such as, for
example, via
antibody-dependent cell-mediated cytotoxicity (ADCC)). A protein may exhibit
its tumor
inhibitory activity by acting on tumor tissue or tumor precursor tissue, by
inhibiting
formation of tissues necessary to support tumor growth (such as, for example,
by
2 0 inhibiting angiogenesis), by causing production of other factors, agents
or cell types which
inhibit tumor growth, or by suppressing, eliminating or inhibiting factors,
agents or cell
types which promote tumor growth.
Other Activiiieg
2 5 A protein of the invention may also exhibit one or more of the following
additional
activities or effects: inhibiting the growth, infection or function of, or
killing, infectious
agents, including, without limitation, bacteria, viruses, fungi and other
parasites; effecting
(suppressing or enhancing) bodily characteristics, including, without
limitation, height,
weight, hair color, eye color, skin, fat to lean ratio or other tissue
pigmentation, or organ
3 0 or body part size or shape (such as, for example, breast augmentation or
diminution,
change in bone form or shape); effecting biorhythms or caricadic cycles or
rhythms;
effecting the fertility of male or female subjects; effecting the metabolism,
catabolism,
anabolism, processing, utilization, storage or elimination of dietary fat,
lipid, protein,
carbohydrate, vitamins, minerals, cofactors or other nutritional factors or
cornponent(s);
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effecting behavioral characteristics, including, without limitation, appetite,
libido, stress,
cognition (including cognitive disorders), depression (including depressive
disorders) and
violent behaviors; providing analgesic effects or other pain reducing effects;
promoting
differentiation and growth of embryonic stem cells in lineages other than
hematopoietic
lineages; hormonal or endocrine activity; in the case of enzymes, correcting
deficiencies
of the enzyme and treating deficiency-related diseases; treatment of
hyperproliferative
disorders (such as, for example, psoriasis); immunoglobulin-like activity
(such as, for
example, the ability to bind antigens or complement); and the ability to act
as an antigen
in a vaccine composition to raise an immune response against such protein or
another
material or entity which is cross-reactive with such protein.
ADMINISTRATION AND DOSING
A protein of the present invention (from whatever source derived, including
without limitation from recombinant and non-recombinant sources) may be used
in a
pharmaceutical composition when combined with a pharmaceutically acceptable
Garner.
Such a composition may also contain (in addition to protein and a Garner)
diluents, fillers,
salts, buffers, stabilizers, solubilizers, and other materials well known in
the art. The term
"pharmaceutically acceptable" means a non-toxic material that does not
interfere with the
effectiveness of the biological activity of the active ingredient(s). The
characteristics of the
2 0 carrier will depend on the route of administration. The pharmaceutical
composition of
the invention may also contain cytokines, lymphokines, or other hematopoietic
factors
such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8,
IIr9, IIrlO, IL-11,
IL-12, IL-13, IL-14, I1r15, IFN, TNFO, TNF1, TIVF2, G-CSF, Meg-CSF,
thrombopoietin, stem
cell factor, and erythropoietin. The pharmaceutical composition may further
contain other
2 5 agents which either enhance the activity of the protein or compliment its
activity or use
in treatment. Such additional factors and/or agents may be included in the
pharmaceutical composition to produce a synergistic effect with protein of the
invention,
or to minimize side effects. Conversely, protein of the present invention may
be included
in formulations of the particular cytokine, lymphokine, other hematopoieHc
factor,
3 0 thromboiytic or anti-thrombotic factor, or anti-inflammatory agent to
minimize side effects
of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-
thrombotic
factor, or anti-inflammatory agent.
A protein of the present invention may be active in multimers (e.g.,
heterodimers
or homodimers) or complexes with itself or other proteins. As a result,
pharmaceutical
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compositions of the invention may comprise a protein of the invention in such
multimeric
or complexed form.
The pharmaceutical composition of the invention may be in the form of a
complex
of the proteins) of present invention along with protein or peptide antigens.
The protein
and/or peptide antigen will deliver a stimulatory signal to both B and T
lymphocytes. B
lymphocytes will respond to antigen through their surface immunoglobulin
receptor. T
lymphocytes will respond to antigen through the T cell receptor (TCR)
following
presentation of the antigen by MHC proteins. MHC and structurally related
proteins
including those encoded by class I and class II MI~iC genes on host cells will
serve to
present the peptide antigens) to T lymphocytes. The antigen components could
also be
supplied as purified MHC-peptide complexes alone or with co-stimulatory
molecules that
can directly signal T cells. Alternatively antibodies able to bind surface
immunolgobulin
and other molecules on B cells as well as antibodies able to bind the TCR and
other
molecules on T cells can be combined with the pharmaceutical composition of
the
invention.
The pharmaceutical composition of the invention may be in the form of a
liposome
in which protein of the present invention is combined, in addition to other
pharmaceutically acceptable carriers, with amphipathic agents such as lipids
which exist
in aggregated form as micelles, insoluble monolayers, liquid crystals, or
lamellar layers
2 0 in aqueous solution. Suitable lipids for liposomal formulation include,
without limitation,
monogIycerides, diglycerides, sulfatides, lysolecithin, phospholipids,
saponin, bile acids,
and the like. Preparation of such liposomal formulations is within the level
of skill in the
art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent No.
4,501,728; U.S.
Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are
incorporated herein
2 5 by reference.
As used herein, the term "therapeutically effective amount" means the total
amount of each active component of the pharmaceutical composition or method
that is
sufficient to show a meaningful patient benefit, i.e., treatment, healing,
prevention or
amelioration of the relevant medical condition, or an increase in rate of
treatment, healing,
3 0 prevention or amelioration of such conditions. When applied to an
individual active
ingredient, administered alone, the term refers to that ingredient alone. When
applied to
a combination, the term refers to combined amounts of the active ingredients
that result
in the therapeutic effect, whether administered in combination, serially or
simultaneously.
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In practicing the method of treatment or use of the present invention, a
therapeutically effective amount of protein of the present invention is
administered to a
mammal having a condition to be treated. Protein of the present invention may
be
administered in accordance with the method of the invention either alone or in
combination with other therapies such as treatments employing cytolcines,
lymphokines
or other hematopoietic factors. When co-administered with one or more
cytolcines,
lymphokines or other hematopoietic factors, protein of the present invention
may be
administered either simultaneously with the cytolcine(s), lymphokine(s), other
hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or
sequentially. If
administered sequentially, the attending physician will decide on the
appropriate
sequence of administering protein of the present invention in combination with
cytolcine(s), lympholcine(s), other hematopoietic factor(s), thrombolytic or
anti-thrombotic
factors.
Administration of protein of the present invention used in the pharmaceutical
composition or to practice the method of the present invention can be carned
out in a
variety of conventional ways, such as oral ingestion, inhalation, topical
application or
cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection.
Intravenous administration to the patient is preferred.
When a therapeutically effective amount of protein of the present invention is
2 0 administered orally, protein of the present invention will be in the form
of a tablet,
capsule, powder, solution or elixir. When administered in tablet form, the
pharmaceutical
composition of the invention may additionally contain a solid carrier such as
a gelatin or
an adjuvant. The tablet, capsule, and powder contain from about 5 to 95%
protein of the
present invention, and preferably from about 25 to 90% protein of the present
invention.
2 5 When administered in liquid form, a liquid carrier such as water,
petroleum, oils of animal
or plant origin such as peanut oil, mineral oil, soybean oii, or sesame oii,
or synthetic oils
may be added. The liquid form of the pharmaceutical composition may further
contain
physiological saline solution, dextrose or other saccharide solution, or
glycols such as
ethylene glycol, propylene glycol or polyethylene glycol. When administered in
liquid
3 0 form, the pharmaceutical composition contains from about 0.5 to 90% by
weight of protein
of the present invention, and preferably from about 1 to 50% protein of the
present
invention.
When a therapeutically effective amount of protein of the present invention is
administered by intravenous, cutaneous or subcutaneous injection, protein of
the present
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invention will be in the form of a pyrogen-free, parenterally acceptable
aqueous solution.
The preparation of such parenterally acceptable protein solutions, having due
regard to
pH, isotonicity, stability, and the like, is within the skill in the art. A
preferred
pharmaceutical composition for intravenous, cutaneous, or subcutaneous
injection should
contain, in addition to protein of the present invention, an isotonic vehicle
such as Sodium
Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and
Sodium Chloride
Injection, Lactated Ringer's Injection, or other vehicle as known in the art.
The
pharmaceutical composition of the present invention may also contain
stabilizers,
preservatives, buffers, antioxidants, or other additives known to those of
skill in the art.
The amount of protein of the present invention in the pharmaceutical
composition
of the present invention will depend upon the nature and severity of the
condition being
treated, and on the nature of prior treatments which the patient has
undergone.
Ultimately, the attending physician will decide the amount of protein of the
present
invention with which to treat each individual patient. Initially, the
attending physician
will administer low doses of protein of the present invention and observe the
patient's
response. Larger doses of protein of the present invention may be administered
until the
optimal therapeutic effect is obtained for the patient, and at that point the
dosage is not
increased further. It is contemplated that the various pharmaceutical
compositions used
to practice the method of the present invention should contain about 0.01 ug
to about 100
2 0 mg (preferably about O.lng to about 10 mg, more preferably about 0.1 pg to
about 1 mg)
of protein of the present invention per kg body weight.
The duration of intravenous therapy using the pharmaceutical composition of
the
present invention will vary, depending on the severity of the disease being
treated and
the condition and potential idiosyncratic response of each individual patient.
It is
2 5 contemplated that the duration of each application of the protein of the
present invention
will be in the range of 12 to 24 hours of continuous intravenous
administration.
Ultimately the attending physician will decide on the appropriate duration of
intravenous
therapy using the pharmaceutical composition of the present invention.
Protein of the invention may also be used to immunize animals to obtain
3 0 polyclonal and monoclonal antibodies which specifically react with the
protein. As used
herein, the term "antibody" includes without limitation a polyclonal antibody,
a
monoclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-
grafted
antibody, a humanized antibody, or fragments thereof which bind to the
indicated protein.
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Such term also includes any other species derived from an antibody or antibody
sequence
which is capable of binding the indicated protein.
Antibodies to a particular protein can be produced by methods well known to
those
skilled in the art. For example, monoclonal antibodies can be produced by
generation of
antibody-producing hybridomas in accordance with known methods (see for
example,
Goding, 1983, Monoclonal antibodies: principles and practice, Academic Press
Inc., New
York; and Yokoyama, 1992, "Production of Monoclonal Antibodies" in Current
Protocols
in Immunology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons).
Polyclonal
sera and antibodies can be produced by inoculation of a mammalian subject with
the
relevant protein or fragments thereof in accordance with known methods.
Fragments of
antibodies, receptors, or other reactive peptides can be produced from the
corresponding
antibodies by cleavage of and collection of the desired fragments in
accordance with
known methods (see for example, Goding, supra; and Andrew et ai., 1992,
"Fragmentation
of Immunoglobulins" in Current Protocols in Immunology, Unit 2.8, Greene
Publishing
Assoc. and John Whey & Sons). Chimeric antibodies and single chain antibodies
can also
be produced in accordance with known recombinant methods (see for example,
5,169,939,
5,194,594, and 5,576,184). Humanized antibodies can also be made from
corresponding
marine antibodies in accordance with well known methods (see for example, U.S.
Patent
Nos. 5,530,101, S,S85,089, and 5,693,762). Additionally, human antibodies may
be
2 0 produced in non-human animals such as mice that have been genetically
altered to express
human antibody molecules (see for example Fishwild et al., 1996, Nature
Biotechnology
14: 84S-851; Mendez et al., 1997, Nature Genetics 15: 146-1S6 (erratum Nature
Genetics
16: 410); and U.S. Patents 5,877,397 and S,62S,126). Such antibodies may be
obtained
using either the entire protein or fragments thereof as an imrnunogen. The
peptide
2 5 immunogens additionally may contain a cysteine residue at the carboxyl
terminus, and
are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods
for
synthesizing such peptides are known in the art, for example, as in R.P.
Merrifield, J.
Amer.Chem.Soc. $5, 2149-2154 (1963); j.L. Krstenansky, et al., FEBS Lett.
21,10 {198.
Monoclonal antibodies binding to the protein of the invention may be useful
3 0 diagnostic agents for the immunodetection of the protein. Neutralizing
monoclonal
antibodies binding to the protein may also be useful therapeutics for both
conditions
associated with the protein and also in the treatment of some forms of cancer
where
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abnormal expression of the protein is involved. In the case of cancerous cells
or leukemic
cells, neutralizing monoclonal antibodies against the protein may be useful in
detecting
and preventing the metastatic spread of the cancerous cells, which may be
mediated by
the protein.
For compositions of the present invention which are useful for bone,
cartilage,
tendon or ligament regeneration, the therapeutic method includes administering
the
composition topically, systematically, or locally as an implant or device.
When
administered, the therapeutic composition for use in this invention is, of
course, in a
pyrogen-free, physiologically acceptable form. Further, the composition may
desirably
be encapsulated or injected in a viscous form for delivery to the site of
bone, cartilage or
tissue damage. Topical administration may be suitable for wound healing and
tissue
repair. Therapeutically useful agents other than a protein of the invention
which may also
optionally be included in the composition as described above, may
alternatively or
additionally, be administered simultaneously or sequentially with the
composition in the
methods of the invention. Preferably for bone and/or cartilage formation, the
composition would include a matrix capable of delivering the protein-
containing
composition to the site of bone and/or cartilage damage, providing a structure
for the
developing bone and cartilage and optimally capable of being resorbed into the
body.
Such matrices may be formed of materials presently in use for other implanted
medical
2 0 applications.
The choice of matrix material is based on biocompatibility, biodegradability,
mechanical properties, cosmetic appearance and interface properties. The
particular
application of the compositions will define the appropriate formulation.
Potential
matrices for the compositions may be biodegradable and chemically defined
calcium
sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic
acid and
polyanhydrides. Other potential materials are biodegradable and biologically
well-
defmed, such as bone or dermal collagen. Further matrices are comprised of
pure proteins
or extracellular matrix components. Other potential matrices are
nonbiodegradable and
chemically defined, such as sintered hydroxapatite, bioglass, aluminates, or
other
3 0 ceramics. Matrices may be comprised of combinations of any of the above
mentioned
types of material, such as polylactic acid and hydroxyapatite or collagen and
tricalciumphosphate. The bioceramics may be altered in composition, such as in
calcium-
aluminate-phosphate and processing to alter pore size, particle size, particle
shape, and
biodegradability.
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Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and
glycolic
acid in the form of porous particles having diameters ranging from 150 to 800
microns.
In some applications, it will be useful to utilize a sequestering agent, such
as
carboxymethyl cellulose or autologous blood clot, to prevent the protein
compositions
from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as
alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose,
ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-
methylcellulose, and carboxymethylcellulose, the most preferred being cationic
salts of
carboxymethylcellulose {CMC). Other preferred sequestering agents include
hyaluronic
acid, sodium alginate, poly{ethylene glycol), polyoxyethylene oxide,
carboxyvinyl
polymer and polyvinyl alcohol). The amount of sequestering agent useful herein
is 0.5-20
wt%, preferably 1-10 wt% based on total formulation weight, which represents
the
amount necessary to prevent desorbtion of the protein from the polymer matrix
and to
provide appropriate handling of the composition, yet not so much that the
progenitor cells
are prevented from infiltrating the matrix, thereby providing the protein the
opportunity
to assist the osteogenic activity of the progenitor cells.
In further compositions, proteins of the invention may be combined with other
agents beneficial to the treatment of the bone and/or cartilage defect, wound,
or tissue in
2 0 question. These agents include various growth factors such as epidermal
growth factor
(EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-
a and
TGF (3), and insulin-like growth factor (IGF).
The therapeutic compositions are also presently valuable for veterinary
applications. Particularly domestic animals and thoroughbred horses, in
addition to
2 5 humans, are desired patients for such treatment with proteins of the
present invention.
The dosage regimen of a protein-containing pharmaceutical composition to be
used in tissue regeneration will be determined by the attending physician
considering
various factors which modify the action of the proteins, e.g., amount of
tissue weight
desired to be formed, the site of damage, the condition of the damaged tissue,
the size of
3 0 a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and
diet, the severity
of any infection, time of administration and other clinical factors. The
dosage may vary
with the type of matrix used in the reconstitution and with inclusion of other
proteins in
the pharmaceutical composition. For example, the addition of other known
growth
factors, such as IGF I (insulin like growth factor n, to the final
composition, may also effect
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the dosage. Progress can be monitored by periodic assessment of tissue/bone
growth
and/or repair, for example, X-rays, histomorphometric determinations and
tetracycline
labeling.
Polynucleotides of the present invention can also be used for gene therapy.
Such
polynucleotides can be introduced either in vivo or ex vivo into cells for
expression in a
mammalian subject. Polynudeotides of the invention may also be administered by
other
known methods for introduction of nucleic acid into a cell or organism
(including, without
limitation, in the form of viral vectors or naked DNA).
Cells may also be cultured ex vivo in the presence of proteins of the present
14 invention in order to proliferate or to produce a desired effect on or
activity in such cells.
Treated cells can then be introduced in vivo for therapeutic purposes.
Patent and literature references cited herein are incorporated by reference as
if
fully set forth.
