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CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
RAT TOXICOLOGICALLY RELEVANT GENES AND USES THEREOF
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to provisional U.S.Serial No. 60/264,933 and
60/308,161, filed January 29, 2001 and July 26, 2001, respectively, both of
which are
hereby incorporated by reference herein.
TECHNICAL FIELD
This invention is in the field of toxicology. More specifically, the invention
provides a set of rat genes useful fox determining toxicological responses to
various
agents.
BACKGROUND OF THE INVENTION
Every year, many new drugs and chemical compounds are discovered,
produced, and introduced into the public domain. Guidelines set forth by the
U.S.
Food and Drug Administration (FDA) require toxicity studies to be conducted
before a
new drug or compound can be approved for human consumption or use.
Toxicological
studies are an important part of drug development but toxicity studies
traditionally have
required long periods of clinical trials, using both animal models and humans,
and are
quite often very expensive to conduct. A two year toxicity study in rats can
cost
approximately $800,000. See, for example, Casarett and Doz~ll's Toxicology,
4th
Editions M.O. Amdur et al., eds. Pergamon Press, New Yorh, N.Y. p. 37 (1991).
1
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Further, traditional toxicology studies are no longer sufficient to assess
toxicity of a
drug or compound because there are too many compounds derived from high
throughput screening of combinatorial chemical libraries. In addition,
traditional
toxicological methods have offered little insight into molecular mechanisms of
toxicity,
which makes extrapolation of toxicity results from animal models to humans
difficult.
Furthermore, traditional toxicity methods often result in numerous failures in
subsequent stages of development and post-launching of the drug.
In recent years, a new field of toxicogenetics has emerged whereby
toxicological
responses to drugs or compound are studied at a molecular level, e.g.,
differential gene
0 expression. One major focus of toxicogenetics is the study of differential
gene
expression induced as an response to chemical or environmental stress. One
major goal
of most applied toxicology studies is to identify the organ or organs, system,
or systems
that are damaged by exposure to a drug or other environmental agent. Examples
of
some major toxic target organs include but are not limited to the liver,
kidney, pancreas,
l5 heart, lung, brain, thymus, and hypothalamus. Examples of major toxic
target systems
include but are not limited to the immune, nervous, digestive and circulatory
systems.
By studying patterns of gene expression, toxicologists can learn a great deal
about the
fundamental mechanisms of chemical toxicity. Further, measurement of gene
expression may allow us to identify threshold concentrations, below which,
there is
~0 little health risk.
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Some methods and kits for determining toxicity have been reported. See, for
example, WO 00/47761, U.S. Patent Nos. S,S8S,232; S,S89,337; and 5,811,231;
and
pending U.S. provisional patent applications 60/220,0S7 and 60/254,232.
However,
toxicogenetics allows for a better understanding of mechanisms of organ and
system
S toxicity and facilitate prediction of deleterious outcomes prior to their
detection by more
laborious and time-consuming means. If toxicity manifested at the organism
level is
preceded by altered expression of related genes, then detection of altered
gene
expression may serve as an early warning for subsequent deleterious outcomes.
Altered
gene expression may precede organ or system outcomes by weeks, months or even
0 years. To the extent that a causal relationship can be demonstrated between
early
alterations in gene expression and delayed manifestations of toxicity,
measuring the
alterations in gene expression may reduce reliance on the observing delayed
manifestations of'toxicity. Better understanding ofmolecular mechanisms
through
toxicogenetics may also improve the predictive accuracy of animal models to
humans,
S and in vitro systems to ira vivo settings. A molecular approach to
toxicology could save
time, money and animal resources.
With the advent of molecular and recombinant technology, genetic and
molecular analysis provides another method by which toxicity may be measured.
Differential gene expression technology involves detecting the change in gene
?0 expression of cells exposed to various stimuli. The stimulus can be in the
form of
CA 02440008 2003-09-03
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growth factors, receptor-ligand binding, transcription factors, or exogenous
factors such
as drugs, chemicals, or pharmaceutical compounds.
Several methods have been reported for detecting differential gene expression.
One method is to use an array of polynucleotides which includes, for example,
genes for
which full-length cDNAs have been accurately sequenced and genes which may be
defined by high-throughput, single-pass sequencing of random cDNA clones to
generate expressed sequence tags (ESTs). Researchers focused on detecting
changes in
expression of individual mRNAs can use different methods to detect changes in
gene
expression, e.g., microarray, gel electrophoresis, etc. Other methods have
focused on
( 0 using the polymerise chain reaction (PCR) and/or reverse transcriptase
polymerise
chain reaction (RT-PCR) to define tags and to attempt to detect differentially
expressed
genes. Many groups have used PCR methods to establish databases of mRNA
sequence
fags which could conceivably be used to compare gene expression among
different
tissues (Williams, J. G. K., Nucl. Acids Res. 18:6531, 1990; Welsh, J., et al.
Nucl. Acids
Res., 18:7213, 1990; Woodward, S. R., Mamzn. Genome, 3:73, 1992; Nadeau, J.
H.,
Mamm. Genome 3:55, 1992). This method has also been adapted to compare mRNA
populations in a process called mRNA differential display.
The process of isolating mRNA from cells or tissues exposed to a stimulus,
e.g.,
drugs or chemicals, and analyzing the expression with gel electrophoresis can
be
laborious and tedious. To that end, microarray technology provides a faster
and more
efficient method of detecting differential gene expression. Differential gene
expression
4.
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analysis by microarrays involves nucleotides immobilized on a substrate
whereby
nucleotides from cells which have been exposed to a stimulus can be contacted
with the
immobilized nucleotides to generate a hybridization pattern. This microarray
technology has been used for detecting secretion and membrane-associated gene
products, collecting pharmacological information about cancer, stage specific
gene
expression in Plasmodium falciparum malaria, translation products in
eukaryotes, and a
number of other scientific inquiries. See, for example, Diehn M, et al. Nat
Genet.
25(1): 58-62 (1993); Scherf, U., et al. Nat Genet. 24(3): 236-44 (1993);
Hayward R.E.,
et al. Mol Microbiol 35(1): 6-14 (1993); Johannes U., et al. Proc Natl Acad
Sci USA
I O 96(23): 13118-23 (1993). Microarray technology has also been used in
exploring drug-
induced alterations in gene expression in Mycobacterium tuberculosis. See, for
example, Wilson M., et al. Proc Natl Acad Sci. 96(22): 12833-8 (1999).
There exists a need for methods that are fast, efficient, cost-effective,
capable of
generating large amounts of toxicology data, and could spare many animals from
being
15 the subjects of laboratory tests. There also exist a need for a method of
effectively
selecting genes which are toxicologically relevant to agents being tested and
can predict
toxicity on a cellular, organ, or system level. There also exists a need for a
toxicological database of information whereby one can obtain information about
one or
more agents being tested and how that agents) affects a particular organ or
system and
20 algorithms which may be used to identify toxicologically relevant genes and
correlate
toxicity between agents and target genes.
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Molecular toxicology analysis or toxicogenetics can provide a vast amount of
information in the form of a database from a collection of toxicological
response data
that would be useful in toxicological analysis. The invention and its
embodiments
provided herein fulfill the aforementioned needs.
The disclosure of all patents, patent applications, and publications cited
herein
are hereby incorporated by reference in their entirety.
SUMMARY OF THE INVENTION
The invention provides toxic response genes and uses thereof.
0 In one aspect, the invention provides a method of evaluating the toxicity of
an
agent by (a) exposing a test animal to the agent; (b) measuring the expression
of one or
more toxic response genes selected from the genes corresponding to the partial
gene
sequences in 'Tables 6, 7, 8, 9, and 10 in the test animal in response to the
agent, thereby
generating a test expression profile; and (c) comparing the test expression
profile with a
L 5 reference expression profile indicative of toxicity, wherein toxicity of
the agent is
evaluated by determining whether a significant correlation exists between the
test
expression profile and the reference expression profile. In one embodiment,
the group
of genes corresponding to the partial gene sequences is responsive in kidney,
liver,
spleen, heart, lung, testis, or brain. In other embodiments, the test animal
is a rat, dog,
ZO non-human primate, or a human. In other embodiments, the agent is
administered at
various dosages or for various lengths of time.
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In another aspect, the invention provides a method of evaluating the toxicity
of
an agent by (a) exposing a test animal to the agent; (b) measuring the
expression of one
or more toxic response genes selected from the genes corresponding to the
partial gene
sequences in Tables 6, 7, and ~ in the test animal in response to the agent,
thereby
generating a test expression profile; and (c) comparing the test expression
profile with a
reference expression profile indicative of toxicity, wherein toxicity of the
agent is
evaluated by determining whether a significant correlation exists between the
test
expression profile and the reference expression profile. In one embodiment,
the group
of genes corresponding to the partial gene sequences is responsive in kidney,
liver,
0 spleen, heart, lung, testis, or brain. In other embodiments, the test animal
is a rat, dog,
non-human primate, or a human. In other embodiments, the agent is administered
at
various dosages or for various lengths of time.
In another aspect, the invention provides a method of evaluating the toxicity
of a
agent by (a) exposing a test animal to.the agent; (b) measuring the expression
of one or
l5 more toxic response genes selected from the genes corresponding to the
partial gene
sequences in Table 4 in the test animal in response to the agent, thereby
generating a
test expression profile; and (c) comparing the test expression profile with a
reference
expression profile indicative of toxicity, wherein toxicity of the agent is
evaluated by
determining whether a significant correlation exists between the test
expression profile
~0 and the reference expression profile. In one embodiment, the set of
toxicologically
relevant genes consists of at least 25 genes. In another embodiment, the set
of
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toxicologically relevant genes consists of at least 50 genes. In another
embodiment, the
set of toxicologically relevant genes consists of at least 100 genes.
In another aspect, the invention provides an array which includes one or more
polynucleotides selected from the genes corresponding to the partial gene
sequences in
Tables 6, 7, 8, 9, and 10 or fragments of at least 20 nucleotides thereof. In
one
embodiment, the group of genes corresponding to the partial gene sequences is
responsive in kidney, liver, spleen, heart, lung, testis, or brain.
In another aspect, the invention provides an array which includes one or more
polynucleotides selected from the genes corresponding to the partial gene
sequences in
0 Tables 6, 7, and 8 or fragments of at least 20 nucleotides thereof. In one
embodiment,
the group of genes corresponding to the partial gene sequences is responsive
in kidney,
liver, spleen, heart, lung, testis, or brain.
In another aspect, the invention provides an array which includes one or more
polynucleotides selected from the group consisting of the genes corresponding
to the
l5 partial gene sequences in Table 4 or fragments of at least 20 nucleotides
thereof. In one
embodiment, the set of toxic response genes consists of at least 25 genes. In
another
embodiment, the set of toxic response genes consists of at least 50 genes. In
another
embodiment, the set of toxic response genes consists of at least 100 genes.
In another aspect, the invention provides an array which includes a set of
ZO polynucleotides of at least 20 nucleotides in length substantially
homologous to a set of
CA 02440008 2003-09-03
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toxic response genes selected from the genes corresponding to the partial gene
sequences in Tables 6, 7, and 8.
In another aspect, the invention provides an array which includes one or more
polynucleotides which are homologous to the polynucleotides contained in the
array
which includes one or more polynucleotides selected from the genes
corresponding to
the partial gene sequences in Tables 6, 7, and 8 or fragments of at least 20
nucleotides
thereof. In one embodiment, the polynucleotides correspond to human, murine,
non-
human primate, or canine genes.
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BRIEF DESCRIPTION OF THE FIGURES
Figure 1 depicts the consistency of differential gene response in two
microarrays
spotted with 700 rat genes listed in Table 4. The slides were hybridized with
cDNA
preparations from the liver of a rat exposed to aflatoxin at 1 mg/kg for 72
hours as a
p differential expression compared with cDNA preparations from appropriate
control rats
hybridized on the slide at the same time. For each of the 9 genes shown one
bar is from
one microarray and the second bar is data from a second microarray.
Figure 2 depicts the similar differential gene expression response in two
different organs from two rats given the same treatment of lipopolysaccharide
(LPS)-
0 treated rats at 6 hours post-exposure. The data shown is liver data from two
rats (the
first and second bars for each gene) and kidney data from two rats (the third
and forth
bar for each gene). For two of the five genes shown, the differential
expression was
increased in the kidney more than in the liver and for three of the genes
shown the
differential expression was increased in the liver more than at in the kidney.
Figure 3 depicts the progression of toxicity-induced differential gene
expression
in rat liver over time. Rats were treated with lipopolysaccharide (8 mg/kg) by
a single
intraperitoneal injection. The data shown is from two rats sacrificed at 6
hours (the first
and second bars for each gene), 2 rats at 24 hours (the third and forth bar
for each gene),
and 2 rats at 72 hours (the fifth and sixth bar for each gene). For the five
genes shown,
?0 the differential expression was greater at~6 hours than at 24 hours in the
liver and there
is very little differential expression by 72 hours.
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Figure 4 depicts the progression of toxicity-induced differential gene
expression
in rat heart over time. Rats were treated with lipopolysaccharide (8 mg/kg) by
a single
intraperitoneal injection. The data shown is from 2 rats sacrificed at 6 hours
(the first
and second bars for each gene), 2 rats at 24 hours (the third and forth bar
for each gene),
and 2 rats at 72 hours (the fifth and sixth bar for each gene). For the
thirteen genes
shown, the differential expression was greater at 6 hours than at 24 hours in
the heart
and there is very little differential expression by 72 hours.
Figure S depicts a correlation of erythromycin estolate-treated liver with
tetracycline-treated liver in rats treated in vivo with these agents. The
white squares
0 delineate the area with the most correlation between experiments. There was
high
correlation between the experiments where the rats were dosed with
erythromycin
estolate (white squares) and high correlation between the experiments where
the rats
were dosed with tetracyclin. The correlation of the experiments of one
compound with
the other compound was not very high (dark gray and boxes) showing that the
700
l5 genes expressed in the liver of rats exposed to these two toxins were
different. This is
expected since erythromycin and tetracycline have different mechanisms of
liver
toxicity.
Figure 6 depicts a correlation matrix of four mechanistic classes of toxic
compounds. The gene expression data from a rat CT array tested in rat liver
was
ZO identified by successive pairwise gene identification. The areas of white
boxes signify
higher correlations. The abbreviations are as follows: PAH: Polyaromatic
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Hydrocarbons, TCDD, Benzo(a)pyrene, Dimethylbenzanthracene; PP: Peroxisome
Proliferators, Gemfibrozil, Diethylhexyl phthalate, Wy 14,643; CS:
Corticosteroids,
Prednisone, Triamcinolone; NM: Nitrogen Mustards, Mechlorethamine,
Cyclophosphamide, Melphalan, Chlorambucil.
Figure 7 depicts the very similar response of the gene cytochrome P450 1A2
using the microarray platform (O symbols and dashed line) and the the TacMan
real
time PCR platform (D symbols and solid lines).
Figure 8 depicts the very similar response of the gene fatty acid synthase
using
the microarray platform (O symbols and dashed line) and the TacMan real time
PCR
platform (0 symbols and solid lines).
Figure 9 depicts the very similar response of the gene multidrug resistant
protein-1 using the microarray platform (O symbols and dashed line) and the
the
TacMan real time PCR platform (~ symbols and solid lines).
BRIEF DESCRIPTION OF THE TABLES
Table 1 is a list of pharmaceutical agents which can potentially cause greatly
heightened toxic responses in some individuals.
Table 2 is a list of industrial agents which can potentially cause greatly
heightened toxic responses in some individuals.
!0 Table 3 is a list of the drugs and chemicals used to generate the data
shown in
tables 7, 8, 9, and 10. These compounds were selected for their ability to
induce the
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following pathologies: Iiver degeneration/necrosis, hepatocyte hypertrophy,
hepatocyte
vacuoles, renal tubular degeneration/necrosis, renal glomerular necrosis,
myocardial
degeneration, myocardial inflammation, splenic lymphoid depletion / apoptosis,
splenic
Lymphoid hyperplasia, neurotoxicity, skeletal muscle degeneration and
inflammation,
multiple tissue necrosis and inflammation, repair, including proliferation.
Table 4 is a list of the 700 rat genes and/or gene sequences that have been
determined to be toxic response genes.
The table is split into three sections. The first section lists the genes
discovered
using empirical data from the 17,241 gene set which matched a known complete
rat
0 gene when the genes were searched in the GenBank database. The second
section lists
the genes discovered using empirical data from the 17,241 gene set which did
not match
a known complete rat gene when the genes were searched in the NCBI GenBank
database. These genes are listed in numerical order by Phase-1 RCT number. The
clones for the genes in the first and second section use the pT7T3D-PAC
vector. The
.5 gene sequences in this table may include a small portion of vector in the
sequence.
Portions of the following vector sequence are what may be included in the
sequence
listed in Table 4 and should not be included when referring the gene or gene
sequence
itself. Sequences using M13 reverse primer include:
TAATACGACTCACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTC(SEQID
ZO NO: 701 ) which can be followed by an insert which can also be followed by
GCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAAT (SEQ ID NO: 702). The
13
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sequences of the reverse complement are as follows:
ATTAAGCCTCACTAAAGGGAATAAGCTTGCGGCCGC (SEQ ID NO: 703) which
can be followed by an insert which can also be followed by
GAATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAGTCGTATTA (SEQ ID
N0:704).
The third set of genes in this table refer to the genes chosen on the basis of
their
possible role in critical cellular pathways and empirical data toxicity
responsiveness.
The clones for this third set of genes used the pCRII-TOPO vector. The gene
sequences
in this Table 4 may include a small portion of vector in the sequence.
Portions of the
0 following vector sequence are what may be included in the sequence listed in
Table 4
and should not be included when refernng to the gene or gene sequence itself.
Sequences using T7 promoter as primer include: ATATCTGCAGAATTCGCCCTT
(SEQ ID NO: 705) followed by an insert which can then be followed by
AAGGGCGAATTCCAGCACACT (SEQ ID NO: 706). The sequences of the reverse
l S complements include: AGTGTGCTGGAATTCGCCCTT (SEQ ID NO: 707) which can
be followed by an insert which can also be followed by
AAGGGCGAATTCTGCAGATAT (SEQ ID NO: 708). The genes designated "Phase-
1 RCT" are further detailed iri Table 5.
Table 5 is a list of the Phase-1 RCT genes and their homology with known
20 genes (rat, mouse, human) identified by a BLAST search in NCBI GenBank. The
phrase 'no significant homology found to a known complete gene' indicates that
the
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BLAST search did not reveal significant (>97%) homology to any known complete
gene.
Table 6 is a list of the genes discovered by testing of 17,241 genes on a
17,241
gene microarray and the response data that provided the basis for choosing
each gene.
These 400 genes were selected after a first filtering of all gene data for
acceptable fold
induction values (>2), coefficient of variance (COV, <30), and fluorescent
value (fluor,
>400) then ranking the genes that met these criteria by the number of
experiments in
which the gene responded, COV between duplicate slides, and fold induction.
The
name of the gene is followed by the list of compounds that induced an
acceptable
0 response (passed the filters) and the specifics of the tissue evaluated, the
dose of the
drug or chemical, and the timepoint that the animal was sacrificed after
intraperitoneal
injection of the compound.
Table 7 is a list which shows the tissue specific response of the toxicology
genes
chosen empirically from the 17,241 gene set. The data evaluated for.this
tissue
l5 response was obtained by dosing rats with the compounds listed in Table 3
and then
determining the differential gene expression to compile a database with
approximately
2500 experiments (i:e., data from one microarray). The tissue response is
greater than 2
fold in 1 % of the experiments for the specific tissue for liver and kidney
and greater
than 2 fold in 2% of the experiments for the specific tissue for heart, lung,
spleen, testis,
20 and brain. This table is organized by data for each gene.
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Table 8 is a list which shows tissue specific response of the toxicology genes
in
Table 7 with organization by tissue.
Table 9 is a list which shows the tissue specific response of the toxicology
genes
chosen by description of their role in critical cellulax pathways. The data
evaluated for
this tissue response was obtained by dosing rats with the compounds listed in
Table 3
and determining the differential gene expression to compile a database with
approximately 2500 experiments. The tissue response is greater than 2 fold in
1 % of
the experiments for the specific tissue for liver and kidney and greater than
2 fold in 2%
of the experiments for the specific tissue for heart, lung, spleen, testis,
and brain. This
0 table is organized by data for each gene.
Table 10 is a list which shows tissue specific response of the toxicology
genes in
Table 9 with organization by tissue.
DETAILED DESCRIPTION OF THE INVENTION
l5 The present invention provides a set of toxicologically relevant rat genes
which
can be used to evaluate a toxic response to drugs, chemicals, and/or
compounds.
I. General Technigues
The practice of the present invention will employ, unless otherwise indicated,
20 conventional techniques of molecular biology (including recombinant
techniques),
microbiology, cell biology, biochemistry, nucleic acid chemistry, and
immunology,
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which are within the skill of the art. Such techniques are explained fully in
the
literature, such as, Molecular Cloning: A Laboratory Manual, second edition
(Sambrook et aL, I989) and Molecular Cloning: A Laboratory Manual, third
edition
(Sambrook and Russet, 2001), (jointly referred to herein as "Sambrook");
Current
S Protocols in Molecular Biology (F.M. Ausubel et al., eds., 1987, including
supplements
through 2001); PCR: The Polymerase Chain Reaction, (Mullis et al., eds.,
1994);
Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor
Publications, New York, and Harlow and Lane ( 1999) Using Antibodies: A
Laboratory
Manual Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (jointly
referred
0 to herein as "Harlow and Lane"), Beaucage et a1. eds., Current Protocols in
Nueleic
Acid Chemistry John Wiley & Sons, Inc., New York, 2000).
II. Definitions
"Toxicity", as used herein, refers to the exaggerated microscopic or
macroscopic
l5 responses of cells, tissues, organs or systems to low or average doses of
an agent.
These responses may lead to observable symptoms such as dizziness or nausea
and can
also result in toxic outcomes. Toxicity often results in toxic side effects
that are
different, in either degree or kind, from the response of the majority of
individuals at the
recommended dose.
Z0 "Frank toxicity" refers to toxicity in which macroscopic responses can be
observed. Examples of frank toxicity responses include but are not limited to
clinical
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observations, serum chemistry values, hematology values, urinalysis values,
histopathology results, or gross appearance of the tissues and organs at
necropsy.
A "toxicological response" refers to a cellular, tissue, organ or system level
response to exposure to an agent and includes, but is not limited to, the
differential
expression of genes and/or proteins encompassing both the up- and down-
regulation of
such genes; the up- or down-regulation of genes which encode proteins
associated with
the repair or regulation of cell damage; or the regulation of genes which
respond to the
presence of an agent.
The terms "toxicity genes)", "toxicologically relevant genes)", and "toxic
0 response gene(s)" as used herein are interchangeable. These terms can be
defined as a
gene whose message or protein level is altered by adverse stimuli. The
specific set of
genes that cells induce is dependent upon, ifater czlicc, the type of damage
or toxic threat
' caused by the agent and which organs are the most threatened.
"Gene expression indicative of toxicological response" as used herein refers
to
1 S the relative levels of expression of a toxicity gene or toxic response
gene. Profiles of
gene expression profiles may be measured in a sample, such as samples
comprising a
variety of cell types, different tissues, different organs, ox fluids (e.g.,
blood, urine,
spinal fluid or serum). These profiles can include "test expression profile"
and
"reference expression profile".
20 "Substantially homologous" or "substantially identical" refers to sequence
homology wherein at least 70°f°, preferably at least
80°f°, preferably at least 85%, and
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more preferably at least 90% nucleotide or amino acid residue identity, when
compared
and aligned for maximum correspondence, as measured using one of the following
sequence comparison algorithms or by visual inspection. Two sequences (amino
acid
or nucleotide) can be compared over their full-length (e.g., the length of the
shorter of
the two, if they are of substantially different lengths). For sequence
comparison,
typically one sequence acts as a reference sequence, to which test sequences
are
compared. When using a sequence comparison algorithm, test and reference
sequences
are input into a computer, subsequence coordinates are designated, if
necessary, and
sequence algorithm program parameters are designated. The sequence comparison
0 algorithm then calculates the percent sequence identity for the test
sequences) relative
to the reference sequence, based on the designated program parameters. Optimal
alignment of sequences for comparison can be conducted, e.g., by the local
homology
algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology
alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the
5 search for similarity method of Pearson & Lipman, Proc. IVatl. Aced. Sci.
USA 85:2444
(1988), by computerized implementations of these algorithms (GAP, BESTFIT,
FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics
Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see
generally
Ausubel et al., Current Protocols Ira Molecular- Biology, Greene Publishing
and Wiley
?0 Interscience, New York, supra).When using any of the aforementioned
algorithms, the
default parameters for Window length, gap penalty, etc., are used. A further
indication
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that two nucleic acid sequences or polypeptides are substantially identical is
that the
first polypeptide (e.g., a polypeptide encoded by the first nucleic acid) is
immunologically cross reactive with the second polypeptide (e.g., a
polypeptide
encoded by the second nucleic acid). Thus, a polypeptide is typically
substantially
identical to a second polypeptide, for example, where the two peptides differ
only by
conservative substitutions.
As used herein, the term "gene" refers to polynucleotide sequences which
encode protein products and encompass RNA, mRNA, cDNA, single stranded DNA,
double stranded DNA, complement strands, and fragments thereof. Genes can
include
introns and exons.
The term "gene sequence(s)" refers to gene(s), full-length genes or any
portion
thereof.
As used herein, "array" and "microarray" are interchangeable and refer to an
arrangement of a collection of nucleotide sequences in a centralized location.
Arrays
I S can be on a solid substrate, such as a glass slide, or on a semi-solid
substrate, such as
nitrocellulose membrane. The nucleotide sequences can be DNA, RNA, any
permutations thereof, and include nucleotide analogs. The nucleotide sequences
can
also be partial sequences from a gene, primers, whole gene sequences, non-
coding
sequences, Boding sequences, published sequences, known sequences, or novel
sequences.
CA 02440008 2003-09-03
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An "agent" to which an individual can exhibit a toxicological response can
include, for example, drugs, pharmaceutical compounds, household chemicals,
industrial chemicals, environmental chemicals, and other chemicals and
compounds to
which individuals may be exposed. Exposure to an agent can constitute physical
contact as well as secondary contact, such as inhalation and environmental
exposure.
"Differential expression" as used herein refers to the change in expression
levels
of genes, andlor proteins encoded by said genes, in cells, tissues, organs or
systems
upon exposure to an agent. As used herein, differential gene expression
includes
differential transcription and translation, as well as message stabilization.
Differential
gene expression encompasses both up- and down-regulation of gene expression.
The term "rat" refers to a mammal from the Rattus genus which can include any
one of numerous rodents (Rattans and related genera) differing from related
mice by
considerably larger size and by structural details (e.g., size of teethj. Rats
strains which
may be used include but are not limited to Sprague-Dawley, Wistar, and Fisher.
The term "sample" as used herein refers to substances supplied by an
individual.
The samples may comprise cells, tissue, parts of tissues, organs, parts of
organs, or
fluids (e.g., blood, urine or serum). Samples are characterized in a preferred
embodiment by comprising at least two different genes and may also include
genes
from multiple cell types. Samples include, but are not limited to, those of
eukaryotic,
;0 mammalian or human origin.
21
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The terms "protein", "polypeptide", and "peptide" are used interchangeably
herein to refer to polymers of amino acids of any length. The polymer may be
linear or
branched, it may comprise modified amino acids, and it may be interrupted by
non-
amino acids. It also may be modified naturally or by intervention; for
example,
~ disulfide bond formation, glycosylation, myristylation, acetylation,
alkylation,
phosphorylation or dephosphorylation. Also included within the definition are
polypeptides containing one or more analogs of an amino acid (including, for
example,
unnatural amino acids) as well as other modifications known in the art.
As used herein, the term "significant correlation" has the normal meaning in
the
0 art and means that the probability of the observed difference (or in the
case of "similar"
measurements, the probability of a observed absence of difference) occurring
by chance
(the p-value) is less than some predetermined level, i.e., a p-value that is
<0.05,
preferably <0.01 and more preferably <0.001. A variety of suitable statistical
methods
are well known to those of skill can be used to measure statistical
significance (e.g.,
5 standard statistical methods such as Student t-tests {for comparing two
samples},
ANOVA {analysis of variance}, and confidence interval analysis; software such
as the
SAS System Version 8 (SAS Institute Inc., Cary, NC, USA) can be used for
analysis).
An "individual" is .a vertebrate, preferably a mammal, more preferably a
human.
Mammals include, but are not limited to, farm animals, sport animals, pets,
primates,
?0 mice and rats.
22
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III. Identif n~n,g a set of toxicolo ically relevant enes
Identification of a set of toxicologically relevant genes can be achieved by
several methods. One method which can be used is to clone genes previously
described
to be potentially relevant in toxicology. Using published sequences, for
example in
literature or from GenBank, primers can be made and then used to PCR amplify
from a
relevant library to obtain the candidate toxicologically relevant gene of
interest which
can then be cloned into a plasmid or an expression vector, depending on the
use desired.
The gene sequence (full or partial) can be placed amongst other
toxicologically relevant
genes in a microarray for high-throughput testing, as disclosed infra.
Q . Alternatively, for replication to high copy numbers, a plasmid may be used
to
grow high copies of the candidate toxicologically relevant gene of interest
which can
then be purified by any commercially available kit (e.g., from Qiagen or
Promega). The
purified candidate toxicologically relevant gene may be used for "spotting" in
a
microarray or alternatively, the purified nucleic acid can then be inserted
into an
5 expression vector, transfected into mammalian cells, e.g., rat cells, and
then the cells
can be exposed to a compound and observed for toxicological responses. Frank
toxicity
may be ascertained by,observing changes in cell morphology or re-arrangement
of
cytoskeleton, which can be determined by examination under a microscope, or
alternatively, cell apoptosis or necrosis. In another alternative,
"transcriptome
?0 profiling", described in greater detail below, may be used whereby nucleic
acid can be
isolated from both the exposed and unexposed cells and examined to determine
which
23
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level of the compound causes the up-regulation or down-regulation of the
toxicologically relevant gene of interest.
Another method which can be used to identify a set of toxicologically relevant
genes is to test available rat genes, of which there are approximately 17,421
known rat
genes, for the genes' response using tissues from rat toxicity studies and
select those
with differential expression. Differential expression may be assessed by any
number of
methods. One method which may be used is by microarray analysis. Provided
herein
are methods of using microarray analysis to determine differential gene
expression.
Another method of determining differential gene expression is by reverse
transcriptase-
polymerase chain reaction (RT-PCR), e.g., Taqman~ technology. Provided herein
are
methods of using Taqman~ technology. Yet another method which could be used to
detect differential gene expression is InvaderCR~ technology, commercially
available
from Third Wave. Yet another method which may be used to determine
differential
expression is Northern blot analysis. Other methods which may be used include
AFLP
and SAGE (Klein, P.E., et al. Genome Res. 10(6):789-807 (2000); Wang, X. and
Feuerstein, G.Z., Cardiovasc Res.35(3):414-21 (1997)) Feuerstein, G.Z. and
Wang X.
Can J. Physiol Pharnaacol. 75(6):731-4 (1997); Hough, C.D. et al., Cancer Res.
60(22):6281-7 (2000); Ye, S.Q., et al., Anal Biochem. 287(1):144-52 (2000)).
One method which can be used to identify a set of toxicologically relevant
genes
is to use an "open system" to compare gene expression profiles from control
rats and
rats treated with an agent to select responsive genes. Alternatively,
comparisons
24
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between gene expression profiles from control rat cells (or rat cell lines)
and rat cells (or
rat cell Lines) treated with an agent can be used to select responsive genes.
This is
referred to herein as "transcriptome profiling". This method empirically
determines
which genes are toxicologically relevant by analyzing differential gene
expression. In
one embodiment, experimental rats are divided into two groups. One group is
exposed
to one or more agents) at different concentrations for different lengths of
time.
Another group of rats is not exposed to any agent and serves as the control
group. Rats
are then sacrificed and organs such as liver, spleen, kidney, testes, heart,
lung, and
thymus are harvested for cells to perform molecular analysis of gene
expression. In
0 addition, analysis of serum proteins in the circulating blood can provide
another
measure to compare with unexposed rats.
Once the experimental group is exposed to at least one agent, then RNA of both
groups is isolated and reverse transcribed in PCR reactions to generate cDNA
which in
turn is amplified to generate double stranded DNA. The PCR is performed in the
L 5 presence of a radioactive DNA substrate that is incorporated into the
double stranded
DNA. On a polyacrylamide gel, the DNA derived from the treated cells is
separated by
length next to the DNA derived from untreated population. The intensity of the
resulting band or bands is compared between the treated and untreated groups
of cells.
Bands that show different radioactive intensity are excised from the gel,
amplified by
?0 PCR, cloned, and sequenced. The sequences are compared with known gene
sequences
in the public databases such as GenBank. In this manner, novel rat genes, in
addition to
CA 02440008 2003-09-03
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known rat genes with varying degrees of similarity, which are toxicologically
relevant
are discovered and identified. The examples disclosed herein illustrates how
this aspect
of the invention may be practiced by the skilled artisan.
If a partial sequence of a rat gene which has no match to any publicly
available
gene sequence databases is discovered, the technology, texts (see Sambrook et
al. if fray,
and resources available to a skilled artisan would enable the sequencing of
the of
remainder of the gene and obtain a full-length gene without undue
experimentation. In
one embodiment, a full-length gene is obtained by using the portion of the rat
gene
sequence which is known to make primers and then use the primers in
combination with
0 random primers in PCR reactions with a rat cDNA library. The PCR reaction
are run
on a standard agarose gel and amplified bands are identified, excised from the
gel, and
sequenced.
Each of these methods is disclosed in greater detail below. Other factors to
consider in identifying toxicologically relevant genes include, but are not
limited to,
l5 selection of one or more agent(s), the dosage amount to administer, and
routes of
administration.
IV. Selection of a~ent(s)
The agent to be tested can selected on the basis of different criteria. In one
20 aspect, the basis of a compound to test is damage observed in specific
organs. In one
embodiment, cisplatin, amphotericin B and gentamicin are selected because they
have
26
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been observed to cause kidney tubular epithelial cell damage. In another
embodiment,
clofibrate, gemfibrozil, and WY 14643 are selected because liver peroxisome
proliferation has been observed to be affected by clofibrate, gemfibrozil, and
WY
14643. In another aspect, a basis for selection is function. For example,
cisplatin
causes apoptosis and reactive oxygen species, amphotericin B causes increased
permeability of cell membranes to ions and renal vasoconstriction, and
gentamicin
causes phospholipid accumulation in lysosomes.
Other toxicants affect an organ in general, for example, some kidney toxicants
include but are not limited to cisplatin, gentamicin, puromycin, and
amphotericin B.
l0 Liver toxicant include but are not limited to chlorpromazine, clofibrate,
diflunisal,
tetracycline, erythromycin, and ethanol. Immunotoxicants include but are not
limited to
cyclosporin A, lipopolysaccharide (LPS), hydroxyurea, phenylhydrazine,
dexamethasone, estradiol, and tamoxifen. Heart toxicant includes but is not
limited to
doxorubicin. Multiorgan toxicants include but are not limited to methotrexate
and
cadmium chloride.
Other criteria for selecting an agent to tested is to select those agents to
which an
individual might be exposed to on a regular basis, either in the environment,
by
prescription or over-the-counter drug. Another criteria by which an agents is
to be
tested are those agents which are required to tested for toxicity for FDA-
approval or
alternatively fox other toxicity requirements, for example in pre-clinical or
clinical
trials. Tables 1 and 2 list some agents which may be selected given the
criteria above.
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V. Determination of dosage
Dosages of agents to use in rat experiments can be determined using several
methods. In one aspect, reported dosages are used as a starting point and dose
incrementally above and below the reported dosage. Increments can be at least
about
~1%, 5%, 10%, 25%, 35%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%. Upregulation or
downregulation of markers in the blood including but not limited to: serum
chemistry
values and hematology values can be used to determine if toxicity has been
reached. In
another aspect, examining the histopathology of organs, in particular, organs
which are
0 the specific targets of the compound of interest, may be used to determine
if a
pathological change has occurred in response to administration of the
compound. In
one embodiment, pathological changes include liver degeneration/necrosis,
hepatocyte
hypertrophy, hepatocyte vacuoles, renal tubular degeneration/necrosis, renal
glomerular
necrosis, myocardial degeneration, myocardial inflammation, splenic lymphoid
5 depletion / apoptosis, splenic lymphoid hyperplasia, neurotoxicity, skeletal
muscle
degeneration and inflammation, multiple tissue necrosis and inflammation,
repair,
including proliferation. In one embodiment, In another aspect, the molecular
changes in
response to administration of different doses of one or more agents is
determined by
analyzing the gene expression associated with exposure to such agents.
?0 Determination of the dosage experimentally using cell cultures is affected
by
many factors: the nature of the agent, its potency, mechanism of action, type
of cell
28
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which is the target of the agent, and number of cells, To determine the dosage
requited
experimentally, a low dosage level of the agent is added and then in a step-
wise manner,
the dosage is increased as well as length of time exposed to the agent. If the
agent is
lipophilic and easily crosses the lipid bilayer of cells, a lower initial
concentration may
S be used and/or shorter length of time exposed to the agent. If the agent
possesses the
nature that would not cross the cell barner easily and would need to be
actively or
passively transported across cell membranes, then a slighter higher initial
concentration
may be used andlor longer length of time exposed to the agent. Increasing
dosage step-
wise while monitoring toxicological response and morphology of the cells, rate
of death
of the cells, and growth patterns allows the skilled artisan to determine the
dosage at
which a toxicological response occurs. However, it should be noted that
toxicological
responses may occur which are visible changes, including but not limited to,
physical
structure and integrity of the cells (e.g., morphology, growth pattern, etc.).
Monitoring
for cellular toxic responses as well as molecular toxic responses, e.g.,
differential gene
expression increases the likelihood of fording preferable dosages.
Changes in gene expression are toxicologically significant at that dosage at
which removal or diminishment of the treatment no longer results in a return
to
normalcy, i.e., the state of a cell, organ, or system that existed prior to
the treatment
with the compound. Treatments beyond a certain dosages or time period may
commit
the cell to a toxicologically-relevant fate. This toxic dosage is reflected by
an
identifiable gene expression pattern, which is distinct from the pattern
observed below
29
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the toxic dosage. Methods of analyzing gene expression and how to correlate
gene
expression data are described herein.
VI. Administration of an agent
Administration of the agent of interest to rats may be achieved by various
routes.
It will be readily appreciated by those skilled in the art that the route can
vary, and can
be intraperitoneal, intravenous, subcutaneous, transcutaneously,
intramuscular,
enterally, transdermally, transmucously, sustained release polymer
compositions (e.g., a
lactide polymer or co-polymer microparticle or implant), perfusion, pulmonary
(e.g.,
0 inhalation), nasal, oral, etc. Injectables can be prepared in conventional
forms, either as
liquid solutions or suspension, solid forms suitable for solution or
suspension in liquid
prior to injection, or as emulsions. The agents can be administered in a
pharmaceutically acceptable form, for example, with an excipient. Suitable
excipients
include, for example, water, saline, aqueous dextrose, glycerol, ethanol or
the like.
.5 Formulations for parenteral and nonparenteral delivery of one or more
agents are known
in the art and described in greater detail in Rernington: The Science and
Practice of
Pharmacy, Mack Publishing (2000).
If a carrier is used to administer the agent, the carrier must be acceptable
in the
sense of being compatible with the agent to be tested and not deleterious
(i.e., harmful)
ZO to the rat to be treated. For solid compositions, conventional non-toxic
carriers include,
for example mannitol, lactose, starch, magnesium stearate, magnesium
carbonate,
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
sodium saccharin, talcum, cellulose, glucose, sucrose, pectin, dextrin,
tragacanth,
methyl cellulose, sodium carboxymethyl cellulose, a low-melting wax, cocoa
butter,
and the like may be used. The active compound as defined above may be
formulated as
suppositories using, for example, polyalkylene glycols, for example, propylene
glycol
as a Garner.
In one aspect, the agent to be administered will preferably contain a quantity
of
the agent in an amount sufficient to effect some sort of toxicological
response in the rat,
either on a molecular level or on a physiological level.
0 VII Method of identifying toxicologically relevant genes using known rat
genes
In one aspect, rat genes which are candidate toxicologically relevant genes
have
been described, either in the art or in a publicly available database, e.g.,
GenBank.
Using the candidate toxicologically relevant rat sequences, primers are
designed and
used in PCR reaction to amplify the rat gene from a cDNA library. The cDNA
library
can be made from different rat cells, obtained ex vivo or from a commercial
source, for
example, American Type Culture Collection (ATCC). The generation of a cDNA
involves reverse transcribing isolated RNA and is well-known in the art (see
for
example, Sambrook et al. supra). The rat gene fragments, amplified by PCR, are
cloned into any standard plasmid expression vector which can be obtained from
'0 numerous commercial sources (e.g., Promega, InVitrogen, New England
BioLabs, etc.)
and sequenced. The resulting sequence information is then compared to the
GenBank
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CA 02440008 2003-09-03
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database to confirm that the cloned DNA is the specific rat gene for which the
primers
were designed. Upon positive confirmation of the sequence, the amplified gene
is then
added to the panel of genes to be included in the array.
In another aspect, sequences of non-rat (e.g., human) genes which are
candidate
S toxicologically relevant genes have been described. Primers to these
toxicologically
relevant non-rat genes are designed, synthesized, and are subsequently used in
PCR
reaction with rat cDNA libraries to amplify the homologous rat gene. The
homologous
rat gene may or may not be the exact sequence as the non-rat gene with which
the
primers were designed. Amplified rat gene is then added to the panel of genes
to be
l0 included in the array.
In yet another aspect, rat genes or gene sequences which are toxicologically
relevant or are candidate toxicologically relevant genes are used to determine
toxicologically relevant genes in other rodents, e.g., mice. The high homology
between
rat and mouse gene sequences, which is believed to be about 97%, allows for
reliable
15 identification of non-rat toxicologically relevant without undue
experimentation.
In yet another aspect, target sequences for inclusion in a rat array are
obtained
by de novo _synthesis of nucleotides which are immobilized on a substrate,
e.g., a glass
slide. The target sequences are from genes which can indicate one or more
toxicological responses.
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VII. (Al Differential Display
Several methods of differential display can be used to identify genes of
interest.
Differential gene expression can be observed by using techniques involving gel
electrophoresis and polynucleotide microarrays or commercially available
technologies,
e.g., Invader~ or TaqmanC~.
In one aspect, the results of PCR synthesis of mRNA (converted to cDNA
before PCR) isolated from tissues of treated and control rats or cell lines
are subjected
to gel electrophoresis, and the bands produced by these mRNA populations are
compared. Bands present on an image of one gel from one mRNA population, and
not
l0 present on another, correspond to the presence of a particular mRNA in one
population
and not in the other, and thus indicate a gene that is likely to be
differentially expressed.
Messenger RNA derived from control and treated rat or cell lines can be
compared by
using arbitrary oligonucleotide sequences of ten nucleotides (random 10-mers)
as a 5'
primer and a set of 12 oligonucleotides complimentary to the poly A tail as a
3'
fluorescent labeled "anchor pritmer". These primers are then used to amplify
partial
sequences of mRNAs with the addition of deoxyribonucleotides. These amplified
sequences are then resolved on a sequencing gel such that each sequencing gel
has a
sequence of 50-100 mRNAs. The sequencing gels are then compared to each other
to
determine which amplified segments are expressed differentially (Liang, P. et
al.
Science 257:967, 1992; Welsh, J. et al., Nucl. Acid Res. 20:4965, 1992; Liang,
P., et al.,
Nucleic Acids Res. 21(14): 3269-75 (1993)).
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VII~B) Transcriptome profiling
An open system may be used whereby rat cells are exposed to drugs and/or
chemicals at different concentration and then harvested at different time
points. Rat
cells can be obtained from various sources including, but are not limited to,
tissue
samples, organs, blood, skin, biological fluids (e.g., urine, spinal fluid,
semen, etc.), and
cell lines. Transcriptome profiling may also be obtained in rats dosed ih
vivo.
Immortalized cell lines are obtained from commercial sources, e.g., Gibco BRL
Life
Sciences, or from other sources,, e.g., American Type Culture Collection
(ATCC).
Other methods of obtaining rat cells include isolating cells obtained from
tissue
biopsies, blood, skin, or biological fluids, for example from rats dosed in
vivo. As is
well known to one of skill in the art, isolating cells from tissue samples can
be achieved
using any variety of techniques.
Sources from which cells are obtained can be any number of organs, including
but not limited to liver, lung, heart, testis, kidney, spleen, thymus, and
brain. In one
embodiment, liver cells may be used for toxicity studies where the agent to be
administered is known or thought to induce liver malfunctions or liver
toxicity. In other
embodiments, when the target of the action delivered by the agent is known,
the use of
cells deriving from the target organ may yield more beneficial information
regarding
toxicological responses than if a tissue were selected at random. In another
embodiment where the agent to be tested has unknown effects, a panel of cells
isolated
34
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
from different sources may be used. In the alternative, liver cells may be
used in the
absence of knowledge of the agent's target of action because the liver ~is
known to
process many toxins. Although the toxicological responses may not be the most
ideal
compared to the results that one of skill in the art would obtain if the
target tissue of the
agent's action had been used, the benefits of using liver cells would be that
toxicologically relevant genes may be identified and then subsequently tested
on other
organs to determine toxicity in the other organs or alternatively, to identify
which
organs) is the target for the agent. Time would be saved testing cells from
one tissue
source (liver in this situation) instead of isolating cells from many tissue
sources.
l0 Rat cells obtained ex vivo or from a commercial or non-commercial source
can
be used fresh from a necropsy or frozen for storage and then cultured in media
at time
of experimentation. A wide variety of basal cell-sustaining media that can be
used to
keep the pH of the liquid in a range that promotes survival of rat cells. Non-
limiting
examples include F12/DMEM, Ham's F10 (Sigma), CMRL-1066, Minimal essential
medium (MEM, Sigma), RPMI-1640 (Sigma), Dulbecco's Modified Eagle's Medium
(DMEM, Sigma), and Iscove's Modified Eagle's Medium (IMEM). In addition, any
of
the basal nutrient media described in Ham and Wallace Meth. Enz., 58:44
(1979),
Barnes and Sato Anal. Biochem., 102:255 (1980). Cells can be grown in plates
or in
flasks. Cells are grown and expanded to a level desired and needed for DNA or
RNA
isolation. Cells are removed from the plate or flask to isolate DNA or RNA. If
the cells
are adherent, trypsin or another equivalent may be used to release the cells
from the
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
plate or flask. Preferably at least about lxIOZ cells, more preferably at
least about
1x103 cells, more preferably at least about 1xI04 cells, more preferably at
least about
1 x I O' cells, more preferably at Ieast about I x 10~ cells, and even more
preferably at least
about lxl0~ cells are used as sources for DNA and RNA. In one embodiment, rats
are
S dosed, tissues harvested (and nucleic acids isolated) after exposure to
toxic doses of
drugs/chemicals in vivo. This embodiment is further described in the Examples.
The isolated nucleic acid is then amplified to generate a product which can be
attached to a substrate. In a preferred embodiment, the substrate is a solid
substrate
(e.g., glass slide). The amplification process involves using primers which
have a
0 reactive group (e.g., amine group or derivative thereof) on one end of the
primer, which
is incorporated into the amplification product: One example of reactive
primers that can
be used is Amine Primers from Synthegen. The gene fragments which are attached
to
the glass slide can vary in length. The more nucleotides of a gene that are in
the array,
the tighter the binding and the greater the specificity in binding can occur.
However, it
is important to consider that longer fragments are more difficult to amplify
and may
contain point mutations or other errors associated with amplification.
Therefore, the
desired length of a gene or a fragment thereof~that is to be included in the
array should
take into consideration the balance between a high specificity of binding
obtained with
a long (e.g., >1 kb) gene sequence with the high mutational rate associated
with a longer
?0 fragment. The gene fragments attached to the glass slide are at least about
25 base pairs
(bp) in length, at least about 50 by in length, more preferably at least about
100 by in
36
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
length,, more preferably at least about 200 bp, even more preferably at least
about 300
bp, even more preferably at least about 400 bp, even more preferably at least
about 500
by in length. In a preferred embodiment, the gene fragments are about 500 by
in length.
The region of a gene that is used to attach to a solid substrate to generate
an array can
S be any portion of the gene, coding, non-coding, 5' end, 3' end, etc. In a
preferred
embodiment, about 500 base pairs of the 3' end of rat gene related to
toxicological
responses are selected to be included in an array.
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WO 02/066682 PCT/US02/02935
VII~CI Pre aration of Microarra_y
Several techniques are well-known to a skilled artisan for attaching a gene or
a
fragment thereof to a solid substrate such as a glass slide. One method is to
attach an
amine group, a derivative of an amine group, another group with a positive
charge or
another group which is reactive to one end of a primer that is used to amplify
a gene or
a gene fragment to be included in the array. Subsequent amplification of a PCR
product
will then incorporate this reactive group onto one end of the product. The
amplified
product is then contacted With a solid substrate, such as a glass slide, which
is coated
with an aldehyde or another reactive group which will form a covalent link
with the
l0 reactive group that is on the amplified PCR product and become covalently
attached to
the glass slide. Other methods using amino propryl silicane surface chemistry
and
other methods of preparation of microarrays have been disclosed. See, for
example,
Nuwaysir, E.F., et al. Molecule~r Carcirzogenesis, 24:153-159 (1999); Kane,
M.D., et al.
Nucleic Acids Res. 28(22):4552-7 (2000); MacBeath G. and Schreiber, S.L.,
Science
289(5485):1760-1763 (2000); Lockhart, D. J. and Winzeler, E. A., Nature
405(6788):827-836 (2000); Cortese, J.D., The Scientist I4(17):25 (2000); and
Cortese,
J.D., Tlae Scientist 14(11):26, (2000). Other embodiments of the invention are
described further in the Examples.
Other methods using arrays are known, for example, arrays of polymers, such as
nucleic acids, immobilized on a solid substrate, are disclosed, for example,
in U.S. Pat.
Nos. 5,744,305; 5,510,270; 5,677,195; 5,624,711; 5,599,695; 5,451,683;
5,424,186;
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WO 02/066682 PCT/US02/02935
5,412,087; 5,384,261; 5,252,743; and 5,143,854; as well as PCT WO 92/10092;
PCT
WO 93J09668; and PCT WO 97110365. Photolithographic and fabrication techniques
to allow each probe sequence to occupy a very small site on the support, for
example, a
few microns, are described in U.S. Pat. No. 5,631,734. Substrates having a
surface to
which arrays of polynucleotides are attached include silicon or glass.
Substrates that are
transparent to light and optical detection can be used, as described, for
example, in U.S.
Pat. No. 5,545,531.
VIII. Algorithms for analysis and evaluation of toxicolo icallyrelevant genes
0 A mufti-step approach can be used in ranking candidate genes from rat genes,
for example, asset of 17,421 rat genes, known herein as "17K array", for
possible
inclusion on a comprehensive toxicity (CT) array. First, three cutoff criteria
can be
specified fox individual gene values from whatever experiments result from
using the
17K array: 1) Fold Induction/Repression level, 2) Average Fluorescence level
of the
t5 replicate spots (reflection of the expression level) and 3) Coefficient of
Variation of the
replicate spots. The initial screening to make the "cut" may be based on
expression
level and measurement quality.
Second, gene values that would made the cut were aggregated into overall
scores, and ranked for each gene, may be based on six ranking criteria: 1)
Number of
20 slides on which that gene met the cutoff criteria (NC), 2) Percent of
consistency
between slides (% of time the gene value made the cutoff criteria on the
replicate slide
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for that initial slide) (CC), 3) Average magnitude (absolute value) of fold
induction for
all occurrences where that gene made the cutoff criteria (Fl), 4) Coefficient
of Variation
of those fold induction scores (unlike all the other ranking criteria, lower
is deemed
better) (CV), 5) Average fluorescence value of all replicate spots of
occurrences where
that gene made the cutoff criteria (FL), and 6) Tissue consistency (what
percent of
cutoff meeting occurrences of the gene were in the same tissue) (CT).
Each gene was assigned a score between 0 and 100 for each ranking criterion.
Each ranking criterion score was computed as follows: The range of values for
all genes
was computed for the criterion by subtracting the lowest value present among
all scores
from the highest. The score for each gene was then calculated by subtracting
the lowest
value present from the value for that gene, then dividing by the range and
multiplying
by 100. In other words, the score for each gene is the percent above the
minimum
present toward the maximum. For example, if a gene's score was three-fourths
of the
way between the minimum present and the maximum for that criterion, its score
would
be 75%. Since for the CV factor (coefficient of variation of fold inductions)
lower was
deemed better, the score thus computed was subtracted from 100 to invert the
percentage.
The final ranking score for each gene can be computed via a weighted
combination of its score on the six ranking criteria. if a score could not be
computed
for a particular criterion, the entire value of that criterion would be
removed from the
equation, and ranking was based solely on the remaining factors.
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IX. Methods of using toxicolo ig rally relevant genes
In one aspect, the invention provides methods of determining toxicity to a
particular agent by exposing a test animal (e.g., rat) to an agent and
measuring the
expression of one or more toxicologically relevant genes in the test animal.
This
generates a test expression profile which can then be compared to a reference
expression profile to determine the toxicity of the agent. This can be
accomplished, for
example, by determining a significant correlation, for example, by routine
statistical
analysis between the test expression profile and the reference expression
profile. In one
embodiment, the agent is selected from Table 1 or 2. In another embodiment,
the agent
is a drug, drug candidate, or pharmaceutical compound. The toxicity dosages
and time
of exposure which is required to reach a toxic dose are determined by using
the methods
described herein. .In another embodiment, the test expression profile includes
genes or
gene sequences from Tables 4, 6, 7, 8, 9, or 10. In another embodiment, the
reference
profile includes one or more expression profiles which have been empirically
derived,
for example, from Table 4, 6, 7, 8, 9, or 10. In another embodiment, the test
gene
expression profile may be compared with a reference gene expression profile
stored in a
database, for example, a comprehensive toxicity (CT) database. In another
embodiment, the gene expression profiles are associated with responsiveness in
a
;0 particular organ, for example, kidney, liver, spleen, heart, lung, testis,
or brain.
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In another aspect, rat toxicologically relevant genes are used to obtain an
array
comprising polynucleotides which are selected from genes corresponding to
partial gene
sequences of toxicologically relevant genes. In one embodiment, the array
includes
genes or partial gene sequences of at least 20 nucleotides each. In another
embodiment,
the array includes genes or partial gene sequences of at least 50 nucleotides,
at least 100
nucleotides, at least 200 nucleotides, at least 300 nucleotides, or at least
500 nucleotides
each. In another embodiment, the array comprises toxicologically relevant
genes
corresponding to the partial gene sequences in Table 4. In other embodiments,
the array
comprises toxicologically relevant genes corresponding to partial gene
sequences in
l0 Table 6, 7, 8, 9, or 10. In yet another embodiment, the array comprises
toxicologically
relevant genes corresponding to partial gene sequences associated with
responsiveness
in a particular organ, for example, kidney, liver, spleen, heart, lung,
testis, or brain.
In another aspect, toxicologically relevant gene sequences from non-rat
animals
(e.g., humans, dogs, non-human primates) can be obtained by using the arrays
described
herein to select for sequences which are substantially homologous. As known to
one of
skill in the art, homology may be determined by using computerized sequence
alignment, as described above, or by hybridization techniques. Nucleic acids
will
hybridize will depend upon factors such as their degree of complementarity as
well as
the stringency of the hybridization reaction conditions. Stringent conditions
can be
used to identify nucleic acid duplexes with a high degree of complementarity.
Means
for adjusting the stringency of a hybridization reaction are well-known to
those of skill
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in the art. See, far example, Sambrook, et al., "Molecular Cloning: A
Laboratory
Manual," Second Edition, Cold Spring Harbor Laboratory Press, 1989; Ausubel,
et al.,
"Current Protocols In Molecular Biology," John Wiley & Sons, 1996 and periodic
updates; and Homes et al., "Nucleic Acid Hybridization: A Practical Approach,"
IRL
Press, Ltd., 1985. In general, conditions that increase stringency (i.e.,
select for the
formation of more closely-matched duplexes) include higher temperature, lower
ionic
strength and presence or absence of solvents; lower stringency is favored by
lower
temperature, higher ionic strength, and lower or higher concentrations of
solvents.
Identifying toxicologically relevant genes in other non-rat animals may assist
in
t 0 determining which species is best suited for animal models by assessing
which species
is most susceptible to toxic responses.
In another aspect, gene expression profiles of rats can be compared when dosed
with one drug and then compared to a second gene expression profile when dosed
with
another drug. The toxicologically relevant data may be correlated using the
algorithms
disclosed herein. The effects of drug-drug interaction may induce a similar
set of genes
to be up-regulated or down-regulated. The effect may be additive or
multiplicative. In
another embodiment, the effects of the drug-drug interaction may induce
different set of
genes which are not related in function. In another embodiment, the methods
and set of
toxicologically relevant genes disclosed herein allow target organs and toxic
doses
therein to be determined, as shown in Table 7, 8, 9, and 10. This is useful in
drug
design where the drug may have an intended target of one organ but have toxic
multi-
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organ effects. In another embodiment, the methods and set of toxicologically
relevant
genes may be used to predict toxic response to agents which may take repeated
exposure over a period of time for frank toxicity to appear. Examples of such
agents
are one-hit carcinogens (e.g., afiatoxin B1, dimethylnitrosamine, ENLT, etc.)
or multi-
dose carcinogens (e.g., phenobarbital and WY14643). The molecular toxic
response to
these carcinogens may be determined in advance of any macroscopic changes
which
may occur in response to exposure to these agents.
X. Method of using toxicolo ical response data to generate a toxicologLcal
database
I O By collecting data from cells, tissues, or organs from rats in response to
one or
more agents at different dosages and/or at different time points, a database
can be built
with collection of information about toxicological responses, e.g., reference
expression
profiles. With the database, it will be possible to evaluate toxicological
response to
specific agents or combinations thereof.
I S One practical application of toxicogenetics is to help rank a series of
agents
based upon gene expression. Initial ranking~is done by determining the average
percent
of maximum alteration for a set of genes indicative of a specific stress or
damage, for
example, DNA damage (e.g., waf I, DNA Pol beta, c-abl, cyclin G, Ape, and
Mgmt).
Another method to use gene expression data for prioritizing lead agents is to
20 construct a thorough dose-response curve for all the genes of interest. The
ECSO's for
each gene induced beyond a threshold level is determined (the ECSO is the
concentration
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that induces a gene to half maximum for that agent). Agents can then be ranked
by the
ECSO average for the genes of interest. Agents with the lowest ECSO's would be
considered as more toxic.
The rat gene array can also generate information that can be used to predict
downstream effects, such as which pathways are affected by certain agents.
This is
accomplished by looking at the differential gene expression and analyzing
which
pathways contain the toxicological response, genes and also which pathways the
genes
can affect. This information in turn can be used to predict tissue responses,
whole
organ responses, and/or system responses. The ability to predict whole organ
responses
has great potential in the development of drugs, pharmaceutical compounds, and
even in
the use of chemicals.
The following Examples are provided to illustrate but not to limit the present
invention in any manner. It will be apparent to one of skill in the art that
modifications
can be made while keeping in the spirit and scope of the present invention.
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EXAMPLES
Example 1 Discovery and characterization of toxicology relevant genes by
empirical
data
Section 1. Preparation and printing available rat genes ora a
nzicroarr°ay
a. Polymerase chain reaction
Seventeen thousand two hundred and forty one rat genes were amplified by
polymerase chain reaction (PCR) using M13 forward and M13 reverse primers. The
sequence of the Ml 3 forward primer was CTCAAGGCGATTAAGTTGGGTAAC
(SEQ ID N0:709) and the sequence of the M13 reverse primer was
GTGAGCGGATAACAATTTCACACAGGAAACAGC (SEQ ID N0:710). The M13
reverse primer had a C12 amine link attached to insure binding of the sense
strand (5'-
3') of the PCR product to the glass microarray slide. The amine linker can be
added
during synthesis of a primer at several any commercial sources, e.g.,
Synthegen.
The following ingredients were combined for the PCR reaction: 21 ~,l HZO, 2.5
~,1 lOX PCR buffer, 0.12 ~,l of lOmM dNTPs, 1 p.1 of 25 ng/~,1 M13 forward
primer, 1 ~,1
of 25 ng/~l M13 reverse primer, a sample of the clone from glycerol stock, and
0.5 ~,l
Taq polymerase for a total volume of 25 ~,1. The reaction mix was run at
95°C for 5
minutes and then cycled 35 times under the conditions of 95° C for 30
seconds, 45°C
for 30 seconds, 72° C for 30 seconds, and followed by 72° C for
5 minutes and finally
4°C until samples are removed from the thermocycler. About 4 ~,1 of the
PCR product
was removed and run on a 1% agarose gel to ascertain the success of the PCR
reaction.
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b. Attaching-toxicologically relevant eg nes to Mass slides
The amplified product was purified by a standard ethanol precipitation method
and
alternatively by commercial PCR clean-up kits, e.g. Millipore, Qiagen. The
cleaned-
up PCR product was then immobilized or "spotted" onto a glass slide which can
react
with the amine group on the amplified product and form a covalent linkage. PCR
product was spotted on the coated glass slide using an MD Generation II Array
Spotter.
The terminology and equipment used in this example comprised the following:
Spotter: MD Generation II Array Spotter main instrument
Spotting Chamber: Area of spotter enclosed in glass which houses the pins,
plates,
0 trays and most spotter machinery.
Controller: Dedicated Dell Computer and Monitor to right of Spotter Unit
Pins: (6) fine tubes in the Spotter Unit which pick-up and spot the Target
Slides: Std. size glass microscope slides with a special coating on one side
Plates: Plastic 96 well plates which hold the Target solution to be spotted
. 5 Target: A solution of PCR product which the spotter deposits on the
slides.
N2 Tank: 5 ft. high steel gas tank labeled "Nitrogen, Compressed"
N2 : The N2 gas from the N2 tank
Air Conditioner: Kenmore air conditioner installed in window of spotting
chamber
Humidifier 1: Essick 2000 Evaporative Cooler against the window
?0 Humidifier 2: Bemis Airflow with white flexible duck into the Spotter Unit
Humidifier 3: Bemis Airflow against the wall
Humidifier 4: Kenmore QuietComfort 7
Vacuum Pump: Gast Laboratory Oilless Piston Vacuum Pump
Dampbox: The plastic sealable container containing an NaCl 1 water slurry
Materials used for reagent solutions were: Nanopure water, 0.2 M KCl (1/10
dilution of Stock 2M KCL in water), and 95% EtOH. The temperature control was
adjusted to 60°. The spotter chambers were adjusted to be greater than
39 °1o relative
humidity and less than 65° C. The spotting pins were pre-washed for 20
cycles. The
glass slides were first each blown with N2 gas for about 2 seconds per side.
The slides
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were inserted into the Spotter following Array Spotter Run V alues. The slides
were
aligned using a clean narrow rod orienting it on the center right edge of the
slide and
gently pushed to the left until the slide was aligned vertically against the
metal pins.
After slides were loaded and straightened, a visual check was done to make
sure no
more debris had fallen. The humidity was confirmed to be greater than 39%
relative
humidity. The MD spotter recognizes 16 plates as a maximum for a run and will
pause
automatically after 8 plates. The MD spotter also advances sequentially to
plates in an
invariable order and is not programmable to accommodate unique plate sourcing
scheme. Therefore, it was important to manually rotate (or shuffle) plates to
accomplish the spotting for the rat arrays. The genes (PCR products) were
spotted in
duplicate on each slide and a total of 3000 genes were printed on a single
slide (total
6000 spots). There were 6 slides in a set for inclusion of all 17,241 genes.
The printed
(spotted) microarrays were examined for quality control purposes under a phase
contrast microscope to evaluate spot morphology and presence of all genes.
c Blocking (Slide Preparation post-spotting)
This blocking procedure is important because it reduces the non-specific
background signals. The amounts provided in this protocol are for 19 slides,
however, a
skilled artisan may make modifications accordingly. More staining dishes and
slide
racks will be required if more than 19 slides are to be blocked. A clean glass
container
was obtained and filled with Nanopure H20. The container was placed on a hot
plate
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and heated to a high temperature. A blocking solution was made by adding 2.5
ml of
20% SDS to SOOmL blocking solution bottle. The blocking solution was warmed in
microwave for 2.5 minutes and checked to determine if the temperature had
reached
$0°C. If the temperature of the solution was not at yet 50°C,
then the solution was
warmed in the microwave at 10 second intervals until it reached the desired
temperature. One staining dish was placed on an orbital shaker with 4x SSC
solution
and turned to an agitation speed of 75 rpm. Slides were placed in metal racks
and placed
in boiling water for several minutes (e.g., 2 minutes). The slides were taken
out of
boiling water and allowed to cool briefly. The slides were then transferred to
staining
container containing 4x SSC solution on orbital shaker for several minutes
(e.g., 2
minutes), rinsed with nanopure water in a staining container, and then briefly
placed in
blocking solution for about 15 minutes. After 15 minutes, the slides were
taken out of
the blocking solution and rinsed three times by dipping into three separate
containers
with nanopure water each time. The tops of the slides were dabbed lightly with
a tissue
and the slides were placed in a centrifuge for about 5 minutes at a speed of
1000 rpm.
Section 2. Toxicity studies to obtain pat cDNA to test determine differential
expression ofgenes
a. Dosing of rats and harvesting of tissue after exposure to toxic doses of
dru~,s/chemicals in vivo
Sprague-Dawley male rats, approximately 2.5 months old, were used for toxicity
testing. The experimental design of exposing rats to toxic doses of
drugslchemicals
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includes determination of the toxic dosage and the route of administration of
the
compound. Rats are divided into treated rats that receive a specific
concentration of the
compound and the control rats that only receive the vehicle in which the
compound is
mixed into solution or suspension (e.g., saline). Where possible, saline was
used as the
vehicle. Rats are injected with a drug, compound, or appropriate vehicle
intraperitoneal
with a volume of l Oml/kg body weight. The concentrations of each drug or
chemical
dosed are the dose at which toxicity has been documented by traditional
toxicology
methods (e.g. histopathology, serum chemistry, hematology) and a second dose
is 25%
of the toxic dose. The rats are dosed after not having food for 10 hours and
then
sacrificed at 6h, 24h, and 72h later. Three control rats and three treated
rats are
euthailized at each timepoint for each drug. Each rat is heavily sedated with
an
overdose of C02 by inhalation and then a maximum amount of blood drawn. This
blood is separated into a clot tube for isolation of serum, and into a
heparinized tube for
isolation of blood lymphocytes. Exsanguination of the rat by this drawing of
blood kills
the rat. The method of collecting the tissues is very important and ensures
preserving
the quality of the mRNA in the tissues. The body of the rat is then opened up
and
several prosectors rapidly remove the specified organs/tissues and immediately
place
them into liquid nitrogen. Blood lymphocytes, serum, urine, liver, lung,
heart, testes,
spleen, bone marrow, brain, and other targets that may be specific targets of
the
drug/chemical were harvested. All of the organs/tissues are completely frozen
within 3
minutes of the death of the animal to ensure that mRNA does not degrade. The
CA 02440008 2003-09-03
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organs/tissues are then packaged into well-labeled plastic freezer quality
bags and
stored at -80 degrees until needed for isolation of the mRNA from a portion of
the
organ/tissue sample.
Serum chemistry changes were evaluated at 24 hours and 72 hours.
Histopathology was evaluated by a pathologist at 72 hours for evidence of
toxicity.
Hematology and urine analyses were evaluated at 72 hours.
b. Isolation of total RNA From Animal
To isolate high quality and high purity total RNA from tissue samples, the
following materials axe used: Qiagen RNeasy midi kits, 2-mercaptoethanol,
liquid NZ,
tissue homogenizer, dry ice.
It is important to take precautions to minimize the risk of RNA degradation by
RNase. Samples should be kept on ice when specified, gloves are worn at all
times and
work areas and equipment are treated with an RNase inhibitor, e.g." RNase Zap
(Ambion~ Products, Austin, TX). In order to prevent RNA degradation, it is
highly
preferable that the work area and materials used for this procedure are clean
and RNase-
free. Autoclaving tips and microfuge tubes does not eliminate RNases. The
following
protocol is based on Qiagen~ RNeasy~ midi kit with modifications for optimal
results.
This total RNA isolation technique is used for RNA isolation from animal
tissue and
can be modified to accommodate smaller samples.
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If tissue needs to be broken, it can be placed on a double layer of aluminum
foil
which is placed within a weigh boat containing a small amount of liquid
nitrogen. The
aluminum foil was placed around the tissue and then a blunt force was applzed
to the
tissue with a small foil-wrapped hammer.
For liver or kidney, about 0.15-0.20 g of tissue was weighed and placed in a
15
ml conical tube. All tissue were kept on dry ice when other samples were being
weighed.
About 3.8 ml of RLT buffer was added to the tube containing the sample. The
RLT bufferC~ from Qiagen can be prepared beforehand by adding 10 p1
betamercaptoethanol to each 1.0 ml of lysis buffer needed. The tissue was
homogenized using the rotor-stator homogenizer fox 45 seconds. A IKA Ultra
Turrax
T25 homogenizer set at speed 4 with the S25N-l OG dispersing element can be
used.
Alternatively, a Virtishear Cyclone 750W rotor/stator homogenizer (Virtis item
#
278077) can be used with the 7 mm microfine sawtooth shaft and generator (195
mm
long with a processing range of0.25 ml to 20 ml, item # 372718). After
homogenization, samples were stored on ice until all samples were homogenized.
Ta
clean the homogenizing tip between samples, the tip was first run for a few
seconds in
95 % ethanol and then rinsed by squirting with fresh 95% ethanol. This process
was
repeated with nanopure water.
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The tissue lysate was centrifuged at room temperature for 10 minutes at 3700-
3800 rpm in a Beckman GS-6 (or equivalent) centrifuge to remove nuclei thus
reducing
DNA contamination.
The supernatant of the lysate was transferred to a clean 15 ml conical tubes
containing an equal volume of 70% EtOH in DEPC treated HZO, being careful not
to
include any of the pellet or fatty layer and mixed. About 3.8 ml of sample was
added to
the RNeasy spin column placed in a 15 ml centrifuge tube and centrifuged at
3000 x g
(3690-3710 rpm, Beckman GS-6) for 5 min. The flow-through was discarded. The
remaining sample was added to the appropriate column and spun at 3000 x g for
5
l0 minutes and the flow-through was discarded.
About 4.0 ml of Buffer RW 1 (Qiagen~) was added to the column and spun as
before then about 2.5 ml of buffer RPE (Qiagen~) was added to column and spun
at
3000 x g (3690-3710 rpm, Beckman GS-6) for 2 minutes. In this example, RPE
buffer
was supplied as a concentrate so 4 volumes of 95% EtOH was added before use.
For
15 the midi kit, about 220 ml of 95% EtOH would be added to 55 ml of RPE.
Another 2.5
ml of buffer RPE was added and spun for 5 minutes to also dry out column. The
column, including the tip, should be dry for the next elution step.
For elution, the column that has the RNA bound to a clean 15 ml tube was
transferred and 200 p.1 of RNase-free water was added to the column, allowed
to sit for
20 1 minute, and spun for 3 minutes at 3000 x g (3690-3710 rpm, Beckman GS-6).
This
step was repeated into the same tube but with 200 p.1 RNase-free water.
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c. Removal of contaminant DNA
Isolated RNA samples can be precipitated using the following lithium chloride
(LiCI) process either before or after measuring absorbance reading for
quantitation
purposes. The volume of the sample was measured. To this, about 1/3 volume of
LiCI
PPT Solution from Ambion (Cat # 9480) was added and mixed by inverting the
tube.
The LiCI should be in solution. If not, it may be necessary to adjust the pH
to 8Ø The
solution was placed at -20 ° C fox 30 minutes and centrifuged at
4°C and 13,000 RPM
for L O minutes. If there is no visible pellet, it may help to return the
sample to -20°C
L O overnight and then repeat the centrifiigation. The supernatant was
transferred to a
separate tube and washed by adding 1 ml of ice cold 70% ethanol in DEPC
treated
water and gently inverted. Then the tube was centrifuged at 4° C for 10
minutes and
the supernatant was discarded and the pellet was air dried. The pellet was
resuspended
in RNA storage buffer (Ambion Cat # 7000).
Alternatively the contaminant DNA was removed by incorporating the DNAse step
in Qiagen~ midi kit procedure as described in the instructions for the kit.
d. Measure quantity of RNA
To measure yield, the O.D. at 260 nm was taken and about 2.0 ~l RNA was
added to 98 p.1 H20. The following formula was used for calculations:
(Absorbance) x (dilution factor) x (40)/1000 = amount of RNA in pg/ml
For a sample calculation:
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absorbance = 0.45
dilution factor = 50
(0.45 x 50 x 40) / 1000= RNA concentration in pg/ml
S e. MicroarraY reverse transcription reaction
Fluorescence-labeled first strand cDNA probe was made from total or mRNA by
first isolating RNA from control and treated cells, disclosed supra. This
probe is
hybridized to microarray slides spotted with DNA specific for toxicologically
relevant
genes. The materials needed to practice this example are: total or messenger
RNA,
L 0 primer, Superscript II buffer, dithiothreitol (DTT), nucleotide mix, Cy3
or CyS dye,
Superscript II (RT), ammonium acetate, 70% EtOH, PCR machine, and ice.
The volume of each sample that would contain 20pg of total RNA (or 2pg of
mRNA) was calculated. The amount of DEPC water needed to bring the total
volume
of each RNA sample to I4 p1 was also calculated. If RNA is too dilute, the
samples are
1S concentrated to a volume of less than 14 p.1 in a speedvac without heat.
The speedvac
must be capable of generating a vacuum of 0 Milli-Torr so that samples can
freeze dry
under these conditions. Sufficient volume of DEPC water was added to bring the
total
volume of each RNA sample to 14 p.1. Each PCR tube was labeled with the name
of the
sample or control reaction. The appropriate volume of DEPC water and 8 p.1 of
20 anchored oligo dT mix (stored at -20°C) was added to each tube.
Then the appropriate volume of each RNA sample was added to the labeled
PCR tube. The samples were mixed by pipeting. The tubes were kept on ice until
all
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CA 02440008 2003-09-03
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samples are ready for the next step. It is preferable for the tubes to kept on
ice until the
next step is ready to proceed. The samples were incubated in a PCR machine for
10
minutes at 70°C followed by 4°C incubation period until the
sample tubes were ready to
be retrieved. The sample tubes were left at 4°C for at least 2 minutes.
S ~ The Cy dyes are light sensitive, so any solutions or samples containing Cy-
dyes
should be kept out of light as much as possible (e.g., cover with foil) after
this point in
the process. Sufftcient amounts of Cy3 and CyS reverse transcription mix were
prepared for one to two more reactions than would actually be run by scaling
up the
following recipes:
_For labeling with Cy3
8 u1 Sx First Strand Buffer for Superscript II
4 u1 0.1 M DTT
2 u1 Nucleotide Mix
2 u1 of 1:8 dilution of Cy3 (e.g., 0.12SmM cy3dCTP).
1 S 2 u1 Superscript II
For labelin wg ith C
8 u1 Sx First Strand Buffer for Superscript II
4 u1 0.1 M DTT
2 u1 Nucleotide Mix
2 u1 of 1:10 dilution of CyS (e.g., O.ImM CySdCTP)
2 u1 Superscript II
About 18 w1 of the pink Cy3 mix was added to each treated sample and 18 ~.l of
2S the blue CyS mix was added to each control sample. Each sample was mixed by
pipeting. The samples were placed in a PCR machine for 2 hours at 4S°C
followed by
4°C until the sample tubes were ready to be retrieved. The samples were
transferred to
Eppendorf tubes containing 600 L~l of ethanol precipitation mixture. Some of
the EtOH
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precipitation mixture was used to rinse the PCR tubes. The tubes were inverted
to mix.
Samples were placed in -80°C freezer for at least 20-30 minutes. If
desired, samples
may be left at -20°C overnight or over the weekend.
f. Removal of impurities from the reverse transcription reaction
In addition to the desired cDNA product, the completed RT reaction contains
impurities that must be removed. These impurities include excess primers,
nucleotides,
and dyes. One method of removing the impurities was by following the
instructions in
the QIAquick PCR purification kit (Qiagen catalog #120016).
Alternatively the completed RT reactions were cleaned of impurities by ethanol
precipitation and resin bead binding. The samples were centrifuged for 15
minutes at
20800 x g (14000 rpm in Eppendorf model 5417C) and carefully the supernatant
was
decanted. A visible pellet was seen (pinklred for Cy3, blue for Cy5). It is a
preferable
to centrifuge the tubes at a fixed position so the pellet will be at a known
area in the
1 S tube. In some rare instances, the probe is seen spread on one side of the
tube instead of
a tight pellet. If the pellet is white or nonexistent, the reaction has not
occurred to
maximal efficiency. Ice cold 70% EtOH (about 1 ml per tube) was used to wash
the
tubes and the tubes were subsequently inverted to clean tube and pellet. The
tubes were
centrifuged for 10 minutes at 20800 x g (14000 rpm in Eppendorf model 5417C),
then
the supernatant was carefully decanted. The tubes were flash spun and any
remaining
EtOH was removed with a pipet. The tubes were air dried for about 5 to 10
minutes.
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protected from light. The length of drying time will depend on the natural
humidity of
the environment. For example, an environment in Santa Fe would require about 2
to S
minutes of drying time. It is preferable that the pellet is not overdried.
When the
pellets were dried, they are resuspended in 80 u1 nanopure water. The
cDNA/mRNA
hybrid was denatured by heating fox S minutes at 9S°C in a heat block
and flash spun.
Then the lid of a "Millipore MAHV N4S" 96 well plate was labeled with the
appropriate sample numbers. A blue gasket and waste plate (v-bottom 96 well)
was
attached. Wizard DNA Binding Resin (Promega catalog #A11S1) was shaken
immediately prior to use for thorough resuspension. About 160 p,1 of Wizard
DNA
Binding Resin was added to each well of the~filter plate that was used. If
this was done
with a multi-channel pipette, wide orifice pipette tips would have been used
to prevent
clogging. It is highly preferable not to touch or puncture the membrane of the
filter
plate with a pipette tip. Probes were added to the appropriate wells (80 p,1
cDNA
samples) containing the Binding Resin. The reaction is mixed by pipeting up
and down
1 S ~10 times. It is preferable to use regular, unfiltered pipette tips for
this step. The plates
were centrifuged at 2500 rpm for S minutes (Beckman GS-6 or equivalent) and
then the
filtrate was decanted. About 200 p1 of 80% isopropanol was added, the plates
were
spun for S minutes at 2500 zpm, and the filtrate was discarded. Then the 80%
isopropanol wash and spin step was repeated. The filter plate was placed on a
clean
collection plate (v-bottom 96 well) and 80 p,1 of Nanopure water, pH 8.0-8.S
was added.