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SEQUENCE LISTING
<110> Valenzuela, Dario
Yuan, Olive
Hoffman, Heidi
Hall, Jeff
Rapiejko, Peter
<120> SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
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agagccaaac acttttctcc cctgtgtgga aaagtaggta tgctttacaa taaaatctgt 960
cttttctggt agaaacctga gccactgaaa ataaaagaga caactagaag cacagtagag 1020
tcccagactg agatctacct ttgagaggct ttgaaagtaa tccctggggt ttggattatt 1080
ttcacaaggg ttatgccgtt ttattcaagt ttgttgctcc gttttgcacc tctgcaataa 1140
aagcaaaatg acaaccagta cataaggggt tagcttgaca aagtagactt ccttgtgtta 1200
atttttaagt ttttttttcc ttaactatat ctgtctacag gcagatacag atagttgtat 1260
gaaaatctgc ttgcctgtaa aatttgcatt tataaatgtg ttgccgatgg atcacttggg 1320
cctgtacaca taccaattag cgtgaccact tccatcttaa aaacaaacct aaaaaacaaa 1380
atttattata tatatatata tatatatata aaggactgtg ggttgtatac aaactattgc 1440
aaacacttgt gcaaatctgt cttgatataa aggaaaagca aaatctgtat aacattatta 1500
ctacttgaat gcctctgtga ctgatttttt ttttcatttt aaatataaac ttttttgtga 1560
aaagtatgct caatgttttt tttccctttc cccattccct tgtaaataca ttttgttcta 1620
tgtgacttgg tttggaaata gttaactggt actgtaattt gcattaaata aaaagtaggt 1680
tagcctggaa atgaaattaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1738
<210> 2
<211> 84
<212> PRT
<213> Homo sapiens
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
<400> 2
Met Gln Arg Phe Leu Arg Gly Val Phe Ser Ile Pro Val Asp Met Lys
1 5 10 15
Thr Leu Ala Phe His Leu Phe Phe Pro Phe Leu Phe Lys Gly Phe Asn
20 25 30
Phe Gly Ile Phe Gln Arg Lys Phe Gly Gln Cys Gln Ile Pro Arg Asn
35 40 45
Leu Gly Gly Phe Leu Ser Phe Gln Leu Lys Leu Tyr Leu Ile Pro Thr
50 55 60
Val His Val Ser Asp His Leu Ile Thr Glu Pro Asn Thr Phe Leu Pro
65 70 75 80
Cys Val Glu Lys
<210> 3
<211> 2198
<212> DNA
<213> Homo Sapiens
<400> 3
gctctgtgga ttctggccag gccgggttcg gcggttgctg tgagagcggg cttcccaaca 60
ccatgccgtc cgccttctct gtcagctctt tccccgtcag catcccagcc gtgctcacgc 120
agacggactg gactgagccc tggctcatgg ggctggccac cttccacgcg ctctgcgtgc 180
tcctcacctg cttgtcctcc cgaagctaca gactacagat cgggcacttt ctgtgtctag 240
tcatcttagt ctactgtgct gaatacatca atgaggcggc tgcgatgaac tggagattat 300
tttcgaaata ccagtatttc gactccaggg ggatgttcat ttctatagta ttttcagccc 360
cactgctggt gaatgccatg atcattgtgg ttatgtgggt atggaagact ttgaatgtga 420
tgactgacct gaagaatgca caagagagaa gaaaggaaaa gaaaaggaga aggaaagaag 480
actgaggggc agcagctgct tggagtttgc gtccttcccg tccacccagt gcagctccca 540
gtgctgcagt gtgcgtggcg tgggcatcct tccagctgac tcatggtttg aaaaaccgtt 600
gttttattta aatatccaca gtggtagggc acacactgaa gttggctttt cagccagcac 660
tgaatgtatc catcaggaca tgcgtcttca ggtgcctgat ctttgtagtc aggctgtggg 720
aacggtctct gcagagcttc ataactggga atttgatttg aagaagtcca tgtcatatgt 780
gtaactagta ctaattataa atataaaata cacaatataa aatatgaaac tcaataataa 840
acagtgccac ctgtacatgg gcaccatgcc ctcctcctcg tgctgtgttt tctagtgcat 900
gccacagttc gcagtagagg gtgttttcac cttccaagac atggggcaaa gtttggagac 960
acctggttgt cactggaggg ggtggtgctc ctggcttctc ctgtggagcc cggggtgatg 1020
cataaaatcc tgtgtgcctg ggtcagccgc atcacagaca atgacttgac atgaaatgtc 1080
agctgtgctg gggcagagag accttggaag gaagctcttg gaaaatacgt tgtatctcag 1140
tttgatgaac caattcacaa gaggctaggc cctctctagc aaagttatgg gctgctttac 1200
tgaaaacaga atggaagccc tgaagtcaac actccatgga gaagcgtgtc tttcctaatg 1260
tcctggtgtt ctgttgattt aggtgcttgg gaacacaatg ctcccagttc tgttaggaca 1320
ggcatactgt tactttgcaa tatccacttt ataaaatagc tcctgcccag tggctcttgg 1380
ttcctgtcaa atgtggacct gtagtttaag aatgacaggt ggttagagac ccagatattt 1440
aaaaataggt gttcaataag ggaatactga ttgtgcattg tatctggata gcatgcctaa 1500
ttgtgcattt ctgaaagtta ccaattcaaa atgtaattgg aacagttatc tttgattaga 1560
caagcctggg aagagaatgt tgaggtgcag agctcaccag ccaagttcat gcccctctcg 1620
ggcctttgtg gctgagaagt gggacagaaa gatgattaag gtaatgtgtc ctccctgtag 1680
cattgtccag ggccgttgtg tagatatttg acttcactga cagaaaagaa accagggagt 1740
ttgtagagac tgtgcatttt tagtataaca ttttcaccat ctgatatggt ttggctttgt 1800
gtccccaccc aaattgcatc tcaaattgta atccccatgt gtcaagggag ggacctgatg 1860
ggaggtgatg ggatcatggg ggtggtttcc cctatgttgt tatcataata gagagggagt 1920
tctcacaaga tctgctcgtt ttaaagacag cagtttcccc tgctgtcact gtctctctcc 1980
tgctgccttg tgaagaaggt gcttgtttct ccctctgcca tgattgtaag tttcccgagg 2040
2
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
cctccccggc catgtggaac tgagtcaatt aaacttcttg tttataaagt aaaaaaaaaa 2100
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 2198
<~210> 4
<211> 140
<212> PRT
<213> Homo sapiens
<400> 9
Met Pro Ser Ala Phe Ser Val Ser Ser Phe Pro Val Ser Ile Pro Ala
1 5 10 15
Val Leu Thr Gln Thr Asp Trp Thr Glu Pro Trp Leu Met Gly Leu Ala
20 25 30
Thr Phe His Ala Leu Cys Val Leu Leu Thr Cys Leu Ser Ser Arg Ser
35 40 45
Tyr Arg Leu Gln Ile Gly His Phe Leu Cys Leu Val Ile Leu Val Tyr
50 55 60
Cys Ala Glu Tyr Ile Asn Glu Ala Ala Ala Met Asn Trp Arg Leu Phe
65 70 75 BO
Ser Lys Tyr Gln Tyr Phe Asp Ser Arg Gly Met Phe Ile Ser Ile Val
85 90 95
Phe Ser Ala Pro Leu Leu Val Asn Ala Met Ile Ile Val Val Met Trp
100 105 110
Val Trp Lys Thr Leu Asn Val Met Thr Asp Leu Lys Asn Ala GIn Glu
115 120 125
Arg Arg Lys Glu Lys Lys Arg Arg Arg Lys Glu Asp
130 135 140
<210> 5
<211> 2229
<212> DNA
<213> Homo sapiens
<400> 5
ggagccgggc aaccagtgga aggagcctgg gagaggccag gcctccccgg actgctagcc 60
tgcttttcct ggggtccctg gagccggagg aagaaccagg atgttgctgc ctgcagaagc 120
tcagctcagg aagacttcca ggaacctgag gaggagctgc cactaacagc catatttccc 180
aatggagact gtgatgacct tggaaggggg tcaaaagcct gtgatggagt cgtacacact 240
cctgctgagc ccaccggaga ctcaagatga aggctggacc cttgcgctgt ccctggctct 300
aacctacaga ctggggcctg gctccgtctt actggccccc aggtctccat ggagactgca 360
gaaacccccg cctgctggag gcctgccaca ctcacagtta ccagctagac agtggggctt 420
actaagacaa gcaggaccta aaacagtgtc tcccctggga acctactccc cacccagcat 480
ttgctaagtc tgatcacagg gaggttattt tgtctctctg tctcggtttc tctgagccac 540
tgagacagat ggctgtccgc tttgaggctc tgcagagctg tggcacccca tggtgtgtct 600
gcagtgttct gggcacatgc atgggcaccc atcgttgaga gtgcagctgg gaagaactct 660
gaaccagaag tcatcagagc tgaggcatgg ccttgaacat gtcactcagt ctctggggct 720
tctgtttcac aaatgcatga gggggccacc agcccagtgg ctttaaacca ggggcaggtt 780
gtccctccag gcagcattgg aaatgtgtgt gtgttgaggg ggtcacagtg actgtggggg 840
cacccctggc atctagtggg catcccacaa tgtgcagaac agtctctgac agcaaagaat 900
tggtccattc aatgccaatt gtagtacctt tgagacattc tggctgagcc aatgccttct 960
3
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
Ccctgtcaga gtcccccaga gcagagaggg tcaggcttcc ctggaccttg gctcccagag 1020
caagccaaaa taaagactac actgttgcct tgggggcttg tcgggccagg gccaagacgg 1080
tctgcgtgct gcagggccag gacagaaata gccacacatg ccggtgagaa caaagagcct 1140
ctttctttct catgttgaca tcgactttct gtgccaagtc ctttgggtat aaggatgcta 1200
gggaattcct ataggcacca aacagaagga aagctagggg cttggactac tgggtatagg 1260
acttgctcta gctctcaggt cctagcccaa gctcaatgca aacacagccc ctccgggctc 1320
tctgtttctg tgaggttctg gaatcccttc ctctgtgtcc gtgagtctga cagaatcgat 1380
gatgttccct tagagctggg aaatccatgt gtttattcac ggagggaact caccattacc 1440
tcccttgtct tctttgcctg ccttggagaa atccagagtc ttcggaatgg caaaggcagc 1500
tcctggattt ccctggaggg gaggcactag ctgagggaag tagctccctt cattcatgat 1560
gcacagttta cgcagcagac acacaactgc gcctactatt tgctcggtgc cctgcaaggt 1620
gctgcctaac tttgatttgt tatttcagct ctctccagga tagtgccaaa tggtgcaatg 1680
ggaaacctgt tttgctgggg ggctctagat cactggctcc agaactcccg gctgccaggg 1740
tagcccctac ccccagcccc ttgctcctgg acagcagtgg gtctcacctt tagcctctgc 1800
ccccagttct ggtctgaccc aacagagggg ctctatgata ttaagaaggg gcccttcctg 1860
ctctgtgcct caacctattc tccataatag ggagtctaat cctattcctt ccctgcctga 1920
tgaggatggt gtgaggatga ggaggacggc atctcatttg gggctttttg gcagtgggcc 1980
tcattttaat cctgcagggc tgcctgccag tggatctatc cagctgcttc cttgtagcca 2040
agaatgagtt caatgaattg tgattcactg attttattga ttttgtttta aaacagggag 2100
actggtattt ttgaagctgc tatcattttc tatttcttta ttaatttctt tgtaatcatc 2160
ttattaaagt tttcttattt agtggaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2220
aaaaaaaaa 2229
<210> 6
<211> 111
<212> PRT
<213> Homo sapiens
<400> 6
Met Leu Gly Asn Ser Tyr Arg His Gln Thr Glu Gly Lys Leu Gly Ala
1 5 10 15
Trp Thr Thr Gly Tyr Arg Thr Cys Ser Ser Ser Gln Val Leu Ala Gln
20 25 30
Ala Gln Cys Lys His Ser Pro Ser Gly Leu Ser Val Ser Val Arg Phe
35 40 45
Trp Asn Pro Phe Leu Cys Val Arg Glu Ser Asp Arg Ile Asp Asp Val
50 55 6
Pro Leu Glu Leu Gly Asn Pro Cys Val Tyr Ser Arg Arg Glu Leu Thr
65 70 75 80
Ile Thr Ser Leu Val Phe Phe Ala Cys Leu Gly Glu Ile Gln Ser Leu
85 90 95
Arg Asn Gly Lys Gly Ser Ser Trp Ile Ser Leu Glu Gly Arg His
100 105 110
<210> 7
<211> 915
<212> DNA
<213> Homo sapiens
<400> 7
gcgtgagcac cctatctcag ctgctattcg ggcatgatgc tttgtagagg gtagagtaga 60
cagccccctc ccctactcac catggtattt ctccttgaat tcctctttct tgttttcttt 120
cctggttgtg tgaaccagtt gctgctgtca tacccctggc agggccaggg gacctctctt 180
4
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
tggtcatttc tgtcctttca ctggctgctg ccccaggaag actcctctag gctctccatc 240
tttcccttga gagctggctc cccaccccaa cctgctcagg caccaccgag gatctaggtc 300
tctggctccc catacctgga cccacatggg tgggtgcctg ttgcatgttt aagagagagg 360
ggctgtgagg tgacagggca ctagggcctt cactcctttc tccccttcca tcctttcttt 920
accagtgcca cccatgtccc tagctcccgg gtattggggc tgaggctctg gggcctgtct 480
ccctgccagc gtgagggcaa gaccccagag ccttagctga gcaagcccag aggggcagcg 540
tggcccctcc ctcccctttt cctgccccgt cccatgcctc agcttgctgc ttgtgccagt 600
tgcctgtttc gcttcagtgt ttgattctag cacttacatg tgtcctcccc accaagccct 660
ctatctcctt ctaatccttc aacccctggc cccctcccca taacagtgac ttttccaggg 720
aggaagaggc agcaggagct gttggccttg gtttgcacag agcgggtagg gctgtaggga 780
aagcgggtga gctgttgtgc tgctgggcct ccctttggcc ctcgcttccc accctacgat 840
gtatgaaatg tatgtacaga ccagagatgt ttatacagcc gataaagatg gaaaaaaaaa 900
aaaaaaaaaa aaaaa 915
<210> 8
<211> 71
<212> PRT
<213> Homo Sapiens
<400> 8
Met Val Phe Leu Leu Glu Phe Leu Phe Leu Val Phe Phe Pro Gly Cys
1 5 10 15
Val Asn Gln Leu Leu Leu Ser Tyr Pro Trp Gln Gly Gln Gly Thz Ser
20 25 30
Leu Trp Ser Phe Leu Ser Phe His Trp Leu Leu Pro Gln Glu Asp Ser
35 40 4S
Ser Arg Leu Ser Ile Phe Pro Leu Arg Ala Gly Ser Pro Pro Gln Pro
50 55 60
Ala Gln Ala Pro Pro Arg Ile
65 70
<210> 9
<211> 1100
<212> DNA
<213> Homo Sapiens
<400> 9
tgacccccaa gacggaagag gatggccgcg gcggctctga ggagattttg gtcccggcgc 60
cgcgcagagg cggggcgcgc cgctgtgtat gtgggtctgc tgggcggcgc ggcggcctgc 120
ttcacgctgg cgcccagcga gggtgccttc gaggaggcgc tgctggaggc gtcggggacc 180
ctcctgctgc tggcgccggc cacccgcaac cgcgggtcct ggacgtgggc ttcgtgggtc 240
gctggtgggt gctgggggcc tggatgcgcg actgcgacat caacgacgac gaattcctgc 300
acctgccggc gcatttgcgg gtggtcgggc cccagcagct gcattccgag accaacgagc 360
ggctcttcga tgagaagtac aagcctgtcg tgctcaccga cgatcaggtg gaccaggcgc 420
tgtgggagga gcaggtcttg cagaaggaga agaaggacag gctcgccctg agccaggccc 480
actcgctggt gcaggcggag gccccgagat gaaaccctga ggcccccgag tcctggcaaa 540
ctgcttgcct ggggtggtgc agttctgagt gtgcctcacc tgcagaacag ctgagacaga 600
tgatgtgcaa agtgttttct cactggattt gcacaagttt ggggagcctt tctgcccccc 660
gtctttgttc tttattagct gaagctaatt cagagccacc tgggtccggg agttggggac 720
agcagaacga cttgacacat gttcatcact ggcagagctg gtcatgagcc ttttatataa 780
gcctttttca tcgggcctca gaggccctcc ttaaggaggt accacattgg tcagctgact 840
tgcaaactct tctaaggcca cttagatttt ctttttcaag tttgggttgt ggcctggcat 900
ggtgatgtct gtaatcccag cagtttgcaa actgaggcaa gagaatcgct tgaggccagg 960
agtttgaggc cagctagagt gacatagcaa gactccgatg ctacaaaaaa gaataataat 1020
agtaattaac taaataaaat ttgagctgaa atgttaaaaa aaaaaaaaaa aaaaaaaaaa 1080
S
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
aaaaaaaasa aaaaaaaaaa 1100
<210> 10
<211> 149
<212> PRT
<213> Homo Sapiens
<400> 10
Met Ala Ala Ala Ala Leu Arg Arg Phe Trp Ser Arg Arg Arg Ala Glu
1 5 10 15
Ala Gly Arg Ala Ala Val Tyr Val Gly Leu Leu Gly Gly Ala Ala Ala
20 25 30
Cys Phe Thr Leu Ala Pro Ser Glu Gly Ala Phe Glu Glu Ala Leu Leu
35 40 45
Glu Ala Ser Gly Thr Leu Leu Leu Leu Ala Pro Ala Thr Arg Asn Arg
50 55 60
Gly Ser Trp Thr Trp Ala Ser Trp Val Ala Gly Gly Cys Trp Gly Pro
65 70 75 80
Gly Cys Ala Thr Ala Thr Ser Thr Thr Thr Asn Ser Cys Thr Cys Arg
85 90 95
Arg Ile Cys Gly Trp Ser Gly Pro Ser Ser Cys Ile Pro Arg Pro Thr
100 105 110
Ser Gly Ser Ser Met Arg Ser Thr Ser Leu Ser Cys Ser Pro Thr Ile
115 120 125
Arg Trp Thr Arg Arg Cys Gly Arg Ser Arg Ser Cys Arg Arg Arg Arg
130 135 140
Arg Thr Gly Ser Pro
145
<210> 11
<211> 2010
<212> DNA
<213> Homo sapiens