The pH was adjusted with NaOH. The filter plate was secured to the collection
plate
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with tape to ensure that the plate did not slide during the final spin. The
plate sat for S
minutes and was centrifuged for 7 minutes at 2500 rpm.
~. Fluorescence Readings of cDNA Probe and Hybridization on the Microarray
It is optional to semi-quantitatively assess the incorporation of fluorescence
into
cDNA probes. This incorporation of fluorescence provides a measure of the
quantity of
dye incorporated in the cDNA of the cleaned-up RT product and provides
evidence if
the enzyme action or dye incorporation failed. Visual evaluation of the color
of the RT
product cleaned up using the QIAquick PCR purification kit (Qiagen cat#120016)
is an
alternative method to determine if the RT reaction failed.
It is preferable that a consistent amount of cDNA is pipeted into each well of
the
384-well, 100 p1 assay plate (Falcon Microtest cat#35-3980) plate because
readings will
vary with volume. Controls or identical samples should be pooled at this step,
if
required. The probes were transferred from the Millipore 96 well plate to
every other
well of the 384 well assay plate. This was done using a mufti-channel pipette.
For
replicate samples that have been pooled, 60 ~.I aliquots were transferred into
wells of
the assay plate. The Cy-3 and Cy-5 fluorescence was analyzed using the Wallac
Victor
1420 Multilabel counter workstation programmed for reading Cy3-Cy-5 in the 384-
well
format and the data was saved to disk. The typical range for Cy-3 (20pg) is
250-
700,000 fluorescence units. The typical range for Cy-5 (20~,g) is 100-250,000
fluorescence units. Settings for the Wallac 1420 fluorescence analyzer were as
follows:
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CW lamp energy = 30445
Lamp filter = PSSO slot B3
Emission filter= D572 dysprosium slot A4
S Emission aperture = normal
Count time = 0.1 s
Cy5
CW lamp energy = 30445
0 Lamp filter . = D642 samarium slot B7
Emission filter= D670 slot A8
Emission aperture = normal
Count time = 0.1 s
L S h. Dry-down Process
Concentration of the cDNA probes is often necessary so that they can be
resuspended in hybridization buffer at the appropriate volume. A sample of
control
cDNA (Cy-S) is mixed with each test cDNA (Cy-3). This is very important
because it
allows hybridization of treated and the appropriate control cDNA samples on
the same
~0 microarray. Eppendorf tubes were labeled for each test sample and the mixed
cDNA
samples were added to the appropriate tubes. These tubes were placed in a
speed-vac to
dry down, with foil covering any windows on the speed vac. At this point, heat
(4S°C)
may be used to expedite the drying process. Time will vary depending on the
machinery. The drying process takes about one hour for I SO pI samples dried
in the
2S Savant. Samples may be saved in dried form at -20°C for up to I4
days.
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i. Microarra~Hybridization
To hybridize labeled cDNA probes to single stranded, covalently bound DNA
target genes on glass slide microarrays, the following material were used:
formamide,
SSC, SDS, 2 pm syringe filter, salmon sperm DNA (Sigma, cat # D-7656), human
Cot-
1 DNA (Life Technologies, cat # 15279-O11), poly A (40 mer: Life Technologies,
custom synthesized), yeast tRNA (Life Technologies, cat # 15401-04),
hybridization
chambers, incubator, coverslips, parafilm, heat blocks. It is preferable that
the array is
completely covered to ensure proper hybridization.
About 30 p.1 of hybridization buffer was prepared per cDNA sample (control rat
cDNA plus treated rat cDNA). Slightly mole than is what is needed should be
made
since about 100 ~.1 of the total volume made for all hybridizations can be
lost during
filtration.
Hybridization Buffer: for 100 u1:
~ ' S0% Formamide 50 p,1 formamide
~ 5X SSC 25 p1 20X SSC
~ 0.1 % SDS 25 ~.~1 0.4% SDS
The solution was filtered through 0.2 ~m syringe filter, then the volume was
measured. About 1 p1 of salmon sperm DNA (lOmg/ml) was added per 100 ~l of
buffer.
Alternatively, the hybridization buffer was made up as:
Hybridization Buffer: for 101 u1:
50% Formamide 50 ~.I formamide
~ lOX SSC 50 ~.l 20X SSC
~ 0.2% SDS 1 f.~,l 20% SDS
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The solution was filtered through 0.2 ~m syringe filter, then the volume was
measured. One microliter of salmon sperm DNA (9.7mg/ml), O.S p,I Human Cot-1
DNA (S p.g/pl), O.S ~,l poly A (S p.g/wl), 0.25 p.1 Yeast tRNA (10 p.g/~,1)
was added per
100 p1 of buffer.
S Materials used for hybridization were: 2 Eppendorf tube racks, hybridization
chambers (2 arrays per chamber), slides, coverslips, and parafilm. About 30
~.l of
nanopure water was added to each hybridization chamber. Slides and coverslips
were
cleaned using N2 stream. About 30 p,1 of hybridization buffer was added to
dried probe
and vortexed gently for S seconds. The probe remained in the dark for 10-1 S
minutes at
room temperature and then was gently vortexed for several seconds and then was
flash
spun in the microfuge. The probes were boiled for S minutes and centrifuged
for 3 min
at 20800 x g (14000 rpm, Eppendorf model S417C). Probes were placed in 70
°C heat
block. Each probe remained in this heat block until it was ready for
hybridization.
Pipette 25 p.1 onto a coverslip. It is highly preferable to avoid the material
at the
1 S bottom of the tube and to avoid generating air bubbles. This may mean
leaving about 1
p.1 remaining in the pipette tip. The slide was gently lowered, face side
down, onto the
sample so that the coverslip covered that portion of the slide containing the
array.
Slides were placed in a hybridization chamber (2 per chamber). The lid of the
chamber
was wrapped with parafilm and the slides were placed in a 42°C humidity
chamber in a
42°C incubator. It is preferable to not let probes or slides sit at
room temperature for
Long periods. The slides were incubated for 18-24 hours.
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j. Post-H bridization Washing.
To obtain only single stranded cDNA probes tightly bound to,the sense strand
of
target cDNA on the array, all non-specifically bound cDNA probe should be
removed
from the array. Removal of all non-specifically bound cDNA probe was
accomplished
S by washing the array and using the following materials: slide holder, glass
washing
dish, SSC, SDS, and nanopure water. It is highly preferable that great caution
be used
with the standard wash conditions as deviations can greatly affect data.
Six glass buffer chambers and glass slide holders were set up with 2X SSC
buffer heated to 30-34°C and used to fill up glass dish to 3/4th of
volume or enough to
l0 submerge the microarrays. It is important to exercise caution in heating of
the 2X SSC
buffer since a temperature of greater than 35°C might strip off the
probes. The slides
were removed from chamber and placed in glass slide holders. It is preferable
that the
slides are not allowed dry out. The slides were placed in 2X SSC buffer but it
is
recommended that no more than 4 slides be placed per dish. Coverslips should
fall off
15 within 2 to 4 minutes. In the event that the coverslips do not fall off
within 2 to 4
minutes, very gentle agitation may be administered. The stainless steel slide
carriers
were placed in the second dish and filled with 2X SSC, 0.1 %SDS. Then the
slides were
removed from glass slide holders and placed in the stainless steel holders
submerged in
2X SSC, 0.1 %SDS and soaked for 5 minutes. The slides were transferred in the
20 stainless steel slide carrier into the next glass dish containing O.1X SSC
and 0.1%SDS
for 5 minutes. Then the slides are transferred in the stainless steel Garner
to the next
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glass dish containing only O.1X SSC for 5 minutes. The slides, still in the
slide carrier,
were transferred into nanopure water (18 megaohms) for 1 second. To dry the
slides,
the stainless steel slide earners were placed on micro-earner plates with a
folded paper
towel underneath. The top of the slides was gently dabbed with a tissue. Then
the slides
were spun in a centrifuge (Beckman GS-6 or equivalent) for 5 minutes at 1000
rpm. It
is very important that the slides spin dry instead of air dry, as air drying
leads to
increased background.
Section 3. Evaluation of differential expression of 17,241 ge~zes in rats
exposed
L 0 to toxins
a. Identification of rat toxicologicall~relevant genes
Sprague-Dawley male rats, approximately 2.5 months old, were used for toxicity
testing. Three rats were injected intraperitoneally with a drug/chemical at
each dose per
sacrifice timepoint and three other rats were used as control animals as
described above
in section (a) of Toxicity studies. The drugs/chemicals dosed for the testing
of the
17,241 gene array were as follows:
Compound testedDosage used Organ samples collected
cadmium chloridelmg/kg 6h liver, 24h liver, 72h lung,
24h testes
chlorpromazine 30 mg/kg 24h liver
25% ethanol 2.5 mllkg 24h liver
methotrexate 5 mg/kg 72h liver, 72h lung, 72h spleen,
72h testes
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aflatoxin 1 mgJkg 72h liver, 6h liver
DL-ethionine 300 mg/kg 72h liver
tetracycline 200 mg/kg 24 h liver
puromycin 150 mglkg 72h kidney
cisplatin 10 mg/kg 72h kidney
gentamicin 150 mg/kg 24h kidney
diflusinsal 100 mglkg 72h kidney
amphotericin 20 mg/kg 24h kidney
B
busulfan 10 mg/kg 72h Iung
endotoxin 8 mg/kg 24h spleen
benzo-a-pyrene 30 mg/kg 72h spleen
TODD 0.03 mg/kg 72h spleen
cyclosporin A $0 mg/kg 24h spleen
doxorubicin 9 mg/kg 72h heart
The tissue samples shown in the table above along with the corresponding
tissue
from a rat injected with the vehicle were processed for cDNA with dye
incorporated as
described in section 2. The set of 6 microarray slides these cDNA samples were
hybridized on was described in section 1 and the target spotted on them were
the PCR
products from 17,421 genes. The washed and dried hybridized slides were
scanned on
Axon Instruments Inc. GenePix 4000A MicroArray Scanner and the fluorescent
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readings from this scanner converted into quantitation files on a computer
using
GenePix software.
b Use of algorithms to identify select and evaluate toxicologically relevant
5. enes
A two-step approach was used in ranking candidate genes from the array
comprising approximately 17,421 rat genes, known herein as "17k array", for
possible
inclusion on the comprehensive toxicity (CT) array.
First, three cutoff criteria were specified for individual gene values from
experiments involving expression analysis of the 17,421 rat genes: The three
cutoff
criteria were: fold inductionlrepression level, average fluorescence of the
replicate spots
used to calculate expression level, and coefficient of variation of the
replicate spots.
To calculate fold induction/repression level, the stored inductionlrepression
level of a
gene in a particular experiment has been calculated as follows:
1 S 1 ). arrive at a treatment score for the gene. The treatment score was
represented
by the amount of Cy3 labeled cDNA from a treated source (e.g., laboratory
animals
dosed with a compound) that had bound to a complementary target DNA spot of
the
microarray slide. The amount of Cy3 labeled cDNA was detected by a microarray
laser
scanner at a wavelength of 532nm.
2) arrive at a control score for the gene. The control score was represented
by
the amount of Cy5 labeled cDNA from an untreated source that had bound to a
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complementary target DNA spot of the microarray slide. The amount of Cy5
labeled
cDNA was detected by a microarray laser scanner at a wavelength of 635nm. The
unit
of measure was the pixel intensity or the average of several pixel intensities
reported by
a microarray laser scanner at coordinate on a microarray slide. The pixel
intensity at
that location was proportional to the number of photons detected by a
photomultiplier
tube when a spot of target DNA labeled with fluorescent probe was illuminated
by a
Iaser with a wavelength to which the dye is sensitive. For an Axon Instruments
Inc.
GenePix 4000A MicroArray Scanner, which was used in these experiments, these
values are between 0 and 65535.
l0 3) compute an un-normalized treated-to-control ratio by dividing the
treatment
score by the control score
4) compute a final, "normalized" induction score by dividing the un-normalized
ratio by some normalization factor. For example, using the following 4-steps
procedure
above, calculation of Gene A is performed as follows: 1) Suppose that the
average of
its set of four raw treated values is 100,000 2) Suppose that the average of
the set of its
four raw control values is 25,000 3) The un-normalized ratio would thus be 4,
and
finally 4) If the normalization factor (designed to take into account
environmental
effects) turned out to be 2, one would end up with at a final, normalized
induction score
(often called fold induction) of 4 divided by 2, ar 2. In this example, Gene A
was
induced two-fold. In all experiments conducted with respect to this invention,
there
were four replicates of each gene, with each replicate having a treated and a
control
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value. Thus, the calculation of an expression level for each gene in an
experiment
involved aggregating eight data points.
The average fluorescence level of the replicate spots used 'to calculate the
expression level is accomplished by a simple average of the four treated
replicate values
used in any experiment to calculate the expression level of a gene.
The coefficient of variation of the replicate spots was a conventional measure
of
variability, expressed as a percentage, that in this case was derived by
dividing the
standard deviation of the four replicate treated-to-control ratios by the
average of the
four replicated treated-to-control ratios. The latter criteria represent
useful measures of
data quality. Thus, initial screening is based on expression level and
measurement
quality.
Algorithms were written specifically to perform the entire process of ranking
genes to be included from the 17K array on to the CT array. In the initial
part of the
program, the three criteria above were "ended" together, so that in order to
"make the
first cut" the gene would have to meet all three criteria. This was considered
the first
tier in the program.
The criteria are adjustable within the algorithms. For the actual ranking of
the
17k array, the following criteria were used: induction/repression level: 2;
fluorescence
level: 400; and a coefficient of variation: 30%. To make the first cut and be
selected as
a potential toxicologically relevant gene, a gene only had to meet the 3
criteria within
one experiment stored in the 17K warehouse of data. Likewise, relevant values
for the
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gene would have been included each time it met the criteria within a different
experiment. The data for genes that made the cut (and hence were selected as
potential
toxicologically relevant genes) and each time the genes made the cut were
stored in a
separate, temporary data table for ranking (the second tier in the process). A
gene's
data could be included more than once: one time for each experiment in which
that gene
met the three criteria.
Each of the factors listed in the table below was given a relative weight, as
indicated:
RELATIVE WEIGHT OF
EACH SCORING FACTOR
(0 - 5)
I~3umber of Compounds 3 Avg. of Fold Induction3 Avg. Fluorescence3
Gene Made Cut Magnitude
Consistency Across 3 COV of Fold Induction3 Tissue Hit Consistency3
Duplicate Slides
Next, gene values that made the cut were aggregated into overall scores. It
was
necessary to "aggregate" the potentially more-than-one values for each gene
into overall
scores for the gene because data for a particular gene were included for each
experiment
in which that gene's values met the 3 cutoff criteria described above. Overall
scores
were aggregated for each six factors, as shown in the table above, and ranked
for each
gene, based on six ranking criteria: 1 ) Number of slides on which that gene
met the
cutoff criteria (NC = number of compounds). As noted, a gene could meet the 3
cutoff
criteria described above in more than one of the experiments stored in the 17K
warehouse. NC is a simple count of the number of different compounds (not
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experiments, as duplicate experiments were performed for each compound) in
which
that gene met the 3 criteria, 2) Percent of consistency between slides (%
time~the gene
value made the cutoff criteria on the replicated slide for that initial slide)
(CC). As
mentioned above, duplicate experiments were performed for each compound. CC is
a
S count of the number of times the gene made the cutoff in both of the
duplicate
experiment pair. Thus, a gene could have an NC (number of compounds) of 3 but
a CC
(compound consistency) of 2, meaning that in two of the three compounds it
made the
cutoff in each of the duplicate experiments, and in one of the compounds, it
did not.
3) Average magnitude (absolute value) of fold induction for all occurrences
where that
gene made the cutoff criteria (FI). This is a simple average of the magnitude
of the
expressian/repression levels for each set of data values for a particular
gene.
4) coefficient of variation of those fold induction scores (unlike all the
other ranking
criteria, a lower coefficient of variation is deemed better) (CV). The
coefficient of
variation applied to the set of expression values for a particular gene to
assess the
variability of its scores. 5) Average fluorescence value of all replicate
spots of
occurrences where that gene made the cutoff criteria (FL). This is a simple
average of
the fluorescence levels of the treated values for each occurrence of a gene
that had made
the cut. 6) Tissue consistency, i. e., what percent of cutoff meeting
occurrences of the
gene were in the same tissue (CT). Expression levels were measured not only in
several
compounds but in several tissues as well (liver, kidney, etc.) CT was
calculated as the
percentage of time the gene data values which made the cutoff were measured in
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same tissue. For example, if a gene had made the cut in four experiments,
twice in liver
and twice in kidney, its tissue consistency would be 50%.
The following weightings were used in the actual process of ranking genes for
inclusion on the CT array: NC=3, CC=I, FI=5, CV=0, FL=0, CT=0. Thus, the final
three criteria received no weight in this case.
Each gene was assigned a score between 0 and 100 for each ranking criterion.
Each ranking criterion score was computed as follows: The range of values fox
all
genes was computed for the criterion by subtracting the lowest value present
among all
scores from the highest. The temporary data table compiled from the I7K
warehouse
LO included scores for every gene that had met the initial 3 cutoff criteria.
A gene would
be present in the table with values for each experiment in which it had met ar
surpassed
the 3 cutoff criteria. Scores were then aggregated from the gene occurrences
of each
gene into an overall score for that gene for each of the six criteria
described above. For
example, if Gene A made the cut in three experiments with respective induction
scores
I S of 4, 6, and 8 then the aggregated induction score for Gene A would be 6
(the average
of the three values). Further, for example, suppose the gene with the highest
overall
score on the induction factor had an overall score of 10, and the lowest an
overall score
of 2. Then, Gene A would receive a rating of 50%, because its score was
halfway
between the highest and the lowest. The score for each gene was then
calculated by
20 subtracting the lowest value present from the value for that gene, then
dividing by the
range and multiplying by 100. In other words, the score fox each gene is the
percent
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above the minimum present toward-the maximum. For example, if a gene's score
was
three-fourths of the way between the minimum present and the maximum fox that
criterion, its score would be between the minimum present and the maximum for
that
criterion, its score would be 5%. Since for the CV factor (coefficient of
variation of
fold inductions) lower was deemed better, the score thus computed was
subtracted from
100 to invert the percentage.
The final ranking score for each gene was computed via a weighted combination
of its score on the six ranking criteria. If a score could not be computed for
a particular
criterion, the entire value of that criterion was removed from the equation ,
and ranking
was based solely on the remaining factors. Each of the ranking criteria could
be
weighted between 0 and 5, and weightings are relative, so that 2:2:2:2:2:2
would be the
same as 4:4:4:4:4:4, etc. A zero weighting would drop the factor from the
equation.
For example, suppose that Gene A had the following scores: NC: 75%, CC: 50%,
FI:
80%, CV: 25%, FL: 50%, and CT: 30%. Using the weightings described above (3,
1, 5,
0, 0, 0) the final score for Gene A would be calculated as follows:
(75*3 + 50* 1 + 80*5 + 25*0 + SO*0 + 30*0) / 9 (NOTE: 9 is the total number of
"weightings" or 3+1+5)
(225+50+400+0+0+0)/9
67519
75 would be the final score for Gene A.
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A score was then computed for each discrete gene based on aggregating the
individual values for that gene from one or more experiments where that gene
had made
the initial cut. The list of genes was then rank-ordered on the basis of final
scores. The
obj ective determination of how many genes to take from the top of the list to
be added
to the CT array was based on the number of experiments that genes showed a
response
in. At about gene number 450 on the Iist of rank-ordered genes the number of
experiments that genes showed a response in started of often be only one
experiment or
one compound. It was desired that most genes on the array have response to
different
mechanisms of toxicity or different in different tissues. Therefore, the
number of genes
l0 chosen from the top of the Iist of rank-ordered genes was 450. Since we
wanted to
minimize the number of duplicate genes added to an already established in-
house set of
rat genes (See Example 2) there were 50 genes that were excluded because of
duplicity.
Ultimately 400 genes were empirically chosen from the 17,241 rat gene set of
microarrays as new genes for further evaluation of response to toxicity by
specif a
toxicants and in specific tissues. These 400 genes are listed in Table 4.
Section 4. Evaluation of empirical data ota specific tissue response of rat
genes
GOYrespO7ZClb12g to the partial sequence discovered from tire 17,241 gene set.
a. Toxicity Studies for further evaluation of~enes discovered empirically
Male Sprague-Dawley rat were exposed to drugs and chemicals listed in table 3,
tissues
harvested, and cDNA samples prepared and hybridized following the description
in
Section 2 of Materials and Methods.
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b. Microarrays
Microarrays were printed with the 40'0 genes discovered empirically following
the description for PCR and spotting slides in Section 1 of Materials and
Methods. The
washed and dried hybridized slides were scanned on Axon Instruments Inc.
GenePix
4000A MicroArray Scanner and the fluorescent readings from this scanner
converted
into quantitation files on a computer using GenePix software.
c. Analysis of guantitation files to evaluate toxicologically relevant enes
Quantitation files were imported into Phase-1 Matrix Express Software designed
for analysis of differential gene expression data. The ratios if the
fluorescent values of
the treated and control cDNA samples hybridized on the same slide were
determined for
each spot and termed fold induction values (positive value for induction of
gene
response and negative value for suppression of gene response). These fold
inductions
are then normalized by the median fold induction value. The fold inductions
for each
gene is an average of the fold inductions for the 4 spots on the slide for
each gene. If
the coefficient of variance for the 4 spots is greater than 50% then the data
for the gene
is not entered for that gene on that slide. The Matrix Express software allows
development of a warehouse containing the fold induction data from multiple
experiments (microarrays). A warehouse was constructed by importing
quantitation
files and analyzing fold inductions for rats treated with drugs and chemicals
listed in
table 3. In addition, most samples were hybridized in duplicate and the data
from 2
high-quality slides was averaged in the warehouse. For rats treated with every
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compound the liver and kidneys were always processed and evaluated for gene
expression. Spleen, heart, testes, lung samples were evaluated the multiple
organ
toxicants. Spleen was evaluated fox all immunotoxicants and 5 non-
immunotoxicants,
heart samples were evaluated for all heart toxicants, testes was evaluated for
flutamide
and all steroid compounds, lung was evaluated for all lung toxicants, and
brain was
evaluated for all brain toxicants. This warehouse contained approximately 2500
final
experiments (primarily averages of 2 duplicate experiments to make 1 final
experiment)
at the time of evaluation for tissue specific response of the genes.
A gene was determined to be response in liver if it had a 2-fold induction
(stimulation or suppression) in more than 1 % of the experiments for liver
samples.
Similarly a gene was determined responsive in the kidney if it had a 2-fold
induction in
more than 1 % of the experiments far kidney samples. A 1 % cut-off was a
generous cut-
off for liver and kidney because these organs were evaluated for all toxicants
{including
non-hepatic or renal toxicants). A gene was determined to be responsive in the
heart,
l 5 spleen, lung, testis, or brain if it had a 2-fold induction in Snore than
2% of the
experiments for the respective organs. The heart, spleen, lung, testis, and
brain cut-off
was higher at 2% compared to 1 % because there were fewer total experiments in
the
warehouse for each of these organs and a higher cut-off miniriiizes false
positive results
when dealing with this smaller number of experiments.
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Results
Discovery of 400 toxic response enes
Four hundred genes were empirically chosen from the 17,241 rat gene set of
microarrays as new genes for further evaluation of response to toxicity by
specific
toxicants and in specific tissues. These 400 genes are listed in Table 4.
Use of the 400 toxicology responsive enes in formation of a database
demonstrating
specific tissue res onse.
The toxicology database contained approximately 2500 final experiments
(primarily
averages of 2 duplicate experiments to make I final experiment), based on the
compounds listed in Table 3, at the time of evaluation for tissue specific
response of the
genes. Table 7 shows the tissue specific response of toxicology genes chosen
empirically from the 17,241 gene set demonstrated for each gene and Table ~
shows the
same information from Table 7 with the genes with tissue specif c response
listed by
1 S tissue. Figures 1 through 6 show the differential gene expression of rats
dosed with
toxic compounds from this toxicology database. The differential expression
between
replicate microarrays, over time, between organs, and between different
compounds is
demonstrated in the figures showing the power of having a set of toxicology
relevant
genes to process rat toxicity studies with.
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Example 2 Production and characterization of known genes for toxicity response
Section 1. Production of clones
a. Identifying and isolating toxicolo ig~ally relevant genes from rat or human
databases
One method that was used to identify and isolate toxicologically relevant
genes
for inclusion in a rat array was to search a public database (e.g., GenBank)
for genes
that have been identified as part of critical cellular pathways (e.g.
metabolism, DNA
synthesis). ' Once these genes were identified, primers were designed and used
in an
amplification process with cDNA library made from rat liver cells. The
amplified
l0 product was cloned into an expression vector and sequenced to confirm that
the
sequence matched or was substantially similar to the gene sequence information
obtained from GenBank. Confirmed amplified gene products were then
incorporated
into a rat array using the methods described in Example I, section 2.
Potential
toxicologically relevant genes which have been identified and isolated in this
manner
15 are included in Table 4.
b. Identifying and isolating genes using de novo primers
Another method used to identify and isolate genes with some evidence of roles
in critical cellular pathways was by first finding the sequence a public
database (e.g.,
20 GenBank) and sequences corresponding within these genes were synthesized de
novo
and used in amplification reactions. The amplified product was~cloned into an
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expression vector and sequenced to confirm that the sequence matched or was
substantially similar to the gene sequence information obtained from GenBank.
Confirmed amplified gene products were then incorporated into a rat array
using the
methods disclosed herein to immobilize the gene product, or target sequence,
to a glass
slide.
Section 2. Evaluation of empirical data ofa specific tissue response of known
genes
a. Toxicity Studies for further evaluation of enes discovered empirically
l0 Male Spraque-Dawley rat were exposed to drugs and chemicals listed in table
3,
tissues harvested, and cDNA samples prepared and hybridized following the
description
in Example 1, Section 2 of Materials and Methods.
b. Microarrays
15 Microarrays were printed with the 300 genes produced as described in
Section 1
of Materials and Methods in this Example 2. The washed and dried hybridized
slides
were scanned on Axon Instruments Inc. GenePix 4000A MicroArray Scanner and the
fluorescent readings from this scanner converted into quantitation files on a
computer
using GenePix software.
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c. Analysis of quantitation files to evaluate potentially toxicologically
relevant
enes
Analysis of experiments in an approximately 2500 experiment warehouse
produced from tissue samples from rats exposed to toxic doses of drugs and
chemicals,
Table 3, is the same as described in Example 1, Section 4.
Results
Potentially toxicology relevant genes which have been identified and isolated
in
this manner are included in Table 4. Table 9 shows the tissue specific
response of
l0 genes with potential roles in critical cellular pathways demonstrated for
each gene and
Table 10 shows the same information from Table 9 with the genes With tissue
specific
response listed by tissue. Figures 1 through 6 show the differential gene
expression of
rats dosed with toxic compounds from this toxicology database. The
differential
expression between replicate microarrays, over time, between organs, and
between
15 different compounds is demonstrated in the figures showing the power of
having a set
of toxicology relevant genes to process rat toxicity studies with.
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Example 3 Discovery Of Novel Toxicity Responsive Genes BY Transcriptome
Profiling
Section 1. Ident~ing arzd isolating genes
a. Processing treated and control tissue samples for RNA isolation
Liver tissue from a rat sacrificed 24h after intraperitoneal injection of a
toxic dose of
aflatoxin B I (I mg/kg) and the appropriate liver tissue from the saline
injected vehicle
control rat were used to determine the differentially expressed genes in a rat
exposed to
a liver toxicant (aflatoxin). RNA was isolated from both liver samples using
an RNA
isolation kit from Qiagen (RNeasy Midi kit) followed by use of a Messageclean~
kit
from Genhunter~. The protocols from the MessageClean° kit were modified
to
generate more optimal conditions for removing DNA contamination. Then, these
ingredients were added: 50 ,u1 total RNA, 5.7 ~l l Ox reaction buffer, 1.0 ~ul
DNase I ( 10
units/lCl) for a total volume of 56.7 ltl. The ingredients were mixed well and
incubated
for 30 minutes at 37° Celsius. Then 40 ,u1 phenol/chloroform mixture
(1:1 volume) was
added and the mixture was vortexed for 30 seconds and allowed to sit on ice
for 10
minutes. Then the tube containing the mixture was spun in an Eppendorf
centrifuge at 4
degrees for 5 minutes at maximum speed. The upper phase was collected,
transferred to
a new tube and 5 ,u1 of 3M NaOAc and 200 ,u1 95% ethanol was added to the
upper
phase. The mixture was allowed to sit for at least one hour at -80° C
and then spun for
about 10 minutes at 4° C. The supernatant was removed and the RNA dried
for a few
minutes. Subsequently, the RNA was suspended in 11 ,u1 DEPC H20. 1 ~,l was
used to
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measure AZ~oizao in 50 ~.1 H20. The RNA was stored as 1-2 ~,g aliquots at -
80°C.
Immediately prior to differential display, the appropriate amount of RNA was
diluted to
0.1 ~,g/~Cl with DEPC H20. It is important to avoid using the diluted RNA
after freeze-
thaw cycle.
RNAimage~' kits were used and protocols from the RNAimage kits were altered to
optimize more successful mRNA differential display. The following section
describes
the method by which this was accomplished:
b. Reverse transcription
LO In a tube, the following ingredients were added: 9.4 ~.1 dH20, 4.0 ,u1 Sx
RT
buffer, 1.6 ~,l dNTP (250 ~,M), 2.0 ~,l of O.I ~,g/~,l freshly diluted total
RNA that was
DNase-free, 2.0 ~.l H-T11M (2 ~,M) for a total volume of 19 ~.1. The
ingredients were
mixed well and incubated at 65°C for 5 minutes, 37°C for 60
minutes, 75°C for 5
minutes, and held at 4°C. After the tubes had been at 37°C for
10 minutes, and 1 ~,l of
Superscript II reverse transcriptase (Life Technologies Inc.) was added to
each reaction,
and quickly mixed by finger tapping the tubes before the incubation continued.
At the
end of the reverse transcription, the tubes were spun briefly to collect
condensation.
The tubes were set on ice for PCR or stored at -20°C for later use.
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c. Pol erase chain reaction
The f~Ilowing ingredients were used for a PCR reaction: 10 p,1 dH20, 2 ~,l l
OX
PCR buffer, 1.6 ~,1 dNTP (25 p,M), 2 ~,l of 2 p,M H-AP primer, 2 p,I of 2 ACM
H-T"M, 2
~.1 RT-mix described above (must contain the same H-T~ 1M used for PCR), 0.2
~,I a-33P
dATP (2000 Ci/mmole), 0.2 ~Cl Taq DNA polymerase from PE Biosystems for a
total
volume of 20 ~.1. The tube containing all these ingredients were mixed well by
pipetting
up and down and placed in a thermocycler at 95°C for 5 minutes and then
amplified for
40 cycles under the conditions of 94°C for 30 seconds, 40°C for
2 minutes, 72°C for 30
seconds and finally held at 4°C until the samples are removed from the
thermocycler.
0
d. Gel electrophoresis
A 6% denaturing polyacrylamide gel in TBE was prepared and allowed to
polymerize for at least 2 hours before using. Then the gel was run for about
30 minutes
before any samples were loaded. It is important fox all the sample wells in
the gel to be
L 5 flushed and cleared of all urea prior to loading any samples in the wells.
About 3.5 ~Cl
of each sample was mixed with 2 ~,1 of loading dye and incubated at
80°C for 2 minutes
immediately before loading onto the 6% gel. In this example, the loading dye
was
xylene and after the gel was loaded with the samples obtained from the rounds
of PCR,
the gel was run at 60 watts of constant power until the xylene dye was about 6
inches
20 from the bottom of the gel. Once the power was turned off, the gel was
blotted onto a
large sheet of exposed autoradiograph film. The gel was covered with plastic
wrap and
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under dark conditions, the gel was placed in a large autoradiograph cassette
with a new
sheet of unexposed film, marked for orientation, and the film was exposed to
the gel at
-80°C. The exposure period can be anywhere from overnight to 72 hours.
Once the
film has been developed, bands of interest were identified by alignment with
the
S developed film and subsequently isolated by cutting the band of interest out
of the
polyacrylamide gel with a clean scalpel blade. The isolated band was placed in
100 ,u1
of water and boiled at 9S% for S minutes.
e. PCR to amplify gel band
L 0 PCR was set up to amplify the gel band. The re-amplification should be
done
using the same primer set and PCR conditions except the dNTP concentrations
should
be at 20 p,M. The following ingredients were combined for the PCR reaction:
20.4 p1
HZO, 4 ~Cl lOX PCR buffer, 3.2 ,u1 of 2S0 p,M dNTPs , 4 ~tl of 2 ,uM H-AP
primers, 4 ~Cl
of 2 p,M H-T1 ~M, 4 p1 template (out of the 100 p,1 containing gel band), and
O.S ~.1 Taq
1S polymerase for a total volume of 40 p1. These ingredients were heated to
9S°C for S
minutes and then cycled for 40 cycles under the conditions of 94°C for
30 seconds,
40°C fox 2 minutes, 72°C for 30 seconds followed by a final
extension at 72°C for S
minutes and finally held at 4°C until the samples are removed from the
thermocycler.
About 4 p1 of the PCR reaction was removed and run on a 1% agarose gel to
ascertain
20 the success of the PCR reaction.
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Section 2. Cloning amplified fragments and Screening colonies
a. Clonin~plified fro ents
To clone the amplified fragments, products from different sources Ce:g.,
GenHunter or InVitrogen) may be used to achieve the desired cloned product. In
this
example, InVitrogen's TOPO TA Cloning Kit~ was used and the following material
was combined in a reaction tube: 2 ~,I of freshly run PCR product, 2 p1 of
sterile H20, 1
p,1 of PCR-TOPO vector for a final volume of 5 ~,I. The combined ingredients
were
mixed gently and incubated for 5 minutes at room temperature. Then 1 ~,l of 6x
TOPO
Cloning Stop Solution was added and all combined ingredients were mixed for
about 10
0 seconds at room temperature and then set on ice. One ShotTM cells were
thawed on ice.
2 p.l of the TOPO Cloning reaction was added to the One ShotTM cells, mixed,
and
incubated on ice for 30 minutes. The cells were heat shocked at 42°C
for 30 seconds
without shaking and incubated on ice for 2 minutes. Then 250 ld of room
temperature
SOC was added to the heat shocked cells and mixed. The cells were then placed
at
L 5 37°C for 30 minutes. About 50-100 ~,l of the cells were spread on 2
XYT plates
containing 100 p,g/ml ampicillin and X-gal. The plates were incubated
overnight at
37°C and the next morning, 3 white colonies were selected for analysis.
b. Screening colonies far correct recombinant- nlasmids
20 PCR was used to ascertain whether the white colonies selected contained the
correct recombinant plasmid. The following ingredients were combined for the
PCR
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reaction: 21 ~l H20, 2.5 ~tl l OX PCR buffer, 0.12 ~,l of lOmM dNTPs, 1 ~,1 of
25 ngl~,l
T7 primer, 1 ~,1 gene specific left or right primer at 25 ng/~,1, template (a
toothpick was '
used to transfer colony from transformation plate to tube by swishing the
toothpick
around in the reaction mix), and 0.5 ~,1 Taq polymerase for a total volume of
25 ~.1. The
reaction mix was run at 95°C for 5 minutes and then cycled 35 times
under the
conditions of 95° C for 30 seconds, 45°C for 30 seconds,
72° C for 30 seconds, and
followed by 72° C for 5 minutes and finally 4°C until samples
are removed from the
thermocycler. About 4 ~,l of the PCR product was removed and run on a 1%
agarose
gel to ascertain the success of the PCR reaction. Bacterial colonies
corresponding to the
0 colonies which yielded positive PCR results were grown overnight in LB media
containing 100 ~,g/~,1 ampicillin at 37° C with constant shaking.
Plasmid DNA were
isolated from the overnight cultures and sequenced using a T7 primer.
Sequences were
then compared to sequences in the GenBank database to confirm that the correct
gene
fragment was cloned. Gene fragments were then amplified by PCR from the
plasmid
5 DNA. The unincorporated primers and dNTPs were removed and the resulting
gene
fragments were arrayed on glass slides for the purposes of measuring
differential gene
expression using the Phase-1 Molecular Toxicology Microarray products.
Results
'0 RCT-289 and RCT-290 are the two toxicologically relevant genes identified
using methods disclosed in this example. The gene sequences are listed in
Table 4.
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Example 4. Real Time PCR reaction
Materials and Metlaods
Total RNA was isolated from tissues and/or organs from rats dosed with toxic
compounds listed in Example 1, Section 3, and then the mRNA within this total
RNA
was converted into cDNA using 3 ~,g total RNA and 1.5 ~,l random hexamer
primers.
After a 10 minute incubation at 70°C, the following components were
added to the
reaction mixture: 6 p,1 of Sx first strand buffer, 3 p.1 0.1 DTT, 1.5 p,1 l
OmM dNTPs, 1.5
~,l Superscript enzyme, and 6.5 ~1 DEPC-treated water. The reaction was
incubated for
two hours at 45°C and 1 p1 of this reaction was used for the Real Time
PCR (RT-PCR)
0 assay. For the RT-PCR assay, 50 ~.l reactions were set up with Rnase-free
water,
Taqman~ Universal PCR Master Mix (available from Applied Biosystem), target,
and
control primers /probes and cDNA. This method measures PCR product
accumulation
with a dual-labeled fluorogenic probe. The probes are labeled with 6-FAM on
the 5'
end and TAMRA on the 3' end. TAMRA is a quencher dye. This assay exploits the
5'-
l 5 3' exonuclease property of Taq polymerase. When the probe hybridizes to
its target the
reporter dye (FAM) is cleaved by the 5' exonuclease activity of the Taq
polymerase and
can emit a fluorescent signal. With increasing cycles of amplification, more
signal is
emitted and detected using an ABI 7700 sequence detector. For each gene, a set
of two
primers and a fluorogenic probe are designed and synthesized. For quantitation
of
20 mRNA, optimal design for probes and primers requires primers to be
positioned over
exon-intron junctions. This step rules out amplification of contaminating
genomic
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DNA. For our studies, primer and probe sets have been designed for 16 genes
that are
part of the 700 rat toxicologically relevant gene array, also referred to
herein as
"comprehensive toxicity array" or "CT array". These genes were up-regulated or
down-regulated by toxic drugs/chemicals in rats exposed ire vivo or rat cells
exposed in
culture. The probes and primer sets were tested for their ability to amplify
genomic
DNA. If genomic DNA was amplified the probes and primers for that particular
gene
were not used fox the RT-PCR assay.
Results
Real-time PCR analysis was performed using RNA from the same rats that were
0 dosed with various toxic chemicals/drugs used for CT array studies. Figures
7, 8 and 9
show the results of linear regression analysis of TaqMan vs. CT array data for
42 toxic
chemicals/drugs. There is an excellent correlation (r=0.97395) between TaqMan
data
and CT array data for Cytochrome P450 1A2 (Figure 7). Analysis of TaqMan and
CT
array data for Fatty Acid Synthase showed a correlation of 0.8634b (Figure 8).
5 Comparison of TaqMan and CT array data for Multidrug Resistant Protein-1
produced a
correlation of 0.73414 (Figure 9).
Example 5 Isolation of total RNA from adherent cultured cells
Total RNA of high quality and high purity was isolated from cultured cells by
using Qiagen RNeasy midi kits and 2-mercaptoethanol. Precautions were taken to
Z0 minimize the risk of RNA degradation by RNases by wearing gloves, treating
work
areas and equipment with an RNase inhibitor, for example, RNase Zap (Ambion~
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Products, Austin, TX) and keeping samples on ice. This total RNA isolation
technique
was based on a Qiagen~ RNeasy~ midi kit and was used with some modification
for
IiepG2 (human hepatocyte) cells in T-75 flasks and maxi kit RNA isolation for
cells in
T-175 flasks.
Cells were checked under the microscope to make sure that they were viable.
Cells were dosed with an agent, which could be a drug, chemical, or
pharmaceutical
composition, when they reached 60-80% confluence. It is preferable to avoid
isolating
RNA from flasks that have reached 100% confluence.
For adherent cells, media was discarded and flasks were washed with lx cold
0 PBS twice (20 ml then 10 ml for T-75 flasks; 40 ml then 20 ml for T-175
flasks). After
the second PBS wash, the remaining PBS was removed with a pipette. Freshly
prepared
RLT buffer (RLT buffer requires the addition of 10 ~.1 beta mercaptoethanol
for each
1.0 ml RLT) was added directly to the cell culture flask. T-75 flasks received
3 ml RLT
buffer and T-175 flasks received 5.0 ml RLT buffer. It is preferable to
lightly agitate
5 the flasks at this point. Flasks were lightly agitated to distribute the RLT
buffer and the
cells became a gelatinous layer. The cells were allowed to sit for 4 minutes,
then fluid
was withdrawn and placed in RNase-free tubes. An equivalent volume of 70%
ethanol
was added to each tube and vortexed to distribute evenly. If a precipitate
with a string-
like appearance forms, it is acceptable to remove and discard this string-like
precipitate.
?0 The fluid was applied to a spin column and spun for 5 min at 3650 rpm in
the Beckman
GS-6 (or a similar centrifuge). The flow-through was discarded. About 4 or 15
ml (T-
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75 or T-175, respectively) of RW 1 buffer was applied and spun for. 5 min at
3650 RPM.
The flow through was discarded. About 2.5 ml RPE buffer (midi columns) or 10
ml
RPE buffer (maxi columns) was applied and centrifuged for 3 minutes. The flow-
through was discarded. Another 2.5 or 10 ml buffer RPE was applied and
centrifuged
for 5 minutes to dry out column before proceeding to the elution step. The
column,
including the tip, should be dry for the next step.
The column that has the RNA bound to it was transferred to a clean tube for
elution. Then 150 p.1 of RNase-free water was added to midi columns and 500 ~1
of
RNase-free water to columns, allowed to sit for 2-4 minutes and spun for 3 min
at 3000
0 x g (3690-3710 rpm, Beckman GS-6 or a similar centrifuge). The elution was
repeated
with another 150p1 or 500 p1 of RNase-free water into the same tube. The
elution was
precipitated using the LiCI precipitation protocol, exemplified in Example 2,
and
resuspended in RNA storage buffer.
To measure yield, the O.D. reading was taken at 260 nm. About 2.0 ~.1 RNA
~ 5 was added to 98 p.1 H2O and the O.D. reading was taken and calculated as
follows:
(Absorbance) x (dilution factor) x (40)/1000 = amount of RNA in ~g/ml
Example: absorbance = 0.45
dilution factor = 50
(0.45~x 50 x 40 = RNA concentration in ~.g/ml
?0 1000
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The yield should be between 200-400 ~.g of total RNA from a T-75 flask with
greater
than 50% confluency. The sample was stored in -80°C freezer.
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TABLE 1
Generic Name
acetaminophen attapulgite carisoprodol
acetaminophen/codeineazathioprine carmustine
acetohydroxamic acid azelastine carvedilol
actinomycin D azithromycin cefaclor
acyclovir aztreonam cefepime
adenosine bacampicillin cefprozil
albuterol baclofen ceftibuten
alendronate beclomethasone cefuroxime
alendronate sodium belladonna celecoxib
alglucerase benazepril cephalexin
allopurinol benazepril cephalosporins
alosetron benzodiazepines cerivastatin
alprazolam benzoyl peroxide cetirizine
alprostadil benztropine chenodiol
alteplase beta carotene chlophedianol
ambenonium betamethasone chloral hydrate
amifostine betamethasone chlorambucil
amiloride betamethasone valeratechloramphenicol
aminobenzoate potassiumbethanechol chloroquine
aminoglutethimide bisacodyl chlorpropamide
aminopurine bismuth subsalicylatechlorthalidone'
plus
aminosalicylate sodiumbisoprolol/HCTZ chlorzoxazone
amiodorone bleomycin cholestyram ine
amitriptyline bradykinin antagonistcimetidine
amlodipine bromfenac cinoxacin '
amoxapine brominide tartrate ciprofloxacin
amoxicillin bromocriptine (+)-cis-3,5-dimethyl-2-(3-
amphetamine mixed bronchodilators rid I thiazolodin-4
salts
ampicillin buclizine cisapride
amprenavir budesonide cisplatin
amyl nitrite bumetanide citalopram
anagrelide bupropion HCL clarithromycin
ancrod buspirone clavulanate
androgens busulfan clavulanate
anistreplase calcipotriene clavulanic acid
anthralin calcitonin salmon clidinium
araC calfactant clindamycin
aspirin candesartan cilexetilclofibrate
aspirin capsaicin clomiphene
astemizole captopril clonazepam
atenolol carbamazapine clonidine
atorvastatin carbenicillin clotrimoxazole
atovaquone carbidopa cloxacillin
atropine carboplatin clozapine
codeine
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colchicine dihydrolazine felbamate
colestipol diltiazem felodipine
collagen-alginate dimethyl sulfoxide felodipine SR
conjugated estrogens dinoprosfone fenofibrate
copolymer-9 dione fenoldopam mesylate
cortisone diphenidol fentanyl citrate
courmarin diphenoxylate fexofenadine
cromolyn dipyridamole fialuridine
cyclacillin dipyridamole finasteride
cyclandelate disopyramide flavoxate
cyclizine disulfiram flecainide acetate
cyclobenzaprine divalproex flosequinan
cyclopegic divalproex sodium fluconazole
cyclopentolate docusate sodium flunisolide
cyclophosphamide dolasetron mesylate fluoroquinolones
cycloserine donepezil fluorouracil
cyclosporine doxazosin fluoxetine
cyclosporine A doxercalciferol flutamide
cytoxin doxorubicin fluticasone
dalteparin injection doxycycline fluticasone
danazol enalapril fluticasone propionate
dantrolene enoxaparin fluvastatin
dapsone entacapone fluvoxamine maleate
daunomycin ephedrine foscarnet sodium
daunorubicin epirubicin fosinopril
dehydrocholic acid eptifibatide fosphenytoin
desmopressin ergoloid mesylates furazolidone
desogestrel ergonovine furosemide
dexamethasome erythromycin gabapentin
dexti-omethorphan estradiol ganciclovir
dextrothyroxine estramustine ganirelix acetate
diazepam etanercept gemcitabine
diazoxon ethacrynic acid gemfibrozil
dichloralphenazone ethchlorvynol glimepiride
diclofenac ethinamate glipizide
diclofenacdihydrazineethinyl estradiol glucagon
dicloxacillin ethinyl estradiol glyburide
dicyclomine ethionamide glycopyrrolate
didanosine etidronate gold compounds
difenoxin etoposide gold sodium thiomalate
digitalis glycosides etretinate granisetron
digoxin exemestane grepafloxacin
dihydrazine famciclovir griseofulvin
dihydroergotamine famotidine guaifenesin
mesylate I
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guanabenz isoxsuprine masoprocol
guanadrel isradipine mazindol
guanethidine itraconazole mecamylamine
guanfacine kanamycin mechlorethamine
haloperidol ketoconazole meclizine
heparin ketorolac medroxyprogesterone
hismanol lactulose medroxyprogesterone
hydantoin lamivudine, 3TC mefloquine
hydralazine lamotrigine melatonin
hydrochlorothiazide lansoprazole melphalan
hydrocodone latamoxef menotropin
hydrocortisone latanoprost meprobamate
hydroxychloroquine leflunomide merbarone
hydroxyurea letrozole mercaptopurine
hydroxyzine leucovorin meropenem
hyoscine leuprolide mesalamine
hyoscyamine levamisole metformin
hyoscyamine levetiracetam methenamine
hyperozia levobupivacaine methicillin
ibuprofen levocabastine methotrexate
ibutilide fumarate levocarnitine methylcellulose
imiglucerase injectionlevodopa methyldopa