<400> 11
tggtgagctg cagagaagag gaggttggtg tggagcacag gcagcaccga gcctgccccg 60
tgagctgagg gcctgcagtc tgcggctgga atcaggatag acaccaaggc aggaccccca 120
gagatgctga agcctctttg gaaagcagca gtggccccca catggccatg ctccatgccg 180
ccccgccgcc cgtgggacag agaggctggc acgttgcagg tcctgggagc gctggctgtg 240
ctgtggctgg gctccgtggc tcttatctgc ctcctgtggc aagtgccccg tcctcccacc 300
tggggccagg tgcagcccaa ggacgtgccc aggtcctggg agcatggctc cagcccagct 360
tgggagcccc tggaagcaga ggccaggcag cagagggact cctgccagct tgtccttgtg 420
gaaagcatcc cccaggacct gccatctgca gccggcagcc cctctgccca gcctctgggc 480
caggcctggc tgcagctgct ggacactgcc caggagagcg tccacgtggc ttcatactac 540
tggtccctca cagggcctga catcggggtc aacgactcgt cttcccagct gggagaggct 600
cttctgcaga agctgcagca gctgctgggc aggaacattt ccctggctgt ggccaccagc 660
agcccgacac tggccaggac atccaccgac ctgcaggttc tggctgcccg aggtgcccat 720
gtacgacagg tgcccatggg gcggctcacc aggggtgttt tgcactccaa attctgggtt 780
gtggatggac ggcacatata catgggcagt gccaacatgg actggcggtc tctgacgcag 840
gtgaaggagc ttggcgctgt catctataac tgcagccacc tggcccaaga cctggagaag 900
6
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
accttccaga cctactgggt actgggggtg cccaaggctg tcctccccaa aacctggcct 960
cagaacttct catctcactt caaccgtttc cagcccttcc acggcctctt tgatggggtg 1020
cccaccactg cctacttctc agcgtcgcca ccagcactct gtccccaggg ccgcacccgg 1080
gacctggagg cgctgctggc ggtgatgggg agcgcccagg agttcatcta tgcctccgtg 1140
atggagtatt tccccaccac gcgcttcagc caccccccga ggtactggcc ggtgctggac 1200
aacgcgctgc gggcggcagc cttcggcaag ggcgtgcgcg tgcgcctgct ggtcggctgc 1260
ggactcaaca cggaccccac catgttcccc tacctgcggt ccctgcaggc gctcagcaac 1320
cccgcggcca acgtctctgt ggacgtgaaa gtcttcatcg tgccggtggg gaaccattcc 1380
aacatcccat tcagcagggt gaaccacagc aagttcatgg tcacggagaa ggcagcctac 1440
ataggcacct ccaactggtc ggaggattac ttcagcagca cggcgggggt gggcttggtg 1500
gtcacccaga gccctggcgc gcagcccgcg ggggccacgg tgcaggagca gctgcggcag 1560
ctctttgagc gggactggag ttcgcgctac gccgtcggcc tggacggaca ggctccgggc 1620
caggactgcg tttggcaggg ctgagggggg cctctttttc tctcggcgac cccgccccgc 1680
acgcgccctc ccctctgacc ccggcctggg cttcagccgc ttcctcccgc aagcagcccg 1740
ggtccgcact gcgccaggag ccgcctgcga ccgcccgggc gtcgcaaacc gcccgcctgc 1800
tctctgattt ccgagtccag ccccccctga gccccacctc ctccagggag ccctccagga 1860
agccccttcc ctgactcctg gcccacaggc caggcctaaa aaaaactcgt ggcttaaaaa 1920
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2010
<210> 12
<211> 506
<212> PRT
<213> Homo sapiens
<400> 12
Met Leu Lys Pro Leu Trp Lys Ala Ala Val Ala Pro Thr Trp Pro Cys
1 5 10 15
Ser Met Pro Pro Arg Arg Pro Trp Asp Arg Glu Ala Gly Thr Leu Gln
20 25 30
Val Leu Gly Ala Leu Ala Val Leu Trp Leu Gly Ser Val Ala Leu Ile
35 40 45
Cys Leu Leu Trp Gln Val Pro Arg Pro Pro Thr Trp Gly Gln Val Gln
50 55 60
Pro Lys Asp Val Pro Arg Ser Trp Glu His Gly Ser Ser Pro Ala Trp
65 70 75 80
Glu Pro Leu Glu Ala Glu Ala Arg Gln Gln Arg Asp Ser Cys Gln Leu
85 90 95
Val Leu Val Glu Ser Ile Pro Gln Asp Leu Pro Ser Ala Ala Gly Ser
I00 105 110
Pro Ser Ala Gln Pro Leu Gly Gln Ala Trp Leu Gln Leu Leu Asp Thr
115 120 125
Ala Gln Glu Ser Val His Val Ala Ser Tyr Tyr Trp Ser Leu Thr Gly
130 135 140
Pro Asp Ile Gly Val Asn Asp Ser Ser Ser Gln Leu Gly Glu Ala Leu
145 150 155 160
Leu Gln Lys Leu Gln Gln Leu Leu Gly Arg Asn Ile Ser Leu Ala Val
165 170 175
Ala Thr Ser Ser Pro Thr Leu Ala Arg Thr Ser Thr Asp Leu Gln Val
7
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
180 185 190
Leu Ala Ala Arg Gly Ala His Val Arg Gln Val Pro Met Gly Arg Leu
195 200 205
Thr Arg Gly Val Leu His Ser Lys Phe Trp Val Val Asp Gly Arg His
210 215 220
Ile Tyr Met Gly Ser Ala Asn Met Asp Trp Arg Ser Leu Thr Gln Val
225 230 235 240
Lys Glu Leu Gly Ala Val Ile Tyr Asn Cys Ser His Leu Ala Gln Asp
245 250 255
Leu Glu Lys Thr Phe Gln Thr Tyr Trp Val Leu Gly Val Pro Lys Ala
260 265 270
Val Leu Pro Lys Thr Trp Pro Gln Asn Phe Ser Ser His Phe Asn Arg
275 280 285
Phe Gln Pro Phe His Gly Leu Phe Asp Gly Val Pro Thr Thr Ala Tyr
290 295 300
Phe Ser Ala Ser Pro Pro Ala Leu Cys Pro Gln Gly Arg Thr Arg Asp
305 310 315 320
Leu Glu Ala Leu Leu Ala Val Met Gly Ser Ala Gln Glu Phe Ile Tyr
325 330 335
Ala Ser Val Met Glu Tyr Phe Pro Thr Thr Arg Phe Ser His Pro Pro
340 345 350
Arg Tyr Trp Pro Val Leu Asp Asn Ala Leu Arg Ala Ala Ala Phe Gly
355 360 365
Lys Gly Val Arg Val Arg Leu Leu Val Gly Cys Gly Leu Asn Thr Asp
370 375 380
Pro Thr Met Phe Pro Tyr Leu Arg Ser Leu Gln Ala Leu Ser Asn Pro
385 390 395 400
Ala Ala Asn Val Ser Val Asp Val Lys Val Phe Ile Val Pro Val Gly
405 410 415
Asn His Ser Asn Ile Pro Phe Ser Arg Val Asn His Ser Lys Phe Met
420 425 430
Val Thr Glu Lys Ala Ala Tyr Ile Gly Thr Ser Asn Trp Ser Glu Asp
435 440 445
Tyr Phe Ser Ser Thr Ala Gly Val Gly Leu Val Val Thr Gln Ser Pro
450 455 460
Gly Ala Gln Pro Ala Gly Ala Thr Val Gln Glu Gln Leu Arg Glri Leu
465 470 475 480
Phe Glu Arg Asp Trp Ser Ser Arg Tyr Ala Val Gly Leu Asp Gly Gln
485 490 495
Ala Pro Gly Gln Asp Cys Val Trp Gln Gly
g
CA 02340616 2001-02-23
WO 00/11015 PCTNS99/19351
500 505
<210> 13
<211> 2830
<212> DNA
<213> Homo sapiens
<400> 13
ggcagaggca tgctcatggt gctccttccc cagcagcaat cctatgctcc ccttccaggt 60
cttctcttcc ttcttttcct cagccagctg gctgctggta agagaggtct ggcgagagtg 120
tgtcccagta gctgctgcta tggatggaac ggagcgggca ggacgtaggc tggaggagtc 180
tgtcttcccg gcatctttac gagatcgctg ctgcaggacc ttaatcatag catctttctc 240
tatgattttg gcatggagat ttttaatagt gtattccatg tcctgacacc ttctgttggc 300
ctgcaccacc tcctcctcct cttgccagat gtgggcctcc agcgagctct ctccgtagct 360
gccattccgt gagtggttga tgatcgtggt gtccctctca gctgctgcag tggctgcggc 420
attcatggca aagtgtcgga tggtgctctc ctccaggtac ttctgctccc actttgtcat 480
gtcggcctcc agggccagga tccgctcctc cttctcccgc acaagttcca ggagggctgg 540
ggcattgtat tccggcatgt tggctggctg gccatttcca tgtttctgct gggttctcag 600
tgcatccagc tctctctcca gccaagtccg cagtctccgc tccatctgtt ctcgcttctc 660
acatgcagac tgcagctggg tcagggcctg ctgcagcttc tcaactttct caacatatgc 720
ttgcttctct cgtaactcct cttccagctt gatgaccctg gcctgggcgt tgctcaaagc 780
ctggtccagg atctcgatgt gtctccgatg gtcctcactt gcagtccgca ctgctgctaa 840
ctccatttct aatttctcct tttccttcaa gaattctttg ttctgggaag cataatgccc 900
ctctgcagct ttgtcttcat gcccttcgta ttccctgctg gatagttgcc tgttagcagt 960
ctctagtcga tctcggaggt ctctgttgaa atcatgaagt cttctaatct cgccttccaa 1020
tttgtttctc atggccttgt ccagcgattc tcgcttggtg gtagacttga ccagactttc 1080
ataggcttcc gaaattctct gaagttcttt ttcaaacttg tggagcttgt cggcattgtc 1140
gtagtaaccc tgaagttcct ggtgaagcac ccggttctcc tctgttaata tctccaccat 1200
ttgctgggct cgctccacaa tcgcasaggc atctggacca agctgctggc tgggggaggc 1260
ggcaggcggg ggctgtggag cacccagggc catcgggagt ggaagcggca gggagacaga 1320
gtgcagtggc ccgctggcgg aagaggtctg ggaggacatg gggctgtgct gctgcatggt 1380
tgatgggaac ggaagttggc atgggcggct cgttacccca tactcagggg gtggctggta 1440
ccgcaggacg gccacatctg ttctcacagg ctgaggagca gggtagggct tgaccatctc 1500
gtggagcatc ccggggtgct ggtcaccata aaaaagtccg tgctcctggg tcttgctgac 1560
tggggacatc atttgcttgg tcttgaaggg gtactcaggt ggaggacccc gagggtccag 1620
cactttacct gcaggctggg caggggaggg cccccctcct actttgaagc cctttccatt 1680
ccccgagccg ggaaggtgtt gcttggcccc attcctctcc agggacagct gcatgattct 1740
ctcgctgagc gagcggacgt ggccctgctt cagttccttc agcgcctcgt ccttatgcgc 1800
ctgtccactg ttggcacggt tcacagtggg cctcccctca gttcgggact tctgactggt 1860
gccccctgcc atgtagtaac catggcccac cgccccctgc tgctgttgct gctgctgctg 1920
ccccctgaag aactgcgact gtgctttggc ctcctcgtaa gtgggcagtt cctcgttgtt 1980
ctgctgaggc tgcgtggacc ggacctgttt ctccatcact gtattgtcca cctggtgttc 2040
ttgaccctgc ggttcttggc gtgctgactg gtagaccatt tgtgggtctt cttgagtgag 2100
gttttccgtg gaagaaaagt tgtttgtagg atgggctggt cctgcactcc ctgtggcctg 2160
gtgctgaatg gccagcaagt tcatgttctc ggttggggtg ccataccgca gttgttcctg 2220
gatcagccgc tgcaatactg ttccagctgc cgcatcctcg gaacctctca tttccacctc 2280
tgagatcctc aggaagtttg gggagtggaa gttacaaaga ggatcttcaa caactttttc 2340
cctgatgcta ctggttgcct ccaccgtcaa agcagatgtt tcatgcctcc cagaatagag 2400
ctgaaagtct ggggaaaagt aggtggagtc ttctagaacc tggacaggac tactggggct 2460
ataacaagca gaaggggacc ctaactcgtc tgggctgtag gatgcgggcg aggcttccac 2520
aaactcactg tctgggggag aagaaaagca gaaaacaact cgaatcgcta ccattcagga 2580
cgaacccgcc aagcaccagc tcaagcgcag gtccccggga aaagcgcggg cttctctctc 2640
ccagcgctca gaatccctga gccggaggcc ccgcgggatt cagaccgcca gatccccagg 2700
gagtgacaaa tcgccgcaga aacttggggg acaactcggc cctggcaccg cgcggcttcc 2760
aggcgcggtc aggcgcgcgc caactttccc cgcgtgccac cccgcggctc ccccggccgg 2820
gcgctgggcc
2830
<210> 14
<211> 171
9
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
<212> PRT
<213> Homo sapiens
<400> 14
Met Ile Val Val Ser Leu Ser Ala Ala Ala Val Ala Ala Ala Phe Met
1 5 10 15
Ala Lys Cys Arg Met Val Leu Ser Ser Arg Tyr Phe Cys Ser His Phe
20 25 30
Val Met Ser Ala Ser Arg Ala Arg Ile Arg Ser Ser Phe Ser Arg Thr
35 40 45
Ser Ser Arg Arg Ala Gly Ala Leu Tyr Ser Gly Met Leu Ala Gly Trp
50 55 60
Pro Phe Pro Cys Phe Cys Trp Val Leu Ser Ala Ser Ser Ser Leu Ser
65 70 75 80
Ser Gln Val Arg Ser Leu Arg Ser Ile Cys Ser Arg Phe Ser His Ala
85 90 95
Asp Cys Ser Trp Val Arg Ala Cys Cys Ser Phe Ser Thr Phe Ser Thr
100 105 110
Tyr Ala Cys Phe Ser Arg Asn Ser Ser Ser Ser Leu Met Thr Leu Ala
115 120 125
Trp Ala Leu Leu Lys Ala Trp Ser Arg Ile Ser Met Cys Leu Arg Trp
130 135 140
Ser Ser Leu Ala Val Arg Thr Ala Ala Asn Ser Ile Ser Asn Phe Ser
145 150 155 160
Phe Ser Phe Lys Asn Ser Leu Phe Trp Glu Ala
165 170
<210> 15
<211> 2000
<212> DNA
<213> Homo sapiens
<400> 15
gcagaagctg tacgggctcc aggctgacat taccatcagc ctggacggcg tgcccttcct 60
catgcatgac accaccctgc ggcgcaccac caacgtggag gaggagttcc cggagctggc 120
ccgcaggcct gcctccatgc ttaactggac caccctgcag agactcaacg ctggccagtg 180
gttcctgaag actgacccct tctggacagc cagctccctg tcaccctccg accacagaga 240
ggcccagaac cagtccatct gcagcctggc agagctcctg gagctggcca agggcaatgc 300
cacactgctg ctcaacctgc gtgacccgcc ccgggagcac ccctaccgca gcagttttat 360
caacgtgact ctggaggccg tgctgcactc cggcttcccc cagcaccagg tcatgtggct 420
gcctagcagg cagaggcccc tggtgcggaa ggtggctccc ggcttccaac agacatcagg 480
ctccaaggag gcagtcgcca gcctgcggag aggccacatc cagcggctga acctgcgcta 540
cactcaggtg tcccgccagg agctcaggga ctacgcgtcc tggaacctga gtgtgaacct 600
ctacacagtc aacgcaccgt ggctcttctc cctgctgtgg tgtgcggggg tcccatccgt 660
cacctctgac aactcccaca ccctgtccca ggtgccttcc cccctctgga tcatgccccc 720
ggacgagtac tgtctcatgt gggtcactgc cgacctggtc tccttcaccc tcatcgtggg 780
catcttcgtg ctccagaagt ggcgcctggg tggcatacgg agctacaacc ctgagcagat 840
catgctgagt gctgcggtgc gccggaccag ccgggacgtc agcatcatga aggagaagct 900
tattttctca gagatcagcg atggtgtaga ggtctccgat gtgctctccg tatgttcaga 960
1~
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
caacagttat gacacatatg ccaacagcac cgccacccct gtgggccccc gagggggtgg 1020
cagccacacc aagaccctca tagagcggag tgggcgttag ctgaagacat gtctgtccca 1080
cctgtacctg acacagaagc tggggagcct aggagagctg gtggaagtgt gtctgaactc 1140
ggagtgctct gggagcgggc tccacagcct ccttgtgggc tccagcccct tgtcagccgc 1200
agcctctctt gagggggact ccctgtcccc tgaggcccag ctgggccagg actccatcct 1260
ttcagatgcc cctgcaggcc tggggctcct tctgggaagt atggggccta gggcttggtc 1320
cccctcttct gaggccctct cctgtatccc gacctggaag ctttgatggg tcatgggcca 1380
tgccataccc cctgtggcaa tggagtgtgt ggatgctcac ctgtgccatc tgtcctcctg 1440
tctgtgccag gaggcacctg agttctctgc tgttatcctg ccccaagggc ctgggccgag 1500
cctctacctg aagcaactct gctcttcctg tcagtctcaa agcacaagga ggttcagccc 1560
aggaggaagc cagctgcaat gtggagacac gtcctcctcc ccaacccacc tcatgccacc 1620
gccaaccccc tgccccagga gcgggcctga gccacgtccc ctaggagcag ctggagatgg 1680
ccaaaagagt gagctcaagg actactggga tcccaatgcc agtgtccagc agacctcaag 1740
gcagaagggt cacctaaccc aggagtccac agactgatgt gacctcaggt tcccacatca 1800
gtggccacag ggcagggccc acctggtaga agtgttctgg atatggccag ggtgggtgtg 1860
tggctaagtg ggcctgaaca gagggaacct agggcccttg gcccaatgtg attaaaggct 1920
gccatcttga aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980
aaaaaaaaaa aaaaaaaaaa 2000
<210> 16
<211> 332
<212> PRT
<213> Homo sapiens
<400> 16
Met His Asp Thr Thr Leu Arg Arg Thr Thr Asn Val Glu Glu Glu Phe
1 5 10 15
Pro Glu Leu Ala Arg Arg Pro Ala Ser Met Leu Asn Trp Thr Thr Leu
20 25 30
Gln Arg Leu Asn Ala Gly Gln Trp Phe Leu Lys Thr Asp Pro Phe Trp
35 40 45
Thr Ala Ser Ser Leu Ser Pro Ser Asp His Arg Glu Ala Gln Asn Gln
50 55 60
Ser Ile Cys Ser Leu Ala Glu Leu Leu Glu Leu Ala Lys Gly Asn Ala
65 70 75 80
Thr Leu Leu Leu Asn Leu Arg Asp Pro Pro Arg Glu His Pro Tyr Arg