imiquimod 5% cream levofloxacin methylergonovine
inactivated hepatitislevonorgestrel methylphenidate
A vaccine
indapamide levothyroxine methylprednisolone
indinavir lidocaine methyprylon
indomethacin lincomycin ~ methysergide
insulin liposomal amphotericinmetoclopramide
B
interferon-beta-1 lisinopril metoprolol
a .
recombinant lispro insulin metoprolol
interferon-beta-1 lithium metronidazole
b
bi
t
recom I
nan l
-norgestre metyrapone
iodinated glycerol
I
l/
thi
iodo -norgestre metyrosine
uinol e
nyl estradiol
q l
ti
ipecac
omus mexiletine
ne
l ib
id f
i1
iphosphamide operam m
e e
rad
l i
b
f
ipratropium oracar m
e conazole cream 2%
I i
di lit
i
irbesartan orata g
ne m
o
L i
tidi Ii
/P
h
d
d
i
irinotecan ora m
ne nocyc
seu ne
r
ne
oep
e
l i
idi
isomethe orazepam m
tene nox
l
p l i
t
isoniazid osar m
an soprostol
l i
t t
ti l
isoproterenol ovas m
a sopros
n o
l it
i t
A oxap m
isosorbide mononitratene ane
S o
. i
. d
isotretinoin magnesium sulfate m
xe
amphetamines
l l
maproti moc
ine obemide
101
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molindone oxycodone potassium phosphates
mometasone oxyrnetazoline pramipexole
moricizine paclitaxel pravastatin
_
moxifloxacin pancreatin prazosin
mupirocin pancrelipase prednisolone
nabllone papaverine prednisone
_
nab_umetone paraldehyde primaquine
nafarelin paramethasone primethamine
nafcillin paregoric primidone
nalidixic acid paroxetine probenecid
naltrexone pediculisides probucol
naproxen pemoline procainamide
naratriptan penicillamine procarbazine _
natamycin penicillin progestins
navirapine pentamidine promethazine
nedocromil pentoxifylline propafenone _
ne_fazodone pepsin propantheline
neomycin pergolide propoxyphene
Neomycin/Polymx/HC perhexiline propranolol
neostigmine perindopril propulsid
~
nicardipine perphenazine pseudoephedrine
nicorandil pexiganan acetate psoralens
nicotine phenazopyridine psyllium
nifedipine phendimetrazine pyridostigmine
nimodipine phenformin pyridoxine (vitamin
b-6)
nitrofurantoin Phenobarbital quinacrine
nitroglycerin ~ phenolphthalein quinaprii
nizatidine _ phenothiazines quinidine
norethindrone phentermine quinine
norethindrone/ ethinylphenylephrine rabeprazoie
estradiol
norgestimate phenyiephrine raloxifene
norgestimate/ethinyi phenylpropanolamine ramipril
estradiol
norgestrel phenylpropanolamine ranitidine
norgestrel/ethinyl phenytoin recombinant clotting
estradiol factor V111
nylidrin pilocarpine recombinant interferon
alpha-2b
nystatin pioglitazone recombinant OspA
ofloxacin piroxicam remoxipide
olsalazine podophyllum reserpine
omeprazole poloxamer 188 rezulin
orphenadrine polycarbophil calciumribavirin
oxacillin polyethylene glycol rifampin
oxaprozin polythiazide rimantadine
oxtriphylline potassium chloride risedronate
oxybutynin potassium iodide risperidone
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ritodrine ~~_ ~~ tetracyclines verapamii
~ ~
rosiglifazone theophylline vincristine _
_ ~
salicylates thiamine warfarin V
_
saimeterol thiazide xanthine
saquinavir thioguanine xyiometazollne
~
scopolamine thiopurlne zafirlukast
J
_ _
seldane thiothixene zalcitabine
selegifine tiagabine zidovudine
~~- tic(opid(ne zolpidem
sertraline
sibutramine tienilic acid
sildenafil citrate timolol
simethicone tiopronin
simvastatin tlrofiban
s-mephenytoin tobramycin
sodium ferric gluconatetobramycinldexamethasone
soman tocainide
somatostatin tolbumamide '
sotalol tolcapone
spironolactone toiterodine
stanol esters topotecan
streptozotocin toremifene
succinimide tramadol
sucralfate trandolapril
sulfacytine trastuzumab
suifadoxine trazodone
suifamethoxazole tretinoin
'
sulfamethoxazole triamcinolone
suifasaiazine triamterenelHCTZ
sulfinpyrazone triamterine
sulfisoxazofe triamterine
sumatriptan triazolam
(s)-warfarin trihexyphenidyl
tacrine trilostane
tamoxifen trimeth/sulfameth
tamsuiosin trimethobenzamide
telmisartan tr(methoprim
temazepam troglitazone
terazosin trovafloxacin
terbinafine MC! urokinase
terbutaline sulfate ursodlo!
terfenadine valproic acid
terpin hydrate valsartan
testolactone vancomycin
tetracycline HCI venlafaxine
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TABLE 2
Industrial Chemicals
1,2-Dibromomethane Cyclophosphamide Monobromomethane-
2,4-dinitrotoluene DDT Monochlorobenzene
2-methylpentane DEHP n-hexane
3-methylpentane Dichlorobenzene Nickel
4,4'-methylene bis Dichloromethane Nitrobenzene
7, 12- Dieldrin Nitroglycerine
dimeth Ibenz a anthraceneDiethylamine Nitrous oxide
'
A
t
ce Diethystilbesterol Organophosphorus
one
Acrylamide Dimethylacetamide Parathione -
~
A
l
it
i1
cry Dimethylformamide Pentachlorophenol
on
r
e
Apha methylstyrene pinitroorthocresol Phenol
~
Aluminum pioxane Phtalic anhydride
~
-
Aniline _~~ Endrin Polychlorinated biphenyl
Antimony Enflurane Polycyclic hydrocarbons
,
Arsenic Ethylbenzene Propyleneglycol
Barium Ethylene oxide Selenium
B
aygon Ethyleneglycol dinitrateSilver
Benzene Ethyleneglycol(s) Stryrene
Benzidine Fluoride Synthetic pyrethroids
Berylium . Furfural T-butylhydroperoxide
t
B Furfuryl alcohol TCDD
a-napthylamine
Biphenyl Germanium Tellerium
Cadmium Halothane Tert-butylphenol
C
b
ar Hexachlorobenzene Tetrachloroethylene
amate(s) -
b
Car Hexachlorobutadiene Thalium
aryl
_
C
b
di
lfid
ar Isopropanol Toluene
on
su
e
Carbon monoxide Isopropylnitrate Toluene diisocyanate
C
arbon tetrachloride Lead Trichioroethane
Chl
f
oro Lead tetraethyl Trichloroethylene
orm
i
Ch
VI
rom Lindane Triethylamine
um
lt
Coba Malefic anhydride Triethylbenzenes
Copper Manganese Uranium
Cumene Mercury Vanadium
id
Cyanam
e Methanol Vinyl chloride
Cyanides Methylchloride Xylene
h
l
o Methylethylketone Zinc
exane
Cyc
~
l
h
o Methylmercury
Cyc
exanone
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Table 3. List of compounds dosed in rats for toxicity studies
Liver Immuno I Bone Marrow
chlor romazine c clos orin A
clofibrate h drox urea
clafibric acid hen !h drazine
dif(unisal dexamethasone
tetrac cline estradiol
a prom cin tamoxifen
ethanol azathio rive
chloroform busulfan
al ha-na hthol isothioc 5-fluorouracil
anate
dimeth Initrosamine benzene
isoniazid c clo hos hamide
carbon tetrachloride cloza ine
ketoconazole thalidomide
c cloheximide di rone
acetamino hen rednisone
bromobenzene
benzo-a- rene Brain
aflatoxin naloxone
halloidin henobarbital
2-AAF vincristine
colchicine
thioacetamide Heart
val roic acid doxorubicin
atorvastatin theo h lline
lovastatin uinidine
simvastatin nifed! ine
caffeine
Kidne
cis Latin Lun
entamicin carmustine
urom cin Para uat
am hotericin 8
stre tozotocin Multior an
anciclovir 1i o of saccharide
indomethacin methotrexate
mercuric chloride cadmium chloride
na roxen
Testes
flutamide
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Table 4 Phase-1 Rat CT Gene Names, Accession Numbers, and Seciuences
Gene Name A Gene or Partial Gene Sequence, 5'-3'SEQ ID
n NO:
Number
Genes Discovered
b Em irical
Data that
match the
se uence
of a known
ene
TATGACATGATfACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCACCTGCCGCGTCA
AGGCTGAGGGTGGAATCCGAGCTCCGGTCGCTTGCCAAGCGAG
CGCTCGCCCAATACTTGCTGTT1'CTAAAGTTCTATCCGGTGGTCA
CCAAAGCTGTCAGCAGTGGCATTTTGTCAGCCCTTGGAAACCTTC
TGGCCCAGATGATTGAGAI~GAAGCAGAAAAAAGACTCTCGAAGT
22kDa integral CTAGAAGTCAGTGGGCTTCTCAGATATTTAGTTTATGGGTTGTTT
peroxisomal NM 031587GTCACAGGTCCCCTGAGTCACTACCTCTACCTCTTCATGGAGTACSEQ Ip
N0:1
membrane protein TGGGTCCCTCCTGAGGTTCCCTGGGCCAGAGTCAAGAGGCTCCT
GCTGGATCGCCTGTTCTTTGCCCCAACCTTTCTGCTGCTGTTCTT
CTTCGTCATGAACTTGCTGGAGGGAAAAAACATCAGTGTCTTTGT
TGCCAAGATGAAGAGTGGCTTCTGGCCTGCTCTGCAAATGAACT
GGAGGATGTGGACACCCTTACAGTTCATCAACATCAACTATGTGC
CCTTGCAGTTCCGGTGCTCTTTGCCAACATGGCAACTCTGTTCTG
GTATGCCTACTGGCCTCNCTGGGGAANTGGATGTCTGATACACC
CGTGGANGAAGGNGTGGGGAAAATCCA
NGCCAAGCTAAAATTAACCCTCACTAAAGGGAATAAGCTNGCGN
CCCGCAANGNTATTTNTTTNATANTTTTTTNNNTTAAAGCCATTAC
AATATTTATTGCTTTATAAATCAATGAGATATAACCAAAGCAGGAT
GTGATTTAGGACTTGAAGAGGAACAGAAAAGTAATACTCAGCTCT
AAGTGACAGGAAATt'GTCATTGGTGAAGCCTTTGGTCAGAGCAGC
TGAGGCACAACTACCTGTGTGTCTCTGGACAGGGGATTAGGGAA
3-beta-hydroxysteroid GAAAGCTTGTGGACTAGCAAGGCTTCCAGTGAAGTCATAAAGAC
dehydrogenaseAA923963 ATAGAGTTAGAGTCTGTGTCAAAAGAGGGCATCAGGACCTGGATgEQ ID
N0:2
(HSD3B1) TGTGCCTCTGTCCTAGCTGGAGGACCTGGTAACAGCCAGAACCA
CATCCTTGCCCCCTTTCTGTCACTGAGACTTTGTGTCCAGTGTCT
CCCTGTGCTGCTCCACTAGTGTCCCGATCCAGTCCGAGGTTTTCT
GCTTGGCTTCCTCCCAGCTGACAAGTGGCACATAGCGCAGATCT
CTCTGAGCTTTCTTGTAGGAGAAAGTGAACTTGCTATTTGACAGT
GTGACCAAGTGGCAGTTAAAGGGTGGCCTATAGTTGTAAAATGCT
CGTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAG
TAGTATTAAATTCGTAATCATGTCATAGAG
CCNNNNCTATGACATGATTACGAATTTACTACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGAGCGACAC
TTACAACCCTGTACCTGGGGTTATGGATGGAGTTCCCTCATCTAA
TAACTACCAAGGTGGATTTGGGACAACACTCATGGCCAAGGATCT
GGGATTAGCTCAAGACTCTGCCACCAGCACCAAGACCCCAATTC
TCCTCGGAAGCGTGGCCCATCAGATATACAGGATGATGTGTTCA
AAGGGCTACTCAAAGAAAGAC,TTCTCCTCTGTGTTCCAGTATCTG
3-hydroxyisobutyrateX04628 CGGGAGGAGGAAACCTTCTGACTGCCCTGTGGTCATGGACACTGSEQ
ID
N0:3
dehydrogenase TTAGGAACCAAACTGTGTCCTGAGCTTCGTTCTAGCTCATTCTAG
AAGTCATGGGTTTAATGAAAGGTCATGTGTCTGCTTTTGATTGTC7
ACATTATAGCAA'TCCCTGGGGATTTTTATCCATTTTAAATGCTGCT
GCTTTCATCTGTTTAGCAAACACACCCAATGGTTTCCACTGACTA
GCCCAG'tTGACCTTTTTTAAGTTfGAACCTTGAGCACCTTAAACAA
AATTGAGCACTCTGATCAGGATATTTTATTTTACTCTGCTTTACNA
ATAAAACCAAATGGTTTGTTTAACAAGATGGAACCATGGTAAAAAA
GGAAAAAAATCAGTTN
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CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGAGCTGAGGAAGAGT
AAGCCCCATTGCAGCCGGAACCCTGTCCTGGTGAGAGGAATCGG
CAGGTATTCACGATCTGCTATGTATTCCAGAAAGGCCTTGTACAA
AAGGAAATACTCTGCTGCCAAGACAAAGGTTGAGAAGAAGAAGA
AGAAAGAAAAGGTCCTTGCTACCGTCACAAAAACAGTTGGTGGG
GACAAGAACGGTGGCACCCGGGTGGTGAAGCTTCGAAAAATGCC
60S ribosomalXg7107 TAGGTATTACCCTACTGAAGACGTGCCTCGGAAGCTGCTGAGCC
protein
SEQ ID
L6 (alternate ACGGCAAGAAGCCCTTCAGCCAGCACGTGAGGAGGCTGCGCTCN0:4
clone 1)
CAGCATCACTCCCGGGACTGTCCTGATCATCCTCACTGGGCGCC
ACAGGGGCAAGAGAGTGGTTTTCCTCAAGCAGCTGGGCAGTGG
CTTGCTACTTGTGACTGGACCTCTTGCCCTCAACAGAGTTCCTCT
GCGTAGGACACACCAGAAGTTTGTCATCGCCACCTCTACAAAAGT
TGATATCAGCAAGGGTAAAATTCCCAAACACCTGACTGATGCTTA
CTTCAAGAAGAAGCCACTTCGCAAGCCCAGGCATTAGGANGGTG
AGA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGGACAGAGGCATCG
GCATGGAACTTGGACCGCAGCCGCCCTCTGCCAGAACCTGAGTG
CTGCAGCCCCTGAAGTCCGCTGCTGTGTGGATGCTGTGAACTTT
GTGGCTGAGAGCACAAGGGACCAGGAAGCCACTGGAGAGGAAC
TGTCTGACTGGGTGCGTATGGGGAAGGCCCTCGACAATGTCTGT
TTTTGGGCAGCGTTGGTGCTCTTCAGCGTCGGTTCTACGCTCATC
Acetylcholine TTCCTTGGAGGTTACTTCAACCAAGTTCCTGATCTCCCCTACCCA
receptor
epsilon NM 017194CCGTGCATCCAACCATGAGCCTGCACCAGGACCCACCTCATCCCSEQ ID
NO:5
CACCCCCCAAGAAAGAGATTTTGAAAACAGGCTGCTGACAATAAA
TCTGGTTTGTGAACTTGCAAAANNNANANNANNNANNAAANANAA
NNANANNTTCTCGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTT
AATTl-f~AGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGATGGG
AAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCC
TTTCCCACTGGNGTAATAGCGAANAGGCCCGCACCCGATCCCCT
TCCAACAGTTGCGCANCCTGAATGGCGAATGGGACNCNCCCTGT
ACGGCNCA
ATCGATTTCTCACTGACACGAGTGAAGGCTGCTTTGTGAACAAGT
GGACAGATAATATGGCAATCTCAGTTCAAGCAAGTCTGGGTCAAC
ACATCATTCATCCTCCTCCCTCAGTAACCTTGCATGTGTAATGGG
CTGTGGGGCCATCAGACTGCTCATGTGCTGTGGCTCTGACTTCT
CCATGGAGGAGCCCCGGTCCTGGGGATGGGGCAGCAGGGAAAA
GGGAGTTATACAAGCACAACCCACTTCACCTCAGAAGGAACGGC
Acetyl-CoA AGGAAAGCAGCCTTCATACCACTGGGTGTGGGACTGGATGTGCC
carboxyiase X925393 GTAGCAAAGTGTAGAGGCTGGAGACAAATCCCACCCTTACCTACSEQ ID
N0:6
AAGGTGAGCTGAGAACCAGGGGCCAGGGAGCTTCCTTCTAACTG
AGGATGCTCCCCACCTGATCTGGCCCTGGCCCTCCTGTTCGCTT
GTAGGAGTTGGGCAACTTGCATCTATAGTCCCTTGGATGTCCGCT
TGCAATGTGGCACCATTGAGAAGGTCCTCTGGAATATCTGCTCGA
GGTGCTCCTGAATGGGAGGTCAGCTCTTTTTGTGGAGTCCAGGT
TAAGGCTCAGACTCCTCGTGCCGAATTCTTGGCCTCGAGGGCCA
AATTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATAGA
TTAAGATTTTCCAGAAAGTTTTTAGTTTTAATAATGGGAGAAAATG
CATATAAACTTTTTTACTCTTTTGCAATACAAGGGAAATATAATCAA
AATTATGAAACAGCTCAGCACAGAAATGCTCTCTCTTCACAGTGT
GATGGGTCCAATCCGCCACATTCGTCAGTGTCTGTGTAGAATCCT
GAGTTCTTTCGTGACAGGCTACCTTTCTTGTCACTTGAATGAGCA
TTAGAACTCCAGGGTATTTCTCCATCTCAAGTGATCAAGGAGCAA
Acyl-CoA ATTAACACAATTCGGGGCCAAGGACTGACCACTCACTGTCCAAAA
dehydrogenase,AA925220 CCAAACCTATCTAGAAAGGGTCACTGTGGAACTCAACAGAGGCASEQ ID
NO:7
medium chain CCCTCCGCCGTGGGACCCCATTGCACAGATCTGTGACACGCGTC
TTTTATCTCATTTCTGTGGGAAGACAAGTAAAGCCCTTTCCCCCT
GAAGCAGCAACAGTGCTCTGAGCGTAGTTACATGAGGGTGAAGC
ATCGTTCGATAGTAATTTCTGTTAATTTTTATACTTTTCAATGTGCT
CACGAGCTATGATCAGCCTCTGAATI?GTGCAGTACCTTCGTAAA
TCTGATCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCCT
ATAGTGAGTCGTATTAAATTCGTAATCATGTCATAGA
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GGTGACAGCCCTCCTCCGAGGAGCAGCAGTGGGCAGCAGTAGC
AGCAGCAGGTCACGGTGGGGTTGGGAATGTTAGTCTGGCCAGCT
GGTGCTTATCCCTCCGGCTGGTGTCGGATGAGGACAGGGACCTA
GACAGTGAGCTGGGACACTGAAGAAGCTCAGTCGGCAGTAAAGA
CACGACTGGAAATGTCATCGAGGAGCCAGTCGATGCCAGGCAGC
AGGTCCTCCCCTGTGACGGCACTGCAGCCTTGGATGCGCCAGTG
ADP-ribosylation GTGGCTGCGGATGGAGTCCAGCTCTAGGGCCTCCTGAATAGCAT
factor-like AA817697 TACAGGACAGTGCTCCAGGCAGGTCCTGCTTGTTGGCAAAGATGSEO ID
protein N0:8
ARL184 , AGGAGGGTCGCTCCAGCCAGGCGCTCCTCCACCAGTAGACTCT
GCAGCTCTCGCTGACAGTCCTGCATGCGCTGGCGGTCAGCGCT
GTCCACCACCCAGATGAGGCCATCTGTGCTCTCGAAGTAGTTCC
TCCAGTAGGAGCGCAGAGACTTCTGGCCACCCACATCCCAGATG
TTCAGCTTGAATCCCCGGTGCTCCAGGGTCTTGCCTCGTGCCGA
ATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAGTCGTATTAA
ATTCGTAATCATGTCATAG
ATTNTGNCATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCCTGCGCTCAGCA
'CTAAGGAGTCACTGTTAGCTGTTCTGCCGGCGGGTTGCTCTTCT
CAGCCATGGCTCCTCGCTGCTGGCGCTGGTGGAGCTGGTCCGC
GTGGCCTGGGGTTCGGCCGCTTCCCTCCAGGAGCACTCCGACC
CCTGGCTTCTGCAAGAAGTTCTCCACACAGGAGACAACCCCTCA
GATCTGTGTGGTCGGCAGTGGCCCAGCTGGCTTCTACACAGCCC
Adrenodoxin AACACTTGTTGAAGCACACACCCGGGCCCACGTAGACATCTATG
reductase NM 024153AGAAGCAGCTCGTCCCCTTCGGCCTGGTGCGCTTTGGTGTGGCASEQ ID
N0:9
CCTGACCATCCTGAAGTAAAGAATGTCATCAACACATTTACACAG
ACAGCCCGCTCAAACCGCTGTGCC'f-T'CCGGGGCAATGTGGTGGT
GGGCAGGGACGTGTCCGTTCCAGAGCTTCGGGAAGCCTACCAT
GCTGTGGTTCTGAGTTATGGAGCCGAGGACCACCAACCCCTGGA
AATCCTGGGGAGGAGCTGCCTGGAGTGGTCTCAGCCGGGCCTTT
GTGGGCTTGTACAATGGGCTTTCTGGAGAACCAGAANCTGGCTN
CGGATCTGAGCTGGTGACACGGCTGTGATTTTGGGGCAAGGGAA
TGTGGCTCTGGGATGTGGGCCCGGANC
GCCAATGANTCGTTCTTGATACNTCATACAATACANTTCAGACAG
CTTCAACGGGTGGAACAGGTTANTCAGCAAACATGGTTGTACATA
CGCAAGTGACATTCTCATTGAGTGGGCAGTCTTAATTTGGATCCT
GGGAAGGCAATGAGACCTCTGCAGCTTGGAGCTTCAGGCCTAAC
CAGGCCCTGGCAGCAGGGCCACACAGATCTCTCTGCCACATCCC
CGTGTAGCCATGTTAGGGTCTGACAGAGAATGCTGCCCCGCTTG
Aldehyde CTCAGGTGCGCTTCTGGCCATCCCATCGCTTCAGTGTGCCCCCT
CAGCTCACGGTAGTCTCCAACAACCCTGCCCCATGAGTTCTGAA
dehydrogenase,AA956846 SEQ ID
N0:10
microsomal GCCTCATGTCTAATAACCCCCCTTTCACTACAGGAACAGGTGCAT
GCTAAGATCTGTAGGAATCTCTCTAAGAT1-1'CAAAAGTAAATTTTT
TTTGTGTTGTGCTGTGAAAATAAGCAGATTTATCCTGAAGACCTAT
ATAACATTCAAATCGAGGGTCTCGAGGGGATTGTTATGGAGGAAT
AATAATGAGAGGGTCCCATTATGTTGCCTAGGTTGGCCTCAAACT
CCCGGGCTCCGGAATCTTCTGCCCTCGGGCTCTGGCCTCGTGC
CGAATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAGTCGTAT
TAAATTCGTAATCATGTCATA
ATGCNGGCCTAAGGATCCTTCTTGGTCTCCTTCTTAGTCTCCTTC
TCCAGCTCCAGTGCTGNTTNTGATGCTCACTGCACTTATCCTTTG
TCCAGTCGACAAATACGATTTCTGATTCATCCATGCCCACATCTTT
GACAGCCTGCTGGAATATTTTCCGCAGCTCTGGGGACAAGTCTG
GCTTTTTAGCATAGAAGGACAGCCCCCGGTTCTCATCTGTCAGGT
TAAAGGCAAGCATGAAGGTCCCATGTTTCTTCAGCACTATCAAAT
GGGCAAAGATTTTCACTGCTCCTGCACACTTGGATAAGGTCCCAT
Alpha-1 acid A1029162 TCTCTCTCTGGACTCCTAGATGGGTGAAGTTATAGACACACTGGTSEO ID
N0:11
gfycoprofein CGTCTGTGGTCTGAAACTCCCGAAGTTCAATTGTGTCGTTTATCA
AGTTGGGGGTAAGGTAAAAATATTCCGTCTGTATCGTTTGAACTG
CCTGCTTGAACACGGGGTCTCGGAAAGCTGCTCCCATGTAAAAC
CATTTGTCTGAGAGCCATTTCAGGGTCTCATTGGTAATAGGTATG
CCTAGGGTGATGTTGGCAGGTTCTGGGTTCTGAGCTTCCAACAA
GGGCAGGAGGCTCAAAACGACAAGAACCATGTGCAGCGCCATG
CCGAAGACCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATTC
CCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATA
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RGCNNCNCCNCCCCTTGCACGCCATGNTTCCTTCTNTCCTGGGA
AGGTGGTTTACTCATGCCCTGAGCTTCCNTTCCTNTCCAATACGC
TTATTGTGACAATGAGATGCTAACACACAGAATGCTAGGAAATGA
CAGCTTGTTTTATTGGGTCCAGATCATCTAAGCTGGACTGCACAG
TGACGGACCGTGGCTACCCTCTGGCTTGCAGACCGGCTCCTTCA
ACTGCGTGTTAGCTCCTCGTACCCATCACCAGGGACTCCACAGT
Alpha-1 ACTCCTTGCACTCCTTCTCAGAGTAGAACTTGTTGCCGTTGCCTT
microglobulin/bikuninA1043784 TGCAGCCCCCATAGATGAATTGGATGCACTTCCGTTGCGCTGCATgEQ
ID
N0:12
precursor CA~TGCCCAGAGTTCTGCAAAGGCTCGGCAGGGGCCTTGGACT
(Ambp)
ATGGGGAGATTGCAGGCCGCTAT1GTCCGGCACGTCTGCAGGCA
TTCCTTCTCGGAGGCGAAGTTGTTACCATTGCCTAGGCAGCCGC
CATACTGGAAGGTCTCGCAGGCCATGGAGGCGCCATTGTAGTAA
TACTTGTGCTGCATCCCCAGGCAGGGACCTTCTGAGTAGTTGAG
CTGGCAGGAGTCTTCTTTCTTGAGGGTCCCAGTTATGAGTGGCT
CACCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCCTAT
AGTGAGTCGTRTTAAATTCGTAATCATGTGATA
TATGACATGATTACGAATTTAATACGAGTCACTATAGGGAATTTGG
CCCTCGAGGGCAAGAATTCGGCACGAGGTGCAAGGCAGCCAGG
TCTCCGATCCTTTCCGCAGCATGGGGAAGCACAGGCTCGGGAGC
CTGGCCCTGCTGGCACTGCTGCTGCGGCTGCTGCTGCTGGTGCT
GCCCACCGATGCCTCAGCTCCACAAAAACCAATCTACATGGTGAT
GGTTCCCTCCCTGCTCCACGCAGGAACCCCCGAGAAGGGCTGCT
Alpha-2- TCCTGTTCAGCCATCTAAACGAGACAGTGGCTGTGAGAGTGTCC
macroglobulin,NM TTGGAGTCTGTCCATGGGAACCAAAGCCTCTTCACTGACCTTGTASEO ID
012488 N0:13
sequence 2 _ GTTGACRAGGACCTATTCCACTGTACCTCCTTCACCGTCGCACAG
TCTTCATCTGATGAGGTGATGTTTTTCACTGTCCAAGTAAAAGGA
GCAACTCATGAGTTGTGGCCCCTAAGTATCGCCGCCGTCTGTTTT
ATTTAGTGTACAGTAGTATAGGTGCGCACTCTGGTCATTTTCCAA
GCCATGTTTTATCATATCTGITI'TCTACTTTCCGTGAGCGAGGTTT
GCTGTCCAAGGTGTAAATACTCATGGGAATAAAACTGGCATGGTA
CTTTGCCTTGCTTTCTCATTTTCTTGGGTCTGAGATTTCAAAGGTA
AGGGCCCATCAACAAGC
TTCTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAAl-fCGGCACGAGGATCAGCAGAGAGATT
GTCCCGACAGAGAGGCAATTCTATTCCCTACCAACATGAAGCTGT
TGCTGCTGCTGCTGTGTCTGGGCCTGACCCTGGTCTGTGGCCAT
GCRGAR6AAGCTAGT-fTCGAGAGAGGGAACCTCGATGTGGACAA
GCTCAATGGGGATTGGTTTTCTATTGTCGTGGCCTCTGATAAAAG
AGAAAAGATAGAAGAGAACGGCAGCATGAGAGTTTTTGTGCAGC
ACATCGATGTCTTGGAGAATTCCTTAGGCTTCACGTTCCGTATTA
Alpha-2-microglobulinAB039825 AGGAAAATGGAGTGTGGACAGAA1?TTCTTTGGTTGGCGACAAAASEQ
(D
N0:14
CAGCAAAGGATGGCGAATATTTTGTTGAGTATGACGGAGAAAATA
CAT'(-f'ACTATACTGAAGACAGACTATGACAATTATGTGATGTTTCA
TCTCGTTAATGTCAAGAACGGGGAAACATTCCAGCTGATGGAGCT
CTACGGGAGAACAAAGGATCTGAGTTCAGACATCAAGGAAAAGTT
TGGAAAACTATGTGTGGCACATGGAATCACTAGGGACAATATCAT
TGACCTAACCAAGACTGATCGCTGTCTCCAGGCCCGANGNTGAA
NAAANGGCTGAGCCTCGAGANTGCCTCTGTGTCCAGAAGTCAAT
CCAAGAAGT
TCTATGACATGATTAGGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCATGAGGCTCAAAAACTCACT
ATTTGATTTTGAAAAGAACAACAAGGATTCTAATTCACTGACCAGG
AATATCATGGAGTATTTGAGAGGGGACTTCGGTAACGCCAACAAC
TTTGATAACACT'fTCGGGCAAGTGTCAGAGGACCTGAGGCGCAG
AATTGAGATCGTAAAGCGCAAAGTCATAGAGAAAGGGGAACAGAT
TCAGGTTCTGCAGAAAGACGTCCGGGATCAGCTGATAGACATGA
Alpha-fibrinogenX86561 AGCGCCTGGAGGTGGACATTGATATCAAGATCCGCTCTTGCAAASEGt ID
N0:15
GGATCCTGCAGGAGGTCTGTAAGCCGTGAGATAAATCTAAAGGA
CTACGAAGGTCAGCAAAAGCAACTTGAACAGGTCATTGCTAAAGA
GTTGCTTCCGGCAAAAGACAGGCAGTACTTGCGAGCAATAAAAAT
GTCTCCAGT7CCCGACTTGGTTCCCGGAAGTTTTAAGAGCCAGCT
TCAGGAGGGGGCCGCAGAGTGGAAGGCATTAACAGAAATGAGG
CAGATGAGAATGGAGCTGGAGAGGCCGGGAAGGATGGGGCTTC
GCGAGGAGATTTACCAGGAGATTCGCGAGGAGACTGTGCNACAC
GT
109
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TACTGGAATGTCAGAATAAGATTGTTTT1'TGGTGGTGTTTTTGTTT
TTTTACAAGGTTT7-fITTCTCCTTGAGAGTATAATGAACATGGTCA
CACCACAAGTAAAGTCTGAAGTAGGACAGAAAACGCTCTGAAGG
CTGGTTTGGTCACCCGTTATCATTAAAAATGGCTGACCCCTAACA
ATATGTAGAAAAATATAAAATGTAAATAAAAAATACAAACAAATTTT
CCTTTTAAAGTATTTTTAAGAAAAAAAGCAGGGCCTGGGAAGTTC
TGGTTCTTTTGTCCTCCCATGTTGCCAATTCATGTTGTGGT1TTGG
Alpha-prothyrnosinAA875070 TGGGGTGGTGAAGAGCGCATGTCATGTGTGGGTGGCACTGCCCSEQ ID
N0:16
GCAGTGGGCCGGCGGGGGCCTGCTTCTCTACTCGAAGGTGACC
ACGTTTAAATTCTGAGACGGGAAGTGGAGGGTGAATAGGTCACG
GTGCGTAAGGTTAGCTTTTCCTTTTGCTGTCTAGTCATCCTCATCA
GTCTTCTTCTGCTTCTTGGTCTCAACATCATCATCC'TCATCATCCT
CAGCTACCCGCTTGGCCGTAGGAGCCTCAGCTTCCTCATCTTCAT
CTCCATCTTCTTCCTCACCCTCGTGCCGAATTCTTGGCCTCGAGG
GCCAAATTCCCTATAGTGAGTCGTATTAAATTGCGTAATCATGNT
NGGAGA
NCCCNATTCAGGTTGCGCAANTTTTGGGAANGGNCAATCGGTGC
GGCCTTNTTCGCTATNACNCCAGCTGGGGAAAGGGGNATGTGCT
GCAAGGGATTAAGTTGGGGAAACNCCAGGNTTTTCCCAGTCACG
ACGTTGTAAAACGACGGCCAGTGCCAAGTAAAATTAACCCTCATA
AAGGGAATAAGCTTGCGGCCGCAATGTTTTNNNNNNNNNNNNNN
NNNNNTTCTCTAGAAGTTTTTATTGGTATTTGAAGAGGGACCTGG
CCCGTCACGTGGCCCTCTTTGCTGCTGCGAGGTGGCTCGCCAG
ApolipoproteinAA955662 GCAGTCAGGCAAATGTGG1'TTTTAATTTCTCCTTCATTTTGTTGAGgEQ ID
C1 N0:17
CGTGTCTGAAAACCAGTTCCGAGTCTTGATCATAATTTCCTTCTGT
TTGATATGCTCAATGGCTGCCCGGGCCTTATCTTCCAAAGTGTTC
CCAAACTCTTTTAGTTTATCCGGTAAGCTCTCCATTGCGCTGGAA
AAGTCAGGGGCCGCCTGGGCAGGGGCTGGGCCTTCCAAAGCCA
TGGCTACGACCACGATCAGGACAGGAAGTGCGATGAAGAGGCTC
ATCCTGGCTGGAGGGGCACCCTGGATCTAAGGTTCTCTCCCTCG
TGCCGAATTCTTGGGCTCGAGGGCCAAATTCCCTATAGTGAGTC
GTATTAAATTCGTAATCATGTCATA
TCTATGACATGATTACGAATTTRATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGCTTCACCGCCAA
CAGCACGGCCATGGCTGGAGCTCTGGTGCGCAAAGCAGCGGAC
TATGTCCGGAGCAAGGACTTCCGGGACTATCTCATGAGTACGCA
CTTCTGGGGCCCAGTTGCCAACTGGGGTCTCCCCATTGCTGCTA
TCAATGACATGAAGAAATCTCCAGAGATTATCAGTGGGCGGATGA
Apoptosis-regulating C~CGCCCTCTGTTGCTATTCTCTGACATTCATGAGATTTGCCTA
basic pKoteinAF304429 CAAGGTACAACCCCGAAACTGGCTTCTGTTTGCGTGCCATGTGASEQ ID
N0:18
CAAACGAAGTCGCTCAGCTCATTCAGGGAGGACGACTTATCAAC
TACGAGATGAGTAAGCGGCCATCTGCATAGCAGTGCAAGGACCA
GCTCTTGAAAGGGACAGTGCTCCAGCCACTGTTGCGGCCACAGA
TCACGTCAGCATGAATAGTCGTGCTGAGGGGAAAACACGGAAGA
CTATCTTTAATGACCATGCCAACATTATTGAATAGCCRAGAATCCC
CAAACCAACTCTCGGCTGCCTTATCAATGCTAAACTTTATTTTGTC
TTCATCAGGAGTAGTTCAAAATATGCAGCTAATTTTATNATT
CAACTGTTGGAAAGGGGGATCGGGGNGGNCCTNTTCGTTATTAC
GCCAACTGGCGAAAGGGGGATGTGTGCAAGGCGATTAAGTTGG
GTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGC
CAGTGCCAAGNTAAAATTAACCCTCCCTP,P.AGGGAATAAGCTTGC
GGCCGCGAGATTTTTTTNTTTTTANTTTTTTTTTNTTTTTTTTTTTTT
TCCTGTCAAATGCATACATTTTATTCTTTTCTTTATATATAAAAGGC
AACAGTACATTGTTGATTGGGGGATTAAAGGAAGGAAGACCCTTT
TAAAAAGTGGAGTT'1'CCCACCCCTATTCCTAAAACTGTAACATATA
Aquaporin-3 A1045067 TATGTATGTATATATTTATATATTTAAAAAAAACAAATTATGAAACTSEQ ID
{AQP3) N0:19
TACGACCAGGACTTTAGCGCCTCCCAATGTCTATCT'fATAACAGA
AACATATTACATACACAGCCCCTAGTTGAGGATCACAGCTCCAGA
TGTGAGCTACGCCCCTCTTATGCCTCCCCCGCTCCCTAAGCCTA
GAAGTCCATTTCGAAAACTCAGTAGACACATACATACTTAGAAAC
GGACTCCTGGGTCCACCTCCACACTGGAGTCCCTGAAGCAAGTA
TACTGTGGCACTTTCCTGCCTCGTGCCGRATTCTTGGCCTCGAG
GGCCAAATTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCA
TA
110
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGGTCCACTAAC
TCCAGGGACTGTGGGACAGAGGAACAAACAAGAAAGAACTCGAG
GCCTCGCTGAGTGGCGCGCTTGCTGAGTGCTGCCACATCCCGC
AAGCTGAGCAGGTATCCCAACTCTGTTCCTGCCCGGTAGACCAC
CCGAGGTGGTGAGTGTGGTCTTGTCTTCCAGATTCGTAGGACAG
Argininosuccinate AAGCTCCAGGAGGAGGACCCGCCCAACATGGCATCGGAGAGCG
lyase D13978 GGAAGCTATGGGGTGGCCGATTTGCAGGCTCGGTCGACCCCACSEO ID
N0:20
CATGGACAAGTTCAACTCATCTATCGCCTATGACCGGCATCTGTG
GAATGTGGACCTGCAGGGAAGCAAGGCCTACAGCAGGGGCCTG
GAGAAGGCAGGGCTTCTCACCAAAGCTGAGATGCAGCAGATACT
GCAAGGCCTGGACAAGGTGGCTGAAGAGTGGGCCCAAGGCATC
TTCAAATTGTACCCTAATGATGAAGACATCCACACGGCCAACGAG
CGGCGCCTGAAGGAACTCATTGGTGAAGCTGCAGGGAAGTTACA
CACAGGCAGAAGTCGCAA
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTGACAAAGAGGC
GCGGGCCTCCCCGCTCTGCAGCTCTCCCAGGCTCCAGCATTAAT
Arginosuccinate TGTTGTGATAAATTTGTAATTGTAGCTTGTTCTCCTACCACCTGAC
synthetase M36708 TGGGGCTGCTGTGCCCCCCCTCACCTCCCCCCCACCCACAGGCSEQ ID
1 N0:21
TTTGTTCCCTGGTCCCCTATAGCCTACAAAAGTGGTCATCGAAGG
GAAGGGGGGGTGGCAGGCAGCTGCAGAAAGCGCGTAAAATGAC
AATTAAAAGAAGTTACATTAGTCTTTCATTTGTCAAAAAAAAAAAAA
AAAAAAAAAAA
CTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCAAAAACTGGAAAC
TCCTCACGGGCTACCCAGGCTGTGGTTACTGGTTCCCGCCACCG
TCTCAGTCCAACATCTCTGAGGTACCTTCAGTGGACTCACCAACC
AAGACTCTCTGGCTCTTTGACATCAATCGGGACCCTGAAGAAAGA
CATGACGTGTCCCGGGAACATCCCCACATCGTCCAGAACCTTCT
Ary(suifataseD49434 TTCCCGCCTACAGTACTACCATGAACATTCTGTGCCTTCTTACTTCSEQ ID
B N0:22
CCACCTTTGGACCCCCGCTGTGATCCCAAGGGTACCGGTGTATG
GAGCCCCTGGATGTAGGGCTCAGGGGAGGTGGGGCTGGAGTAC
ATTTCTGTGCAGGCTAGCCCTCAGGCCCATACTCTCCTGGCTTCT
CCATCATCCCCCACCCTGTCACCTGGCCCTCACGCTGTATAACC
CACTGAGGGAGTCCAATTTCAACCCACAGTACATTTTTAAAGCCA
GTAAAATCTGGAAGGATCCTGANAAACAAAAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGAGCTCTGTATTTTT
CACTTCTCACTTAGATCTAAACTTGGAAACTTTTCTCAGAAGTTAA
GTGTCCTTTGACCTCCTCTCTTCTGAATTGCAGAAACCAGACCAG
ATTTTGGTATTTGGTAAAATGACTTCTTGTGTTGCTGAAGAACCTA
TTAAAAAGATTGCCATCTTCGGAGGGACTCATGGAAATGAACTGA
CTGGAGTGTTTCTAGTTACTCACTGGCTAAAGAATGGCGCTGAAG
AspartoacylaseNM 024399TTCACAGAGCAGGGCTGGAAGTGAAGCCATTCATTACCAACCCASEQ ID
N0:23
AGAGCGGTGGAGAAGTGCACCAGATACATTGACTGTGACCTGAA
CCGTGTTTTTGACCTTGAAAATCTTAGCAAAGAGATGTCTGAAGA
TTTGCCGTATGAAGTGAGAAGGGCTCAAGAAATAAATGACTTATT
TGGTCCAAAAAATAGTGATGATGCCTACGATGTCGTTTTTGACCT
TCATAACACTACTTCTAACATGGGTTGCACTCTTATTCTTGAGGAT
TCCAGGAATGACTTTTTAATCCAGATGTTTCACTATATTAAGACCT
GCATGGCTCCATTACCCTGCTCTGTTTACCTCATCGAGCCATCCT
TCCTCAANGGGGGGGGGGGGGG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGACCTTTGGGACTGAC
CCCTGCCTCCACTCTCATGATGCCCTATACTATTCCCCTTAAGGT
CTAGGATGAATTTGTATCCTGTCCATTGAAATGTGTCATCCAGTAT
ATTCCAGATGCTGCTGGCCTAAACTTGTCTGAGGAAGGGGTTGTT
ACTCACCTCTTCAAAATGAGTGGATTCCTGCTTGTTTGCTTTTAAC
ATP-stimulated AGCTCAGATGTCTTTTCTACATATTAGAAGACCACAACACCACTG
glucocorticoid-NM 024381GATATTTCAATGGAAACGTCTAAAGCATTATTGGATAATAACTTGCSEO ID
N0:24
receptor translocation- TATTCTTGTTGCTTAGACATTTTCTGTACAGTGTTTGCCAAAATTG
promoter (Gyk) AAATTTTTCAGGTGTTTTACACTGTCTCACTAATTGTCATGGTTCA
TGGCTTTCTGTCTGGATCTTACAGGGATAGATAGAATACTTTC'1-1'T
TTCTGCTTTTTTTTTCATTCCTCCTTTTTATATTTTTACTCTGTATGT
ATAACATACATACCTATATATTTTATATGCTGAGGGTAGCCCATTT
TTAAATTAAGAGCACATTATATTCAGTAAGTTATAAGAGGGCTGGT
CTTAAGTGGACTACTATGTATATAAATTTGAGGGGGGCAAGCTGT
ACACATTTTTGGGCAACNGTTATGCATAT
111
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGAAAGTGGGGGTGGGAGGGTCATCCTACTGAGTGGTTCCATG
GGTTTCTCTGTTTTGCTGTTCAAAGGGAAAGCCGCACCTACCCCC
ACACTACCCCTGAAGCAATACCAGGAGCCATCTGACCCTCAGCA
GCTCTTGCTTCTAAATACAGTCTGACCTANGGATACTTTGCCCTG
GGCTTGTATCCTAGTGTCCTCTTCTCTCTCTGGGACCTATCCACT
GCACCTCATTGGGCTCAGGTCCAGGAGCAGGGGATCCTGTGGG
Axin AF017756 GGCCTCTGTATATTGTNCATGTCACTGAGTGCCTTCAACATAGNTSEQ ID
N0:25
GTNTCTTGCCTGCCACTGTGTGAATCTGGCGGCTGAATATCTNAN
GCCTCTTTGCCTGTCTCCAGCCACCAGCTTGGTTCAACAANAGG
GGGGGGGTCTGGTCCCTTCCAAGTGNCCATGGAAATATNTACAT
TTCNCAGGCCAGGGCCANGCAGGGGATACCCTGAGCCCGTTTTT
CATGCCATGAACTTGTACAATGATCTTTTTCAAAGGGTCCTCGGG
ACAATAATGAAATAAAAAGGTTTi'ITGAACCCCC
TGACATGATTACGAATGTAATACGACTNCTATAGGGAATTTGGCC
CTCGAGGCCTAGAATTCGGNACGAGGCAGGATTNAAAAACTGGA
ACGGTGAAGGCGACCGCAGTTGGTTGGAGCAAACATCCCCCAAA
GTTCTACAATGTGGCTGAGGACTTTGATTGTACATTGTTTI-TTGTT
TTTGGTTTTTTTAATAGTCACTCCAAGTATCCACGGCATAGATGGT
Beta-actin TACAGGAAGTCCCTCACCCTCCCAAAAGCCACCCCCAACTCCTA
sequence
V01217 AGGGGAGGATGGCTGCATCCATGCCCTGAGTCCACACCGGGGASEQ ID
NO:26
AGGTGACAGCATTGCTTCTGTGTAAATTATGTACTGCAAACATTTT
TTTAAATCTTCCGCCTTAATACTTCATTTTTGTTTTTAATTTCTGAA
TGGTCAGCCATTGTGGCCTGCCCCTTTTTTTTGTCCCCCCAACTT
GATGTATGAAGGCTTTGGTCTCCCTGGGAGTGGTTTGAGGTGTT
GAGGCAGCCAGGGCTGGCCTGTACACTGACGTGAGACCGTTTTA
ATAAAAGTGCACACCTTACAAACN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTGAAATCATCTTCAA
CCCTTCAGCCACCATTGGAGAACTCAGTGAGTCCATGTGGCCGA
TCGAAGCCAGAAACGCAGCCATCGCTAATCACTGCTTCACCTGT
GCCCTCAACCGTGTGGGTCAGGAACACTACCCCAATGAGTTTAC
TTCTGGAGATGGAAAGAAAGCTCACCATGACCTCGGCTACTTCTA
CGGTTCGAGCTACGTGGCAGCTCCTGACGGTAGCCGGACCCCC
GGCCTCTCACGCAATCAGGACGGGCTGCTGGTCACTGAGCTCAA
Beta-alanine M97662 CCTCAACCTATGCCAGCAGATTAATGATTTCTGGACTTTCAAGATSEQ ID
synthase N0:27
GACGGGCCGACTTGAGATGTATGCCCGGGAGCTTGCCGAAGCT
GTCAAACCCAACTACAGTCCCAACATTGTGAAGGAAGACCTGGTT
CTAGCCCCTAGCTCGGGTTAGGTTCGGGGGCAGTGGTTAAGTTC
TAAACATTGTGTGCGAGAGAGTTTTCAATACCCAGGCAGGAGGA
GGGTAGACTGGGCAAGCGTGTGTGTGATAACTGTTGATAAGGGA
TATGAGATTTTTCTTCTGGGGATTTGGAAATGTTTTGGGGTTCAAA
ANGTGATCCGACAGCATTGAAACTTCAATAAACATAACTGGATCG
TAAAAAAAAAAAAAAAAA
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCTTCGAATAGCTTC
CGGCAGACCGTACAATCCTTCGATGTCCAAGCCGGATGCTTGGG
GAGTGACGAAAGGGGCAGCAGAGCTGATGCAGCAGAAGGAAGC
CACCACTGAGCAGCAGCTGAGAGCGCTCTTCGAAAAACAAAAAT
TCAAATCCGCACAGTAGCCACAGGCCAGCGGTTCGGGGCGAATT
Betaine homocysteine CCTCCAGGTCCGGGCCACAGTGTGCACCCGGAAGGAGAAGGCA
meth ItransferaseNM 030850TCTCTAAACCAGCGTTTGTGTTGATGCCGGCTTACACCTGTGATT
y SEQID N0:28
(BHMT) - GGTGCTAGTTAGACAAAATGGAATCACAGATAGCATTTCACAGTT
ACAAAACTACGCTTTAGAATTTTACCTAGAAGGAAGAAAGGAGAA
GTCCACAGTAAATCCTGAACACATTTCCTACGTGCCTGTCGCATT
ACAGGCGCACAGGAGTCACTGCAGCGAAGAGAAAGTCACCCGA
CATCAATCTCATTTCAGATAGGGGGATAGGACACCACCCTCCAC
GAGTGACATAGAACCATTCAGGGACCGTATCATAAGTGACACAG
CAACCATCTATATCTAAGATGCTTCCCAAGTGGGATTCCAAGATC
TTTTGAGCANGGACCTTANGCAGAAAACA
112
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGAATTATTACAGTA
AACCGTAGCCATGAGGGAAATCGTGCACATCCAGGCCGGACAGT
GTGGCAACCAGATCGGTGCTAAGTTCTGGGAGGTGATAAGCGAT
GAACACGGCATCGACCCCACCGGCACCTACCACGGAGACAGCG
ACTTGCAGCTGGACCGAATCTCTGTGTACTACAATGAAGCTACAG
GTGGCAAGTATGTCCCTCGAGCTATCTTAGTGGATCTAGAACCC
Beta-tubulin,AB011679 GGGACTATGGACTCCGTTCGCTCAGGTCCTTTrGGCCAGATCTTSEQ ID
class I N0:29
CAGACCGGACAACTTTGTTTTTGGTCAGTCTGGGGCAGGCAACA
ACTGGGCTAAGGGTCACTACACAGAGGGAGCTGAGCTGGTTGAC
TCTGTCTTGGATGTGGTGCGGAAGGAGGCGGAGAGCTGTGACT
GCCTGCAAGGCTTTCAGCTGACCCACTCGCTGGGTGGAGGCAC
GGGCTCTGGCATGGGCACCCTGCTCATCAGCAAGATTCGAGAAG
AATACCCCGACCGCATCATGAACACCTTCAGCGTGGTGCCCTCA
CCCAAAGTGTCTG
ATCAATGTTTTCCATCAGTACTCTAGGAAGTATGGACATCCTGAC
ACCCTGAACAAGGCGGAATTCAAAGAAATGGTGAATAAGGACTT
GCCAAATTTTCTGAAGAGGGAGAAAAGAAATGAAAATCTCCTAAG
AGACATCATGGAGGACCTGGACACAAACCAGGACAATCAACTGT
CCTTTGAGGAGCGTATGATGCTGATGGGAAAGTTGATCTTTGCCT
GTCATGAGAAGCTGCATGAGAACAACCCACGTGGGCATGACCAC
Calgranulin NM 053587AGCCACGGCAAAGGCTGTGGGAAGTAATTAAGAGGTCAGCCATGSEQ ID
B N0:30
TAACATCTGCCCAACCAAGTCTAAAGGGAATAGCTTACTAAATGA
CCTTGGNTCTGGGGCTGGGAAATAATTTAAAAATGAATAAATAAA
GTCTTTATCCCT'f-I'NNNAAGGCTACCCTGNNAAAAAAANACNTCT
T1'f-fGNGGGNGGCTNANTTT1TT'CCT1T1~TTGNGGGGGGNAATTT
TCTNTGGGCCCCGGCNNTNTTT'fl'ACAANTTGNCNNNTTGGGAAA
AACCCCCGGGGTTANCCAAAATAAAA
ACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGCCC
TCGAGGCCAAGAATTCGGCACGAGGCTAGGGAGGCTCTCTGCAA
TAGGTGCCCGGCCCAGCTTTTTTTTCAAAATGTCTACTGTCCACG
AAATCCTGTGCAAGCTCAGCTTGGAGGGTGATCATTCTACACCCC
CAAGTGCCTATGGGTCGGTCAAACCCTACACCAACTTCGACGGT
GAGAGGGATGCTTTGAACATTGAAACAGCAATCAAGACCAAAGG
CGTGGACGAGGTCACCATTGTCAACATTCTGACTAACCGCAGCA
Calpactin ATGCACAGAGGCAGGACATTGCCTTCGCCTACCAGAGGAGGACCSEQ ID
I heavy NM 019905N 0:31
chain GGAACTGCCATCGGCGATGAAGTCGGCCTTGTCTGGTCA
CCTGGAGACCGTGATGTTAGGCCTGTTGAAGACACCTGCTCAGT
ACGATGCCTCTGAGCTCAAAGCCTCCATGAAGGGCCTGGGGACT
GATGAGGACTCCCTCATCGAGATCATCTGCTCAAGAACCAACCA
GGAGCTGCAGGAGATTAACCGAGTGTATAAGGAAATGTACAAGA
CCGATCTGGAGAAGTGGCCCTTACCTGTGCCCCAACCTAATGTT
CTAGAGAATCAGCCTGCCACTAATGGGACCCCTGAACTCCTCCT
GGGAANATGACGACAGANCTTGCCN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATTGCATAACCCTCGG
TAAGGTCAGAGAGAGCTTTATGCCTGTACATAGTATATCCTTTCTA
CTTCTACACATCGTCTC'I-fCATAGCAATATTAAACCAGGAAGGAC
TGTTGAGAGGTTTAAGTAATTGGGCAAACAGCAAATTGATCTCAG
AGGCCACAATGCCTTGATGGGAATATITAAAGAAATTtAAAAATiT
AAGATGCAGTGGTGGCATCTTCCACAGCAGGCCAGAGAGAAACA
Catpain 2 NM 017116GAGAGAGAGAGAGAGAGACTTGGAAATACAATAATAAAGTAATCTSEQ ID
N0:32
GTGGAGGCGTCTAAAGAATCCAGTCTGATGGAGGCATCTAAAGA
ATCCAGTCTGATGGAGGCATCTAAAGAATCCAGGAGCCAGGAGT
ATCTGACACAAGGCCAACCTGGGCTAGCTAGCAAGACCTGATCT
CAAAAAATAAATGTCAATTAAAAAAAAAGAAGGCATGTTTCCATCA
TTTGGTTCTAACAAAAGATGGTTTTTATACACCTTTGTGAACAGCA
AGCCCTCTTAGACTCAAGTCCTTGACCATATTTGGCCTTTAGACA
TTGAAGTAGTGAGTAGTGAGATCATTTGACTGACCAACTGACCAN
GTCTGCCATCTGAAAGAAA
113
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCAACGCCAACAATGTTCCTGCCACCCCAGTGGCTTGCCATCT
CAGGAAGGACAGAATCCCAGCCTCTCT'fCCATCAGAAAGTTGATA
AGAGACGGAAGCATTGACCTAGTGATTAACCTCCCCAATAACAAC
ACCAAATTTGTCCATGATAATTATGTGATTCGGAGGACAGCTGTG
GACAGTGGAATTGCTCTGCTCACCAATTTCCAGGTGACCAAACTT
Carbamyl phosphate TTTGCTGAGGCTGTGCAGAAAGCTCGTACTGTGGACTCCAAGAG
synthetase X12335 TCTGTTCCACTACAGGCAGTACAGCGCTGGAAAGGCAGCATAGASEQ 1D N0:33
I
GCAATATGCTGGTCTAGTGAATTCATCCTTCAGTCAGCAGGAGCC
ACACTGTACCAAAGGGACTGGTCCCAGCCTATCGCCAGAAATGG
ATGTTGTTGCCAAACCTTATTTTTGGTTTCCCTGTTCTTAGTAGTC
TGTATCTTTAACCACTGAATTGTTGTCAGTCACTGTTTCAAAACCA
TCANGGTCTTCCCAAGTCTCTTGTCTTCACAAGGAATCCAACCAT
TCATACATTATCTTTTGTANACCGACTTGTACATI-T
CATGGG
CTAACCCAGAAGCATGAATTTCACACCTAACCTTTTTAATAAGTAC
CT'ITfCTAAAAAAATTAGTATTTCTAGTATAAATTCAGTGAAGAAG
AAATAGATGGAAAAATAACGACAGTGACAGTGGCTTATTAAGCAT
ATl'AAGTTTCTCAGAATCTCAGCACTCGTGT-fTTCAGGGTGAGTTA
CTGACAAGTGATGGGTCCATGCTATGTATGTGGGTATGGAGGCA
Carbonic anhydrase TGTGCCCACCTTACCACATTTGATTGAAAGCACAAGTTAAGATCA
111, sequenceAB030829 CTGTAGATTTCAGAAGGTGAATACATAATGTTTACCTCAAATAATASEQ ID
N0:34
2
CCATCGCTACTCTATCAGTTTTTAAAAATTTGCCTACTACCAACTT
CGCCTGGTTTTAAATTACCGATAAACACACACCCATAAGGCCAGG
TCTTTTAAATTTT'fTGATCCAGCATTTAAATTTCTTGTTCATAAAGA
TGGTTTTCTTTGCCCAATCTAGGGTCATTTATTTTTTATTTCACTAC
TTTAATCTTTGCATGCCTATTAAAAACAAAGCAAAACAAACAAACA
p~~aAAAAAA.ACC
TTATCACATGATTACGAATTTGAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCCAGCTTCTCTCAC
CCTACTCTTGGGTTCAAGATCTTAGCAACCATGAAACTTCTTATCC
TCACCTGCCTCGTGGNTGCTGCTCTTGCTCTGCCTAGAGCTCATC
GTAGARATGCAGTCAGCAGTCAAACTCAGCAAGAGAATAGCAGC
AGTGAGGAACAGGAAATTGTTAAACAACCAAAGTATCTCAGTCTT
AATGAGGAGTTCGTCAACAACCTGAACAGACAGAGAGAGCTTCT
GACAGAACAGGATAATGAAATCAAGATAACTATGGACTCATGAGC
Casein-alpha J00710 TGAGGAACAAGCAATGGCAAGTGCTCAGGAAGATTCCTCCTCAASEQ ID N0:35
GCAGCTCATCAAGCGAGGAATCCAAGGATGCTATTCCCAGTGCT
ACTGAGCAGAAAAACATTGCAAACAAAGAAATACTCAACCGATGC
ACCCTGGAACAGCTTCAGAGACAGATTAAATACAGCCAACTTCTC
CAGCAAGCTTCACTGGCTCAGCAAGCTTCCCTGGCTCAGCAAGC
TTCTTGGCCAGCAAGCTCTCCTGGCCCAGCAACCTTCCTGGCAC
AGCAAGCTGCCCTGGCACAGCRRGCTTCCCTGGCACAGCAAGCT
TCCCTGGNACAGCAAGCTTCCCTGGCACNAGAAACATCATCCAA
GNAC
GACCTCGACCATGGGGi-fCTGGTGGTTGGCTATGGTTATGAAGG
AACAGATTCAAATAAGGATAAATACTGGCTTGTCAAAAACAGCTG
GGGTRAAGAATGGGGTATGGATGGCTACATGAAAATAGCCAAAG
ACCGGAACAACCACTGCGGACTTGCCACCGCAGCCAGCTATCCT
ATCGTGAATTGATGGACAGCGATAATAAGGACTTACGGACACTAC
Cathepsin Sg5184 ATCCGAAGGAGTTCATCTTAAAACTGACCAAACCCGTCTCTGAGTSEQ ID
N0:36
L,
sequence 2 GAGACCATGGTACTTGAATCGTTCAGGATCCAAGTCACGATTTAA
ATTCTGTTGACATTTTTACATGGGTTAAATGTTACCACTACTTAAA
ACTCCTGTTATAAACAGCTTTATAATATTGGACACTTAATGCTTAA
TTCTGATTCTGGAATATTTGTTTTATAAAAGTTGNATAAAACTTTCT
TTACCTTTTAAAAATAAATTTTAAGCTCAGTGCAA~AAAAAAAAAAAA
AAAAAAAAAAAA
114
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTAAGCTTGGTCTTTC
TGCCCCAGGACTGTCAACAATACCAGCCACAAGATTCTGATCTCC
TCCCGAAGGTGCCCCAGCCTCACAATGATGACCGAAGAGCACAC
AGATCTGGAGGCACGGATCATCAAGGACATTCACTGCAAGGAGA
TAGACTTGGTGAACAGAGACCCCAAGAACATCAATGAGGACATT
GTGAAGGTGGAT'rfTGAAGATGTGATTGCGGAGCCCGAGGGCAC
Caveolin-3 NM 019155TTACAGCTTCGATGGCGTGTGGAGGGTGAGCTACACCACTTTCASEQ ID N0:37
- CCGTCTCCAAGTACTGGTGCTACCGCCTGCTGTCTACACTGCTG
GGTGTTCCACTGGCCCTGCTCTGGGGATTCCTGTTTGCCTGTATC
TCCTTCTGCCACATCTGGGCCGTGGTGCCCTGCATTAAGAGCTA
CCTGATTGAGATCCAGTGCATCAGCCACATCTACTCACTGTGTAT
CCGCACCTTCTGCAACCCGCTCTTTGCCGCACTGGGCCAGGTCT
GCAGCAACATTAAGGTGGTGCTGCGAAGGAAACTGCTCAACCTA
CCATGATCCCCAGCGACCCTGCCTGAGCAGAAGGTTCCTTAAAA
GCAACTATCACAAGGCTTTGNGNGGGGNNGGNNT
TATGACATGATTACGAATT'TAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGGCCCGCAGGGGTC
CCCGTGGCCGCTGCGATGCAGAAATACGAGAAACTGGAGAAGAT
TGGGGAAGGCACCTACGGAACTGTGTTCAAGGCCAAAAACCGGG
AAACCCATGAGATTGTGGCTCTGAAGCGAGTCAGGCTGGACGAT
GACGATGAGGGTGTGCCAAGTTCAGCCCTCCGGGAGATCTGTCT
ACTCAAAGAACTGAAGCACAAAAACATTGTCAGGCTTCATGATGT
Cdc2-relatedL02121 CCTGCATAGTGACAAGAAGCTCACATTGGTGTTTGAGTTCTGTGA
protein
SEO ID N0:38
kinase(NCLK) TCAGGACCTGAAGAAATATTTTGACAGCTGCAATGGTGACCTGGA
CCCTGAGATTGTGAAGTCACTCCTCTTCCAGCTGCTGAAAGGCCT
GGGATTCTGTCACAGCCGTAACGTGCTGCACAGGGACCTGAAGC
CCCAGAATCTGCTCATTAACAGGAATGGGGAACTGAAATTGGCT
GATTTTGGCCTGGCCCGAGCCTTTGGTATCCCAGTCCGCTGCTA
CTCTGCTGAGGTGGTCACGCTGTGGTACCGCCCACCGGATGTCC
TCTTTGGGGNCAAGCTGTACTCCACGTCCATCGACATGTGGTCA
GCCGGCTGCATCTTTCAGACTGGCCAATGCAGGC
TATGACATGATTACGAATTTAATACGACTCAGTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCCCAACTTCCTAATG
GATGCAGATAAACACAGTGTACAGATTTTTGATAATCACCGTAATA
AGTATTTAGACTAGGGGTTAAGCTCTGGTTTTTAGAATTCTTAAGA
TCATCTGTGGTGAAAAGTAGTTATGAAGCTGGGCTTGGTGACAGA
CCACCATGGGATCCCAGCACTCAACAGGCAGATGTTAGTTCAAG
GTCGGTCTACATAGCAAGTTCCAGACCAGCCACAGTTACAAGGT
CDK102 Y17321 GGGATGCTACCTACTGGTTATGGGAATTTCATAATTCAGGATAACSEO ID NO:39
AGTGGTGTATCTTACGTACTTTTGTGACTTGCCCATATCCACCAC
TGGATTTTGGTCCGAGACTTCGTGTCTTCTCCTTGGAAATGCTGG
GCCTGTGGGGAGGTGTTGTGCAGTGTCAGATGCAGGAGATTCCC
GTCTTTGTCTCGTCTTGTGCTGTTCTCGCACGGTGAACACTGGCT
TTGCAACACTGAGAAATAAATAAAACACTCATGTCCTTGGTTAAAA
CACTGCGGCCGCAAGCTTTATTCCCT
TTAANGAGGGTTAATTTTANCTTGGCACTGGCCGTCGTTTTACAA
CCGCCTNGACTGGGAAAACCCCTGGCGGTTACCCAACTTTAN
TCTTNACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCAGTGCTGTATGTG
GACTCCCGGGAGGCTGCCCTAAAGGAGTCAGGAGATGTTCTGTT
GTCAGGGGCTGACATCTTTGCTGAGCTTGGAGAAGTGGTTTCAG
GAGCGAAGCCTGCATACTGTGAGAAGACCACGGTGTTCAAGTCT
TTGGGGATGGCAGTGGAGGACCTGGTCGCAGCCAAATTAGTGTA
CGATTCGTGGTCATCTGGCAAGTGAGCAGAAGGAGCTGTGCCTG
CDK108 Y17328 TGCTGGATGGACGTCACGGCTCAAACGCTGGCTCAGTGTCTAGASEQ ID N0:40
TCAAAGGAGGCCTAGTCCCCAGTGAACGGGAGTGAGAGTCACTG
ATAAGTATTGACATCCCTATTCATGI-fT'GTGGTTGGATAGCTAAAC
CCTTCTGTTAGGGGGTGATGGCCACATTACCTACCCTTGATCTTA
CTAGCCTTGTGTGTCTCTGAAATAAATCATTTCCAGTTAAAAAAAA
AACCTTTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTT
TAGCTTGGCACTGGCCGTCCGTTTTACAACGTCGTGACTGGGAA
AACCCTGGGCGTTACCCNACTTATCGCCTTGCAGCACATCCCCC
TTTNCGCCACTGCCGTAATAAC
115
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGGATCCCGGCAGCA
GCTGCGGCGGCTCTGTTCTTCTGTAGCTCTTTTCTGTCTCCCTTT
CGTTTCCGGAAACATGGCCTCTGGTGTGGCTGTCTCTGATGGAG
TCATCAAGGTGTTCAATGACATGAAAGTTCGCAAGTCTTCAACGC
CAGAAGAAGTGAAGAAACGCAAGAAGGCAGTGCTCTTTTGCCTG
AGTGAGGACAAGAAGAACATCCCTCCCACCCCCTGGACCGTCCT
TTTCCCTCCATCCCTGACGGTTCTGGCCTTCCCAAACTGCTTTTG
Cofilin NM 007687ATCTTCTGATTCCTCTTGGGTTGAAGCAGACCAAGTCCCGTCCTASEO ID
N0:41
GGCACCCAGTTTGGGGGGAGCCTGTATTTTTTTTTTTTAACGACA
CCCCTACTCCTCATCTGTCCCATCCCATGCTGCCAACTTCTAACC
ACAATAGTGACTCTGTGCTTGTCTGGTTAGTTCTGTGTGTAAATG
AACTGTGGAAATGACCCTCCCCTGCACCAGCTGGGTGCCTCCCC
T-fTTCCTTGATCTTGGGCACTCATGGAAACAGGACCAGTAANGGA
CCTTCAATTAAAAAAAAAAAAAAAAAAAAAAAATTGCGGGCGCNA
AGCTTATTCCCTTTANNGANGGGTAAATTTAACTTGGCNCTGGGC
CN
TCTCTNCATGATTACGAATTTAATACGACTCACTATAGGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGACTGGCTAAAGCC
TAACTCTCAGTTGGCAGTTCAGGGAGTGAGCAGAGTTGTCGTTC
ATGAAAAGTATAACGGAGCCACCTACCAGAATGACATAGCTTTGG
TTGAAATGAAAAAACACCCGGGCAAGAAAGAATGTGAGCTCATCA
ATTCTGTCCCTGCCTGTGTCCCATGGTCTCCATATCTATTCCAAC
CGAATGACAGATGCATCATTTCTGGATGGGGTCGAGAAAAAGATA
Complement y1 gg65 ACCAAAAAGTCTACTCACTCANGTGGGGCGAAGTCNACCTAATA
factor I
SEO ID
(CFi) GGCAACTGCTCGAGGTTTTACCCGGGTCGCTACTATGAAAAAGANO:42
GATGCAGTGTGCGGGTACCAGTGATGGGTCCATTGATGCCTGCA
AAGGAGACTCTGGAGGCCCCTTGGTCTGCAAGGATGTCAACAAT
GTCACTTATGTTTGGGGCNTTGTGAGCTGGGGANAAAACTGTGG
GAAACCAGAGTTCCCAAGNGTTTACCCCAGANTGGCCAGCTNTT
TTGATTGGATTACCTACTACGNGGGAAGACCCCTTGTTTCTCAAA
TACAATGTCTGAAGGCTACCACCTCCTTCTTCTGCACTTCTTCTTT
CCAGGGTTNATACTTTAATTGAAATGAAATTNTNTAAATTAC
TGACATGATTACGAATNTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGCAGACTACAACCTGGAG
GAGGTCCTTCCAGAGCTGGGAATTAGGAAAATCTTCTCCCAGCA
AGCTGATCTGAGTAGGATCACAGGGACCAAGAACCTGCATGTCT
CTCAGGTGGTCCACAAAGCTGTGCTGGATGTGGATGAGACAGGC
ACAGAAGGAGCCGCTGCCACAGCAGTCACAGCAGCCCTAAAAAG
Contrapsin-like TTTACCGCAAACTATACCTCTTCTGAATTTCAACCGGCCATTCATG
protease inhibitorD00751 CTGGTTATCACTGACAATAATGGTCAGTCTGTCTTCTTTATGGGCSEO ID
N0:43
(CPi-21) AAAGTCACTAACCCCATGTGAGTCTGAAGCTCCCCAAAATCTGAC
AATTCTGCCCAGGATCCTGGAACAGAGCCTGGATGCTGATCTCT
GTATATGCCCTGACATACATGCTCTGATTGGCTATTGCAAAGTTG
GCTTAGACAGTGACATCAACTATCTCTATGGCTCCCATGTGCACT
GGAGCCTTTGGATTGTCAAGTGTCAGGCACTTANGACCCTTGGG
AGCATCTACACATGTTTCTGAACTTGGAATCTTTCTTTATTCTTCTT
NCCTGGTGACTCCTCTTTCTGTGTTCATACCCCAAACCAAG
CTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTAAAGAAGAAAGT
GAAAGATGTGGAGGAAAAGTCAAAAGAATTTGTGCAGAAAGTGG
AGGAGAAGAGCATCGACCTCATCCAGAAGTGGGAGGAGAAGTCC
CGAGAGTTCATTGGAAGTTTCCTGGAAATGTTTGGTCCAGAAGGA
GCGCTGAAGCACATGCTGAAAGAGGGAAAAGGTCGGATGCTGCA
GGCCATCAGTCCCAAGCAGAGTCCCAGCAGCAGCCCTACTCATG
CTP:phosphocholineM36071 AGCGCTCCCCCTCCCCCTCCT'1-1'CGGTGGCCCTTCTCTGGCAAGSEO
ID
N0:44
cytidylyltransferase ACTTCCCCATCTTCCTCCCCAGCAAGTCTCTCTAGGTGCAAGGCT
GTGACCTGTGACATCAGCGAGGATGAAGAGGACTAACTTTTCATC
CCTGTTCCCTCTCTCTCCCCCTGCCCGTCACCTCCAGAAGCTCTG
TCGAATTCCATTTTGTGATCCCAACACTAAACCTAAGGACATCTAC
AAAGAACAGACAAACGGGGCAAGAGGACCTGGGAACGGGGGAA
CCAAAACAGCCCATGCCCTGCCTGAGACATTCTCAGCCACACCA
CGGAGGCTGCCCACACCTTAGAAGACTGCTCTGCATTCATCTTTT
CTNCCCANAACGTTGCTTTTCTGGTTATTN
116
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGGCCGCAAGGGNTTTNGGGTANNCNNCCANTTCGGANAAAAG
ANAGGCGGTNTCCACACCCNCCCCGGGAGGAAGATGTCAAACG
TGAGAGTGTNTAACGGGAGCCCGAGCCTGGAGCGGATGGACGC
CAGACAAACCGAGCACCCCAAGCCTTCCGCCTGCAGAAACTTNT
TCGGCCCGGTCAATCATGAAGAACTAACCCGGGACTTGGAGAAG
CACTGCCGAGATATGGAAGAAGCGAGCCAGCGCAAGTGGAATTT
Cyclin-dependent CGACTTTCAGAATCATAAGCCCCTGGAGGGCAGATACGAGTGGC
kinase 4 inhibitor AGGAGGTGGAGAGGGGCAGCTTGCCCGAGTTCTACTACAGACC
P27kip1 (alternateD86924 CCCGCGCCCCCCCAAGAGCGCCTGCAAGGTGCCGGCGCAGGASEQ ID
N0:45
clone) GAGCTTGGATGTCAGCGGGAGCCGCCAGGCGGTGCCTTCAATT
GGGTCTCAGGCAAACTCTGAGGACCGGCATTTGGTGGACCAAAT
GCCTGACTCGTCAGACAGTCCGGCTGGGTTAGCGGAGCTGTGTC
CAGGGATGAGGAAGCGACCTGCGGCAGAAGGTGATGATTCTTTG
GAAAACTTAAAATGTCTGTCTGTCTCCGTAGCTCCTCTTTGCTAG
ACCCTGTTCGCTTGCCCTCGTGCCGAATTCTTGGCCTCGAGGGC
CAAATTCCCTATAGTGAGTCGTATTAAATNCGTAATCATGTTTNGA
GANNNNCNC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCGGAACCATGGCCA
GCCCGCTGCGCTCCTTGATGCTACTGCTGGCCGTCCTGGCCGTG
GCCTGGGCCGGAACCTCCAGGCCACCCCCGCGATTGTTGGGAG
CTCCGCAGGAGGCAGATGCCAGCGAGGAGGGCGTGCAGCGAG
CGTTGGACTTCGCCGTAAGCGAGTACAACAAGGGCAGCAACGAT
GCGTACCACAGCCGCGCCATACAGGTGGTGAGAGCTCGTAAGC
Cystatin C X16957 AGCTTGTGGCTGGAATAAACTATTATTTGGATGTGGAGATGGGCC
SEQID N0:46
GAACTACATGTACCAAGTCCCAGACAAATTTGACTAACTGTCCTT
TCCACGACCAGCCCCATCTGATGAGGAAGGCACTCTGCTCCTTC
CAGATCTACAGCGTGCCCTGGAAAGGCACACACACCCTGACAAA
ATCCAGCTGCAAAAATGCCTAAGAGCTGAGTCTCATAGGACCATG
CCAATGGTCCCTTACTTGTTCCCCTACCCTGTAGTGTTTTATCCCT
GAAAAGGGTGCTCCAGCTCTGGAGGGCATCTNCGGGGTGTTCC
CACCAGGAGACAGTAAAGAAACTGCTGCAGGCAGGTTCTGCACG
TCAGAACAGCTGTCCCCTGGTTCTCTTCTCCTTGCAGTAN
TNCTTCTCTATGACATGATTACGAATTTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTTAACTA
TTT'fTfCCCTCCACCTAGCCGGGGTGTCTTCTATCTTAGGAGCTA
TCAACTTTATCACCACTATCATTAATATAAAACCCCCTGCTATAAC
CCAATATCAGACACCTCTCTTTGTATGATCCGTACTAATTACAGCC
GTCCTACTACTTCTCTCACTGCCAGTATTAGCAGCAGGTATCACT
ATACTCCTTACAGACCGAAATCTAAATACTACTTTCTTCGACCCCG
Cytochrome S7g304 CTGGAGGTGGAGACCCAATTCTCTATCAACACCTATTCTGATTCT
c oxidase
SEQ ID N0:47
subunitl TCGGCCACCCAGAAGTGTACATCTTAATTCTTCCAGGGTTTGGAA
TTATTTCACATGTAGTTACCTATTACTCTGGAAAAAAAGAACCCTT
CGGATATATAGGTATGGTATGAGCCATAATATCTATTGGCTTCCT
AGGGTTTATTGTATGAGCACATCACATATTCACAGTAGGCCTAGA
TGTAGACACCCGAGCCTACTTTACATCTGCCACTATAATTATCGC
AATTCCTACAGGGCGTAAAAGTATTCAGCTGACTCGCTACACTAC
ATGGAGGGGAATATCAAATGATCCCCCGCCATATTATGAGCCTTA
NGGTTTAC
CTTCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGA
ATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTTAACTATTT
TTTCCCTCCACCTAGCCGGGGTGTCTTCTATCTTAGGAGCTATCA
ACTTTATCACCACTATCATTAATATAAAACCCCCTGCTATAACCCA
ATATCAGACACCTCTCTTTGTATGATCCGTACTAATTACAGCCGTC
CTACTACTTCTCTCACTGCCAGTATTAGCAGCAGGTATCACTATA
Cytochrome CTCCTTACAGACCGAAATCTAAATACTACTTTCTTCGACCCCGCT
c oxidase
subunit 1 S79304 GGAGGTGGAGACCCAATTCTCTATCAACACCTATTCTGATTCTTCSEQ ID
N0:48
(alternate
clone) GGCCACCCAGAAGTGTACATCTTAATTCTTCCAGGGTTTGGAATT
ATTTCACATGTAGTTACCTATTACTCTGGAAAAAAAGAACCCTTCG
GATATATAGGTATGGTATGAGCCATAATATCTATTGGCTTCCTAG
GGTTTATTGTATGAGCACATCACATATTCACAGTAGGCCTAGATG
TAGACACCCGAGCCTACTTTACATCTGCCACTATAATTATCGCAA
TTCCTACAGGGCG1'AAAAGTATTCAGCTGACTCGCTACACTACAT
GGAGGGGAATATCAAATGATCCCCCGCCATATTATGAGCCTTAN
GGTTTAC
117
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCCAAAGTTCATGAGG
AACTTGACCGTGTGATTGGACGCCACCAACCCCCCAGCATGAAG
GACAAGATGAAGCTGCCTTATACCGATGCTGTATTGCATGAGATT
CAAAGATACATGACTCTCCTTCCTTCCAGTCTGCCCCATGCTGTG
GTCCAGGACACAAAATTCAGAGACTATGTCATCCCCAAGGGTACT
ACTGTACTCCCGATGCTGTCTTCCGTCATGCTGGATCAAAAGGAG
Cytochrome X55446 TT~GCC'4ACCCAGAGAAGTTTGATCCAGGACACTTTCTGGATAAASEQ iD
P450 N0:49
2C23 AATGGCTGCTTCAAGAAGACAGACTACTTTGTTCCCTTCTCCCTT
GGAAAGCGGGCCTGTGTTGGTGAGAGTTTGGCCCGGATGGAGC
TCTTCCTGTTCTTCACCACCCTTCTGCAAAAGTTTTCCCTGAAGAC
TCTGGTGGAGCCCAAGGACCTTGACATCAAGCCTATTACTACCG
GGATTATCAATTTGCCGCCACCTTACAAGCTGTGCCTTGTTCCTA
GATAAGGGTTTATCCTTCTAATCATTCAAATCAAAGTAATTGGTTC
CTTTTTCTATAAATATTCTTTTTATGCTAAGCACTGNCTANGGCAG
AAACATCATGCATG
TNTATGAGATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGAGAGATTCATTAAC
TTTGTCCCGACCAACCTGCCCCATGCAGTGACCTGTGACATTAAA
TTCAGGAAGTACCTCATCCCGAAGGGAACAAAAGTGTTAACATCA
CTGACATCAGTGCTGCATGACAGCAAGGAGTTCCCCAACCCAGA
GATGTTTGACCCTGGCCACTTTCTAGATGAGAATGGAAACTTTAA
Cytochrome NM 017158G~GTGACTACTTTTTGCCTTTCTCAGGAGGAAAAGGAGCTTGgE0 iD
P450 N0:50
2C39 - TGTTGGAGAGGGCCTGGCCCGCATGCAGTTGTTTCTATTCTTGA
CAACCATTTTACAGAACTTTAACCTGAAATCTCTGGTTCACCCAAA
GGACATTGATACGATGCCAGTTCTGAATGGTTT1'GCCTCTGTGCC
ACCCACTTACCAGCTCTGCTTCATTCCTTCCTGAATAGATCAGGC
.
ATTTTGGGTTCTACTGTGTTGCCTTCTGCAATCCCCTTCAGGTTTT
TATCCAGTCCCTTCCCTCTATCATCCATCCTGACTCTTGTCTTAAG
ATCCAGAAAGCACATGCAGTTTCTGGAGTTATAGCACAAATCCAC
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT'1'G
GCGCTCGAGGCCAAGAATTCGGCACGAGGCTGGCCACTT'fCTAG
ATGAGAATGGAAACTTTAAGAAAAGTGACTACTTTTTGCCTTTCTC
AGCAGGAAAACGAGCTTGTGTGAGAGGGCCTGGCCCGCATGCA
GTTGTTTCTATTCTTGACAACCATTTTACAGAACTTTAACCTGAAA
Cytochrome TCTCTGGTTCACCCAAAGGACATTGATACGATGCCAGTTCTGAAT
P450
2C39 (alternateNM 017158GG~GCCTCTCTGCCACCCACTTACCAGCTCTGCTTCATTCCTgEQ ID
clone N0:51
- TCCTGAATAGATCAGGCATTTTGGCTTCTACTGTGTTGCCTTCTG
CAATCCCCTTCAGGTTTTTATCCAGTCCCTTCCCTCTATCATCCAT
CCTGACTCTTGTCT'~AAGATCCAGAAAGCACATGCAGTTTCTGGA
GTTATAGCACAAATCCACTTGTATTATCTCTTTCATATAAGAATTTA
TGATCCCTTGTGTCATTGTGTATCCATTCCTGAGTTAAAATAAAGC
TTCACTATAAAATAAT GTGT
GGCGGCCGCAAGCTTATTCCGTTTAGTGAGGGTTAATT
ATTATTTTATAGTGAAGCTTTAT
TTTAACTCAGGAATGGATACACAATGACACAAGGGATCATAAATT
GTTATATGAAAGAGATAATACAAGTGGATTTGTGCTATAACTCCA
GAAACTGCATGTGCI'TTCTGGATCTTAAGACAAGAGTCAGGATGG
Cytochrome ATGATAGAGGGAAGGGAGTGGATAAAAACGTGAAGGGGATTGCA
P450
2C39 (alternateAA818043 G'~GGCAP'CACAGTAGAAGCCAAAATGCCTGATCTATTCAGGAASEQ iD
clone N0:52
GGAATGAAGCAGAGCTGGTAAGTGGGTGGCAGAGAGGCAAAAC
CATTCAGAACTGGCATCGTATCAATGTCCTTTGGGTGAAGCAGAG
ATT'fCAGGTTAAAGTTCTGTAAAATGGTTGTCAAGAATAGAAACAA
CTGCATGCGGGCCAGGCCCTCTCACACAAGCTCGTTTTCCTGCT
GAGAAAGGCAAAAAGTAGTCACTTTTCTTAAAGTTTCCATTCTCAT
CTAGAAAGTGGCCAG
118
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTGATCGCGTC
CCTCCTCTTTGCCTGCCGCTTTGAATACAATGACCCACGCTTCAT
CAGGCTCCTGGACTTGCTGAAGGACACTCTTGAGGAGGAATCTG
GATTCCTGCCCATGCTCCTGAATGTGTTCCCGATGCTCCTACACA
TCCCAGGGCTTCTTGGCAAGGTATTCTCTGGAAAGAAGGCCTTC
GTTGCCATGCTGGACGAGCTGCTAACTGAACACAAGGTGACCTG
Cytochrome U48220 GGACCTGCGCAGCCACCCCGAGATCTGACTGATGCCTTCCTGGC
P450
SEO ID N0:53
2D18 TGAGGTGGAGAAGGCCAAGGGGAATCCTGAGAGCAGCTTCAATG
ATGAGAACCTGCGTGTGGTGGTGGCTGACCTGTTCATGGCGGG
GATGGTGACCACCTCCACCACACTGACCTGGGCCCTGCTGTTCA
TGATCCTGCATCCAGATGTGCAGTGCCGAGTACAACAGGAAATC
GATGAGGTCATAGGGCAGGTGCGGCGTCCAGAGATGGCAGACC
AGGCACGAATGCCGTTCACCAATGCTGTCATCCATGANGTGCAC
GCTTTGCAGACATTCTCCCTCTTGGTGTGCCTCACAAAAACTTCT
CGTGGCATTTGAATGCANGGCTTTCTTTATCCTAANGGG
AATTTGGGNCNCCAGGGGTTTTNCNNNNCCCCCNGTTTAAAAAC
CGCCCCNNNNNAAAAAATAANNCCCCCCCCCAAAAANNAAAAAG
CNGGGGGCCCCCCCAAA GACATNC
ACTACAAAAAACCTTTATTAGTGCTAAAACAGTGAAGTTTTTTCAC
ATATGAAAAATTGGAACTGGTTCACAAAGAATTGAAAAAAATGTAG
GCAGTTCAGAGGAGCATCCCTGCCATTCAGGAAGGACTGCAGTT
ACAGGTACACAGNACAGGAGGACCTGTTTGCTCACAAGTAGAAG
Cytochrome A1058887 CAGGGTCTCAGTCATCTGTGTGAAAGACTATGCCGCTTCAGACTSECT ID
P-4.50Md N0:54
GGAATGAAACAGAGCTCAAAGGGTGGGGGCACAGACAATAAACC
AGGTTGAACTGGGGTTGTGTCGATGTCCTCTGGATTGCAAGAGG
TTTTAAAGTAAAATGCTGTAAAATGCTGGTCAGGATTAAGAACATC
TCCATGCGGGCTAAACCTTCTCCAATACAGGCTCTTCTTCCTGCT
GAGAAAGCCATGAAGTAGTCACTCTTCTTGAAGTTGCCCCTCNGT
GCCGAATTCTANGGNCTCGAGGGCCAAATTCCCTATAGTGAGTC
GTATTANATTCGTAATCATGTCATACCCTGN
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCTCCCCGTGTTCCT
TTTCTGGAACCTCAACTGGCTCCCACTGCTCTCTCGGTGCAGTTA
CCGTTTGGCGATCCCTCTCCTGCTAACATGCCGTTCGTTGAGTTG
GAAACAAACTTGCCGGCTAGCCGCCTACCCGCAGGGCTGGAGA
ACCGGTTGTGTGCGGCCACAGCCACCATCCTGGACAAACCCGAA
GACCGCGTGAGCGTGACGATACGACCGGGCATGACCTTGTTGAT
D-dopachromeNM 024131G~'CAAATCCACAGAGCCCTGCGCCCACCTCCTGATCTCTTCCATSEO ID N0:55
tautomerase - CGGTGTTGTGGGCACCGCGGAGCAGAACCGCAGCCACAGCTCC
AGCTTCTTCAAGTTCCTCACCGAGGAGCTGTCCCTGGACCAGGA
CAGGATCATTATCCGATTCTTCCCCTTGGAGCCCTGGCAGATCG
GAAAGAAAGGAACTGTTATGACGTTTCTGTGATGGAGACAAGGAA
CGCAGGGCGTTTGCTTGAGCCTGTCCAGAGCCCTTCCAGAGAGG
CCTCCTGGCAGATACGATACCAGATCCCTCTTTTGCATAAGTGTC
TGTGATCTCACTGACCTGGTTTCCTCTCCCCCAGCCTCGTGGAAC
GAGGAGAGCAAATTAAAGAAGAGAGCC
ANNNCNTCTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTCGGAT
ACATCCGCATCTCAGACACCAACATAACTGCTATTCCTCAAGGTC
TGCCCACTTCTATCAGTGAACTGCATCTGGATGGCAACAAGATCG
CCAAAGTTGATGCAGCCAGCCTGAAAGGAATGTCTAATTTGTCTA
AGCTGGGTTTGAGCTTCAATAGCATCACCGTTGTGGAAAATGGCA
GTCTGGCTAATGTTCCTCATCTGAGGGAGCTCCACTTGGACAACA
Decorin X59859 ACAAACTCCTCAGAGTGCCTGCTGGGCTGGCACAGCATAAATATSEO ID N0:56
GTCCAGGTCGTCTACCTTCATAACAACAACATCTCCGAAGTTGGG
CAGCATGACTTCTGCCTCCCTTCATACCAGACTAGGAAGACTTCC
TACACTGCCGTGAGTCTTTATAGCAACCCTGTCCGGTATTGGCAA
ATTCACCCACACACCTTCAGATGTGTCTTCGGGCGCTCTACCATT
CAACTTGGGAACTACAAGTAACTCCCAAACAGCCTCATTTTTATAA
TCGGGAACAAAAAAACCAATCTGTCAATATTATGCTAAAAAGAAAA
AAAATATTTTGAAAAAGAAAGAATGCTAGATTCTGGGAAATTCAAG
TATAGCGCGGATGCCTT
119
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATCACATGATTACGAATCTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAAGTGGAACTTGACTGCT
TCCCTCTTCTGAGCTTGCTCCCGCGCTTTCAGCATCCAGGTCACC
TCGCCAGTATGTCTCAGGGTGATTTTGACAAAGCCGCTGAGGAG
GTGAAGCGCCTCAAGACTCAGCCAACTGATGAAGAGATGCTGTT
CATCTACAGCCACTTCAAACAAGCTACTGTGGGCGATGTAAACAC
AGATCGGCCGGGGCTGTTGGACCTCAAGGGCAAAGCCAAGTGG
Diazepam bindingM14201 GACTCGTGGAACAAGCTGAAAGGAACTTCCAAGGAAAATGCCAT
SEQ ID
inhibitor Gp~p~GACCTATGTGGAAAAGGTAGAAGAGGTAAAGAAGAAATATGN0:57
GAATATAAACGACCAGATTTGGTGGCCAGCCACATGTGTGACATA
ATACCTGTGAGGACATAATGCCTTGGTGTTTTTTTTT'ITfTCTAAT
GTAGATGACATGGCTCTGATATGTTAGGGCCAGAGTTAATTACTG
CTCCTCCTTCCTTTGGAGTTTTTACCTGAAATCAATTAAAAGTACA
TTTGTTACTCT CTTGCGGCCGGAAG
CTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGT
CGTTTTACAACGTCGTGACTGGGAAAA
TTCTNAGAACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGATGAT1TATTAC
AATCATCTCCTCAATAGACACACTATTTATTTTATTTCAATTAAAAA
TTTCTTCCCAAACCTTTCCTGCACCTCCCTCACCCAAAACTATAG
CCACAGAAAAAACGAATAACCCTTGAGAATCAAAATGAACGAAAA
TCTATTTGCCTCTi-fCATTACGCCCACAATAATAGGTCTACCAATT
Dimethyfarginine GTTGTGACCATTATTATGTTCCCATCAATTCTATTCCCATCATCAG
dimethylaminohydroiaNM 022297~CGCCTAATCAGCAACCGACTACACTCATTTCAACACTGACTAASEO
ID
N0:58
Se - TCAAACTTATCATCAAACAAATAATGTTAATCCACACACCAAAAGG
ACGAACCTGAGCCCTAATAATTGTATCCCTAATTATATTTATCGGC
TCAACCAACCTTCTAGGGGTTCTTCCCCATACATTTACCCCTACC
ACATCTCCTCTTACAAAGCAAACGTCACCTTACCTCACTGGAGGA
TAATGAATCCTAGTCATTAGAGAAAATGTTTTAGCTGATCTAAATT
TACAATGGATTCTTTTATTATCACGTATGCTGTAGAATGTAAGCGT
CTCCTCTCTGGACAATGTAAATGTAGAAAAAGTGCTAGATATCAG
AGATTTNCAT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTGGAGGCCAAGAATTCGGCACGAGGGAAGTACATGCTGTCT
GTGGATAATCTGAAGCTGCGTGATGTGGAGAAGGGCTTCATGTC
AAGCAAGCATATTTTTGCCCTCTTCAACACTGAGCAGAGGAATGT
CTACAAGGATTACCGGCAGCTGGAACTGGCCTGTGAGACACAGG
AGGAGGTGGACAGTTGGAAGGCTTCCTTTCTGAGGGCTGGCGTG
TACCCTGAGCGTGTTGGGGACAAGGAGAAAGCCAGTGAGACTGA
GGAGAACGGCTCTGACAGCTTCATGCACTCCATGGACAGCTGTT
Dynamin-1 X54531 CTGTGACTTGACAGTGGCTCCCCCGACCCCAAAGCGTCCTATTCSEQ ID
(D100) NO:59
ATCATCTGTGACTTAGTCTGTTGTAGTGGTGAGCTGATACATCCA
AATGTGATGTTGGTGAAAACTTGTGGCCCTCTGTGGTATTGCTCC
TGCGACATTCTATAAATATCTATAAATATACCTATATATACATATAT
ATACATATATATGGCTGACACAGCCTCGCCTGTAGTGTCAGAATC
AACCACCATGCTGTCCTTGTGGAGTCCTGTGGTCCAACTACAAN
GGAACGCTGTCATCCTGACATCCCCCCTCCAATGTGCCACCTCC
AGTGAGCCTCCCTGTCCCTTGGNCTGTGGACAGCCATCCCCTTG
GCCATCCCCAC
NNNNNNNNNNTTCTACATGATTACGANTTTAATACGACTCACTAT
AGGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCC
GCAATG ATTTTTTTTTTTACGGTCAA
ACACAATGATTTATTAAAAATAAAACGTAAAAATGATTTTTGTACAT
ATGCTTCCAAATTTCAGGCATGGGATCCAAGTAGGTTTCATAGAA
AACGCTGTAGCCAGGTATCAAGTCCTTAGAACAAAGTAAACTACG
CTCCCACCCAACCCCCACCCCGGTTTTGCTACAGAATCAGCAAG
TTCAGCCCCCCGCCCGCCNCCCCCCCAAAAAACACAAATTAAAA
eIF-4E X83399 CGACACATCTTGNTAGTNTAAAAACNACCNAGGTCCAAGTAATNASEQ ID
N0:60
TAAAAAAATAGAGTCCNTCAATGACTGTAACACNAAAATGTGTGT
GTGGGGCCGAGTCCACCTTCCGGGGGGACCGGGACGGGCAAG
CAANCGGGGGGTCCCCCCCCCGGGGGTGAGCGGCTCTNCCGG
GGGCACCTGGGGTGGGCNCGGAAGGCCAAGGAAGCCCCCCCTN
CCGCCCCCGCGGNTTGGCATTCGGNAACCCGGCTTTTNAAACNA
ACCTCCGNCNTTATCCGCCGNCCGCCNNCCGCCGNAACCGCCN
GTNGTACNGGNCCACNTGTTGCTTGCGGGGCNNCAACTTTATTN
CCTTTANTGANGGTNNATTTTTNCCN
120
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGTTCCTCTGCTAGGC
TCCGAGCTGTCTGTTTCTTGGGCCCTGTGTATAGGTGCCGGCCG
CCCCTGGCGTTCAACACCGCTTCCAGGTGCCGGCCGTGTCTGCC
ATGGACGACTATGCGGTTTTGTCCGATACTGAGCTGGGCGCAGT
GCTACGCCAGTAGAACATCCCGCATGGGCCTATTGTGGGCTCCA
CTCGCAAGCTCTACGAAAAGAAAATCTTCGAGTACGAGACCGAG
Emerin NM 012948AGAAGGAGGCTTTCGCCCCCCAGCTCGTCATCGTGTTCATTCTCSEQ ID
N0:61
- CTATCGGTTCTCAGACTTGGATTCAGCCTCCGTGGACTCAGACAT
GTATGATCTGCCCAAAAAGGAGGACGCCTTACTTTACCAGAGCAA
GGACTATAATGATGACTACTATGAGGAGAGCTATTTGACTACCAG
GACATACGGGGAGCCCGAGTCTGTGGGCATGTCCAAGAGCTTCC
GCCGGCCAGGGACCTCACTTGTAGATGCTGATGATACCTTCCAT
CACCAGGTGCGTGATGACATTTTCTCTTCTTCAGAAGAAGAANGC
AAGGATAGGGAACGCCCCATCTATGGNCGANACAGTGCCTTACA
GANCATCGCACACTACCGCCCATT
'fT'ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCACTGACAGAAGCA
CATGGGTGGAGGAAAGACCTCTGCGACTGGCTGATTGATCCCTG
CTGAAAGCCGAGGACCTTGTCCACAGACAGGAACAGTTCTCTTC
ATGAATGAAGGTCAGAGAGAAGTGGGTGCTGCCATGGTGGACAA
CACAATGTCATCTAGAATGGCTGAACCTCTACCCCCCCAGCACAT
Endogenous CAGCGCCACAGATGCCTTTGCCATCTCTTGGATGCCCTGATAAA
retrovirai
sequence, D90005 GCCAACAACTGTGAGTACTATTCATTGCCCAGGAAAACAGGAGGSEQ ID
5' and 3' N0:62
LTR GAAGAGATTCAGTGACATGGGGCAGTGACAAAACAAATAAAGTG
GCTCGGGAAATGGCTATAGAGGAGCCTATCCTGGTTACAGGCCT
GCAAGAGACAGCCACTGAGAACTAGGATTAAACTAAGGGGATGG
CCTCACTTAGAAAAGGCCCAAGTTGTTTTAAAAGATAAAAAGACN.