85 90 95
Ser Ser Phe Ile Asn Val Thr Leu Glu Ala Val Leu His Ser Gly Phe
100 105 110
Pro Gln His Gln Val Met Trp Leu Pro Ser Arg Gln Arg Pro Leu Val
115 120 125
Arg Lys Val Ala Pro Gly Phe Gln Gln Thr Ser Gly Ser Lys Glu Ala
130 135 140
Val Ala Ser Leu Arg Arg Gly His Ile Gln Arg Leu Asn Leu Arg Tyr
145 150 155 160
Thr Gln Val Ser Arg Gln Glu Leu Arg Asp Tyr Ala Ser Trp Asn Leu
165 170 175
Ser Val Asn Leu Tyr Thr Val Asn Ala Pro Trp Leu Phe Ser Leu Leu
180 185 190
11
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
Trp Cys Ala Gly Val Pro Ser Val Thr Ser Asp Asn Ser His Thr Leu
195 200 205
Ser Gln Val Pro Ser Pro Leu Trp Ile Met Pro Pro Asp Glu Tyr Cys
210 215 220
Leu Met Trp Val Thr Ala Asp Leu Val Ser Phe Thr Leu Ile Val Gly
225 230 235 240
Ile Phe Val Leu Gln Lys Trp Arg Leu Gly Gly Ile Arg Ser Tyr Asn
245 250 255
Pro Glu Gln Ile Met Leu Ser Ala Ala Val Arg Arg Thr Ser Arg Asp
260 265 270
Val Ser Ile Met Lys Glu Lys Leu Ile Phe Ser Glu Ile Ser Asp Gly
275 280 285
Val Glu Val Ser Asp Val Leu Ser Val Cys Ser Asp Asn Ser Tyr Asp
290 295 300
Thr Tyr Ala Asn Ser Thr Ala Thr Pro Val Gly Pro Arg Gly Gly Gly
305 310 315 320
Ser His Thr Lys Thr Leu Ile Glu Arg Ser Gly Arg
325 330
<210> 17
<211> 1170
<212> DNA
<213> Homo Sapiens
<400> 17
aagtttgttc cccgagttcg gagcctagga gccccccgcg gctgcggcgc aggtgccctc 60
ggcctgagtc gggatggagc tgcctgctgt gaacctgaag gtgattctcc taggtcactg 120
gctgctgaca acctggggct gcattgtatt ctcaggctcc tatgcctggg ccaacttcac 180
catcctggcc ttgggcgtgt gggctgtggc tcagcgggac tccatcgacg ccataagcat 240
gtttctgggt ggcttgctgg ccaccatctt cctggacatc gtgcacatca gcatcttcta 300
cccgcgggtc agcctcacgg acacgggccg ctttggcgtg ggcatggcca tcctcagctt 360
gctgctcaag ccgctctcct gctgcttcgt ctaccacatg taccgggagc gcgggggttt 420
ccttgggtct tctcaggacc gtagtgccta ccagacgatt gactcagcag aggcgcccgc 480
agatcccttt gcagtcccag agggcaggag tcaagatgcc cgagggtact gaagccagcc 540
acgctgcgcc cggccctgcc ccgggccttc ctcgtgcctg ggaggtcgtt ctagggatgc 600
tcctgacctc cgtctcttgg acctaagatg gaatgtgtcc ccagctcagg gattgcctga 660
accaagaggc caggagcccc catgggccgc ccagtaccat gcacactcct gtcccgaact 720
ccctgaggcc tcccctccct tcagggcacc cactggttcc caggctggaa ccagggtctc 780
tctttacctc ctaccccatg gtggcaccac agaggccctc agccgagtcc tgcctgagtg 840
ttgcaagctc aggcctttaa ggactgctga tgccccctca ggcctccccc aagtttgctg 900
ggctttggtg gaagccctga gagcttcagg tcctgctcag cccgaggagc agtctgacat 960
gggagtgagg ccctgtcctt ctcactgcct ggtcacatgg tgcctaggga tgcagggctg 1020
gaggccagag gtgtcagcaa cactgtgacc caccacaacc tccagcctcc cttttcagag 1080
cacagcatta aagtttgggg aattctgtaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1140
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1170
<210> 18
<211> 152
<212> PRT
<213> Homo Sapiens
12
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
<400> 18
Met Glu Leu Pro Ala Val Asn Leu Lys Val Ile Leu Leu Gly His Trp
1 5 10 15
Leu Leu Thr Thr Trp Gly Cys Ile Val Phe Ser Gly Ser Tyr Ala Trp
20 25 30
Ala Asn Phe Thr Ile Leu Ala Leu Gly Val Trp Ala Val Ala Gln Arg
35 40 45
Asp Ser Ile Asp Ala Ile Ser Met Phe Leu Gly Gly Leu Leu Ala Thr
50 55 60
Ile Phe Leu Asp Ile Val His Ile Ser Ile Phe Tyr Pro Arg Val Ser
65 70 75 80
Leu Thr Asp Thr Gly Arg Phe Gly Val Gly Met Ala Ile Leu Ser Leu
85 90 95
Leu Leu Lys Pro Leu Ser Cys Cys Phe Val Tyr His Met Tyr Arg Glu
100 105 110
Arg Gly Gly Phe Leu Gly Ser Ser Gln Asp Arg Ser Ala Tyr Gln Thr
115 120 125
Ile Asp Ser Ala Glu Ala Pro Ala Asp Pro Phe Ala Val Pro Glu Gly
130 135 140
Arg Ser Gln Asp Ala Arg Gly Tyr
145 150
<210> 19
<211> 4144
<212> DNA
<213> Homo sapiens
<400> 19
ctccttgggc aggtgaggat aacagccctg tggcgagctg gtcctgagca tctgagtgag 60
cagtgatgcg gagaaatgac cttggtggga ggggacgtcc acagacgtga cccggacgtc 120
gggacaggtg gatctggggt caaggggagt gtttagaata cttgttggca tccatgacgc 180
agtggtgtga gcgtgagata tccagcatcg cacctggaga gctgtgctgt ctgctccttt 240
ccttcctgcc tcaggaggag tgtcagaact acgtgcgagt cctgatcgtc gccggccgga 300
aggtgttcat gtgtggaacc aatgcctttt cccccatgtg caccagcaga caggtgggga 360
acctcagccg gactattgag aagatcaatg gtgtggcccg ctgcccctat gacccacgcc 420
acaactccac agctgtcatc tcctcccagg gggagctcta tgcagccacg gtcatcgact 480
tctcaggtcg ggaccctgcc atctaccgca gcctgggcag tgggccaccg cttcgcactg 540
cccaatataa ctccaagtgg cttaatgagc caaacttcgt ggcagcctat gatattgggc 600
tgtttgcata cttcttcctg cgggagaacg cagtggagca cgactgtgga cgcaccgtgt 660
actctcgcgt ggcccgcgtg tgcaagaatg acgtgggggg ccgattcctg ctggaggaca 720
catggaccac attcatgaag gcccggctca actgctcccg cccgggcgag gtccccttct 780
actataacga gctgcagagt gccttccact tgccggagca ggacctcatc tatggagttt 840
tcacaaccaa cgtaaacagc attgcggctt ctgctgtctg cgccttcaac ctcagtgcta 900
tctcccaggc tttcaatggc ccatttcgct accaggagaa ccccagggct gcctggctcc 960
ccatagccaa ccccatcccc aatttccagt gtggcaccct gcctgagacc ggtcccaacg 1020
agaacctgac ggagcgcagc ctgcaggacg cgcagcgcct cttcctgatg agcgaggccg 1080
tgcagccggt gacacccgag ccctgtgtca cccaggacag cgtgcgcttc tcacacctcg 1140
tggtggacct ggtgcaggct aaagacacgc tctaccatgt actctacatt ggcaccgagt 1200
cgggcaccat cctgaaggcg ctgtccacgg cgagccgcag cctccacggc tgctacctgg 1260
13
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
aggagctgca cgtgctgccc cccgggcgcc gcgagcccct gcgcagcctg cgcatcctgc 1320
acagcgcccg cgcgctcttc gtggggctga gagacggcgt cctgcgggtc ccactggaga 1380
ggtgcgccgc ctaccgcagc cagggggcat gcctgggggc ccgggacccg tactgtggct 1440
gggacgggaa gcagcaacgt tgcagcacac tcgaggacag ctccaacatg agcctctgga 1500
cccagaacat caccgcctgt cctgtgcgga atgtgacacg ggatgggggc ttcggcccat 1560
ggtcaccatg gcaaccatgt gagcacttgg atggggacaa ctcaggctct tgcctgtgtc 1620
gagctcgatc ctgtgattcc cctcgacccc gctgtggggg ccttgactgc ctggggccag 1680
ccatccacat cgccaactgc tccaggaatg gggcgtggac cccgtggtca tcgtgggcgc 1740
tgtgcagcac gtcctgtggc atcggcttcc aggtccgcca gcgaagttgc agcaaccctg 1800
ctccccgcca cgggggccgc atctgcgtgg gcaagagccg ggaggaacgg ttctgtaatg 1860
agaacacgcc ttgcccggtg cccatcttct gggcttcctg gggctcctgg agcaagtgca 1920
gcagcaactg tggagggggc atgcagtcgc ggcgtcgggc ctgcgagaac ggcaactcct 1980
gcctgggctg cggcgtggag ttcaagacgt gcaaccccga gggctgcccc gaagtgcggc 2040
gcaacacccc ctggacgccg tggctgcccg tgaacgtgac gcagggcggg gcacggcagg 2100
agcagcggtt ccgcttcacc tgccgcgcgc cccttgcaga cccgcacggc ctgcagttcg 2160
gcaggagaag gaccgagacg aggacctgtc ccgcggacgg ctccggctcc tgcgacaccg 2220
acgccctggt ggaggacctc ctgcgcagcg ggagcacctc cccgcacacg gtgagcgggg 2280
gctgggccgc ctggggcccg tggtcgtcct gctcccggga ctgcgagctg ggcttccgcg 2340
tccgcaagag aacgtgcact aacccggagc cccgcaacgg gggcctgccc tgcgtgggcg 2400
atgctgccga gtaccaggac tgcaaccccc aggcttgccc agttcggggt gcttggtcct 2460
gctggacctc atggtctcca tgctcagctt cctgtggtgg gggtcactat caacgcaccc 2520
gttcctgcac cagccccgca ccctccccag gtgaggacat ctgtctcggg ctgcacacgg 2580
aggaggcact atgtgccaca caggcctgcc cagaaggctg gtcgccctgg tctgagtgga 2640
gtaagtgcac tgacgacgga gcccagagcc gaagccggca ctgtgaggag ctcctcccag 2700
ggtccagcgc ctgtgctgga aacagcagcc agagccgccc ctgcccctac agcgagattc 2760
ccgtcatcct gccagcctcc agcatggagg aggccaccgg ctgtgcaggg ttcaatctca 2820
tccacttggt ggccacgggc atctcctgct tcttgggctc tgggctcctg accctagcag 2880
tgtacctgtc ttgccagcac tgccagcgtc agtcccagga gtccacactg gtccatcctg 2940
ccacccccas ccatttgcac tacaagggcg gaggcacccc gaagaatgaa aagtacacac 3000
ccatggaatt caagaccctg aacaagaata acttgatccc tgatgacaga gccaacttct 3060
acccattgca gcagaccaat gtgtacacga ctacttacta cccaagcccc ctgaacaaac 3120
acagcttccg gcccgaggcc tcacctggac aacggtgctt ccccaacagc tgataccgcc 3180
gtcctgggga cttgggcttc ttgccttcat aaggcacaga gcagatggag atgggacagt 3240
ggagccagtt tggttttctc cctctgcact aggccaagaa cttgctgcct tgcctgtggg 3300
gggtcccatc cggcttcaga gagctctggc tggcattgac catgggggaa agggctggtt 3360
tcaggctgac atatggccgc aggtccagtt cagcccaggt ctctcatggt tatcttccaa 3420
cccactgtca cgctgacact atgctgccat gcctgggctg tggacctact gggcatttga 3480
ggaattggag aatggagatg gcaagagggc aggcttttaa gtttgggttg gagacaactt 3540
cctgtggccc ccacaagctg agtctggcct tctccagctg gccccaaaaa aggcctttgc 3600
tacatcctga ttatctctga aagtaatcaa tcaagtggct ccagtagctc tggattttct 3660
gccagggctg ggccattgtg gtgctgcccc agtatgacat gggaccaagg ccagcgcagg 3720
ttatccacct ctgcctggaa gtctatactc tacccagggc atccctctgg tcagaggcag 3780
tgagtactgg gaactggagg ctgacctgtg cttagaagtc ctttaatctg ggctggtaca 3840
ggcctcagcc ttgccctcaa tgcacgaaag gtggcccagg agagaggatc aatgccatag 3900
gaggcagaag tctggcctct gtgcctctat ggagactatc ttccagttgc tgctcaacag 3960
agttgttggc tgagacctgc ttgggagtct ctgctggccc ttcatctgtt caggaacaca 4020
cacacacaca cactcacaca cgcacacaca atcacaattt gctacagcaa csaaaaagac 4080
attgggctgt ggcattatta attaaagatg atatccagtc aaaaaaaaaa aaaaaaaaaa 4140
aaaa 4144
<210> 20
<211> 999
<212> PRT
<213> Homo sapiens
<400> 20
Met Thr Gln Trp Cys Glu Arg Glu Ile Ser Ser Ile Ala Pro Gly Glu
1 5 10 15
Leu Cys Cys Leu Leu Leu Ser Phe Leu Pro Gln Glu Glu Cys Gln Asn
14
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
20 25 30
Tyr Val Arg Val Leu Ile Val Ala Gly Arg Lys Val Phe Met Cys Gly
35 40 45
Thr Asn Ala Phe Ser Pro Met Cys Thr Ser Arg Gln Val Gly Asn Leu
50 55 60
Ser Arg Thr Ile Glu Lys Ile Asn Gly Val Ala Arg Cys Pro Tyr Asp
65 70 75 80
Pro Arg His Asn Ser Thr Ala Val Ile Ser Ser Gln Gly Glu Leu Tyr
85 90 95
Ala Ala Thr Val Ile Asp Phe Ser Gly Arg Asp Pro Ala~Ile Tyr Arg
100 105 110
Ser Leu Gly Ser Gly Pro Pro Leu Arg Thr Ala Gln Tyr Asn Ser Lys
115 120 125
Trp Leu Asn Glu Pro Asn Phe Val Ala Ala Tyr Asp Ile Gly Leu Phe
130 135 140
Ala Tyr Phe Phe Leu Arg Glu Asn Ala Val Glu His Asp Cys Gly Arg
145 150 155 160
Thr Val Tyr Ser Arg Val Ala Arg Val Cys Lys Asn Asp Val Gly Gly
165 170 175
Arg Phe Leu Leu Glu Asp Thr Trp Thr Thr Phe Met Lys Ala Arg Leu
180 185 190
Asn Cys Ser Arg Pro Gly Glu Val Pro Phe Tyr Tyr Asn Glu Leu Gln
195 200 205
Ser Ala Phe His Leu Pro Glu Gln Asp Leu Ile Tyr Gly Val Phe Thr
210 215 220
Thr Asn Val Asn Ser Ile Ala Ala Ser Ala Val Cys Ala Phe Asn Leu
225 230 235 240
Ser Ala Ile Ser Gln Ala Phe Asn Gly Pro Phe Arg Tyr Gln Glu Asn
245 250 255
Pro Arg Ala Ala Trp Leu Pro Ile Ala Asn Pro Ile Pro Asn Phe Gln
260 265 270
Cys Gly Thr Leu Pro Glu Thr Gly Pro Asn Glu Asn Leu Thr Glu Arg
275 280 285
Ser Leu Gln Asp Ala Gln Arg Leu Phe Leu Met Ser Glu Ala Val Gln
290 295 300
Pro Val Thr Pro Glu Pro Cys Val Thr Gln Asp Ser Val Arg Phe Ser
305 310 315 320
His Leu Val Val Asp Leu Val Gln Ala Lys Asp Thr Leu Tyr His Val
325 330 335
Leu Tyr Ile Gly Thr Glu Ser Gly Thr Ile Leu Lys Ala Leu Ser Thr
15
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
340 345 350
Ala Ser Arg Ser Leu His Gly Cys Tyr Leu Glu Glu Leu His Val Leu
355 360 365
Pro Pro Gly Arg Arg Glu Pro Leu Arg Ser Leu Arg Ile Leu His Ser
370 375 380
Ala Arg Ala Leu Phe Val Gly Leu Arg Asp Gly Val Leu Arg Val Pro
385 390 395 400
Leu Glu Arg Cys Ala Ala Tyr Arg Ser Gln Gly Ala Cys Leu Gly Ala
405 410 415
Arg Asp Pro Tyr Cys Gly Trp Asp Gly Lys Gln Gln Arg Cys Ser Thr
420 425 430
Leu Glu Asp Ser Ser Asn Met Ser Leu Trp Thr Gln Asn Ile Thr Ala
435 440 445
Cys Pro Val Arg Asn Val Thr Arg Asp Gly Gly Phe Gly Pro Trp Ser
450 455 460
Pro Trp Gln Pro Cys Glu His Leu Asp Gly Asp Asn Ser Gly Ser Cys
465 470 475 480
Leu Cys Arg Ala Arg Ser Cys Asp Ser Pro Arg Pro Arg Cys Gly Gly
485 490 495
Leu Asp Cys Leu Gly Pro Ala Ile His Ile Ala Asn Cys Ser Arg Asn
500 505 510
Gly Ala Trp Thr Pro Trp Ser Ser Trp Ala Leu Cys Ser Thr Ser Cys
515 520 525
Gly Ile Gly Phe Gln Val Arg Gln Arg Ser Cys Ser Asn Pro Ala Pro
530 535 540
Arg His Gly Gly Arg Ile Cys Val Gly Lys Ser Arg Glu Glu Arg Phe
545 550 555 560
Cys Asn Glu Asn Thr Pro Cys Pro Val Pro Ile Phe Trp Ala Ser Trp
565 570 575
Gly Ser Trp Ser Lys Cys Ser Ser Asn Cys Gly Gly Gly Met Gln Ser
580 585 590
Arg Arg Arg Ala Cys Glu Asn Gly Asn Ser Cys Leu Gly Cys Gly Val
595 600 605
Glu Phe Lys Thr Cys Asn Pro Glu Gly Cys Pro Glu Val Arg Arg Asn
610 615 620
Thr Pro Trp Thr Pro Trp Leu Pro Val Asn Val Thr Gln Gly Gly Ala
625 630 635 640
Arg Gln Glu Gln Arg Phe Arg Phe Thr Cys Arg Ala Pro Leu Ala Asp
645 650 655
Pro His Gly Leu Gln Phe Gly Arg Arg Arg Thr Glu Thr Arg Thr Cys
16
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
660 665 670
Pro Ala Asp Gly Ser Gly Ser Cys Asp Thr Asp Ala Leu Val Glu Asp
675 680 685
Leu Leu Arg Ser Gly Ser Thr Ser Pro His Thr Val Ser Gly Gly Trp
690 695 700
Ala Ala Trp Gly Pro Trp Ser Ser Cys Ser Arg Asp Cys Glu Leu Gly
705 710 715 720