' ATGACACACTTGAGGGGAAGGGTATACTCCCCAGAAAACAAAGA
AAAAGACTCACTTTGCCAAATACAGAAATGGACTCATTTAGGAGA
TAAAAANTTTGTCCCAAGTAGTTARGGTATATGTRATANACTTTAA
AAATTTTANCCCAAGAGAGACAGTAAAAA
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGCAGCACTGTGTC
CCTAGCAATGAGCACCCTCCAAAGGTATCCAGGCCTAGAGGTTTT
ATCCGAGTCCCTAGGCCCAAGTGCGCCATGAGGACGGACACCC
GCTGAAGCTTTGCTGGTCATTGCAGCCTGGTCAGGACAGCCGCT
GGTTGCCGGTCCTGGTCGCCTGCAGGGTTGTGTTTATCCCGCTG
Equilbrative CTGATGCTCTGCAATGTGAAGCAGCACCACTACCTGCCCTCCCT
nitrobenzylthioinosine- CmAAGCATGATGTCTGGTTCATCACCTTCATGGCCGCCTTTGC
sensitive AF015304 CTTCTCCAATGGCTACCTCGGCAGCCTCTGGATGTGCTTCGGGCSEQ ID
nucleoside NO:63
transporter CCAAGAAAGTCAAACCGGCTGAGGCAGAGACTGCCGGAAACATC
ATGTCCTTCTTTCTGTGTCTGGGCCTGGCTCTGGGAGCTGTGTTG
TCCTTCTTGTTAAGGGCAC'(-fGTGTGAGCGACCCTGTGTGGACA
GAGGAACTACACTGCCTGCTTCCTGCTCACTTCCTTCGCTGTTAG
GGACGAGCAGGGGTCCAGAGGGCTGCTCTTCTGCTTTCCTCCG
GGCTGGGCCCAGATGTCCAGGAACAAAGGANGGACCTCTGAGG
ATGGACTTGGGATTGGGGGTCANANTGGTANGGGGACAATGGTC
TCTGA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTAAGGCCTGGAGGG
AACTGGGACACCAAAACCTATCTCATCCTCTCACTTACATCACTG
GGTTTGGCTCCTATCTGGAACGCACACCGGTCCCCATGGCATTG
TCTGGCACAGGTACGCTGGTGGCTTCTATTGCCTCCAAGGTGGC
ATCTTCAGTGGCCGTGGTCAAAGCCGGAGGGGCGGTATCCAGC
ACCATCCTAGCTAGCTCACAGGGGCTCAACTTTAGCCCAGACTG
ERG-2 AF154572 CACTGGGCTCTGGAGCTTCTGCACTTGGATCTGCATTGGGAGCASEQ ID
N0:64
CTGAAGGCTGGCACCGTTTTATCCAGCCTCCCTGCCTCCGCCTT
GGCTGTTTGCCCCATTGGAGTCAAGAC1'GCTGTCGCCATGCTTG
GGGGAGCCATGACAGTAGCTGCGGTTCCACCTGTGCTGAGTGC
CGTGGGCTTCACTGGGTCAGGCATTGCAGCCTCCTCTCTAGCAG
CCAAGCTGATGTCTGTGTCAGCCATTGCTAATGGGGGCGGAGTC
CCAGCTGGTGGCCTGGTGGCCACTCTGCAGTCTGCTGGANCTG
CTGGACTCTCCATGACATCTAANGTCCTCGTGGGCTCTACANGG
TCTGCCGTTGTGGCCAGTGTGATGGGT
121
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTACCCAGTCTCA
GGACAGCTGTTCACTCCAGGCCTCCGACTCTGAGCCCGTTGGTC
TTTGCCAAGGTTCACTGATTAAAAGTCCCGGGGTCCCTCCTCAAC
GCTTTAAAAAGACTGTCACTGTGTCGTGCGAGTTTTTCGAATCTC
AGGACCAGGTCCCTGGAGGTGAGAACCCTGCTGATACCCAAGAT
GCTAAGAAACTCCCTCAGAAAAACACAGCCCCTACCAGCTCACC
Fefuin beta NM 053348CTCCATAACTGCACCAAGAGGATCTATCCAACACCTCCCTGAGCASEQ ID
(Fetub) ** N0:65
GGAGGAGCCTGAAGACTCCAAGGGAAAGAGTCCTGAGGAACCC
TTTCCTGTGCAGCTGGATCTAACCAGAAACCCACAGGGTGACAC
ACTGGATGTCTCCTTCCTCTACCTGGAGCCTGAGGAAAAGAAACT
GGTGGTCCTGCCTTTCCCTGGGAAGGAACAGCGCTCCCCTGAGT
GCCCGGGGCCCGAAAAGCAAAGAACCCCCTGATGCTCCCCGCT
GAGACTCACTAGCAGGGTTCCACGGGGTACGGTCCCCTGCAGTA
GATGGGAGGTGGTGGGCATTGGGAANGCACAGACAATCAAATGT
AGACCGGCTAATAAAGTGTGT
GAGTTTATAAAAAAAGAATAAAAGTGTTGGAGTCAACATAGCTAAA
AGTTTACACTTGAGACTTATTGTGGACTTCATGGCTTATCCTTGCT
GTATCCATTTTGCTATGAATCAGCAGGAACATTATGGGTTGGCTT
TAATACACCATTACTATGTAGATTGAAAATAATTTCCCTGCTTCCA
GAATTATCTATTGAAATAATAAGAGAAGGGTGCCAAAACTTCACTC
Four repeat TAAACCCCATTGGGAATACCACAACATAATTATATTTTCCCCACAC
ion
channel AF078779 CAATGCTCCAGGTTCTCTGGGAAAAGTGGAAATATAAAATTATTGSEQ ID
N0:66
GAAAGCATTGATGGGCCCTGGCTGGGCAGAGTCTCCCCTGAGTT
GTCATTATCAATTGCATATTTGATGATCAGATTATTTTAAGAGATT
GAGTGTGTAAAAATTCCCTGATGCCTAGGTTGCTTTATGATATCC
TTTTGTCTATTTAACCTTCTTCAAATAGCCAAACATTGTGTCCTTC
CTACACAGAAGATGTGATATAATGTGCCCATCTACTGCTTTTATGA
TTACTTGTGACTATT
CTTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGATTTGCCCTGG
CAAATGTACACACCTCATGCTAGCCTGATGAAACTGGAATAAGCC
TTTGAAAAGAAATTTGTCCTTGAAGCTTGTATCTGATATCAGCACT
GGATCGTAGAACTTGTTGCTGATTTTTGACCTTGTATTCAAGTTAA
CTGTTCCCTTGGTATTAACCAACAGCAGACTTCCAGGATTTCCCG
AGGCTGGCAAGGGTTCCTGAACTAGTTACCACTTCTTTTCTTGCC
Gamma-actin, X52815 AGTCTAACAGGGTGGGAAAGTCCGAGCCTTAGGACCCAGTTTCTSEQ iD
N0:67
cytoplasmic GTTCTGGTTTTTTCCCTCCTGACCTCCATGGGTTGTTACTTGCCTT
GAGTTGGGAACGTTTGCATCGACACCTGTAAATGTATTCATCCTT
TTAATTTATGTAAGGTTTTTGTACTCAATTCTTTAAGAAATGACAAA
TTTTGGTTTTCTACTGTTCAGTGAGAACATTAGGCCCCAGCAACA
CGTCATTGTGTAAAGAGAAATAAAAGTGCTGCAGTAACNNCNTAA
AAANNCCANCNNNAACNNANAAACCNATTGCGGCCGCAAGCTTA
TTCCCTTTAGNGANGGGTTAATTTTAGCTTTGGCNCTGGCCGCCG
TTTTTACAACGTCNGNGACTGGNNAAAN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCAAGAATTCGGCACGAGGAGCAGTTGCAACCAGGT
GTGGCAGTGCCAGGGAGGTGTGAATGAGGCAGGATGAACTGGA
CAGGTCTATACACCTTGCTCAGTGGCGTGAATCGGCATTCTACAG
CCATTGGCCGAGTATGGCTGTCCGTCATCTTTATCTTCAGAATCA
TGGTGCTGGTGGTGGCTGCAGAGAGCGTGTGGGGTGATGAGAA
GTCTTCTTTCATCTGTAACACCCTCCAGCCGGGCTGTAACAGCGT
Gap junction CTGCTATGACCATTTTTTCCCCATCTCCCATGTGCGCCTGTGGTC
membrane channelNM 017251CCTGCAACTCATCTTGGTTTCCACCCCAGCTGTCCTCGTGGCAATSEQ ID
N0:68
protein beta ) GCACGTGGCTCACCAACAACACATAGAAAAGAAAATGCTACGGC
1 (Gjb1
TTGAGGGGCACGGGGACCCCCTTCACCTGGAGAGGTAAAGAGG
CACAAGGTGCACATCTCAGGGACACTGTGGTGGACCTATGTCAT
CAGTGTGGTGTTCCGGCTGCTGTTTGAGGCTGTCTTCATGTATGT
CTTCTATCTGCTCTACCCGGGCTATGCCATGGTGCGGCTGGTCA
AGTGTGAGGCCTTCCCCTGCCCCAACACGGTGGACTGCTTCGTG
TCCCGCCCCACTGAGAAAACCGTCTTCACTGTCTTTATGCTCGCC
GCCTC
122
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCTGAGTGGAGAAGA
AGCCACGATTCTCGCTAGACAGTGAAGCACAGTTGCTGCTATGT
CTGGGAAGCCAGTGCTTCACTACTTCAATGCCCGGGGCAGAATG
, GAGTGCATCCGGTGGCTCCTGGCTGCAGCAGGAGTGGAGTTTG
ATGAGAAGTTTATACAAAGTCCAGAAGACTTGGAAAAGCTAAAGA
Glutathione AAGACGGGAATTTGATGTTTGACCAAGTGCCCATGGTGGAGATT
S-
transferase NM 017013GACGGGATGAAGCTGGCACAGACCAGAGCCATTCTCAACTACATSEQ ID
alpha N0:69
subunit CGCCACCAAATATGACCTCTATGGGAAGGACATGAAGGAGAGAG
CCCTGATTGACATGTACACCGAAGGCATTTTAGATCTGACTGAAA
TGATTATGCAATTGGTAATATGTCCCCCAGACCAAAAAGAAGCCA
AGACCGCCTTGGCAAAAGACAGGACCAAAAACCGGTACTTGCCT
GCCTTTGAAAAGGTGTTGAAGAGCCATGGCCAAGACTACCTTGTA
GGTAACAGGCTGACCCGGGTAGACATCCACCTGCTGGAACTTCT
CCTCTATGTTGAAG
GCGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTGCCAGAGCTGGAAGGAGGA
GGTGGTTACCATAGATGTCTGGCTTCAAGGCTCGCTCAAGTCCA
CTTGTCTGTATGGGCAGCTCCCCAAGTTTGAAGATGGAGACCTC
ACCCTTTACCAATCTAATGCCATCTTGAGGCACCTGGGTCGCTCT
TTAGGGCTTTATGGGAAAGACCAGAAGGAGGCTGCCTTGGTGGA
TATGGTGAATGATGGGGTGGAGGACCTTCGATGCAAATATGGTA
Glutathione X02904 CCCTCATCTACACTAACTATGAGAATGGTAAGGATGACTATGTGA
S-
SEQ ID
transferase AGGCCCTGCCTGGGCATCTGAAACCTTTTGAGACCCTGCTGTCCN0:70
P1
CAGAACCAGGGAGGCAAAGCTTTCATTGTGGGTAACCAGATTTC
CTTTGCAGATTACAACTTGCTGGACCTGCTGCTGGTCCACCAAGT
CCTGGCCCCTGGCTGCCTGGACAACTTCCCCCTGCTCTCTGCCT
ATGTGGCTCGCCTCAGAAGGGCGAATTCCAGCACACTGGCGGC
CGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGC
TTGAGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGT
CATAGCTGTTTCCTGTGTGAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCAGCCTTTGACAAGTG
GGTCATTGAAGAAGCCAACTGGTTGACTCTGGACAAAGATGTGC
CAGCAGGAGATGGCTTTGACGCTGTCATCTGCCTTGGGAACAGT
TTTGCTCACCTGCCGGACAGCAAAGGTGACCAGAGTGAGCACCG
GCTGGCGCTAAAGAACATCGCAAGCATGGTGCGGCCCGGGGGC
CTGCTGGTCATCGACCACCGCAACTACGACTACATCCTCAGCAC
Glycine NM 017084GGGCTGTGCACCCCCAGGGAAGAACATCTACTATAAGAGTGACCSEQ ID
NO:71
methyltransferase- TGACCAAGGACATTACGACGTCAGTGCTGACAGTAAACAACAAA
GCTCACATGGTAACCCTGGACTACACAGTGCAGGTGCCAGGTGC
TGGCAGAGATGGCGCTCCTGGCTTCAGTAAGTTTCGGCTCTCTT
ACTACCCACACTGTTTGGCGTCTTTCACGGAGTTGGTCCAAGAAG
CCTTTGGGGGCAGGTGCCAGCACAGCGTCCTGGGTGACTTCAA
GCCTTACAGGCCCGGCCAGGCCTACGTTCCCTGCTACTTCATCC
ACGTGCTCAAGAANACAGGCTGANCCTGGCTNCNGCTTCCACCC
TAANAACATCCCTACCACAGATATTGCAGANAT
TTNTGACATGATTCGAATNNAANACCGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGACCCGCTACCTGG
GTGACCTCTCAGGGGGTCAGGTCCTGAAGAAGATTGCGCAGAAG
GCCATGGCCTTGCCAAGCTCTGGGGAAGGCCTGGCTTTTTTCAC
CTTCCCGAGCATCGACAACCCCACCAAGTTCAAACAGCTCTATCG
TGCTCGCATGAACACTCTGGAGATGACCCCCGAGGTCAAGCACA
GGGTGACAGAAGAGGCTAAGACCGCCTTCCTGCTGAACATTGAG
Heme oxygenaseNM 012580CTGTTTGAGGAGCTGCAGGGACTGCTGACAGAGGAACACAAAGASEQ ID
N0:72
CCAGAGTCCCTCTGCAGAGACGCCCCGAGGAAAATCCCAGATCA
GCACTAGTTCATCCCAGACACCGCTCCTGCGATGGGTCCTCACA
CTCAGTTTCCTGTTGGCGACCGTGGCAGTGGGAATTTATGCCAT
GTAAATGCAGTGTTGGCCCCCAGAGGCTGTGAACTCTGTCTCAT
GTAGCCTTCTCTCTGCAGGGGAGAATCTTGCCTGGCTCTCTTTTC
TTGGGCCTCTAAGAAAGCTTTTGGGGTTCCTCGCCCCCTTCCTGT
GTCNTTCCTTTNCTCTCTTGGAATGGGAAGGAGATGCCTGGCAC
ATTTCT
123
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GNNNCTATNTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAAT'i~t'GGCCCTCGAGGGCAAGAATTCGGCACGAGGCAGGAA
GCAATCATGGTGCTCTCTGCAGCTGACAAAACCAACATCAAGAAC
TGCTGGGGGAAGATTGGTGGCCATGGTGGTGAATATGGCGAGG
AGGCCCTACAGAGGATGTTCGCTGCCTTCCCCACCACCAAGACC
TACTTCTCTCACATTGATGTAAGCCCCGGCTCTGCCCAGGTCAAG
Hemoglobin GCTCACGGCAAGAAGGTTGCTGATGCCCTGGCCAAAGCTGCAGA
alpha 1
chain NM 013b9&CCACGTCGRAGACCTGCCTGGTGCCCTGTCCACTCTGAGCGACCSEQ ID
N0:73
TGCATGCCCACAAACTGCGTGTGGATCCTGTCAACTTCAAG1?CC
TGAGCCACTGCCTGCTGGTGACCTTGGCTTGCCACCACCCTGGG
GA'l'TT'CAGACGTGCCATGCACGCCTCTCTGGACAAATTCCTTGCG
TCTGTGAGCACCGTGCTGACCTCCAAGTACCGTTAAGCCACCTC
CTGTCGGGCTTGCCTTCTGACCAGGCCCTTCTTCCGTCCCCTGA
ACCAGTCTTTGAATAAAGCAGAAGTAGGAAAGAAAP,AAAAAAAAA
TCTCGCG
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCRAGRATTCGGCACGAGGGACTCAGGRAGCAA
TCATGGTGCTCTCTGCAGATGACAAAACCAACATCAAGAACTGCT
GGGGGAAGATTGGTGGCCATGGTGGTGAATATGGCGAGGAGGC
CCTACAGAGGATGTTCGCTGCCTTGCCCACCACCAAGACCTACTT
CTCTCACATTGATGTAAGCCCCGGCTCTGCCCAGGTCAAGGCTC
Hemoglobin ACGGCAAGAAGGTTGCTGATGCCTTGGCCAAAGCTGCAGACCAC
alpha 1
chain (alternateNM 013096GTCGAAGACCTGCGTGGTGCCCTGTCCACTCTGAGCGACCTGCASEO ID
clone) N0:74
T GCCCACAAACTGCGTGTGGATCCTGTCAACTTCAAGTTCCTGAG
CCACTGCCTGCTGGTGACCTTGGCTTGCCACCACCCTGGAGATT
TCACACCCGGGA'f'GCAGGCGTCTCTGGACAAATTCCTTGCCTCTG
TCyAGCACTGTGCTGACCTCCAAGTACCGTTAAGCCGCCTCCTGC
CGGGCTTGCCTTCTGACCAGGCCCTTCTTCCCTCCCTTGCACCTA
TACCTCTTGGTCTTTGAATAAAGCGTGAGTAGGAAGCAAAAAAAA
AAAAAAAAAAAAA
NTRTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GGGCTCGAGGCCAAGAATTCGGGACGAGGGGCCATGGTRRACTA
AGAAATGGAACTGCTCATGGGAATAGCACCCATCCTATGCATTCG
CGTTGTAACGCAGATCCTGGCCTGTCTCSCACTGCTGTCTGACCA
TCGAGGTGCCACCTATGCCTTGAGTGGCTCGCACTACTGGCGTC
TGGACTCCAGCCGTGATGGGTGGCATAGCTGGCCCATTGCTCAT
Hemopexin CACTGGCCCCAGGGTCCTTCAGCAGTAGATGCTGCCTTTTCCTG
(alternate
clone) M62642 GGATGAGAAAGTCTATCTGATCCAGGGCACTCAAGTATATGTCTTSEQ ID
N0:75
CCTGACGAAGGGGGGCAATAACCTAGTAAGTGGTTATCCAAAGC
GGCTGGAGAAGGAACTTGGGAGCCCTCCCGGGATCAGCCTTGA
TACCATAGATGCAGCCTTTTCCTGCCCTGGTTCTTCCAAGCTCTA
CGTCACATCAGGACGGCGGCTTTGGTGGCTGGACCTGAAGTCAG
GAGCCCAGGCGACATGGGCAGAGCTTTCCTGGCCCCATGAGRA
AGTTGATGGTGCCCTGTGTTTGGAAAAGTCCCTTGGTCCCTACTC
ATGCTCTTCCA
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTCTGCAGCCTTGGG
ATGGGGCAGAGCCGTAGTCTGTCTCGTCTGTTGCCGGAGATAGG
CTACGGCTCTGCAGCCTTGGCATGGGGCAGAAAGCAAGACTGAT
GACAGTGCGCTGCTGATGCTGAAGCGAAGGAAGCGAGACACCA
ACTTCCCCATATGCCTCTTCTGCTGTAAATGCTGTAAGAATTCCTC
CTGTGGTCTCTGTTGCATAACATAGAGAGCCAAGAGCCTTGTCCT
Hepcidin antimicrobial GACCTCTCAACACACTGCCTCCCCTCCCyCCCCATTATTTATTCCT
pepfide (Ramp)NM_053469GTCCTACCCCAGCAATGACCTTGAAATAAAAATGATGATTTTATTTSEQ ID
N0:76
TCAAAAAACCCAANATNAANTAAACRARAATAAAAAGTGTGGCGG
CCGCAAGCTTATTCCCTTTANTGAGGGNTAATTTTACTTGGNACT
GGGCGGCGTTTTACAACGTCGTGACTGGGAAAACCTGGNGTTAC
CCAACTTAATCGCCTTGNAGNACATNCCCCTTTCNCCANCTGGN
GTAATAACGAAAAAGGCCGCACCGATTGCCCTTCCAACAGTTGC
NCANCCTGAATGGNGAATGGGAACCNCCCTGTNCGGCGCATTAA
AACGCGNCGGGNGNGGGGGGTACCCNCACGGNGACCGCTACA
CTTGNCAGAGGCCCTAACGCCCGCTCCTTTNCTTTTTTT
GCGAAGGAAGCGAGACACCAACTTCCCCATATGCCTCTTCTGCT
Hepcidin antimicrobial GTAAATGCTGTAAGAATTCCTCCTATGGTCTCTGTTGCATAACATA
peptide (Hamp)NM 053469GAGAGCCAAGAGCCTTGTCCTGACCTCTCAACACACTGCCTCCCSEQ ID
NO:77
(alternate CTCCGCCCCATTATTTATTCCTGTCCTACCCCAGCAATGACCTTG
clone)
AAATAAAAATGATGATTTTATTTTC
124
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGCGTGATCACCAGC
CCCCAGCGCTGCAGCCCCCGCCCAGGATGATCCCAGCGGTGAT
CTTGTTCTTGCTCCT-t'TTGGTGGAAGAAGCAGCTGCCCTAGGAGA
GCCGCAGCTCTGCTATATCCTGGATGCCATCCTGTTTTTGTATGG
TATTGTCCTTACCCTGCTCTACTGTCGACTCAAGATCCAGGTCCG
High affinity AAAGGCAGACATAGCCAGCCGTGAGAAATCAGATGCTGTCTACA
IgE
receptor gammaL04306 CGGGCCTGAACACCCGGAACCAGGAGACATATGAGACTCTGAAASEQ ID
chain N0:78
(FcERlgamma) CATGAGAAACCACCCCAATAGCTTTACAACACGTGTTCTCAGCTG
CATTCCTTTTCCGCTTTTAATTCTCTCCTCGCCCTCATGATTGACG
TGGCTGTGCTACCTCCGTGCTTCTGGAACTAGCTGACCTTATTCC
CAGAACCATGCTAGGCTCTAAATCAATGTCCCCATATCCACCAAA
GACTTACTCACTGACATTTCTCTTCTCCCATCCTCCTTTGCTTCAT
TCCTCTTTCCTTCCCTGATCCTCTGTGCTCACTAAACAATGGGAA
GGGATTACCCCCCAATAAAGCTGCCAGAGATCACGCTCAAAAAA
AAAAACATTGC
CACCCTCATGGNCAGCATCCCCATGGACACCACCCCCATGGTCA
CCATCCTCATGGTGACCATCCCCATGGACACCACCCCCATGGAC
ATGATTTCCTTGACTATGGACCTTGTGACCCACCCTCCAATAGCC
AAGAACTCAAGGGTCAAGTATCATCGGGGACATGGTCCACCACA
CGGACACTCAAGGAAAAGAGGGCCAGGTAAAGGACTCTTTCCTT
Histidine-rich TNCACCAACGACAAATCGGATATGTCTACCGACTCCCTCCACTGA
glycoprotein AF194029 ATGTAGGTGAAGTTCTCACTCCTCCTGAAGCCAATTTGCCCATCTSEQ ID
N0:79
TCTCTTTGCAAATTGCAACAGACCCCCACAACCAGAGATTCNGCC
CTTCCCTCANACAGCCTNAAAGTCCTGTNCAGGGAAATTTGAGG
GTAAGTTTCCACAAGTTCCAACTTTTTTTGAACATACGCCTNCCAA
AATAAAACCTGATTTCTTGGTAGGGGAAAGAGTCAATATTCTGAA
TAAATAAAATATGACCAGTTAGAAATGANAAANGGGGGGGNGAN
ANNTAGGNGGGGNGGGGGGGGGGGGGNTTTTTTTTTTT
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGAACGAGGTAAAAATTAGAA
AAT1?AACCTACGTT'fTCACATAGTGTGATTAGCCAAAAGGAATTT
CACTTCAAGATCTAGAAATAGAATTCATAACATTTTTTCCTAAACTT
TGACTTTTAAAACAACGAAAATTACCACATGAGATGAACAAGAAAA
TTCATTAGAAAGTTCTCTGGGTGATTTTI'GGTGCTGAACTGACAT
HMG-CoA synthase, GAGCCTCATAGACTGTAAAACAGAGGTAGTTGAAACTAATGTACA
cytosolic NM 017268GAACTACATTTTTTAATTTTATTTGCATTTAATTCTGTGAAGTTTCASEO ID
N0:80
GTTATCTAAAATAAACACATAAACGTGTAATGTTTCAGATTGCAAG
GTGAGATGTAATGTAGCATTTGTAAGATATTCTTGTCAATATTAAC
TGGTAGGATTTTGATTTGTACAGTTTTAATTGGTTAAAATGATCTC
ATT'(-f'AACATCCACTGCTATAGATGAATGATGTAAGCTCAGAT'!TA
ATGAATGGTGGGGAAATGGTGCATGTAATTTT'f-fCGCAAGTATCG
AGAGTTCTGTATGTTTTGAAAAGAATAATTTAACGTTGGGTGCCA
GGAAGGGGGCTTTCCCAGAGTCCN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTGGCTTTCTGTTGATA
CCTTAGAGATGCAGCGGCTTTTGGCTCCAGCAAGGCGGGTCCTG
CAAGTGAAGAGAGTGATGCAGGAATCTTCGCTCTCACCCACTCA
CCTGCTCCCCGCAGCCCAGCAGAGGT1-fTCTACAATCCCTCCTG
CTCCCCTGGCCAAAACTGATACATGGCCAAAAGATGTGGGCATC
CTTGCCCTGGAGGTCTACTTTCCAGCCCAATATGTGGACCAAACT
HMG-CoA synthase,M33648 GACCTGGAGAAGTTCAACAATGTGGAAGCAGGGAAGTACACAGTSEQ ID
N0:81
mitochondrial GGGCTTGGGCCAGACCCGTATGGGCTTCTGTTCGGTCCAGGAG
GACATCAAGTCCTTGTGCCTCACAGGTTCTGCTGTGGACCAGAG
CCCCCCTGTGGAGAGGGAGAAAGAAAGGGGAGCCGCTGACCTG
CAGGGATACAGACCTTCCCCACAGCCTGGCAGCCGCCCGTTTGT
TGCAGCTTATTATCAGACTGTGGGCTATCATAGTTCATGCTCGTT
TCTTAAAGTTTCCCGAGAATTTCTAAAATTTT~TGTATCTAAACTTr'f
AATATGGCGATTAAAAGGAGAGAAGGAAAAAAAAAAAAAAAAAAA
AAACATTGCGGCCGCAAGCTTATTCCCTTTANGGA
125
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCAGGTTGCGAAACTGTTTGGAAGGGCGATCGGTGCGGCCNTNT
TCGCTTATTACGCCAGNTGGGCGAAAGGGGGAATGTGCTGCAAG
GCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTT
GTAAAACGACGGCCAGTGCCAAGCTAAAATTAACCCTCACTAAAG
GGAATAAGCTTGCGGCCGCGTGATGTGGCTGGGAAGGACAAGT
ACCAGGTCAACAACAAGCACGACAAGGAGTACACTCCGCTGCCT
CTGAACAAGATCATCCAGCGAGCTGAGGAGCTGGTGGGGCAGG
AGGTGCTGTACAGGCTGACCAGTGAGAACTGTGAGCACTTCGTG
H-rev107 NM 017060AACGAACTGCGTTATGGAGTCCCTCGGAGTGACCAGGTCAGAGASEQ ID
N0:82
TGCCGTCAAGGTGGCGACCGTCACTGGAGTGGGCTTGGCGGCC
TTGGGCCTCATTGGAGTCATGCTCTCAAGAAACAAGAAACAGAAG
CAGTGAGCTGAATGACTATCCAGCTTTAGGGCTCTTCTTTTGCTA
GAGGGTTGGAGTTTGATTTATAGATTCTACTGCTTTATAATTAGGT
ATATTTTCACAATATACAATAAACCACAAGAAGGGAATTTTCATGG
AAAAAAAAAACCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATT
CCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATAGANNNN
NNCNN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGAGCACTAACCAGG
AAAATGGCAGACGGCTTCTCGCTTAATGATGCCTTAGCTGGCTCC
GGAAACCCAAACCCTCAAGGATGGCCTGGTGCATGGGGGAACC
AGCCTGGGGCAGGAGGCTACCCAGGGGCCTCCTATCCTGGGGC
CTACCCAGGACAGGCTCCTCCAGGGGGTTATCCTGGACAGGCTC
CTCCTAGTGCCTATCCGGGCCCAACTGGCCCTAGTGCTTATCCT
IgE bindin NM 031832GGCCCAACTGCCCCTGGAGCTTATCCTGGCCCAACTGCCCCCG
rotein SEQID N0:83
gp
- GAGCCTTCCCAGGGCAACCTGGGGGACCTGGAGCCTACCCCAG
TGCTCCTGGGGCCTATCCTGCTACTGGCCCCTATGGTGCCCCGA
CTGGACCACTGACAGTGCCCTACGATATGCCCTTGCCTGGAGGA
GTCATGCCTCGCATGCTGATCACAATCATGGGCACAGTGAAGCC
CAACGCAAACAGTATCACTCTGAATTTCAAGAGAGGGAACGACAT
CGCCTTCCACTTTAACCCCCGCTTCAATGAGAACAACAGAAGAGT
CATCCGTGTGCAACACGAAGCAGGACAATTAACTGGGGAANGGA
AAAAAAGACAG
NCNNNCGACTCCCANNTCTTATATGACATGATTACGAATTTAATA
CGACTCACTATAGGGAATTTGGCGCTCGAGGCCAAGAATTCGGC
ACGAGGGAACTGACTATAGCTCATTTCTTCTCTCTCCCATTTTGT
GGGAGTGAGTTTCAAGTGATAATTACTAGAAACCTTTCAGTTITAC
CTTTTTTTCTTACAATATTGACTTGTTACCTGGGTGTGATTCAGGA
ACTCTCAGGCTCATCTGGTGAACACTATTTTGAATCTTAAGAGGC
AGTTTGAGATGGTATCAACTTATATACAAGGAATTCNGAAACTCG
Inositol polyphosphateAY014898 AGCTCTGGGCACACCAGCTGAGGAAAGTCTTTGCTCTACCGCTG
SEQ ID
multikinase -~~CA.t.TTCAGAAGCCAGCATCCTGCCCCTCCGACCACTANN0:84
(Ipmk)
GNTTTGTCTGAATAAAACAGGAAGTGATTCTTATCCCTGGTTCTC
AGGGAAGGGATTAGCATTCAGTTCTTCTTGTTTACATTTTTACTAA
CTGCTGCCCTCTTTGTGNTACTTTGTGCTCTTTGTTGACATGATCA
ACTCNTATTGTGATGNAAGCAACCTGNGGGCANGCGTTCAGGTC
TGCCCTGTCTTTTAAATGATACTGAGATTTNCCNCTTTGGGTNGA
AAGAGGCCATGTGTNCCTAGCCCNAAGCCNAATGTGGAACCACN
CCCGANAATTTAAAGAAAATAAANNCAAAATGNAGGCNGGTTN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT1'GG
CCCTCGAGGCCAAGAATTCGGCACGAGGGACCGGCAAAAGAAT
CCACGGACCTGGGCTGCCCCTATAAGGCCCAGTCCTGTTCAAGA
TGGTGAAATGGGCCCCTGCCGCAGACACTTGGATTCAGTACTGC
AGCAGCTCCAGACTGAGGTCTTCAGAGGCGGAGCAAATGGGCTC
TATGTGCGAAACTGTGACCTCAGAGGTTTCTACCGCAAGCAGCA
GTGTCGTTCCTCGCAGGGGAATCGCCGTGGTCCCTGCTGGTGTG
Insulin-like TGGATCCGATGGGCCAGCCTTTGCCAGTGTCTCCAGATGGCCAG
growth
factor bindingNM 013104GGAAGCTCTCAGTGCTCTGCCAGGAGCAGCGGGTGAAACCTGGSEQ ID
protein N0:85
6 TGGGAGCCTCGAGGACCCTGGCAGGAGCATGGGGCTGTCATTT
GAGCTCTATGTGAAGTGATGATAACTCTGTGCCCCGAGATGAGA
CCCACCTTCAAGCCCTACCCCATTGTCCCTGTCACCCCTGGGCC
TTTACACAGCAAGTTAGAAAGATTGTTGTTGGCTTGTGTACTAATA
AAGCTGCCTTGGGAGGGTCTCGG
CATTGCGGCCGCAAGCTTATTCCTTTAGTGAGGGTTAATT1'TAGC
TTGGCACTGGCGTCGTTTTACAACGTCGTGATGGGAAAACCCTG
GCGTTNCCAACTT
126
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAAT1-fAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATCCTATTCTCCAAAG
ACTATCAAGTGCTCGAAAACATTGTAAAATGAGTCTACTCCACTG
AAAAAGTTAATGCATCi'CTCCATTATAATCTATTfTCCTGCGGTTA
AAAAAAAATCCTTTTTTAAATACCCACACACACACACACACACACA
CACCTATTCACCCTAAGAGTTAGAAGAAATCATTTCCTTGAAAAAT
CCTATCTTTAAAAAAAAAAAAAAATCGACCCATGCCGCTTGAGAC
Insulin-like S43941 TCCTTCTCCTTCTTTGAATGTCAATGTAAAACGTGGTTATGTCTGT
growth
SEQ ID
factor I, AGATGAAACCGTCTCAGACGCCACGGCTCCAGGGTTTCTGTTACN0:86
exon 6
AGT1-fGTGCACTTGGGAGGATGCGCAGAAGACAGGACGCAGCGT
GTTTTGCTT'1'CCCCTTTACTGTTTGGCCAGCTACGCCAATGTGGT
GCTATTGTTTCTTTAAGAAAGTACTTGACTTAAAAAAAANNNGAAN
AANANNAANAAAAAACCTTTGCGGCCGCAAGCTTATTCCCTTTAG
TGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTC
GTGGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCC'I-T'GC
AGCACATCCCCCTTTCGCC
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCACAGGATCTAAAC
TGCTGACATCCAGGCTGAGAGGAAATAGGTTCCAGACATTGTCC
AGACTCGGGGATGGTCTCGTTGGATCTAGACAATACATGCCTCC
TCCTGGACTTCCTGGACCTCCTGGACTTCCTGGACCTCCTGGGC
CTCCCGGACATCCTCATTTTGCTTCTAGCATTGACTACGGCAGGC
AGCCTTCCTTGGGAAGGGTGCTAGACCTGCCATCCTTATCCTCA
Inter-alpha-inhibitorNM 019369C~GATCCAGCCGGCCCAAGTCTAGCCATGTTACCGAAAGTGGT
SEQ ID
H4 heavy chain- GGAACAAGAAGGCACCACACCAGAGGAATCCCCAAACCCAGACCN0:87
(Itih4)
ACCCCCGGGCTCCTACCATCATCCTGCCGCTTCCGGGATCTGGT
GTGGACCAGCTCTGTGTGGATATCTTACATTCTGAGAAGCCCATG
AAGCTGTTTGTAGACATCAATCAGGGGCTGGAGGTGGTTGGCAA
GTATGAGAAGAATATCGGGTTCTCATGGATCGAAGTGACCATCCT
GAAGCCTCACCTGCAGGTCCATGCAACGCCTGAACGACTGGTGG
TGACAANGGGGCCGAAAAAACTCTGAATACAAGTGGAAGAAGAC
CTGTTCTCTGNGGTTACTGGCTT
AACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGCC
CTCGAGGCCAAGAATTCGGCACGAGGGTGATGATGTAAACATGA
GAATTGCTGCTGGCGAATCTTTGGCACTTCTGTTTGAATTGGCCA
GAGGAATGGAGAGTGAACGGGATTTTCCAACAGAAACTGTTAAAT
TCGGTCCTGAGCGCATGi'ATA1-fGATAGCTGGGTCAAAAAGCACA
CCTATGACACGTTTAAAGAGGCTCTTGGATCAGGGATGCAGTAC
Interferon CACTTGCAGACAAATGAATTCCTTCGCAATGTATTTGAGCTGGGA
related
developmentalNM 019242CCCCCTGTGATGCTCGATGCTGCAACACTTAAAACCATGAAGATTSEO ID
N0:88
regulator CCTCGTTTTGAAAGGCATTTATATAACTCTGCAGCTTTCAAAGCTC.
IFRD1 (PC4)
GAACAAAAGCCCGAAGCAAATGCCGAGATAAGAGAGCAGATGTT
GGAGAATTCTTCTAGATGTCTGACTTTGATGTCTGTTTTCTAATTT
CTTCCTTTATTATTATTTTTGCTACTTCTAATGTATATAAGCTTTTA
GAGACTTTTTTTATCTTGGTCAACTTAGATAATT'f~fTGATGTANGG
ATGGGTTATATTTTAATTTAATGNACAGTGGTACAAATTAATGAGT
TCTTTATTCTGTAAAAATAACTGATNACCACAAATNAAAGTGGTTG
TGGATGC
CNNNCNNNNNNNNNNNTTATGACATGATTACGAATTTAATACGAC
TCACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGA
GGATCAATGTTTTCCATCAGTACTCTAGGAAGTATGGACATCCTG
ACACCCTGAACAAGGCGGAATTCAAAGAAATGGTGAATAAGGAC
TTGCCAAATTTTCTGAAGAGGGAGAAAAGAAATGAAAATCTCCTA
AGAGACATCATGGAGGACCTGGACACAAACCAGGACAATCAACT
GTCCTTTGAGGAGCGTATGATGCTGATGGGAAAGTTGATCTTTGC
Intracellular CTGTCATGAGAAGCTGCATGAGAACAACCCACGTGGGCATGACC
calcium-
binding proteinL18948 ACAGCCACGGCAAAGGCTGTGGGAAGTAATTAAGAGGTCAGCCASEQ ID
N0:89
(MRP14) TGTAACATCTGCCCAACCAAGTCTAAAGGGAATAGCTTACTAAAT
GACCTTGGTTCTGGGGCTGGGAAATAATTTAAAAATGAATAAATA
AAGTCTTTATCCATTTCNNAAAAACANNNAAAAAAAAAANANAACC
TTTGCGGNCGCAAGCTTATTCCCTTTAGNGAGGGTTAATTTTAGC
TTGGCACTGGNCGCCGTTTTACAACGTCGTGACTGGGAAAACCC
TGGNGTTANCCAACTTAATCGNCTTGNAGACATNCCCTTTCGCCA
GNTGGNGTAATANCGAANAGGNCCCANCGATCGCCCTTTNCAAN
AGT
127
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGAATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGCTGGTATAAAAGGGAAT
CACCATGCCCTCTACAGGGATGACTTCAGGAAAATGGTCACTACT
GAGTGCCCTCAGTTTGTGCAGAATAAAAATACCGAAAGCTTGTTC
AAAGAATTGGACGTCAATAGTGACAACGCAAT1'AACTTCGAAGAG
TTCCTTGTGTTGGTGATAAGGGTGGGCGTGGCACCTCATAAAGA
Intracellular CAGCCACAAGGAGTAACAGAGCTTCTGGCCTGGGGCTGGGCCC
calcium-
binding proteinL18891 TTGGATATGTCTACAGAATAAAGTCGTCATATCTTANGAAAAAAAASEDt ID
N0:9D
(MRPB) CATTGCGGCCGCAAGCTTATTCC
'
~
C
i
fTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTAC
AAGGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGC
CTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCNAAGA
GGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATG
GCGAATGGGACNCNCCCTGTAGCGGCGCATTAACGCGGCGGGG
TGTGGTGGTTACGCCAGCGTGACCGCTACACTTGCCNGCGCCCT
AAGCGCCCGCTCCTTTCCTTGGGGGGGGGNGGGTTG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGGAAGACCTTCCAG
GCCGTGATGAGGTTCGACACCGATGTGGAGCTCACTTACTTCCA
CAATGGAGGCATCCTGAACTACATGATCCGAAAGATGGCCCAGT
AGGTGCTGGCCTCTCAGGAGACCCGCGCTTGGTGCTAGAGCCAA
TGAGGTACCAGGCCTCCGCTGGTGGAGGCC1'GGCGAGCAGCCA
Iron-responsive CCTCTACTTCTCGTGAGGGTGCTAGCAAGATGAGCAAGTGGGCC
element-bindingNM 017321CTGCCATTCCTGGAGGCTCAGCGGCAGGAGTCTCTAGTTCGGTGSEO !D
N0:91
protein ATTTGTTAATCTTTTTATCCTTTTCTGTAATCCGGAATCTAGAATCA
TGGGAAGGTCCATAGTCCCAAAGAGAGCTACCTTCTCTTTAAAGT
CACTCATCACCGGTCATTGATTTTTTTCACTCTGACTAATCTTCAG
CAGAACTAGCCAGTATCTCAGAAGTGTCTCCTACCCTTTGTGTTA
CTCTGTCTGTCTGTGCTCAGTGACACCCTTCCCTGGAGAGCCCA
TTCCTCCGTGTATCACACCAATGGTAAGGACATAGCTTCAGACTC
TGTCACACTTCAATTCATAGTAATCGNGTGATCCCTTNCT'fCCAA
GTGAGCGAAAAACCTTGTGGCTAAGGGCG
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGATGGGTATGTGCGG
GATGAGACAGTGCGGGCTGCACCCTATGACTGGCGTCTGGCAC
CCCGCCAGCAGGATGAATACTACCAGAAGCTGGCAGGACTGGTA
GAGGAGATGTATGCTGCTTACGGGAAGCCTGTTTTCCTTATTGGA
CACAGCCTTGGCTGCCTACATGTGCTCCATTTCTTACTGCGTCAG
CCACAGTCCTGGAAGGACCACTTCATTGATGGCTTCATCTCTCTT
Lecithin:cholesterolNM D17024GGGGCCCCATGGGGCGGTTCCATCAAGCCCATGCGGATCCTGGgEQ ID
N0:92
acyltransferase- CCTCAGGTGACAACCAGGGCATCCCGATCATGTCCAACATAAAG
CTGAGAGAAGAACAGCGCATAACCACAACTTCCCCCTGGATGTTT
CCAGCTCACCACGTGTGGCCTGAAGACCACGTGTTCATTTCCAC
ACCAAACTTCAACTACACAGGCCAAGACTTCGAGCGTTTTTTTGC
AGATCTTCATTITGAAGAAGGCTGGCACATGi'TTCTACAGTCTCG
TGACCTACTAGCAGGCCTCCCAGCGCCTGGTGTAGAAATATATT
GTCTATACNGTGTAAGGCATGCCCACAGNCCACACCTACATCTAT
GACCACNACTTTCCTACAAAGACCCGGNGGCTGCACTC
TGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGGACCAATCTCACTTTCC
TGTGGGCAGAATCAGCACACACTGTTACAGTTCTGGCCATCAATT
CCATCGGTGGCTCCCTTGTGAATTTTAACCTTACGI-fCTCATGGC
CCATGAGTAAAGTGAATGCTGTGCAGTCACTCAGTGCTTATCCCC
TGAGCAGCAGCTGCGTCATCCTTTCCTGGACACTGTCACCTAATG
ATTATAGTCTGTTATATCTGGTTATTGAATGGAAGAACCTTRATGA
Leptin recepkorNM 012596TGATGATGGAATGAAGTGGCTTAGAATCCCTTCGAATGTTAACAAgEQ ID
(fatty) N0:93
GTATTATATCCATGATAATTTTATTCCTATCGAGAAATATCAGTTTA
GTCTTTACCCAGTATTTATGGAAGGAGTTGGAAAACCAAAGATAA
TT'AATGGTTTCACCAAAGATGATATCGCCAAACAGCAAAATGATG
CAGGGCTGTATGTCATTGTACCGATAATTATTTCCTCTTGTGTCCT
GCTGCTCGGRRCACTGTTAATTTCACACCAGAGAATGAAAAAGTT
GTTTTGGGACGATGTTCCAAACCCCAAGAATTGTTCCTGGGCACN
AGGACTTAATTTCCAAAAGTCACTTTTTTAAGTATTTACCCAAGAT
ATGTAAAGGGTGCAGT'1-fAGA
128
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCACAAGCACAATGGG
AACTGACCTCTCCTCCTGACCACAAAGAAAGGCTGGGCTCTGGG
CGGGTCCTCTCTGCCTTCGGCATCATTTCCCTTACATCCAGGCAA
GAAGTGGCCTCTCACTCAAATTCCTGTTAGCATTTCCATGGGTCA
CACATAAACTGCAATCCTCTCAGGAGAAGGGGGATCCCTGATAC
ATCATATCTATCCAGACTAAGGATGTGGTTCTTCCTAGATTCTATG
L-gu(ono-gamma-p12754 GCTCCACCAGGTATAGAGAGATTCCTGGGGCCTGCAGTTCTGCAgEQ ID
N0:94
lactone oxidase TCCCTCTTCAGAAGGGAGGGATCCCTTGGCGAGAGTTTGGCTCA
GAGGTGGCATGAAGCATGCTCTGCTCTCTCTTACCCTTGAAGGT
CCTTCGGATGCCCAGAGATGTCTGCTGGTCCTGGGCAAGCCATC
ATTCAAACGGGTCCAACCTGGCCTTCTGTCTGCCATGGCCTGAC
CCTCGCAGTGTCTCTTCCAGAGGTGTTTAGAGTGGAACTCGCTTC
AACCTCTTAACCAGTTGCTGATCCCTGTGTTTCTCTCCCTTCTCCT
TGGAGACTACTCTTGGAGGGGGATCCCACCATGTCCTTGGCTTT
CCCTGGGTATTGTTCTCCTC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCCTCGTGCCGCCT
CGTGCCCCAAGGAGAACTTCAGTTGCCTGACTCGATTGGACCAC
AACCGAGCAAAATCTCAAATTGCTCTTAAACTCGGTGTAACCGCT
GATGATGTAAAAAATGTCATTATCTGGGGAAATCATTCATCAACC
CAGTATCCAGATGTCAATCATGCCAAGGTGAAATTGCAAGGAAAA
Malate GAAGTTGGTGTGTATGAAGCCCTCAAAGACGACAGCTGGCTCAA
dehydrogenase,AF093773 GGGAGAGTTCATCACGACTGTGCAGCAGCGTGGTGCTGCTGTCAgEQ ID
N0:95
cytosolic TCAAGGCTCGGAAGCTGTCCAGTGCCATGTCTGCTGCGAAGGCC
ATCTCGGACCACATCAGAGACATCTGGTTTGGAACCCCGGAGGG
CGAGTTCGTGTCGATGGGCGTAATCTCTGATGGCAACTCCTATG
GTGTCCCTGATGACCTGCTCTACTCGTTCCCTGTCGTGATCAAGA
ATAAGACCTGGAAGTTTGTTGAAGGCCTCCCCATTAACGACTTCT
CCCGTGAGAAGATGGACCTGACAGCAAAGGACTGACCGAGGAAA
AGGAAACGGCTTTTGAGTTTCTCTCCTCCGCATGACTACACAGTC
GTGTTGACGTCAGCAAACAN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAAAGTCTTAAGGCCTG
AAGTACACTGAGCTGAATGAGCACCGGGCCTGAGAGTTTAGTTT
CTCCAAGTCCTTGGAAGGTATCCCCAGCGTAGGCCCTACGTCCT
CCAGACAAGATGCCCATAATGAGGCGGCCTCTGTTTTCACCAGT
GTCTCAGGAATACTTAATGGAGTGAAAAGAGGGAGTCTTGCCTTC
TGGGCCAGGCAGCCCGGATCTCCTCTGCCTCTGCCCACACCCA
Matrin F/G NM 022667GGAGAGCCAGAGGAGAAGCAGGTAGTTGGTTTCTTATCAGCTCCgEQ ID
N0:96
- AGCGGGGCTAAGGGAGCTGGCTGTGTCCACTTTTCATCTGGATT
CCGTCTAGCATGAAAGCCGTGCCCTCGAGGCTGTTTTGGAAACC
ACCATTTTGGGAAGTATCCCTCTCTATAAACTATGCCCCGGTATC
TGAGGAGGAATGAAGGGACCAACAAGGCTGGATCATCCAAAACT
GTTCACAGGAACCTGAGGCCTATCCTCCCGTCGGCATACGCTTC
TTTCTGCCTTTCACCCAACAGAGTCACAAGGAACCACCTTAGAAN
GGCCAGTCTNCCANCCTCACAGTGGAGACAAAGGCTTTTCCTTC
AAANACACNAATGGCGATCTCT
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTCTTAAGCTTCC
ACAGTAAGAATACCCCAACATGAACGCTGACCTCAAAAGAAAGCC
ACATTTCTGTGGCTGGGGTTTCTGGGATTTTTCCTTCAAGATCCT
GTCACAGGGCCAGGGAGATCGCTCAGTGGTAAAGCCCTAAGGG
TGTAAGCTTGAGAACCCAAGTTTGACCCCCAGAACCCAGGAAAAT
GTGGAAGGAGAGAACCAACTTCACAATATTTTCCTTTGGTTTCTAT
Melanoma-associatedNM 017125ACTCATGCCACAGTGCACCCTCTCTCCTAGATTGTGTGTACATGCgEQ
ID
N0:97
antigen ME491- AGAR.TTACCTTACAGACAACAAAACGGCCACCATTTTGGACAAAT
TGCAGAAGGAAAATAAATGCTGTGGAGCCTCTAACTACACAGACT
GGGAGCGCATCCCCGGTATGGCCAAGGACAGGGTCCCCCGATT
CTTGCTGCATCAACATCACTGTGGGGCTGTGGAAACGATTTCAAG
GAATCCACCATCCATACCCAGGGCTGCGTGGAAACTATAGCCGG
CATGGCTGANGAAGAACGTACTGCTGGTGGCTGGAGCAGCCCT
GGGCATTGCTTTTGTGGAGGTCCTGGGCATTATCTTCTCCTGCTG
TCTGGNGGAAGANTATCCCGGAGTGGCTACGAAGTAATGG
129
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTGCACTACCCTG
CAAGGCTGTGTTGCAGGGCCCGGAAGGCTCACTGTTCCGAAATG
GCCGAGCAGTCAGACAAGGATGTGAAGTACTACACTCTGGAGGA
GATTCAGAAGCACAAAGACAGCAAGAGCACCTGGGTGATCCTAC
ATCATAAGGTGTACGATCTGACCAAGi"f'~fCTCGAAGAGCATCC'fG
GTGGGGAAGAAGTCCTAAGAGAGCAAGCTGGGGGTGATGCTACT
Membrane boundNM 022245GAGAACTTTGAGGACGTCGGGCACTCTACGGATGCACGAGAACT
SEO ID
cytochrome - GTCCAAAACATACATCATCGGGGAGCTCCATCCAGATGACAGATNO:98
b5
CAAAGATAGCCAAGCCTTCGGAAACCCTTATCACTACTGTCGAGT
CTAATTCCAGTTGGTGGACCAACTGGGTGATCCCAGCCATCTCA
GCCCTGGTGGTAGCTCTGATGTATCGCCTCTACATGGCAGAAGA
TTAACCTGTCTGTCCGAAGCCAAGGAAGGAAAAGACTGCCCCAG
AGAGGGGAGAAAAGAAGCCAGTGTTAATCACTTCCACTGACAGA
AACCCTCCCCCTGAGAATGTAATTGTAATATATCTGTCTCCCTCTC
CTCCTATGCTAGGAGAACAAACATGGGA
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGATAAAAATGGCTGTC
CTCTGAGGCATTCTAGAGCTCACTTAAAAGGGGTGTTCAATTTGC
TGTCCTTGGTGCAGGTGTCCTGTCAAAGATTGGCAGGAGCGGTG
AGAACCCATACCCTCCCCTGAACCTCCTGGCCGACTTTGGTGGC
GGTGGCCTCATGTGCACATTGGGCATTTTGCTGGCTCTCTTCGAA
Methylacyl-CoA CGCACGCGGTCTGGCCTAGGGCAGGTCATTGATGCTAACATGGT
racemase alphaNM 012816GGAAGGAACGGCATACTTAAGTACTTTCCTGTGGAAAACTCAGGSEO ID
N0:99
CCATGGGTCTGTGGGCACAGCCTCGAGGGCAAAACCTGTTAGAT
GGCGGGGCACCTTTCTACACAACCTACAAGACCGCAGATGGGGA
GTTCATGGCTGTAGGTGCAATAGAACCCCAGTTCTACACACTGCT
GCTTAAAGGACTTGGACTTGAGTCTGAGGAACTCCCCAGCCAGA
TGAGCATAGAAGATTGGCCAGAAATGAAGAAGAAATTTGCAGATG
TGTTTGCAAGGAAGACTAAGGCAGAGTGGTGCCAGATCTTTGAC
GGGACAGA
CCAAGAGCGAGGGGCGGNNTTTCACCCCCATCCAGAGGAATGTA
TGGCTTGTGACGTGGGAACGGAACGGGAANCCTCCTCCGCGGG
TAATAAGGCAGGACGCTTACGACGGCCGCGATTACATCGCCNTG
AACGAAGACCTGAAGACGTGGACGGCGGCGGACTTTGCGGCAC
AGATCACCCGGAACAAGTGGGATCGGGCTGGTGTTGCAGAGAG
ACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGC
AGATACCTGGAGCACGGGAAGGAGACGCTGCTGCGCTTAGATCC
MNC class Xgg767 CCCAAAGGCACATGTGACCCTTCACCCCAGACCTGAAGGTGATG
! antigen
SEQ ID
RT1.A1(f) TCACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCNO: 100
alpha-chain
TCCCTGAGCTGGCAGTTGAATGGGGAGGACCTGACCCAGGACAT
GGAGCTTGTGGAGACCAGGCCTGCAGGGGATGGAACCTTCCAG
AAGTGGGCATCTGTGGTGGTGCCACTTGGGAAGGAGCAGAATTA
CACATGCCGTGTGGAGCATGAGGGGCTGCCTGAGCCGCTTACC
CAGAGATGGGAGCCTTCTCTATCCACCGACTCCAACATGGAAAC
CTATGTCATTTATGCCTCGTGCCGAATTCTTGGCCTCGAGGGCCA
AATTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATAGA
CGGGNTATGACATGATTACGAATTTAATACGACTCACTATAGGGA
ATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGGAAACCTG
CCCCCATCTTTCCGCATCAAATCCTGCAATTCTTCTGTCCCTACA
GAGCCAGAGCAGTTAGCACCCCCCCCCCCCCCGGGGNAANCNT
TGGCTTNGGAAAAAAAAAAANGGNACCNTTTTCAANCNTNNNANT
AANNTAAAAANTNNNCNNCCNNCCCNNGNTTANAANCCANATTTT
TTTNGGGNNAAAGGGNNCNTNNCNTTNANGGGGGGGGGNCCCA
MHC class X56596 N~CNTTNANGGGNNAAANNCCCCNTTTNNNTTTTNAAAAANNCSEO ID
II antigen NO:
RT1.B-1 beta-chain CCNTTTNTNNNTNANGGGGNCCNAAANNNTTNNNCCCANTTNNA101
AAANNCCNTANTTTTTGNNANNGGAAGGGNTTTTTTTTTCCNAGG
GAANGANGGGGGGCNTTTTCNANNNNTCCCNNCCCNTTTTAAAN
AGN7TNNTTTAAGGGNNGGANGGANGGCCNT-TTTTTNCCCCNNC
CCAAATNAANNNTTGCCAAAGTTTGAAAACCCNANTTNCCCNTTT
TCNTTTTTTTNTCNAAAGCCCTTTGANGGGACNTTTNNTTTCNTAA
CNTNGGGAAAAGGGAAAGGCTTGNANTTTTTTTTGGNNCAACCC
CTTTAAAAAAAATTNTTTTTGNTTTTGNAAAAAAAAAA
130
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTGATACGACTCACTATAGGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTCTCGACTATGA
GAAAGAGGCAATTAAGTGTCAAGTGTGCCCAGACAGCTGCGACC
AGTTGTGAAATACCCTAGCTTCTGATAACGGAATGAGTTACTTCTT
CCCAGGTCAGGAAGGTAGGTCCCTTTCCAGCACTCCCCACCCCA
TCTGAACAGGTTTGTCTCAGGGTTGGAAGGATGGCACTCCTTTAC
MHC class CCCCTCCCCAATAACATACTGCCAAAGCTCGAGAAGCCCAGCTT
II antigen
RT1 X56596 ACGCATATTCCTATATATGTCACAAGCCCCTTGATGTGAGCATTGSEQ 1D NO:
8-1 beta-chain 102
. AATTCCTAACCTGTGGAACAGGGAAGGCTTGTGATCTGATTTGGG
(alternate
clone)
TCAGACCCGTATAATAAAGATTCTCTTTGTTCTTGP,~~AAAAAAAAA
A TTGGAAGCGGCCGCAAGCTTATTCCCTTT
AGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACG
TCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTG
CAGCACATCCCCCTTTCCCAGCTGGCGTAATANCGAANANGNCC
GCACCCGATCGCCCTTCCCAACAGTTGCGCACCTGAATGGCGAA
TGGGACNCNCCCTGTANCCGGGGCATT
TATGACATGATTACGAATTNANTACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGACAGGGACAGATGG
GCTGTGCGCGCTGCGCGAGCTGAGCGTGGACCTTCGAGCAGAG
CGCTCAGTGCTCATCCCGGAGACCTACCAAGCCAACAACTGCCA
AGGCGCCTGTGCATGGCCACAGTCGGACCGTAACCGACGGTAC
GGGAACCACGTGGTGCTGCTGCTAAAAATGCAGGCACGCGGGG
CCGCCCTGGGTCGCCTGCCCTGCTGTGTGCCCACTGCCTACACC
Mullerian GGCAAGCTGCTCATCAGCCTGTCGGAGGAGCACATCAGCGCGC
inhibiting
substance S98336 ACCACGTGCCCAACATGGTGGCTACCGAATGCGGCTGCCGGTGSEQ ID NO:
103
ATGTCCGCCCTACCCCATCCCCCGTGTCCCCAGTCAGCGCCCCA
ATAAAGATTAGCAAGC CATTGCG
GCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCA
CTGGCCGTCGTTTTTACAACGTCGTGAGTGGGAAAACCTGGCGT
TACCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGGTGG
CGTAATANCGAAAAAGCGCCNCCCGATCGCCCTTCCCAACAGTT
GCNCACCCTGAATGGCAATGGGACCCCCCTGTAGCGGCGCANTT
AACCCGGCGGGGGTGGNG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCAGCATCTGAATGCCT
ACCGCCAGGAGGCTCACAACCGCATGTCCAGCCACATTCCATTG
ATCATCCAGTATTTGATCTTGAAGATGTTTGCTGAGAAGCTGCAG
AAGGGCATGCTCCAGCTCCTGCAGGACAAGGATTCGTGCAGCTG
GCTCCTGAAGGAAAAGAGTGACACCAGTGAGAAGAGGAGATTCC
TGAAGGAGCGGTTGGCAAGGCTGGCCCAAGCTGAGCGCAAGCT
Mx1 protein NM 017028AGCCAAATTCCCTGGTTAAGCTGGCCCTGTCCTTTCCTGTGTCTCSEQ ID NO:
104
CTGGATAATGATTCAGGGACAGAAGGGCTCCTGCCTTCCCTTCA
GCTAACCACTACCCTTTATCCTATTATAAATATTAGTTCTAAGATG
TGAAGGAGCTTTCTGTTCACTCTGAGATGATAAAGAGAAAGAGAT
TCTCAAAACTCAGCAATTAGATGAGTAGGAGAAGCCACTTTGCTG
ATAAGACAATAGCTTCAGTCTGAGTACCATTCCTATTCACCATATC
CTCATTTTAGAACCCTGCCAGGAACAAATATTTGCTGAACAAATG
.GGCCATGATGTTTGGGAGCTTCCTATAGCATTTGTTAATAAACTA
CNTTTCTATGGAAANNGGGGGGGGGGGNTT
GNAANGGGNATTAAATTTGGNAACCCAAGGTTTTTCCNACCCCCC
CNNTTTTAAANCCCNNCCNNGGCCNAAATNAAANTNANCCCCCN
AAAAANGNAAAANCNTTCNNCCCCCANTTI-T'TTTFTTTTTTTTTTTT
TTTTAAAAACTCACATTGATTTATTAGAATATGAAAAAAGGTTCAG
TTTCCTCTGTACAGGCGGCAGAGAGGCAGCGGCTGCGGTGGCT
TTGTACATGGTTGTCGATGTCACCTTGCATGGCAACTCCTGCCTA
NalH antiporterppgg8340 AAACAGCACTTGCATGGAGAGGAGACAGCTGGGCCAAGCACCCASEQ ID NO:
105
(APNH1) TAGCCCCATCCCCTGGGAGGGACCCCTCTGACTATTGCACGATC
CTGGGGAGGGAGTGCTCAGGGGTTGGACAGACACCCACGGGCT
GGCCCAGCCATGGCGGTAGGAGTACATGCCTGTGAGCAAAGGC
CGCTAGGGGTCCACTGCTGTCTACTCTACAGGATGCAGGTAAGA
GAGTGGTCTAGACGAGGGGTGGTGCCCTCGTGCCGAATTCTTGG
CCTCGAGGGCCAAATTCCCTATAGTGAGTCGTATTAAATTCGTAA
TCATGTCATANCGNNNC
131
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGACAGAGAGAGAGG
AGTCAGAGAGCTGTTAGTACCATGTCTACCCGTTACCATGGACC
GCAATGTGTAGTAAGGAAATGAAAGGTAAACAGTTATCTACAGTC
CTAGGAACCATGCCTGTCACCTAACCACCTACTGCCTTAGGCTAT
GGCCTGGTCTGTGCCCCTAAACACTACATTAGACAGTGACACCC
AGAGGTTCTCTTAGGAGGGTGTCTGGCAGTGACAGGCCAGCCCC
NADH-cytochromep00636 CACTTGCTGGCCAGGAGTTCCTTGGGTCAGCACGTGGACCCTTC
b5
SEQ ID
reductase CAAAACCCCACACACTGCCCCTCCCCTCCATGATGCCTTGAGCANO: 106
CCCTAAGTTGTCAGCCCAACAGAGTTTGGTAGACCTTGGGGTAC
CTGGCTTGTTTCTCCATCCCATACCTCCCTCCCATCTGGTTCCCA
GCCTGGGGGGTTCTGAGCAGAGCCTCTTTTCTCGGAGACAGACC
CGGTGCCTGGCGCTGCCTTCAGCAGACAGCAGACAGCCTCCTG
CACACTGGCTTTTTTTAGTCATTTATGGGCAAAATGAGTTAAAATA
AAACTTTGCAAATCCTGAANANNNANNNNNNNNNNNNNNNNNNN
NCNTTTGCGGCCGCAAGCTTATTCCC
TCTCNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAA
TTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGAAGGTTTTT
TTAATTGTATTTTACTGTGTAATAGCAGTCTAGGAATTGTGTTAGT
ATCTGTTCACAATTAACTGTCACTTTTTCTTf'GCTCTAATGTAAATG
ACCAAAATCAGAAATGCTCCAAGGGTGAACAATCACTACACTATG
NADP-dependent TTTCCCCGTAAAGGTGAAGGAGAGGCTCACCTCCCCTACTGTCC
isocitrate ATGAGTGTGAACACAGGGAGCTTTTGTGTGCAAATGTTGCACTGT
dehydrogenase,L35317 GTGTGGAAGAGACTGGAACAAATAGAATGTGTGTAGCTGAAATGSEQ ID
NO: 107
cytosolic CATGGCAGCCATGTTTGTAAAGAGCACTTATGTGTCCAATATACT
AATTATACGTTAAGACCACTGGAGAATTCCAAGTCTAGAATAAATA
CAGACTGGAGGTTTCTGCTCTTTGATTTCTCCTGTGGCCGAGCCC
AAGTATGATCCTACCCCAGACAGCACAGCATTTCACCCATGTGCA
ATAATGGGAGCTGCATCGTTTTCGGATTTCTGCTGGCCTACTACA
TTTCTTTTATATAAATGTGATTGTTTTTCAGAAGTTGATATTAAACA
CTATNCCAGTCTAGTCCTTCTAAACTGGTAATTT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTTAATCCTACACTGG
ACTCTCTCACTTTGGAATGGGACCCTCCAAGCCACCCAAATGGTA
TCCTGACTGAATACATCTTAAAATATCAGCCAATTAATAGCACACA
CGAACTAGGCCCTCTGGTAGATTTAAAAATTCCTGCCAACAAGAC
ACGCTGGACTTTGAAAAATTTAAATTTCAGCACTCGGTACAAGTT
Neuronal CTACTTCTATGCACAAACATCAGTGGGATCGGGCAGTCAGATCAC
cell
adhesion U81037 AGAGGAAGCAATAACAACTGTGGACGAAGCAATGGCAAGTCGGCSEQ ID
molecule NO: 108
(NrCAM) AAGTGGATATTGCGACCCAAGGCTGGTTCATAGGTCTAATGTGTG
CTGTTGCCCTCCTCATCTTAATTTTGCTAATCGTTTGCTTCATCAG
AAGAAACAAAGGTGGTAAATATCCAGTTAAAGAAAAGGAGGATGC
TCACGCAGACCCTGAAATCCAGCCCATGAAGGAGGATGACGGAA
CGTTTGGAAAATATAGTGATGCAGAAGATCACAAGCCTTTGAAAA
AAGGAAGTCGAACACCTTCAGACAGGATGTGAAAAAAGAANATA
GTGATGACAGCCTGGTTGACTATGGCGANGGGGTGAATGGGCAA
TTCCATGAGGATGGCTNCTTT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTCCTCGCAGAGGCGC
CCAGAGCAGAGCACCCGCTGCGCAGAGACCACAGCCCGCCCGC
CATGATGCTAGGTAACAAACGAATGGGGCTGTGTGGACTGACCC
TCGCTCTATCCCTGCTCGTGTGTTTGGGCATTCTGGCTGAGGGG
TACCCCTCCAAGCCGGACAATCCGGGCGAGGACGCGCCAGCAG
AGGACATGGCCAGATACTACTCCGCTCTGCGACACTACATCAATC
NeuropeptideNM 012614TCATCACCAGACAGAGATATGGCAAGAGATCCAGCCCTGAGACASEQ ID
Y NO: 109
CTGATTTCAGATCTCTTAATGAGAGAAAGCACAGAAAATGCCACC
AGAACAAGGCTTGAAGACCCTTCCATGTGGTGATGGGAAATGAA
ACTTGCTCTCCTGACTTTTCCTAGTTTCCCCCCACATCTCATCTCA
TCCTGTGAAACCAGTCTGCCTGTCCCACCAATGCATGCCACCAC
CAGGCTGGATTCCGACCCATTTCCCTTGTTGTCGTTGTATATATG
TGTGTTTAAATAAAGTATCATGCATTCAAAAAAAAAAAAAAAAAAA
AACAATTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTT
TANCTTGGCACTGGCCGTCGTTTTACAACGTCGTGGACTG
132
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCTAGAGCCAGCCA
GTCACCCTTAGTGAGGATCCCCTTCCCCATGTCTCTCCACTGCC
GTGGCATCCCATGTCCTGGATTTCTCAATTCCTCAGTTTCTACTC
AAAGGTGCTACTTACCAAACACTCTGCCCGTCCCGCTCTCCCCA
GCTTCGCACAGCCGTCCCAGGTGGCTTCGTCTCTCCTGCTTTAA
NGF-inducible AGTTAACTTTGGGCCCACAGACCCGAGAGCTGTGGGTTGAAGCA
anti-
proliferativeItt60921AAGCTGTGAATCGCTCCAGATGGTCCCTGTGTTCTGTCCACACAC
putative
SEQ ID
secreted protein AGGTCCCCGCCTT'f-fTAGAAGCAGCCTCCTGGTCTCATGCTTAAANO: 110
(PC3) TCTGTTCCTCACTGCCCGTGTTCACTTTAGAAATGGCAGAACCAC
AGAGCTGGACTGTTGAGCAGGCCTGTCTCTCTCA1~'AAATAAAAA
TAAGTAAGTTTGTAAGCTATTCCGACAGAAGAGACAAAGGTTACT
GATTGTACAATAGCGCTT'(-T'ATATGGAAGACTGTACAGCTTTATG
GACAAATGTAAAACTTTTTTGTTTTTAATAAAAATGTAGCAGACCA
AAAAAAAAAAAAAAAAACACATGCGGGCCGCAAGCTTATTCCC'f-f'
TTAGTGAGGGTTAATTTTACC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTTACTATTACTTCTCA
AGAATGAATAAAATGCTGCCTGACCCTGGTACCCTGGGAGAATA
CATTGAACAGTTCAAAGCTGGAAAAGTGCTGTGGGGCTCCTGGT
ATGACCATGTAAAGGGATGGTGGGATGTGAAAGACCAACACCGT
ATTCTGTATCTCTTCTATGAAGACATGAAAGAGGACCCTAAAAGA
N-hydroxy-2- GAAATTAAGAAGATAGCAAAATTCCTGGAAAAAGACATATCAGAG
acetytaminofluoreneX22339 G~GTTCTTAP'TAAAATCATCTACCACACCTCCTTTGATGTAATGA
gEQ ID
sulfotransferase AGGAAAACCCAATGGCCAACTATACCACTCTACCCTCCAGTATCANO: 111
(ST1C1) TGGACCACTCTATATCTCCTTTCATGAGGAAAGGGATGCCTGGAG
ACTGGAAGAACTACTTTACTGTGGCACAAAGTGAGGATTTTGATG
AAGACTACCGGAGGAAGATGGCAGGGAGCAATATTACCTTCCGC
ACAGAGATCTGAGAGCAGTGAGGAAGAGGGAAGCCCTAGATTTC
CTGACTATATGCTTTAGCTATTTGAGCTTCCATTCCTGAGTTTTGT
ATGTCCTGNGATACTATTTCATCAAATGNAAATCAGACCTTCCACA
CTAGGTGATTATTCTTATTGATACC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCGGCGTCCGGGTGC
CGCAGCACTTTAGCAGCGGAAGCGGCTGCTGTTGAGTACGTGAC
GGCTGGGGTCTGGCACGGGCGTGCTGGGACTCCGAGATAGGCT
CAGTGAGGCTGGCAGCGGi'CCACGGGCGCGGGCGCAGGCGGC
TCTGAGACCCCAGGACAAGATGCGAGCCACATCTCTGGCTGCTT
CTGCCGATGTTCCCTGCAGGAAGAAACCGTTGGAGTTTGATGAC
NIPK AB020967p'p'CATTGATGTCGAGTGTCCAGTCTTAAAACGAGTGAGAGATGAGSEO ID
NO: 112
CCTGAGCCTGGACCAACCCCCAGCCTACCTGCCGCCTCAGACTT
GTCACCTGCTGTGGCCCCTGCAACCCGGCTGGGGCCCTATATCC
TTTTGGAACGAGAGCAAGGCAACTGCACCTATCGGGCCCTGCAC
TGCCCCACAGGCACAGAGTACACCTGCAAGGTGTATCCCGCCAG
TGAGGCCCAGGCGGTGCTGGCACCGTATGCAAGACTGCCTACC
CACCAGCACGTGGCCCGTCCCACAGAAGTCCTGCTGGGCTCTCA
NCTCCTATACACCTTTTTCACGAANACCATGGGGACTTTGCACAG
TCTGGTGCGCAACCGCCGCGGTATCCCCGAC
TTCTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCATCTGGTTTCCATT
CACATTCTTCTTCTGTAGGTTCATAAATTGCATTAATGATCTCAAA
TCGCTTATCAAACAGAGGCTGATAGAGAACAGCATACTTTCTCTC
AAGGTCATGAACTTCCTCATAGAATTTGGCTTCTATCTGTGCACAT
TTAACTTGAAGATTCTTGAGAGCATTCACCCGTCTTTTGACTACCT
TAGGCAAGCTTTCAATGTATCCTGTTGGTGTGTCTACCAGACCAT
Nucleosome AF062594C~GTCTTTCCTGAAGAGCTGCAAGAATCTGAGGATTTTGCATCA
SEQ ID
assembly protein TCTGAACAGTTAGCTGACGTGCTTTGATITTTGTTI'CTTCACCCGTNO: 113
TTCTTCTTCTTCTACTTCTTCAACATCTTCCAAATCTTGATCAAGTT
CAGACTGTTCT'I-f'GTTGTCAATGTCTGCCATCTTT1'AAGAACTCCA
AATATCGTi'CCAGGAGGCTCGGACGCGGAGCCGAGCGGCCGGA
GCTGCGCAGGCAGTGACTCAAGGCGGCGGCGGCGGCGGCGGC
GGCGGCGGCGGCNGGAGGACGGGANGCGCCCCCNAGCAGATG
GCGCT CCTTTGCGGCGCAGCTTTA
TCCCTTTAGNGAGGGGGTNATTTTAACC
133
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CNGGGTATGACATGATTACGAATTTAATACGACTCACTATAGGGA
ATTTGGCCCTCGAGGCCAAGAATTGGGCACGAGGGCCGGCACT
CTGACTCCTGGTGGATGGGACTAGGGAGTCAGAGTCAAGCCCTG
ACTGGCTGAGGGCGGGCGCTCCGAGTCAGCATGGAAAGTCTCT
GCGGGGTCCTGGTATTTCTGCTGCTGGCTGCAGGACTGCCGCTC
CAGGCGGCCAAGCGGTTCCGTGATGTGCTGGGCCATGAGCAGT
ATCCGGATCACATGAGGGAGAACAACCAATTACGTGGCTGGTCT
OsteoactivinAF184983 TCAGATGRAP;ATGAATGGGATGAACAGCTGTATCCAGTGTGGAGSEQ ID
NO: 114
GAGGGGAGAGGGCAGATGGAAGGACTCCTGGGAAGGAGGCCGT
GTGCAGGCAGCCCTAACCAGTGATTCACCGGCCTTGGTGGGTTC
CAATATCACCTTCGTAGTGAACCTGGTGTTCCCCAGATGCCAGAA
GGAAGATGCCAACGGCAATATCGTCTATGAGAGGAACTGCAGAA
GTGATTTGGAGCTGGCTTCTGAGCCGTATGTCTACAACTGGACCA
CAGGGGCAGACGATGANGACTGGGAAGACAACACCAGCCAAGG
CCAGCACCTCANGTTCG
TTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCAGGAGGCAGGACAGCAACGGGA
AGACCAGCCATGAGTCAAGTCAGCTGGATGAACCAAGCGTGGAA
ACACACAGCCTGGAGCAGTCCAAGGAGTATAAGCAGAGGGCCA
GCCACGAGAGCACTGAGCAGTCGGATGCGATCGATAGTGCCGA
GAAGCCGGATGCAATCGATAGTGCGGAGGGGTCGGATGCTATC
GACAGTCAGGCGAGTTCCAAAGCCAGCCTGGAACATCAGAGCCA
Osteopontin M98252 CGAGTTTCACAGCCATGAGGAGAAGCTAGTCCTAGACCCTAAGASEQ iD
NO: 115
GTAAGGAAGATGATAGGTATCTGAAATTCCGCATTTCTCATGAAT
TAGAGAGTTCATCTTCTGAGGTCAATTAAAGAAGAGGCAAAACCA
CAGTTCCTTACTTTGCTTTAAATAAAAACAAAAAGTAAATTCCAAC
AAGCAGGAATACTAACTG.CTTGTTTCTCAGTTCAGTGGATACATG
TATGTGGAGAAAGAAATAGATAGTGTTTTGGGCCCTGAGCTTAGT
TCGTTGTTTCATGCAGACACCACTGTAACCTAGAAGT'I-fCAGCAT
Tr'TGCTTCTGGTCT1TCTGTGCAAGAAATGGAAATGGNCACTGCA
TTTTTAATGATTGCTATTCTTTTATGAATAAAATGTATG
TTCANGGNCANTAATTTGGGAACNCCAGGGTTTTCCCAGTCNCN
ACGTTGTAAAACGCGGNCAGGGCCANTTAAAATTAACCCNCCCTA
AAGGGAATAAGCTTTCGGCCNCNAAATTTfTTTT'1'TfTTfTTTTTAT
GTTCAGATGCATTTATTCAGCAAACCTTCTTGCTAAACATTATGGT
AGCCCTAAAAGATTTCGAAATCAGGACATTCAGCAAAGCCCTCTC
Pancreatic CTCTGAATGCGGATAGATGTTCCAAATTTGCTGTTTTCAAAGCATA
secretory
trypsin inhibitorM27883 GAATGCATTCATTGGCGTAAGTTTTTCCGTCAGTACCACACACAGSEQ ID
type II NO: 116
(PSTI-! I GATCATAATCCCTGGGGCATCCAACAAGTGTATTAGGGCAAT'fAG
)
CCTTTTTCCCAATCACCTTAGCTGTAGTGTTACCTGCTAAATTGAG
GAGGGCCAAAGCACTGAGAAGAAAGATAATTGCTACCTTCATGGT
TGTAGAGCTAGGTCCAAAACTCAGAAGAACTGTGCAGGGTGCTT
CTCTTCAGCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATTC
CGTATAGTGAGTCGTATTAAATTCGTAATCATGTCATAA
GNNNNNTCTATGACATGATTACGAATTTGAATACGACTCACTATA
GGGAAT'f-fGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGAA
GAGAAGCACCCTGCACAGTTCTTCTGAGTTTTGGACCTAGGTCTA
CAACCATGAAGGTAGCAATTATCTTTCTTCTCAGTGCTTTGGCCC
TGCTCAP.TTTAGCAGGTAACACTACAGCTAAGGTGATTGGGAAAA
Pancreatic RGGCTAATTGCCCTAATACACTTGTTGGATGCCCCAGGGATfATG
secretory
trypsin inhibitor ATCCTGTGTGTGGTACTGACGGAAAAACTTACGCCAATGAATGCA
type II
(PSTI-II) M27883 TTGTATGCTTTGAAAACAGGRAATTTGGAACATCTATCCGCATTCASEQ ID
(alternate NO: 117
clone) GAGGAGAGGGCTTTGCTGAATGTCCTGATTTCGAAATCTTTTAGG
GCTACCATAATGTTTAGCAAGAAGGTTTGCTGAATAAATGCATCT
GAACATARAAAAAAAAAAAAAARAATCTCGCGGCCGCAACSC'f-i'AT
TCGCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTGGTTT
TACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATC
GCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAA
GAGGCCCGCACCGA
134
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCTTTCTTGGGCATG
CTTCAAGGCAAGCAGCAGAAGCTGCAGCAAAACCTGCAGCAAGG
GAATCACTCGTCTGGCTCCAGTCGCCTCTACGATCTCTACTGGCA
GGCCATGAACTTGCTTGGAGTGCAGCGTCCAAAGTCAGAAAAGA
AGAATGTGAAGGATATTCCTAGTGACAGCCAGAGTCCCATTAGCA
CAAAGCGGAAGAAAAAGGGATTCTTGCCAGAGACCAAGAAGCGA
PAR interacting~g3690 '~G~CTTAAP'TCTGAGGGTACCACATCAGAAAAGAAGGCTGCA1
SEQ
protein TCACAGCAGGATGCAGTGACAGAGGGTGCCATGCCTGCTGCCACD NO: 118
TGGTAAAGACCAGCCCCCCAGCACAGGCAAGAAAAGAAGGAAGA
GAGTGAAGGCTAACACCCCATCCCAGGTGAATGGAGTAACTGTG
GCCAAGAGTCCGGCTCCCAATAACCCCACCCTGAGTCCCAGCAC
CCCCCCTGCCAAGACCCCAAAAGTGCAGAAGAAAAAAGAGAAGC
TGTCACAGGTGAATGGATCCACTCCTGTGTCCCCCCGTAGAGCC
TGAAAGCAAAAAGCATCAGAANGCTCTCAGCACAAAGGAGGTCA
AAAAGAAAGTCCTCCAGTCTGGCCTGNCAAAAAAAAANAA
TACATGATTACTACTTTAATACGACTCACTATAGGGAATTTGGCCC
TCGAGGCCAAGAATTCGGCACGAGGCCTCGTGCCGAGAGGACC
CTGGGAGCCATTGTCAGGAAGCGGAATCAGCCCATGACTCCCGA
GGCAGTGAGGGACAACTGGGTGAAGATCTGTGACTTCAGCAATG
CCAGCAAGCCGAAGAGCATTCAAGAGTCCACAGGTGGTATAATC
GAAGTTTTACATAAAATAGATTCAGAAGGAATCTCACAAAATCACA
Peroxisomal CCGGTCAAGTGGCATCTGCAGATGCATCAGGATTTGCTGGCGTC
multifunctionalNM G~GGCCACAAACTTCCTTCATTTTCTTCTTCATATACGGAACTGCgEQ ID
024392 NO: 119
enzymetypell _ AGTGCATTATGTATGCCCTCGGAGTAGGAGCTTCAGTCAAAAATC
CAAAGGACTTGAAGTTTGTT'i'ATGAAGGGAGTGCTGACTTCTCCT
GTTTGCCTACATTTGGAGTCATTGTCGCTCAGAAGTCCTTGATGA
GTGGAGGCTTAGCAGAGGTTCCTGGGCTGTCAATCAACTTTGCA
AAGGTTCTTCATGGGGAGCAGTACTTGGAGTTGTATAAGCCACTT
CCCCGATCAGGGGAATTTAAAATGTGAAGCAGTTATTGCTGACAT
CCTGGATAAAGGCTCTGGCATAGTGATTGTTATGGACGTCTATTC
TTATTCTGGCAAGGACTTATATGCTATNATCAGTTC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTGAAGTGGGAGCGG
CCCCAGCACGCGCTGAGGGTCGACTACGGCGGAGTAACGGTGG
ACGAGCTGGGCAAAGTGCTGACGCCCACCCAGGTCATGAATAGA
CCAAGCAGCATTTCATGGGATGGCCTTGATCCTGGGAAGCTCTA
CACCCTGGTCCTCACAGACCCCGATGCTCCCAGCAGGAAGGACC
CCAAATTCAGGGAGTGGCACCACTTCCTGGTGGTCAACATGAAG
Phosphatidylethanola GGCAACGACATTAGCAGTGGCACTGTCCTCTCCGAATACGTGGGgEQ
ID
NM 017236N O: 120
mine-binding CTCCGGACCTCCCAAAGACACAGGTCTGCACCGCTACGTCTGGC
protein
TGGTGTATGAGCAGGAGCAGCCTCTGAACTGTGACGAGCCCATC
CTCAGCAACAAGTCTGGAGACAACCGCGGCAAGTTCAAGGTGGA
GTCCTTCCGCAAGAAGTACCACCTGGGAGCCCCGGTGGCCGGC
ACGTGCTTCCAGGCAGAGTGGGATGACTCTGTGCCCAAGCTGCA
TGATCAGCTGGCTGGGAAGTGGGGGCGCTGCAGACCCGCAGCC
CCGGGGACCCCACAGTACAGTCAAGTCGTATTAAAGCATGTGCT
TGTGGGGTGTCCCCCCACGNCCCATCCT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT1?GG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTCCTTGTTGCCTCCA
CTGGGGAGCAAAGAGGGGATGATACCTTTAGAAGTGTGGACATA
GCTGGGGCTTCCGCTCAGCGGCAGTTGCTAGCCGTTGGGCCCT
ATCGTGCCTGGATCCTTGCCCCACACCCTGAGTTCTGAGGGCAG
TGCCCTTTGATCCTTGGGGAGGACATCTCTGAGGACTCCTAGAG
AATCACAGAGGACCTTTACTTGAGAAGTAGCCAAAGGGAGCACT
PhospholipaseD88672 CCCAAGCCTGGCCTGGGAAAGCAGGAGAGAGTTCTAGAGAGGTTgEQ ID
D NO: 121
TGCCTTCTTGTCACCATGTTCAGACCACTATGCCACAGAACCTAG
TCCTACGAGGAGGCCTGAGGTCAAGCCT'1-fTATTCCAGGAAAAG
GGACTCCTGCCCTGGGTCGTCTTCATCTCACTCTTCCTCCTGCCC
TTGAACCCCTACATGCCCTGGGCCTCTCCCAGCCCGTTGCTGCA
AAGATGGGGGGGGGGGAGTATAGAGCCACTTTGACTGCAGTCC
CCACCAGCGGTGGTGAGGACACCTTAACTGCCTCCACCAGCCTG
CTGACAGACACTAACTCTGTACCGGTTCACCAAAGCATTTCATAA
ATAAATGNGGTAGAAAANGCC
135
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCCCACTAGCCTCTG
GCACAATGAAGTGGGTAACCTTTCTCCTCCTCCTCTTCATCTCCG
GTTCTGCCTTTTCCAGGGGTGTGTTTCGCCGAGAAGCACACAAG
AGTGAGATCGCCCATCGGTTTAAGGACTTAGGAGAACAGCATTTC
AAAGGCCTAGTCCTGATTGCCTTTTCCCAGTATCTCCAGAAATGC
CCATATGAAGAGCATATCAAATTGGTGCAGGAAGTAACAGACTTT
PreproalbuminV01222 GCAAAAACATGTGTCGCTGATGAGAATGCCGAAAACTGTGACAASEQ ID NO:
122
GTCCATTCACACTCTCTTCGGAGACAAGTTATGCGCCATTCCAAA
GCTTCGTGACAACTACGGTGAACTGGCTGACTGCTGTGCAAAAC
AAGAGCCCGAAAGAAACGAGTGTTTCCTGCAGCACAAGGATGAC
AACCCCAACCTGCCACCCTTCCAGAGGCCGGAGGCTGAGGCCA
TGTGCACCTCCTTCCAGGAGAACCCTACCAGCTTTCTGGGACAC
TATTTGCATGAAGTTGCCAGGAGACATCCTTATTTCTATGCCCCA
GAACTCCTTTACTATGCTGAGAAATACAATGAGGTTCTGACCCAG
TGCTGCCAGAGTCTGACAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGACCCCACTAGCCTCTG
GCACAATGAAGTGGGTAACCT'1TCTCCTCCTCCTCTTCATCTCCG
GTTCTGCCTTTTCCAGGGGTGTGT'f-TCGCCGAGAAGCACACAAG
AGTGAGATCGCCCATCGGTTTAAGGACTTAGGAGAACAG.CATTTC
AAAGGCCTAGTCCTGATTGCCTTTTCCCAGTATCTCCAGAAATGC
Preproalbumin CCATATGAAGAGCATATCAAATTGGTGCAGGAAGTAACAGACTTT
(alternate V01222 GCAAAAACATGTGTCGCTGATGAGAATGCCGAAAACTGTGACAASEQ ID NO:
clone) 123
GTCCATTCACACTCTCTTCGGAGACAAGTTATGCGCCATTCCAAA
GCTTCGTGACAACTACGGTGAACTGGCTGACTGCTGTGCAAAAC
AAGAGCCCGAAAGAAACGAGTGTTTCCTGCAGCACAAGGATGAC
AACCCCAACCTGCCACCCTTCCAGAGGCCGGAGGCTGAGGCCA
TGTGCACCTCCTTCCAGGAGAACCCTACCAGCTTTCTGGGACAC
TATTTGCATGAAGTTGCCAGGAGACATCCTTATTTCTATGCCCCA
GAACTC
NTATGACATGATTACGAAT'I-fAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGCAGCAAGAAACC
TGGGAAGAGTGGGCACCAAGTGTTGTACCCTTCCTGAATCTCAG
AGACTGCCCTGTGTGGAAGACTATCTGTCTGCCATCCTGAACCG
TCTGTGTGTGCTGCATGAGAAGACCCCAGTGAGCGAGAAGGTCA
CCAAGTGCTGTAGTGGGTCCCTGGTGGAAAGACGGCCATGTTTC
Preproalbumin, TCTGCTCTGACAGTTGACGAGACATATGTCCCCAAAGAGTTTAAA
sequence 2 V01222 GCTGAGACCTTCACCTTCCACTCTGATATCTGCACACTCCCAGACSEQ iD NO:
124
AAGGAGAAGCAGATAAAGAAGCAAACGGCTCTCGCTGAGCTGGT
GAAACACAAGCCCAAGGCCACAGAAGATCAGCTGAAGACGGTGA
TGGGTGACTTCGCACAATTCGTGGACAAGTGTTGCAAGGCTGCC
GACAAGGATAACTGCTTCGCCACTGAGGGGCCAAACCTTGTTGC
TAGAAGCAAAGAAGCCTTAGCCTAAACACATCACAACCATCTCAG
GCTACCCTGAGAAAAAAAGACATGAAGACTCAGGACTCATCTCTT
CTGTTGGTGT
TTCTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTCTGTCTGCCATCCT
GAACCGTCTGTGTGTGCTGCATGAGAAGACCCCAGTGAGCGAGA
AGGTCACCAAGTGCTGTAGTGGGTCCCTGGTGGAAAGACGGCCA
TGTTTCTCTGCTCTGACAGTTGACGAGACATATGTCCCCAAAGAG
TTTAAAGCTGAGACCTTCACCTTCCACTCTGATATCTGCACACTC
CCAGACAAGGAGAAGCAGATAAAGAAGCAAACGGCTCTCGCTGA
Preproalbumin, GCTGGTGAAACACAAGCCCAAGGCCACAGAAGATCAGCTGAAGA
sequence 2 V01222 CGGTGATGGGTGACTTCGCACAATTCGTGGACAAGTGTTGCAAGSEQ ID NO:
(alternate 125
clone 1 ) GCTGCCGACAAGGATAACTGCTTCGCCACTGAGGGGCCAAACCT
TGTTGCTAGAAGCAAAGAAGCCTTAGCCTAAACACATCACAACCA
TCTCAGGCTACCCTGAGAAAAP,AAGACATGAAGACTCAGGACTCA
TCTCTTCTGTTGGTGTAAAACCAACACCCTAAGGAACACAAATTT
CTTTGAACATTTGACI-fCTTTTCTCTGTGCCGCAATTAATTAAAAA
TAGAAAGAATNTTAAAANNNNNNCNNNNNNNNNNNNNNNAAAGT
GTGGCGGNCGCNAGCTTATTCCCTTTAGNGAGGGTTAATTTTACT
TGGCACT
136
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTGGGGACGAGGAAACGATGAAAACTTC
GATAACTTTGTGGCTGACAAAGATACAGTGCTCCTGGAGI"TCTAT
GCACCGTGGTGTGGACACTGCAAGCAATTTGCTCCAGAATATGA
GAAAATTGCCAGTACTTTGAAGGATAATGATCCTCCCATTGCTGTi
TGGAAAGATTGACGCGACCTCAGCATCCATGTTGGGCAGCAAATT
Protein disulfide CGATGTGAGTGGGTACCCCACCATCAAGATCCTGAAGAAGGGAC
isomerase NM 053849AGGGTGTTGACTATGACGGCTCCAGGACCCAGGAAGAAATTGTTS~Q ID
related NO: 126
protein - GGCAAAGTCAGAGAAGTTTCCCAGCGTGAATGTGTACAGCATGC
TCAAACACCAGACTCTGGTCCTCACCCTGCCTTCCGTCGGCTTCC
TGGAGGACAAGCTACTCTGGCAAGATTCAAGATACACACCACTCT
ACGCCTTGCGCTTGCCCTACAGTGACTTGCCCTAACCCTGCCCT
GGTCACCTAGGGGCTTGCTCCACTCGGGGGCCAGGTGAGCAAG
CACACCAGCCATCCCCAAAAAAATCAGTTTCCTGGAGTCTGTCGG
ACCTTGTTACCANGANGGAAAAACTGCACAGANTCAAAATGATCC
CTGCCGGGGATCTCTTTTGTCACATNNGGGGGGNGGGCT
TATGACATGATTACGAA1-fTAATACGACTCACTATAGGGAATTTGG
CGCTCGAGGCCAAGAATTCGGCACGAGGGTTTGCCGTCAGAACG
CAGGTGTTGTGAAAGCCACCGCTARTi'CAAAGCAAAAATGGGAAA
GGAAAAGAGTCACATCAACATTGCCTATTGGCTGCACCCCAGGA
CCAGTGCCCAGATCCACTTGCTTGGAAACATCGTGATCTGGACTT
CAGCCAGCCTCGCCACAGTGGCATAGACCCTACTCTTCTTCTGG
Protein O- TACCTGGTCCGCCGTCGAAGGAAGATCTGTGACCTCCGTGAGGA
mannosyltransferaseNM TGCCTGGTCCGACTGGGTGCTGGCTGGAGCTCCAGGAATGAATTSEQ iD
053406 NO: 127
1(Pomt1) _ CCAATTTCATCTCAAGAGCCCTGTTTGAAGTGATTTCTCCTCACA
CAGTGAAGAATGTGCCCAGCCACAGCATCACCCATGAGGCCCAA
CTCTGACCAGTGTTTGAGCTGCCAGTGTAGGACTCACCTACAGTA
CACCTAAGGCAGGAGGAGCAGCCAGTGAAGGAGTGAAGTGGAG
GCCCCGCCCAGCTGTGCGCGCACCAATGGGGTCTTAGCTCTCTC
CCGANGCCGACAGTACTGCCACTCATTTGTGTGCAGGTACAGTG
GCCCTCTGTAAAGCCTGGTTTGARRNCTGCCTTCACTCACACTGA
GTCCTCACCAATGCGACTCTANAAATC
GGGGATCGGTGNGGNCTTTTTNGTTATTACGCCAGCTGGCGAAA
GGGGNATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTT
TTCCCAGTGACGACGTTGTAAAACGACGGCCAGTGCCAAGCTAA
AATTAACCCTCACTAP.AGGGAATAAGCTTGCGGCCGCCACACNN
NT'fTi'TTTi'TTTTNNNTNNNNNNNNNNNNNGGTCCAAGCCAAAGG
TAACI"fTATT'GATTCATGAATCTGGAAAGTTGAAGTACAGGTTTTA
Protein tyrosine TTCCAGAAAAGAACTGATTCTGAGCACAGTGTAGTCAGTGCTCCA
phosphatase,NM 019140TCACTCTGGGTTGCCCAAAAAAAGACTTGCACAATGATTCCAGTT$EQ ID
receptor NO: i28
type,D GACATGCAACATGGACAGAAACATTTGAGAAAGCCACACCCATAT
ATGAAGAGCTAGAGGTAATCAGCTGCTGAGAAAAGGACAATCCG
TTTTCTTCAGGGATAGACCTCCTGATAGATTATCCAGTCTCAAGT
GTTCAACAAAATACAAGAAACACTAAATGTAATCAGTAAGATGGAT
TACTGATAGATGATAGATAGATAGATAGATAGATAGATAGATAGAT
AGATAGATAGATAGATAGATGGATGGATGGATGGATGGATCCTC
GTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAGT
CGTATTAAATTCGTAATCATGTCATAA
TCNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTTCTAATAGTT
GAACCAGGGCACATAGAAAGCACTGTAATTGTACGTGTGAATTGG
CAAGAAGCAAGTGGTCi'CCCTTGATTCTGCTCCACGAGGAGGAG
AATGGGCTGTGATCTGAACTGTGGGCTCATTACTGGAGCCATTAT
TGGTGCTGTCCTGGCTGTGTTTGGAGGCATTCTCATGCCGGTTG
GAGACCTGGTCATTGAGAAGACAATCAAAAGGGAAGTTGTCCTTG
Putative ~G~GGAACCATTGCTTTCAAAAACTGGGTGAAAAGGGGCACC
membrane
fatty acid AB005743 ACTGTGTACAGACAGTTTTGGATGTTTGACGTGCAAAACCCAGAGSEQ 1D
transporter NO: 129
GAAGTGGCAAAGAATAGCAGCAAGATCAAGGTTAAACAGAGAGG
TCCTTACACATACAGGTCAGAAACAAGCGTAACACCCGTCAACTG
CTACAACAAGTGGATGGAACAGACTCGACCTGGTTATTTCRAACT
CCTTTGTGGAAATCAGATATGAGT1'CAGTGTTGAGAACCACAGAA
ATGAAATGATTGTGCATAGCTGCAGCCCCTGCTAAGTGTCGAAGT
CAGATATGCATTGAGATTGAAATAGCAATTTAAAGCTTACAATGGT
TCACTCTGTTATACTTTTAAATAT'fTTAATAG'iTTATTTAATAAAGTT
ATAAATAAAAT
137
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGCATGCAGCACCTG
ATTGCCCGAGAGGCAGAGGCTGCCATCTACCACTTGCAGTTATT
CGAGGAACTCCGCCGCCTGGCGCCCATTACCAGCGACCCCACA
GAAGCTGCCGCCGTGGGTGCCGTGGAGGCCTCCTTCAAGTGCT
GCAGTGGGGCCATTATGGTGCTCACCAAGTCTGGCAGGAGTGCT
CACCAAGTGGCCCGGTACCGCCCAAGGGCTCCTATCATTGCTGT
Pyruvate M24361 GACACGCAATCCCCAGACAGCCCGCCAGGCCCATCTGTACCGTG
kinase,
SEO ID
muscle GCATCTTCCCTGTGCTGTGTAAGGATGCCGTACTGGATGCCTGGNO: 130
GCTGAGGACGTTGATCTTCGTGTGAACTTGGCCATGAATGTTGG
CAAGGGCCGAAGCTTCTTCAAGAAAGGAGATGTGGTCATTGTGC
TGACTGGATGGCGCCCTGGCTCTGGCTTCACCAACACCATGCGT
GTANTGCCTGTACCATGATGATCCTCTGGAGCTTCTCTTCTAACC
CCTGTCCCTTCCCCTCCCCTATNCTATTCATTAAGGCACAACGCT
TGTAGTGCTCACTCTGGGNCATAATGTGGCGCTGGTGGGCTGGG
ACACCACGAAAAAATAATGNCTCTGAA
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCACATCTGAGATGAT
GGAGGTAGCGGTCAGCAAGGCACGGGCCAAAGTGACCATGAAC
GACTTCGATTATCTCAAACTCCTCGGCAAGGGCACCTTCGGCAAA
GTCATTCTAGTTCGAGAGAAGGCCACTGGCCGCTATTATGCCAT
GAAGATCCTGCGGAAGGAGGTCATCATTGCAAAGGATGAAGTCG
RAC protein CCCACACAGTCACAGAGAGCCGAGTCCTACAGAATACCAGGCAC
kinase
beta D30041 CCCTTCCTTACAGCCCTGAAGTATGCCTTCCAGACCCATGACCGSEQ ID
NO: 131
CCTGTGCTTTGTGATGGAGTATGCCAACGGGGGCGAGCTGTTTT
TCCACCTCTCTCGGGAGCGAGTCTTCACGGAGGATCGGGCACG
CTTTTATGGAGCAGAGATTGTGTCAGCTCTGGAGTACTTGCA~TC
GAGGGATGTGGTGTACCGCGACATCAAGCTGGAAAACCTTATGC
TGGACAAAGATGGCCACATCAAGATCACTGACTTTGGCTTGTGCA
AAGAGGGCATCAGTGATGGGGCCACCATGAAAACCTTCTGTGGT
ACCCCGGAGTACTTG
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT1TG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCCTTCTCAGACTCC
CTCAGGAGGGAGCTCACCTACTTTGGGGTGAAGGTGGCTATTAT
AGAGCCTGGTGGGTTCAAGACCAATGTCACTAATATGGAGAGGC
TATCAGACAACCTGAAGAAGCTGTGGGACCAGGCCACTGAGGAG
GTCAAGGAGATCTACGGCGAGAAGTTTCGGGACTCCTATATGAA
' Retinol AGCAATGGAGTCACTGGTGAACATGTGCTCAGGGGACCTGTGTC
dehydrogenaseU33501 TGGTAACCGACTGCATGGAGCACGCCCTGACTTCCTGTCACCCTSEQ ID
type NO: 132
III CGCACCCGGTACTCAGCTGGTTGGGATGCCAAGTTCTTCTACCT
CCCCATGAGCTACCTTCCCACCTTTCTTTCGGATGCCGTAATCTA
CTGGGGCTCTGTAAAGCCTGCCCGAGCCCTGTGAATCTGCACAT
GTGTGCAGACTTGGGGAAGTAAGGCGGGTGGAGGGAGATAACA
ATGTGGGGTCCATTGTTCACCATACTCATTAAAATAATTCTGCTTC
CGTACT GTGTGGCGGCC
GCAAGCTTATT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGTTTCTCTGGGCTCT
GGTATGCCATCGCCAAAAAGGATCCCGAGGGTCTCTTTTTGCAA
GACAACATCATCGCTGAGTTTTCTGTGGACGAGAAGGGTCATATG
AGCGCTACAGCCAAGGGACGAGTCCGTCTTCTGAGCAACTGGGA
AGTGTGTGCAGACATGGTGGGCACTTTCACAGACACAGAAGATC
Retinol-binding CTGCCAAGTTCAAGATGAAGTACTGGGGTGTAGCCTCCTTTCTCC
protein (RBP)M10934 AGCGAGGAAACGATGACCACTGGATCATCGATACGGACTACGACSEO ID
NO: 133
ACCTTCGCTCTGCAGTACTCCTGCCGCCTGCAGAATCTGGATGG
CACCTGTGCAGACAGCTACTCCTTTGTGT'f~ITCTCGTGACCCCAA
TGGCCTGACCCCGGAGACACGGAGGCTGGTGAGGCAGCGACAG
GAGGAGCTGTGCCTAGAGAGGCAGTACAGATGGATCGAGCACAA
TGGTTACTGTCAAAGCAGACCCTCAAGAAACAGTTTGTAGCAATG
TCAAGGATGTATAAAGTTGGAAAACTTCTGATTAGCTCTCATCCA
GTCTTCA
138
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGARTTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTGGGCACGAGGGAGGCAGCCATGGCG
CCCAGCCGGAATGGCATGATCCTGAAGCCCCACTTCCACAAGGA
CTGGCAGCAGCGAGTGGACACGTGGTTCAACCAGCCGGCCCGC
AAGATCCGCAGACGCAAGGCCCGGCAGGCGAAAGCGCGCCGCA
TCGCCCCTCGCCCCGCGTCCGGTCCCATCAGGGCCATCGTGAG
GTGCCCTACAGTTAGATACCACACCAAGGTCCGGGCTGGCAGGG
Ribosomal NM 031101GCTTCAGCCTGGAGGAGGTCAGGGTGGCTGGTATCCACAAGAAASEQ ID
protein NO: 134
L13
ATGGCACGCACCATCGGCATCTCCGTGGACCCAAGGAGGCGAA
ACAAATCCACGGRGTCACTGCAGGCGAACGTGCAGCGCCTGAAG
GAGTACCGCTCCAAGCTCATACTTTTCCCCAGGAAGCCTTCTGCT
CCGAAGAAGGGAGACAGTTCTGCTGAAGAACTTAAATTGGCCAC
GCAGCTAACAGGACCTGTGATGCCCATCCC7GAATGTGTACAAAA
AGGAGAAGGCCAGAGCCATCACGGAAGANGAGAAGAACTTTAAG
GCTTTCCCAGCCTTCCRTGGNCCGAGCCAATGCCNGCTCTTCGC
ATNCGACAAAGAGGCGAAAGRNCCGCAAACRAAACNTTGANAA
CNTNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCCTGCTGCTC
GCTGTCGAAATGGGCAAGTTTATGRARCCCGGGAAAGTGGTGCT
GGTCCTGGCTGGACGCTACTGCGGAGGCAAAGCCGTCATCGTAA
AGAACATTGATGATGGGACCTCCGACCGCCGTTACAGCCATGCC
CTGGTGGCTGGAATTGACCGCTATCCCAGARARGTGACAGCTGC
CATGGGCAAGAAGAAGATCGCCAAGCGATCCAAGATCAAGTCCT
Ribosomal NM 022514TTGTGAAAGTTTATAACTACAACCACCTCATGCCCACAAGGTACTSEQ ID
protein NO: 135
L27
CTGTGGATATCGCCTTGGACAARACTGTTGTCAACARGGATGTGT
TCAGAGACCCAGCACTGAAACGCAAGGCCAGGCGGGAGGCCAA
GGTCAAGTTTGAGGAGCGATACAAGACAGGGAAGAACAAATGGT
TTTTCCAGAAGCTTCGCTTTTAGATGTATTTTTGTTTTCGTCATTAC
AAAAATAAAAAATANTAAAAAACAAAAAAAAPu4AAAAATCTGGCGG
CCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCAC
TGGCCGTC
TTCTATGACATGATTACCAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTTTTTTTTTTTAC
CGAGACCCGTCAACATGGGCGGCGTTCGCACCAAGACTGI'GAAG
AAGGCGGCCCGGGTCATCATCGAGAAGTACTACACGCGCCTGG
GTAATGACTTTCACACCAACAAGCGCGTGTGCGAGGAGATCGCC
ATCRTCCCCAGCAAAAACCTTCGGAACAAGATAGCCGGCTATGTC
ACGCATCTGATGAAGCGGATTCAGAGAGGTCCTGTGAGAGGCAT
Ribosomal NM CTCCATCAAGTTGCAGGAAGAAGAGAGGGAGAGGAGAGATAATTSEQ ID
protein 017152 NO: 136
S17 _ ATGTTCCTGAGGTCTCAGCCCTAGATCAGGAGATCATTGRGGTA
GATCCTGACACCAAGGAAATGCTGAAGCTTCTGGACTT1'GGCAG
TCTCTCCAACCTCCAGGTCACTCAGCCTACGGTTGGGATGAATTT
CRARACRCCACGTGGAGCTGTTTAATCCATTATGGCATATTTTCAA.
TAAACCTGAAAACAAAAAAAAAAAAAAAACAAAAAAAAAAAAAAAA
ACCTTTGCGGCCGCAAGCTTATTCCCTTTANGNGAGGGTTAATTT
TRGCTTGGCACTGGGCCGTCGTTTTACAACGNCGNGACTGGGAA
AACCCTGGGNGTTACCCAACTTAATCGCGTTGCA
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGARTTCGGCACGAGGGAAGCTTTGCGCTT
CCTCTTTCCAGCCAGCGCCGAGCGATGGGCATCTCTCGGGACAA
CTGGCACAAGCGCCGCAAGACCGGGGGTAAGAGAAAACCCTAC
CACAAGAAGCGGAAGTATGAGCTGGGRCGGCCGGCCGCCAACA
CTAAGATTGGCCCTCGCCGCATACATACAGTCCGAG,TTCGAGGA
GGCAATAAGAAGTATCGTGCTCTGAGATTGGATGTGGGGAACTTT
Ribosomal NM 031706TCCTGGGGCTCAGAGTGTTGTRCTCGCARAACAAGGATCATTGATSEQ iD
protein NO: 137
S8
GTTGTCTACAATGCATCCAATAACGAGCTTGTCCGCACCAAGACC
CTGGTGAAGAACTGCATTGTGCTTATTGACAGCACACCGTACCGA
CAGTGGTACGAGTCCCACTATGCACTGCCCCTGGGCCGCAAGAA
GGGGGCCAAGCTGACTCCTGAGGAGGAAGAGATTTTAAACAAAA
AACGATCAAAGAAAATTCAGAAGAAATATGATGAAAGGAAAAAGA
ATGCCAAAATCAGCAGTCTTCTGGRGGAGCAGTTCCAGCRNGGC
AAGCTTTCTCGCCTGTATTGCCTCAAGAACAGGCCAGTGTGGCA
GANCAGATGGCTATGTGCTCNAANGCAANGAGCTGGAGT
139
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGAACTGTAGCTGCCC
CTCCTGTAGGAGCTGGCGCCGCCGGGGCTCCTGACTTTCTCCGT
CTTTCTCCAGCAGGCTGAAAGCCTTAGTTCCCACAGAGGACACA
GATCTGTCACTCCTAGGGGCTGGGCAAACATCGGCCTCTTGCGT
CACGGCTGGACAAGCAGTTCCAGATCCTGACCAGTCTGCACACA
CACTCTGGCGCTGTATCTGGCCCTTCTCCTACAGTCTCTGCTGTC
Scavenger pgg655 ACCTGAACACTGAATTGGCCACTGTAAGTGGCAGCGGTGGCAGGSEQ ID
receptor NO: 138
class B type CCCCCTCAGGGTCCTTATTTTTCAGGCGTGGGGTCAAAGAGAGA
I
GGTGTGGGCCGTCTAGCCCTGGCACCTAGTATATCTCACCAGAG
GGTAGGGTATACAGAGGCCCAGCGTCCCACAATCGACCCCTTTT
TTTCTACTGGAAGAGAAATTTTATCGTCTTTTGAAAGAAAGTCATG
ACTGAAGCAATAAACCTTTTCACAAATTCAAAAAAAAAAAAAAAAA
AAAAACAATTGCGGCCGCAAGCTTATTCCCTTTANTGANGGTTAA
TTTTANCTTGGCACTGGCCCGTCGTTTTACAACGTCGTGACTGGG
AAAACCCTGGCGTTACCCAACTTTATN
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCACAAATCCTAGGC
CATGCTAGCAGTCTCTATGGGGCTATGTATAGCAAGGCATCTATT
TTTCTATTTGAACCCTCATTTCCTACGAGGTATCGATAATAGGATG
TGAGATGGTGATATTGCTCGTTTAATCATTGATGTGCTGTATTTTT
CACGTTCATATTGTTGTGTTGTTTGTGCTGTAAATAACGCCTGTAA
AGGTATI-fACAGCATTGGGTTTTCATTAGAGTATTACTCTTTATTT
Schlafen-4 AF168795GAGATGTTGGTATTTCCTTCATAAAGAAAGAAGTGTCTTTATTGTASEQ ID
NO: 139
CATGTACATTTGTGAAGGATAAACTCTCTCAACATTCGGCCCTTA
GCGGCTATTGATAAGCAGTGGTAACCTGTTGTGACTTTTGATAGA
GTTTATCAAAAGAACGGTTGCCCTTCACGAAAAGTCTGATGACTG
GGCTATGAGCTGGGTGCTCACAGCAACCAATCCTCTTANCCATG
GTTTCTCTTTTGATCTATTTCTTTATCGATATGATTATTTTAAAATCT
ACATCGTTTTCATCTACTCTGGTCTCAGAACTGGGTGGTATGAAN
ATAATTCTTCNGCTTGGAACCTTTCNCCTGGAANNAANCTCCANT
GGCTGGACTTGG
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGCAAGTGAAGGCT
TGCAACTTTCACTTGCCCAGAGGAAGCTCTGACGAAGGGGATGC
ATAAACCAGCTCCTGTGTAAGTTATCTGAGGAGTCTGGGGCAGC
TACCAGTAGCTGCTGCTGCCACTGCCGACACCTCATATTTGAGAA
GTCAGGATCTGCAATCACTTGACAGTGTGCCGAAAACCTCCCATC
CTTGTGTAGCTGACAGGGGCTTTTCGCGGAGGAGAAAGTCATTG
SelenoproteinNM 019192~TCCTGTCAATGTAGATCACCTCCAGCTGCCTGACACAGTCAGCSEO ID
P NO: 140
ATGTAAGCCCCACAGAAGCCAGCCCCAACTGAAGCTGAAATAAT
AAGACCAAGAAGTGAAAATGAAATTTGAACTAAATATTTAAAATAA
AGGGTACTCTCCCCAACTCCATCTAAAGACACAATTTCATTTCTAG
AATGTTTCCAATCCATTTAATTAATTAGTGAAGTAAAAGTAGTTGA
AATTGGATTTGTGCAAACATGGAGAAATCTACCACATTGGCTTCT
AAAATTTAAAATTTTTATGCCACAAACCATTTCATCCAAATCAGATT
TGTACCGTGGGGCAACTGAAAAGTGATTGCGGNCATTGGGTAAT
ATGGCTTTCTTTTCTTTCC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCAGGCGGCTCGGA
CTGAGCAGGGCTTTCCTTGCCAGTGGATTGTGTAGAGTGTACAG
CCAGTCTCTTGTCTTCTGTCCAACATGGCATCTTCTGATATTCAG
GTGAAAGAGCTGGAGAAGCGTGCTTCCGGCCAGGCTTTTGAGCT
GATTCTCAGCCCTCGATCAAAAGAATCTGTCCCCGAGTTCCCCCT
TTCCCCCCCCAAAGAAGAAGGATCTTTCCCTGGAGGAAATTCAGA
Stathmin NM 017166''G~'~AGAAGCTGCAGAAGAAAGACGCAAGTCTCATGAAGCASEQ ID
NO: 141
GAAGTCTTGAAGCAGCTCGCTGAGAAGCGGGAGCATGAAAAAGA
AGTGCTCCAGAAAGCCATTGAGGAGAACAACAACTTCAGCAAAAT
GGNAGAGGAGAAACTGACCCACAAAATGGAGGCTAACAAAGAGA
ACCGGGAGGCGCAAATGGCTGCCAAGCTGGAGCGTTTGCGAGA
GAAGGACAAGCACGTTGAAGAGGTGCGGAAGAACAAAGAATCCA
AAGACCCCGCGGACGAGACCGAGGCTGACTAAGTTGTTCCGAGA
ACTGACTTTCTCCCGACCCCTTCCTAAATATTCANAGACTGTACT
GGNGCAG
140
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCG.GCACGAGGCCAGAACATCAGCTCA
GGAGGACACGCTGAAACTCTCACTCTGGGCGAGTCCTGATAAAA
CAGGCTCCTAATACTGACCTACCTCAAGGGCAGTTCTGAGGTGA
TTAGAGCCTTTTCTTTTTTTAAGCAAGTGTTTGGAGATGCATGGCA
GAGGTTTTCCTGCAGACTTGTAAAGAGCTAGATGTGTTCTAAAGA
CCATCTTTAGTCTACATTGCTCTTCCCAGAGATCTACAACTATGAC
Stearyl-CoA J02585 CCAGCCAAAGTGCAAGCCTACCTACTCACTGCCATAAAAACTATT
SEQ ID N.O:
desaturase, CAGGAAACCTTTTCCTGGCCTGAATGAGATTTTCTTTTTTTTTTTTT142
liver
ATGTGGGGCGGTTATTTGTGACCCAAGTGTAATTTGGATGATTTT
TAATTAATATCAACTCTTGAAGCCTAATTGTACTGATTTGAGATTG
CATTTGTTCCTAATAAAAGTGGATCTAGCTGTGCTGCCAAANNAA
AAANNCNANCAAAAAAATTGGAAGCGGCCGCAAGCTTATTCCCTT
TAGNGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACCAA
CGTCGNGACTGGGAAAAACCCTGGGGGTTACCCAACTTAATCNC
CCTTGCCACGGGNNGGGGGGGNNNGGN
TNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCTTCTGCCCTTGAG
GTATCCAGGTACCATTGTGCACTGAGCAGGACTGAAAAGAACAA
AGTTTATTCTGGAACTAAACCTTCTTCCCTGAGACATCATGGCCC
TGGCCCCAGAATTGAGCAGACAGACAAAACTGAAAGAGGTCGCA
GGGATCCCACTGCGGGATTCAACTGTCGACAACTGGAGTCAGAT
TCAGACCTTCAAGGCGAAGCCAGATGACCTCCTCATCTGTACTTA
SulfotransferaseAJ238392 CCCTAAATCAGGGACAACATGGATTCAAGAAATTGTCAACATGATSEQ ID
NO:
K2 143
TGAGCAGAATGGGGATGTAGAGAAGTGCCAGAGAACCATCATTC
AACACCGACACCCTTTTATTGAGTGGGCTCGGCCACCCCAGCCT
TCAGGTGTGGACAAAGCCAATGCGATGCCAGCTCCAAGGATATT
AAGGACCCATCTTCCCACTCAGCTGCTGCCACCGTCTTTCTGGA
CAAACAACTGTAAGTACCTTTATGTGGGTCGAAACGCCAAAGACT
GCATGGTTTCCTTCTACCACTTCTACAGAATGTGCCAGGTGCTCC
CCAATCGANGCACCTGGAATGAGTATTTTGAAACCTTCATCAATG
GAAAAGTAAGTTGTGGATC
GNCNAAAANGGTTATAATGAAAGTAGTGAATAATGATAAAAAAGG
GTANAATTAATATTTTCATTGTCATNTATAATCANAGGCAGTTGGG
TATAGACTCTCNCNCANTTCATAGGNTATTTTTGNAAANTAAAAAA
GNNACAGGTTTTNACGNNNTGGAGCTGGTNNCACTTTCCAGAGC
ATGATTAGNCNAACTCCGTAATAGTGGCTTCGAGCTTTTCCTTGT
TAGCACCAGAGNACTCCCCAACCTTTTGACCCTTTANATANANCT
Thioredoxin-1X14878 GNAAGGTCGGCATGCATTTGCTCACAGTCNGCANCAACATCCTGSEQ ID NO:
(Tnc1 j 144
GCAGTCATCCACGTGGTACTTCAAGNAACACCACATTGGAATACN
TGTCACAGAGGGAATGAAAGAAGGGCTTGATCATTTTGCAAGGT
CCACACCACGTGGCAGAGAAGTCCACTACCACATAGCTTGTCTC
CCGCAGCGGCCANGGCGTCCTGAAAAGCTTCCNTGCTCTCGATC
AGCTTCNCCATTTTGGCTGTTGCGGGGAGGGAGCCNCACGAGTT
TCGGCAGAACCCGATGGAAATGG
TTTCCNCCNCNTAAAANGGAAAANANNTNNGGCCCGGNCCCCNN
TTGAATGGNTAANTTTNAGCNTCATTTTAAAAGTGTGAAAAANCNT
TGGAATTTATTATTNCAGTACAGCATAATNCAGAGTTCTAGTAACA
CAGTAAAAACNTAAATAGATTCNAATATANATATACTAGTGTCATT
TCATCGAATATTAAAATCATACAGTTCTCCCAGCCATCTGGAAAGT
TTATAAAGAAAAAGACATCTACACTGTGACAAAGGGATATGCCCC
Tissue plasminogen RAGAGTTGAGGATTGTGGGAGGATGGGGAATATTTGATTTCAAG
activator X924878 GGTTTTAGGGGGCTGTGGTCTGATCAGCTAACCCCTTCCTTCTCTSEQ ID NO:
145
TGGAGGCCATGCTGGGCCCCTGTGTAACTATAAAAACACATTCTT
GTCCTCAGTGCAGACTTTTACTCCTGAAAGATCAAGTTGTATTTCA
CTGTTGAGACACGATCTTGTGGTTCAGTGTACAAAATAGTGGTCC
AGGAAGGGTGGACTTTGGTCTACTTCTCTTTTTAAAATCTTAGAGT
TATAGGAAGGTTGGCACCTCGTGCCGAATTGTTGGCCTCGAGGG
CCAAATTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATA
NCNNNNNC
141
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTATGACATGATTACGAATTTAATACGACT'CACTATAGGGAATT
TGGCCGTCGAGGCCAAGAATTCGGCACGAGGGTGACCTGTGTAT
TGGCCCAGCAAAATGTGCTCCGAACAACAGAGAGGGATATAATG
GTTATACAGGGGCTTTCCAGTGCCTCGTTGAGAAGGGAGACGTA
GCCTTTGTGAAGCACCAGACTGTCCTGGAAAACACGAACGGAAA
GAACACTGCTGCATGGGCTAAGGATCTGAAGCAGGAAGACTTCC
AGCTGCTGTGCCCTGATGGTACCAAGAAGCCTGTAACCGAGTTC
Transferrin NM 017055GCCACCTGCCACCTGGCCCAAGCTCCAAACCATGTTGTGGTCTCSEO 1D
N O: i46
ACGAAAAGAGAAGGCAGCCCGGGTTAGCACTGTGCTGACTGCCC
AGAAGGATTTATTTTGGAAACGTGACAAGGACTGCACTGGCAATT
TCTGTTTGTTCCGGTCTTCCACCAAGGACCTTCTGTTCAGAGATG
AGACCAAGTGTTTGACTAAACTTCCAGAAGGTACCACATATGAAG
AGTACTTAGGAGCAGAGTACTTGCAAGCTGTTGGAAACATAAGGA
AGTGTTCAACCTCACGACTCCTAGAAGCCTGCACTTTCCACAAAA
GTTAAAATCCAAGAAGTGGGTGCCACTGTGGTGGAGGAGGATGC
CCCCGTGGATCCATGGGC
CNCAAAANNNANANNNTTNGGNAAACCCAGGGT'l~Tl'NCCNNNC
CCNNNTTTTNAAAACCNNNCCNNGGCCNAANTAAAANTNACCCC
CCCNAAAANNAAAAAANNTNNGNCCCCNNGGGGNTTTTTTTTTTT
TTTTTTTTCCCNTTTNNCCCCANNNTTNTTNNNCNT'f~TTCNANAAN
Transitional TTTTTTT'ITTTTTTTTTTTGGTTTAGAAACTGCTTATGATTAGTCTTC
SEO ID
endopfasmic A1059675 CAACAGTAACTCAAAAGCATGTAAAATAAAAATCAACCTACTTTCTNO:
reticuium
147
ATPase ATATAAACACCCAGCAAACTGAGGCCCCTTGTCCACCTACCCAG
GCTGGCTAGAGGTAAGGGAGGGCTTGGACAGCATTGAGTATAGA
TGCTTTACTGTGGTGATGGTGGGGGCAGCGCCTCGGTTCACACC
ACACAGGTTACCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAA
TTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCATANC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGGCCTCGAGGCCAAGAATTCGGCACGAGGAGCTACTCACATAT
AAGCAGACATGAGGACTCTTTTCTCACTCGGCCTCTGACTGCAGA
CATGGCTTCCTGCGTCTGTGTTGTGCGTTCGGAGCAATGGCCAT
TAATGACCTTTGACACGACCATGAGTGACAAAGTGAAGAAAATCA
ATGAGCATATTAGGTCCCAAACGAAGGTCTCTGTGCAGGACCAG
ATCCTTCTGCTAGACTCCAAGATCCTGAAGCCCCATAGAGCGTTG
TCATCTTATGGGATTGACAAGGAAAACACTATCCACCTCACCCTA
gEQID NO:
Ubiquitin NM 053299AAGGTGGTGAAGCCCAGTGATGAAGAGCTGCCCTTGTCTCTGGT
D (Ubd)
148
GGAGTCGGGCGACGAGGGGCAAAGGCACCTCCTTCGAGTTCGA
AGATCGAGCTCCGTGGCCCAGGTGAAGGAAATGATCGAGAATGT
GACCGCTGTGCCTCCCAAGAAGCAGATCGTGAATTGCAATGGAA
AGAGGCTGGAAGATGGAAAGATCATGGCCGACTACAACATCAAG
AGTGGTAGTTfGCTCTT'TCTCACAGCGCACTGCATTGGGGGGTG
AGTACGGGAGTGGGGTGGATGAGAACTCCAAAACCCGACTTCCT
TTAATCAATTACCAATTGCATCTCTTGATGATATAAAAAAATAATGA
N
AGAATACTCAAGTATGCATCAAGCTTGGTACGGAGTCGGATCCAC
TAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTCGCGGGATC
CCCACCCACCTTAGGACCCAP.TACCAGACTCTAGAAGTGGCTTC
CCCAAAATGATCTTCTTGGTCATCCAAAAACCAAAGCCTTTGTAA
CGCATGGTGGAGCGAATGGCATCTATGAGGCGATCCATCATGGA
ATCCCTATGATTGGCATTCCCTTATTTGGAGAGCAACATGATAAC
UDP- ATTGCCCACATGGTGGCCAAAGGAGCAGCTGTGGAAGTAAATT'f
gEQID NO:
glucuronosyltransferaY00156 CAGGACAATGTCAAAGTCAGATTtGCTCRRTGCACT'GGAGGAAGT
149
se CATAGACAATCCTTTfTATAAAAAGAATGCTATGTGGTfGTCAACC
ATTCACCATGACCAGGCTACGAAGCCACTGGACAGAGCTGTCTT
CTGGATTGAGTTTGTCATGCGCCACAAAGGGGCCAAGCACCTGA
GATCACTTGGACATAACCTTCCCTGGTACCAGTACCACTCTCTGG
ATGTGATTGGATTCCTACTTTCCTGTGTGGCAGTCACTGTAGTCC
TTGCAGCTTGGCCRAGGGCGAATTCTGCAGATATCCATCACACT
I GGCGGCCGCTCGAGCATGCATCTAGAGGGCCNATTCAC
142
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTTTGAAGATCAATC
TCACTGCAATGGGAAAGCCTATCTTGCTGCTCCCACTGGGCCTG
TCTTTGCTCATGAGCTCCCTGCTAGCT'I-fGCAGTGCTTCAGATGT
GAAAGCCTCGAI'TCTACAGGACTTTGTCGTGTTGGAAGACGTATA
TGTCAGACTTATCCTGATGAGATTTGTGCCTGGGTTGTAGTAACC
Urinary proteinAF198441 ACTCGAGATGGAAAATTTGTATATGGAAACCAGAGCTGTGCTGAGSEO ID
2 NO:
precursor TGCATCGGTACGACTGTTGAGCATGGAAGTCTTATAATATCAACA150
AACTGTTGCTCAGCCACCCCTTTCTGCAATATGGTACATCCCTGA
TACTTAATTGTATGGAAGGATTTTAGTGCTCTTTATTGAGTCTTGA
CAGTGGAGCATGCCAGAAAGAATAATCTACTGACCATGTCTGGA
CAACTCACTATGATTTCTACATCGTGTTTTCTGACTACATGTATAT
CATATGTTCTTGGGTGATCTGTAATAAATTGAAAGCCTTACATATT
TTAATTTGAACT
TATGACATGATTACGAATTTAATACGACTCP,CTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAAATAAGCAGAGAGTT
TTTATCTGCAGAAGTTAGCGTGGTGGAGCCTGCCTTACATCGGG
AGGGCTCTCACCAGGAAGGAAGATCCCCATTTCCAACCTGTACT
GATTTTTAAAACATTTCTCCCTGAAAGCAGTTTAGTCCACATTTTA
CACTGACATACTTTTGCTTTCTTTGTTAAGGTAAGGTCTCCACCCT
CGATTCAATCCACATTGTATTCCTTAGGGTGGATATGATGTTCTG
Vacuole membraneAF411216 CTGCAAACTTAACAAAACTGGCCTTCTGACACTTTCACAGGGCCASEO ID
NO:
protein 1 CATGGTCCAACTGGAGAACCTCGGCCACACAGAACCTTCTGACG151
TATGTTAAATATGCCAGGCTTTTCAGGCTTGTCACAAATGATTGGT
TTTTCTAAGTCACCAAATGTATATAAGTTATATATGTTGGATAGCA
GTCTTGCATGCCTATCATGGAACAATGTAATATGCCTTCCTTTCC
CACCCTCAAAAAGGCCATTTTATGATGCATTGCACACCCTCTGGG
GAAATTGATCTTTAAATTTTGAGACAGTATAAGGAAAATCTGGTTG
GTGTCTCACAAATGGAGTACGCCATTTTTTATTCTGTATATTTAGA
ATGAAGTCCGTGGAAAA
TCCTCATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTAGATTTTGTTG
AAGAAGTGAATGTTTACGGTGTGCCCGTGCCAGGTCATGAAGGT
CGCATCGGGATGGCCTCGATCAAGATGAAAGAAAACTACGAGTT
CAATGGAAAGAAACTCTTTCAGCACATCTCGGAGTACCTGCCCAG
TTACTCGAGGCCTCGGTTCCTGAGAATACAAGATACCATTGAGAT
CACCGGGACTTTTAAACACCGCAAAGTGACCCTGATGGAAGAGG
Very long-chainp85100 GCTTTAACCCCTCAGTCATCAAAGATACCTTGTATTTCATGGATGASEQ ID
acyl- NO:
CoA synthetase CACAGAAAAAACATACGTGCCCATGACTGAGGACATTTATAATGC152
CATAATTGATAAGACTCTGAAGCTCTGAATGTTGCCTGGCTCCTA
ACACTTCCAGAAAGAAACACAATAGGCCTAGCATAGCCCCTTCAC
ATGTGTAATCCAACTTTAACTTGATTAAAGGT1'ATAGGTGTGATTT
TTCCTAGGAAATTATTCATTTAAAGGACAATTGTTTGTTTGTTTGTT
TGGTTTTTATTAATTACACCAGAACGTTTGCAAGTAAAAAGATTTA
AAGTCACTTATT7-1-fCAATGTGCACCTGCCATTTGTCCTTGCAAAC
TTAACTTCTTGGAGAGAG
TCTTATGACATGATTACGAATTTAATACGACTGACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTGTTTTTTTTTTT
TTTCAGTCTCTCTGCATCTTCCTCTTCAGTGGACCTCTCTCCTCTA
GATTCCCTTCTTGTTTTCTCACCATCCCACGTGAGATGCTTGTTAG
TAACTGTTACAGATCTTCTTTACCACTGAGGAAAGACAGAATCCT
GCTAGAGGCCAGAAAGAATGTTCCAGACATGGATGGAAGGCTCC
TGACTGTTGACTTCAATGCCCCTGAAGGTAGGGAGTGCTCCAGG
VL30 elementM91235 TCTGCCCCCAGGCTCCGAGGGTGGGTCTCGTAGGGGCTGGAAASEQ ID
NO:
ATGCCCCACCAATCTGGCTAAGATAAGGAAAGGATATGAAGAGA153
AAGTTACAGAAACTTGAAGGGTAAAGCTA.4GTCACTGAGAGAGTT
ATTGTAAGTTGCAGAGAAAATAAGTTGATGCGTGGTTCAGGGTCT
GTGCAGAAAAGTGGACAGCACCTAATAGCTGTAGAAGAAGATGC
AGAGAGACTGAAAAAAAAAAGAAAGAAAGAAAGAAAGAAAGAAAG
AAAGACAGGAAAAAAAAAAAAA~4AAAACACATGCGGNCGCAAGCT
TATTCCCTTTAATGANGGTTAATTTTACTTGGCNCTGGNCGCGTTT
TTCAACGTCGTGACTGGG
143
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTCTCCTTCACTTCG
CCCTCCAGCCGCGGTGGCTGCAGCGCAACTTCCAGATAGGGGA
GTGGCCTCAGCTGCGAGCCGAGCGGTGGCGGCAGCGCCCCTCA
GGACACCCGCAGATCACCTI'TTCCCCGCGACTTCGCCATGGCTG
AATGTTGTGTACCGGTATGCCAACGGCCAATTTGTATCCCTCCAC
Voltage-dependent CCTATGCTGACCTTGGCAAAGCTGCCAGAGATATTT'fCAACAAAG
anion channelNM 031354GATTTGGTTTTGGGTTGGTARAGCTGGATGTGAAAACGAAGTCATSEQ ID
2 NO:
(Vdac2) GCAGTGGTGTGGAATTTTCAACATCTGGCTCATCTAATACAGACA154
CTGGTAAAGTCAGTGGGACCTTGGAGACCAAGTACRRATGGTGT
GAGTATGGTCTGACTTTCACAGAGAAATGGAACACTGACAACACT
CTGGGGACGGAGATTGCAATTGAAGACCAGATTTGTCAAGGTTT
GAAACTGACCTTTGACACCACGTTTTGACCAAACACAGGAAAGAA
AAGTGGTAAAATCAAGTCTGCTTACAAGANGGAATGTATAAACCT
TGGCTGTGATGTTGATTTTGATTTTGCTGGGACCTGCCATCCATG
GGTCACCCGTNTTTGG
NTACGGGGGGGGGGGGGGNG
_
AGGTGTGNAAATGACCGAGGAACTCAGATTTCTI'GAATTGACTAA
GACTTCACCAATGGGGTCAGAGGTAAACTTTGGTCGTGGGCGAA
AGTTCNTCCGAACTGTCTGAAGATTCGCTGCTGACATCAGAGTTCj
AGGGTATTGGTCTCTAAGTTATAATTAAAGCCGGAGCTGATCAGA
GAGTCCTCTGGGGGACTAGAAGAAATCTTCAGTTCTGATTCCTCC
TTCCTCTCCCGTGCTAGAATGATTTTGGTCCACAGGTCTTCCTGG
TTGTCAAATTTTATCTCAGAGGCTGACACGTAGCAGGGCTCACTC
Zinc finger AF001417 TGAAGATAGCGTTCCAACTCCAGGCAGGTCTGTTGCCAATATTGCSEO lD
protein NO:
TCCAGGGACGGCAGAGCCGAGAAGTAGCCCGTTTCGTGCACAAT155
CTGTAGTTCCTGGAAGATGCTACACATTGGGAGCACATCCATGTC
GGGTTGGAAAAGACAGTCCCCGCTGTCGGGAAAACAGGGAGGT
GAACGATCAGGAGTCGGAGCAGAAACTGTTCCCGGGAGCGCAG
GTGAAAGTTTGATGCAAACTGGATGGCGCTGCAATCGGACGCCG
GGTCCGGACCCTCCCGCAGCCCGCAGCGCGCCGAGCCCACGCA
ATATTTGCCTCGTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCC
TATAGTGAGTCGTATTAAATTCGTAATCATGTCATANNNNG
Genes Discovered
by Empirical
Data that
do not match
fihe sequence
of a known
gene
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTCACACGTCACTT
TCCAATTCTGCGCCCACTCCAGGGCTGGCTCCTCCCCCTTCACC
CTCCAGGGCTGGCTCCTCCCCCTTCACATTCCAGGGCTGGCTCC
TCCCCCTTCACACTCCAGGGCTGGCTCCTCCCCCTTCACACTCC
AGGGCTGGCTCTTCCCTCTTCACTGCTTTGTGACTCTGGTTTTTA
TTTCTGAATAAAAAAAAAAAAAAAATCCCGTGTGCCATTCCCACTC
Phase-1 RCT-002 TCCCAGTGTTGCTATTGTGTGGAATGAGGTCACAGGAGGACGAGSEQ (D
NO:
TCCTCCACAATAAAAACCTCTGTTTTCCTTT 156
AAAAAAAAAATGGAAGCGGCCGCAAGCTTAT1'CCCTTTAGTGAGG
GTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGAC
TGGGAAAACCCTGGCGTTACCCAACTTAATGGCCTTGCAGCACAT
CCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCG
ATCGCCCTTCCCAACAGTTGCGCACCTGAATGGCGAATGGGACC
CGCCCTGTANCGGCGCAT-('AACGCGGCGGGTGTGGNGGNTACN
CCACGTGACCGCTACACTTGC
144
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
NNNNNNNTCTATGACATGATTACGAATTTAATACGACTCACTATA
GGGAAT'i-fGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCCGC
TATATTGGTGACTCCAAGATCCTGCGCTGGGAGGGTACCCGTTT
CTCAGAGGTGCAAGCCCTTCCCTCCCGAGGTTCACTGGCCCTAC
AGCCCTTCCTGGTGGGCGGTCACCGCTACCTGGCACTGGGCAG
TGACTTCTCCTTCACCCAGATCTACCAGTGGGATGAGGGGCGAC
AGAAATTTGTACGGTTCCAAGAACTGGCAGTACAGGCCCCTCGGSEO10 NO:
Phase-1 RGT-003 GCCTTCTGCTACATGCCTGCTGGAGATGCCCAGCTGCTCCTGGC
. 157
CCCCAGTTTCAAGGGACAAACACTGGTTTACCGACATGTTGTGGT
GGACCTTAGTGCCTAGAGGGAGGCTAAGTCCTTTGGGTTCCTCA
GGGTGGTACTGTATGATGGTGAAGACCTCTGTGAGCAACTTGTG
GCCCCAAATGAGGTCACATGTGGCTAACCTGTCTATGTAAGACAC
ACACACATGTACACAGAAGTGGGCCTGGGCACACTCCAGAGAGT
AGCCCAGGGGAGCCATTCCATTACTGTAGTCAGCACCTACATAT
GCGCCAGGCACCCAACATCCAG
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTGCTAGCCCTAGAG
AGCAGTGCTCACTTCAGACCAACCAGCCTCCGGTGCTTCTCGCC
CGAGCAAGAAAGTTTTCAGCGAGGARAGTAAGTTTCCATCTGTCC
AGCCATGGGAGAGGACGCTGCACAGGCAGAAAAGTTCCAGCAC
CCAAATACAGACATGCTCCAGGAGAAGCCATCCAACCCCAGTCC
AATGCCTTCCTCCACACCGAGCCCCAGCCTGAATCTGGGGTCCA
GAGAGGAGGCCATCCGAGACAACTCACAGGTGAATGCTGTCACC
Phase-1 RCT-006 GTGCACACTCTCCTGGATAAATTGGTCAACATGCTGGACGCCGTSEO ID
NO:
GAGGGAGAACCAGCACAACATGGAGCAGCGGCAGATCAACCTG158
GAGGGCTCGGTGAAGGGCATCCAGAATGACCTCACCAAGCTCTC
CAAGTACCAGGCCTCCACCAGCAACACAGTGAGCAAGCTTGCTG
NAGAAGTNCTCGCAAGGTCAGCGCTCACACGCGTGCTGTTCGGG
AGCGCCTAGANAAGCAGTGTGTACAGGTGAAGAAGCTGGAGAAC
AACCANGCTCAACTCCTCCGANGCAACCACTTCAAAGTGCTCATC
TTCCAGGAAGAAAGTGAGATCCCTGCCAGTGTGGTTTGTGAAGG
AGCCNGTCCCAGCACNTGCNNAAAGCNRGGACTTGCTTGATGAA
AACNAGNCCTTGGGAGGAAACTNT
NNGCTAGNCTAGGNCTATCAAGGATTCGANTCAAATACGACTCAC
TATANGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGA
GCTTGACATGGGTGTGGCTGTGCCAAAAATCCTTCAGGCCTTCA
AGCC'fTATGTTGATCACCAAGGACTCTGGATCGATTTGGAAATGT
CTTACAATGGGTCCTTTCTGATGACTCTCGAGACCAAAATGAACT
TGACCAAACTAGGTAAAGAGCCTCTTGTTGAAGCCCTGAAGGTTG
GAGAAATTGGCAAAGAAGGTT'GCAGGCCCAGGGCATACTGTTTG
GGTGACAGTGATGAAGAATCCTCCAGTGCCGGTTCCTCTGAGGASEQID NO:
Phase-1 RCT-007 AGATGATCCACGAGAACCCAGCGCTGGAGACAAACAGCCACTCC
159
CTGGGGCTGAANGGTATGTTGGAGGTCATCNAACAAGTAAGATT
ATGAGGTTTGTTGATAAGATCAGCAAATCGAAATATTTCCAAAAG
GCGACAGAGACAGAATTCATTAAAAAGAAGATGGAGGAAGTCTCT
AATACCGACTGCTGCTAACTGTGGAANTGCANGAGTGTCGCGGG
ACTTGGCGGTCAACATTCCTCCGGCCGCNACTGACCGGATGTGG
TATGGTTTNCCGNAAGCCACCATATGTGGGAGCTGAAAACTCGG
CCAAAAC'iTGGTGAGAGAAAAAGTAACTTTNTTTTCCCNTTGGAC
AAANNTGGATATAP,AAAAAAACTGG
CTAANNCTAANNTTTTNACATGATTACGAATTTAATACGACTCACT
ATAGGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGA
GAGTATGGATTCCAAAACGCCGTTCTGGTTCGATACACCCAGAAA
GCACCTCATGTGTCGACCCCAACTCTCGTGGAGGCAGCAAGAAA
CCTGGGAAGAGTGGGCACCAAGTGTTGTACCCTTCCTGAAGCTC
AGAGACTGCCCTGTGTGNGAAGACTATCTGTCTGCCATCCTGAA
CCGTCTGTGTGTGCTGCATGAGAAGACCCCAGTGAGCGANAAGG
Phase-1 RCT-008 TCACCAAGTGCTGTATTGGGTCCCTGGTGGAAAGACNGCCATGTSEQ ID
NO:
TTCTCTGCTCTGACAGTTGACGAGACATATGTCCCCAAAGAGTTT160
AAAGCTGAGACCTTCACCTTCCACTCTGATATCTGCACACTCCCA
GACAAGGAGAAGCAGATAAAGAANCAAACNGCTCTCGCTGAGCT
GGTGAAACACAAGCCCNAGGGCCCAGAAGATCANCTGAANACG
GTGGATGGGTGACTTCGCAAAATTCGTGGACAAGTGGTTCCAAG
GCTGTCNACAAAGGATAACTGCTTCGCCCCTGAGGGGCCAAACC
TTTGTTGCTAGAANCNAAAAANCCTTAACCTTAAACACATCACAAC
CATCTCAGGNTACCCTNGAGAAAAAAAANACCTTGANTAN
145
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCGCCCTGAATGCC
CTCCTCTTCTACCGTCTCTGGTCTCTGGAGAGAACAGCCCATACC
TTTGAGTCCTGGCACAGCCTGGCACTGGCCAAGGGCAAGTTCCC
CCAGACAGCCACGGAGTGGGCCGAGATCTTGGCTGTGCAGAAG
CATTTCCACAGCGTTGAGGTGCACAAGTGGAGGCAGATCCTTCG
CGCATCCGTGGAGCTCCTGGATGAGATGAAGTTCTCCTTGGAGA
Phase-1 RCT-009 AGCTAGATCAAGGAATCAGTGTGCCAGATCCTCCGGTGGACACTSEO 1D
NO:
CAGCCACATCCCGATGACAGTTTTCCCTGAGGACTCCTGATTGAA161
AAGCCACTCCCCTGAACGGACAGAAGGACACACGGAACCCTGG
CAGCCACTGCTGGCACGGTGTAAACGGGGCCGGGAGGTTCCTG
CCTGCCCCTCACAGTGGCCCCGCCAAGAGCCACACAGACCTGG
GGACCATAGAACCAAGATGCACTTTAGATCTGTGTGTGCCTGTAC
CGGTCCAGCTGCCACTGCCTGCTCAGCGAGGGAGCTGGCCTGG
TCTTTGGCANGCTCCCCTCCAACTAACTTATTTTGCGCAGCTGGG
GTTGTGGGGGACACCTTTTTGGGGTGC
TCTCTANNACATGATTACGAATTTAATACGACTGACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCAGGATAACACC
AACGCCAGGCCTTCACTi'GTTCTCCATACTTCTCTACGGTTTTTG
AGGTTAACTGTTGTTAAGTGTGAAGTGTTTGCGTAGAATAAGAGC
TTAGAAGTGTCTTCTAACAATTCTTTTCTGATGACTTGGAGGGACA
ACGTAGGGGCAGATCTTGCAATCACTGAAACTGTTCATCCTCTGA
GGCTCAATTATAGCCCTCGACCAGTGCCCAGAGTATCAAACATGT
Phase-1 RCT-010 AACCTAGTTTTACTTATCCCAGCATGGTGATGACTGCTTTTCTGCTSEQ ID
NO:
CAATACCACTTTCTTCATGGCCACTATTTAATTCTATCCATTTCTT162
GCTTCTTAAAATACTTGTCAAGGTACCTCAGGATGAAGTGATAAG
TTAGCTTTTTGTTACATGTGCCATTCTTCATGGTTTGCCTCAACAA
TCATTAAACCAATACTCTAGCCATTAATTCAGATACAAATAAATCC
TTAGACAAAATATTTCACAAATGGTTTTTGACCCAGAAATCAAAGG
ATCTCCAATCCTGAAAGTGAATAGACTCTTGCCTTAAGTAGCCTT
ACCTATTATTTGCAAAATATGTTATTCTTTCTTTTGACAGCATTTCT
C
CNTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGAATTCAGGTC
AGCTCAATGATAAGTCTTCGACTTGCCCGAATGTTAGTGCTGCAT
TGCTAGCTCTTAAGAGATGCAATGACACTTACTGGCTCATTGTTG
TCAAGTTGGATGCGGTAGCGGGAGATGAAGGTGGGTTTTCCTGT
Phase-1 RCT-012 TCTGTCGACCATCAGTAGAAGGCCATTGAAGCCCGAGAAGCACASEQ !D
NO:
GCCCCGGCACGAGGACAACACCTGAGGCAGAGAGCAAAGGGAC163
TTAGAGCAGCCCCAGGTACCACAGTGGCTCACCAGGAAGGAAAA
TGAACAGGCACATGGATCTGTCTCCTGTCTGGTGACTGACTGTTC
AAGTCCTAGCTATGGAACCTGAACAAGTCAGTAAGTGTCTGTATT
TGTTCTGTCTTGTCTGTCTCTGTCCCCTTTGCACCGTGTGTGTGT
GTGTGTGTGTGTGTGTGT
TCNTGACATGATTACGAATTTAATACGACTCACTATAGGGAATfT'G
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGTGGCCATGCATG
CTGCTGGCATCACTTGTACAGACCAGAATGGAGTTTTTAATATCA
TTGAGTTTGGTTTfACTATGGAATCCATTCTTGCTAATATTAAGCA
AACTAAAGAGTGGTATGATACCATTTTTGTAAATGATCGGGATGC
AGAAATGCTGAGCACAGACTCCTGAGGACTGGAAAGGGTGTATT
CTAGTTCACAACTTTAAGGGAATTGCCTAAGGTGTTTTTCTTCAGA
Phase-1 RCT-013 TAATAATGTTTTATGAACTTTCAAAATGATTAATTTGACCCAATAATSEGt 1D
NO:
CATAGTTCTAGAGTGTATCTTAACTATCAAGCATTTTCATGGTTi'A164
TTAAAACAAACAATCAAAAACAAAACTATCAATTGAACTATTTGTG
TAAAGTAGCATGAAAAAGAGGATTAAGTGCTGATGTGGGATCCGA
GGGTCAGGAGATGCTAAGATGTGAAAAAGTTGAGAGCATAAACT
GGAGTTATTAGCCAGAAGATTCATGGAAAAGAAAGAAGCCTACCA
CGTTCCTTGAAACTTAAACCAATTTCAAACTCACTCATTTGGTTGT
ACCCATATCTTCCTTCTCTGCTGACCAGAGCTCACCAGGACACTG
AATCC
146
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CNNNCTNNNTCTATGACATGATTACGAATTTAATACGACTCACTAT
AGGGAATTTGGCGCTCGAGGCCAAGAATTCGGCACGAGGAT1'AG
GCACGCCCCGGAGTGGGCAAAGACCTGGCACGAAGGCACTCTT
GCACATGCGCACACAGTTAACTTCCTGAAAGGAAGTCGGCTGGC
GCGGCGGAGGCCAGCGCCATCTTGTAATGGCAAAAGCTATCCCG
GCTTTCCACGTGGGGCACAGTGGAAGCCAGCGCCATCTTGTGGT
GGTGAATGTTATTGCGGCTCTCCACAGGTCCTTACTTGGGTTTAA
AAATCATTTATGTATGTGCTGGTGTGTATTGTGTATATGCCACAGCSEQID NO:
-
'
Phase-1 RCT-014 CCAAGTGTTAAAAGAAGAGAAAAAT 165
f
fGTAGGAATAAGATGGGCA
TTTCAGGGATTGAACTCAGATTATTAGGTTTAGCAACAACCAACTT
TACCTACGGAGATAATTCTCTGGCATTCATT1'GTAGTTCTGAGAAA
GTGTTATGAGCAAATGTTTACTCAGAATAAATTAACAAATTAAAAA
AAAAACAGTAGTCTGGGTTCGGTCCCCAGCTCCAAAAAAAAAAAA
ARAAAAAAAAACAATTGCGGCCGCAAGCTTATTCCCTTTAAGGGA
GGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTG
ACTGGGAAAACCTGGCGTTACCCAAGTTAATCCCCTTGCAGCAGA
TC
AGGTCTTATGANNTGATTACGAATTTAATACGACTCACTATATGGA
ATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGACACTTGC
TTTGAGTTTGGTGTTTTCCCCGCCATCCTGAGTTTCCCACTTGAC
TACCCTTTGAGCCCTCCGAAAATGAGATTCACCTGTGAGATGTTC
CATCCCAACATCTACCCTGACGGAAGAGTGTGCATCTCCATCCTG
CATGCCCCAGGGGACGACCCCATGGGCTATGAGAGCAGTGCCG
AGCGGTGGAGCCCAGTGCAGAGTGTGGAGAAGATCCTGCTTTCG
GTGGTGAGCATGCTGGCAGAGCCCAATGATGAGAGTGGAGCAAAgEQID NO:
'
Phase-1 RCT-015 CGTAGACGCTTCCAAGATGTGGCGGGACGACCGTGAGCAGTI
CT
166
ACAAGATTGCCAAGCAGATCGTACAGAAGTCTCTGGGGCTCTGA
NGCTACAGCCGTGTGCACACTGAGCAGTCCAGTGCTGTCCTGAA
GACCACGTGGCGACATGCTGCCATGCCAACACCAACACAGGCAG
CTGCAGAGCCTCGGCCCCCATTGTTTCTTCCTTTNCACCCCAGAC
AGGCAGCTCCCCTGAGATCATGACTGGGATAATGACAGCTACTG
CACTGCAAAANAATCCTCCTGCTGCGCCTCAGGGANGGTCCAGG
CTGTCCTCACTACCTCTCCAANCATGGGGCCTCANTCTGCTTCTT
CTGANGACATGGG
CNAGCNNCGNNACNTCTCNNAGTGATTCNTCNATAATACGACTCA
CTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCNGCNNNAGGT
AAGATATCANAAAGAATCTTTTGAAGAAACAAGNGGAAACAGGGG
ACNGCANATGGTCNGANGANAATCACGCCTCTTNGNGTAGCACA
GCTGGACACTGGGGACTTCTCCACGGCATTCTTCAACTAGCATC
CCGCTCTGNANCTCCCTCGNAGGCACTATGCTCTCCTCTCCTAGT
GGTCAGCANCTACTGCCACTGGACTCCAGNACCCCTTCCTTCNG
CNCCTCARAGCCCTNGCANAGAACCAGTGGNAGCCACCTANTGN
CAGGCCTACAGGCGAGCCCTGNTCNNNAAGGACAGCTATGAATGgEQID NO;
Phase-1 RGT-017 CTACCTCTACTCCTGCTGCATTGTCAGCCTCCGTGTTAAACAACC
167
CCCATTCCNAGNATTGNAACCCCNTGAAAAGCGTTTTGATTCCCG
GGTTCACAGGAGCGGTTCCAAAGCCNCCCCCNAGCGTNANATGC
TGNCTCCTGCCCACTGAAAGGGTGGCTGNGTNTGCTTTCAAGTA
NTAACNGAATGCACCCAATTTGCGGAGAGCCACCGTACCCTTGG
GNATNCCT'fNAGGGGNATNATT'GCAAGTCCTGCANANTGGCACC
CCNAACNCCCCTNTGNTAAAANNCAAAP,NCC'i'TTi~CTTGCANNC
NTGGGACTATTTTTTT'GNAACTAAAAATTTTTNCTNAANNTCGGGA
AATATNNGNAGTTTTNTTATTGGGGCCGAATCACGGNANNTCCNT
NATAAAGCCT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATfTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGRAGTTATACGCCCTG
GGAATGGCTGCCCCAAAACTGAAATCATTTTCTGGACCAAGGCC
AAGAAAGCTATATGTGTGAATCCTACTGCCAGATGGTTACCAAAA
GTATTAAAATTTGTCCGAAGCAGAAGTATTACTTCAACTCCCCAA
GCTCCAGTGAGTAAGAAAAGAGCTGCCTGAAGCCACTGTCACCC
CAAAAGAACCTGCACCCTTTCTTAATCCCTGCTCGGAATCTTAGT
GTTACGTTCTTAG'1-fGAAGAATTTCCAAGAAAATAACTTCCCTCTAgEQID NO:
Phase-1 RCT-018 CAAACACGGCTGTAGATTAAAAGAAAAAAATCCTGCAGTAGCTGA
168
GAGGAGACACTCGAGCTCCTTCCCATACTCAACCCATATTCTTGT
TCCTTAAGGGAGGATATTTTGGAGCAGGCATTTAGTGACAAGCCA
CTTTGGTAATAGACCTGTTGTTTAGTGTTAAACTATCCTAGACCTA
GAGGAATAAAAGCATACATGTCGAATCTGAACCATAGCTCCTACT
AACAAGAGGTTTATGAGATGGACTTCAGTTAGTTTGCACCCTTGC
AAAAATCAGGCTTCCAGAATAGTTTCCAGAAAGTCCCTAAGAAGC
AGACGCATTACCAGGCTAAGGNGANGCAGAGCAGGTCTCCNTTA
GAGAGAATCTTCTGGAGGGAAATAATGNTTN
147
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TNCTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTTTCAAGGAAG
GTAAGGTTTATTATTTTGGCTCACGGTTCCAGAGGATACAATCTAT
AATGGCTGAGGAGGCAGCAGTGGAAGTATGGGACAGAGGTAATT
CATACATCCTGACTGGATAAGACCAGCAGGAGTATATAATCCTCA
CCCATCGATATCCTTAAGGTTTCACAGCCTTCAAAATAGAGCCTT
AAGTTGAAAGACCAACAGCTCAAAACAAGCCTCCAGGTACATTTC
Phase-1 RCT-020 AGATTCAAGCCTCAACACACACCTTAATATATTTCAACGAAGCTACSEO ID
NO:
ACATTCACAATTTAAATACAGTTTTTCATCAGGGAGACAGATATAA169
TTCATAAGAGTGTTTAGACTACAAATCAGATACAATTTAGTCAAAA
TACCATAAAGAGTACTTTAAGTAATCAGGAAAGAGATTTTAACATT
ATTGCTTACTCTTATGAATTTT'AACCAAATTGATAATTCTATAATCT
TAGTTTATTTTCTATAGACTTAAATTATACTGCTTGCCAAGTAATG
CAAGTATTGATGCAACTTTCTGAAATTAATTGAACTGCAAACCAAA
TTATTAAACTTAGCCAGCCACACACATTTTGACTCCCACTGCTTCA
GAAGTAGTACCTATAAAAAGTAACCCACTGTAN
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGTCGGGCTACATGT
GGGAAATTTGCCCTAACTACCGAGTCAGGAGTGATTGGCTCTGA
GTAAGGCCCAGAAGCTCCCTTGGGTCCCAAACCCCAGGCACTGG
CTGCCTCTTGGTCCTGCTGACTCTTCTCTCCTAACCCCAGCCACT
TAATTTTCTCTGTTGTTCCCTCGAACACACGGAAGCTGTTGATGA
ATCCTTTTCTTTGCTGTGCCAAGGCAGGTCAGAAGCAGATCAATG
Phase-1 RCT-022 GATAAGGGCAAGGTGTCCCGAGGAGCCAGCTGTCCTTCCTCCCTSEO ID NO:
CTTTAGACCTCCACAGGGACAGACCTGATTTATTTATTTTGGTTTA170
CNTTGCGGCCGCAAGCTTATTC
CCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTA
CAACGTCGTGACTGGGAAACCCTGGCGTTACCCAACTTAATCGC
CTTGCACACATCCCCCTTTCGCCAGCTGGCGTAATAACCGAAAAA
GCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAACCTGAATGG
CGAAATGGGACGCGCCC'fGTACGGCCATTAANCCCGGCGGNTG
TGGTGGTTTNCCCCCACCNGTGAC
GTTAGNTTTNANATGATTACGAATTTAATACGACTCACTATATGGG
AATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGATATTG
AGCGCCCCACCTATACCAACCTCAATCGCCTCATCAGCCAGATT
GTCTCCTCCATCACGGCCTCTCTCCGCTTTGATGGAGCCCTCAA
CGTGGACCTCACAGAGTTCCAGACCAACCTGGTACCCTACCCCC
GAATCCACTTCCCGCTGGTCACTTACGCACCCATCGTCTCTGCC
GAGAAAGCCTACCACGAGCAGCTGTCTGTGGCAGAGATAACCAG
CTCTTGCTTCGAGCCCAACAGCCAGATGGTGAAATGTGACCCAC
SEQID NO:
Phase-1 RCT-024 GTGACGGCAAATACATGGCCTGCTGCATGCTCTACCGTGGTGAT
171
GTGGTACCCAAGGATGTGAATGTCGCCATTGCTGCCATCAAGAC
CAAGAGAACTATTCAGTTTGTTGAGTGGTGTCCCACAGGCTTCAA
GGTGGGCATTAACTACCAGCCACCTACTGTCGTGCCAGGAGGAG
ACCTGGCCAAAGTCCAGCGAGCAGTATGCATGCTGAGCAACACC
ACAGCAATCGCAGAGGCCTGGGCCCGCCTTTGACCATAAGTTCG
ACCTCATGTATGCCAAACGGGCCTTTGTACATTGGTATGTTTGGA
GANGGAATGGAAAAAAGGAGAATTTTCTGANGCCAGGGAGGACT
GGCTGCTTCTGGANAAAG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCTGCGCTCTGATAGC
TGCACAGAAGCTCTTTGGCACCACACTTACTTTAGTGTGCTGATT
AAAGTTAACAGAGAAAATGGTTTTCATTTACTTGGTGAACAAAGTA
ATGTAATTTT1-ACATTATTTATCTGTATGAAATTCTAGCAGTTAATT
TGAACGTTTATGTATAGGATGTTTGTATTTTTAGGTCTTTACTACG
GTGTTTCTACCTCTCATTTGTAACTGCATTATCTTCAAACCAGGTA
SEQID NO:
Phase-1 RCT-025 AAACCCACTGAGTCGTTGTGGAATAGTCTTTTTAAATTGCTTGTAC
172
AAATGTATATCAAGGTTAAATAAAGCTGACAGTGTTTTTAGGGTAC
CAAAAAAC NAAACCCAANAAAAAAAANAAAAA
AAGTGAGCGGCCGCAAGCTTATTCCCTTTAGNGAGGGTTAATTTT
AGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAA
CCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTT
CGCCAGNTGGCGTAATAACGAAGAGGCCCGCACCGATCGCCCC
TTCCCAACAGTTGCGCAGCC
148
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCATCAAGCAAGGA
TCCAACCTGGGAGGACCGATTCCCAGACCGATCCACAATGACTG
TGCTGGTACCCACGGCCTTTGAATGGTTCGAGGAGTGGCAGGAG
GAGCCTAAGGGCAAGCGAGGTGTTGACTATGAGACCCTCAAAAA
TACCTTCCTGGAAGCCTCTATGTCGGTGATCATGAAACTGTTCGC
ACAGCTGGAAGGCAAGGTGGAGAGTGTGACTGGAGGATCCCCA
Phase-1 RCT-027 CTGACCAACCAGTACTATCTGGCTGCACACCGAGGAGCTACTTATSEQ ID
NO:
GGGGCTGACCATGACCTGGCTCGTCTGCATCCTCATGCAATGGC173
TTCCCTAAGAGCCCAAACCCCCATCCCCAACCTCTACCTGACAG
GCCAAGATATCTTCACCTGTGGGCTGATGGGGGCCCTGCAAGGG
GCCCTGCTGTGCAGCAGTGCCATCCTGAAACGGAACCTGTACTC
AGATCTGCAGGCTCTTGGCTCAAAGGTCAGGGCACAAAAGAAGA
AGAAGTAGTCTATTCAGAGATGAGCTAGAGGAACAGCGCCTGCC
CAGCTTTTCATGGTGTCCTCCTACGTAATTNCTTGCACATAGAAA
CNAAAACCATTTTGNTTCTC
CNNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGAATTCAGCCTCG
CGGACGGCTGTCATTTCATTTTGAAGTTCCTTTTGTTTGAAGTTGA
CCTGAAATCTTTATCACAGTAATAAACTCTTTAATCGGTTTTTTAAT
ATTATAACTGATTCCCTTTGTTTACAG'T-T'ACTCTATATGGCATTGT
GCAATGTTTCATTGACTCCTTGTTTATTGTTCCTGTTTTCTATTCTT
TGGAATCCT'T-rCTTGGTGACAGAATT1TGTAAAATTGTATACTACC
Phase-1 RCT-028 TTCGAGGACCCCCATTGTCAGAAGTTCTATTTTCCAGAGTCAGGGSEQID NO
:
CACTTGTTAGTCACCGAGACCCAGCATTTCANCAGTTTGCAGAAG
174
AAGTGATTTGAATGGACAGCTGCAAGTGAGACAGCCTAGACCTG
AAGAGATGAAACACTCACTTCACTTGGAGGAAAGAAGGAAGCAA
GCCTAGGGCTTAACAGACGTATCTGCAGTACGTCCAGCCCTCCC
AGAGCCTGGCCCCANCCATTGGACGCCCTCGGCTTTCATTGCCT
TGGACAGCGGATGTACCAGGNCTGGCCCAGCGGGATCCTGCNA
AGGCTGAACATGAAGAGCTATGAAGAGTACCAGTTGGNGATANA
TGGGGGAACCCCNGGGCGNAGNTTGGGTTTCGATGTCACAAGAA
ATGGTNCAGANAATGGAGGANCATTCCGATTCTGGCTTACTGG
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCGAT'TCT1TTAC
ACAATCTGGGTTCATGATAGGGTATACACCTGTCACCAGCACGAC
CCGACAGATAATGGAGAAGGTAGCTGCTGTCCCTTTCATGGCAG
Gi'AGAAAAGTCCTGGGACTGTTGGATGAAGAAAACATCAGGGAA
TTAACAGAAAGTCATCAGGAAGTAATAAGAGTCATTTTCTCTGATA
CGTTCTCATATCATCTGAAATTfCAATTTGGACAGAGAATCCCAAA
Phase-1 RCT-029 SEQ D NO
GTCAAGGGAACATGGAGATCATGAAGGTAGTTCTCCAGATACAC:
AGTCCCACTATTCTCTATTCCAATGGTGTTGACCCATTCATAAGG
ATGGATGTTATTATATCAAATTAGAGAACTTCTARRAA~fGTCTATT
CATGTTGAAATGTAACATATTCCATGTATGATTTCTCCACATGGCT
AGATGTATATATGCTAGATATGTGTCTATTTGCAAATGTATTTGTG
TATATACATTTAAATACAAAGTGGTATTTGi'AATACAGAACTGTAA
AATGTGTATGTATTTACAAATGTATATGTGTATGTACACTTACCAA
AACAAATAGTGGTGGTTGTAGTATGTAATNGNAA
TCTATGACATGATTACGAATTTAATACGACTCAGTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTAGACGTTGCCA
AGGGCATGGAGTACCTGCACAGCTTGACCCAGCCAATCATACAC
CGCGACCTGAACAGCCACAATATTCTGCTCTATGAGGATGGCCA
TGCTGTGGTGGCAGATTTTGGAGAATCAAGATTTCTGCAGTCCCT
GGATGAAGACAACATGACAAAGCAGCCAGGGAACCTGCGCTGGA
TGGCCCCTGAGGTGTTCACACAGTGCACGAGATACACCATCAAG
Phase-1 RCT-030 GCTGATGTCTTCAGTTACTCCCTGTGTCTGTGGGAGCTCCTCACTSEQ ID
NO:
GGAGAAATTCCATTCGGTCATCTCAAGCCAGCCGCTGCAGCAGC176
AGATATGGCGTATCACCACATCAGACCGCCCATCGGCTATTCCAT
CCCCAAGCCCATCTCATCCCTGCTGATACGGGGCTGGAATGCAT
GTCCTGAAGGACGACCAGAGTTCTCTGAAGTCGTTAGCAAACTG
GAGGAGTGCCTATGCAATGTGGAGCTCATGTCTCCAGCATCAAG
TAACAGCAGTGGCTCTCTGTCACCTTCCTCTTCTTCCGATTGCCT
GCTGAACCGGGGAGGGCCTGGCGGGAGCCACGTGGCAGCCTTA
CNGA
149
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATNACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGRATTCGGCACGAGGGAACGTTGTCTTCA
CATGTTTTTACAGGATGAAATCATAGATAAAAGCTATACTCCATCT
AAAATAAGACATGCCTGAGTTTGGCAAGAAGAGGCAAACCCCAA
GACCATGAATGATTCGTCCGTACCAATGAAGACGTTGTAACTAAC
TTAGCATGCTGCAGACACTGCTGTAACAAACGCGCACGCCCTGG
ATGTACTAACACTCACGCTCCCTTTCATTCTGTCTGTTTGGCAAG
Phase-1 RCT-031 ACGTTCATTTGCTTTAGTGGAAACTCCCTCACTTGTCGAGCCTTTCSEQ ID
NO:
TAAGTAGCCCTTCCCACCGTGTCCCTCCGTGTGCACTGTAGCCT177
CAGCCCTGTAGACCTGCAGTGTTCTGACTAAAGCTGCCGACTTG
CTCGAATTTGCAGTTTCTGTGTCGTGTGCTT'CTTGAATCTGATTGA
CTAGGATATTTCTCCCCACCCTGATGTGTGATGTCACCACTTGGT
CCTAATTTATGTGCAGGAGCACGACACCATTTGTCTCCAGTGCCA
CACATACGAGGTGTACTTTGTGTGCAGAATGTGTCTTCCTTCTGG
CCTGTAATCCCCTTCACATGAGAGATTAATGAGGGAAATCTTTAT
ATTCTGTATAAA
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTCCCTCTTTTGT
CCCAGTTACCGACTGAAGAAGTAGCACCTGCTGGTGCTCAGTGA
TTAGGAAAGAAACCTGGGTACATCTGGGATTCTGTCAGATAAAAG
AACTTGGAGAGTTTTTAAACTCCTTCACATCTAATTTCCCCAGGAA
AGGGGTCACAGTTCCATGATGGTGGTGGGAGATCAGGAAGAGA
GCTTGGCCAAATTTAAGAAACACCAGGCAGCCCTGCCCTCCATT
SECtID NO:
Phase-1 RCT-032 CTTGGAAGACAGGGATTGTGGTGAGCCCCTTCAATGCTTCCCTA
178
GAATTTACAGGAAAATCTTAAAATCCAAGGCCAGGAGAGAAGAAT
CCAAAAAAGCAATATTTTTCATCATATGCCAAAAATGGGATAGAGA
GAAGGAGTGGCAGGCCTAGGCCCCTCCGATTGTCCCTTGGGGTT
TACCCCTTAGCCCACCTCAATATGGTGCTGGGTAGAGGGGTAGC
TGGGTTCTAACCTTAAACAGGGAAGACTCCAGCCTCTATACAGAG
ACCCTTTAATTT1-TTTATTCTGATTAGCCATTTTTAACCAACAAAGA
ATAAAATAAATCCTGATCT TCT
TTCCNAGGCATGATTACCAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGAAAATCCAGG
GACAATCAAAGTGGGAGACCCTGTGTACCTTCTGAGCTAGTGAT
GGGAACTGTGCGTTCCGGAACAACAGATGTCTCTTP,AAAAAAAAA
AAAAGTT1-fAAAAACTGACACCGCTGGAAATCGTTCTTCAGCCTA
TTCTTTGGATCTGTGGGTTCCAAGTTTCTCCTCTTTCAGATi-fCCT
TCTGTTTCAGTGTTTGCTGGGGCCAGGACGGAAAGCAGGGAAAT
SEQID NO:
Phase-1 RCT-033 ACGGTCTGGCGAATTTAGGCCCCCATTAAGTTTCTTGAAGAATGA
179
AGGGATTATCACATCGCCCTGTTTATAATTATGGAGTAATTTTTCT
ATTTGGGCATTCACTTGCCAAGACAGCAGATGTCCGTCATCTCCC
TAGCCTTCTTTTGGGAAAGAGGAGAAAAAAGGAGGACGACTGTG
TAAGCCAGAAGAATGTTCCAGAATGTTTTGCTACCCCTGGACATG
GTGCGTACAATGGAAATTAAATACTCTCCCAAGTAAAAGCTGGAA
TGACGGCATTCACTTTTCTCCTCGGGCCCAGGCTTTGGAAAGGG
TTTAACGAGCAAATTCCGAAGATACAAATTGTTCCATAGATCN
ACTAAANNAANNCTCNTATGACNTGNTNACGAATTTAATACGACT
CACTATAGGGAATTTGNGCCCTCGAGGCCAAGAATTCGGCACGA
GGCAAAAGAAACTACAAATCCTAGATTCGTCTGAATATACAGACT
CAGAGAATATTTAGTTTCATCTGAAAAGGAAAACCTTTTCCNTCTA
TGTACACCAAGAGCTCTGTCAAATGTCTGCTCTCCATTACCACCT
GTCTGACCTCTGCTGAGAACAGTCGTCAGTGCAGCCACCAGGTT
TCCGCCCTCTCTCAAGTTTGCTGTAGCAGATTGGCAGACTGTCTT
CTAACAGCCATTCATTTCATTCCAGATTTTCCCAGGGGAATAGTC
SEQID NO:
Phase-1 RCT-034 TGCATCCTGCTTGCTTTCTGTATAAAACTTACAAATCAATCATGAA
180
ATGCNCTAATTTTTGTGAATCAGGACCCTAAGTGTTTAATTGNAAA
ATAATTTTGTTTCATAGATTGCTTTAGGTTTGTGTTATCTTTTTAAT
TGTTAAACTGNAATTTAACTACNTTCTAAAGTAACTGGAACTGCAG
ATTAAAGCCAAGGCTTTACAGATAAAAAAATAATTTACTGGNAATG
NCTAAATTTTGGAAAGAATGGCAATTAAAGCCCACTTTCAGGCTT
AAAGCCTTTTAANACCACCNNTANTCATCTACACCTCNCCCNTCA
AGNNGTGGGCGGCCCCCCANANCCTTTATTTCCCCTTTNANNGG
AGGGGGTTAAATTTT
150
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CCNCGCGCTATCTCATNACATGATTACGAATTTAATACGACTCAC
TATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGC
CAACCCCCCCCACCCCCCCAACCAAACTTTTGGAAACAGGCTTC
CTGTGAATGTGTAAATTACAGAACTCTCGGTTCCCAAAGCTAGAA
CCTGT'rfTfCTTGTTAGCCTTCCTGTAACCAGATGCTCTGTTGTAC
CTTCATAGCTGGAAGTGTTTCAAGATGAGCTTCAGAAGCAAACCT
GAAGCTTCATCTTCACAATGGCATGCTGACTGCTCTGACCTGGCA
Phase-1 RCT-035 CTGCGGGTCCTAAGCACATATGTGGAATCCCTGTTGGCCCTAGTSEQ 1D
NO:
CCCCGCGCCCCTGCCCCCCTTGCCCCGTGAGGACTCCACTTTAT181
AGCCTAAACCTTTTATACAAAAGCTTTGGATACTGTGAAGATGTTT
TACATTCCATTTCGTTCGTGTTGTT'i-fTTTTT'f-fTTAACTACATTTG
ACCAGATGTTTTGATGTTATCACTTATGTTAATAGTAATTCCCAGA
TGTGTTTTGTTCTCATTGCTTTCCCTGCCGTGTATTCACTAAAATC
ACTCGATCAATAACAGCGTGAGTTGTGATTGGCCCAAAAAAAAAA
AAAAAAAAAATCTCGCGGGCCGCAAGCTTATTCCCTTTAGTGAGG
GTTAATTTTANCTTTGGCACTGGCCGGCGTTTT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCGCGCAGGGGAGC
GTGCCCACGGGACTGTTGGGCCGAAGTCTACCTGGTTTTAGAAC
GATCCAAAGRRATGGCAGGAATGGATTCAGTGTATTCCTCTTTCT
AGCCCTGCTCCAGATCTCTCACAATGAACTGCTACCCGCAAACAA
TTTATAGTACTCAATGGCAGACATCTGTCTCCTCCCAAACGAACG
GTTGGCTGGAGGACTCTAACATGCCCCAACTGTGCACACGTCCT
SEQID NO:
Phase-1 RCT-036 CCTTTAGATTAAACCTCAAGGGCTCCCTTCAGCTGAGTGCAATGT
182
GTCTGATTCACCAAGAGATCTCCAGGGTTTGCAGGGAGTTTAAG
GTCAATGTGATTTTCAATATGGAGCTAAGGAGAGAAATGACACAA
ATTTAGTCATGCCTTCTATATACACACACCTATGAGCAATAAAAAT
GACACTTTTCCCG GGT
TGTGCGGCCGCAAGCTTATTCCCTTTAGNGAGGGTTAATTTTACT
TGGCACTGGCCGTCGTTTTACAACGTCGTGGACTGGGAAAACCC
TGGCGTTACCCAACTTAATCCCTTGCAGCN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCACCACCCCTCCCCC
AATGTATTTATTGCACATCTGCTCTGTCTGGCACAGATGATAGATA
GTGCTAGTTCATTTTTTTTTAATGGAGAAGGCTGTTTTGAGCCCTG
TTTCATTCACCTCTTGGTCCAGACTCCCTGAATTTCTTAGCAACTC
CTGAGTGGAAAGGAAGTCTGAGTGACCAGTGGGACTTTAGAGGT
CCACTGGGTATGACTACGAGGAAATTACTCAAAGAGACTGGGGA
Phase-1 RCT-037 GTTTTTAACCCTTGGAAAGGAATGGCTCTTTCCATTCAAAAATACCSEQ ID
NO:
AAAGAGCAGAGATAAACCCAACATTCCAAAAGCTGTGATTCTACT183
AATGGGAAGAGGGATGGCTTTGCCTATCTCTCAGACACTTCTCTG
AGCCTCCCTGGCCCTCTGCATTGACTCCAGATATTTAAGAAATAA
ATGTTGCTGAGAACTCCTTTTCCTCCTTCCAATGAGTGGTGATCA
TAGCCATTCATTGTTTAACAAACATTTAGTGACTGGGTGAATAGTT
AGTGATGTGTTGCCCATTCAATAGGCCAGGTAGTATTCTACAACC
TGGGAGCCGAGCAGTGACCAAGACAGCCCAGATTCCTGCTCCCA
AGGGGTATGTANGGAA
TNATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTCCTTCCCTATCAA
AGCCAGATGCTTGAGAAGCCATGAAAGAGACCTCTGAAGTGACA
GAAAGGAGGAAACAGCCTCAAGCCCCATCTGGAATCTTCCTGGC
TGCTGTCCTCAGCCCGTTCTTCTGGCTGTTGAGCATCGATGAGCT
GTCGTCCCTTCCAATTGAGTGACATATCACTCCTGAGTATGCCCA
CTAGATGCGGTGGAGATGCAGAGGCATCCGGACCCCACGCCCC
ACCCCCTCCCCTCACACACTTACTCTCTGCCTAGTAATGCCACAG
SEQID NO:
Phase-1 RCT-038 AGCTTCCATCCCCATCCAAAGGTCATCAGGCATGGCTATCAGTTG
184
GCTCTCAGGGTGGATTTGACATTCTCAGATGATTAGAAGTTGGCA
AGAAGCAACCTTGGTGAATAACTGTGGTGTCTAAACTCTGTACTT
GAGTTTACAGTCTCAGTAGAGGAGACGCCAAAGCTGTTGCGAGT
GACGGCAGGATTATTGAACAGTCATGATGCTTGGCTTTCAAAGGC
GATTATCGCTTTAAGGCTTANAATTAGTAAGGCATCTTTATAACCA
GGCATAGCTAGATCATAAACTACTGGAGGGCCAAAGGACCTAGA
ACGNGCTTCTTACCTTNCTCTCTAGNTACATTACGACAAACATAAT
CNCCANNCTCAGGGGAAAACTTGCTGATTCAAGTA
151
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTAAAACTGGCCA
GGCTCATGTACAAGAAAAGACATGGTCCTCTATGGTTGTCTGAAA
CTCCTGGGGAGCCCTGGAAACCTTGTAGAGGGCACTGGGGACC
CTCATTATATACAGAAGTCACTGATGTGGACAAAGCTGGATACAG
CTATGACCAGGCTGGAGGGACAAGAAGCAAAGGGGTAGGTAAAA
GAGCTCATGGTGTCAACTGCAGACAAGCCAAGTTGTGAATCCTG
SEQID NO:
Phase-1 RCT-039 GTCAGCACACCCAGAGACTTAGTCTAGAAATCCCTCCAGGATGC
185
CTGGATACCTGTGCTCCCACTGACCTCAGATGAGGGCCTGCTGT
GGGACTGTGGTCCTTGGAAATCACTACCCTCTTGACGACCCAGG
CACAACGGCATTACGTCATTCTGTTCTCATTCATATTGTTTGCTCA
TGGTCAAGTTTGCCCATGGCTTTGGTAGGTGTCTTGAGCATTGGC
TTGTTTGGGGAATGGGGGGAGCGTTGGGAGCAGAGTCCATGAA
CAATTTTGTCCCTCAGACTGTCTTCATTTTTGGATGAGAGTGAATA
ACTCTTTCCACATGGCCCTTTTGTGAGGCACACGTCTCCCCTGAA
NTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGAAAGATCCAGTCACT
GGGTTAGACTACTGGATTGTCAAGAACAGCTGGGGCTCTCAATG
GGGTGAGAGTGGCTACTTCCGGATCCGCAGAGGAACTGATGAAT
GTGCAATTGAGAGTATAGCCATGGCAGCCATACCGATTCCTAAAT
TGTAGGACCTAGCTCCCAGTGTCCCATACAGCTTTTTATTATTCA
CAGGGTGATTTAGTCACAGGCTGGAGACTTTTACAAAGCAATATC
S EQID NO:
Phase-1 RCT-040 AGAAGCTTACCACTAGGTACCCTTAAAGAATTTTGCCCTTAAGTTT
186
AAAACAATCCTTGATTTTTTTCTTTTAATATCCTCCCTATCAATCAC
CGAACTACTTTTCTTTTTAAAGTACTTGGTTAAGTAATACTTTTCTG
AGGATTGGTTAGATATTGTCAAATATTTTTGCTGGTCACCTAAAAT
GCAGCCAGATGTTTCATTGTTAAAAATCTATATAAAAGTGCAAGCT
CCTTTTTTAAATTACATAAATCCCATGAATACATGGCCAAAATAGT
TATTT-(-fT'AAAGACTTTAAAATAAATGATTTAATCGATGCTATAGAA
TTCCTATGTGTGTTAC
TATGACATGATTACGAAT1?AATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCTTTCCCAGTCTTGT
CTGCTTCCTGATACGGCTGGAAACCATGTCAAAGGCATTCCGCA
ACCTCTCCAAGGATGGCAAAAGCATCTACCTGACAGAAATGGAG
TGGATGAAGCTGGTCATGTACAGCTAAAGTGTGAAATGCAGCAG
AGCCCTCTGGACCAGGACAAGCTCCTGGTGGTCACCCGAGGAAA
CGGCTTTCTCCGTGGAGTTGTACCAACCCAATGGCAGGTCTGCA
Phase-1 RCT-041 GCTAAACCTGGTATTTGAAATGGAGTCAAAGGCGCCTGTGAAGASEQ ID
NO:
GCCTGAGTGGAGGTCTTAGCTGAGGCAGGCCCTGGGAAACCCA187
AGGTCATAGGTCACCAGAGCACTTTCTGACGTCAGTAGGCACTT
GCAGGAAAACAAAACAGGAAGTGTCCACTCCCACTCCCGAGAGG
AAGCAGGAAGAAACTGGCATTCCATCCCCTCTCACACGATCAATC
ACTGGATCCATTTATTGTGGAAAAAAAAAAAACAGTCTGATCCAG
TTTATGCACCCCCGGGATTGGTCTAATCAGTGTCATTTGCCAAAA
ATCCACATGCTTTTTGTATCTGCACCCAAGTTGTTTCACAGCTAAA
TGGCAAAATNAAATTTATTTCTACNAAAAAAAAAA
TNNNNNNTNNNGNNNNNTCTATGACATGATTACGAATTTAATACG
ACTCACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCAC
GAGGGTGGGTGGGACCACCCCTGGTAGTTCTGGGAACTATAAGA
GAGCAAGCAGAGCAAGCAATGGGGAGGGAGCAAGCCAGTAAGC
AGCATCCCTCCATGGCCTCTGCATCAGCTCCTGCCACCAGGTTC
CTGCTTTGCTTGGGTTCCTATCTCGACTTCCTCCGAT,GACAAACG
GTGATATGGAATGTAAGCCATATAAACCTTCTCCTCAATTCGCTTA
CGTTCACAGTGTTTCATCAATAATAACCCTGAGACAAGCAGGAAG
SEQID NO:
Phase-1 RCT-042 CACTCTTAACCACAGAACCAACTCTCCAGCCCCACGGTGACACT
188
CTTGTCTCAAAGAAGGTAACAGCCACAACCACAAAGCCAATCAGA
ACCATGTGCACGGAACACACAATTCTACGATGCTGGGTTAAAGAT
CAGAACACGTGTCTTCAGAAAAAAAAAAA,4AAAACCTTTGCGGCC
GCAAGCTTATTCCC'I-1'TAGTGAGGGTTAATTTTAGCTTGGCACTG
GCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTAC
CCAACTTAATCGCCTTGCAGCACATTCCCCCTTTCGCCAGCTGG
GCGTNATAGCGAAANAGGNCCGCACCGATCGCCCTTTCCAACAG
TTNCGCAN
152
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGCACGAGGCAACAGAACCCAAAGAGGATGCTTTCCGGAAGCTT
TTCCGCTTCTACAGGCAGAGCCGGCGGGGTACGGCGGACCTAG
GAGCGGTCATCGACTTCTCAGAGGCTCACGTGACTCAGAGCCCG
AAGCCCGGCGTGCCCAAGGTGGTCAGATTCCCTCTGAACGTGTC
CTCAGTGACTGAGCATGATACCTCTAGGGCAGGACTTCAACCTG
CCTGGAGACACCTCTCCCAGCTGTCCTCCCTAGCGGATCATTGC
TTGAGCCCTGTTCTGTGGAAGACTGGCAGGTGTGTGCCACCTAC
SEQID NO:
Phase-1 RCT-043 TTGAAAACTGCCCGAGTTAATATGACTGTTCGGCAGGTACTGGCC
189
ACAGGCCAGGACTTTCCTTTAGAACCCATGGAGGAGCCAAAAAG
AGACATTACTGCAGATGGTTTGTGCCATCTGCATGACCAGAAAAG
CCCTGTAAAACGGAAGAGGTTAAATACCAACGACTAAAGCTTAGG
GGACTCTCTGGTTGCCTCACACAGGGGCAGGGAAGAACTCACCT
GTCATGCTTCTGCCTTGGGCTCATCTTANAGCATAAACTGAGTTT
GTCCAGANAAATGTCCTACTCGGCCAGTTCTAGCTCTTATTANGN
GNGNGNGNGTTTGTCATACCC
TNNTNACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCAGGCTACCCTGT
CTCCTCCAGGCACACAGGTGCACACACAACTCATGCACATGCAT
ATAAATGACCACAAATATATACTGACACCCCACACATATGTAGAC
ACCTGTATATGCACAGGTCCCAGTACCACACAAACTCACCTGGGA
AGGTTTTCTTTAGATGAAGCGTTCCCTACCTGGTATCTCTTCCTTC
CCAGCCTGGTGCCTGGTGGTAGTGCCTCTCTGAACAGTGCTGGG
Phase-1 RCT-045 TAGAGGTGAGAGGAAGCCCTACTTTCTACCCTCTCCCCAGCCTCSEO ID
NO:
CTCTAGGCTGTGGCTACAATCTGATTCTCCTGAAGAGACTGCTTG190
GTCAGCTTCCTACCATAACACCTACCCCAGGGCTTATCCTACTGG
GAGCTGAGACAGGTCCCAATGAGGTCCCACTGTGCACTGTGCCT
ATTCCTCAACTCCAGGGCAGAAGAGCCACAACATCACCATTCTGC
CACTTACAAGGTGGAGAAAGACAGGTCTGGTGGCTTANGCATGA
CCTGGANGTCCTCACAGCCCATTTAGCCTGTCTCAATGTCCTCAG
TTTGGCGGTGCTAATGGGGGTANCTCANANACCCNCCTNAANTT
CANGGGGAG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTTTTTATGGCAGTGGC
TTTCGTTTAATCAAAGACAACCATGACAAATCCGACAACTATCAAA
AGCTACATTTTACTAAAAACAAATCATCTTTAAAAACATTTAATCAT
ACATATATACAACACATGCTGCTTTCCTTTCAGGGTTTCACTATTG
CCTTCAGTTCTCCAGCTGGCATCAGGCACTTAGTCGCTGCTGGC
TCTGGCTCAGAGAGATCACAGGCTCAGAAATCTCAAAGGTCTTCA
Phase-1 RCT-047 CAATCTCCTCCCAGTCATGATAACTCAAAGCTATAATTCCTTGACTSEQ ID
NO:
CCTAAATTGAATGT'(-fTGGTCAATCCCCTCACTTTCTTCATTAATC191
ACGGGCTCTATTATTGGCAGCCGGTCTTGGTCGAGTCTTATTCTT
GCAAAACCATCCCGTATGATGAAGGAAACATGAAAGATGTTTTCC
ACTGTACGTGGGAAAGAATGTGGATCAACCACAAAATCAAAGAAC