Phe Arg Val Arg Lys Arg Thr Cys Thr Asn Pro Glu Pro Arg Asn Gly
725 730 735
Gly Leu Pro Cys Val Gly Asp Ala Ala Glu Tyr Gln Asp Cys Asn Pro
740 745 750
Gln Ala Cys Pro Val Arg Gly Ala Trp Ser Cys Trp Thr Ser Trp Ser
755 760 765
Pro Cys Ser Ala Ser Cys Gly Gly Gly His Tyr Gln Arg Thr Arg Ser
770 775 780
Cys Thr Ser Pro Ala Pro Ser Pro Gly Glu Asp Ile Cys Leu Gly Leu
785 790 795 B00
His Thr Glu Glu Ala Leu Cys Ala Thr Gln Ala Cys Pro Glu Gly Trp
805 810 815
Ser Pro Trp Ser Glu Trp Ser Lys Cys Thr Asp Asp Gly Ala Gln Ser
820 825 830
Arg Ser Arg His Cys Glu Glu Leu Leu Pro Gly Ser Ser Ala Cys Ala
835 840 845
Gly Asn Ser Ser Gln Ser Arg Pro Cys Pro Tyr Ser Glu Ile Pro Val
850 855 860
Ile Leu Pro Ala Ser Ser Met Glu Glu Ala Thr Gly Cys Ala Gly Phe
865 870 875 880
Asn Leu Ile His Leu Val Ala Thr Gly Ile Ser Cys Phe Leu Gly Ser
885 890 895
Gly Leu Leu Thr Leu Ala Val Tyr Leu Ser Cys Gln His Cys Gln Arg
900 905 910
Gln Ser Gln Glu Ser Thr Leu Val His Pro Ala Thr Pro Asn His Leu
915 920 925
His Tyr Lys Gly Gly Gly Thr Pro Lys Asn Glu Lys Tyr Thr Pro Met
930 935 940
Glu Phe Lys Thr Leu Asn Lys Asn Asn Leu Ile Pro Asp Asp Arg Ala
945 950 955 960
Asn Phe Tyr Pro Leu Gln Gln Thr Asn Val Tyr Thr Thr Thr Tyr Tyr
965 970 975
Pro Ser Pro Leu Asn Lys His Ser Phe Arg Pro Glu Ala Ser Pro Gly
17
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
980 985 990
Gln Arg Cys Phe Pro Asn Ser
995
<210> 21
<211> 2820
<212> DNA
<213> Homo Sapiens
<400> 21
agaatgggag ctgtcagtta tcattcagga caaaggcaat cctcagctac ataccaaagt 60
ccttctgaag tgcatgatct ttgaatatgc agagtcggtg acaagtacag caatgacttc 120
agtaagccag gcatccttgg atgtctccat gataataatt atttccttag gagcaatttg 180
tgcagtgttg ctggttatta tggtgctatt tgcaactagg tgtaaccgcg agaagaaaga 240
cactagatcc tataactgca gggtggccga atcaacttac cagcaccacc caaaaaggcc 300
atcccggcag attcacaaag gggacatcac attggtgcct accataaatg gcactctgcc 360
catcagatct catcacagat cgtctccatc ttcatctcct accttagaaa gagggcagat 420
gggcagccgg cagagtcaca acagtcacca gtcactcaac agtttggtga caatctcatc 480
aaaccacgtg ccagagaatt tctcattaga actcacccac gccactcctg ctgttgaggt 540
ctctcagctt ctttcaatgc ttcaccaggg gcaatatcag ccaagaccaa gttttcgagg 600
aaacaaatat tccaggagct acagatatgc ccttcaagac atggacaaat ttagcttgaa 660
agacagtggc cgtggtgaca gtgaggcagg agacagtgat tatgatttgg ggcgagattc 720
tccaatagat aggctgttgg gtgaaggatt cagcgacctg tttctcacag atggaagaat 780
tccagcagct atgagactct gcacggagga gtgcagggtc ctgggacact ctgaccagtg 840
ctggatgcca ccactgccct caccgtcttc tgattatagg agtaacatgt tcattccagg 900
ggaagaattc ccaacgcaac cccagcagca gcatccacat cagagtcttg aggatgacgc 960
tcagcctgca gattccggtg aaaagaagaa gagtttttcc acctttggaa aggactcccc 1020
aaacgatgag gacactgggg ataccagcac atcatctctg ctctcggaaa tgagcagtgt 1080
gttccagcgt ctcttaccgc cttccctgga cacctattct gaatgcagtg aggtggatcg 1140
gtccaactcc ctggagcgca ggaagggacc cttgccagcc aaaactgtgg gttacccaca 1200
gggggtagcg gcatgggcag ccagtacgca ttttcaaaat cccaccacca actgtgggcc 1260
gccacttgga actcactcca gtgtgcagcc ttcttcaaaa tggctgccag ccatggagga 1320
gatccctgaa aattatgagg aagatgattt tgacaatgtg ctcaaccacc tcaatgatgg 1380
gaaacacgaa ctcatggatg ccagtgaact ggtggcagag attaacaaac tgcttcaaga 1440
tgtccgccag agctaggaga ttttagcgaa gcatttttgt ttccatgtat atggaaatag 1500
ggaacaacaa caacaacaaa asaccctgaa agaactggca ttgccaaata gttgcattta 1560
tcataaatgt gtctgtgtat attgaatatt aaatactgta ttttcgtatg tacacaatgc 1620
aagtgtgatt attttaatct gtattttaaa aatacatttg taccttatat ttatgtgtaa 1680
tttaacaaac aaattttatt tttttactcc catgacagac atgtttttcc tagtcgtgta 1740
gaaactagcc actgttcaaa tctgatacac tattcaacca caaagtgtaa aggcactgct 1800
tagattagtt ttgttgggga agaattatta tgttgtatga acaaccccac tgaagcatta 1860
tacaattctt aattccatta agtgatccca ctttttttca ataacttttt agaaattaag 1920
aatcattaaa attgttaagc tattttattg ttattttctc tactttctac tagccccaat 1980
agttgaactc ttataggaaa atcgaaagat aaagtgaaag tttatttcag gactgagaaa 2040
tatcttgaag gttatttatt agatgactat ctcaaatgaa ctttttatag acsatgatga 2100
aaacagaatt aaagtcaatg tttcctgact cccaggcccc tactattcca ggccatcaca 2160
ctggcctgtt ccggagaata tttctctcac aatattatta tctacttata attatggtaa 2220
acaataaatt ttattccatc cttgtagtat gaaacatgct ccaaggaaat ggaatctgtc 2280
ctttaaatgg ataacagtat gtgttctaat ggcataaaat attactggat aaaaacagtt 2340
gtgtcagtgt ctctcctaag gtagtaaata taattgactt attctgaacc cattctattt 2400
tgaatctccc ctttcctctc acaatacttg aacattttaa tcttttggaa tattgtcttt 2460
ctttgttata actattcatt tttagctttt gtctccagtg catgatctca tatttttgct 2520
tttattttta gtataagaac atttataaaa tcatattttt gttactgcaa ttgttttatt 2580
tgttgtgtgg caaatgagaa atcctttatt~tattgtgctg tgatctctct gtgtggaatg 2640
ccttggtgag agagatgctt attatgacta ttatcatttc tgaccaagct tctattaatg 2700
ttatttctaa taatacacta tcttgattgt actctccaga aaatttttct gtcagtgaaa 2760
ataaaagaaa aattaaagta aagctaagga actgtcaaaa aaaaaaaaaa aaaaaaaaaa 2820
Ig
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
<210> 22
<211> 460
<212> PRT
<213> Homo sapiens
<400> 22
Met Ile Phe Glu Tyr Ala Glu Ser Val Thr Ser Thr Ala Met Thr Ser
1 5 10 15
Val Ser Gln Ala Ser Leu Asp Val Ser Met Ile Ile Ile Ile Ser Leu
20 25 30
Gly Ala Ile Cys Ala Val Leu Leu Val Ile Met Val Leu Phe Ala Thr
35 40 45
Arg Cys Asn Arg Glu Lys Lys Asp Thr Arg Ser Tyr Asn Cys Arg Val
50 55 60
Ala Glu Ser Thr Tyr Gln His His Pro Lys Arg Pro Ser Arg Gln Ile
65 70 75 80
His Lys Gly Asp Ile Thr Leu Val Pro Thr Ile Asn Gly Thr Leu Pro
85 90 95
Ile Arg Ser His His Arg Ser Ser Pro Ser Ser Ser Pro Thr Leu Glu
100 105 110
Arg Gly Gln Met Gly Ser Arg Gln Ser His Asn Ser His Gln Ser Leu
115 120 125
Asn Ser Leu Val Thr Ile Ser Ser Asn His Val Pro Glu Asn Phe Ser
130 135 140
Leu Glu Leu Thr His Ala Thr Pro Ala Val Glu Val Ser Gln Leu Leu
145 150 155 160
Ser Met Leu His Gln Gly Gln Tyr Gln Pro Arg Pro Ser Phe Arg Gly
165 170 175
Asn Lys Tyr Ser Arg Ser Tyr Arg Tyr Ala Leu Gln Asp Met Asp Lys
180 185 190
Phe Ser Leu Lys Asp Ser Gly Arg Gly Asp Ser Glu Ala Gly Asp Ser
195 200 205
Asp Tyr Asp Leu Gly Arg Asp Ser Pro Ile Asp Arg Leu Leu Gly Glu
210 215 220
Gly Phe Ser Asp Leu Phe Leu Thr Asp Gly Arg Ile Pro Ala Ala Met
225 230 235 240
Arg Leu Cys Thr Glu Glu Cys Arg Val Leu Gly His Ser Asp Gln Cys
245 250 255
Trp Met Pro Pro Leu Pro Ser Pro Ser Ser Asp Tyr Arg Ser Asn Met
260 265 270
Phe Ile Pro Gly Glu Glu Phe Pro Thr Gln Pro Gln Gln Gln His Pro
275 280 285
19
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
His Gln Ser Leu Glu Asp Asp Ala Gln Pro Ala Asp Ser Gly Glu Lys
290 295 300
Lys Lys Ser Phe Ser Thr Phe Gly Lys Asp Ser Pro Asn Asp Glu Asp
305 310 315 320
Thr Gly Asp Thr Ser Thr Ser Ser Leu Leu Ser Glu Met Ser Ser Val
325 330 335
Phe Gln Arg Leu Leu Pro Pro Ser Leu Asp Thr Tyr Ser Glu Cys Ser
340 345 350
Glu Val Asp Arg Ser Asn Ser Leu Glu Arg Arg Lys Gly Pro Leu Pro
355 360 365
Ala Lys Thr Val Gly Tyr Pro Gln Gly Val Ala Ala Trp Ala Ala Ser
370 375 380
Thr His Phe Gln Asn Pro Thr Thr Asn Cys Gly Pro Pro Leu Gly Thr
385 390 395 400
His Ser Ser Val Gln Pro Ser Ser Lys Trp Leu Pro Ala Met G1u Glu
405 410 415
Ile Pro Glu Asn Tyr Glu Glu Asp Asp Phe Asp Asn Val Leu Asn His
420 425 430
Leu Asn Asp Gly Lys His Glu Leu Met Asp Ala Ser Glu Leu Val Ala
435 440 445
Glu Ile Asn Lys Leu Leu Gln Asp Val Arg Gln Ser
450 455 460
<210> 23
<211> 1219
<212> DNA
<213> Homo Sapiens
<400> 23
gtggccattc ctcggtacag actagtcctg gtccttgggt gtgggcagtg ggggaggaac 60
caactggtcg aggtttcaga gccaaacctt gcctttggtt ggtgagtcct tgccccccag 120
gcctgcgctc cacgatgccc ttcacccttg gcaatctcag ggccatcctg ggtagtaacc 180
ccactcctct ctgctcccgc ccgcacctgt ggctctcact ctgggctcaa cccctgcaac 240
cctccaggag cccgacagca gccagctgcc tgcactgtcg cctccgtaag ctccaacttc 300
cagacccaga agtccctctg cttccctctg ttggaaaaag cctaaaagaa ttagcttcca 360
gattcctcta gcccctgctc cattcccacc cagtccttct gaagaggaat gagcaataca 420
tctgagctgg atttctctct agtcctttct ccagacaaat ccttcttaaa gcaaaagtcc 480
tggctgagca cctgtccttg gggaccgatc tgccgtgtga ccaggggaag aaagttcccg 540
aaagcctgtt ccaccaattc tgcttctgtg ttgtgaatcc agtctgcttt ccattagaaa 600
accgcttcgg cacttatggt cactttaata aatctagtat gtaaaaaaag aaagaaagaa 660
aagaaacaga aaaacgtgca ggcaaatgta aaatacaatg ctctctgtaa gataaatatt 720
tgcctttttt tctaaaaggt gtacgtattc tgtatgtgaa attgtctgta gaaagtttct 780
atgttcttaa atggcaatac attccaaaaa ttgtactgta gatatgtaca gcaaccgcac 840
tgggatgggg tagttttgcc tgtaatttta tttaaactcc agtttccaca cttgcatctt 900
gcaatgttgg tatggtatat atcagtgcaa aagaaaaaac aaaacaaaaa caaaaaaaaa 960
aacaaaaatc cacgcaggtc taaagcacag agtctgacgt acaaaaggaa aaatgctcag 1020
tattgaagtg tgtgaccttt gttgtaaatt acatctgtac tgtgaatgag aagtttttac 1080
aagtataata attgccttta ttacagctct ggctgagtgt tcagcctgag gatatttttt 1140
aaaaaaaaaa gaattagcat gttggaataa atttgaaaat cccaaaaaaa aaaaaaaaaa 1200
20
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
aaaaaaaaaa aaaaaaaaa 1219
<210> 24
<211> 78
<212> PRT
<213> Homo Sapiens
<400> 24
Met Pro Phe Thr Leu Gly Asn Leu Arg Ala Ile Leu Gly Ser Asn Pro
1 5 10 15
Thr Pro Leu Cys Ser Arg Pro His Leu Trp Leu Ser Leu Trp Ala Gln
20 25 30
Pro Leu Gln Pro Ser Arg Ser Pro Thr Ala Ala Ser Cys Leu His Cys
35 40 45
Arg Leu Arg Lys Leu Gln Leu Pro Asp Pro Glu Val Pro Leu Leu Pro
50 55 60
Ser Val Gly Lys Ser Leu Lys Glu Leu Ala Ser Arg Phe Leu
65 70 75
<210> 25
<211> 2411
<212> DNA
<213> Homo Sapiens
<400> 25
ggccagaagg cggggagcca gaggcgccag gaccctagcg tggcgctcca gcaccccaga 60
ccgtggcggc gcctcgcctt agggaagagc aagggaagaa ctttatttga accgcgaaca 120
ttttttggtc actgagatcg agtctcccag tgctttggct tcccgcctct ttatcgtggg 180
tttgatccct gagctgctct cctttcccga acctcccggg gtgcagccta gagccctccc 240
gcgcggctga ctccagagta gaggaaggga ggcggcctcc ggctggtccc ccgaagccct 300
cgctgccccg cagatgcgga tggccagcca gtagcgggcg gtggccccgc gtcccgggag 360
cgcacagcaa tgcaggcgct tsacattacc ccggagcagt tctctcggct gctgcgggac 420
cacaacctga cgcgggagca gttcatcgct ctgtaccggc tgcgaccgct cgtctacacc 480
ccagagctgc cgggacgcgc caagctggcc ctcgtgctca ccggcgtgct catcttcgcc 540
ctggcgctct ttggcaatgc tctggtgttc tacgtggtga cccgcagcaa ggccatgcgc 600
accgtcacca acatctttat ctgctccttg gcgctcagtg acctgctcat caccttcttc 660
tgcattcccg tcaccatgct ccagaacatt tccgacaact ggctgggggg tgctttcatt 720
tgcaagatgg tgccatttgt ccagtctacc gctgttgtga cagaaatcct cactatgacc 780
tgcattgctg tggaaaggca ccagggactt gtgcatcctt ttaaaatgaa gtggcaatac 840
accaaccgaa gggctttcac aatgctaggt gtggtctggc tggtggcagt catcgtagga 900
tcacccatgt ggcacgtgca acaacttgag atcaaatatg acttcctata tgaaaaggaa 960
cacatctgct gcttagaaga gtggaccagc cctgtgcacc agaagatcta caccaccttc 1020
atccttgtca tcctcttcct cctgcctctt atggtgatgc ttattctgta cagtaaaatt 1080
ggttatgaac tttggataaa gaaaagagtt ggggatggtt cagtgcttcg aactattcat 1140
ggaaaagaaa tgtccaaaat agccaggaag aagaaacgag ctgtcattat gatggtgaca 1200
gtggtggctc tctttgctgt gtgctgggca ccattccatg ttgtccatat gatgattgaa 1260
tacagtaatt ttgaaaagga atatgatgat gtcacaatca agatgatttt tgctatcgtg 1320
caaattattg gattttccaa ctccatctgt aatcccattg tctatgcatt tatgaatgaa 1380
aacttcaaaa aaaatgtttt gtctgcagtt tgttattgca tagtaaataa aaccttctct 1440
ccagcacaaa ggcatggsaa ttcaggaatt acaatgatgc ggaagaaagc aaagttttcc 1500
ctcagagaga atccagtgga ggaaaccaaa ggagaagcat tcagtgatgg caacattgaa 1560
gtcaaattgt gtgaacagac agaggagaag aaaaagctca aacgacatct tgctctcttt 1620
aggtctgaac tggctgagaa ttctccttta gacagtgggc attaattata acaatatctt 1680
cataattaat gcccttcaga ttgtaaccca aagagaaaat tattttgagc aaaggtcaaa 1740
tactcttttt attcttaaga tgatgacaag aagaaaacaa atcatgtttc cattaaaaaa 1800
21
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
tgacacgaggctagtccaag tgcagtgatg attgatcacaatcatttaac1860
tttacaacca
agatttctgtgttccttctc attcccactg ctagccttaaaaaagcaaca1920
cttcacttga
tggaaggccaggcacggtgg ctcatgcctg actttgggaggcctagacgg1980
taatcccagc
gcggatcacgaggtcaggag atcaaaacca cacggtgaaaccccatctct2040
tcctggctaa
gctaaaaatacaaaaattag ccgggcgtgg ctgtagtcccagctacttgg2100
tggcgggcac
gagcctcaggcgggagaatg gtgtgaaccc gcttgcagtgatccgagatc2160
gggaggcgga
atgccactgcactccagcct gggcgaaaga ccgtctcaaaaaaaattttt2220
gcgagactcc
ttgaaaaattcgtaaaccat acttttaaga ggatttttaaaaatcttgta2280
ttatttcagt
cagaaatcagggttcttagc tagcagtttt agtcactgtaatgtgactat2340
tctcccacgc
gtattgctagattgaataag aaaataaaat tccttgaaaaaaaaaaaaaa2400
aatatcttct
aaaaaaaaaaa 2411
<210>
26
<211>
431
<212>
PRT
<213> sapiens
Homo
<400>
26
Met Gln Leu Asn Ile Thr Pro Glu Ser Arg Leu Arg
Ala Gln Phe Leu
1 5 10 15
Asp His Leu Thr Arg Glu Gln Phe Leu Tyr Leu Arg