GACATCGGAGTGTCAGGGTCCTCTCGAAAGTATGTCTGCAACAA
TCCCAAGATCCTCTCCACTTCCTTCTCGGTGGCTTCTTGATGAGA
TTCCTCCATGCATTTCAACTGAGCANGCATTGCCCGCTGCTCTT'C'
GATCATGCGAG
TGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGCCTGGAGCGAGCTAGC
TCTCAATAGCTGGAGGCGGGAGGGGCTGGCACAATAGGAGCAA
GGGCCAAGCCGGGAGCCGAAGGCGGATTGGGCCAGAGCTTACC
ACATTATGGCTGAAGAGAGAAGCAGACAGATTCTCACACCGGCA
CAGGACTCCTTGACATGGGACTCCCTTGCCATGGGTCCCCCTTT
TCCCTGGTTGGTCCCCTTCTGTCTCCCCCTCCTTCCCATCI-fCTA
Phase-1 RCT-048 TCATTTTTTAAATCTCTTCTCCCACCATGAAATTAATTTGTTTCATASEG2 ID
NO:
TTTTTGGCTGAGTAGAGTTGAGAGGGCTCTGCCCTCCCCTTCTCC192
CACTTCATCACCAGCCCAACTGCCCTTCCCTCTTTTGGTCTTCAT
GAATATATTTATATGGACAGAATTAAGAAAAATAAATTGATTTCCC
CATTCGTTCAATTCCCCCACCTTGTCTCCCCAAACCCCACAGAGT
TAAAACTTGGGACTCCCCCGACCCCTGATCCAACCCCAGAACAC
i-fGTATATTGTTTGGTTGAGGTTTGTGCCACCACAGTAACAGACA
CAGTATTTAATTGCACATACAGATGGTTGCTGGGGTCACTGTAAA
ATTTTATTTAATCTGGGTT
153
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATCCATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTGAGGTGTTCTCGTG
GTTACGATAGGTCTCTTCCCTGTGATATTCATTTGCAGATGGCTG
GACTGATCAAGCAGTACAGAATGGAGGTCGGAGGGAGAGAAGG
TCCTCCAGGGAGATGAGAAATCGCCGAGCACCTTAAGTCTCAAG
GTTTGCTGACGGCCAAGACCAGGCTTTGAATGAATGGTGAACTC
AGAGGGGAGCGCGTTGGCCTGAGGAACCCACGGATGCCAGTGT
Phase-1 RCT-049 TGGTCTATTCTTGCTTTCAGGTACCCCTTGGAACACAGAATAGCASEO ID
NO;
GTCTAGTCCTGCTGCCACCCCCACAAGGCTGGGCATGGTTCAAA193
GGCATGCAGGATGCAAAGAAGAGTCAGCTTTGGCTGGGGAGGA
GTGGTTTGGTGTACACTGCTACTGAAATAGAAACTTTTGGCCTTC
TGTCTGTAGAAATAAAAATCTGACTTGGTGATGTTTTTAAAAAAAA
AAAAAAAAAAAAAACATTGCGGCCGCAAGCTTATTCCCTTTAGTG
AGGGTTAATTTTACTTGGCACTGGCCGTCGTTTTACAACGTCGTG
ACTGGGNAAAACCTGGCGTTNCCCAACTTAATCCCTTGCACACAT
TCCCCTTTCGCCAGT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCAATCATGGCTCCG
GGTTGGCCGCGGCCTCTGCCGCAGCTCCTCGTGTTGGGATTCG
GGTTGGTGTTGATACGCGCCACGGCCGGGGAGCAAGCACCAGG
CAACGCCCCATGCTCAAGCGGCAGCTCCTGGAGCGCGGACCTC
GACAAGTGCATGGACTGCGCTTCTTGTCCAGCGCGACCACACAG
CGACTTCTGCCTGGGATGCGCAGCAGCACCTCCTGGCCACTTCA
Phase-1 RCT-050 GGATGCTATGGCCCATTCTGGGAGGCGCTCTTAGTCTGGCCCTGSEQ ID NO:
GTTTTGGCGCTGGTTTCTGGTTTCCTGGTCTGGAGACGATGCCG194
CCGGAGAGAAAAGTTTACTACCCCCATAGAGGAGACTGGTGGAG
AAGCTGCCCAGGTGTGGCACTGATCCAGTGAGGAGCACCCGCG
CTGGTGCCCATTCATCGTCCATTCATTCATTCTGGAGCCAGCCTG
GCTTTCCAGAGACAAGCCGCGCCAGACTCTTCCAACCACAAGGG
GGTGGGGCGAGGTGGTGATTCACCTCCAAGGACTGGGCTTANG
GTTCAGGGGANCCTTCCAGGGTGTCTAATTGCCCTGTCTCTGGN
TCTGGGGCAGACAGANANGCTCAAGCTAGGTCACAA
GACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGCC
CTCGAGGCCAAGAATTCGGCACGAGGGCAAAAGCCCACTTTGCC
ATTATATTTGTAGGTGTAAACATAACATTTTTCCCTCAACACTTCC
TAGGATTAGCGGGGATACCTCGTCGTTACTCTGATTATCCAGATG
CTTACACCACATGAAATACAGTCTCCTCTATAGGCTCATTCATCTC
ACTTACGGCCGTCCTTGTAATGATCTTCATGAT'TTGAGAAGCCTT
CGCATCAAAACGAGAAGTACTCTCAATTTCCTACTCCTCAACTAA
Phase-1 RCT-051 CCTAGAATGACTGCATGGATGCCCCCCACCCTACCACACATTCGSEQ ID NO:
AAGAACTTCCTACGTAAAAGTTAAATAAGAAAGGAAGGATTCGAA195
CCCCCTACAACTGGTf-i'CAAGCCAATTTCATAACCATTATGTCTTT
CTCAATAAAAAAAAAAAAAAAAAAAAAACAATTGCGGCCGCAAGC
TTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTC
GTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTT
AATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAG
CGAANAAGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAACC
TGAATGGCGAATGGGACC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTGGAGGCCAAGAATTCGGCACGAGGGCACGGTTCCATGTCA
CAAACAGAAAGGTCAGGAACACTGAGGTCTGTGAATGTCACTGC
TGCAGCGAGGTCATGTCACTCCTCTGTCTACTCTGTCAAGTGTCT
TACTCTACTGGACGCCAGATAGAAACTTAAGGTAACTTCTGACAT
GTGTCAGTCTAACAATAAACTAGGGCTTCGTCATCTTCTGGTTGG
TAAAAGATGTGGTCCAGAGAACGTAGGAACATGCCTGGAGAGAC
Phase-1 RCT-052 CTAATGTGCTCTTGTTCTGCAAACCCATGGGCATTATTTCCCTCTSEQ ID
NO:
CCGCTCAAGAGCTCATACTGGAAGCATGCTGACCACCTGGCTGG196
AATTCGAAAACCTCAAGCCTGAAGGCAAAGTGCAGCACATGTCT
GTGGAGAAATGGCAAGCGGTCGAGATGAGGGTGTAAAGGATATT
GGGGTATGGCATAAAGACAGGCAGGTTGCAGAAAAGCTCAGATC
TTTCCCCGTGGTTGACTGTGCTAGAAAAACTGTTTGAAGCAGGGC
GTAGGGAAAAGCGGGATTAAAGAGTACTACCTTTATTACTCCTTC
CCTCCAGAATANGTGCAAATCCCTCACCATGCCCATTTCCTGCCA
CCTGGGGGTAAGGATGTGGCAC
154
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAT~t-T'ATTTACTTTATGT
ATGTGAGTACACTGTTGCTATCTTCAGACACACCAGAAGAAGAGG
GCATCAGATCCCATTACAGATGGTTGTGAGCCACCAAGTGGTTG
CTGGGATTTGAACTCAGGACCTCTGGAAGGGCAGTCAGTGTTCC
TAACCGCTGAGCCATCCCTCCAGCCCCAGCCTGTTT1-f'ATGGAA
GTGATTCTCAACTCATGGGTCATGACCCCTTTGGGGGTTAAATGA
Phase-1 RCT-053 CCCTTTCACATATCAAATATCAAATCAAATACCCTGCAGAGCAGATSEQ ID
NO:
ATTCACATTGCAATCCGCAACAGCAGCAAAATTACAGTTACGAAG197
TAGCAAAGAAAATAATCTTACGGTTGAAGGTCATCACAACACGAG
GACCTGTACTACAGAGGTCTCGGTGTCAGGAAGGTCTAGAACCT
GCTGTCATGGGGGGGTTGCAGATCAGCCGGGGCTACACAATGA
GACTCATTCTCAAGAAAGAAAAAAAAATGACAGGAAATATAAGCC
TGACTGTGCGCTCCACCAGCTCTACCCCAGCCCTCACCTACAAC
CACGCAAGGATCTGCTTCGTTCTCCGAGAGAGTGTACTTCCCAC
ATTGCTTTATGCCTCNAAGTCATCCCTACNATGNGGGCC
TGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGGGAATTTCTGACATATA
AGTGGGCTATTGTTTTCAGAAGAACTTCATCATTGTGCAACTAAC
AATAACTAGCCCTAATTATGTGACAGTTCCTTATTGATATGTGTGC
AATTACTCTAGCAGCTTCTACAGTATAACACAGTTGAATGATCCC
CATACATCCTATCACTCAGATCATTTATAGGTCTATTAACTGTGAG
ATTGATAAAGTATTACTGATTTAAGAAAAATAAGAGTATCTAAGGA
Phase-1 RCT-054 ~~CAGAAAATTATTTGGTGTGGCCATCCTCCATGCTTASEQ ID NO:
CGTCTTATACAGAGTGCTAACCCCTAGCAGTGGTGTAATGAGTTA198
CAGCCTACTGCGATGTATGTGTGCTCTGGTGCACAGATGTCGTTT
TGTTGTCACAGCACTACAGTGAGATACAGAAATAAAGACTTAAAT
TCATAGAAAAAAAAAAAAAAAAAATCTCGCGGCCGCAAGCTTATT
CCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTT
ACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATC
GCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAA
NANGCCCGCACCGATCCC
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTGCGGAATGA
CATTGCTGCCAAGTACAAGGAGCTGGGCTTCCAGGGCTGAGCCA
TGGGCTCCCACTGTCCAGCCCAGCAAGCTGGGACCCAATGTTGT
GTAGAAGGTAGAGTGTGCTGTGCCCTAGGTTAGCAGAGAACAGA
AGAGGGGAGCATAGTGTGGCATCTACCCACACCCCTGGGGACA
GAGCTCTGGGCAGCATTGTCCTGGAACCCAGAGGTGCAAAGTGG
Phase-1 RCT-055 CCTCTGC't'f'CCTCAGCTCTGCTGGGTCATGCTCAGGTCTCCTGTCSEQ !D
NO:
ACCTAAGTCCCAACCCACTTTCCTCCTGGTTTTGGGAAAAATCTC199
TTTTCCACTGTCACATTTGACCCCAAATGCAAGTCACCAGCTAGC
AGACACTGACCTTTGAAGGAGACAGAGGGTTACTTANAGGGAGT
GGAGGGTGGAAAGTGGGCAGGTGAGCATCGGAAGTCTCCAGCT
GCTTAGCTTCCCCCTGACCACCTGGTTTCAATAAAACATCCTGCA
ACTCCTCNTTTNGGCNCNNNNNTNTCCACNCCNNNAAAAAATANA
ANNGTTGTGCGGCCNCAAGCTTTTCCCTTTAANGGAGGGTTAATT
TTACCTTGCCTGGCCGNCGTTTNACACC
TGAGGAGTGCAGNATGTTTATTGAANCCAGGTGGGTCAAGGGGA
AAGCTAANCAGCTGAAGACTTCCGATGCTCACCTTGCCCACTTTC
CACCCTCCACTCCCTTTAAGTAACCCTCTGTCTCCTTCAAAGGTC
AGTGTCTGCTAGCTGGTGACTTGCATTTGGGGTCAAATGTGACA
GTGAAAAGAGATTTI'TCCCAAAACCAGGAGGAAAGTGGGTTGGG
Phase-1 RCT-056 ACTTAGGTGACAGGAGACCTGAGCATGACCCAGCAGAGCTGAGGSEQ ID NO:
AAGGAGAGGCCACTTTGCACCTCTGGGTTCCAGGACAATGCTGC200
CCAGAGCTCTGTCCCCAGGGGTGTGGGTAGATGCCACACTATGC
TCCCCTCTTCTGTTCTCTGCTAACCTAGGGCACAGCACACTCTAC
CTTCTACACAACATTGGGTCCCAGCTTGCTGGGCTGGACAGTGG
GAGCCCATGGCTCAGCCCTGGAAGCCCAGCTCCTTGTACTTGGC
AGCAATGTCATTCCGGAAC
155
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATCACAGTGTGGAGAT
GAGGTATCAAAGCCCGGATACTGATGAGTGGTATCTGCCTGTGG
AGTGGTCGGTAACGTAGACCTTATATATTTCTCATCTGTGGCTTA
CAGTCTGCCCCTGGAAGTTTTGTTCCCTAATTCAGAGGTTTAAAT
TAATCCAATCTTCTTAATGAAAGCAGAAACTCTGTGATAAACTGTA
CCCTAGGATTATGTTGAGAATCACCAGGTCTTAGCACAAGAAGGA
Phase-1 RCT-057 GTTTAAACTGTTCGGGTCTCAGGCTCGCTTCTGATGCTCTGTGGASEQ ID
NO:
CTCTGCTCTCCTGTTCCCGATGCTCTGGGAGAACTGGAAAATGG201
CAGTAGGTCAAAGATGAACTTCCAGGTTCTTGCTGTTTGCTGCTC
TTCCACCGCTGCTTTAGACCCTCAGCACCTGACCCCTCATGTCCA
AACAAAGTCTGGACACTTGAGCATCAAGTGCTGTGTCCCAGTGAA
CCATCCAATGTCACATATGATATTAAGTTGGGATCCACAACAAAG
TTAGGAAAC,4AACAGGTCACAGAGTCTCCAACGATTGAATTTATT
TAACTTAAAATCGATGTCTTAAATGGGTGTGTGGCACCTGGGAGA
TTTATTTTACATTGTAGACTGGGGACTC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCCTGTTCAGAATCA
CTACTTGAAGCTTCAGATCCCTTCTCTACAATGAACCTCAGCACT
GCAAACCACCACATACCCGTAAATGATGGTAACAGCATTCCGATC
ATCGGGCTTGGAACCTACTCAGACCCTAGACCGGTACCCGGCAA
GACCTTTATAGCAGTGAAGACAGCTATTGACGAGGGGTACCGGC
ATATTGATGGGGCCTACGTCTACCGAAATGAACATGAAGTTGGTG
Phase-1 RCT-058 AGGCCATCAGAGAAAAGGTGGCAGAAGGGAAGGTAAAGAGGGASEQ ID
NO:
AGAGATTTTCTACTGTGGAAAGTTATGGAGTACAGACCATGATCC202
AGAGATGGTCCGCCCAGCCCTGGAAAGGACCCTGCAGACCCTC'
AAGCTAGATTACATAGACCTTTATATCATTGAGATGCCCATGGCC
TTTAAGGCACTGGAAGCTCAAAGACGCTGGCTTGGTGAAATCCC
TTGGGGTGTCTAATTTTAACCGCAGGCAGCTGGAGGTCATCTTGA
ACAAGCCAGGACTCAAGTACAAGCCTGTCACCAACCAGGTGGAG
TGCCACCCGTATTTCACCCAGACAAAACTCTGGCAGACCTCTCAN
GAGAATCANGGTCGTGTCAGCAGAA
CCNNNTTCTATGACATGATTACGAATTTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCAAGATGG
TGCCTCGGGGGCTGAGGGAGCTCACAGGAACTGAGCAGTGACT
GGTCCTTTCCCAGTATTGAATACTGAGCCCCTGTGGGTGTCGAA
GCACTTAGTGGGTCTGGCCCCAACCCCAAACACCCCTGTTTCTG
TAACACCCTGAGCTGGACTGTTTATCTTTAGCCGGGAGAACATGT
ATTTTGGTCCCTTCCCTGTCTCCGCTCAGATTGTAAACCTCCCAC
SEOID NO:
Phase-1 RCT-059 GTGTGGGGATCACACCCTGCACTGTCCCGAATCTTTACACCCTAT
203
CCCAAAGCTGGTGCTCAATAAATACTTCTAGATGATTAAAAAAAAA
AAAAAAAAAAAAAAAAAATTGGAAGCGGCCGCAAGCTTATTCCCT
TTAGTGAGGGTTAA'(TTTACCTTGGCACTGGCCGCCGTTTTACAA
CGTCGTGACTGGGAAAACCCTGGCGGTACCCAACTTANTCGCCT
TGCAGCACATCCCCCTTTCGCCAGCTGGGCGTAATACCGAAAAG
GCCCGCACCGATCGCCCTTTCCCAANAATTGCNCAACCTGANTG
NCAAATGGGACCCCCCCCTGTAACGGCNNATTTAANCGCGGGC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGCCAGGTGGAACC
TCTGGACCCTCCTGCAGGCTCTGCCCCTGGTGAACGGGTATTTG
TACAGGGCTATGAGAAGGGCCAACCTGACGAGGAGCTCAAGCC
CAAGAAGAAAGTCTTTGAGAAGCTGCAGGCCGACTTTAAGATTTC
TGATGACTGCGTCGCACAGTGGAAGCAAACCAACTTCATGACCA
AGCTGGGCTTTGTCTCCTGTAAATCACTAAAAGGGGGCAACATCA
Phase-1 RCT-060 GCTAGCCGCTCGGCTGCTCCCACCATCCTGTCTGCCGGTCGTTCSEQ ID
NO:
CACCTCTCACCCGCTCCCATCTCAGGACACTGAAGCACCGGTCT204
GGACTGCTGACTAGACGCAGGACTTGGAAAGGGACAGCTCACCT
TCCTACCATGTGGGCTCATCCCGCCTGGCTGAAAGGAGACGGAG
TGCCTGGGCTAAGGATCTTGCCTTGCAGCAAACAGCTCTACCTTC
TTCCCTTGGCAGCTGACTTGAGAAATCTGGTTTCAATAGAACCCA
CAGAAAAAGTTTATTCCTCGGTCCTTGTAATTGGAAAAACACTGG
TTCCCAAGATTCCATGGGGTTTTNCCTGCAGCTGTACCTCTAGCT
GAGATCTGNTGCCTGGTCTGGGCTAATTACAGCTTC
156
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CNNNNNNNAATNNNNNNNNTNCTATGACATGATTACGAATTTAAT
ACGACTCACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGG
CACGAGGTGCTTTATTGTACAAAGCAGCGTCTCTGTGTTTTGATC
CCCCATNGTTTGAATTCTCGNCTTTAGCTGGTAGAGTCTCANATA
TCCCTGACACGGGGCATTCTGTGTGCGGTGAGGGGTTCCCGAG
AGGNTCCGGAGCCCTGCGTGAAAGCAAGCTCTCAGNGTACGGG
NGATTGTGCAAAGNTCAGCACGGCANAGCATCCTCTGGTCCAGG
Phase-1 RCT-061 TCTCACTTCTGCTCTTTATTGAAGACAAAGATTCNCCANTAAAGAASEQ ID
NO:
AAAAAAAAGAGAAAGATGTTTTGAGANAAACTAATTTTCTTTGACA205
AGAGTATTACTTAATTTTTTGGCCTATTAAGGTTCCCCTAGTTAGN
ACTCNATTCCCTGTGCTAATCGTTCAACTGTATATTGTTAAAACAC
ACTGCTGATTCTGTACCAAACTGGTCTCAAAANAAAAAGAAAAAA
AAAAAAACNTCTAGCGGCCGCAAGCTTATTCCNTTAAGGGAGGG
TTAATTTTANCTTGGCCCTGNCCGNCGTTTTACAACGTCGNGACT
GGGAA?,ACCCTGNCGTNACCCCACTTAATCGCCTTGCAGCACAT
CCCCC
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCAGGAGGATTCCCAAAACTGAGT
GGCCCCTTATTCAGCAGCATTCTGTGACTTGGGATTCATTCCTCA
TGTTTACCTTAAATTCTACCAAAGAAACTGTAGACATCAGGACCAA
GGTCTCTTACAAGCTAGATTCACGTGCTGTAGTCTGAAGACCT'I-('
TTTGTTTGTTTGAGACAGGGTCTTTATGTTGTCCTGGAGCTTGCT
GTATAGACCAGGCTGGCCTCAAATAGAGACTTGGCTGCTTCTGC
Phase-1 RCT-062 CTTTCTAGTGCTGGGATTAAAGGTGTGTGCTCTCACACCCTGCCCSEO ID
NO:
CTGTTGAGCATACTGACGGCAGAACTCTGATACAGCATCCATTTA206
AGGACGACCAGTGCGAGAACGTGAATAGAACTAGCTAATAGATG
TTGAGTCCTGAAAAATGCTCATCTGGACATGTCAGTTTATGCTTTC
GTTTGAAGCAATGATGGTAACATCTAGGACCTGAAGCACCACATT
AAATTTTGAACTATTTGAAATTTAGACAGTACAATTTTAGAAATAAA
TTATGAATTTATTCCTAAAAATATACNAATGTAAAAGGGAAAACTG
GAAGTTCTTCTGNATTGCATAAGTAAGTTCANAATTCTCTGGGGG
AAAACCATNAAG
CNNNNNNNNNNNTCTATGACATGATTACGAATTTAATACGACTCA
CTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGG
TTGAGCCTTTGTCCTATTGAGCTGCTGGCCACATGCTCTCCTCCT
CCAGGCCTCCGCAGTCTCCACAGTGGAATGTGAAGTCTCCAGCC
AGGAGCCAAGACAACCCCCGGTCCGGCAGAAGGTCCCTTCGCA
AGGCCCCGCTGAAGACAGCCAACTGAGACCTGCGGGGATATCT
GCCTTCCCCGTGTGTGTGCAAGGAGGAAAGATGGTGTGGCCTGC
Phase-1 RCT-063 ACCCACACAGGAGAGACCCGCTGCGCCCTGCCAACTCCTGTCTASEO ID NO:
GGACACCAATGCAACTTTGTGCAGCTTGTATCTCTCCTTGTGTGC207
ATCATCGTTGTTGAGATTTGTAAATAGAGACATGATGTATTTAGAC
TTTCTCACAATAACATTAAGCTATTTAATACTGTGATGTTCTATTTG
AGTATCAAACCTTCTGTGGTAAGTTACACTCTGGTCTTTAAGGAA
CACGATTTTAGAAACCAGCTTTCTTCTGTGTAACATAAGTGTCTAT
AGTTTGTGTGAATTCAATATAATAGATATGTCCCCTTAGCTAATGG
GAAAANTTTGAANATTTTTCTATTATTTATAATTGCAAAATTGTATT
AAAAAGAGATGTACAGTCTTTCTAAAACAAATAAANGNCNNATAT
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCTACTAGGTGGGCA
CAGCCTCTCCTCACCTGGGGACTTCAGGGTTTGTCCCAGTGAAT
AACTGGCTGCCTCTCTGAGGCAAACTGAATGGGGCATCCTATGT
TCCGTGTTTTGTTTGT'fTGTTTGTTTGT'I-fGTTTGTTTGGCTTGGG
ATGGGGATCGTGTCTCGGCGCTCCCTGTCTGATCAGAAGACACA
TGTGGTTCGCACTCAGTCCCTGGTTAAGCCAAAGAAAATGCCAGSEQID NO
:
Phase-1 RCT-064 ATGAGACCCGAGAAAACGTCTTTTTGTAATGAGGCTTATTAGACT
208
TCTAGGCATCCAAGCAGGGGCAAAAATGATTCCCTCTTTTTCTTT
TCTCAAGAGAATAAAATGACATTTTGTTCTTCAAGTGGCCCCAGT
AGGGCAGGACAGCCATCTTATGGACAGGCTATCTCCAGAGGTAC
AGGGGGAATGGATAGGAGGCTTGGATACGCCATGGCTGGCAGA
GACCAACTGCCTCGGACTCCGGGGCTCTGTAAGCCCTTTCTTCC
CAAGTGGAGCCAACACTGGGCCTTCACTCCATGCCTCCTGCAGA
CTGGCCACCCTCATGGTACCATGAGTGGCCTACT
157
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGATAGAAAGTGAAGG
GCTGAGGGTTGGGAATTCATTTTCAAATGATGAGATGATTGGCTG
GGTTCTCTGTCTACCTTACCTGCTGTGAGGGGCTCTCCTAGGGC
CGCTCTTACATTTACAGCTGCCTTCTTTGTGACAGACTTTTTCTTT
TCTCTTTTTTGTGGTGCTTGGGATGGGACCCAGGGCTTTGTGCAG
GCCTGGTAAGGCTCTGTCCCTGGGCTGCACCGAGCCCCACCTCT
Phase-1 RCT-065 CTATGGGTGACCGTATGTAATCCTGACAAAGACCAGCATGTGAGSEQ ID
NO:
CCACTCAGAAGTTAGCCAGGATCGGGGGAGTTTGCCGAAGTGCT209
ACGTACACTTTACTGTGGAGAGGGGTGAAGAGTGTGCCACCTTA
AACTCCGTGACGCTCAGGCTGCCACGGGCTCCTGTCCCACCTCC
ATTTGCATCAGACCGAGTGAGGGGTCCTTCACTTCTCTGGGGAT
AATAGTGGTTGTCATAGTGAGTGTGTATTTTCCAGTTTTGCTTGTC
AGTCCCCCCCAAAGAAGAAGGAAGCCNCTGATTTCTTGCTGTTTG
GTTTGAGACAAGGATGTTACTCTGGANCCCTGGGTTGACTGGAA
GCGTCATAAATANACCACGCTGGTCTCAAACTTATGGCAC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGAGCACTTTGCTTTA
ATCCACAAGAGGCAGAGGCAAACACACAACTGAGATCCAAGCCA
GCCTGGGCTACATAGTGAGACCTTATACATCTAAAAACCAAAAGA
AATCCCATAATCCAGGCTATTTGGGGGAACTTGGAAGAATACTTA
GAAATGGCCGTGGATTTGTCACACGGGTGACCTAAAAAGACAGT
GGGGACCTTGCTTGGGTTCCTGGGGTGCCCACTGTCCAGCCACT
SEQID NO:
Phase-1 RCT-066 AGGACACTTGTAAGGAGCTCTGTGCTATGGCACCGGGCCCGGTC
210
TTCACTGTATATTCAAGGATAGCACACATATATATTAACTCTATTTA
TTTTGCTGACCCTGACTGCTGCACTTGTCGGTGACGTTTCTCCAG
GTTAGGCTGGGGTGATACTCTGGGATGCTCTGCGTACAAAGATT
ATTTGAATGAACTGATCTCAGGCCTGTCCTGTGTGTGTTGCTTTG
GGGGTGGGAACTGCTTTGAAACCCTTGTTCGGATGTTTTTATAGG
CTGAGAATGTCTTGCTGTGATGGATTAAATTCCTTTTTGAAAACTT
AAAANNNNNNACNNCNNNNNCNNNNAAAN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCTATTTAGTCTCACT
GCACTGTGTGCTTATTTGCACAATTATAATTGACACTGTAGTAAGT
ACACCCAGCATCTGGTAAGCAGTAGCATACACAGTAGCTAACCC
AGAGGGGATTACTTCATTCATGAGACTGTGCCAAAACAGCATAAG
CTGGATGGCTTGTAGACAATAGGACTAAGTCCAAAGTCACAGTTC
AGTGTCCCCTGACAACACATGTTCCCTCACATCATAGAAGGATGA
Phase-1 RCT-067 GGTGGCTTTCTGAGGGCCTTTTTGTTTTTCTTGGATCATTAATACC5EQ ID
NO:
ATTTCAGGAGGATGCCATATTTATGATCTTACTGCTTCTTAGAGG211
CCCCACCTCCTCTGCTGTGTTGGTAATTGGATTTCAACATGATGG
ATCTGGAGAGACAAACCATCAGACCCAGCAGGAGGCATTGAATA
GTTCCCAACAAGATTACTGGTGAAATGCTTGGGAAAGGAGCTTG
GAAAAGCTGGCTCTCTAAATTACATCAAAGGAACTTCTGTGAGAA
TTTCCCATTTCAAGCGTGTTTTITfCTCAAGCCGAGCTATTTGAGG
TACTGTACCTCAAAAACTACACGATGGCATGACTCACTGGGAACA
AGACTGAANATANGGGNGGGGNGTCT
TATTACATGATTACGAATTTAATACGACTCACTATAGGGAAT1-fGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTTGATAGAATCAGTAA
GTTTCTAAGGGAAAGGAAATTGATATTTTGCAGACCAATTTGTTCT
AACCAGCATCCCAACTCTAGCTCTGTCAGCCACGTTACCGCATCC
ACCCTTTACTGCATGCTCAGGTCGCTGCAGTCTGGTTCTCCTGG
GAGATTTTCATGATGTAGCTATTGGATACAATTATGAAAACCAACT
GTTGAACATATTTGGAGTAGCTGTTTCTTTCCTAGAGAACCAAAG
Phase-1 RCT-068 CTGTTTCAGCTGGTAGAACAGGTTGAAGCCCGCCTGCATTAGCTSEQ ID
NO:
GTGCTTTGCGTTATGTTTAGAGGGATGCACAGGCACGACATCATT212
CCAGGAAGGAAAATTGTGGTTAAGAATTTCCAGTAAGATCATACT
TAATAGCTGAGATTTTTAAGGCATTTTTATGTTTTCAATGACATAA
CAAAAGTCAACTCATGCTTATAGCAAGGTGAACAAACCCTAGGTT
CTCTTCAGACGTTAATTGATAGTATTTAATGTACGTTGAAAGTTAA
CCTCCATTAATGACATCTTTTCTTTGTGGTANGGCCTACCTTCTGC
TTTCCTGGAAAAGATGAAATATACATCATTTGAACCTATTTTGAGT
TTTCTGTTGGGGGGGGGGGGGGGTT
158
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTGAAGGAGGAGGAT
CTGTTCCATAGCTACACAACCATCATGGCTCTCGTTCACCTGGGG
GCCTCCAAGTGAGCTGCCTTGTTGAGTGGATTTCACATTATGTAA
CTTTGGGGCTTTCTCTTTTTTAGAAAAATGGAATCTCGGATACAAA
TATTTTAAACAAAACTAGCTATTGTGTGTTTTGTAGCTTTGATTGAT
GCTCTGAGGTCACTCCGGGATGATTTTTTAATACGCAGATGAAGG
Phase-1 RCT-069 ACAGCGTTAACATTGTGAGCACACAAGTCAAGAAATGAGGCTGTTSEQ ID
NO:
GTTAGTGCAAGCAGCCGCTGTGGCTGAACAGATTCTGCGGCCAC213
TGCGTAAGTGCCCTGGGAGGTTGAGAGGCCACCCGGAAGGTGG
AGGTTCAAGTAGTGGTTGGTGACTTTTAGCAGAATCATGAGAAAA
TTAAAGAAATGGTTTGAGAAGTCTTTCTCTGCTTTTCTGTTTTTTAC
AGAAGCTGTAACAAATATTACTGACTGTTCACTTTTT1TGAGAGTT
AGTGTTTTCCTCTTCCTAGTAAAGAGACTGCAAGGGAACAGTCTT
TATCACATAATTCTAAAAATCATATCACCATATTTTTGGTTTTACAC
CAATAAAATATACTTGAAAACCCAAAAAAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGCGGGACTACTTAGT
CAAACCGTTATTACGGTTTGATGTTATGGGACAACGTTAAATTCCT
TGAGGGGCTTCAGAGTTGCCATTTGCAGCCTGTCAGTTAAGTTCA
GCATTAGAGTTTGATTCTGATCTTTAACCCTGTTCAGGGCGGTCT
GCCCTCACAATCCAGATCAGCACACAGCGGAAGTATCTGACTTTC
CAATGAATTGTAGTTTTTTATTGTATTTTAATTGGGCTATCTGCTCT
Phase-1 RCT-070 GCACCCAGCCCCACTCTAAAGGTAAAAGCTACGATCTGTGGAGTSEO ID
NO:
ACACTGGACCCTGGTAGGTCCAAAGCATTAGGTGGGAGCTCAGA214
AAATATTTGTCAAGTAGGTGAACTGTATTTAAATGAAACAAAAAGG
CATCGCAACTCTACATTAATGAGACAGCAGGTGCCAATACCTCTT
AATCTATTCAAGACACCAAAATTAATCATTTTGCAGCTACTAAGTC
ATGTGCAATTTTAGTAAGTGTTGAAAAGTGACCTTTTCACCTAAGG
CATGAATCCCCTGGGCTGGGGATTGAACCCCAGACCTGCCTGGT
ATATGCTACATAATTGCTCAACCACAGNAGTACGCCTTCCATCCC
CACNNATGNNGGNNNNGGGGTTTT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAAATTCGGCACGAGGCAAAAAGAAGTCTAA
AAGCCTATAAGAAACCTGAGCTGCTTGCCCGACTGCAGAAAGAT
GGTGTCAATCAAAAAGACAAGAACTCCTTGGGAGCAATTTTGCAA
CAGGTGGCCAATCTGAATCCTAAGGACCTCTCCTATACTTTAAAG
GATTATGTATTTAAGGAGCTCCAGCGGGACTGGCCAGGTTACAG
TGAGACAGACAAACAGACACTGGATTTGGTGCTCTCTAGAAAATT
Phase-1 RCT-071 AAATCCATCTCAGAATGCTGGCACTAGCCGGCCAGAGTCTCCCASEO ID
NO:
TGTGTTCCAGCAAAGATGCTGCCTCATCTCCTCAGAAACGACCTT215
TGGATTCAGATTTCATTGATCCTTTAACGAACAAAAAAGCTCGAAT
ATCTCACCTGACAAACAGAGTCCCACCGACATTAAATGGCCATTT
GAATCCCACCAATGAAAAATCTTGTGCAAGCCTTCTACCGCCCCC
TGCAGCTGCTGCCATCCCCACCCCCTCACCACTGCCTTCAAACC
ACCTGCCTGTCTCCAATCCTACCCAGACTGTAAATTCCAACTCCA
ATTCCCCTANCACTCCAGAAGGNCNGGGGGACTCAAGAACTACC
TGTTGACAGTTTTAGTCCAAAGGGGNNGGGGGGGGGN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTCAGACACTGAGGAT
TGGAAATAAGGGCCTGGAGTAATACCCAGTCTTCAGTAACCATAG
GCCCAGCCAGAGACCTGTGGTGGTTCAGCCACAGCAGGGGCTG
GGCAGAAAACCCCTCTGAGCTGCCAAAGCTTGTAAGTGCCAAGT
AAGCCCCTTTCCTCCCAGCATGCTCTGGCTGAAGGGGTTGGCCC
TGCCCTGACACCTTCTCAGTGCCTCTCCCTATGCTTCCCCAATGA
Phase-1 RCT-072 TGGTGCCCAGCCTGGGGCTGGGCCCACATATGCCAGTATGAAGSEQ ID
NO:
GCCGCCTGGATGAAGAGGGCAGGCTCCCACTCCCTTCATTTCCC216
CTAATGGGTGCTGGCCi'CCCCACAAGTTTCAAGACTGACATTTCA
AGGCAGCTCTCAGGACTGCCATTTTTCTCTACACCTGTGGGTTTA
GCTTTTGTATTTTTTAAGTCACAACTTTGATACAAAAGTGTTTCTAT
CTTACTGGTTGAATTTAGCTTACTAATTCACACACCTGGAAGCAG
CAACTTGTAGCATGTAACCAAGCCAGTTGGTTACTCTGGAAATGG
GACAGTATGATGCCATCCCATGTTGAACACTTGCGTCCNATNAAA
CAACGCTGGAATTC
159
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGGAATTAGCAA
AGGAAGCAAAAGGAAGGAATGTTCTATTAAGTGGAGTCCTCCTAA
ATCACTCACAGGATGAGCAGAAGCTACNAGAGAGTTTAGTACAAA
GTGCAGCCATCATAGCTGCCTTGGTTAAGGAAAGAAATTCTGCAC
TCGTCGGGCAGCTCCTGGTGGCATGAAGAACACAGACAAAAATC
ATCTATAAGCTTCCAAAGATCCTTCCCTAAGGCCCCCCACCCCAC
TTGACTGCCTCGCCACCTCAATGTCTCTTCCTTGTGCATACAATASEO ID NO:
Phase-1 RCT-073 TTTTCATTGTTTTCTTATCTTGCCACTTATTGGATGTGACGCTTAG217
GTTGTGACAATTGGTTAATGTGTGTGTTCATGAAC'f-T'ATGTATCCA
ATACAATTGGCTCCAACTACAAAAGGATAAATAAATGGAAAATATT
GCTTTCATGTAAAGAATATGTTCACTACTGCAGCAAGTCCAATTG
ACATGATAGGGTTAGCCATTCCTTCAAGGGCCAAGAGTTTAGACA
GCTTGGTGGTTATGGTAAGTTTATGCTAATTAACATATTATTCACA
TTATAGTGGAGCTTATGGATANGCTTTCAGAATTATACCCNATTCC
AAAATCATCGTCTTCCTATGT
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCAACTTTTTTCCGAG
ATATCCGCCAGACCCCTGAGTTTGAACAATTCCACTATCAATACT
TTTGTCCCCTCAGGCGATGGI-f'TGCCTGCAAAATCCGCTCAGTG
GTGAGCCTGCTCATTGACACCTGAGAAGGCATGACTCCTCCCAA
TAACTAGCCAGGTGGACCAAGGAACCCGGCTCCCCATTCCCAGC
AATGGGACCCATCGCGGAACCATCGGCACCCACACCAAGTCCTCSEOID NO:
Phase-1 RCT-074 TCATGACTCAAAGTCCACTGCAGCCTAGGAGGGTTGTTTCCCAG218
AAGAAAGGGATATAGGCTAATGCTCTGTAAACTGGGAACATTCAA
TTTCTTCAGAGGCTCTTCCA-4A~4AATGGCTCAGCAACGCAAATGT
TTCTCATCCTTCAATATGCAGGATAATTTTGGGGTTTGAACGTTAA
TTTTTCATAGATGTGTATTATTTTGAAAGTATCCAAATAAAAGTCAT
TTATTTTACTATTNNNNNNAANAAANNAAANAAAAAAGTTGTGCGG
CCGCAAGCTTATTCCCTTTAGNGAGGGGTTAATTTTAGCTTGGCA
CTGGCCGTCGTTTTACAACGTCGNGACT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGAAAGCCTTCCACAA
CTTCAACTACTTCCTGTTTTTCTACAACGTGCTGCTGGGCCTGGG
TGCCTGCCTCTCCAGGCTGCTCATCAGCTGCCTCCTGGGCACAT
GGCTGATTGCACGCATCGACAGGACCATCATGCAAAGCGGCTAT
GAGGGTGCAGACATGGGCTTCGGTGCATGGATCGGGATGCTCTT
TGTGGACCATTACCACACCAACCCTGTGCTGGTCAGCTTTTGCCA
CATTCTGATCACAAGCCACAAOGATGGAAAGCTGCAGAAGACTGSEO ID NO:
Phase-1 RCT-075 CGAAACATGGGTGCCCAAACCAGTCCGCAGGTCCCCGATTCTCG219
GCCAGGGCCAGAACGAGGTGGTTCCTGCTGCAGACGCTGATCA
ACAACCCCAGGCTCGCCATGCTTAGAAAATCAAAATCAGGCCATA
GTTTCAGAGAGTTCACACAGATTCTGCTGACCTGCTCAGACTGCT
GATTGGGCCACCAGCTTCAGCTCCGAGGCTAGGCCATCATCCCC
T'f'f'CACAAGGGACTCAGGCTAACTATCAGCCATTCCCTACCATGG
GACAGGATGACATGGGCACTGTTCTGCACATGATANACAACACT
GATCACTTGTGCGATGGCGATGTAAAACCAATGGT
ANCNGAGANNNNNTNNTCACATGATTACGNATTNAATACGACTCA
CTATAGGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGG
CGCTTGCCTAGCAAGTGCAAGGCCCTGGGTTCGGTCCCCAGCTC
TGAAAAAAAAAACAAAAAAAAAACAAAACTTCTGTAANTAGTTGGA
TTTAGGCCCCACTCCTCAGCACTGTGAGATGAATTCACGTCATTT
ATGTTTCACAGNGTTTTTGGAAAGCATAGCTTGTAACATCAGTTAT
ACTACTTCTTGATGACTTCATGTAACCTTCGAAGTTAACGNGAAG
CGATGCTTCATCTTTGCTCCGNAAACTCCAGTCACTGTTTTCNCASEO ID NO:
Phase-1 RCT-076 TTAAACCTGTAAANAGCNANACGGNGAAANNAGAAGAAAAAAAP,A220
GAAAAAGGTGGGGCGGCCGCAAGCTTATTCCCTI'TANTGAGGGG
TANTTTTAGCTTGGNACTGGCCGNCGTTTTACAACGNCGTGANTG
GGAAAACCCTGGCGTTACCCAACTTAATCNCCTTGNACAACATCC
CCCTTTCNCCAGCTGGCGNTAATAACCNAAAAGGCCCCACCGAT
CGCCCTTCCCAACAGTTGCCNCAGCCTGAATGGNCAAATGGGAC
NCNCCCTGTAANCGNCCCCATTAAACCCCNNCGGGNTGNGGGN
GGTTACCCCGCAAGCNTGACCGCTTACNCTTGCCCAGNCCC
160
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGTGAGGACCCAGG
AAGTCTGATTAAAGTGGTCCACTTGCTGGTCTTGTCTGGTGTCTG
GGGCATGCAGATGTGGGTGACCTTTGCCTCAGGCTTCCTGCTTT
TCCGGAGCCTCCCGAGGCACACGTTTGGACTTGTGCAGAGCAAG
CTCTTCCCAGTCTATTTTCACGTCTCCTTGGGTTGTGCCTTCATCA
ACCTCTGCATCTTGGCACCACAGCGGGCCTGGATCAACCTCACG
gEQID NO:
Phase-1 RCT-077 CTGTGGGAAATCAGTCAGCTTACCCTACTGCTTCTGAGTCTCACA
221
CTGGCTACCATCAATGCTCGCTGGCTCGAGGCTCGCACCACAGC
TACCATGTGGGCCCTGCAGAGTATAGAGAAAGAGCGAGGCCTGG
GGACAGAGGTGCCAGGCAGCCTCCAGGGCCCTGACCCCTACCG
CCAGCTGCGGGAGAAGGACCCCAAGTACAGTGCTCTCCGGCAG
AAATTCTTCTACTACCATGGCCTGTCTTCCCTCTGCAACCTGGGG
TGTCTG.CTGAGCAATGGTCTCTGCCTTGTGGGCCTCGCCCTGGG
GCTCAGGACCTCTAACATGGGGCCCTGTGTTTC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATTTTGTAATTTGTGCA
TGAAATTCATGTTATTTCCTGGGGAGAGAAGAGGGCCAACTGAGT
GGGTGGGGGGCACGTGTGGGAAGCAGGCAGAGGGCTCCTTCCC
TGCAGGGGTGGGGAGGGGTCGCAGAGGGCATGCTACGCAGCTC
ACCTGAAGAGGGCTCTTGAACCAGCCGTTTTGGGTTGTGTTAAAT
GTGGGAACTTTCCTCCATTAATGTACAATCTTGAACTAACTGCTAA
Phase-1 RCT-078 T~TGGGATTCTGTTTGT 5EQ ID NO:
AAAAAAAAAAAAATCTCGCGGCCGCAAGCTTATTCCCTTTAGNGA222
GGGTTAATTTTAGCTTGGCACTGGCCGTCGTT'rfACAACGTCGTG
ACTGGGAAAACCCTGGCGTTACCCAAGTTAATCGCCTTGCAGCA
CATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAAAGGCCCGCAC
'CGATCGCCCTTCCCAACAGTTGCGCAACCTGAATGGCGAATGGG
ACCCCCCTGTAACGGCGCATTAAGCGCGGCGGGTGGGGTGGTT
ACCCNCAACGTGACCGCTACATTGCCAGCGCCCTAACNCCCCCT
CCTTTTCCTTTCTTCCCTTCTTTNTCGCCCG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGAACTGGAAGTAATT
TTAGGAAAATAATCACATTTCAATTACTGGGGGCCACTACTTAATG
CGGAAGAGAAAATCAAGTTGCTTTTCCGCCTGTGACTCACTGAGT
TCACAAGCAAGATGTCTTGGCCCCTGGAGATGTGACTGTACCAC
CATCATCCCTCAGTTTTTCATGTTATCACTAATCTACCACAATTTA
AATTGGGGAATGTACTTGCAGCTAAGGTTTCTGCTTTCTTCCTCTT
Phase-1 RCT-079 AAGTGAATTCTTGAAAAATCAAGACAGTATAGCCATAGGGTTTAGSEQ ID
NO:
TGTGGACACAGCCCAGAAGGCCAAGAGCTGAGAACGAAGCAGC223
AGAACTGTCTTGCAGCTGCCAGTGAGGTAGATGAACTTCAAAGA
GCCACGGCAACAAAGCATAGGACTTGTAATCTTTTTTTGCTAATAT
TCAACACGTATTTATTGTCCTTTAATGTCATACCTTACCTATGAGG
AAAGAAGGAGCCAGCACAGCCCAGGTACTGCTCTCTTACCACCC
ATCATGGAGACTCTACCTATATTCCTGGGCTGAAGGCTGGACCA
CGGGACTTNCANAGTTCTGGCAGCTTTTTGGGATGACCGCACTG
GCAAANGGTCTATNANGGNNNTTTTGA
CTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTGTGCCTGATG
GCTGACAGAAAACAAGCAGGAGAAATATACACAAGGGCTGCTTC
TAGACTGTTCAGAGGAAGTTAGGTGGCTGACTCACCTGACCGGT
AACCAACCCTGCCTTCTAAGTATGGCCACGAACAGATCAACACCT
GCTCCTTCCTGGCATACCTGAAAGTGTTAAATACAAGGGAATTCA
AAGCAGTTCATGTCATCATCACGTCTATCCAGAATCTTTCAATTTA
Phase-1 RCT-080 A~~1TCTTCTTGGTTTTTTCAGAAGTGACATTTTGGCTTT'ATT1TCSEQ ID
NO:
CTTTCTAACTCTTCATCTTATCACGTATGATGATACCTTTTACAGA224
ATAAAAGTGAACTATGAGACACTCTCTTACCTTAGAAGTTACCAAA
AAAAAAAAAAAAAAAAAAACATTGCGGCCGCAAGCTTATTCCCTTT
AGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACG
TCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTG
CAGCACATCCCGCTTTCGCCAGCTGGCGTAATANCGAANANGNC
CCCACCCGATCGCCCTTCCAACAGTTGCGCAACCTGAATGGCGA
ATGGGGACC
161
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCAGTTTGATGCTGT
GTTCGCCGTAGAGCAGTAGTTCTCTACGTGTGGGCCGTGACCCT
TTTGGGAGCCACACCTCAGATAGTTACCTTACAATTCATAACGGT
AGCAAAATTAGTTATGAAGTAGCAACATAGAAAATTTTATGGTTGG
GGTCACCCAAGGATAAAGAACTGTATTAAAGGGTCATAGTGTTTG
GAAGGTTGAGGACCAGTGAATTAAGTGGAATTTTTACACTAAGAG
AGTGGTAGAACCAGGATGCAGGCAGTGTACACATTGTTGGGGAG
SEOID NO:
Phase-1 RCT-081 CTGCAGGCTCAGTTCTCAGGACAGGACCTGGATGCGGGCAGAG
225
TGCAGTGTTGGGGAGCTGTGGGTAACAGTCACTTAAGTGGGTTG
ATCAAAACGTGAACACTACCTCCATGCCAGACAAGGGCCTTGCT
GATGATACAGGGACGGCAAGATTGGAACACGGCAACAGCTCTGA
AGCCTGTGGCCCTGACCAGTGAGCCCCGCCTTCTCACAGGCTGC
CAGCACCCANGCAGCTGTNCCGGCTCTGTCTGCACCTGCTCTAG
CCGGCCACACATCTTCATCANTTGGGATTGGGATTGANCCTGAN
CTGCCGGTGTCTGTAATTATCTAATTTCGCTGGNGGNATTCCACC
ANCCTCTG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGAAGAAGAAGCTGA
CAACAAAGACTTCAAAGAAGATGGAGAGAAAGGGGAGCCTGTGA
GCACTGTCTAGATCTGCCCTCTGTGAGATCATAATTTGGTAACAC
GTACCTTCCTGTTGTAATGTTAATAGAGATAAATATTTTTATCAGA
TATTTTATAAACAGTGCTTTTCTTTAGCATCATTCAATCTCAGATCA
TCATCATACCAGTTATTAGTTGCAAAATACCTAACATGACACCTTT
Phase-1 RCT-082 ATACATTTTGTGATTATAGTAGTGCAAAATAGGAAATGTATACTTGSEQ ID
NO:
CAACTTTGTGAATTTCATTGTGTGTAAGTTATGTATTAAATCTTTGA226
GTTTCAACTTTATTCTTATACGTGGTAATTTTGCAGAGTAAGAGAA
TTCCAAAAGAAAGAGTTTGGCACAACTTTGCTGTAGTTCTCTAGG
TTGCTTTTATAAAGAAGGTCAACTATTTTCAGGTAATGCCAAGAGT
TAGGATTGCCATTACCAAATATAACTGTATTAGTAGCTTGGAAAGA
ATATAAAATTTTAATTTCATTTTTGAAGAAATTTTGAATGTTTATTTC
AGGAGGGCAGTTTTGACTATATGTGTATGCACAAAGTTTTGCTGG
GATTTATCCATAATAAAACC
TATGACATGATTACCAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAAATTCGGCACGAGGTGATTATTGTGATGG
AAATTCTCTTTGTACCACCTTAAATTAGTTTGTTAATCCAAAGTGG
AGGAAGACAGCAATAAAATGAATCCAAGTTTAAAAATGGGAAGAC
ATAGGGTAAGAGCTCTCTATTATAAAACTGATTGCATTGTGTTTCT
TCTTACACATCAGTATATTGCATAGCTCTCAATGAAACATTGACGA
ACTTGCTAAGCTTACTTTTCACAAACTCAAAAAATCCTTTAAAGGG
SEOID NO:
Phase-1 RCT-083 CATAGGAAAAAAAATCATTCAACAATAATACCCTTTTGCTTCCTTA
227
GAGCTATACTAAAGTATAGAATTTCAAAACAGGACACCCTTAGATT
TTCCACCTATTCGTAACATGGACGCTGGAACTCACAGGAGAGCT
GTCTGTGGTTCCACAAACATCATATTTTTTGGTGAGTGACTGTGG
TTGTGATTACAGAGCAAGAAGTAAGGCTCTCCAGGCAGTGATGG
CTACTTCAGGTATGACTACCATGAAAGACTATGTGGAATTTCTTTT
ACCTTTGGAAATGTTTGAAAAGCTAGTAAAAAGAATTAGGGAATTT
AAAATTTCANGGGAAAAATATG
TNATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGACAAAAGTCACCATG
GCGTACCTATGAAGAGACCAACAGGTACCGTCTTGTATGCACATA
TATTACCCACACACGCATCACGCATATCCGCACCGTTTGTTTCCT
ATATACAGGCATAAAATAGAGTAAGCCCAGGTAGTTTTTAAAGTA
CCCTTCCGTGTGACTACCGTTGTCGTTCGCAAAGCTGAGAATAAA
AAGTTGTTCATTATGTCTGGAAAGGAGTCGAGTTTTGTCCTGTGA
GCATGTCGGGCTAAGAAGAACATCAGGGCTCCCACTAAGGTTAT
Phase-1 RCT-084 CTTCCCGCTGACAAACCGTAAGGGAGCCATCGGAGCTCACAACCSEO ID
NO:
AAATTGTTCTCTGTGGAATGAAGCTAGTGCCAGCCTGTGGCTTTC228
GGGCTCAGCAGGAGCTAGGGTAAGGNAAGTGTCTTGGTACATTT
CAATGCTGTTGCTTACTAAAGGTflTAACCCCACACGCACTTGCG
TGCGCGCGCGCGCACACACACACACACACACATATGCTTCTTTC
CTCTGCAGTCTGGTTTGGCCTTGTGCTTTTGAGTTTGCCTTCTGN
CAGCCACTAAGGTCACATGTTGTCTTTGGTGTAGTGGAGATTACA
TGCGTANAGGNCCNCATATGGACTCCTCCGTTTCCATTTCGGAN
CATACANAANGNCAGAGGGI-fTTTGGTTTNGGTTGGNTTTTCCTT
TAAAAA
162
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GNNNCNCNNTCTCGACATGATTACGAATTTAATACGACTCCTATA
GGGAATTTGGCCCTCGAGGCCAAGAAATTCGGCACGAGGGTGAT
TTCCTGCCGAGATTTTGGAAGCTTCGTTCTTAAGCATTTTCTCATA
CTCAAGGAAACNAGNCATTAGCAACTTGCTTTTCTTGNTCNCTGA
TGTNNNAATATTTTTTGAATCTGTGTGTTTTTATTTATTCCAAGCTG
CTTTCCAAATGTGAAATTTTCATTTTCAATGTACTGTTCAAATATTT
AAGAGACTGAATACTTGTGGTGTATCAGATATGAATGTGAACATG
Phase-1 RCT-085 ACTTGCCCAACTTCTTGGGATAGCTAGCACTAAGTTCAGAAGACGSEQ 1D
NO:
ATGGTTACTAAAATAACAGAAGGCAATATACGTTAGCAATCTTAAC229
GTGTCTCAGCATCAACATGGCAAAACCATTTCATTATGAACTTATA
GATTTGGATTAAATTTTAGGTTCCAGGAGACCAGAAGCTGATTTA
TGAACACTTTATTCAATCATTCCACTGGGGTAATACTTATACCTTG
CCAAGTATACTAGAAATTCCTTTCTTGCCAGATGCAATATTATAAA
GAAGGAGAGTAATTTCAAAGATATNATTATTTT'GGATGAATTTAAA
ATTGGNAATTTATAAAAAGAAAAATATTTTGCCTAAAAAAACTGTC
CATGGATNTATTCCAAANGTGTTTCN
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCAAACTGCACAGA
GGGGAAATCAAGCTGAATTCTGAGCTGGACTTAGATGACTCCATT
TTAGAGAAGTTTGCCTTCTCCAACGCTCTTTGCCTGTCAGTGAAA
CTGGCTATTTGGGAAGCAACACTGGACAAATTTATTGAGTCTATT
CAGTCCATCCCAGAGGCTTTAAAAGCTGGGAAGAAAGTCAAACT
GTCTCATAAAGAAGTTATGCAGAAAATGGGTGAGCTCTTTGCCCT
SEQID NO:
Phase-1 RCT-086 CAGGCATCGAATAAACCTGAGCTCAGACTTCTTGATCACCCCTGA
230
CTTCTACTGGGACAGAGCGAACCTGGAGGAGCTTTACGACAAGA
CCTGCCAGT1CCTCAGCATCACTCGAAGAGTTAAGGTCATGAATG
AAAAACTGCAACACTGCATGGAACTAACAGACCTAATGCGCAATC
ACCTCAATGAGAAGCGAGCGCTCCGCCTGGAGTGGATGATCGTC
ATCCTCATCACCATTGAGGTAATGTTCGAGCTGGGGAGAGTCTTC
TTCTGATCTTGTGATCATGAAAGCACCACTGGAAGAGAGTAGTCA
AGTTCTGCAACCAAAAAACCAGCGTTCCT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCTCCTGGGTTCCCA
GTCTGAGCTTTCCAGGTATTGATGCTTCACAGGCACTGCTACATA
CTGCTGAGGGAAACATGTCCTGCGTGACTTTACTGGGAAAATTCC
TAGCAAAAATTTTGTGCCTGATTTCCTCTGGACGTGTGCTGAATA
GACTTCCACAAGAGTTGTGCACACACATTCCTGAAATCCTTCTCT
GCTTCCTGCCCTTGGAATCTAACTGCCTCAGCCTAGAGGAATTCT
Phase-1 RCT-087 AATCATTCCCTGCTCACCCAAGGACCGCTGGCCCTGTTTATCTTGSEO ID
NO:
TCATTACCTAGAAATTCGTTCTTATCAGAAGGCGCATCTCTTTCAT231
TGTCCCTTTTCCCCTCGTCCTTCACTACTTATAGAGGAATATTTAA
AAGAAACACAGAGGGGATGAATTCACTCGAAAATTGTTGTATGAA
ATTCTCAAGGAGTTAAAACCATGTTTCAAAAGAACAAAATGTGGA
CAGCATGCTGCCATTTGCTTAAGGAAGTGAGATAGAGAAATGCAC
CGAAGGATTTCTGGAGGCGTCCAGGCTGCTTCTTGCTACTTCAG
CAGACTGGTGCCCACTGGTGGGGCCTCTCCGGGGTTCTTCTGGA
CAGAA
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTGTGTTCCTCTGAAA
TTCTGGACTGATTTGGACAACTGAATCTGGAGCGTGTGGGATACA
CAGGGGAGTTGATTTTTTATAAGCACATGAAACAGACAGTAGATT
TCACACTTTTCAGGACCATAGTGTTTGTCATGCTTTAGTTATATGT
GAGTGAAGTGGCAGAGGAGGTCATGAGGCAGTTGGATTCTGACT
GTACTGGAACTGACCTTAAATGAGTAGAGAACATTCTTGGCCAGA
SEQID NO:
Phase-1 RCT-088 ACGTGGCACTGTGTAGAGGCAGCCCCAACACTACCTCTTAATTG
232
GTTTATTACATGTAACTTTCCATATTTTCCCTCCCTTTTAAAGTCAG
CAGTATTTTCGTTTTAAATGTCATCTTAGAGCCGCTCTACAAAATG
TTCCAACAGACACCACTAAAACTAGACCATTCCGAATTCATGTTCT
TTCGAGTTTTATCCATTATCCTTAAAAGTAAGTGCTGTTACACCCA
CATTCCTGATTGTATGATCTTCTAGCTCTGTACCAATACAGGGTTT
CCTGTAGTCCAGACTGGCCTCATATTCACTGCATAGCTGAAGATG
ACCTTGAACTTCTGATCTT
163
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGAGAACTCTATTTGT
AGGGGATGTGAGCCCAGTATGGGCTCTCAGCTCTGTGTATAAAC
TGTATAGACTGTCACCTCTGTGTGTGCTTGTGTGAGCTCCTGCTT
CCGCTAGGCCCTGTTCTGCCTGGGCTACCTGCCTGTGCAAACAT
TTCCCTTTGGAAATGACAGGCCTCCTGCCCAGGCCCCCTGTGTT
ATCTGCTGCCAGCTTCCATGTGTCATGTGTCCCCAGGCACGGGT
CAGTGTCTACCAGGAGCCCCCACCCTCTTAACCTTGTGGGGTAA
SEOID NO:
Phase-1 RCT-090 TTCGATGGGAAAACTTAACCTGGGCCCCTCCCCCCAGGAGTCCC
233
TGTGCCAGCCCCACCACATCCTGGAAGAGGAAGGGGCCCCTGG
AAGGGGCCTCCCTCACATCGCTGCTGTCCTTCACGCACTTCTGG
AACAGCCTTAGGGGTAGAGGTTGGGGCTCTGGGCCCCAACTACC
ACCGGACCTGCCCTGGGAGCAGATGACACCTGGGCCCTGCCAA
TTAACAAGGACTTGGTGACCATGGTCTTGTGTGTAGTATTGGTCT
TGGGTATTCCCCCTGCCCTTANGCTGCTTCGAGTGCAGCCCCTA
TCTGGGTGAAGAGTGTTGTGTCNAACACAATAAAGAAAANCCCAA
ANGGCN
TCTATGACATGATTACGAATTTAATACGAATCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCTTTGCTCCAGCAT
GGCTGCCTTAGGGACCTGGCTATCCATAGGTGTCCGGAGGTTGC
ACAGTAGTGCAGTGGCGCGGGCCGGCAGCCAGTGGCGACTCCA
GCAAGGGCTGGCTGCCAATCCTTCCGGCTATGGGCCCCTCACG
GAGCTTCCTGACTGGTCTTTCGCGGATGGCCGCCCTGCTCCCCC
AATGAAAGGCCAACTTCGAAGAGAAGCTCAAAGGGAGAAGCTTG
SEQ ID
Phase-1 RCT-091 CAAGACGAGTTGTGCTGCTGACACAGGAAATGGATGCAGGATTANO:
234
CAGGCATGGAAGCTCAGGCAGCAGAAACTGCAGGAAGAAAGGA
AGCAGAAACATGACCTTAAACCTAAAGGGACGTCACTGAGGAAC
CCACTTCCAAATCAATAAAAAGCTCCTGTCCCACTTTCAAAAAAAA
AAAAAAP,AAAAAAAAAAAGTGAGCGGCCGCAAGCTTATTCCCTTT
AGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACG
TCGTGGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTT
GCAGCACATCCCCCTTTCCCAGCTGGCGTAATAGCGAAAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTGCCTACCCGGTCTCA
TTGTTCATGACTGCATATCATTAGCGCGCTTCAAAGGTGTTCATAT
TTTCGAAGATCTGGGGGGTTTTTTTCTATATCGCAGGATATTTTTG
TACATGCTTAGAGACCTCATTCAGTTGATAATCCCAACATTGTTTG
TCATCCTTAAATCATGAGAGTAAACCCAAGTATGACAAATTAAAAG
AAAACTCTAGTCTTTCTAAATTTGTCTTGTCTAAAAAATATGTTCCC
SEQ ID
Phase-1 RCT-092 ATAGACTGCCAGCATTGCTCTCACCTAAGGACGAACCACTCCTCCNO:
235
TCATTCCTTGTCTTCAACTCATGCATTTGTAAATGATGCTGGCAAC
CTACATGAACAGACAACATTGTCTCCTTGCCTCTGGACAGCCTTA
CCAGCTGGTCTCATCTTCCTGCATGGCCACACCCCTAGTGATGG
AACTCAGGTANCATAGCACAACGTGAAGTTGTAGTCTGTTGAGCC
TCCCATACCAATGAGAAAAGAAGCTTTGGAATTCCAGTTTTCTGA
GATTCTGGTAGTACCTTCATATTTCATGTTGTAGACATTTGAAACT
GNGGTAAACTTTATTTTT
NNGNNNNGCTTATGACATGATTACGAATTTAATACGACTCACTAT
AGGGGAATTTGGCCCTCGAGGCCAAGAAATTCGGCACGAGGCTA
CTCTACAACACCACACCACTTGTCCTACAGAGACAAAACAAGGAG
GCTCTTACTTCATCTCCAAACTCATTTCCTGCTTNCNGATACATGC
CTGCTCTTGTCATCTATTTGATATATTTCTGAAGGTGCAACAATCA
TTTGAAAAGGCAAGTATTAATTCCCAGATGCCCACCATTGATCGG
GCAACCTTGACAAGATATTTCTACCTCTTTCCTGGCAATTGAGAA
Phase-1 RCT-093 CAAAGCAGCTTGAANAAGTGATCTTGGCCAAGGATCATGATATATSEQ ID
NO:
ACCTGCAATTCCAGGATTANGGAAACTGAGGAAAGAATAATTATG236
AATTCAAGACCAGCCTCAGCAATACTGTGGGATTCTGTCACATAA
ACAAGCAAACNNAGCAAAAATGAAACAAACAAACAAAANACTTTG
GTGAGCGGCCGCAAGCTTATTC
CCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTA
CAACGTCGTGACTGGGAAAACCTGNCGNTCCCAACTTAATCGCC
TTGCAGCACATCCCCTTTCGCCATCTGGCGTAATAGCGAAGAGG
CCNCACCGATCGCCTTCCAACAGTTNCGCAGCCTGAATGN
164
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGAAACAGTTTATTT
TAATATTATAAATACTGTTATTTTTGAGCCTCTTTGGCATGTAGGA
GTTCCGGGTCTCAATGTATATTCCGTGGTGTATATGATTCAGGAA
AGAAAAATTAATCAAGAAACACATGGTTCTGTGACAGAGAGAGCT
GTTTTCTGGGAGGTGTTATCCACCTTTTCATTCGTGGATCATGGT
TCTTAT'i1'ATATTTCTGCATTCCATCTAGTTTCCTACATTCCAGCAG
Phase-1 RCT-094 CCCTCTTGTCCCCCAACTAATAAACTGACTGAAATCAAGAGAGCASEQ ID
NO:
CCCCAAAGTTATTTGTAAATAGTTACGTGGGAAAAAAAAAGACAT237
ATTAAACTTGAAGATAAAATGTGNCAAACAANAAANAAAAAAAAAA
AAACCCATGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATT
TTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAA
AACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCT
TTCCCCAGCTGGCGTAATACCGAANAGGCCCGCACCGATCGCCC
TTTCCCAACAGTTGCGCANCCTGAATGGCGAATGGGACCCCGCC
CCTGTAACCGGC
NCTCTTTGCTATTCTAAGGCCAAAAGCCGGNGGCTTCTAGTAATT
AACTCCTATTGTTANCAACAGGNGATTAANAACCCCAATAGGCCA
ATAGGGCCAATAGTGTGGGTTGATGCCCAGGAATAATTAGGCTAT
GTAATCATGACAGGAAAGGCATGACAGGTTGGGGATTTANCACA
SEQID NO:
Phase-1 RCT-095 AGGCCCTGAATTCAGTCCTCACCTCTGGGAAAAAAGAAAGCCTC
238
GTGCCGAATTCTTGGCCTCGAGGGCCAAATTCCCTATAGTGAGT
CGNATTAAATTCNTAATCATGTCATAGCTGTNNCCTGGGGGAAAT
TGTTATCCCCTCCCACNCNNANTNNNNCNCCCTTTTCNNCNNTNN
TTNNNTNCTCCCGC
TTTTTTTTTTTTTTTTTTTTTGCATAAAACAAGTTTAATTTCCAAACC
AGGGTCACAGCCATTGCATTATCCCACATTTTTGAGCAAGGATAG
AGAAGGCAAGTTATTAAACACGTACAGTCTACATTCCAGAGACAG
CAAAAAGAAAAAACCCACTTCAGAACTGCAGATACCACTGTAACA
Phase-1 RCT-096 CCATAAATTCTGGAGGTGGAGGGAAGGGAGAGTCCCCACAAAAGSEQ ID
NO:
AAAGGTAGAACAAGATCAAAAATTAAACTTGAGAAAAGCAAGAGA239
GGGGTTGACAGAAATGGGATGAAATGCCCAACCCTTAAAGACTG
ATTAGGGAATGTAGAAAGCTCCCCAACCCCACCACAAAGCCAGA
TGTTACCAAGATGTCACTGCCCTCTGCTGGACATATCTGGAGCAG
CAGGCACCAAGGCA
AAAACACAAAATGCNGNNNTNGNNANNTNNGNTNCTCNNNNNNN
GAAGGGAANNNGGCCCTCGAGGCCAAGAATTCGGAACGAGGCA
GAAATCAAGGCGAAAATGATGAAGCAGCTTNCCACAGCACGGNG
TGGGCTGATGGAGGACCGGAGAATATTCGGCCATGTGGGGGTG
TTTCCTGAGACCTGCTCAGAGCCAGCACCCCAACCTCCTGTGGT
Phase-1 RCT-097 ACAGGACCANGTCGGTGGGTGTGTCCCTGTTTTTATGTTCCGATGSEO ID
NO:
TCAAGTGAACCCTGGAGGGTACTGGAGCAATCCTCACCGCCCAT240
GGTGGGGCACTGACTGGAGCGCTGGTGGCTCCGACTTACTCAG
CTACCACAGACACCATGTAAGGAAGCTNGTGTNGTGGGACAAAA
CTTTAACCGGCTCTTTTGACTCACNTGCTCTT'GNGCCCGGNCCCC
ANACACCATNGTTGCTTTTGGTNCNTATCCTGGGANCCAACTGAC
CCAACCCTTTGTGAGCAAAGAACTTATTNTTGAACTTGACNTTA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGCCGCCGCCGTCTC
TGCAGCCCACGGGTCCCTGGGCCGTTCCGCCGCCCGCGTGCGG
CCCCGGCGGAGAGATTGAGTTGAGGACTGTGTGGCGGGCTCTC
CCTAGTATGGCCAATGAAGAAGATGACCCAGTCATACAGGAGAT
CGATGTGTACTTGGCCAAAAGTCTGGCAGAGAAGCTGTATCTCTT
TCAGTATCCTGTTCGTCCTGCTTCCCCTGATGAGCAGAAGGTATT
TGCCCTCTGGGAGTCTGGAGACATGAGTGACCAGCATCGACAGG
SEQID NO:
Phase-1RCT-098 TTTTGCTTGAAATATTTTCCAAAAATTACCGAGTACGTCGGAATAT
241
GATCCAGTCTCGGCTGACTCAAGAATGTGGAGAAGAGCTAAGCA
AGCAGGAGGTGGATAAAGTGCTAAAGGACTGTTGTGTAAGCTGT
GGTGGCATGTGGTACCTTAAGGGGACAGTACAATCCTGACAATA
GTAGCAAACCACTAACTCAACGAACCCAAGCCCAGGGAAGGACG
GCAGAGCCACACGTAGTCTCGACTTGCCTCAAGACACAGGAAGA
NGATCTGCCCACCTGGTGGCCTGTGGCACTGCCTGGCCCAGAG
GACAGAAGGGCTCACACTCACCCAGTGGCANGGTCAGCGTAAGT
GAGATCGCTCCAACAN
165
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGATCTCAGTATTTAAA
CTGTTCCTCAATTTTGTGAGGCTGTGTTGGAAATAACCCGCCTCT
GATGCTGTTGGTATGCAAGGCAGCGGTGCTTACACAATATTTCCT
GTGCTCTCCAGAGACGATGGACTGATTTCCTGACACTACTCTCCC
TTCACTTCCGTGGTTACCTTGAGTCTTGACTTACAAGTGCCCACG
ATGGGTGTAGCCTTTATTAAACAGATCGTGTATTCTGATCTCTCG
Phase-1 RCT-099 CTGCAGCCACAGTGCAGCTCCCTATAAACCTGCAGCCCAAACCASEQ 1D NO:
TTTGTATCAGGCATCACCTACTAACACAGACGTGCGCGGCTTTTC242
TGCATCAATTGCTGTGACGGTTCAGAATGTTGGTATACAAGAAGG
AATAGAAAACTGATAAGGTTTTAAATAATCTGTAATI'TCAATCTTTT
TTTTCTGAAATACATTATATTGTATGTTTGAAATAATTCTAGTACAA
AGTATAATAAAACTAGATGTATAATAAACCCTTTAAATCATTGCTA
AGTGTATAAGTGGGAACTGAAGCATTTATTGGACAAAGTAATGTT
AGTCTAATGGTTACTTGCTCGCTCCTGCGTGGGCACACTGGTTAT
NATTT
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGACCCTGCCCATAA
CCTTTCCTCTGGTCCTTCTTCCTCTGTCTTCTCCTTCCCCATCTTT
GTACCTGTTCTCTCCTGTCCTGCCCCATCCTCAGTAGCATCCCCC
GGTGCTGCCTGGCCCCTGCCTCAGCAGTCAAATTCCCAGAAGCA
GTCCAGGCGGCTGGGCTGACTCCTGAGACCCCCGCAGAGATCT
TGGCCCTGGAGCACAAGGAGACACGCTGTACCCCAATGCGGAG
Phase-1 RCT-101 AGGAGATGACTGGACACAGATGCTGCGGGACACGATTGAGGCCSEO ID NO:
CTGTCCCTGCGCTGGAAAGGCTGTGTAGAGAACACCGCAGAATA243
GCCAGGCTGGAATGGGTTTGAAGACTTTTGTCCCAGGGACGGCT
GGGACAAGATGGCTCAGTAGTTAAGAACTTTTGCTGCTCTTCCAG
GAGACCCAGTGCCCATGTCAGAAGACTCACACTATCTATAACTTC
AGCTGTAGGTTT1TTGACACCTCTGACCTCTGTAGGCAATGCACT
CATACACAGATACACATACCTATATGTAATTAAAAATAATAAAGAT
AAGCCTTCTTTTCT TGNGG
GNGGNCGCNAGCTTN
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTGAAGATGAAAAGCA
AAACAACCTTTTTGATAAGCAAGGTATAGATTTTACATTTTTGTCC
TTGCTCCCAATGAAATGGATAAACAAAAATAAAP,TCTGACAATGC
CGTCTCTTCACGGAATGTTGTTGTGTTAGCCGGACTGAAAGCCCA
CCTTAATTTTTATATAACGTCTTTAGCTCTTCCTTTGACAGGGCAG
GCCTTGTTCTGAACTGTTTGCGCTTCTGACTGTTAGACACCAATG
Phase-1 RCT-102 ACGCATGCACTGTCCCTCTCATTCTCTCTTGCTTCCCCTCTGGCCSEO ID
NO:
TGAGTTTCTTGTGCATCCTCCCTACCCCCACCTCTGTTAGGGTAG244
ATATATCAGCTATGTAAATAGAGCAAGGAAACGGTATTGTGCATT
TGTGGCATTTACGNAGAGTTGCAGTTGTACGCTGCTGAAAACGC
ANGCTTTTTGTAACATGTGGTCCTTCCATAAGTACCCNATGTATTT
TAGNCTATTTTAGTCGTATTTGNTCNATAAAATATGCAAGCTATAN
GGTAAACANANAACAAANAAAAAAANACCNTTGCGGCCGCCAAG
CTTATTCCCTTTAATGAGGGGTTAAATTI'TAGCTTGGGCCTGGCC
GCCGTTTAACAANGNCC
TTATNACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCTCCGCTTCCCGCTT
CCTCCTGCGGTCCTTCGTTTTGAGACAATGTTTCATTATTTAGTGC
TAACTGGACCAGAACTCCTGGTGTGGAACAGTCTGGCTTCCAGT
TCACAGATCTTCCGATCTCTGCCTCTCCAGGGCTGGGATTTTCTT
T GATGTGTGGGTGTCTGGCATC
TTAGGAAACCAAGCAGACAGGCCGCGCRGACATATACACAGACA
Phase-1 RCT-103 AAACACCCATAGAAAGCCAAGTGGAGGGGTTGGGGATTTAGCTCSEO ID NO:
AGTGGTAGAGCGCTTGCTTAAGAAGCGCAAGGCCCTGGGTTCGG245
TCCCCAGCTCCGAAAAAAAGAACCAAAAAAAAAAAAAAAAAAAAA
AGAAAGCCAAGTGGAGTGTGATGATGGCCCACCTGCAATTCCAG
TGCACAGGAAACAACTAAGGAAATTCCCGGAGCAAACTGTCTAG
CCAGACTACTGAAATGGNGAGTCTATCTANAACCCTGATTCAGTG
AAAAATGTGGANAGTCATGGAGGGAAAACAACCAATGTCACCCT
CGGNAATTNCATATACCCGTGNGCATACCTGNGNAAATTTTCANA
ACATTCATTACATTGCATTGCC
166
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTGATGTGGAGCTC
GATGACCTAGAGAAGGACGAGTTGTGAGGGCCACAGCCCGGCC
TTCAAATGTCTTTCCTTGGGAATGAGCAGTTTTCCAGCAGGAAGT
TCTTCCGGTCAGCTGTCTGCGCTGGCCTTTCCGAGCAGTACTCG
CCGGCCACTGGAAACTGCCAACAGTGAACCTCAGCGTCTCAAGA
AAACACTGAAGAATTCTATGAATTGTAGCAGTGAATTGGATTGTAT
SEQID NO:
Phase-1 RCT-106 TCTCTGGCATAT'1-T'TGAAGAAAATTGGGCTATTGAAACATTTTTCC
246
CTCCTGACTGCTGCTTGAATGTTCTTGGAAGCTGTTTCGTATGTA
TAGGGTTTTTAAAATGTGATTCCTTTGTTTGAATATTAATGGCTTTT
TCCATTAAAGAATAAAATGATATTTTGGAAAAAAAAAAANNAANAN
AAAANANNAAAAANAAAAAAAAAANANAAAAAAANA,AAAAAAAAAN
AAAATTTNCNGGGCNNCAANNTTTTTCCNTTTNTNGGGGGGTNAT
TTTNANTTGGCCNGGCNGGGGTTTTAAANCCNCNNGATTGGGAA
AACCCTNGGGTTACCCAAATTNNTTCCCTTGGAANCCCN
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAAI?'CGGCACGAGGCTCAAACTCACAATG
TAGCCAAGACTGGCCAAGAGCGGACAAACCTGGCTCCACTTCCC
AAGTGCTGGGATCATAGGAATGTGCCACCACACCTCGGTGTTGA
CCTCAATCCCATAGTAAGCGGTGAGATTAACGTACCACAGAGCAT
TCCCATTGCGATCGCATTCTGCCATGAGGTGGGAAGAAAAATGG
GCGATTATTTTTAGGGAAAGGACAAATTTGTGGTCACCTGATCTG
AAAGGACTGGAGATATTATTTTCCCTCAGGTGTTGGAGGACTGGT
gEQID NO:
Phase-1 RCT-107 GGCTGATTGGTCAGACTCTTTCATGAACCGTGTAGGAGCAGTGC
247
TGATTGGTCAGGTTCATTTAAGAACCGCGGGAAGTGGTGCTGATT
GGTCAGATTCATTTAAGAACCGCGGGAAGTGGTGCTGATTGGTC
AGATTCATTTAAGAACCGCGAGGAGCGGCGTTTGTTCCCACAAC
ACATTTCATCCAGACGCAATGGAAAAAGCACTGTTAGCTTTCCTT
GTTTGTGTGCTAAAGATTTCTTTTGCCTTATGATTGTTACTTTTGCT
TGTTTTGTTTGTCTTTGTAACAAAATGACTTTTTCCAAGGGAAAGG
AACCTTTTAAGAAAAAGAACGGCACTCTCTGCACGATGCGAGAGT
GA
TTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
~GGCCCTCGAGGCCAAGAATTCGGCACGAGGGAGCGGCCCAAAG
GTTI'TTTTTTTTTTTTTTTGCTTAAGTATACTATTAATGAATTACATT
TGTAAAAGTTATCTCTAGTTTTTCTTTTTCCTATTCAACTTTTGTGG
CAATTCAATACATTTTATTTGTAATATAT'fAAGTATTAGGGGTAGG
GAAATGAACCACTGTACTATTCCAATGTTTATATTTAATCTAATTGT
GCAGAATTGAAACTTCTGAAAATTCAATGGTAAACAAATGTCTAAA
gEQID NO:
Phase-1 RCT-108 GGTTTATTTCCTTAACCAGGAGCTTCATGAGTAAACTGATGTTTTT
248
AATGTAATGGTCAGTAAACACAAAAATGATTATCTAAAGAACACAT
GAAAAGCCACATCTCGGGGCTGGGGATTTAGCTCAGTGGTAGAG
CGCTTACCTAGGAAGCGCAAGGCCCTGGGATCGGTGCCCAGCT
CCGGAAAAAAAAGAACCCNNNNAAAAAA CCTTT
GCGGCCGCAAGCTNATTCCCTTTAGGGAGGGTTAATTTTANCTTG
GCACTGGCCGTCGTTTTACAACCGTCGTGACTGGGAAAACCCTG
GCGTTCCCCANCTTAATCC
TCTCAAAGTGATTTTTCCCAAGNATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGAGAAGCTACTAG
GCATGTCAAGCAGTCAGCAGGATTTGTCTTCATGGTCTTCTGCAG