Asn Ile Ala Arg
20 25 30
Pro Leu Tyr Thr Pro Glu Leu Pro Ala Lys Ala Leu
Val Gly Arg Leu
35 40 45
Val Leu Gly Val Leu Ile Phe Ala Leu Phe Asn Ala
Thr Leu Ala Gly
50 55 60
Leu Val Tyr Val Val Thr Arg Ser Met Arg Val Thr
Phe Lys Ala Thr
65 70 75 80
Asn Ile Ile Cys Ser Leu Ala Leu Leu Leu Thr Phe
Phe Ser Asp Iie
85 90 95
Phe Cys Pro Val Thr Met Leu Gln Ser Asp Trp Leu
Ile Asn Zle Asn
100 105 110
Gly Gly Phe Ile Cys Lys Met Val Val Gln Thr Ala
Ala Pro Phe Ser
115 120 125
Val Val Glu Ile Leu Thr Met Thr Ala Val Arg His
Thr Cys Ile Glu
130 135 140
Gln GIy Val His Pro Phe Lys Met Gln Tyr Asn Arg
Leu Lys Trp Thr
145 150 155 160
Arg Ala Thr Met Leu Gly Val Val Val Ala Ile Val
Phe Trp Leu Val
165 170 . 175
Gly Ser Met Trp His Val Gln Gln Ile Lys Asp Phe
Pro Leu Glu Tyr
lao ls5 190
Leu Tyr Lys Glu His Ile Cys Cys Glu Trp Ser Pro
Glu Leu Glu Thr
195 200 205
Val His Lys Ile Tyr Thr Thr Phe Val Ile Phe Leu
Gln Ile Leu Leu
210 215 220
22
CA 02340616 2001-02-23
WO 00/11015 PCTNS99/19351
Leu Pro Leu Met Val Met Leu Ile Leu Tyr Ser Lys Ile Gly Tyr Glu
225 230 235 240
Leu Trp Ile Lys Lys Arg Val Gly Asp Gly Ser Val Leu Arg Thr IIe
245 250 255
His Gly Lys Glu Met Ser Lys Ile Ala Arg Lys Lys Lys Arg Ala Val
260 265 270
Ile Met Met Val Thr Val Val Ala Leu Phe Ala Val Cys Trp Ala Pro
275 280 285
Phe His Val Val His Met Met Ile Glu Tyr Ser Asn Phe Glu Lys Glu
290 295 300
Tyr Asp Asp Val Thr Ile Lys Met Ile Phe Ala Ile Val Gln Ile Ile
305 310 315 320
Gly Phe Ser Asn Ser Ile Cys Asn Pro Ile Val Tyr Ala Phe Met Asn
325 330 335
Glu Asn Phe Lys Lys Asn Val Leu Ser Ala Val Cys Tyr Cys Ile Val
340 345 350
Asn Lys Thr Phe Ser Pro Ala Gln Arg His Gly Asn Ser Gly Ile Thr
355 360 365
Met Met Arg Lys Lys Ala Lys Phe Ser Leu Arg Glu Asn Pro Val Glu
370 375 380
Glu Thr Lys Gly Glu Ala Phe Ser Asp Gly Asn Ile Glu Val Lys Leu
385 390 395 400
Cys Glu Gln Thr Glu Glu Lys Lys Lys Leu Lys Arg His Leu Ala Leu
405 410 415
Phe Arg Ser Glu Leu Ala Glu Asn Ser Pro Leu Asp Ser Gly His
420 425 430
<210> 27
<211> 1995
<212> DNA
<213> Homo sapiens
<400> 27
atcatgccac tcatttcaga acttgagcaa aacagggcag tcaggatctg atgtctttct 60
ggtctcccta agaaaactaa gctcttgagg gacagccctt ggcaatgctt tcctatctgc 120
tgagcatggt gaccttcctt aggacttcca gagttcagtt ccttctggca gagaggtttt 180
ctttctccat gccatatgga tgtgactcaa atgaggggtc ccacagcttt tcctggctac 240
cacttgctgt gaccttatac atgttggggt ttgctcttaa agaggagagc aggaagaaag 300
gttggtttca gaaaccaaga gggtcggcag tggacgcgta cattttgtca cggagtccac 360
agagctgagc ttttgagcag actctgagaa gtatcattgc ttgtgttgaa agaatacaac 420
aggatttaag tttctcttta aaaattgcac tgaagaaagg ccgggcgcgg tggctccccc 480
tgtaatccca gcgctttggg aggccgaggc ggggggatca cgaggtcaag agatcgagac 540
catcctggcc aacatggtga aaccccgtct ctaataaaaa tacaaaaatt agccgggcat 600
ggtgacgtgc acctgtagtc ccagctacta gataggctga ggcaggagaa ttgcttgaat 660
ccgggaggcg gaggttgcag tgagccgaga tcgtgccact gaactccaac ctgccaatag 720
agcgagactc cgtctcaaaa aaaaaaaaaa aaaagaaaga aatagcattg aagaaaatac 780
cgcacatcag aggaaagctt attttctgca tggtgtcttt tcaaagatag aatatttgaa 840
23
CA 02340616 2001-02-23
WO 00/11015 PC'TNS99/19351
gcatgttttc tagcgattgt gtgaatgagg gtgagctggc tgaggcatcg ctcaagctgg 900
ggggtggtgt gtaagaagca cgtggagcca caagaggcac ctcctatagt cagctaaggg 960
cttccctttc tgcgcccagc ttttgggtga agggtgattt ctactagaca catctgtgct 1020
tcagtcatag atgttaatag aggaagcagt tttcctgctg cagattcctg aatagagttg 1080
ctgaaagagt ctacttctgg actcgggaag ttgaaggcca gtctgtgtag aaaggctgag 1140
gcaacgggga aagacctgac agctagttac atacgctctg acatagtact cccatgatgg 1200
cttccagtga cacatgtgct gatagaattc taaacctctg gaatttccct gctggcgact 1260
tctatggccg ttgactgtac agggtaacct gatgccagat gctatgggcg tgatgagaac 1320
tagagcattg cagcatggag gaaactgtga ggcaccagat cctgtgcttc tgcaggccat 1380
tttctgaaaa cccctgttag gaaggttgga tttggcgtga cttgcttgag caagagtcct 1440
ggggagagat tttgaggttt aatttaacgg tatatccaga gctaacagtg actcaactcg 1500
tctagttctg caagtcagat gtatacttag agtctctctg tgaagggttt gggtctgagc 1560
tgtatagtat gtcaaactgc cagtaagcca gcccctcacc ctctgataga tattccttta 1620
atgcaccaga cttcatgttt gataaatgat taatggttga aattgtttct cttcttttgt 1680
gttttcccag ttaatagatg gtcactgttt ccacaatgtt ttatactttc agctttttgt 1740
aacttaacta taattactta attttatttt tttaaagctt gttgtggtct aatgagaagt 1800
atttttcagt gcataatgtt tttctgagct tctgtaaatg ccatcccaat gtggtttggt 1860
tttgttgaac agaaaccaaa ataaatttca aaatgttaaa aaaaaaaaaa aaaaaaaaaa 1920
aaaaaaaaaa aaaaaaaaaa aaaaa 1945
<210> 28
<211> 87
<212> PRT
<213> Homo Sapiens
<400> 28
Met Leu Ser Tyr Leu Leu Ser Met Val Thr Phe Leu Arg Thr Ser Arg
1 5 10 15
Val Gln Phe Leu Leu Ala Glu Arg Phe Ser Phe Ser Met Pro Tyr Gly
20 25 30
Cys Asp Ser Asn Glu Gly Sex His Ser Phe Ser Trp Leu Pro Leu Ala
35 40 45
Val Thr Leu Tyr Met Leu Gly Phe Ala Leu Lys Glu Glu Ser Arg Lys
50 55 60
Lys Gly Trp Phe Gln Lys Pro Arg Gly Ser Ala Val Asp Ala Tyr Ile
65 70 75 80
Leu Ser Arg Ser Pro Gln Ser
85
<210> 29
<211> 2184
<212> DNA
<213> Homo Sapiens
<400> 29
gggcgccctc tggggctccg agcccggcgg gaccatgttc accagcaccg gctccagtgg 60
gctctacaag gcgcctctgt cgaagagcct tctgctggtc cccagtgccc tctccctcct 120
gctcgccctc ctcctgcctc actgccagaa gctctttgtg tatgaccttc acgcagtcaa 180
gaacgacttc cagatttgga ggttgatatg tggaagaata atttgccttg atttgaaaga 240
tactttttgc agtagtctgc ttatttataa ttttaggata tttgaaagaa gatatggaag 300
cagaaaattt gcatcctttt tgctgggttc ctgggttttg tcagccttat ttgactttct 360
cctcattgaa gctatgcagt atttctttgg catcactgca gctagtaatt tgccttctgg 420
attcctggca cctgtgtttg ctctgtttgt accattttac tgctccatac caagagtcca 480
agtggcacaa attctgggtc cgttgtccat cacaaacaag acattgattt atatattggg 540
24
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
actgcagctt ttcacctctg gttcctacat ctggattgta gccataagtg gacttatgtc 600
cggtctgtgc tacgacagca aaatgttcca ggtgcatcag gtgctctgca tccccagctg 660
gatggcaaaa ttcttttctt ggacacttga acccatcttc tcttcttcag aacccaccag 720
cgaagccaga attgggatgg gagccacgct ggacatccag agacagcaga gaatggagct 780
gctggaccgg cagctgatgt tctctcagtt tgcacaaggg aggcgacaga gacagcagca 840
gggaggaatg atcaattgga atcgtctttt tcctccttta cgtcagcgac aaaacgtaaa 900
ctatcagggc ggtcggcagt ctgagccagc agcgccccct ctagaagttt ctgaggaaca 960
ggtcgcccgg ctcatggaga tgggattttc cagaggtgat gctttggaag ccctgagagc 1020
ttcaaacaat gacctcaatg tcgccaccaa cttcctgctg cagcactgat agtcccaggc 1080
caacactggg accggaccgg cagccgagtg acagtgcgtg gtccccacca tcagatcagc 1140
ccggggaccg agcatctctg gtgctgatgt tcttgtggga agagggaggt tccaccgcac 1200
ccctgccctc aaccgcaaga ctgttgccgt tttagtgtgg agataagttt gccattacat 1260
tagcatgtat tttctatcta tatttttatt gggcattttc cctaggttgg agagtcagca 1320
ctcgttttga atgtgtttaa aatgcattaa aatggaagat ttctgcaggc agttgaatgg 1380
cactccagat ggggaattgc tgtaaccctc ttactgtaac atgtcatctc ctgcgtcgtg 1440
atggggagag ggtaatgtta cttcacaaag gacatgtcag atccttcttc atggactttt 1500
ttagttactg ttttttctct caaacttgtt ttcgaatctc ctgggagtga gggagaaaca 1560
gggagctgaa tcctccccca agctgttcca ggccagagga ctctgcagta gcttctccta 1620
catctagtaa caaagaatgg tgataaccat gcactggttc aaggttctgg agttctccat 1680
gaaacttggg ttaattttgc tcagagtatc cagagttagc cactaggctg cgggtgaaat 1740
gggatggaga agaacaacag caggcttcct ggagccacat gggctgacta gggcactctg 1800
tggctggcat ggcatgggct cagcccagga agaggagaaa cgatcccttg cctgcccctc 1860
cctgtggcag ggctaactgc ctggccctcc tggctcgcag ccagccagcc ccctggcagc 1920
aggttctcct cagggcttgg gtcttcaacc tgtggcgaca ggaggcaggg cagactgtgg 1980
aggacaggat gcaggtcagg gagagggaag gcaggggtgg accgccatga gcatgaaaag 2040
acccgaagca agttgactct tgcaatgtgc aactgttatg ttctgcaaaa tgagcaacga 2100
tgtatcaaat tgatgcaaat ttagatgttg atacttacaa taaagttttt aatgtgtttt 2160
aaaaaaaaaa aaaaaaaaaa aaaa 2184
<210> 30
<211> 344
<212> PRT
<213> Homo Sapiens
<400> 30
Met Phe Thr Ser Thr Gly Ser Ser Gly Leu Tyr Lys Ala Pro Leu Ser
1 5 10 15
Lys Ser Leu Leu Leu Val Pro Ser Ala Leu Ser Leu Leu Leu Ala Leu
20 25 30
Leu Leu Pro His Cys Gln Lys Leu Phe Val Tyr Asp Leu His Ala Val
35 40 45
Lys Asn Asp Phe Gln Ile Trp Arg Leu Ile Cys Gly Arg Ile Ile Cys
50 55 60
Leu Asp Leu Lys Asp Thr Phe Cys Ser Ser Leu Leu Ile Tyr Asn Phe
65 70 75 80
Arg Ile Phe Glu Arg Arg Tyr Gly Ser Arg Lys Phe Ala Ser Phe Leu
85 90 95
Leu Gly Ser Trp Val Leu Ser Ala Leu Phe Asp Phe Leu Leu Ile Glu
100 105 110
Ala Met Gln Tyr Phe Phe Gly Ile Thr Ala Ala Ser Asn Leu Pro Ser
115 120 125
Gly Phe Leu Ala Pro Val Phe Ala Leu Phe Val Pro Phe Tyr Cys Ser
CA 02340616 2001-02-23
WO 00/11015 PCT/US99119351
130 135 140
Ile Pro Arg Val Gln Val Ala Gln Ile Leu Gly Pro Leu Ser Ile Thr
145 150 155 160
Asn Lys Thr Leu Ile Tyr Ile Leu Gly Leu Gln Leu Phe Thr Ser Gly
165 170 175
Ser Tyr Ile Trp Ile Val Ala Ile Ser Gly Leu Met Ser Gly Leu Cys
180 185 190
Tyr Asp Ser Lys Met Phe Gln Val His Gln Val Leu Cys Ile Pro Ser
195 200 205
Trp Met Ala Lys Phe Phe Ser Trp Thr Leu Glu Pro Ile Phe Ser Ser
210 215 220
Ser Glu Pro Thr Ser Glu Ala Arg Ile Gly Met Gly Ala Thr Leu Asp
225 230 235 240
Ile Gln Arg Gln Gln Arg Met Glu Leu Leu Asp Arg Gln Leu Met Phe
245 250 255
Ser Gln Phe Ala Gln Gly Arg Arg Gln Arg Gln Gln Gln Gly Gly Met
260 265 270
Ile Asn Trp Asn Arg Leu Phe Pro Pro Leu Arg Gln Arg Gln Asn Val
27s 280 2as
Asn Tyr Gln Gly Gly Arg Gln Ser Glu Pro Ala Ala Pro Pro Leu Glu
290 295 300
Val Ser Glu Glu Gln Val Ala Arg Leu Met Glu Met Gly Phe Ser Arg
305 310 315 320
Gly Asp Ala Leu Glu Ala Leu Arg Ala Ser Asn Asn Asp Leu Asn Val
325 330 335
Ala Thr Asn Phe Leu Leu Gln His
390
<210> 31
<211> 2880
<212> DNA
<213> Homo sapiens
<400> 31
ccggcgtccg ggcgcgctgg agaggacgcg aggagccatg aggcgccagc ctgcgaaggt 60
ggcggcgctg ctgctcgggc tgctcttgga gtgcacagaa gccaaaaagc attgctggta 120
tttcgaagga ctctatccaa cctattatat atgccgctcc tacgaggact gctgtggctc 180
caggtgctgt gtgcgggccc tctccataca gaggctgtgg tacttctggt tccttctgat 240
gatgggcgtg cttttctgct gcggagccgg cttcttcatc cggaggcgca tgtacccccc 300
gccgctgatc gaggagccag ccttcaatgt gtcctacacc aggcagcccc caaatcccgg 360
cccaggagcc cagcagccgg ggccgcccta ttacaccgac ccaggaggac cggggatgaa 420
ccctgtcggg aattccatgg caatggcttt ccaggtccca cccaactcac cccaggggag 480
tgtggcctgc ccgccccctc cagcctactg caacacgcct ccgcccccgt acgaacaggt 540
agtgaaggcc aagtagtggg gtgcccacgt gcaagaggag agacaggaga gggcctttcc 600
ctggcctttc tgtcttcgtt gatgttcact tccaggaacg gtctcgtggg ctgctaaggg 660
cagttcctct gatatcctca cagcaagcac agctctcttt caggctttcc atggagtaca 720
26
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
atatatgaac tcacactttg tctcctctgt tgcttctgtt tctgacgcag tctgtgctct 780
cacatggtag tgtggtgaca gtccccgagg gctgacgtcc ttacggtggc gtgaccagat 840
ctacaggaga gagactgaga ggaagaaggc agtgctggag gtgcaggtgg catgtagagg 900
ggccaggccg agcatcccag gcaagcatcc ttctgcccgg gtattaatag gaagccccat 960
gccgggcggc tcagccgatg aagcagcagc cgactgagct gagcccagca ggtcatctgc 1020
tccagcctgt cctctcgtca gccttcctct tccagaagct gttggagaga cattcaggag 1080
agagcaagcc ccttgtcatg tttctgtctc tgttcatatc ctaaagatag acttctcctg 1140
caccgccagg gaagggtagc acgtgcagct ctcaccgcag gatggggcct agaatcaggc 1200
ttgccttgga ggcctgacag tgatctgaca tccactaagc aaatttattt aaattcatgg 1260
gaaatcactt cctgccccaa actgagacat tgcattttgt gagctcttgg tctgatttgg 1320
agaaaggact gttacccatt tttttggtgt gtttatggaa gtgcatgtag agcgtcctgc 1380
cctttgaaat cagactgggt gtgtgtcttc cctggacatc actgcctctc cagggcattc 1440
tcaggcccgg gggtctcctt ccctcaggca gctccagtgg tgggttctga agggtgcttt 1500
caaaacgggg cacatctggc tgggaagtca catggactct tccagggaga gagaccagct 1560
gaggcgtctc tctctgaggt tgtgttgggt ctaagcgggt gtgtgctggg ctccaaggag 1620
gaggagcttg ctgggaaaag acaggagaag tactgactca actgcactga ccatgttgtc 1680
ataattagaa taaagaagaa gtggtcggaa atgcacattc ctggatagga atcacagctc 1740
accccaggat ctcacaggta gtctcctgag tagttgacgg ctagcgggga gctagttccg 1800
ccgcatagtt atagtgttga tgtgtgaacg ctgacctgtc ctgtgtgcta agagctatgc 1860
agcttagctg aggcgcctag attactagat gtgctgtatc acggggaatg aggtgggggt 1920
gcttattttt taatgaacta atcagagcct cttgagaaat tgttactcat tgaactggag 1980
catcaagaca tctcatggaa gtggatacgg agtgatttgg tgtccatgct tttcactctg 2040
aggacattta atcggagaac ctcctgggga attttgtggg agacacttgg gaacaaaaca 2100
gacaccctgg gaatgcagtt gcaagcacag atgctgccac cagtgtctct gaccaccctg 2160
gtgtgactgc tgactgccag cgtggtacct cccatgctgc aggcctccat ctaaatgaga 2220
caacaaagca caatgttcac tgtttacaac caagacaact gcgtgggtcc aaacactcct 2280
cttcctccag gtcatttgtt ttgcattttt aatgtcttta ttttttgtaa tgaaaaagca 2340
cactaagctg cccctggaat cgggtgcagc tgaataggca cccaaaagtc cgtgactaaa 2400
tttcgtttgt ctttttgata gcaaattatg ttaagagaca gtgatggcta gggctcaaca 2460
attttgtatt cccatgtttg tgtgagacag agtttgtttt cccttgaact tggttagaat 2520
tgtgctactg tgaacgctga tcctgcatat ggaagtcccg cttcggtgac atttcctggc 2580
cattcttgtt tccattgtgt ggatggtggg ttgtgcccac ttcctggagt gagacagctc 2640
ctggtgtgta gaattcccgg agcgtccgtg gttcagagta aacttgaagc agatctgtgc 2700
atgcttttct ctgcaacaat tggctcgttt ctcttttttg ttctcttttg ataggatcct 2760
gtttcctatg tgtgcaaaat aaaaataaat ttgggcaaaa aaaaaaaaaa aaaaaaaaaa 2820
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2880
<210> 32
<211> 172
<212> PRT
<213> Homo sapiens
<400> 32
Met Arg Arg Gln Pro Ala Lys Val Ala Ala Leu Leu Leu Gly Leu Leu
1 5 10 15
Leu Glu Cys Thr Glu Ala Lys Lys His Cys Trp Tyr Phe Glu Gly Leu
20 25 30
Tyr Pro Thr Tyr Tyr Ile Cys Arg Ser Tyr Glu Asp Cys Cys Gly Ser
35 40 45
Arg Cys Cys Val Arg Ala Leu Ser Ile Gln Arg Leu Trp Tyr Phe Trp
50 55 60
Phe Leu Leu Met Met Gly Val Leu Phe Cys Cys Gly Ala Gly Phe Phe
65 70 75 80
Ile Arg Arg Arg Met Tyr Pro Pro Pro Leu Ile Glu Glu Pro Ala Phe
85 90 95
27
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
Asn Val Ser Tyr Thr Arg Gln Pro Pro Asn Pro Gly Pro Gly Ala Gln
100 105 110
Gln Pro Gly Pro Pro Tyr Tyr Thr Asp Pro Gly Gly Pro Gly Met Asn
115 120 125
Pro Val Gly Asn Ser Met Ala Met Ala Phe Gln Val Pro Pro Asn Ser
130 135 140
Pro Gln Gly Ser Val Ala Cys Pro Pro Pro Pro Ala Tyr Cys Asn Thr
145 150 155 160
Pro Pro Pro Pro Tyr Glu Gln Val Val Lys Ala Lys
165 170
<210> 33
<211> 3406
<212> DNA
<213> Homo sapiens
<400> 33
taaagaacaa tcctttaagg gagaacctag aagccattca acaaggttaa aatcttcagg 60
cttccgagga tttggtagac agatcagagg cacgtttccc acaactgcga agaggcgctg 120
aggcaattct gcaagaagat tttggggttt tggaaaagaa gctatggaaa acggaggggc 180
aggcactctg cagataaggc aagtcctgct tttctttgtt ttgctgggaa tgtctcaggc 240
gggctctgaa actgggaact ttttggtgat ggaggaattg cagagcggga gctttgtagg 300
aaatttggca aagaccctgg gactcgaggt gagtgagctg tcttcgcggg gggctcgggt 360
ggtttctaat gataacaaag agtgtttgca gctggacaca aacactgggg atttgctcct 420
gagagaaatg ctagacaggg aggagctctg tggctccaat gagccttgtg tgctgtattt 480
ccaagtgtta atgaaaaacc ccacgcagtt tttacaaatt gagctccagg tcagggatat 540
aaatgatcac tctcccgtct tcttggaaaa agaaatgctc ttagaaatcc cagagaacag 600
tcctgttggt gctgtgttct tgcttgaaag tgcaaaggat ttagatgtag gaatcaatgc 660
tgtaaaaagc tacacaataa atccgaactc tcatttccac gttaaaataa gagtcaatcc 720
agacaatagg saataccctg agttagttct ggacaaggcg ctggattatg aagagcgccc 780
ggagctcagt ttcatcctca ctgctctgga tggcgggtcc cctcccaggt ctggaactgc 840
cttggtcagg gtggtggttg tagatattaa tgacaactcc cctgagtttg agcaggcttt 900
ttatgaggtg aagattctgg agaatagcat ccttggctcc ctggttgtga ccgtctcagc 960
ctgggattta gactctggaa caaacagtga actatcctat accttttccc atgcctcaga 1020
agatattcgc aagacatttg aaattaatca aaagtctggt gacattactt taacagcacc 1080
tttggatttt gaagcaattg agtcatactc aataatcatt caagccacag atgggggagg 1140
actttttgga aaatctacag tcagaattca ggtgatggat gtaaacgaca acgctcctga 1200
aatcactgtg tcatcaatta ccagtccaat cccagaaaac actccagaga ctgtggttat 1260
ggttttcagg atacgagaca gagactctgg ggacaacgga aagatggttt gttctatccc 1320
ggaggacatc ccattcgtgc taaaatcttc ggtaaataat tactacactt tggaaacaga 1380
gagaccgctg gacagagaga gcagagccga gtacaacatc accatcaccg tcaccgactt 1440
ggggaccccc aggctaaaaa ccgagcacaa cataaccgtg ctggtctccg acgtcaatga 1500
caacgccccc gccttcaccc aaacttccta cgccctgttc gtccgcgaga acaacagccc 1560
cgccctgcac atcggcagca tcagcgccac agacagagac tcgggcacca acgcccaggt 1620
caactactcg ctgctgccgt cccaggaccc gcacctgccc ctcgcctccc tggtctccat 1680
caacgcggac aacggccacc tgtttgccct caggtcgctg gactacgagg ccctgcaggg 1740
gttccagttc cgcgtgggcg ccacagacca cggctccccg gctttgagca gcgaggcgct 1800
ggtgcgcgtg ctggtgctgg acgccaacga caactcgccc ttcgtgctgt acccgctgca 1860
gaacggctcc gcgccctgca ccgagctggt gccctgggcg gccgagccgg gctacctggt 1920
gaccaaggtg gtggcggtgg acggtgactc gggccagaac gcctggctgt cgtaccagct 1980
gctcaaggcc acggagcccg ggctattcgg cgtgtgggcg cacaatggcg aggtgcgcac 2040
cgccaggctg ctgagcgagc gcgacgcggc caagcacagg ctggtggtgc tggtcaagga 2100
caatggcgag cctccgcgct cggccaccgc cacgctgcac gtgctcctgg tggacggctt 2160
ctcccagccc tacctgcctc tcccggaggc ggccccggcc caggcccagg ccgactcgct 2220
28
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
cactgtctac ctggtggtgg cgttggcctc agtgtcgtcg ctcttcctct tctcggtgct 2280
cctgttcgtg gcggtgcggc tgtgcaggag gagcagggcg gccccggtcg gtcgctgctc 2340
ggtgcctgag ggcccctttc caggacatct ggtggacgtg agtggcaccg ggaccctgtc 2400
ccagagctac cactatgagg tgtgtgtgac tggaggctcc aggtcaaata agttcaaatt 2460
tctgaaacca attatcccca acttcctacc ccagagcaca ggtagtgaag tcgaagaaaa 2520
tcccccattt cagaataatt tgggtttctg ataaagaatg aaaaataaaa cctgtgttta 2580
tgaatacatt tataattagg aacttatcgt gaggtgcctg taaagtagta tttttgatca 2640
cttcaaatac atactcttca agtcaagaaa taaatttctt tacatagaaa aggatacaga 2700
tttagtacca agaacacttc acaaagcagg aaatgtgcat gtgtaatggt ttatgtcaaa 2760
caattatgct taatataaag tctattaagt ggtaagtctt gtttgagata ttttaaattg 2820
ctttccattg ttttcaatat ttactgtgac ttttgttttc tgagttgatt agaatgctgt 2880
tcgagtatac ctaccctagt ttcagaagca tagattgtag tgtacctttt taaactttat 2940
ttttttaaaa aaagttgttt tatgaatcat acactatttt cacactttta atctcagaag 3000
aaacatatgt gacatggtat tttagtaatg accaaataga cggtcttaga gattcagtaa 3060
gttcactaag gtccactaac taataagtga caaaactgag catccatcct agatctgcct 3120
gactctaagt cagtgacttt gctcccattc catactgttt ttgtcattgg atatcacctg 3180
gcaagtttct gcctaactaa agagaagaaa agtttttatc gtattcatac tactgttcaa 3240
tctttattta gaaataaact ttatctatga tttcattttc ttataaacca gtaatcttgc 3300
ttttctgggt aaattttcag ctattattac taatgctctg atctgcccaa atcttaagta 3360
aaaaacaaaa ttgaaagagc aaaaaaaaaa aaaaaaaaaa aaaaaa 3406
<210> 34
<211> 795
<212> PRT
<213> Homo Sapiens
<400> 34
Met Glu Asn Gly Gly Ala Gly Thr Leu Gln Ile Arg Gln Val Leu Leu
1 5 10 15
Phe Phe Val Leu Leu Gly Met Ser Gln Ala Gly Ser Glu Thz Gly Asn
20 25 30
Phe Leu Val Met Glu Glu Leu Gln Ser Gly Ser Phe Val Gly Asn Leu
35 40 45
Ala Lys Thr Leu Gly Leu Glu Val Ser Glu Leu Ser Ser Arg Gly Ala
50 55 60
Arg Val Val Ser Asn Asp Asn Lys Glu Cys Leu Gln Leu Asp Thr Asn
65 70 75 80
Thr Gly Asp Leu Leu Leu Arg Glu Met Leu Asp Arg Glu Glu Leu Cys
85 90 95
Gly Ser Asn Glu Pro Cys Val Leu Tyr Phe Gln Val Leu Met Lys Asn
100 105 110
Pro Thr Gln Phe Leu Gln Ile Glu Leu Gln Val Arg Asp Ile Asn Asp
115 120 125
His Ser Pro Val Phe Leu Glu Lys Glu Met Leu Leu Glu Ile Pro Glu
130 135 140
Asn Ser Pro Val Gly Ala Val Phe Leu Leu Glu Ser Ala Lys Asp Leu
145 150 155 160
Asp Val Gly Ile Asn Ala Val Lys Ser Tyr Thr Ile Asn Pro Asn Ser
165 170 175
29
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
His Phe His Val Lys Ile Arg Val Asn Pro Asp Asn Arg Lys Tyr Pro
180 185 190
Glu Leu Val Leu Asp Lys Ala Leu Asp Tyr Glu Glu Arg Pro Glu Leu
195 200 205
Ser Phe Ile Leu Thr Ala Leu Asp Gly Gly Ser Pro Pro Arg Ser Gly
210 215 220
Thr Ala Leu Val Arg Val Val Val Val Asp Ile Asn Asp Asn Ser Pro
225 230 235 240
Glu Phe Glu Gln Ala Phe Tyr Glu Val Lys Ile Leu Glu Asn Ser Ile
245 250 255
Leu Gly Ser Leu Val Val Thr Val Ser Ala Trp Asp Leu Asp Ser Gly
260 265 270
Thr Asn Ser Glu Leu Ser Tyr Thr Phe Ser His Ala Ser Glu Asp Ile
275 280 285
Arg Lys Thr Phe Glu Ile Asn Gln Lys Ser Gly Asp Ile Thr Leu Thr
290 295 300
Ala Pro Leu Asp Phe Glu Ala Ile Glu Ser Tyr Ser Ile Ile Ile Gln
305 310 315 320
Ala Thr Asp Gly Gly Gly Leu Phe Gly Lys Ser Thr Val Arg Ile Gln
325 330 335
Val Met Asp Val Asn Asp Asn Ala Pro Glu Ile Thr Val Ser Ser Ile
340 345 350
Thr Ser Pro Ile Pro Glu Asn Thr Pro Glu Thr Val Val Met Val Phe
355 360 365
Arg Ile Arg Asp Arg Asp Ser Gly Asp Asn Gly Lys Met Val Cys Ser
370 375 380
Ile Pro Glu Asp Ile Pro Phe Val Leu Lys Ser Ser Val Asn Asn Tyr
385 390 395 400
Tyr Thr Leu Glu Thr Glu Arg Pro Leu Asp Arg Glu Ser Arg Ala Glu
405 410 415
Tyr Asn Ile Thr Ile Thr Val Thr Asp Leu Gly Thr Pro Arg Leu Lys
420 425 430
Thr Glu His Asn Ile Thr Val Leu Val Ser Asp Val Asn Asp Asn Ala
435 440 445
Pro Ala Phe Thr Gln Thr Ser Tyr Aia Leu Phe Val Arg Glu Asn Asn
450 455 460
Ser Pro Ala Leu His Ile Gly Ser Ile Ser Ala Thr Asp Arg Asp Ser
465 470 475 480
Gly Thr Asn Ala Gln Val Asn Tyr Ser Leu Leu Pro Ser Gln Asp Pro
485 490 495
30
CA 02340616 2001-02-23
WO 00/11015 PCI'/US99/19351
His Leu Pro Leu Ala Ser Leu Val Ser Ile Asn Ala Asp Asn Gly His
500 SOS 510
Leu Phe Ala Leu Arg Ser Leu Asp Tyr Glu Ala Leu Gln Gly Phe Gln
515 520 525
Phe Arg Val Gly Ala Thr Asp His Gly Ser Pro Ala Leu Ser Ser Glu
530 535 540
Ala Leu Val Arg Val Leu Val Leu Asp Ala Asn Asp Asn Ser Pro Phe
545 550 555 560
Val Leu Tyr Pro Leu Gln Asn Gly Ser Ala Pro Cys Thr Glu Leu Val
565 570 575
Pro Trp Ala Ala Glu Pro Gly Tyr Leu Val Thr Lys Val Val Ala Val
580 585 590
Asp Gly Asp Ser Gly Gln Asn Ala Trp Leu Ser Tyr Gln Leu Leu Lys
595 600 605
Ala Thr Glu Pro Gly Leu Phe Gly Val Trp Ala His Asn Gly Glu Val
610 615 620
Arg Thr Ala Arg Leu Leu Ser Glu Arg Asp Ala Ala Lys His Arg Leu
625 630 635 640
Val Val Leu Val Lys Asp Asn Gly Glu Pro Pro Arg Ser Ala Thr Ala
645 650 655
Thr Leu His Val Leu Leu Val Asp Gly Phe Ser Gln Pro Tyr Leu Pro
660 665 670
Leu Pro Glu Ala Ala Pro Ala Gln Ala Gln Ala Asp Ser Leu Thr Val
675 ' 680 685
Tyr Leu Val Val Ala Leu Ala Ser Val Ser Ser Leu Phe Leu Phe Ser
690 695 700
Val Leu Leu Phe Val Ala Val Arg Leu Cys Arg Arg Ser Arg Ala Ala
705 710 715 720
Pro Val Gly Arg Cys Ser Val Pro Glu Gly Pro Phe Pro Gly His Leu
725 730 735
Val Asp Val Ser Gly Thr Gly Thr Leu Ser Gln Ser Tyr His Tyr Glu
740 745 750
Val Cys Val Thr Gly Gly Ser Arg Ser Asn Lys Phe Lys Phe Leu Lys
755 760 765
Pro Ile Ile Pro Asn Phe Leu Pro Gln Ser Thr Gly Ser Glu Val Glu
770 775 780
Glu Asn Pro Pro Phe Gln Asn Asn Leu Gly Phe
785 790 795
<210> 35
<211> 3809
31
CA 02340616 2001-02-23
WO 00/11015 PCTNS99/19351
<212> DNA
<213> Homo sapiens
<400> 35
ggggaccgga gtggggagcg cggcgtggag gtgccacccg gcgcgggtgg cggagagatc 60
agaagcctct~tccccaagcc gagccaacct cagcggggac ccgggctcag ggacgcggcg 120
gcggcggcgg cgactgcagt ggctggacga tggcagcgtc cgccggagcc ggggcggtga 180
ttgcagcccc agacagccgg cgctggctgt ggtcggtgct ggcggcggcg cttgggctct 240
tgacagctgg agtatcagcc ttggaagtat atacgccaaa agaaatcttc gtggcaaatg 300
gtacacaagg gaagctgacc tgcaagttca agtctactag tacgactggc gggttgacct 360
cagtctcctg gagcttccag ccagaggggg ccgacactac tgtgtcgttt ttccactact 420
cccaagggca agtgtacctt gggaattatc caccatttaa agacagaatc agctgggctg 480
gagaccttga caagaaagat gcatcaatca acatagaaaa tatgcagttt atacacaatg 540
gcacctatat ctgtgatgtc aaaaaccctc ctgacatcgt tgtccagcct ggacacatta 600
ggctctatgt cgtagaaaaa gagaatttgc ctgtgtttcc agtttgggta gtggtgggca 660
tagttactgc tgtggtccta ggtctcactc tgctcatcag catgattctg gctgtcctct 720
atagaaggaa aaactctaaa cgggattaca ctggggccca gtcatatatg cacagttaga 780
ccactccggc ggacatcaca gtgacaagat taacaagtca gagtctgtgg tgtatgcgga 840
tatccgaaag aattaagaga atacctagaa catatcctca gcaagaaaca aaaccaaact 900
ggactctcgt gcagaaaatg tagcccatta ccacatgtag ccttggagac ccaggcaagg 960
acaagtacac gtgtactcac agagggagag aaagatgtgt acaaaggata tgtataaata 1020
ttctatttag tcatcctgat atgaggagcc agtgttgcat gatgaaaaga tggtatgatt 1080
ctacatatgt acccattgtc ttgctgtttt tgtactttct tttcaggtca tttacaattg 1140
ggagatttca gaaacattcc tttcaccatc atttagaaat ggtttgcctt aatggagaca 1200
atagcagatc ctgtagtatt tccagtagac atggcctttt aatctaaggg cttaagactg 1260
attagtctta gcatttactg tagttggagg atggagatgc tatgatggaa gcatacccag 1320
ggtggccttt agcacagtat cagtaccatt tatttgtctg ccgcttttaa aaaataccca 1380
ttggctatgc cacttgaaaa caatttgaga agtttttttg aagtttttct cactaaaata 1440
tggggcaatt gttagcctta catgttgtgt agacttactt taagtttgca cccttgaaat 1500
gtgtcatatc aatttctgga ttcataatag caagattagc aaaggataaa tgccgaaggt 1560
cacttcattc tggacacagt tggatcaata ctgattaagt agaaaatcca agctttgctt 1620
gagaactttt gtaacgtgga gagtaaaaag tatcggtttt attctttgct gatgtccttt 1680
ctgcttgaaa taacagtcac catacagcta aaggagagga gtttctttcc ttctaagtag 1740
gcagaaatgg tatcattatg ttgccgctct ccaatctccc agagctcgct ctctagagaa 1800
tcaccttctt tcgctttttt ttttttttga ggtagagtct cactatgttg cccagactag 1860
ccttgaactc ttgggctcaa gtgattctcc ctcctcagcc tcccgagtag ctggaacgaa 1920
ctatagttgc accactgcag ctggcaagaa tcaccttttt tataaagcgt cagtcatgct 1980
tccagcaaga ggcagcatca gtcatggctt tataacagct tcatggtgcc tcaaagactg 2040
ttgaggttaa tgagagccta gattagacag tttggctgtc cttccctaaa acttgttttc 2100