ATGAGGTGGACACGTCGGGGTCAGTGAGTCCTACATCAGGAAGA
AGTACCCCAAACAGACAGAAATCGGTCCACAAAAGGTGGCTCCG
ATTCCTCCCTTTCTAAACCAGGCCAGCACGGGCAGGTCGAGATT
TCTTGTTCCGGGTCCTCAGGGCAGCTCTTCCGATTCAGCTGCTC
CTACTACTCCTTATCGGACTCACCTCCCGTGTACCCATATCGGAA
SEQID NO:
Phase-1 RCT-109 GAAGACTACAGCTGTGCCCTCTCCAACAACTTTGCCAGATCGTTC
249
CATCCCATGCTCAGATATACCAACGGTCCTCCTCCCCTCTGAAGC
AAGCACACGTGCAGGCAGCAAGAGGGGAAGCAGGTCCAAAGCA
ACCCCAGGCTGTCAGAGAAGGTGTGATCTTGGCAGAGGTCATCA
TATGGCAGCTTCCGTTCTCCCTAACCCGTGTATAAAAAGAAGGAA
AAAAAAGCCTTTGGGACATGGGACAGTAAAACAACAGGAGGCAA
ACAAAACTTGTAATTGGTACAGTGNCNATTTGANACTCTGAGCCC
TTAATACTAAAAGAAATTAAGGACATATANGGGTTCCCTANAACC
CATGAAGTCTTGGGCCC
167
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCTGCAGTGAGAAAGT
GGCAAAGGGCTTTTCAGCTAAGGTCACCCCAGTGACCACCATCC
TTTGTCCACTGGGGCAGGTCTTGCATGTGTCCCTAATGCCGCAT
GGGGTCCCTGCCTGCGATCTCCCATCTGACCCACCTCTGTCATG
CATGGTGATGGTGATGTGTTTACTGTCTGGTCCTGTGCCTGTCTG
AGACCGTCTCTGTGGAACTTGCCTTAAACTGAAGTAAACCAGTTC
Phase-1 RCT-110 TTTTAGTAAAACCCCTTCTCCTTGGAAAACAAAAAAAAAAAAAAAASEQ ID
NO:
AAAAAAACCAATTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGT250
TAATTI-fAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTG
GGAAAACGCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATC
CCCCTTTCGCCAGCTGGCGTAATAGCGAANAGGCCCGCACCGAT
CGCCCTTCCCAACAGTTGCGCANCCTGAATGGCAAATGGGACGC
GCCCTGTANCGGCGCATTAACGCGGCGGGTGTGGTGGTTACGC
GCAACGTGACGCTACATTTGCCAGCGNCCTANCGCCCGCTCCTT
TCCTTTCTTCCCTTCCTTT
AATCCCCAANCCCCGGAAGGTAAGTTTTAACCCAATCCTTTTTTG
TGTNACATTCAAGGAATGNAGGGCACAAGAGCAGTTAAGTAACTT
TGCCCAAAGGCACACAGCCAGGGAAGGGTGGGCGAAGGCAAGA
GTGGACCAAGGTTGTACCTTGAGAGTCCATGCCCCACCACGAAG
CCACCCTTGTCTCCTGGCTCCCTCATTTGAGAAGCAGGCCCGCC
ATTCCACCCCGACTCTGCAGCCTACCTAGTCTGAAAGAAGAGCTA
Phase-1 RCT-111 G~AAATGGGAACATATTAACTCAAAGTCAAGAGTCCAGCAGGAASEQ ID NO;
GGAGACTCAGGCAGGGAACCCTGAAGAGCCTATTTGCTGCTAAG251
GCTGCAGCTCATATTGGCCCTCCGTGGCTGTGTAGAAGTCCTCC
AGCACTGACTGCAGGAACTCAAAGGTAGGCCGCTCCTCAGGTCG
GCCTCGCCAGCACTCAGTGATGACGTCATGGTACAACTCAGGCG
GACATGTCTCTGGGCATGGCATTCGGTAGCCATGCTCCAGGCTA
CGGATGACCTCAGGGTTGCTCATTCCTGGGTAGGGAACACGCCC
ATATGTGAC
TTATGACATGATTAGGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTTTTTTTTTTTTTTTA
AACTAAAAGTGTCACTGGGTCACTTCCGTGTAATTGTTACTCATG
AGGACAAAGTACGTTCATGTGGCTGTCATTTCACTCAAGCACCCT
GGTGGGCAAAGGCAGCCATATTGAGATTGGGCAAGATCCACGAG
AGAAGAAACACTGACTTCCAGGGTGGTCCTCAGCTCCTGTTAGT
GCTGCCTCTATGTTTTGGCAAACAGAAAACTCTCTGAAAGCTGCA
Phase-1 RCT-112 GGGAGTGTGTGGGCCAAGTGATTTCATCAAGGGAAAAGAAAGGGSEQ ID NO:
GGAAAAAAAAAAAAAAAAAAACCTTTGCGGCCGCAAGCTTATTCC252
CTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTAC
AACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGC
CTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGA
GGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATG
GCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGG
TGTGGTGGTTACGCGCAGCGTGGACGCTACACTTGCCAGCGCC
CTAACGCCCGCTCCTTTTCCTTTCTTCCCTTCC
GTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTGCTGTGGTTTC
TGGGGCATCTGGTCTTTGTCCATTACAGAAGGACTGGGGGACTT
AATTTCCTTGAAGTGGAGCCTGACTAGAAACAGGGTCAGTGGTA
GATGGCAGACTCTTGGGCAGGAAGAAGCTTAGAGCAAGTGGGAA
AAACTAACTATCCAGCCTACTTTACTGGGCTCACCTCCGGGGCAT
CCCGAGACTTGTCCAAAAGAGGCAGTCAGCACCAAAGGACTTTT
Phase-1 RCT-113 ACACAGGGTTTTTTGGTTTGGGAGATGTTTTTGCTTTTTCATACTTSEQ ID
NO:
AAACTGACTCGATGCAGGTTTTATATCCTGGTGACTTGCTGTCAC253
ATTCTATCAGTTTTCAAGGGCCAGAATGATGAAATAAATAAATAGA
AAATTCCGTCCTTCCATGCCTTAGTTTAACAGGTAGGCCCAGTTC
TGTGTTTTGTGTGTTTCGCTGTGTAAGAACTGTGAAATGGGCAGA
CGACTTTGTGGGTTTGTTTGGTTTTATAAGGCATTTCAATGTACAT
TCTACAAGCACTCCGTTTGCAAAGANAACCTAAAGTCACTGTCTT
CCCCATTCATCTTTGCCCTCCTCCCTGCACCCCCGANCTTTACAG
CTCTGTAAAGAAAC
168
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCCTTCAGTGCTC
GATTCAGACCTTATCATCCAGAGCAACGCCCAACTACAGCAGCT
GGCACTAGTTTGGACCGACTGGTTACTGATGTCAAAGAGAAACT
GAAGCAAGCTAAGAAGTTCTGGTCCTCTCTCCCAAGCAGTGTCTG
CAATGATGAGAGGATGGAAGCAGGAAATGAGAATGAGGATGACT
GTTGGAACGGGAAGAGCAAAAGCAGGTACCTGTTTTCCAGTGAC
Phase-1 RCT-114 AGGAAACGGATTAGCCAACCAGGGCAACAACCCAGAAGTGCAGGSEQ ID
NO:
TTGACACCAGCAAGCCGGACATTCTGATCCTTCGTCAAATCATGG254
CCCTTCGGGTTATGACCAGTAAAATGAAGAATGCTTACAACGGAA
ATGACGTGGACTTCTTTGATATCAGCGATGAGAGTAGTGGAGAG
GGAAGCGGAAGCGGATGTGAATATCAGCAGTGCCCTTCAGAGTT
TGAGTACAACGCCACTGACCATTCTGGGAAGAGTGCCAACGAGA
AAGCTGACAGTGCCGGTGGTGCCCCTGCAGAAGCAAAGCCCTAT
CTCCTCCTGCCCTCTGCATCCTGNTCCTCGCTGTGCAGGGAGAG
TGGGAGATAATTTGTCAAACTCT
TCTAGGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAP,GAATTCGGCACGAGGGGCCGCATGTGTT
TTTTTTTTTTTTTTTAAATCTTTTTTGACTCAGGGACTGTCTGTATA
GCTCTGGCTGACCCAGGGTTGGTTCCTTATGTAGATCAGGCTAG
CCTGAAACTCACAGAGATCCACTTTTCTCTGCCTCCTAAGAGCTT
GAGTGAAAGCATGTGTGCCACATCTAGCCTTCTGTACAGCTTGTC
CCTGCCGTCCTACCTAGAGCTGCCCAGCCTTTCTAAATTTGTAGC
SEQID NO:
Phase-1 RCT-115 AAAAGGTTTAATTTCTCATTAACAAAATCTTTCAAATCCAAATCAGT
255
CCTCTTTTTAAAATATTTTTAAACCCAAATATGTCGTTGTAACTTCA
TTTCTTTCTCTCATAAGCTATTTTCCTTTCTTAAATTTACAAATCAT
GCTATTCCTTAAAATGTTCAGATTTATGTAAAATCAGTCCCTTTCT
CAATAAAATAATTTGCATTTTAAA,F~AAAAAAAAANAAAAAAAAAAAN
AAAACACGTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAAT
TTTAGCTTGGCACTGGCCGNCGTTTTACAACGTCGTGACTGGGA
AACCCTGGCGTTACCCAACTTAATCNCCTTG
TTCCTGTTTCTAATTTGGGGGGTATNTACGGGAAGCATGTTAACA
ACCAAGCATTCAACCGTGNAGACACAGACTTCCAGTCTCCCTAG
CAGGCAGGAAACCCCGTTGTGTGCCTGATGGGTGTTTGCGATGT
GCTGGTTGGTGTTTTACACTGTGATAATAATCCTTCTCGGCTTAC
ATCTCCTTCTTTTTTGAAAGCCCAT~tTTTCCAGGCTTGAGGAGAA
GGGCTTAGCGAACAGACCACCTGTCACGCAAGCATGAGGACCTT
SEOID NO:
Phase-1 RCT-117 AGTTCGAATCCCAGGCATTCACACACAAGCCAAGTATGGACCTA
256
GCTAACCGGCCACACTTAACCCCTATACCCCTCTCACACTCACCT
CTTTTCCAGCCTAGCGTGCGCCTCTCCCCCTAAGACCCATAAACA
GTACAGAAAACCCAGAGAGAGCATGCTCTGAGGCACCGAGAGAG
ATTAGCCGTTTTCGCTGCTTTCAGTTCATCACATCAGCGTTCCAG
CTTTACACCCGCCAGTATCTACGACTCACACCTACTGGACGCCAA
GTCCCCCACGGCTGGTCCAGTTCTCCATTCTCATCCTCAAG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGCTTTCAGAAGGTGA
CTTACGAGAGCCTGACTTCAGGGATTGTGGCCATTCACTCTGGC
TTCAAACTCTAGCTTCTTTGCTATTGTGGAGCAGAAGCCAGGCAT
TTCTACTGAAGCCCGGGGCTGGAAGATCATCTCCCTGATGAGAC
AGTAGCTGAGCATCCATTCCCCTAAGGCTACAAAGCCTTCGATTC
ATGTTCTGCATTGACCAGGCTCAAAAAGGAAGAAACCAATTGCTG
Phase-1 RCT-118 CCTTTTTTGCAGCTCTCATTAGTAGCTGCCCAGGCTGCTGAGGCCSEQ ID
NO:
TTCTCCCACAATTGTCTGGCCTAGCTGTGCACTGTGGGAGTCGG257
GTAAAACCAGCAGGAATGCAGTTTTGAAGCTTATGCGCAGCTTCT
CTATGACAGATGTTTTCTAGAGGGATAATGGATCACTGGGACCCT
AGGAGAATTTGAACCAGCCCTTCAGCCAAAAGCCACAGTCCACTT
CAGAATGTCGGTGCCCCAACCCACCGGTGAGGTGCTCAGTGGT
GAGCACCTGTGAGATCTGGGGCTGTAAACGCAGCACAGTGGAAG
CGCATGCTTGGCCTGNTGAGGCCTGGGCTTGGTGCTCNCCAGG
AACAAGTNAACAGAAGTAGAACCTGGG
169
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGGCAAGAATTCGGCACGAGGATGAGGGGTGCCA
TGAGGGGTGCAGAAGAGCCCTCGACTGCCTCTTTCACTCCATTC
CTGCACACACTACTCCATTGAGAAGCACCGGTACGGAGCTGCCA
CTATGAAAAGATGGCTTTAATGCTTCCCCCAATCTCTTCCCCTGC
AGTCTAGACCTCTCTCCCCACCTTCAAAACATGTATAAAAAGAGG
CGCCTTGTCTACAGCCCTCACTGTTGCAGCTCCAATTATTTATTG
Phase-1 RCT-119 GCAATAGTTCTACGTCTCAGCTTTTCCCCACTGCTCCTTCTCCTGSEQ ID
NO:
CCTGATGCCATGGAAATAAAGATTCTCTCCATCACTCAGTGCTGA258
AGAGCCCCAGCCTCAGGATCAGAGCTATCTGTATACAGCACTTA
CAAGTTTTGGGTAATTTAACCTTTTGGCTAATTTGCGAAGCTTTCT
GTGAGCCTCTGTTTCCTCATCTGANGGAGGGAAGAGTTGTAAGG
CTTACCTCACAGAGTCACTGAGATGACCAAAGGAGATTATGTGAA
GAAANCTTATANCAANGNACCCCAGCAAAAGAATAAGTANCAGAA
ATGNCATTTATTTTGATGATGTCCTGCTCAAGCTANAACTCATGTA
_ ATTCN
TATGACATGATTACGAATTTNATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGATCCAGACTGCAGG
CTCCCTCCTCCCTCTCTCTAAGCCCTACCTCTGCACCTCCTCTTC
CCCAGGTCCATTGTTCCTCTGTTTCCCTTAAAAAAAAAAAAGAGC
AGGCCTCCCAGGGATATCAGCTGAACACAGCATAACAAGATGCA
ATAAGAACAGGCACAAACCCTCTTATCAAGTCTGGATGAGGCAAC
CCAGTAGGAGGAAAAGGATCCCATAAGCAGGCAATAGTTGATAT
Phase-1 RCT-121 CAACATAGTTCCCAAAATAGAGATCTACACTGAGTTATTCTGGTTASEQ ID
NO:
TGAGATGGAAAATGAGTGCAGTGCGCATGTGCTTCTTGTTTGAGA259
AGTTCCTTCTTTTTCCTCCCAAGTTCCTGGCTCCCAGCCACCAGC
TGCCAGCACAACTCTCTCCACAGTTAGTTCTTAGAATTTAGTAACA
GATACTGAGATCTGTCTTTAGTAACAAATATAAAATGAGAATATAA
GTCTAGAAATGATTTTCCTGGGTTTTTCCGCTTTTGCAGTATCATG
TTTATGGAATTTGAATTCTTGCAGCCATTGTATATGAATAGTCTGG
GGTAGAAGATGATCTGGAGACAAATTi-i'TTAGAAATAACTATTAAA
GCTTGCTTTGATGCTGGAAAAAAAAAA
TCTATGACATGATNACGAATTNANTACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGTACCACTGTTCCTC
TAAACGAGCTTCTTCAGCAACAGCCCCCGCCCAGGCTGGACCTG
CATACAGTGTTCCTACCTCAGGAATAATCTCTCTCTCTGTGGCTC
TTGCTGTTCAGCTGCCCTCCTGAACCAGTATCCATTCTCTCACTG
GCCTTGGCCAGCTTAGACCTTATGTCTATGTGTGCTAGTTGCTCG
GCAGGGCCAGCATCGCCTGCAGTGAGCGTGAGCAAATCTGTCTT
Phase-1 RCT-122 TCTCTGGGTGGACAGAATGCCAGGAGTCCCCTCCCAGCAACTTCSEQ ID
NO:
TGCACCAGCCCTCACACAGTGACCCCTCCCCAAGGCACAGTTCC260
TATATCTTCATCCCACTCATGTATGAGACTTAGGAAGGAAAAGCC
GACGACGTTCTTGGGGTGTTGGGACAGAAGTTGCCGTCATTTCC
GGGTTGAAAGAGAATAGTTGTTGAAACTATGACTAAACACTATTC
ATTAATAAAGATTCTATTTTATCAGT
AAAATGGGAAGCGGCCGCAAGCTTATTCCCTTTTAGTGAGGGGT
AATTTT~TGCTTGGCACTGGGCCGTCCTTTTACAACGTCGTGGACT
GGGGAAAACCCTGGGCGTTACCCAACTTAATCGCCTTG
TTATGACATGATTACGAATTTGATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTCCCTCTGTCAGA
GTCGGTGGGAGACAGAAGGGTTGAGAGAGGAGAACACTGCAGC
TTAAGGTGTAAACGAGTATCGCATTTTATTTTCTAATAAATTCTCTA
ATAAGAAAAAAAAAAAP,AAAAAACACATGCGGCCGCAAGCTTATT
CCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTT
ACAACGTCGTGACTGGGAARACCCTGGCGTTACCCAACTTAATC
Phase-1 RCT-123 GCCTTGCAGCACATCCCCCTTTCGGCAGCTGGCGTAATAGCGAASEO ID
NO:
GAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAA261
TGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCG
GGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCG
CCCTAGCGCCCGCTCCTTTCGCTTTCTTCCTTCCTTTCTCGCCAC
GTTCGCCG'GCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTT
TAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAAP,
CTTTGATTANGGTGATGGTTCACGTAATGGGCCATCGCCCTGATA
NACNGGTTTTTCNCCCTTTGACGTTGGAGTCCACCGTN
170
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTCTAGGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCTGGTTCCACT
TCCTGCTAGCAGTTTTCCTCAGTAGGGATCACATGACTCTGCTTT
CTCTAACATCTTTGGGTCTCCAAGGCAACTTCAACTTCATAGTAAT
CATGCTGTGAAACCATGCCTTCAAAACTAGTACCATCTGGGTGAT
TCTTACAGATAACACAGTCCAGCTTCCAGCACAAAGTCTATCTCT
GGAATAAAACTTTTTTGTGGTCTTAGAAAACACTTCCAAGAAAAATSEQID NO:
Phase-1 RCT-125 TTACCTCAGTGATGCTCATCCCTTCTTAATCACTGCTAATTCCTTA2g2
GCTCTAGCCAGCTAATTAGCATCAATATTTCCAGTAACTTCATCTA
TGCTTGTTCATTTGTTTTGGTTCATAAAGACTTTTTTTAAAAGTTAA
AATTCAGTTTACATCTTGGTCACAGCCCATCTCTCTCCTCTTCCTT
AGTCCCATCCTTGCCAATCCCTGTCCCAATTGCCCCCTCCACTTG
GGTACCACCTAACCCTGGGACATCTGCTTCATGTAGTACTAGCTA
TATCCTTTCTCACTGAGGCCTAACCAGGCAGTCTTGGTNAGGGAT
GAGATCCCAATGCTAGGAACTATAGACTGN
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCGACTGACTATGTG
GATGAGATCAAAAAGATCTCCCCCAAAGGAGTAGACATCGTCATG
GACCCTCTGGGTGGGTCGGACACTGCGAAGGGCTACCACCTTCT
CAAACCCATGGGCAAAGTTGTCACTTACGGAATGGCCAACCTGC
TGACGGGCCCCAAGCGGAACCTGATGGCCATGGCCCGCACCTG
GTGGAATCAGTTCAGTGTGACAGCTCTGCAGCTGCTGCAGGCCA
Phase-1 RCT-126 ACCGAGCTGTGTGCGGCTTCCACCTGGGCTACCTGGACGGTGASEO ID
NO:
GGTGGAGCTCGTCAGTAGAATGGTTACCCACCTCCTGGCTCTGT263
ACAATCAGGGCCACATCAAACCCCGAATCGACTCAGTCTGGCCC
TTCGAGAAAGTGGCTGATGCCATGAGGCAGATGCAGGAGAGAAA
AACATAGGCAAAGTCCTCTTGGTTCCTGGGCCTGAGAAGGAGAC
CTAGGGCCAGCGGCTGAGGGCCCTGGAAACCAGGAAAGGGGAA
NATGGGAANTCCTGTTGTGTTGCCACCAACCTCTCACATTTCATC
CTGTCATGATGCTCTACCCTCCCTCCCCAAAAAAGGTCTCTGTGC
TGATGACTGCTTCCTGCTCTGANCTTGCTCN
NTNNNNTCTATGACATGATTACGAATTTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGTTTGT
GGTGTAGGGACAATGGCGCCATTGTTCTTCGCGTCTTCAAAGCA
GTTTCCAGAGGAAACAAAGATGGCGGGGAGCTCAAAGCATCCGA
GAGAATTCGTGAAGGGAGGAAAGTTGCTTAAAACTTGACCATGTT
AAAGTTCTTACTCCTGGCACGTCATGATACTTTCTGCCAGCAGTG
AATGCCAGCCCATTGAGATGCCCGTCCTCTGGGAAGCTCCTGGA
GCAGAAATGCATGGCCAGTGAGAGGAGACTTCTTGCGAAGGAAASEOID NO:
Phase-1 RCT-127 ACTGGATGTGGTGATGTTCAGAAAAAGCAGACACAAGAAGCAAAT264
ACAGAGTATTAGTACTGGGATGTTTGAGATGGGGTCTGCATGGC
CCTTGCTGTGTCCCTCTTAAACTGTCTAGTGGATGGGACAGCATC
TGGTATGGCCTGCAGAGTTGAGCCTTGTGTATACCTTTTGAAGGC
TCTATGTTAATGTATGACAGAGTGTTCTATTCTGGGAAGGTTATG
GGTGAGCTGAGGATACAACTTTACAGACTAGCACAATGAGTGTAC
AATTACTGTAAAAAAGGCAGTTCACATTTTTATTGGTTATGAATTG
NTTCCTTATTCATCCAACAGTGATCACTTGGGAGTGCTGCAATAA
ACT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGAGAAGAATTCGGCACGAGGATACTATTAGACCAAG
CAGCTCTCAAGTGTTTAATGTCTACTGTGACACCCAATCAGGCAC
TCCACGGACATTAATTCAACACCGGAAAGATGGCTCTCAAAACTT
CAACCAAACGTGGGAAAACTACGAAAAGGGTTTTGGGAGGCTTG
ATGGAGAATTCTGGTTGGGCCTAGAGAAGATCTACGCTATAGTCA
AACAGTCTAACTACATCTTACGACTGGAGCTACAAGACTGGAAGG
ACAGCAAGCACTATGCTGAATATTCCTTTCATCTGGGCAATCATGSEQID NO:
Phase-1RCT-128 AAACCAACTACACGCTACATGTGGCTGAGATTGCTGCCAATATCC265
CTGAGGCCCTACCAGAACACAGAGACCTGATGTTTTCTACATGG
GATCACAGAGCAAAGGGACAGCTCTACTGTCCAGAAAGTTATTCA
GGTGGCTGGTGGTTCAGTGACATGTGTGGAGAAAACAACCTAAA
TGGTAAATACAACAAACCCAGAGCCAAATCCAAACCAGAGCGGA
GAAGAGGAATCTCCTGGAGGCCTCGGGGCGGAAAGCTCTACTCT
ATCAAATCATCTAAAATGATGCTCCAGCAGACCACCTAAGGAACG
TCAGCTGAACTGAGACAAATTAAAAGACCAACACATTCAATATTAA
AATCC
171
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATGACATGATTATGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTGATGGTGGTGAT
GATCACGTGCCTGCTGAGCCACTAGAAGCTGTCAGCCCGCTCCT
TCATCAGCCGACACAGCCAGGCCCGGAGGAGAGACGACGGAGG
ACTGTCCTCGGAAGGATGCCTCTGGCCGTCGGAGAGCACGGTG
TCAGGCGGAATGCCGGAGCCACAGGTCTATGCCCCACCTCGGC
CCACTGACCGCCTCGCTGTGCCCCCCTTCGTCCAGCGGAGCCG
Phase-1 RCT-129 TTTCCAGCCCACCTACCCCTACCTGCAGCACGAAATTGCCCTGCSEQ ID NO:
CACCCACCATCTCGCTGTCTGATGGGGAGGAGCCCCCACCCTAC266
CAGGGCCCGTGCACCCTCCAGTTACGGGACCCGGAGCAACAGC
TGGAGCTGAACCGAGAGTCTGTGCGCGCGCCCCGCAAGCGGAC
CATCTTCGACAGTGACCTCATAGACAGCAGCATGCTGGGGGGCC
CGTGTCCCCCCAGCAGTAACTCCGGCATCAGCGCTACCTGCTAT
ACAGCGGNGGGCGCATGGAGGGGCCTCCTCCCACCTACAGTGA
GGTCATTGGTCACTACCGGGGCTCTCCTTCAGCAGCACCAGCAA
AGTNAANGGCP,GTCCTCCT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTCTGCGCAGGAACA
GAAATGGATAAGAACATCTGGACGAGTAGGAGAAGACGAGGGCG
AAGCCACCACCGTAGCCC7GCGCTGAGGCAGTGTGATTCCAGTG
~AGAGGTACACCTCAGGGGCGTCTCAGAGCTCGCAAGATTCCGGC
CACCATGATGTTGAGTGCCCATCAACCTCGTCCAGCAAAGCTGG
AGAGTCTTCAGTGCCAGACCTTCCAGGTTTTTACTTTGACCCTGA
Phase-1 RCT-130 GAAGAACCGATACTTCCGTTTGCTCCCGGGTCATAACAACTGCAASEQ ID
NO:
CCCCCTCACGAAGGAGGGCATCCAGCTCAAGGAGATGGAGAGC267
AGGAGGCTGCAGCTGCTGCAGCAAGAGGACAAGCAGAAAAAGA
AAATTGCCTTTGCTGTTTAATGGCTGTCGTTCTGGGGAGATCTTT
GCCATTGACCTGCGTTCTCCAAGGCCAACATTCCCAGTGTGGCC
TTCTGTCCTCGGCTTGGGGGCCCCCGGGGAGCCCCAGGGCTGC
TCATGGCTGTCCAGCAGGACCTTTACTGNTTCCCATACAGCTCGT
CCTCCAGATGGTCTGAANGAGGGCANGTGGGANCCCTCTTCTGN
TTCTAANGAGGACATTI?ATAAACGGCGCTTGCTGTTCAA
CNNNNNNNNNNTTATGACATGATTACGAATTTAATACGACTCACT
ATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCG
GGGAGCCGGCTGGAGACGGTGGGGAGCGTGTTCTCCCGGACCA
GGGATCTGATGCGGGCTGGGGTGTTGAAGGAGAAGCCACTGTG
GTATGACATATACAAGGCCTTTCCACCTCTGAAAGAACCTGTCTT
CCGAAGGCCTCGTTTGGGATATGGCAAAGCCAAAGCTGACATCC
AGGACATCTTTTACCGAGAGGATCAGATTCGAGCGAAATTCTTTT
CAACCTATGGATCTGGTCACAAAGCTATTGATCTGTTCAACCCAA
SEOID NO:
Phase-1 RCT-132 ACTTCAAGTCTACCTGTCAGCGGTTTGTGGAGAAGTACACAGAG
268
CTGCAGAGTCTTGGAGAAACAGATGAAGAGAAGTTATTTGTAGAA
ACGGGGAAGGCTCTGTTGGCAGAAGGCGTCATTTTAAGACGAGT
CAATGTGAGACTCCAAAGTTCATCAGAAGGAAATGACCCTCTGGA
AGAAGATGGCCAGAAGCAGCGTGTGCAGGTGAAACAGGAGCCA
GAGACAGCCTCCTCGCCCCCCTGANGCCCCTCAGTGTACTGAGC
GTGCCCCCACCACTGGNCTAAGACGTTTGGACTCTGACGGCCTC
TGTCTGTCAGGNCTGNGTGCCTTCTCTTAATTCCTGGNCCCGGG
GTGG
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCGGCACGAGGTGT
TACCATTCTGATGTTGGAGCGGAAGATGCTCTTGAAGCAAGCCC
GGAAGGAGGGCATAGGTGGTCTGTGGCCATGTAGCAGGTAGTC
ATTGTCTTTCAGCCAGTCAGGAAGCACATCGTATGGGATGACCCT
CCAACGCCCCTCCCAGACCTTATATACGAACTCCTCCATCTTCTC
CATGGCATGGTGGGCTTGCAGAGGAAGGGTCAGCACCCGCACC
Phase-1 RCT-134 TCCTCCTCCTCCTCCTGAGGCACGGGGCATGCTTGTTCTTCTTCASEQ ID
NO:
GCCTTGGCTGGGCTGGTGGCTGCCCGCTTACCCTTCTCCTCCAG269
CAGGGGCCCCAGCTCAGCCAGCTCCACCGTGTCCGCTTCTCTGT
TACTAGAAGGAGCCCCATTGCCCTGGGCCACGGCAGATCCTTTG
TGGGAAGACATCTGGCTGGTACCTCAGTGCCTTGCAACTTCAGC
TTGAGGAGAGGTTGGGGTCTCTCAGCCCCAGAGGGCAGAGATCT
CCCAGTGATGATGGACACTTAGGCCTGTCGACTCTCCATCAACCT
CCCCGCCGACCTATCAGGAAGGAGAGCCGTCACG1T'fGACCTGC
GGATCGCGGGTGGGGGCC
172
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AACATGATTACGAATTTAATACGACTCACTATAGGGAATI-f'GGCC
CTCGAGGCCAAGAATTCGGCACGAGGGGTCCCACAGCTCTTCGA
GATGTACCCTTCTCAGCTCTATACTGGTTCAACTATGAGCTGGTG
AAGAGCCAGCTGAATGGGCCAAGACAGAAAGAGCAGACATCTGT
TGGCATCAGCTTTGTGGCTGGTGGCATCTCAGGAATGGTGGCTG
CCACCCTTACCCTACCCTTCGATGTCGTGAAGACACAGCGACAA
ATGTCACTGGGAGCAGTGGAGGCTATGAGAGTGAAGCCGCCAA
Phase-1 RCT-136 GAGTTGACTCCACCTGGCTCCTGCTTCGGAGAATCCAGGCTGAASEQ ID NO:
TCTGGCACCAGGGGACTCTTTGCAGGTTTCCTCCCCAGGATCAT270
CAAGGCTGCGCCCTCCTGCGCCATCATGATCAGCACTTACGAGT
TTGGCAAAAGCTTCTTGCACAGGCTCAACCAGGAGCAGCCTCTG
GGCCACTGAAGGTTGAGGAGCAACTGGCTCTTGCCCGGGTGGG
AACAGGAGACTGAGCCAAGTGCCTTCCCTCCCAGTCCAGTCACC
CAAGCTGTCCTCATTTGGATTCCTGCTGTTTCCTCCCTACCTCCG
AGACCAAATCTGATGATCCCTGCTTTTGTGTCCCTTATGTTTGGTA
TANCTTGGCCCTGAAGANCCGCC
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTGATCTCGGTTCGT
CGCCACCATGGGGAAGCGACAGCACCAGAAGGACAAGATGTAC
ATCACCTGTGCAGAGTACACTCATTTCTATGGTGGCAGGAAGCCA
GATATCACACAGACAAGTTTTCGCCGCTTACCTTTTGACCATTGC
AGTCTCTCTCTCCAGCCTTTTGTCTACCCAGTCTGCACCCCGGAA
.
GGTGTCGTCTTCGACTTGCTGAACATTGTCCCATGGCTTAAGAAG
Phase-9 RCT-137 TATGGGACCGATCCGAGCACTGGAGAGAAACTTGATGGGAAGTCSEQ ID NO:
CCTGATTAAGCTGAACTTTGCAAAGAACAGTGAAGGGCAGTACCA271
CTGTCCAGTGCTGTACTCCGTGTTCACTGACAACACCCACATCGT
GGCCATCAGGACAACTGGCAATGTCTACACCTATGAGGCAGTGG
AGCAGCTAAACATCAAGGCCAAGAACTTGAGGGACCTGTTAACT
GATGAGCCCTTTTCCAGGCAAGACATCATCAGCCTGCAGGACCC
CACCAATCTGGACAAATTTTAACGTCAGCAGCTTCTTCCATGTAA
AGAATAACATGCGAATGATAGATCCAGATGAGGAAAAGGCCAAA
CCAGACCCATCTTTNTATTTG
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTCTGGCCACCAT
GGGGGCCCCAGAGCCCTCCTGGTGCTTTCTGTTCCTTCCTGTCC
TCCTGACTGTGGGAGGATTAAGTCCCGTACAGGCCCAGAGTGGT
AAGCCATAACACCCCTGGTCTTTCTCTCTTCCTCTCAAGATTTCCT
CAGGCTACCCCTTTTCCTTCTAGCTCTCTCTCTCTGCTAACGCCG
AGCCCTGATTGTTAACCTGTGTCTCCCTCTTCATCCTTCTGAGAC
Phase-1 RCT-138 AATTACCCAGGATGCGAATGTTCCTCTGTGAGCCCGGGTGTACTSEO ID NO:
GGCTGGGATTGTGGTGGGCGACTTGGTGCTGACTCTGCTCATCG272
CCCTGGCGGTGTACTCTCTGGGCCGCCTGGTCTCTCGAGGCCG
AGGGACTGCAGACGGGACCCGGAAACAGCACATGGCTGAGACT
GAGTCACCTTATCAGGAGCTTCAGGGTCAGAGGCCAGAAGTATA
CAGTGACCTCAACACACAGAGGCAGTATTACAGATGAACCCACC
CTATGCCCACCAACAACCTGATGCCCGGATCCACTCATTCCAGA
CGCTTACTCAACAAACCCTCCCTGGGATCAGGACTCCCGCTGGA
AATAAATATCCACAGAATGGCCTCTGGGAGATAT
GNGCTAAGNNTATGACATGATTACGAATTTAATACGACTCACTAT
ANNGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGAAAGG
TTTTTTTTTTTTTTTTTTTAAATGATTCCTTAAACAGGCCATCTGAG
TAGGAACTGTAGGTTTATAAAATACATGGNAACTGAAGTTTCTGA
GATGGGACTTGCTCTGTTAGGCAGGCTGATGTGGCTGGTGCTTG
TCCCANCGCTAGGGAGGAGAGAGATGTGTANATTTCCTAGGACA
TGTGGCCAGCCAGCCAGCCTGCTCAGGGACCCACCTGCCTCCAT
SEQID NO:
Phase-1 RCT-139 CGTCCCAGGCGCTGATTACCCATATGCATGGTAGGTTCTAAAATT
273
GAATTCAGGCCCTCAGGCTTGCAAGTTAAACATGACATGAGCAGT
CTCCCTGGCCCACTGGTTTCATGTGATCCCTAAANGCATTTCCCT
TTGGCATANTAATCATGTTTTGACAATGCTACCATCCTTTGGGTAT
AAACTTACATGGTTTCCCCGGATATTTTGTTTAAAATGTGAATATT
CTAAAAATGTTTAGAGACTCNTTCNTACAATTTTCTATGATCAAAA
TATTTTNCTAAGTAGAAAATAAACTTTCNGANTAAAACTCTGTAAC
CCTGGGGG
173
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGACCGGGAAGCCCCAG
CCTGTGATGGTAACTTGGGTGAGAGTCGATGACGAAATGCCTCA
ACATGCCGTTCTGTCTGGGCCGAATCTGTTCATCAATAACCTAAA
CAAAACAGACAATGGTACTTACCGCTGTGAGGCTTCCAACACAGT
GGGGAAAGCTCATTCAGACTATATGCTGTATGTATACGATCCCCC
CACAACTATCCCTCCTCCCACAACAACCACCACCACCACTACCAC
Phase-1 RCT-140 CACCACCACCAGCACCACCATCCTTACCATCATCACAGACACCACSEQ ID
NO:
GGCGACGACAGAACCAGCAGTTCACGATTCTCGAGCAGGTGAAG274
AGGGCGCCATTGGGGCAGTGGACCACGCGGTGATTGGCGGCGT
CGTAGCCGTGGTGGTGTTTGCCATGCTATGTTTGCTCATCATTCT
GGGCCGCTATTTTGCCAGACATAAAGGTACATACTTCACTCATGA
AGCCAAAGGAGCCGATGACGCAGCAGACGCAGACACAGCTATAA
TCAATGCAGAAGGAGGACAGAACAACTCCGAAGAAAAGAAAGAG
TACTTCATCTAGATCAGCCTTTTTGTTCCAATGANGTGTCCAACN
GGCCTGCTTAGATGATAAAGAGACAGTGATNCTGGGAAAAA
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAAACAAACTCCAAACT
CTGAAACAGCTGAAGTGAATCCAGCTCATGAAGATGCAGATGGA
GGTGAAGGAGAAAAACCTCTGATTCCCAGGCCCCCTGTGCTATC
CCCCACTGCTGTTCCAGGAACCGATCTCTTGGTTGAGAGACTCA
ATCCAGGCATTAACATCCATCCCATGTTTTCAGATGAGACCAATA
TATGCAATGGTAAGCCAGTGGATGGACTGACCACTCTGCGCAAC
Phase-1 RCT-141 GGGACGTTAGTTGCATTTCGAGGTCATTATTTCTGGATGCTGAACSEO ID
NO:
CCATTCAGACCACCATCTCCACCACGCAGAATCACTGAAGTCTG275
GGGTATTCCCTCTCCCCTTGACACAGTTTTTACTAGATGTAACTG
TGAAGGAAAAACTTTCTTCTTTAAGGATTCTCAGTACTGGCGCTTT
ACCAACGATGTAATGGATGCTGGGTATCCTAAACTAATTGTCAAA
GGCTTTGGAGGACTAACAGGGAAGATAGTGGCTGCTCTTTCAAT
AGCCAAGTACAAGGACAGACCTCAATCTGTGTACTTCTTCAAGAN
ANGTGGCAACATCCAGCAGTACACTTACNAACAGGAGCCCCGTG
ANGAAATGCACAGGGAGGCAGCCTGNCATC
TCTCCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAA
TTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTCCTGGGGG
TACTTCCTATGAGAGATACGAGTGCTACAAGGTTCCAGAATGGTG
CTTAGATTACTGGCATCCTTCTGAGAAAGCAGTGTATCCTGATTA
CTTTTCCAAGAGAGAGCAGTGGAAGAAACTGAGGATGTGGAGCT
GGGATCGGGAGGTTAAACAGCTGGAGGAAGAAACGTCACCTGAT
GGTATTATGACTGAAGCTTTGCCTCCTGCCAGAAAGGAAGGCGA
Phase-1 RCT-142 CTTGCCCCCATTGTGGTGGCATATTGTGACCAGACCTCGGGAACSEQ ID NO:
GGCCCACATAGAGACAGGCACCGCACTGTTCATGCTTGCAAGTG276
AGAGTTACAGAACACATTCACACTTGCCCTAATAAAAGTAACTAG
AGACCANNNAANAAAGAANNAAAAAAAAAAAAAAGAAAAAAAAAN
GTTGTGNGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTA
NCTTGGCNCTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAAC
CCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTC
CCAGCTGGCGTAATAGCGAAAANGCCCGCCCCGATCGCCCTTTC
CAA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTGATGTACCGCCTGAG
CTCGTCAGTGCTGCCCCGGGCCTTGGCCCAGGCCATGCGCACA
GGACATCTTAATGGCCAAAGCCTTCATAGCAGTGCAGTGGCCGC
TACGTACAAGTATGTGAATATGAAGGCACAGGAACTTGATGTGGA
CATGAAGTCTGCGACTGACAGTGCAGCTCGGATTCTGATGTGGA
CAGAACTCTTCCGAGGCCTGGGCATGACCCTAAGCTACCTCTTT
Phase-1 RCT-143 CGGGAGCCCGCCACCATCAACTACCCCTTTGAGAAGGGCCCACTSEQ ID NO:
GAGTCCGCGCTTCCGTGGGGAGCATGCACTGCGCCGCTACCCG277
TCTGGGGAGGAGCGTTGCATCGCCTGCAAGCTCTGTGAGGCCAT
CTGTCCTGCACAGGCCATCACCATTGAGGCTGAGCCAAGAGCAG
ATGGCAGCCGCCGGACTACACGCTATGACATTGACATGACCAAG
TGTATCTACTGTGGTTTCTGCCAGGAAGCCTGCCCTGTTGACGCT
ATCGTGGAGGGCCCCAACTTTTGAGTTCTCCACCGAGACGCATG
AGGAGTTGCTGTACAACAAGGAGAAACTACTCAACNATGGTGGA
CA
174
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATNANATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGATTCCCCCTTCAGG
AGGTAAATGAAAAACCTAAGAAGAAAAAGCTAAAACCCCAGGAAA
CCCTACAGGAAAATGGAATGGAAGACCCACCTGTCTCTTTGCCTA
AAACCAAGAAAAAGAAAGCTTTTCCCAAGGAGGAGTTGGCCAGT
GATCI-fGAAGAGATGGCTACTAGCAGCATAAGTGTTCCTAAGAAA
AAGAAGTCCTTACCTAAAGAGGAAGTGGCCAGTGAACCTGAAGA
Phase-1 RCT-144 GGCAGCAAGCCCCATCACCCCTAAGAAGAAAAGGAAATTTTCTGSEQ ID
NO:
AGGAGCCTGAGGCTGCTGCAAGCTGCACAAAGAGCAGCACAAA278
GAAAAAGAAAAAGTCGCAGAAGGGCCGGGAGGAGGATTAGAATG
GACCTGCTTGGTGGGAGGGGCATACTTTATGGTGGCAGTTCCTC
CTGCCCATGATAAACCCCAATAAAAACGCAAAACCCGAAAANNNA
NANNNNNAANNNNNNNNNNNNAAAANAAAAAAAANAANNNTTCTC
GCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTG
GCACTGGNCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGG
CGTTCCCAACTTTATTCGCCTTGCAGCACTTCCCCTTTCGCCAGC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCCGAACCTCGCGGG
GCGGGAAGCCGCGAGATGGACACCCCTCCGCTCTCAGACTCGG
ACTCCGGGTCGGATGAGTGCCTGGCCTCAGATCAAGAGTTGCAG
GATGCGTTTTCCCGCGGACTCCTAAAGCCAGGCCTCAATGTCGT
GCTAGAGAAGCCGAAGAAGGCGGTGAATGACGAGAATGGCCTG
AAGCAGTGCTTGGCTGAATTCAAACGGGATCTGGAGTGGGTTGA
Phase-1 RCT-145 AAGGCTCGATGTGACCCTGGGTCCTGTGCCTGAAGCCAGTGAAASEO ID
NO:
CTCAGTCAACACCCCAGAACAAGGACCAGAAGAAAGGTGTTAAT279
CCAGAAGACGACTTCCAGAGGGAAATGAGTTTCTACCGCCAGGC
CCAGGCTGCTGTGCTTGCAGTATTACCCCGACTCCACCAGCTCC
AAGTCCCTACGAAGAGGCCCACTGATTATTTTGCAGAAATGGCCA
AGTCTGATCAACAGATGCAAAAGATTCGACAGAAGCTGCAGACTA
AACAGGCTGCCATGGAGAAATCTGAAAAGGCCAAGCAACTTCGA
GCGCTTAGGAAATACGGAAAGAAGGTGCAAACTGAGGTCCTTCA
GAAGAAGCAGCAGGAGAAAGCGCATATGA
GGGGGGGTCTCNANATGATTCGAATTTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGACATCTG
TAGCTGGGGAGTCAGTTAANGTGGTCTCTTCCTGCGCGAACATG
GTTCGGACCAAAGCAAACTACGTCCNGGGAGCCTACAGNNNAGT
Phase-1 RCT-146 GGTGGCTTCTCAAGCCCCTAGGAAGGTGCTTGGCTCCTCCACCTSEO JD
NO:
TTGTCACCAATTCTTCCGGTTCGTCNAGAAAAGCTGAAAATAAGT280
ATGCTGGAGGGAACCCAGTCTGTGTGCGCCCAACTCCCNANTGG
CAAAAAGGNATCGGNGAATTCTTCAAGCTGNCCCCTCANGATTCT
AANGGATAAAACCNGATTCNTGTANANGCCCGNGGCTGNGGCNT
'f-fNAAAATNCNATANTNGATNAC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTCAAATGTATTTATTT
AAGTCTGAGCCTTCCTTTCCAGTTTTTAGACCAACACTGCTCACC
CCTGCCTACATCCCTGGCCCAAGAGGAAACTGTATAAGGCCTCT
GGGCTCCCGTGGGGGAGGGCCCAGGAGCGGCAGGACCCCTGT
GCCTAAGACACCACCAGAACCAGAAGGAAACAGACCGGATAAAC
AGATCTCTGCACCCAAATCCCGTGGGAGGGAGAGCTGAACCTTC
AGAGACGCAGACAAGCCTGGGAAACCAGAAGAGACTGCTCTCTA
SEOID NO:
Phase-1 RCT-147 CACACACATCTCGGACATGGTGTGGCCACCACCCACGTTCCTCT
281
CTGGCCCTGGAGCCCCAGTGGGCTGCATCACCCACCGCTGGTG
CGTGGTGCATGGCTGTGCCCGAGCAGGCTCAGGCAGCTCTCCT
CACCCACTGCACCTGCCATCACACCTTCTGTGGAGCTACTTAATA
AACACAGCACACTGTGAAGTGTTTTTAAATCCAAAAAAAAAAAAAA
A,~~aAAAAAAAAGTTGTGCGGCCGCAAGCTTATTCCCTTTAGTGAG
GGGTAATTTTANCTTGGGCACTGGCCGTCGTTTTACAACGTCGTG
ACTGGGAAAACCCTGGCGTTTCCCCAACTTGNGGGGNGNGGNG
G
175
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GAGGAAAGGTTCAGCATTTTATT
TCTTGGTGCTTCCAGGAGCTCACTTAAGAATGGCACAAACAACAA
GCAAGGTAGTAGTGAGATACTGCTCTGCAGTTCTCGATGGTCTCA
TCATGGCCTTGGAGAGTTGGGACCCAGAGCAGAGCGAAGCTAG
GCTCCTCAGAAGGAGGACCCCGACTGTGGAGGAAGGCCTTTAG
GGCTAGCCTTCAGATCCAGATGTCAGAACTGCAATCACCCCCTGSEOID NO:
Phase-1 RCT-148 GGTAACGAAGCTCATGAGCCAGTGCTGGCCCAAGAGGCTCTTTC282
CCAAAGTCCACCAGAAAGTTGGGGTTCAACTTCAGCCCTCCATTT
GCTGTATCTACATCAATTTGCAGCATCACAGAGCCTTCCCTAATG
AGATTAGGGTAAAACTGCTTGTCCCAGGCGCTGTACAGTGATGTA
GTGACGTAAAGACGCTTCCCATCTAAGCTGAGCTGGATCATCTGA
GGACCTCCAGGAACTCG-fTTTCCCTTGACCACTAGGGGCTCCGG
CTG
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGCGCGCCTACT
CGGACATGAGAAAGGCCAACTGGAAAAACTCAGACAAATACTTC
CATGCTCGGGGGAACTATGATGCCGCCCGAAGGGGTCCTGGGG
GAGCCTGGGCTGCTAAAGTCATCAGTGATGCCAGAGAGGGTATT
CAGAGATTAACAGGACACGGAGCAGAGGACTCAAGAGCTGACCA
GTTTGCCAACAAGTGGGGCCGGAGTGGCAAAGACCCCAACCACT
TTCGACCTGCTGGTCTGCCCAGGAAATACTGAATTTTCTCTTCATSEO ID NO:
Phase-1 RCT-149 GTTGTTCCCGGGCGCACAGCCCCCCAAGGAAAGGGGCAATTACT283
GAGTTGAGTTATTTCCTAAAACCTGGATCCCTAAACATCCCAATG
TGCTGAATAAATGCTTGTGAAATGCANNANANNNAAP,AAAAAANN
AAANAAAAAAAAAAANAAAAACAAAAAAAAAAGTGAGCGGCCGCA
AGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCC
GTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCA
ACTTAATCGCCTTGCAGCANATCCCCCTTTTGCCAGCTGGCGTAA
TACCGAANAGGCCCGCCCCGATCGCCCTTCCCACAGTTG
TNNTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAA
TTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGCGCCGTAAG
CCTGCAGAGCATCATGGCGCTGAGCTGTCGACTGGTATTGGCCG
CGCTTAGACTGTGGGGTCCGGGAGGTGGGAGAAGGCCCATATC
CCTCTCTGTGGGAGCCTCAGGCGGCTTTGGATGTGGAGGACACA
GTGAGAAGAAGCTGTCTCTGCAGGACGTAGCTGAGCTGCTTCGG
ACCAGAGCCTGCAGTAGGGTTGTGGTCATGGTGGGGGCTGGCASEOID NO:
Phase-1 RCT-150 TCAGCACACCCAGTGGCATCCCAGACTTCAGATCCCCAGGGAGT284
GGCCTCTACAGCAACCTTCAGCAGTATGACATCCCGTACCCTGA
GGCCATCTTTGAACTAGGCTTCTTTTTTCACAACCCCAAGCCCTT
TTTCACGTTGGCCAAGGAGCTGTACCCTGGGCACTACAGGCCCA
ATGTCGCTCACTACTTCCTTCGGCTGCTTCACGACAAGGAGCTG
CTTCTGCGGCTCTACACACAGAACATCGACGGGCTTGAGAAGCA
TCTGGTATCCCTGCCTCAAAGCTGGTTGAAGCTCATGGGTCCTTT
GTATCAGCTACGTG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCCTGTTGAAAGGGC
TGGGCCCCGCCGGCCCTTTTGAAATGGTGTACTGGACAGGAGAC
ATCCCTGCCCATGATGTCTGGCAACAGTCTCGACAAGATCAGCT
GAGGGCCCTGAACACCATCACAGACCTCGTGAGGAAGTTCTTGG
GCCCTGTACCGGTGTACGCTGCTGTGGGCAACCATGAGAGTACT
CCTGTCAATGGCTTCCCTCCCCCCTTCATAAAGGGAAACCAGTCT
TCACAATGTCTTTATGAAGCCATGGCCAAGGCATGGGAACCCTGSEQ ID NO:
Phase-1 RCT-151 GTTACCAGCTGACGCCCTTCACACCCTGGTCTACCGCATGAGGG285
CTGATGAGCAGCTCTTCCAGACCTTCTGGTTTCTCTACCATAAGG
GCCACCCACCTTCAGAGCCCTGCGGCACACCCTGCCGCCTGGC
CACTCTGTGTGCCCAGCTCTCAGCACGTGCAGACAGCCCTGCTC
TGTGTCGCCACTTGATGCCCAATGGGAGCCTCCCAGATGCCCAT
AGCTTGTGGTCACGGCCCCTGCTGTGCTAGTGTGGGAAAAGTTC
ACATATTAGCAAAGGGATGGATTCCTGAGTATCGCTGATCTACCT
GAGGCAAANCTTTCNGGGAAGGAGGGGGGGGGGNGN
176
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCCNAAGTGATTNTGCCNANAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGATGGGTTTCGGAGA
CCTGAAAACCCCCGCCGGCCTCCAGGTGCTCAACGATTACCTGG
CGGACAAGAGCTACATTGAGGGGTACGTGCCATCACAAGCCGAT
GTGGCAGTATTTGAAGCAATCTCTGGTCCACCACCCGCTGACCT
GTGTCATGCTCTGCGTTGGTATAATCATATCAAATCTTACGAAAAA
GAAAAGGCCAGCTTGCCGGGAGTGAAGAAATCTTTGGGCAAGTA
Phase-1 RCT-152 TGGCCCTGTCAGTGTGGCAGATACCACAGGAAGTGGAGCAGCASEO ID
NO:
GATGCTAAAGACGATGATGACATTGATCTCTTCGGATCTGATGAT286
GAGGAGGAAAGTGAAGACGCAAAGAGGCTACGAGAAGAACGCC
TTGCTCAGTATGAGTCAAAGAAAGCTAAAAAGCCTGCAGTTGTTG
CGAAGTCTTCCATCTTGTTAGATGTGAAGCCTTGGGACGATGAGA
CAGACATGACGAAACTTGAGGAGTGTGTGCGAAGCATTCAAGCG
GACGGCTTGGTGTGGGGCTCGTGTAAATTGGTTCCAGTGGGATA
CGGAATTAAAAAGCTTCAAATACAGTGTGTAGTTTGAAGATGATA
AGGTTGGAACAGATATGCTGGAAANANCANATTACTGCTTTT'f'
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGATGTAAAAGAAGCCA
TAAGAAGGCTGCCTGAGAACCTTTATAATGACAGAATGTTTCGAA
TTAAGAGAGCCCTAGACCTGTCTATGCGGCATCAGATCTTGCCTA
AGGATCAGTGGACAAAATATGAGGAGGACAAATTCTACCTTGAAC
CCTATCTGAAAGAGGTTATTCGGGAAAGAAAGGAGAGAGAAGAG
TGGGCGAAGAAGTGATCGTGTAGTTAAGATCTGTGGGTGCGCCT
Phase-1 RCT-153 GGTCTCACCCTATTTTATGACATTGTTTCAACCTGAATCACAACTTSEQ ID
. NO:
AAGAATCATTTGCTCTACACATGCCTCACTTTAAATAAATGTCTAT287
TATAACCGT TGGAAGCGGCC
GCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTG
GCCGTCGTTTTACAACGTCGGGACTGGNAAACCCTGGCGTTACC
CAACTTAATCGCCTTGCANCACATCCCCCTTTCCCAGNTGGCGTA
ATANCNAANAGCCCGCCCGATCGCCCTTTCCCAACAGTTGCGCN
AGCCTGAATGNCNAATGGGAACNCNCCCTNTANCGGCGCNT1'AA
GCCGGCNGGNGGNGNTGGGCCCCCCCCCNTGNCCCCC
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGAGAGAAGCTGCCTT
CTCATTGGCTGAGGCCAAATTCACAGCAGGGGACTTCAGCACCA
CAGTTATACAAAATGTAAATAAAGCCCAGGTGAAGATCCGAGCAA
AGAAAGACAATGTAGCAGGTGTCACCTTACCAGTGTTTGAACATT
ACCACGAAGGAACTGACAGCTATGAACTAACCGGTTTAGCCAGA
GGTGGGGAGCAGCTGGCGAAACTTAAGCGGAATTATGCCAAAGC
Phase-1 RCT-154 AGTGGAACTACTGGTGGAACTGGCTTCCCTGCAGACTTCCTTTGTSEQ ID
NO:
TACTCTGGATGAAGCCATTAAGATAACCAACAGGCGTGTAAATGC288
TATTGAGCATGTCATCATTCCCCGGATTGAACGCACCCTTGCTTA
TATCATCACAGAACTGGATGAGAGAGAGCGAGAAGAATTCTATAG
GTTAAAGAAAATCCAGGAGAAGAAAAAGATTATCAAGGAGAAAAG
CGAGAAGGACTTGGAGCGGCGGAGAGCAGCTGGAGAAGTGATG
GAGCCCGCCACCTCCTGGCGGAAAANAAGGACGANGACCTGCT
GTTCGAGTACTGCCCCTGCTCCCTTCAGGCTGAGCATCATTTAAC
TCATGGGCAGGNTCGGTATGTGCAGGTATT
NCTCNTAACATGATTACGCATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGATTACGAGAGACC
TGTTCTGCACCTGGTTGCTCTCAACACGCCGGTGGCTGGGGACA
TCCGAGCAGATTTCCAGTGTTTCCAGCAGGCCAGGGCTGCAGGA
CTACTGTCCACCTTCCGAGCGTTTCTGTCATCACACTTGCAGGAT
CTCTCCACAGTTGTGCGGAAGGCAGAGAGATTCAGTCTTCCAATT
GTGAACCTCAAGGGCCAAGTGCTTT1'TAACAACTGGGACTCAATA
Phase-1 RCT-155 T~CTGGTGATGGAGGTCAATTCAATACACACATTCCGATATACTSEQ ID
NO:
CCTTTGATGGTCGGGACGTGATGACTGATCCTTCCTGGCCGCAG289
AAGGTTGTTTGGCACGGCTCCAACCCCCACGGTGTCCGCCTCGT
GGACAAGTACTGTGAAGCCTGGCGAACCACGGACATGGCAGTAA
CAGGATTTGCCTCCCCACTGAGCACAGGGAAGATTCTGGACCAG
AAAGCATATAGCTGTGCTAATAGGCTAATCGTTCTGTGCATCGAA
AACAGTTTCATGACAGACGCAAGGGAAGTGATAACCTCCCCATG
GTTCTTAAAAGAATATTCTAATATTTCTTATGTGAAAAGTTGACACT
GNAATCTAAAAAANNNNANNNNATNNANNNNNTN
177
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGCCATGGAGTTTGACT
TGGCTGCTGGTACGCTCCCCGGGAGTGGTGGATTTGCGGTGCA
AGGGGCCGGACTCAAAGCCTGGGATTCCTACAGAAGGGACGTC
CCGTCGCCTACACAACTCATTTAACTCCCCTCTTCTCTGCAGCCC
TGGGCCCTGGTTCTAAGAAGCCAGAGGGGGCTGGTCAAGTGGG
AGACCCCAAACACTGTCCTCTAAAGGCGCCGGGCCGGCCAGAG
GCAGGCGCTGCTCACAAGCCGAGGCATGGCCCTGGCGGCTCCTSEOID NO:
Phase-1 RCT-156 CCGACTCCAGCAGTAGTAGCAGCAGCAGCAGCTCCAGCGACTCA290
GAGGCAGAGGGGAAGGCGCACGCCGCTGGCTGCAAGAAGCATG
AACGCTCCTCAGACAAGGCCAAGAAACCCAAAGTGAAGAAGGAG
AGGAAAAAGAAAGAGAAGACTCCCCATTAACTTATTAAACTTGCA
GCCCTTTCCGCTCCCCGGCGCCCTCTGCCGGGCAGGAGCGGAG
GCCGCGCCGAGCCCAAAAAANNNNNNNNNNNNNNNNANNNNCC
TTTGCGGCCGCAAGCTTATTCCCTTTAGNGAGGGTTAATTTTACT
TGGCACTGGCCGNCGTTTTACAACGTCGNGATGGGAAAACCCTG
GCGTTACCCCAACTTAATCC
ANGACATGATTACGAATTTAATACGACTCACTATAGGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCAAGCGAACAGGG
TCTAGCAAAGAGGAGCTACGGANACAGACAGACATTTTAAGTTTT
CCAAAGAATCATCACCTTCTGCCGCAGGTCGCTTCCTCATCCCTG
GACACAGCTCCGCTAACCCANCCGGACTGTCTGACGAGTCAGGC
ATTTGGTCCACCAAATGCCGGTCCTCANAGTTTGCCTGAGACCCA
ATTGAAGGCACCGCCTGGCGGCTCCCGCTGACATCCAAGCTCTC
CTGCGCCGGCACCTTGCAGGCGCTCTTGGGGGGGCGCGGGGGSEO ID NO:
Phase-1 RCT-158 TCTGTAGTAGAACTCGGGCAAGCTGCCCCTCTCCACCTCCTGCC291
ACTCGTATCTGCCCTCCAGGGGCTTATGATTCTGAAAGTCGAAAT
TCCACTTGCGCTGGCTCGCTTCTTCCATATCTCGGCAGTGCTTCT
CCAAGTCCCGGGTTAATTCTTCATGATTGACCGGGCCGAANAAG
TTTCTGCANGCGGAAGGCTTGGGGTGCTCGGTTTGTCTGGCGTT
CATCCGCTCCAGGCTCGGGCTCCGTTANACACTCTCACGTTTGA
CATCTTCCTCCCCGGGCGGGNGTGGACACCGCCTCTNCTCTCTC
CG CATTGCGGCCNCAA
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGAGCCACTGGGTA
ACCTGGCCAGCAACCTTCTCTGAAGCTGAATCAAAAACTAAATAG
GAGAATATGGCAAGTGCAGACTGGGGATATGAAAGCAAAAATGG
TCCTGACCAATGGAGCAAACTATATCCCATTGCCAATGGAAACAA
CCAGTCTCCTATTGATATTAAAACCAGCGAAGCCAAACATGATTC
CTCTCTGAAACCAGTCAGCGTCTCCTACAATCCTGCAACTGCCAA
AGAAATTGTTAATGTGGGACATTCTTTCCATGTAGTTT'TT'GATGACSEO iD NO:
Phase-1 RCT-161 AGTAGCAACCAGTCAGTGCTGAAAGGTGGCCCTCTTGCTGATAG292
CTATCGGCTCACCCAGTTCCATTTTCACTGGGGCAACTCAAACGA
CCATGGCTCTGAACACACCGTGGATGGAGCCAAATATTCTGGAG
AGCTTCACTTAGTTCACTGGAATTCAGCCAAGTACTCCAGTGCTG
CTGAAGCCATCTCGAAGGCTGATGGGCTGGCAATCATTGGGGTT
TTGATGAANGGTGGGTCCAGCCAACCCNAACCTGCANAAAGTAC
TGGATGCCCTAANCTCAGTTAAAACTAANGGAAAACNANCCCCAT
TCNCCAATTTTGACCTTCCAGTCTCCTTCCTT
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAATTTAAGCATATTAGT
CAGCGGAGAAGCTTCGGCGAGCAGAAGTGGACTTGGAGCGCGT
GCGGGTGTGGTACAAGCTGGACGAGCTGTTTGAGCAGGAACGTA
ATGTTCGCACAGCCATGACCAACAGAGCAGGATTGCTTGCCCTG
ATGCTGCACCAAACCATCCAACACGATCCACTTACTACCGACCTT
CGCTCTAGTGCTGACCGCTGAAAGTCACCAGCCCAGAGCCTCTC
AGCCCTGCATTCAGTCAGGGAGGGGCTCTGCATTTCAGCTCGCTSEO ID NO:
Phase-1 RCT-162 CTTCCTCCGTTCATCTGTTTATTCTACCACCCTTAGTTTTCTTCTTA293
CCATCCATGTTTTGGCTTCTGTTTGCCCTTATCAGAAGGGTCTCT
GCTTTCCCTTTGTCTCCTCTCCATAGTCAGTGCTGGGTGAAAGTC
AAGTTTACTCAGCCTTGCCTATACCCTCCCCCAAAATAAACAGGT
TTTGTTAATAAAATTTTGAACAAGAATAAAAAAAAAAAAAAAAAAAA
AAACAATTGCGGCCGCAAGCTTATTCCCTTTAGNGANGGTTAATT
TTACTTGGCACTGGCCGTCGTTTTACAACGTCGTGGACTGGGAA
AAACCTGGCGGTTACCCAACTTAATCGCCTTGC
178
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
NNCNAATCTATGACATGATTACGAAT-tTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGATCTTACT
GCCCAGTTGTTCTGGCATTCGAAAAAAGGACTGTAGACTATGGTC
TAATGTTCAAGGATGTGGATGGACAGGACTGTGGAAAATAGTGA
GAAACTGGTTCTCCGCTGGAGGAAGTAGGGTTAGGTTTAGGACC
TTTGCAAGTGGGGGTCAGGCACACCACCAGGAACAGCTCCTTCG
ATAAATAAAACAGTTATCACATTCCCACAACAACCTAAACACAGAC
SEQID NO:
Phase-1 RCT-164 TACCTCTTCCCTTACCAGATCTGCTAAGCTGTGAGGTTCTAAGAG
294
GTCTGAGTGTGTTGTTTAAACTTTTGGAGATGGTTTTTCATTATAA
CAATTCAAGCCAGACATTTGAAAGTGACTGTTCTTATAGTGTCCC
CAAGTCTACTAACTGAGGGCCCACCTTCTAGTTTCTAGTTGCACT
TCTGAAATCCCATGTTTTGTT1'GCTGGGACCTGAGTTTGGTGGCT
TTTAAAATACAGATGAGATCAATTTATCCGACTTCATGAGTNATCC
TNCATTCTCTCGAGAAAAANCTGATTTCNATGTNAATTAATTGTAC
TATGACC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATTAAAGACAGGGGG
GGCTACCTGAACAAAGTCTGCAACCTCCTGCCCATTAGGATCCT
GTCCTACATCTTGCTGCCCTGCACTCTGCCCGTGGAGTCGGCCA
TCGCTGCAGTCCACAGGCTGGTGATGTGGCTCCCTGATATCCAT
GAAGATATCCAGTGGCTACAGTGGGCAACATCCCAGGTGTGTGC
CCGAATGACCATGTGCCTGCTCCCCTCTACCAGATCCAGAGCAT
SEQID NO:
Phase-1 RCT-165 CCAAGGATAACCATCAAACACTCAAGCATGGATATCACCCATCTC
295
TGCACAAACCCCAAGGCAGCTCTGCCGGTTTGTAAATTGCTGGT
CTCCGTGCTTCCGATGAACTTGGGCATTCTCCCTGTGGATGGTTC
CAGGAGAGGCCATAGCTGAAGGCACTCTGCCTTCCACCCCAAGT
CCAGTTTGACCTTTATCTAGAGCAACAGTGTCTAGATGATAGGTG
GGTGGGGGGTGCTGTCTCTCTGTTTCCCTCTGGGAAGGGTTCTG
TTAACTTTTGGAGGCAGCTAGGAAATTTGTCTTCAGGAGCTGAGC
CTGTGCAGCTGCCCCCTTGGTGCTGTGTGGTAACCTCATTGC
CTTCANATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGCCGTTGCAGCTGC
TTCTGCCTCTGTCCACCGAGGCAGTTCACCCGAGGCCGATCTCC
GAGGTCTGCCAGCGGCTACTTCCCACAGCCTCCGCCATGGGTCT
GGAGCTCTACCTGGACCTGATGTCCCAGCCCTGCCGTGCCGTCT
ACATCTTCGCCAAGAAGAACGGCATCCCCTTCCAGCTGCGTACC
ATCGAGCTGCTTAAAGGTCAGCATTACACTGATGCCTTTGCCCAG
SEOID NO:
Phase-1 RCT-166 GTGAACCCTTTGAGGAAGGTGCCGGCTTTGAAGGATGGGGACTT
2g6
CGTCTTGGCAGAGAGTGTGGCCATCTTGCTGTATTTGAGTAGAAA
GTACAAGGCACCTGACCACTGGTACCCTCAGGACCTACAGACCC
GAGCTCGTGTGGATGAGTACCTGGCTTGGCAGCACACAGCCCTG
CGGAGCTGTTGCAGCAGGGCCATGTGGCAGAAGATGATGTTCCC
TGTGTTCCTGGGACAGCCGGTTCCTCCTGAGAGGTTGGCATCCA
CCTTTGGCCGAACTGGATGGATGCCTGCAGATGCTGGAGGACAA
GTTCCTGCAGAACAA
TCNATGACATGATTACGAAT'fTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGTAGAAATGGCCGT
GGATTTGTCACACGGGTGACCTAAAAAGACAGTGGGGACCTTGC
1TGGGTTCCTGGGGTGCCCACTGTCCAGCCACTAGGACACTTGT
AAGGAGCTCTGTGCTATGGCACCGGGCCCGGTCTTCACTGTATA
TTCAAGGATAGCACACATATATATTAACTCTATTTATTTTGCTGAC
CCTGACTGCTGCACTTGTCGGTGACGTTTCTCCAGGTTAGGCTG
Phase-1 RCT-168 GGGTGATACTCTGGGATGCTCTGCGTACAAAGATTATTTGAATGASEO ID
NO:
ACTGATCTCAGGCCTGTCCTGTGTGTGTTGCTTTGGGGGTGGGA297
ACTGCTTTGAAACCCTTGTTCAGATGTTTTTATAGGCTGAGAATGT
CTTGCTGTGATGGATTAAATTCCTTTTTGAAAACTTTNNANANAAA
AAANAAAAANAAAAAAAAACACTTGCGGCCGCAAGCTTATTCCCT
TTAGTGAGTCGTATTAATTTTAGCTTGGCACTGGCCGTCGTTTTA
CAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCG
CCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAA
AAGNCCGCACCGATCGCCCTTCCC
179
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGCACGGTGACTTAAT
AGAGCTCGGCTCTGCCATGAAGTCCGTTGCTCTATTCCTCATGG
GCATCATCTTCCTGGATCACTGTGGAGTTCGAGGAACCCTAGTG
ATAAGGAATCAGCGATGCTCCTGCATCAGCACCAGCCAAGGCAC
ATTCCACTACAAATCCCTCAAAGACCTCAAACAGTTTGCCCCAAG
CCCTAACTGCAACAAAACTGAAATCATCGCTACACTGAAGAACGG
AGATCAAACCTGCCTAGACCCAGATTCAGCAAGGGTGAAGAAGC
SEQID NO:
Phase-1 RCT-169 TGATGAAAGAATGGGAGAAAAAGATCAGCCAAAAGAAAAAGCAAA
298
AGAGGGGGAAAAACCATCAAAGGAGCAAGAAAACCCGAAAAGCT
AAAACACCCCACCATCCGGAGTCAAAGAAGACTGCATAAGAGAC
CACTTTACCAACAAGCGCTCTGCATCTAAACAGCTTTTAGATCATA
CTAAAACGCCTTCCCTTTAATACACAACTCGTTCACTACAAAAAAA
AAAAAAAAP,AAGTGAGCGGCCGCAAGCTTATTCCCTTTAGTGAGG
GTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGGA
CTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGGAGCAC
ATCCCCTTTCGC
TTTTTTTTTT'1'TTTTTTTCATTAAATGCTCTTTTTATTTAAATTTGTCA
TGTGTAAAACACTACAAGGATTTGCCGAGCACACCAAGGTGGCC
ATGAGAGCAATCACAAATCAGTAAGCCTTCTATTTAGCCCTCTTTC
TCCAGCCATTCCTTATAGGCCCCGGCATAGTTTCGAGCCCCTGT
GTATCCAAGACCTTGTGCCAGGTGTGTGGCCTGGAGGCCCCGCC
SEOID NO:
Phase-1 RCT-170 TGCCCATCTGACAGAAGAAAATAAGATTCTTGTCTTCTAGCTTTG
299
GCTTCTCAGCACAGTATGAAGTCTGAAAAGCAGCTGGGTCCATG
TTCAAGGCCATTTCCAACTCAGACACTGAGAGGGGACAAATTGG
AAAGCTAGTGGCATGCAGAGGTTCACAAGATGGGGCTGAAAGAG
CTGAATGAATCCTGGCAGCAGCCTATTGCAGAGACCTTCCAAACA
TACG
CTATGACATGATTACGAATTNATACGACTCACTATAGGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGGACGAGGCTTTCCATCCATAT
TACCACCCTGGTTATTTCCCAAGCCAGCTCCACCCCCTCTACTGT
TACCAAACCCACCCTGATTCCCAAAGCCACCTGGATTACCACCAA
ATCTTCCACTNCTTTCTAACTGTNTATTGCTATTATGCTTAGGTTC
AGCATTGGATATATGCACGCTGATTCCTTTAATGATCAAGTCCTCT
CCACAAAGAGACTGGGCAACCTTATCATCTGCAAAGGTAACAAAG
Phase-1 RCT-171 GCAAAAGCTCTGAATGGTTTGGGAATGAAGACATCTACCACTTCTSEO ID
NO:
CCATACTGACAGAAGAACTGCTGAAGCTCTTCAGCAGTCATGTCC300
TCTGTACAACGTCCAAAAAAAACCTTTGCGGCCGCAAGCTTATTC
CCTTTAGTGAGGGTTAATTTTAGCTTGGGCACTGGCCGTCGTTTT
ACAACGTCGTGACTGGGAAAACCTGGCGTTACCCAACTTAATCG
CCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAN
AGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGGAA
TGGCGAATGGGACGCGCCCTGTANCGGCGCATTAAGCGCGGGC
GGGTGTGGTGGGT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCAGACTCTGGAGAAG
GTGTGCGTGCAGACTGTGGAGAGCGGAGCTATGACCAAGGACC
TGGCTGGCTGCATCCATGGCCTCAGCAATGTGAAGCTGAATGAG
CACTTCCTGAACACCACAGACTTCCTGGACACCATTAAGAGCAAC
CTGGACAGAGCTCTGGGCAAGCAGTAGGGGTGGACACTACACTA
CCCAGCTCCAGTGGGTGCTCCGTACATGGTAGAGGGTGGGCGT
Phase-1 RCT-173 TGTAGCCCCCCTCTCTGGTGGCCTTTCTAGGGGATTATTTTTTTASEQ ID
NO:
CATATATATATATATGATGGAGATGTTTTTTAAAGCATGTGAGCAA301
TTTCCCTCACAGTGGACACGAGGCAGGAACGGTGCGCTTTACCT
CAGCCAGTCAGTGTGTTTTGCATACTGTAATTTATATTGCCCTGA
GTCACGTGGTGCCATATTTAGCTACTAAAAAGCTCTTCACAAANN
NNCNNNNNNNNNNNAATNNNNNCAATTGCGGCCGCAAGCTTATT
CCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTT
ACAACGTCGTGACTGGNAAAACCCTGGCGTTACCCAACTTTAATC
GCCTTGNAGCACATCCCCCTTTCGCCAGCTGGCGTAA
180
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGTGGAATTCTACACTAA
AGTCATCATGGGCATTTTCCAGAGATTGATGAAAAATAAGGAACT
CATTCCTTTGGCGTTTTTTATAAGCGCGGCAGCCACTGGAGGCTC
ATCTTTTGCT'(1'GTATGCTTTGAAAAAAACCGACGTGGTTATTGAT
CGAAAAAGAAACCCAGAACCTTGGGAAACGGTGGATCCTACTCA
ACCCCAAAAGCTTTTAACCATCAACCAGGAATGGAAGCCTGTTGA
Phase-1 RCT-174 GGAGCTGCAGAGAGTCCGGAGAGCGACCAGATGATTACTCGCTSEQ ID NO:
GCTCCTTTCTTCCAAAGAACACTCTATGAATCTAGTGGAAACACTT302
CTGCACAAACTCGATTTTGATGCCAGTGTGCGGAAGTGCTTCTGC
TACAITfT-fAGGGTTTGCCTGCATTCTTTGGATCCTGCATAAGCAA
GCGAAGGTAGCACATAGTCGAAAATGGTTTTTCGTGGTTAT1'GGT
GTAAATTTCAATTTTACAGTTGAAATTTTATGTTTGTGATGGGTGG
ATATTTTCGTTGAAATGTATAAACATGTAAAAATTAGATTACTGCCT
GTAATAAATAATTAGATGGCTATCTGTAAAAACGTAAAAAAAAAAA
GGNGCG
TGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
GCTCGAGGCCAAGAATTCGGCACGAGGCTACTTTCCGCCTGGCC
CTCATCCAGCTTCAGGTTTCTTCCATTAAATCAGATAACATTACCC
GGGCTTGTAGCCTAGTCCGGGAGGCAGCAAAGCAAGGTGCCAA
CATAGTTTCTCTGCCGGAGTGCTTCAATTCTCCATATGGAACTAA
CTACTTTCCTGAATACGCAGAGAAGATTCCTGGAGAGTCCACAAA
GAAGCTTTCTGAAGTCGCAAAGGAGAACAGCATATACCTCATTGG
Phase-1 RCT-175 AGGCTCCATCCCAGAAGAGGATGATGGGAAACTGTATAATACCTSEQ ID NO:
GCGCTGTGTTTGGGCCTGATGGAAATTTACTGTGTAAAGCACAGA303
AAGATCCATCTGTTTGACATTGATGTTCCTGGGAAAATTACATTTC
AAGAATCCAAAACACTGAGTCCTGGTGATAGTTTCTCCACGTTTG
ATACCCCTTACTGCAGAGTGGGCCTGGGCATCTGCTACGATATG
CGCTTCGCAGAGCTTGCACAAATCTATGCACGAAGAGGCTGCCA
GCTCTTGGTGTATCCTGGAGCTTTCAATATGACCACTGGACCAGC
CCACTGGGAGTTGCTTCAGCGAGCCCGANCTGTTGATAATCAGG
TGTATGTGGCTACAGCCTCTC
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGATI~f'TCTTCTGTTGC
TGGGGCTGGTGGCTACGGATATAACCGACGGCAACAGTGAACAC
CTCAAGCGGGAGCACTCGCTCATCAAGCCCTACCAAGGAGTCGG
TTCCAGTTCCATGCCGCTCTGGGACTTCCAAGGCAGCACGATGC
TTACGAGCCAGTACGTGCGTCTGACCCCTGACGAGCGCAGCAAA
GAGGGCTCTATTTGGAACCACCAGCCATGCTTCCTTAAGGACTG
Phase-1 RCT-176 GGAAATGCATGTCCACTTCAAAGTCCATGGTACCGGGAAGAAGASEQ ID NO:
ATCTCCATGGAGACGGCATCGCCTTGTGGTACACCCGAGACCGC304
CTTGTACCAGGGCCTGTGTTTGGGAGCAAAGACAACTTCCACGG
TTTGGCCGTCTTCTTGGACACATATCCCAATGACGAGACCACTGA
GCGTGTGTTCCCGTACATCTCGGTGATGGTGAACAATGGCTCTC
TGTCGTATGATCACAGCAAAGATGGGCGCTGGAGCGAGTTGGCA
GGCTGCACGGCTGACTTTCGCAACCGGGACCACGACACCTTCCT
AGCTGTGCGCTATTCCCGGGGNCGCCTCACGGTGGATGACCGA
CCTGGAGGACAAGAACGAGTGGAAGAACTGCC
CCNNNNNNNCTCTATGACATGATTACGAATTTAATACGACTCACT
ATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGAA
GCCTCGGGGAGGAGAGACAGCTCTGTTCCGTTTTTGTTTCTGGT
GAAGAGTGTGGGGATTTTCGTCTTGGCTTCAAATCCGTCCAAGCA
GCACAGCGGGTCAAAATCTCCTGCAGGTGCTCAGATTACCAGTG
ACTAAACTGCACCTAGGCAGACCAGCCATGAGAGCCACTCAGCA
GGACTTCGAAAATGCAATGAACCAGGTGAAACTCTTGAAGAAGG
.