tcctattcac tactccccac cgcacttaaa atctatgagt ttttactttt tactgggaat 2160
ggaaagtgtg gtgaagatca ttcaacactt atgttgtcat ttctcccatt ttctgaattt 2220
ttttttaaat ttcccccctt ttaaaattgt tcgaaagccc acagttatgg aaagaattac 2280
tgtctagatg gtctgcagaa cgtgtttggg gtgagtggga gtgaggggca atgttacttt 2340
ttctccttgt agtttggagt ccattatgag ctgctgcttt ttcttctcat cttgtcatct 2400
tctggggatg tttgaaggct gagttccaac agaattcaca aagggaataa aacaggattg 2460
agattttgag gtgtgcacaa ggtggtaaga taaagggcat atgagcttca aaactaatgc 2520
tgttgcatac atgaagcctt ttgttttttg aggagctatt tttgttattc ttgtaacgct 2580
ccaccttaca tgccacgtct gtgtgagtca acagggatca ggtttggtca ccacacatgt 2640
ctgaagctgg gcagcgtctg ctctgtgttc tgtgtggaat ggagaaaaaa acgcctgccc 2700
tgctgccttc catgttcata ggcccagccc aagagagtga cacacagtgc tggccctgag 2760
acatttccac aaagtggtca actctgcctt gcatcctaaa actttttggg catctatttt 2820
gaaaactata ggagcctttg gaaggcctct tatgtttgga ggggaagggt gttgagattg 2880
tcaccatcct tcaagctgag actcctggtg agcctttgcc accatgaaaa ccacatagct 2940
gaccagggct gtgcttgagg tacagaggac acacatcgta gacaggcctg tgtcatgttt 3000
ccttacagtc gttttttaca gagaaaaggg gcattgtttt ttcactgctt tctcaacagt 3060
tcctgtgaat aaatgaaaca tttcggagct ccctgagagc aagagccttc acttcttctt 3120
gcggtgccgg gaccatgtgt tggtgaagct ggtgctgtgg gggccactca ctcgaatgac 3180
acctggaggc ctgttcctcc cttaccactc ccttccccag cccgacttct tggcctcctg 3240
cccaaccaga cacctcaaac tctgtcagcg ccctggcatt ctggcagaga atcctcacca 3300
gttctcacca accttccccc caggcaaggg cagctgccag catggtgctc tgccaggaca 3360
32
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
ggtttccctg aaggaagctg gatgagcctctcagggcagg acctcttccc3420
ctcacactga
aagccctgca cacccacccc ttggctccccttttccctgt gcctcagcac3480
tgcagccctt
tcctttcctg gttgcagata gttgcctaaagggcagatct gccctctcca3540
acgaactaag
tgtcttcgtc ctggcaaaca aaaattatgcgctaattctg tatgggagca3600
gggtcgtctt
ctcaaaaggc attacttaga tcaaactatctctagttttt caatggaaat3660
gattgaaatt
atatcagcta gggaaaaacc ttattattttttgatcttca gttgtatttt3720
atcaagctca
tgtgaatatt ttaatacatc tctgaaaaaaaaaaaaaaaa aaaaaaaaaa3780
tttttcaatt
aaaaaaaaaa aaaaaaaaaa 3809
aaaaaaaaa
<210> 36
<211> 209
<212> PRT
<213> Homo sapiens
<400> 36
Met Ala Ala Ser Ala Gly Ala Val Ala Ala Pro Asp
Ala Gly Ile Ser
1 5 10 15
Arg Arg Trp Leu Trp Ser Ala Ala Leu Gly Leu Leu
Val Leu Ala Thr
20 25 30
Ala Gly Val Ser Ala Leu Tyr Thr Lys Glu Ile Phe
Glu Val Pro Val
35 40 45
Ala Asn Gly Thr Gln Gly Thr Cys Phe Lys Ser Thr
Lys Leu Lys Ser
50 55 60
Thr Thr Giy Gly Leu Thr Ser Trp Phe Gln Pro Glu
Ser Val Ser Gly
65 70 75 80
Ala Asp Thr Thr Val Ser His Tyr Gln Gly Gln Val
Phe Phe Ser Tyr
85 90 95
Leu Gly Asn Tyr Pro Pro Asp Arg Ser Trp Ala Gly
Phe Lys Ile Asp
100 105 110
Leu Asp Lys Lys Asp Ala Asn Ile Asn Met Gln Phe
Ser Ile G1u Ile
115 120 125
His Asn Gly Thr Tyr Ile Val Lys Pro Pro Asp Ile
Cys Asp Asn Val
130 135 140
Val Gln Pro Gly His Ile Tyr Val Glu Lys Glu Asn
Arg Leu Val Leu
145 150 155 160
Pro Val Phe Pro Val Trp Val Gly Val Thr Ala Val
Val Val Ile Val
165 170 175
Leu Gly Leu Thr Leu Leu Met Ile Ala Val Leu Tyr
Ile Ser Leu Arg
180 185 190
Arg Lys Asn Ser Lys Arg Thr Gly Gln Ser Tyr Met
Asp Tyr Ala His
195 200 205
Ser
<210> 37
<211> 1954
33
CA 02340616 2001-02-23
WO 00/11015 PCTNS99/19351
<212> DNA
<213> Homo sapiens
<400> 37
gagacttggg ctggagccgc cctgggtgtc agcgggctcg gctcccgcgc acgctccggc 60
cgtcgcgcag cctcggcacc tgcaggtccg tgcgtcccgc ggctggcgcc cctgactccg 120
tcccggccag ggagggccat gatttccctc ccggggcccc tggtgaccaa cttgctgcgg 180
tttttgttcc tggggctgag tgccctcgcg cccccctcgc gggcccagct gcaactgcac 240
ttgcccgcca accggttgca ggcggtggag ggaggggaag tggtgcttcc agcgtggtac 300
accttgcacg gggaggtgtc ttcatcccag ccatgggagg tgccctttgt gatgtggttc 360
ttcaaacaga aagaaaagga ggatcaggtg ttgtcctaca tcaatggggt cacaacaagc 420
aaacctggag tatccttggt ctactccatg ccctcccgga acctgtccct gcggctggag 480
ggtctccagg agaaagactc tggcccctac agctgctccg tgaatgtgca agacaaacaa 540
ggcaaatcta ggggccacag catcaasacc ttagaactca atgtactggt tcctccagct 600
cctccatcct gccgtctcca gggtgtgccc catgtggggg caaacgtgac cctgagctgc 660
cagtctccaa ggagtaagcc cgctgtccaa taccagtggg atcggcagct tccatccttc 720
cagactttct ttgcaccagc attagatgtc atccgtgggt ctttaagcct caccaacctt 780
tcgtcttcca tggctggagt ctatgtctgc aaggcccaca atgaggtggg cactgcccaa 840
tgtaatgtga cgctggaagt gagcacaggg cctggagctg cagtggttgc tggagctgtt 900
gtgggtaccc tggttggact ggggttgctg gctgggctgg tcctcttgta ccaccgccgg 960
ggcaaggccc tggaggagcc agccaatgat atcaaggagg atgccattgc tccccggacc 1020
ctgccctggc ccaagagctc agacacaatc tccaagaatg ggaccctttc ctctgtcacc 1080
tccgcacgag ccctccggcc accccatggc cctcccaggc ctggtgcatt gacccccacg 1140
cccagtctct ccagccaggc cctgccctca ccaagactgc ccacgacaga tggggcccac 1200
cctcaaccaa tatcccccat ccctggtggg gtttcttcct ctggcttgag ccgcatgggt 1260
gctgtgcctg tgatggtgcc tgcccagagt caagctggct ctctggtatg atgaccccac 1320
cactcattgg ctaaaggatt tggggtctct ccttcctata agggtcacct ctagcacaga 1380
ggcctgagtc atgggaaaga gtcacactcc tgacccttag tactctgccc ccacctctct 1440
ttactgtggg aaaaccatct cagtaagacc taagtgtcca ggagacagaa ggagaagagg 1500
aagtggatct ggaattggga ggagcctcca cccacccctg actcctcctt atgaagccag 1560
ctgctgaaat tagctactca ccaagagtga ggggcagaga cttccagtca ctgagtctcc 1620
caggccccct tgatctgtac cccaccccta tctaacacca cccttggctc ccactccagc 1680
tccctgtatt gatataacct gtcaggctgg cttggttagg ttttactggg gcagaggata 1740
gggaatctct tattaaaact aacatgaaat atgtgttgtt ttcatttgca aatttaaata 1800
aagatacata atgtttgtat gasaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1860
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1920
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1954
<210> 38
<211> 390
<212> PRT
<213> Homo sapiens
<400> 38
Met Ile Ser Leu Pro Gly Pro Leu Val Thr Asn Leu Leu Arg Phe Leu
1 5 10 15
Phe Leu Gly Leu Ser Ala Leu Ala Pro Pro Ser Arg Ala Gln Leu Gln
20 25 30
Leu His Leu Pro Ala Asn Arg Leu Gln Ala Val Glu Gly Gly Glu Val
35 40 45
Val Leu Pro Ala Trp Tyr Thr Leu His Gly Glu Val Ser Ser Ser Gln
50 55 60
Pro Trp Glu Val Pro Phe Val Met Trp Phe Phe Lys Gln Lys Glu Lys
65 70 75 80
Glu Asp Gln Val Leu Ser Tyr Ile Asn Gly Val Thr Thr Ser Lys Pro
34
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
85 90 95
Gly Val Ser Leu Val Tyr Ser Met Pro Ser Arg Asn Leu Ser Leu Arg
100 105 110
Leu Glu Gly Leu Gln Glu Lys Asp Ser Gly Pro Tyr Ser Cys Ser Val
115 120 125
Asn Val Gln Asp Lys Gln Gly Lys Ser Arg Gly His Ser Ile Lys Thr
130 135 140
Leu Glu Leu Asn Val Leu Val Pro Pro Ala Pro Pro Ser Cys Arg Leu
145 150 155 160
Gln Gly Val Pro His Val Gly Ala Asn Val Thr Leu Ser Cys Gln Ser
165 170 175
Pro Arg Ser Lys Pro Ala Val Gln Tyr Gln Trp Asp Arg Gln Leu Pro
180 185 190
Ser Phe Gln Thr Phe Phe Ala Pro Ala Leu Asp Val Ile Arg Gly Ser
195 200 205
Leu Ser Leu Thr Asn Leu Ser Ser Ser Met Ala Gly Val Tyr Val Cys
210 215 220
Lys Ala His Asn Glu Val Gly Thr Ala Gln Cys Asn Val Thr Leu Glu
225 230 235 240
Val Ser Thr Gly Pro Gly Ala Ala Val Val Ala Gly Ala Val Val Gly
245 250 255
Thr Leu Val Gly Leu Gly Leu Leu Ala Gly Leu Val Leu Leu Tyr His
260 265 270
Arg Arg Gly Lys Ala Leu Glu Glu Pro Ala Asn Asp Ile Lys Glu Asp
275 280 285
Ala Ile Ala Pro Arg Thr Leu Pro Trp Pro Lys Ser Ser Asp Thr Ile
290 295 300
Ser Lys Asn Gly Thr Leu Ser Ser Val Thr Ser Ala Arg Ala Leu Arg
305 310 315 320
Pro Pro His Gly Pro Pro Arg Pro Gly Ala Leu Thr Pro Thr Pro Ser
325 330 335
Leu Ser Ser Gln Ala Leu Pro Ser Pro Arg Leu Pro Thr Thr Asp Gly
340 345 350
Ala His Pro Gln Pro Ile Ser Pro Ile Pro Gly Gly Val Ser Ser Ser
355 360 365
Gly Leu Ser Arg Met Gly Ala Val Pro Val Met Val Pro Ala Gln Ser
370 375 380
Gln Ala Gly Ser Leu Val
385 390
CA 02340616 2001-02-23
WO 00/11015 PCTNS99/19351
<210> 39
<211> 1933
<212> DNA
<213> Homo sapiens
<400> 39
ggggtggggc caggaggaag atggcggcgt ccgcagctgc cgctgagctc caggcttctg 60
ggggtccgcg gcacccagtg tgtctgttgg tgttgggaat ggcgggatcc gggaaaacca 120
cttttgtaca gaggctcaca ggacacctgc atgcccaagg cactccaccg tatgtgatca 180
acctggatcc agcagtacat gaagttccct ttcctgccaa tattgatatt cgtgatactg 240
taaagtataa agaagtaatg aaacaatatg gacttggacc caatggcggc atagtgacct 300
cactcaatct ctttgctacc agatttgatc aggtgatgaa atttattgag aaggcccaga 360
acatgtccaa atatgtgttg attgacacac ctggacagat tgaggtattc acctggtcag 420
cttctgggac aattatcact gaagcccttg catcctcatt tccaacagtt gtcatctatg 480
taatggacac atcgagaagt accaacccag tgaccttcat gtccaacatg ctctatgcct 540
gcagcatctt atacaaaacc aagctgcctt tcattgtggt catgaataaa actgacatca 600
ttgaccacag ctttgcagtg gaatggatgc aggattttga ggctttccaa gatgccttga 660
atcaagagac tacatacgtc agtaacctga ctcgttcaat gagcctggtg ttagatgagt 720
tttacagctc actcagggtg gtgggtgtct ctgctgttct gggtactgga ttagatgaac 780
tctttgtgca agttaccagt gctgccgaag aatatgaaag ggagtatcgt cctgaatatg 840
aacgtctgaa aaaatcactg gccaacgcag agagccaaca gcagagagaa caactggaac 900
gccttcgaaa agatatgggt tctgtagcct tggatgcagg gactgccaaa gacagcttat 960
ctcctgtgct gcacccttct gatttgatcc tgactcgagg aaccttggat gaagaggatg 1020
aggaagcaga cagcgatact gatgacattg accacagagt tacagaggaa agccatgaag 1080
agccagcatt ccagaatttt atgcaagaat cgatggcaca atactggaag agaaacaata 1140
aataggagac tttagcacac ttcacttgtt tctagaagtc cagaattttg gacctccacg 1200
tgaaagaact gttcttacct ctgaactggg ggctcccata agggataatt ttcctcagag 1260
tagcaaagtt tctcttatta gagaaatctt gtgactcaga tgaagtcagg gatagaagac 1320
ccttggacct ggcaggttaa tgctgattat tccttggcct ttcccttgta tttatgcaag 1380
gaaggatata ctgagctgat actcttccaa gcctacaact tcaagtttta tcatttgaac 1440
tcaagtactt ttgctgctga ggaatggaat caaaagaacg tagtctcctg gtaaccacct 1500
cagatctcta ttattaggct agatgtatag cctctactcc cccagcttct tgctcttgac 1560
cctgcactgt aagttgccct tctattagca gccaaggaaa agggaaacat gagcttatcc 1620
agaacggtgg cagagtctcc ttggcaatca accaacgttg ctatgaaata tgcctcacac 1680
tgtatagctc attataggac gtcaggtttg ttgaaaaaag tgggcaagac atgattaatg 1740
aatcagaatc ctgtttcatt ggtgacttgg ataaagactt tttaatttta actttgaaaa 1800
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1860
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aasaaaaaaa aaaaaaaaaa aaaaaaaaaa 1920
aaaaaaaaaa aaa 1933
<210> 40
<211> 374
<212> PRT
<213> Homo Sapiens
<400> 40
Met Ala Ala Ser Ala Ala Ala Ala Glu Leu Gln Ala Ser Gly Gly Pro
1 5 10 15
Arg His Pro Val Cys Leu Leu Val Leu Gly Met Ala Gly Ser Gly Lys
20 25 30
Thr Thr Phe Val Gln Arg Leu Thr Gly His Leu His Ala Gln Gly Thr
35 40 45
Pro Pro Tyr Val Ile Asn Leu Asp Pro Ala Val His Glu Val Pro Phe
50 55 60
Pro Ala Asn Ile Asp Ile Arg Asp Thr Val Lys Tyr Lys Glu Val Met
65 70 75 80
36
CA 02340616 2001-02-23
WO 00/11015 PCT/US99/19351
Lys Gln Tyr Gly Leu Gly Pro Asn Gly Gly Ile Val Thr Ser Leu Asn
85 90 95
Leu Phe Ala Thr Arg Phe Asp Gln Val Met Lys Phe Ile Glu Lys Ala
100 105 110
Gln Asn Met Ser Lys Tyr Val Leu Ile Asp Thr Pro Gly Gln Ile Glu
115 120 125
Val Phe Thr Trp Ser Ala Ser Gly Thr Ile Ile Thr Glu Ala Leu Ala
130 135 140
Ser Ser Phe Pro Thr Val Val Ile Tyr Val Met Asp Thr Ser Arg Ser
145 150 155 160
Thr Asn Pro Val Thr Phe Met Ser Asn Met Leu Tyr Ala Cys Ser Ile
165 170 175
Leu Tyr Lys Thr Lys Leu Pro Phe Ile Val Val Met Asn Lys Thr Asp
180 185 190
Ile Ile Asp His Ser Phe Ala Val Glu Trp Met Gln Asp Phe Glu Ala
195 200 205
Phe Gln Asp Ala Leu Asn Gln Glu Thr Thr Tyr Val Ser Asn Leu Thr
210 215 220
Arg Ser Met Ser Leu Val Leu Asp Glu Phe Tyr Ser Ser Leu Arg Val
225 230 235 240
Val Gly Val Ser Ala Val Leu Gly Thr Gly Leu Asp Glu Leu Phe Val
245 250 255
Gln Val Thr Ser Ala Ala Glu Glu Tyr Glu Arg Glu Tyr Arg Pro Glu
260 265 270
Tyr Glu Arg Leu Lys Lys Ser Leu Ala Asn Ala Glu Ser Gln Gln Gln
275 280 285
Arg Glu Gln Leu Glu Arg Leu Arg Lys Asp Met Gly Ser Val Ala Leu
290 295 300
Asp Ala Gly Thr Ala Lys Asp Ser Leu Ser Pro Val Leu His Pro Ser
305 310 315 320
Asp Leu Ile Leu Thr Arg Gly Thr Leu Asp Glu Glu Asp Glu Glu Ala
325 330 335
Asp Ser Asp Thr Asp Asp Ile Asp His Arg Val Thr Glu Glu Ser His
340 345 350
Glu Glu Pro Ala Phe Gln Asn Phe Met Gln Glu Ser Met Ala Gln Tyr
355 360 365
Trp Lys Arg Asn Asn Lys
370
<210> 41
37
CA 02340616 2001-02-23
DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTS PARTIE DE CETTE DEMANDS OU CE BREVET
COMPREND PLUS D'UN TOME.
CECI EST LE TOME _ 1-DE a
NOTE. Pour les tomes additionels, veuiliez contacter le Bureau canadien des
brevets -
:':, ~ i..
JUMBO APPLlCATIONS/PATENTS
THIS SECTION OF THE APPLICATIONIPATENT CONTAINS MORE
THAN ONE VOLUME -
. THIS IS VOLUME ~OF -
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