ACCCAGGAAATGAAGTGAAGCTGAGACTGTATGCGCTGTATAAGSEOlD NO:
Phase-1 RCT-177 CAGGCCACAGAAGGACCCTGCACTATGCCTAAACCAGGTGTGTT305
TGACTTTGTCAATAAAGCCAAGTGGGATGCATGGAATGCTCTGG
GCAGCCTACCAAAGGAAACTGCCAGGCAGAACTATGTGGACCTC
GTATCCAGTTTGAGTTCCTCATCTGAAGCCTCGAGCCAGGGAAA
GGGTGGAGCTGATGGGAAAGCCCAGGAGTCCAAGGGCATNCTG
GTAACGTCTGAANGTGGCATCACAAAGATCACGTTCAATCGGCCT
CCAAAAAGAACGCCATAACCTTCCAGATGTATCAGGATATTATAC
TCGCGCTTAAGAATGCCAGCACGGATGACACAGTNCATCACCGT
TTTCACANGAGCTGGTGACT
181
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CCCACGAAGTATAACCNTTGGTTGACACAGTAGGCCTNTGAAGTA
GTGAGGAGACACAGTTGCACCTTAGCACTTGGAAACCAGCATCT
TGAATAGCNTTTTCTACCGTCTCNTTCTCCAGGTAGACCCCAGAG
AACTTCTTGGGGCCCACCATATAGTGCTGGAAGCGCAGAGTAAC
CAAGGTAACCAGATGCCCTCCTGGCTTCAGCAGGCCAGCCAGTC
TGCGCAAGGCTGCCCGGTAGGTATCTACATCAGGACAGGCACAC
Phase-1 RCT-178 TCCATGGCCAGAAAGGTCAGCACGCAGTCGGCCAGAGGCACTTSEQ ID NO:
GAGCTGACCCCAGTGGGGGTGTCTTGGTCACATCACACCTCAGT306
ACACGAGTGACTGTCCTTCGGAGCTTGGCCTCCTTCTCCTGCCA
TCTGCTTCTGTCTCCCTCCAGCTCACACACATGTTGTACAATGGA
GGACCAGTCATAGGCTCCTGGCTCCTTCTTCAGCCATTTCTGCAG
CTCCTGCAGGTTCTGTGGGGTGTAGTCAGTGGCGATGATCTCCC
GGAAGACCTCGCATGCTGAAAGCAGCTGGTAGATGGTGGGGCC
AGAGCCAATGTCAATCAAGACATCTCCCCCTACACCTCC
TCCTCATAANATGATTACNAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTCTGCGGAAC
AGTAGGCAGTTGTTTTCCGTCCGGCTTCTCTCACACTCAAGTGCG
CGCCTCCACCTCATGGAAGACTCGATGGACATGGACATGAGCCC
TCTTAGGCCTCAGAACTACCTTTTCGGTTGTGAACTAAAGGCTGA
CAAAGATTATCACTTTAAAGTGGATAATGATGAAAATGAGCACCA
GTTATCATTAAGAACGGTCAGTTTAGGAGCAGGGGCAAAAGATG
Phase-1 RCT-179 AGTTGCACATCGTAGAGGCAGAAGCAATGAACTATGAAGGCAGCSEQ !D NO:
CCAATTAAAGTAACACTGGCAACTTTGAAAATGTCTGTACAACCA307
ACAG'f'1-fCCCTTGGGGGCTTCGAAATTACACCACCTGTGGTCTTG
AGGTTGAAGNGTGGTTCTGGGCCTGTGCACATAAGTGGACAGCA
CCTAGTAGCTGTAGAGGAAGATGCANAGTCANAAGATGAAGATG
AGGAAGATGTNAAACTCTTAGCATGTCTGGAAANAGATCTGCTCC
CGGAGGTGGTAACAAAGTCCCACAGAAAAAAGTAAAACTTGATGA
ANATGATGATGANGATGATGAAGATGATGAGGATGAATGAANATG
ATGATGATGATGATT'f-T'GATC
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTGGTGGCCAAGT
TCAACGCCTCGCAGCTCATTACCCAGCGGGCTCAGGTGTCTCTG
TTGATCCGAAGAGAGCTGACAGAGCGTGCCAAGGACTTCAGCCT
CATCCTGGACGATGTAGCTATCACAGAGCTAAGCTTCAGCCGAG
AGTACACAGCTGCTGTAGAAGCCAAACAAGTGGCCCAGCAGGAA
GCCCAGAGGGCCCAGTTTTTGGTGGAGAAAGCAAAGCAGGAACA
Phase-1 RCT-180 ACGACAGAAGATTGTGCAGGCTGAGGGGGAGGCGGAGGCTGCTSEO ID NO:
AAGATGCTTGGAGAAGCACTGAGCAAGAATCCTGGCTATATCAA308
GCTCCGAAAGATCCGGGCTGCCCAGAACATCTCTAAAACGATCG
CCACATCACAGAACCGGATCTATCTCACAGCTGACAACCTTGTGC
TGAATCTGCAGGATGAAAGCTTTACTCGGGGAAGTGACAGCCTC
ATTAAGGGTAAGAAGTGAGTGTGGACATCAAGAACCCCCACCAC
CAGAGAAGTTGGCACACTTCTCCAGTTTGGAGGGGCCAGCTTAG
GGGGTCAAGCATACCCCANCCCTGACCCAAGCATCATGNGATGG
ATTCTTCTGTATCTGCTCTCTTGGGATTAANGGAAACTGAAGAC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTGAACATCTACGTGC
CACCGTGCGCTGGGATTACCAGCCAGACATCTGTAAGGACTACA
AGGAAACTGGCTTCTGTGGTTTTGGAGACAGCTGCAAATTCCTCC
ATGACCGTTCAGATTACAAGCACGGATGGCAGATAGAACGGGAG
CTCGATGAGGGCCGTTATGGTGTGTATGAAGATGAAAACTATGAA
GTAGAAAGCGATGATGAGGAAATACCATTCAAATGTTTCATCTGT
Phase-1 RCT-181 CGCCAAACCTTCCAGAATCCGGTTGTTACTAAGTGTAAACATTATSEO (D
NO:
TTCTGCGAGACCTGTGCATTGCAGCATTTCCGAACCACTCCACG309
GTGCTATGTTTGTGAGCAACAGACCCATGGGGTTTTCAATCCTGC
CAAAGAACTGATTGCTAAACTGGAGAAATACCGAAAAGCGGAAG
GTGGTACTTCTAACACTTCAGAAGACCCGGATGGAATCTAATTGC
CTTTACTTAGATTTTTTGCAATTGTCAAATCTCAAAGTACTTTTTGT
TTTGGTCACTTCAAACCAAAGCAACCGTAATTGAAGAAATATTAAG
TTTTCTAAGAAGAATATCCAAGTTTTGTATTATATGACAGTGCTAC
AGATGGGAA
182
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTGAATGTCTCCAGCC
AGGCCTCCCAGCGTGCACTGACCAACCATACCGTCTACTGTTCC
ACCAAGGGTGCTTTAGACATGTTGACCAAGGTGATGGCCCTAGA
- GCTTGGGCCCCACAAGATCCGTGTGAATGCAGTAAACCCCACAG
TAGTGATGACACCCATGGGCCGGGCCAACTGGAGTGACCCGCA
CAAAGCTAAGGTCATGCTGGATCGTATCCCACTTGGCAAGTT'i'GC
Phase-1 RCT-182 TGAGGTGGAGAACGTGGTANACACCATCCTCTTCCTGCTGAGCASEQ ID NO:
ACCGAAGTAGCATGACTACTGGTTCCGCTTTGCCAGTGGATGGG310
GGCTTCCTGGCTACCTAAGCCCTCCCTACCAATACTCTGCTCAAC
TCATGTTCAGAACATCGTGCCCTCCATCCCTCCAATAAAGCTCTC
TGCCCAGCCTGTGTGCTGATTCTCCACCCCNNANAAAP,AAAATTC
ACANNAANNANAANAAAAAAAGTTTGGCGGCCGCAAGCTTATTCC
CTTTAGTGAGGGTTAAATTTTAGCTTGGCACTGGCCGNCGTTTTA
CAACGTCGTGACTGGGAAAACCTGGCGTTACCCCACTTAATCGC
CTTGCAGCANATCCCCCTTTCGCC
TCCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGATAGTAGGTA
GGGACAGTGGGAATCTCGTTCATCCATTCATGCGCGTCACTAATT
AGATGACGAGGCATTTGGCTACCTTAAGAGAGTCATAGTTACTCC
CGCCGTTTACCCGCGCTTCATTGAATTTCTTCACTTTGACATTCA
GAGCACTGGGCAGAAATCACATCGCGTCAACACCCGCCGCGGG
CCTTCGCGATGCTTTGTTTTAATTAAACAGTCGGATTCCCCTGGT
Phase-1 RCT-184 CCGCACCAGTTCTAAGTCGGCTGCTAGGCGCCGGCCGAGGCGASEQ ID NO:
GGCGCCGCGCGGGAAACCGCGGCCCGGGGGGCGCACCCGGC311
GGGGGAACCGCCGACGCGGAGGAGAACCCCGAACCCCGGGAA
CCCCCGACCCCGCGGAGGGGGAAGGGGGAGGACGAGGCCGGA
GGAAAACCCCGCGCCGGCGACCCGCCGGGCTCCCCGGGAGCG
GCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCA
CTGGCCCGTCGTTTTACAACGTCCGTGACTGGGNAAACCCTGGC
GTTTNCCCAACTTTAATCGCCTTTGCAGCACATCCCCCTTTCGCC
AGCTGGCGTAATAACCGA
NCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGAATTTAAGCTCCA
GCAGACCAGCTGCCTGAAGAAGGACTGGAAAAAGCCGGAGTGTA
CAATCAAACCAAATGGGAGGAAGCGGAAATGCCTGGCCTGCATC
AAACTGGACCCCAAGGGTAAAGTTCTAGGCCGGATGGTCCACTG
CCCAATACTGAAGCAAGGGCCTCAGCAGGAGCCTCAGGAATCCC
AGTGCAGTAAGATAGCACAGGCCGGCGAGGACTCCCGCATCTAC
SEQID NO:
Phase-1 RCT-185 TTCTTCCCTGGGCAGTTTGCCTTCTCAGGGCTCTACAATCCAAAT
312
AAGCCCTGGACAGGGTTTCATCTTACTTCCTGTACAGCCGTGGC
GGTACCCACCATATGGCCTCCCAAAGACTTTCAACTCCAGGCTAA
TAAAACTGTTCCTTTCC GTGT
GGCGGCCGCAAGCTTATTCCCT(-fAGTGAGGGTTAATTTTAGCTT
GGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTG
GCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCCTTTCGCC
AGCTGGGCGGNAATAANCGAAANAGGNCCCCCACCNNTN
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT1~'
GGCCCTCGAGGCCAAGAATTCGGCACGAGGAAAAGCCGGGGCA
GTATGGACCTCACTCTTCTGTGGGTGCTTCTGCCACTGGTGAGC
ACAGCCTGGGGCCAGTATGGTGACTACGGGTACCATCCATACCA
GCAGTACCAGGACTACAGTGACGACGGATGGGTGAACCTGAACC
GTCAGGGCTTCAGCTACCAGTGTCCCCACGGGCAAGTGGTGGTA
GCTGTGAGGAGCATCTTTAACAAGAAGGAGGGCTCTGACAGACA
SEQID NO:
Phase-1 RCT-187 GTGGAACTATGCCTGCATGCCGACTCCCCAAAGCCTCGGGGAGC
313
CCACTGAGTGCTGGTGGGAGGAGATCAACAGGGCCGGCATGGA
ATGGATGACAACCGAGTACCCAGGCCACTACGGCGAAGACATGG
ACATGATTTCCTATGACTATGATTTCTATATGAGAGGAGCAACAAC
CACTTTCTCTGCAGTGGAAAGGGATCGCCAGTGGAAGTTCATAAT
GTGCCGGATGACTGACTATGACTGTGAAATTGAAAACGTTTAGAT
TCCCATGTAGAGAAGTCCGGGTGAAGGGCAAGGGTCCTGAGGG
TGTCATATCACATCTGCTAATATTAATTAGAACAACTGCACTTTTT
183
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGTTTTGGCCCCATT
TCTTACAGTCTCAGAAATTTAATTTAGCAGTGAACTGTACAATGTT
GTTTTTCTTTGCAAAATATATTTTTGTTTTAGAAAAGGATTAGGATT
TTTTGTTAGGGTGAGAACAGTCTTTCTGGTTTCTTTTAAATGAAAT
GCTTTAAAAAGAATAGTACTAATACCATGCTATTTAAAATATTTTTA
GATTATTTACATTTTAGTCAATGGGGGTTATTGGTTCTCTTATGTG
Phase-1 RCT-188 TAAACACTGTACCAAGTTTTGCAGCTCCTTTCAAATATACATTTCTSEQ ID
NO:
GAAGATTTATTT'fCAAAGTCTGAACATTTTAGAAATGAATCTCTTTT314
CCCCTAATGTTTTCTTTATTTCAACAATTCTCAGGGGCCAATTCAA
ACAGACTTAGAAGCGAGATTCTTTAAGATTATAGAATAP,GTTGGC
CTCTTGGTGCCGGCCCAGTGAGCCAGCAGAACAGCAGTCTGTTT
CTATTGCTGTAGACACCTGCTTCCACGGCTGTCCCTAAAACTGTT
GAATTCGGGAGGTATTTTTAAAAAATTCCACAATTGGTTTGAAGAA
ATGTATAAATAAAAATCTACTTTTGAGAACTTTACCAAGCAAAAAA
AAAAA
GCCNGGGATATGCNCNGATTACNNGATTCACTGGCCGTCGTTTT
ACAACGTCGTGACTGGNAAANCCCTGGCGTTACCCAANTNANTN
GCCTTGNTGGCGACTGTGGAACCGGAAACCACCCCTACCACTAA
TCCCCCACCTGCGGAAGAGGAAAAAACCTTCTGTTTTCTGTCACA
GCATTGTCCTTGCTGTCCTCTTGCTGATGGCTGCTAGATGTTAAT
TTATTTGCTTCCCTCCTTGATAACATTAGGTGATTCTGATTTCAAN
TTTTTCATTTGTTTTGCTTTTGTTTTTTTCCTCATGTAACATTGGTG
Phase-1 RCT-189 AAGGATCCAGGACTATGACAGAAAGGTGGAATAAACATTACATTTSEQ ID
NO:
GTGCATTCTTTGGGTAATTTTTTTGGTTTTTGTAACTACAAAGCTTT315
GCTACAAATTTATGCATTTCATTCAAATCAGTGATCTATGTCTGTG
TGATCCCTAAACATAATTGTGGACTATAAAAATGTAACACCATAAA
TTACATTCCTAACTANAATTAGTTGNCTGCT1?TGAATCTTTATGC
CTGNACTTTAACACT1-fGGGNTACTTAGGTTATTTTGNTTTGGGTT
ACAATGGCTCAAGTAGAAAAGCCGGTCCCATCCTTTTTAAAGACA
GTGTACAAAACTGGNNATNNAATGTGNTCANGNGAATTGTCTTTT
AAAAAAAAAAAAAAAAT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTGAGAAGCTAGTGTC
CAAGTCTGTGTTCCCCGAACAGGCTAACAACAATGAGTGGGCCA
GGTACCTCTACTACACAGGGCGAATCAAGGCTATCCAACTGGAG
TACTCTGAAGCCCGGAGAACGATGACCAATGCCCTTCGAAAGGC
ACCACAGCACACAGCAGTTGGCTTCAAACAGACGGTGCACAAGC
TTCTGATTGTGGTGGAGCTGCTGCTGGGGGAGATCCCAGACCGC
Phase-1 RCT-191 CTGCAGTTCCGTCAGCCCTCCCTAAAGCGCTCTCTCATGCCCTASEQ ID
NO:
CTTCCTTCTCACCCAAGCTGTTAGGACAGGAAATCTTGCCAAGTT316
CAACCAAGTCCTGGATCAGTTTGGGGAGAAGTTTCAAACAGATG
GGACCTACACCCTAATTATCCGACTGCGACACAATGTGATTAAGA
CAGGTGTGCGTATGATCAGCCTGTCCTATTCCCGTATCTCCCTGG
CGGACATCGCCCAGAAGCTGCAGCTGGACAGCCCAGAAGATGC
AGAGTTCATTGTCGCCAAGGCTATCCGGGATGGTGTGATTGANG
CCAGCATCAATCATGAGAAGGGATACGTCCAATCCAAAGANATGA
TTGACATCTACTCCACCCGGGAACTCAGCT
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTTTCCGCTTGCTGC
TCCGCCATGGCTCGCGGTCCCAAGAAACACCTGAAGCGTGTGGC
GGCCCCACGTCACTGGATGCTGGACAAACTGACCGGCGTGTTCG
CGCCCCGGCCATCTGCCGGCCCGCACCGCCTGCGGGAGTGCCT
GCCGCTCGCCATCTTCCTGAGGAATAGGCTCAAGTACGCTCTGA
CCGGCGATGAGGTGAAGAAGATCTGCATGCAGGGCCTCATTAAG
Phase-1 RCT-192 GTCGACGGCAAGGTCAGAACCGATGTGGCCTACCCAGCTGGCTTSEQ ID
NO:
CATGGATGTCATCAGCATAGACAAGAGCGGTGAGAACTTCCGCC317
TGGTCTACGACACCAAGGGCCGCTTCGCGGTGCACCGCATCAC
GCCCGAGGAGGCCAAGTACAAGCTGTGCAAGGTGAGGAAGGTC
TTCGTGGGTACCAAGGGCATCCCGCACCTCGTGACGCACGACG
CGCGAACCATCCGCTACCCTGACCGCTCATCAAGGTCAACGACA
CCGTGCAGATCTCGCTAGACAGCGGCAAAATCACCGATGCCATC
AAGTTTGATACCGGCAACCTGTGCATGGTAACCCGGAAGGGGCC
AACCTGGGCCGCATCGGC
184
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGGACGAGGTTTTTTTTTTAACTTTT
AAAGAAAATACTTTATTACATCATGAAAAAGGTATCCAACAACTAG
ATTCATACTTGCTTGAATCTATAAAAACAAACAAACAAACAAAAAA
CTGAAAGTTTATTCATTAGACTGTATGTGGGGTCATGTTCCACAT
GGGAACAGAGAGGCACAAGGGCTTCTAAGTATTGCACAGTCTTG
AAAAAAAAAAAAAGGAGTTGGGAGGAGAAGATCACATGATACTG
GGAACGTCTCACATTATGAGAAACTACCAAGAAACATTCGAAAAG
SEQID NO:
Phase-1 RCT-193 AAAACCCTCTGTTTCTACAGTAGCTTTAGTCTGCAGTTCTTGGAAT
318
GACTATTCCATTGAAGACATCTTAGTAACAGGAAGCTTCGTTTGA
GCAATCCCATGTGCAAATATTAATAGGAAAATATATAAAATAAAAA
ACCTTTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTT
AGCTTGGCACTGGNCGTCGTTTTACAACGTCCTGACTGGGAAAA
CCCTGGCGTTACCCAACTTAATCCGCCTTGCAGCACATCCCCCTT
TCGCCAGCTGGCGTAATAGCGAAAGAGGCCCCCACCGATCGCC
CTTCCAACAGTTGCGCAACCTGAATGGCGAATGGGACGCGNCCT
GTANCGGCGCAATTAAACNCGGNGGGGTGNGGNG
TATGACATGATTACGAATTNAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTACCAGCGTAAGC
CACGACAAGCTTCCTAAGGTTCAGTGTTATGACCAGTGTGAAAAC
AGATGGACAGTTCCAGCCACCTGTCCCCAGCCCTGGCGTTACAC
AGCCGCAGCTGTGGTGGGGAACCAGATTTTTATCATGGGTGGGG
ATACAGAATTCTCAGCCTGCTCTGCTTACAAGTTCAACAGTGAAA
CTTACCAGTGGACCAAGGTAGGAGACGTGACAGCCAAGCGCATG
AGCTGCCATGCCGTGGCCTCCGGGAACAAGCTTTACGTGGTTGG
SEOID NO:
Phase-1 RGT-194 AGGATAC-I-fCGGCATTCAGCGCTGCAAGACGTTGGACTGTTACG
319
ATCCGACTTTAGATGTGTGGAACAGCATAACCACGGTTCCCTACT
CTCTGATCCCTACCGCGTTCGTCAGCACCTGGAAACACCTGCCT
TCCTAATGCAGAGCAAACCAAGGAGAGCACGAGTGAGCTCACTC
TGACACACACGAGATGTCGTTTCTGCTCTGAAGAAGGCAAGTTTA
ATGAAGAGAAAG GTGAGCGGCCGCAAGCTT
ATTCCCTTTAATGANGGTTAATTTTACTTTGGCACTACCCGTCGTT
TTACAACGTCGTNGACTGGGAAAACCCTGGCGTTACCCAACTTAA
TCGCCTTTGCA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTCCCCGACCAGTCT
GGGTACATGGGGCTCCTGGGCTGGCCCAGATGACGACAAGTTC
AGCGCAATGAAGTACGAGCAGGGCACAGGCTGCTGGCAGGGCC
CCAACCGCTCCACCACAGTACGCCTCCTGTGTGGCAAGGAGACT
GTGGTGACCAGTACCACAGAGCCCAGTCGCTGCGAGTACCTCAT
GGAGCTGATGACACCAGCAGCCTGCCCAGAGCCGCCTCCAGAA
GTACCCACTGATGGAGACCATGATGAACTGTAGCCGGAACCTCA
SEQID N0:
Phase-1 RCT-195 AGGCCTACAGATAGTCTACCGATCCCATAGTCTGCGGACCAATG
320
CCTGCCCACCCTGGGGTCTCTGGCCATTCTCCAGGCAGCAGGAA
CCCGAGGGGCTCTAAGCCCCACTTCTGGCCCAGGCTAGCCAAG
CCATGTTCCTGAGGCCCCAGCGGCCTCCAGAGATGGATAATGAG
CTCACCTACCTTGGATTCCTGAGAGGAGTTAATCCCTGCACCCCA
CCTCACCCCTGTCTCCCTAGCTGGTGGGAGATGGATGTATGACT
TGACCTGTGACCTCAGAACAATAAATGTGACTTGTCCAAAAAAAA
AAAAAAAAAAAAAACACATGCGGCCGCAAGCTTATTNCCTTTAAT
GNAGGT
TTTTTTTTTTTAAAAACTGAATAATCATGTATGGTTTATTTAGTACA
ATGATTATAACCTATAATACAATAAAACGTCTCCATAACTAAGGAG
TGATATGCCATGTATTTTCTCAAAATTTTGTATTGAGTATTTTATTA
ATGTCATTTGCTGTTCAAGTAACACCTACTGCTTTTTCTGATAATG
Phase-1 RCT-196 GGAAGAAP~AAACATAAAGACAGGAAAAAGCTACTACCCCCAACASEO ID
NO:
GGAAGTCAAGGGACAATTGGGCGTTTGTTCTTTTGTAGAGGCAG321
TCTCAACTCTTTACTTCCTTCCTGCTTCAGGGCCACGTGGTTATG
GCCTGCAGCGCTGGAGAAATCTCGGGTACAAGCACACGTCTCGG
ATGTGATACCTGTTCAGAATCCAGCTTAGAAATCGTTCCAAGCCC
AAGCCATACCCTCCGTGAGGACATGTACCATATTTTCTCTG
185
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGAGGTGCCTTC
TGTGTTCTAGCCTTGGTGATCTTAGCAACTTTAAGCCTGTCAACA
ATATCTGATTTTAAGAATGTAGCAGTGTGGGAAGATGGTCATGGA
CCTTTAGATGTCTCAGGAACTGAAAGTTCAGAGACATCTAAACCA
CCACGTCTCACACCACCATGATCCTGATGAACTCAACGGCTGCG
ATGAACTCAACTGCTGCAGCCATTCGTTCCCAGCAAATAGGAGAG
SEQ1D NO:
Phase-1 RCT-197 AAATTAATTGCAGTTACTAATAACATGACTGTTCCAGAAAAGCCCC
322
CCCCTTTGGGAAAGTTTTGTTTAGCATGATTCAGAATAGTAGTGA
CTCTTAGAAAGATCATGGATAAGTTCCAACAAGTTGAGCAAATTTA
TCAAGAGTTAACTAGAAGGAAAAGAGAAACTAACATTGAGCAAGA
AACGAAAGAAATTATAGAATGGTTACAAAAGTTTCCTTTTTATTCT
GAGGGCCCATAGAGTTTAAACTTTATTAAAATAAAGGTAAATGTTA
AATGTATATCTGGGTACCCACAAGTCTGGTAGTATAACTGCAGNT
TTCTAAACTATTGTTTGCGGCTGAGAA
TTNACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGGGAAGGAGAAGGAGCT
GGTGGTGGCCGAGACAGTGGAAGAAGTGAAAAAAGCACCTGTTT
TGGTGTGTCCACCCTTACGAAGCCGAGCATACACACCACCCAGT
GATCTCCAGAGTCGCTTGGAATCTCATATTAAAGAAGTTCTTGGG
TTCATCTCTTCCTAATAATTGGCAAGATATCTCCCTGGATGATGGA
CATGTGAAGTTCAGACTCCTAGCAAATTTAGCTGATGACTTAGGC
CATGCAGTACCTAACTCCAGGCTTCACCAAATGTGCAGGGTCAG
SEQID NO:
Phase-1 RCT-198 AGATGTTCTTGATTTCTATAATGTTCCTGTTCAAGACAGATCTAAA
323
TTTGATGAACTCATTGCTAGTAATTTACCTCCCAATTTGAAAATCA
GTTGGAATTACTGAGCAGTCCAGTCAGAACACAGTGAGATCATTC
TCATTCTTCTCATTGGGTGACTGACAGCGAACTTTGTGAGATGTT
ACCTATTAGAACTTGGTTCAGAACTTCCTTTTTTTTTTTCTTTTCTC
CTTGGAGAAGACACATTTTTTTTTCTCTCTGGAGCATCCACAAAG
AAAACATTATCACATTTGCTAAAGCTATTTATCCCGAATAAAATCA
AGTCTTGGTAATTATGAAAACATTCTTATTCCTGGTATATAGTCAG
GGTTGTTGAGAGGACANAAAGTGGTAACATGN
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCTTCACCTGACCTC
CGGGCGGCAGAATGGAAGAAGGTGAGGACCCAGGAAGTCTGAT
TAAAGTGATCCACTTGCTGGTCTTGTCTGGTGTCTGGGGCATGCA
GATGTGGGTGACCTTTGCCTCAGGCTTCCTGCTTTTCCGGAGCC
TCCCGAGGCACACGTTTGGACTTGTGCAGAGCAAGCTCTTCCCA
GTCTATTTTCACGTCTCCTTGGGTTGTGCCTTCATCAACCTCTGC
SEOID NO:
Phase-1 RCT-202 ATCTTGGCACCACAGCGGGCCTGGATCAACCTCACGCTGTGGGA
324
AATCAGTCAGCTTACCCTACTGCTTCTGAGTCTCACACTGGCTAC
CATCAATGCTCGCTGGCTCGAGGCTCGCACCACAGCTACCATGT
GGGCCCTGCAGAGTATAGAGAAAGAGCGAGGCCTGGGGACAGA
GGTGCCAGGCAGCCTCCAGGGCCCTGACCCCTACCGCCAGCTG
CGGGAGAAGGACCCCAAGTACAGTGCTCTCCGGCAGAAATTCTT
CTACTACCATGGCCTGTCTTCCCTCTGCAACCTGGGGGTGTGTG
CTGAGCAATGGTC
CTTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTAGCTTTCGTTT
CTTTGCTATGTCTGGACGTGGGAAGCAGGGCGGCAAGGCTCGC
GCCAAGGCCAAGACCCGGTCCTCCCGGGCGGGCCTGCAGTTTC
CCGTGGGCCGCGTGCACCGTCTGCTGCGTAAGGGCAACTATTC
GGAGCGGGTGGGCGCCGGCGCCCCGGTGTACCTGGCGGCCGT
GCTGGAGTACCTGACGGCCGAGATCCTGGAGCTGGCGGGCAAC
Phase-1 RCT-204 GCAGCGAGGGACAACAAGAAGACGCGCATCATCCCGCGCCACCSEQ ID
NO:
TGCAGCTGGCCATCCGCAACGACGAGGAGCTCAACAAGCTGCTG325
GGCCGCGTGACCATCGCACAGGGCGGCGTTCTGCCAAACATCC
AGGCGGTGCTGCTGCCCAAGAAGACCGAGAGCCAGCACAAGGC
TAAGGGGAAGTAAGACCAGGGATCACCAAAGGCTCTTTTCAGAG
CCNCCTAT CNATTGCGGCC
GCAAGCTTATTCCGTTTAGTGAGGGTTAATTTTACTTGGCACTGG
CCGTCGTTTTACANCGTCGTGACTGGGAAAAACCCTGGNGTTAC
CCCAACTTAANNCCCTTGCAGCANNTCCCCCTTTCGC
186
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CAACNNCNNNCNCNNTTATGNCATGATTACGAATTTAATACGACT
CACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAG
GTGTGTGTGTAACTGGATCAGCAGCATGTGTTCCAGTCATGGTTG
ACCTTAGCAGACATTAGCAGGATTAACACTGGAGGGAAACAAAG
AAGCAAAATAAATATTTCCTCTGAGGTGGTATCTGCTGCTTGAAC
TGTTGTGCATTCATTGAACTTTGGACTTCAGAGGTTGCCTTATTG
CATCTGAAATTCTTGGTCTAAAGTGAGATCCGAATTTCTTTTGCGC
ACCTTCACGAAAAAGTATAGAAGCCATATAGTTGGAACTTTGTGT
Phase-1 RCT-205 GGGTTATGTCTAAACCTAGGAATAAATGCTGGGTTTCTTTTCCTGSEO ID
NO:
TTGTAATTTCAGTCAAGTTACTGTGAGGGAAGCTGTTAGGTACAT32&
TTTAAATAAATTACAGCAAAGCGCTATCCTTCTGATCACAGCCAA
GCTAACATCTATCTTCCGAACATCATGTCTGCCGCCTGCTGAAAG
GCTGTAANGGTCTGGGTAGTTTTCATTTAATATTGATCAAAGAAG
CGTTTATTTATAAGNGCAAAGTGTTTTTTGGACGTTAATAAAAAAA
AAAGTGTTGNCCAACT TGGAA
GCGGGCCGCAAGCTTATTNCCTTTANTGANGGTTAATTTTAACTT
GGCACTGGCCGGCGNTTTACAACGTCNNGAATGGGGAAAACCTG
GNGG
NNNTCTCTATGACATGA-t-fACGAATTTAATACGACTCACTATAGG
GAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCAGATAAA
TGCAGGCCAGAAAGGCTGCTGCCGCCGCCGCCGCCACCACCAC
CACCACCGCCTCCTGGATTGTCTGCCATGGGTCGCACTGCTGTG
GCAGACGTCTGGACTTGAGCAGAGGGAATAACCTGACTTACTTG
CACTGTGATCCCCCTTGCTCCGCCCAGTGTGACCTTGAACCCCA
TGCACTGTGACCTCTGCCTCCCCCCCTTCCCACTGTGATTGGCAT
Phase-1 RCT-206 GTTGACAAGGGCTGTCGCAAGTCAATAGAAAGGGAAAGGGTGGGSEO ID
NO:
GATTAGGGGAGGATTAGGGGAACCTACCAAGGACTCAGAGTAGA327
GGGTCAGACAGTGCCACTTGGCCGCTTGGGGTAAAGCCAGTGC
CAGCAATAACAGTTTATCATGCTCATTAATTTGGGATTTCAAAACA
CAAATGAGAACTCCCCCACCCACCCCAAGTGCATGTCGCCATCA
CTTAAAGTAAGTTCCATTGAAAATATCCTTACTTTTTTTTTCTTCCT
ATTTTTGTTTGTTTAATACAAATACCTGATTTGCAGAAAAAAAAAAA
A,~~AAAAAAAP,ACNATTGCGGNCGCAAGCTTATTTCCTTTTAATGA
GGGTTAATTTTANCTTGGNCACTGGCCGNCCTTTTACAACG
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTCATGTGCGATGCTC
TCATCAAGGCCATTGGCACGGAGCCTGACTCAGACGTCTTCTCG
GAAATAATGCACTCCTTTGCTAACNGCATTGAANNGANGGGAGAT
GGGNGTCTCAACAATGAACACTTCNAGGAACTGGGAGGTATACT
GAAGGCGAAGCTCGAGGAACATT-i'CAAAAATCAANAGTTGCGGC
AAGTTAAAAGACAAGATGAAGACTACGACGAACAGGTTGAANAGT
SEOID NO:
Phase-1 RCT-207 CNCTACAAGATGAANATGATAATGATG'rf-T'ATATACTGACTAAAGT
328
CTCANATATTTTACACTCAATATTCAGTANCTACAAANAAAAGGTG
TTGCCGNGGTTTGAACAGCTGCTCCCATTAATTGTCAACCTGATT
TGTCCACATAAACCCTGGCCANACANACAATGGGGATTGNGCAT
CTTCGATGATATCATANANCACTGTAGTCCAGCTTCATTTAAGTAT
GCAGAATATTTCTTAAGGCCAATGCTCCAGTATGTATGTGACAAC
ANCCCGGAAGTCAGGCAAGCTGCAGCATATGGCCTTGGCGTCAT
GGCNCAATACGGNGGANATAACTACCGCC
GNNNTCTCTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCGGCAC
GAGGCCGGAGAAGTGAGCCCTTCCCAGCGCCCCCAGAAGATGA
CATAGCCACAGCAAAGGAGGCCTCGAAACCCAGCCCAGCCATG
GATGTGCAGTTGCCGGTGCCAAGTCAGGAGGTCCCAGCACGAC
CATCAGTCATGACTTCCACTCCTGCACCCAAGGGTGAGCCTGTC
ATCATCCCTGCCACGCGGAATGAGCCCATTGGCCTAAAGGCCTC
SEOID NO:
Phase-1 RCT-208 GGACTTCTTGCCCGCCGTGAAGGTCCCCCAGCAGGCAGAGCTG
329
' GTAGATGAGGATGCCATGTCACAGATCCGCAAAGGCCACGACAC
TATGTGCGTGGTGCTCACCAGCCGCCACAAGAACCTGGACACTG
TGCGAGCTGTGTGGACCACAGGAGATATCAAGACATCGGTGGAC
TCTGCAGTGGCCATCAATGACCTGTCTGTGGTCGTGGACCTTGT
GAATATTGTCAACCAGAAAGCCTCCCTGTGGAAGCTGGACCTGT
GCACCACTGTGCTGCCCCAAATTGAGAAACTTCTGCAGAGCAAG
TATGAGAGCTATGTCCAGACTGGGTG
187
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTTGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGCGGAGAATGCCGA
ACTAGAAGAAAGCCCTCCCTTAACCTCTGAACCCTCTGCCCAGC
CTGAGTCACAAGAAGAAACCGAGGTCACAGCAGAAGCAGCATCA
CCCCAAGGCTGATCTGCAAAATTCTATAGTTGCTTTTTTATTTTTA
GTAACCTTAGCCCTCCTTTCTAGAATATTTTAATATACCTTAAAGA
ATTTGGCTTTACTAATAGATATTTGATTGAGATTTGATATTCTACAT
Phase-1 RCT-209 GTCTTAATAGTTTTCTACCCTTTAAAATCAGTCTGTGTTAAGACCTSEQ ID
NO:
TAATCAGTGTTAAGTTTGGATTTAAGTTTTACATTCTAGAAATTGA330
GTTATCTATGCAACCTATGTCACTTTGATTTTGCTCTGCCTTTCTC
TTACTTTATTATATGTAAGACTAGATTGTTGGGTTTGACGTGAACT
CATTTAAATAAAATTAGAAAATCCT
CAATTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTA
GCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAAC
CCTGGGCGTTCCCAACTTAATCGCCTTGCAGCACATCCCCCTTTC
GCCAGCTGGNGTA
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAAGAAGCAGCGAGGA
CGACCCCCGGACGGACCAAACCCGTGCGCCGCTGTAAACCCGT
GCTCAGCGCCGACGTCCCCTGCCGCCGCCATGCCCAAAAGAAAT
GCTGAAGGGGATGCTAAAGGAGACAAAGCCAAGGTGAAGGACG
AGCCACAGAGAAGATCTGCAAGGTTGTCTGCTAAACCTGCTCCT
CCAAAGCCAGAGCCCAAGCCTAAAAAGGCCCCTGCAAAGAAGGG
AGAGAAGGTACCCAAGGGGAAGAAGGGGAAAGCGGATGCTGGT
SEQID NO:
Phase-1 RCT-211 AAGGATGCGAATAATCCTGCAGAAAACGGAGATGCCAAAACAGA
331
CCAGGCACAGAAAGCGGACGGTGCTGGAGATGCCAAGTGACGT
GTGTGCGTTTTTGATAACTGTGTACTTCTGGTGACTGTACAGTTT
GAAATACTATTTTTTATCAAGTTTTATANNNNAAAAAAAAAAAANAA
AAAAAAAACAATTGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGT
TAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTG
GGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATC
CCCCTTTCCCAGCTGGNGTAATAACGAANAAGNCCGCACCGATC
GCCCTTCCAACAGTTTGCGC
ATGTCATTGTACCTGCTTCAAGGGGCNTGGTAGTTAGGGACAGC
GGTGTGTAATGTGGCCCTTCTTTCTCAAAGGGGAATAGGCTGGT
GTCCCGCTTTATGGTTCGGCATAGAGCTCTGTAGACTCAAGTTTC
AGCTGTTCCAGGGCTTCCTGCTGGGCTTCCAGCATGGCTCTGAT
GGCGTCCCTCTCCATCTCATGCTCCTGCTGCTTATACAGTGCCCA
CCTCTTCAGCAGAAGAGCTCTCCGCTCACTCTTCCTCAAAAGAAT
Phase-1 RCT-212 GCTCCTCCTGAGGTCGCTGTCTTGATTTATCCAAGAACCTCACAGSEQ !D
NO:
GGGTAATAAAATCTTCAATAGGAACCAGTTCTTGGGAGGCTCTTT332
CCAGTTTTCGGATCCTCTTTTTCAAGCGATCCTTTGCTGCTTGATC
CTTTCTAGGGTCTACCTTCTTCTTCTTCCGTAGAGGTTCAGCTCTC
ATGGGGATGAGCTCCCAGAAGGACAGCAAGGAAGCTCTCTGGTG
GGTGTGTCTGACCTGTGCCTGGCAGGTTCCTGGGATCCAGCTCC
GAGGTCGCAGAGCCCGCGCAGCACACAGCATCGCAGCGGTAGC
CATAGC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATTGTAGCATCTATGG
AGAAGACACCGTGACAGACGAGGAGGGGAAGTTCCGGTTACGT
GGACTGCTGCCAGGGTGCATGTACCACGTGCAGCTGAAGGCAG
AAGGCAATGACCACATCGAGCGGGCGCTGCCCCACGATCGGGT
GATTGAGGTTGGGAACAATGACGTGGATGACGTAAACATCATAGT
TTTCCGGCAGATCAACCAGTTTGACCTGAGTGGAAATGTAATCAC
Phase-1 RCT-213 TTCCTCCGAGTATCTGTGTACTTTGTGGGTGAAGCTGTACAAGAGSEQ ID
NO:
CGAGAGTCTCGACAACCCCATCCAGACAGTGTCTCTGGGTCAGT333
CGCTCTTCTTCCATTTCCCACCGCTGCTCCGAGATGGTGAGAACT
ACGTGGTGCTTCTGGACTCCACGCTCCCCAGGTCTCAGTACGAC
TACGTCCTGCCGCAAGTGTCTTTCGCTGCAGTGGGCTACCACAA
ACACATCACTCTGGTGTTCAGTCCCACGAGGAACTNCCTGAGCA
AGACATCCGCAAGGGNCTATATTGCCCTGCCTCTGACCTGCTGC
TCCTGNTGGTNGGNTACAACATGANAAGCTCNNCCTTTCTGCTG
CAACTGNCNAATCCNTCNTCANGGAATCAAAGCCCTT
188
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTTTCTTCTGAGCTGC
ATGCCCCTTGCTGGTTAGATGACAGCATACTTGACTCCCTCTATG
ATATTGGAGGTGACAACAACAGGAGACAI'TfCTCCCAGAATAGCA
TTGGACTTCTCAGGCAGACTCACAGTCTACTGTTTTGGTCTTTCT
CTCTCCTCCCCCTACTTCTGTCTCCTGGGTTCATTATCAGAAAGA
TAATACTAAAGTGAAAGCTTTGTTTAAGGTCTTAAAAATTGAAGAA
Phase-1 RCT-214 AATCAGAAATTGTAAAGACAGTAAGACTTCAGACATACATTTTATASEO ID
NO:
AGATCACAGTACAATAGTTAGAAGTACTGATGAGTGTATTCCCAA334
TCCCTGGTCCCTAAGGCTAAATCCACTGCTTGTTCCTTGCTCCCT
CGTATACTCTCAAGGTCTCTTTCAAAGATGGTTGCAGTGTTTGTC
TCCATTGTTTTTCCATAAAGTATTTCCATTTAAAAAAAAAAAAAAAA
AAAAGTGAGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATT
TTAGCTTGGCACTGGNCGTCGTTT'T'ACAACGTCGTGACTGGGAA
AAACCTGGCGGTACCCAACTTAATCGCCTTGCAGCACATNCCCTT
TCGCCAGCTGGNGGTAATAACGAANAGGNCCCCACCGATCC
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTAATTTTGGAGGTTT
CCCCACAGCAAGTCACTCTCCTTT-fCAGCCCCAAACTACAGGTG
GAAGTGCTGGATCAGTAAATGCTAATTTTGCTCATTTTGATAACTT
CCCCAAATCCTCCAGTGCTGATTTTGGATCCTTCAGTACATCCCA
GAGTCATCAGACAGCATCAACTGTTAGTAAAGTTTCAACAAACAA
AGCTGGTTTACAGACAGCAGACAAATATGCGGCACTTGCTAATTT
Phase-1 RCT-215 AGACAATATCTTCAGTGCTGGGCAAGGAGGTGATCAAGGGAGTGSEO ID
N0:
GTTTTGGGACCACCGGTAAAGCTCCTGTTGGTTCTGTGGTTTCAG335
TTCCCAGTCATTCAAGTGCATCTTCTGACAAGTATGCAGCCCTGG
CAGAGTTAGACAGCGTGTTCAGTTCTGCAGCCACCTCCAATAATG
CGTACACATCCACCAGTAATGCTAGCAGCAGTGTCTTTGGAACAG
TGCCTGTGGGTGCCTCTCCTCAGACACAGCCTGCTTCAAGTGGG
CCTGCTCCATTTGGAGCTACGCCTTCTACGAATCCATTTGTTGCT
GCTACTGGTCCCGTCTGCANCGTCATCTACAAATTCATTTCAGAC
CAATGCCAAAAGGANCAACAGCGGCAACCTT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGGATTGTTGTCGTTG
ATGTCCTGGACCACCACTTCCGCGCTGAACAGCTCCAGCGGGTT
CTCTACCACCAACTCCAGAGTTACAGTGCAGGAGGGCAGCGTCC
CACACAGCTCCTCTCGGTCGAGTCGATCGTTGACGAACATCTCTC
CAGTCTCCCAGTTCACCTCAAAGAACCTACGGCTAGCTCCGGAC
ACCACCCGGAGCCTGCGGGCCGACAGACTGCCGAGATCCAAAC
Phase-1 RCT-216 CAAGATCCGTGACCACGTTACCCACGGGAAACCCCTTCTCTCTCTSEO ID
NO:
CCTCCAGGATCTCATAGTGAATGATGGTGGAAGCCTCGGTCAAG336
GCAGCTAGCAGAAGCAAAACTCCCACCGTTCTCCCGGGGCTTAC
CAGTCCGCTGCTCCGGGCCTCTGCGACATCTCACTCAAAAGCAG
CTCCTCTTGGCGGGGTCCAGGTGGTCCCGGAGGTTTGGCAGAG
AAACTTTCAGCGGGTTAGCGCTTGGGCGCTGGGCGCCGAGTNC
GACATGGCTTTCTGGGCGCCGCTGATTTGTTCGCCCGCTGNTCA
GTCTCTGCCTCATCCCGGGGCGCCGAAAGGGGACGGGCCCNGG
NCAAATTCCAGCGTCTTCATTGGNCGACAGCGGCACACAGAN
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGAGCTTGGATGGGAAG
GAGTCTTGATGCTGACCAAGCTGGCACCAGCCTCACAGTAGTCT
CTGTGACCTTCTAAATGTGCTGTTCAGTCTACTGTCCACTGCTGT
CCCCACAGTACTACCCACCCATCCCTTGTTTATGCCATCACTTCT
GATTCCTCAGAGAACCCGGCACGGGTACACAAAGTGCTCACACC
AAGTCCTTGGTGCTGAGGGTATGGGAAAGATATAAAGGAAGTRA
AGACCAAAATAGAGGCAAGCGCATGGCACAGACTGGGCTGGCAA
SEOID NO:
Phase-1 RCT-218 GAGTGGGTGACAGAGTCTCTGAGGCAAAGTGGCCAGGTGCTACT
337
GCAACGTGTGGAGAAAAGACACTTTCCAGGCCAGCTGTGTGAGC
ATGAAACACAGAACCAACCACTTCCAGAGGTGCCTGGGTGGATC
TGGAATCCTTCCGGAGTTGCATTAGCCATAAGCTGGGTTCTTATA
CCTTTTCCATGCCCTGCAACCCAATCAGACCTACCCCAGCCTTGC
CTCTGAAGCAGGAGCCCTGGCAAGAGAGTTGGGTTGTGCTTCCT
CAGACCTCCCCTGGAAATTACCACTGCTTTATAAGTGCCCCCTAC
CCCCCATACCCAGCTTTTTGGGCCCCTCCCACTTATGTGTCTGGN
G
189
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCTCCATCCTCAAGTG
GACAAGAACTGTGCATCTGTCGTCCTGTGAGCCCAGCAGGACCT
GCCCAGGAGGCTCCAGAGTCAGTCATGGCTTTCTGTGCTGCAGG
CCCTTGACCCAGACAGGGCAGGAATCTCCCCAAAATCCCAGTGA
GGGAGGATCCAACCTGTGATCAGACTCCGGTCTTCTGACCCCTG
CCTTCCTACTCCTGCATCCTGTCCCATCACAGACAGCCCTCCTCA
CAGCCTGGTTCATCTGCCTTGTCCTCCAACAGTGCTCTCTTGGGA
SEQID NO:
Phase-1 RCT-219 GACAAGAGATTCAGAAGGGGAGGCAGGAACTCGAGCTTGACTTC
338
CACCTGTCCACCTGTTGGGAGTTCTGTCCAATGTGTGACCAACG
ACAATAAACCATAGCAAGCCGTGAAAAAAAAAAAAAAAAAAAACA
CATGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAAC
CTTGGCACTGGCCGTCGTTTTTACAACGTCGTGAACTGGGAAAAA
CCCTGGCNGTTCCCAACTTTAATCGCCTTGCAGCACATTCCCCCT
TTCGCNAGCTGGNGGTAANAAACGAAAAAGGCCCCCCACCGAAT
CNCCCTTCCAAACATTTCCCACCNTNAATGGGCAAATGGGACCC
CCCCTTGTAAC
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTGTAGTACCTGTAG
GGAGTACGGCCTCTCAGAACACTCAGGTTCTTTATAAACTTTGTC
TTGGTTTTAAGAGAAAAGGAATGTCAGTGTAATGCTCTGGAGGCA
GAGGCAGGCGGGTCACTGGGGGTTCAAGGACAGCTTGGTCTTC
ATAGCAAGTTCCAAGCTGTACAGGGCTACGCTGTAAGACCTGAC
Phase-1 RCT-220 CCAAAAACAGCAAACAAGAAGGAAGGAAGAGAAAATAGTATCTAGSEQID NO
:
AGATGGAACCAACTGATGCAGCAGCAGTGGCGTGGGGTTTCCAG
339
ACTCAGAAATTTCTTCTTTTCTAATTCTTAAGGACATTTGGTTTCCA
TGCTAACCTTTCCCCTGACACAGACTTAAAAGATCTGCAACAAGG
GGAGGCGCTTTCTCTTTAGAATGTAGAGAGGAGAGGAATTTGTTT
TTATTTTAACTATTAAATCATGATAAACTGACTGCTGAGACTTCCC
TAGCATTCCTTTAAAGTATTTTGTACAGAAGAGAAGAACCCTCCT
GGAGCGGCCCAGGTAGGTAAGTCTGTGCTGTACACAGCACCTCT
CTGCCTCTTCCACTGCTGTGTCACCCT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCTAACCGTGTCCACG
CTCCTGCCTGCAACCCTCTCCCTGCTTGGCACAGTCGAGGAGGA
AGATGCTCTTTGCCTATCCCAGCTGCACCCTGGCTTCCTGCTCAA
GGGAAGTGAGCACCCCACTTCCTGTGCTAGTTAGTGCCTGATTC
TCTGGGTGAGTCCCGGGGCGGACTCCCTCAGCCCCTTTCTCTGG
TACAGTGGTGTCCGCCCGACTGCCTCCTGTAACCCCATCTTCTAA
Phase-1 RCT-221 GCCATCAATTTTATGTTACTATATTGCCCTTTGTGGGGTGGGAGASEQ ID
NO:
GGGATCTCCTGGCTCTGCGACTTGCCCCTTTGCCGAATAGTTACT340
GTTCTTGACTTGAAGAGAAGCAACGTGTGGGGACCTCCCCACTG
CCCCAGCCCAGACTTCTTCGGAAGGGTTGGAAGTTGCTAGACAA
ATCAGAATGTAGAAGGTGGAGGATTCTGAGGAGGAGGCAGAGAA
TTCTGACTGGGGAGGTATANGTTGGGTCCTCTGCCTCCCACGGC
TGCAANGTGTGTCTGACCTCTGGAGCTCAGCCCCTCCCCCCTTT
CTCTTCAGTGCTGACAAGATGTCNATAAACTTATTTTCATACAATT
AAAAAAAAAAAA
TNTNGGANATGATTACGANTTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGAGGAACTGTGTCA
GGAAGGTAGAGAGCTGCCGATCTAAAACCTGGGAAAGAATGGAC
CGTCTAGCAAGGGGAGAGCAAGCAGACAAAGAAGCTTCCTTCTT
CCATGTTCATATAGGTTTCCAGCAGAAGGTGTGCCCCAGATTAAA
GGTATGTCTCTAGCTCCAGATGTATTCAAGTTGACAACCAAGAAT
AGTCATCACATAGTTCCTCATTGAGGAAAGTCAAAGCAGGAAGTA
Phase-1 RCT-222 AGGTAAGAATCATGGGAAAATGCTACTTGCTGTTTCCCCATCTCTSEO ID
NO:
GGTTTGCTTTCTCACAGGTTCATGCCTAGCTAGTTTTCTAATATAG341
CTCAAGGACCACCTGTCTAGGGAATGGTGCCACCCGTAGTGGGC
TGGGCAGTCTAGATAATCTACCACACACATCAACCCCCTGCCCC
CTTCTCAGGTGACCCTACACTGTGTCCACCACACACATCTACCCT
TACCCCTTCTCGCTAATTCAGACCNNCNCNCACCNNNNCNNNAC
NCNNNACANNNNNANTTGGAAGCGGCCCAAGCTTATTCCCTTTA
GGGGAGGGTTAATTTTACCTTGGCNCTGGCCGNCGTTTTACAAC
GTCNTGGACTGGGAAANCCCTGGCNTNNCCCAACTGAATC
190
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCCTTAGGANATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCAAGNAATTCGGCACGAGGCGAAGAGACTGT
GTGCCCGCAGNTACCTGTGTTTTCCAATAAACCCTCTTGCTGATT
GCATCCGAGTGGACTCGGCTCGGTCATTGGGCGCTTGGGACTC
CTCCTGAGGGAAAGGTCCTCTCTGGGGGTCTTTCAGTGTTGTGC
ACGCCCATGATGCTAGCACAGTAAGAGGCCAGTTTGGGCTGTGT
ATCAAGTTCATGGTCTACACGATCTATTTAGCAAACCTTGTCCCAT
AACTAAAAGGAACAGAAGACTAGAAAAAACATCACCAGGAAGAAT
SEQID NO:
Phase-1 RCT-225 GGTCCTTAAATAACTGTCCAGTTAGTGCCAGGGAATAATTATAAA
342
AAGTACTGATGTTAATTCCTCCAGAAACACCCGAAGTGTAACCGT
GATTTAAAAGCCTACATTACAAAAATCATTTTCATAGGACATACCT
TGCTTTTTTTTTTGGAGCTTCACACATGTGTGAGGAAAGGAAAAC
AGAACTTAGATGTTCCAGTTAAACTTTAACATATTCACTTCTTCAG
AGAACCCTATTAAGCCTTGGTGCTATGTGTCAGGTTCCCTCTTTT
CTTTATAATTCCTGTTAGCTGCACCACAAACCAATATATGACAAAA
GGAACACCTTGTATACATGGGCTTGGTACCAACAGCCCCTAGAG
A
TCTACATGATTACNAATTTAATACGACTCACTATAGGGAATTTGGC
CCTCGAGGCCAAGAATTCGGCACGAGGCAAGAAGTTAAGATCTG
GAAGGTAGCCACTCTAACTAGGGGCGTGCTGAGACAAGACCACC
TCATTCCTCTGCTGCTTTTCAGACAGGACTGTCCTGCCGACCCAC
CATGATCCAGGCTGCACTGTTCCTTGGCTGTATCTTACTGTCCTC
GGTGACCGCCTTTCCATGGAAGACTCAGGATGGTGGCCTGCCCC
ATCAGCCAGCTGGCACAGAAACTGAGCCTACACAACTGCTCTAC
Phase-1 RCT-227 AGCAAGAGTCCTCCTCCGACCTCCAGTACCTGTCGGAACCTCCTSEQ ID NO:
AAGCATGGCGCCCCTGCGCCCTGTAGCTCCTCTGTCTGAGTCCT343
TGTCCCTCTTAGCACTGAGAGTTGTCCTGGAAAACATCGGCTGC
CCTGCTGAGGCCTACTCTCTACAGCTTCAGCTCAGGGAAATGGG
AGGAAAAGACAGCACAGAAACTCTGATTCTCGAGAGTCAAAAGC
ATAGCCAGGAGGAAGGCATTGGCAATAATGAAGCCATTCTGAGG
CATCTGGTAGCATCCCCTGGAGAAATAAAAGANGGTCGAGCGCT
CAGTTACTGTGCGTGAGGCATGCACCTCTGAACANGGGTTGTGT
GTTGCGTGANTTGGCACAACTGGGGGGGGGGGGGGGT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGACTTAGTGATACTGT
GAGCCTCCATGTGAGTGCTGGGAACCAAACCCTGGTCCTCTAGA
GAGTAGCAAGTGCTCCTGACCACTGAACTATTTCCTGGCCTCCC
CACAAATATTTTTAAGTGATGTGATAACAGTTGTAGTCTGTTGCTC
TTAGATGATCATGAAATGGTCCAGTGTTGAATACACAAGTAGGTA
AAAGGAGATAGAGTTAGAAGGGATGGGTGTGATGCGTGCCTGCA
Phase-1 RCT-228 ACCCCAGCACGTGGGAGACAGAGACTGAGACTCAGCAGTTACAGSEO ID NO:
GCCAGGCTCCACGGGATGAGGAGCTCAAAGCCAGCCAAAAATAA344
ATGGACTTTTAAAAGAAAGAAAAAGTACATATTTGGACAGAGAGA
AAAAATGTTTTCCCATCTCTTGGATTTGCAAAGCATGGGTGTGTTT
TGAGCCGTGAAGTACTGCAGGTGGAGGACGGAAGTGTTGCCTGT
TCTGTCCCTCTCTGGGGCGCTTGGGTAANACAGGGCGTGGCTCC
TGTTCTCAATTATTCCAGCTCTTTTGTGGCTTTTTTTTTTTTTAAAA
TGGGAAAAAAGGTCTGCCTATATACCTCANATATCCTTTGAACTC
-
NTGTGTACCCCAGGCTTCCTGCCTCCTGTCT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTTTTT'rfTTTTTTTTTT
TAATTGAAGACAGGGCCTCCTTATAGTCTGAGATGGTCTGAAGCT
AATTAAGTAGACAAGGCTAGCCTAGAACTCATAAGCAATCTTCTT
GCTTCGGCCTTCTGAGTGCTAGAATTAAAGGTATGTGCTGCCCCA
CCCAGTTTGTTTGCTTGCTCAAAACAGCTTGTCATCTAGTGCCAA
CCGGCCTTGAACTCCCTATATGGCCAAGGGGGACCCTGGACAAC
Phase-1 RCT-229 TGATCCTCCAGCTTCCACCTCCTAACTGCTAACATTGGAGGCTTGSEO ID
NO:
TGACACCACCCCTAGCAGCTTCTATCACCGCTCAGGGAAAACAT345
GGAAGCTTTGGCTCCTTTAAAGCAAGAAAGAGTGGGGTGTGGTA
GCTCACACCTGTAATCTCCACATCCCCGAGGCTAAGGTGAGAAC
ACATGAATTCAGCAACTGAGGAGCAGGGTCCTATGACTCCATGC
CTC AAAACCTTTGCGGCCGCAAGCTTA
TTCCCTTTAATGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTT
TTACAACGTCGNGATGGGAAAACCCTGGCGTTNCCAACTTAATC
GCCTTGCAGCACATCCCCCTTTCNCCAGCTGGC
191
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCACACACACACCCCTC
ATCACTGATATGTTTTATCTTACCCCATCTCTCAGAGTGTTCCCTT
AAAACCCAGGCT'f-T'AACCCGGCATGTTCCCTCAGACTGTCTCCCC
AGAGCAGAGCAAGGCCAGAGTTCTGAAGTTCTCCATCTCATTTAG
TGGCCTCCTCTCTTCTCCCAGTTTGAGTCCTGGAGGCCAGGAAA
CGGGCAAGCTGTTGCTCATGGCTCCGTGGCCTTCTGTTCAGAAA
Phase-1 RCT-230 CTTATTCTTGCCACTGGTTCAATGAATCTCATCACCCTCTCTGCCASEQ ID
NO:
ATGGGAGCTCTTCTCTTGTGGGAGACACTGTAAACAACACCAAAG346
GAAAAAATAAAACCACTGTGTGTGTGACTGAAAAAAAAAAAAAAA
AAAAAAAAAATGGAAGCGGCCGCAAGCTTATTCCCTTTAGTGAGG
GTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGAC
TGGAAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACAT
CCCCCTTTCGCCAGCTGGCGTAATAACGAAAAGGCCCGCACCGA
TCGCCCTTCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACNC
NCCCTGTAACGGCGCATTAAGCGCGGCGGG
TNNTNACATGATTACGAATTTAATACGACTCACTATAGGGAAT'!-fG
GCCCTCGAGGCCAAGAATTCGGCACGAGGAGAAGGACGGGGGG
TGGGGGGGTGGATTTTGGCATCATAGCATATATATTAAAAAAAAT
AATCAGGACATCAGATACATTTTAATACATAGCTGGGGCCTTACG
TTGTAGATGAAGCTTGCTGTTTTTAGCAAGTTCCTGGGTTTCACAT
TCATTTCTGATGCATCGAATAGCTCCACACATTTCATAACACAGTC
TCTTTATTTGTATGCAAAAAAAACCCACTTTACTGTATTAATAAAGA
Phase-1 RCT-231 GCGTCATTTTGTAACAAAGTGACTGGAGCTATTTGGTGCTTGGATSEO ID
NO:
GTGAGCATCCTTTTTACTTTTGCTAAGCCTTATTTAAATTTTGTATA347
CCATGAAATATGTAGAACTTGTCAGATCATCCTAGCTCTGAGGGT
TTTTCTGGGTTGTTTCTGTTGTTGCGATAGGTTTTTATGTTTTGTTT
CGTTTTTTGTTTTGTTTTGTTTCGACGGCTCGTTTTGAATTGTAAG
ACGGCACTTGCTGACTAAGACACAACGCAGACACACTTTTGTAAG
TTGCTTGGGACCATAACAAGACTCTGTTCTCTAAGAAGGAAAAAA
AAAAAAAAAAAACACATGCGGCCGCAAGCTTATTCCCTTTAGTGA
GGGTTAATTTTAACTTGG
TAAACATACATGCCTATTATGCTTTAGAGTATTTGAGAAGATACTA
TGATTTTTAAGACTACTTAAAAACACACAAAATCTTAGATCCACAT
CCTACCCAGGGATAACAAATTCTGATTAGACTTCCATTTAATGCTT
CAAAGGCACTCATTCTTACTGTATTCTTACAGATGTCACTTAAAAT
GCCATAGTATTAAGTGTTAAAATGTATAAAATGTTCAAGGTATAGA
TAAGTATACACTAAGTTACTTTAGCATAGTCTTGATTCTGAAGAATSEQID NO:
Phase-1 RCT-233 CAGCACAGCACAGTAATCTGGGTCGCCTGTGTTGGCAGACACAC
348
AGCCTGGTATAGACACAGTTGCCCTCAGCTTTCTTACTTGATGTC
CTTTAAGATCACGTACTCTAGACTGTGCTGTAGAAAAATGAAGCA
TAGTTTCGAAAGTTCCTGTTACGGATGCATATTCTAAATAGTCTGG
GCTTAATTTTGAAACTAGCAATATAGCATTTGAGAATTGTAAAATA
CCACTTTTTGAAGTTTACCGTAAACTTTTTTTTAGTTGAAGTTTTAA
GGCTTTTAATTTAAGAATGATTTAGAACTTACCCATTATAAT
CTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCAAGACCAAACCA
AACCAGAGGCCCCTGCCAAGAGCACTTGGCTTACTCTTCAGATA
CAGAGTATAAAGTAAACAGCTGTGCTAATTAATCTAGTGGTTTTTC
CTCTGGGTTTTGTGGAGACAGCACATGGTTGAAAGCACTTGCTTC
TCTTCTAGAGGACCGAAGTTCAGTTCCAACATGTACATAAAAGCA
GCCCACAACCACCTGTCACTGCAGCTCCAGGGTATCCAACGCTC
Phase-1 RCT-235 TCTCCGGAGTCCCACAAGTAAATACCATAAATCTTTTAAGCAGATSEO ID
NO:
GGAAGATGATAGCTCATTAGGTAAAAGACTGGAGGTCTGAGTTCA349
ATTCCCAGCAACCACATGGTGGCTCACAACCATCTGTAATGGGAT
CTGATGCCCTCTTCTGGTGTTTGCTCAGTGACAGGATGCTCATAT
ACATTAAAAAAAAAAAACCTTTGCGGCCGCAAGCTTATTCCCTTTA
GTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACTACGT
CGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGC
AGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAANAGGCCG
CACCGATCGCCTTCCAACAGTTGCGCAGCCTG
192
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGACACACACACCCTTT
TTTTTTTAAATCTCATTCTGTAGCCCAGGCTGGCCTACAGCTCTAA
TCATCTGCACTTAGCTTTAAACTGGTTGTGTGTAGTGTTTTACGGT
GTGGTGGCTGCATGGTGAATGTGTTACACACACTTTGATAAACTT
GTCCCTTTTGGTATGTCGTGCATTAGTGCACGCTTTAGTTGCTGC
TGAAGCTAACACTGCTGCCACAGGTGTGTGCCTGTCTGCTCTGA
Phase-1 RCT-236 CATCTTCGTACTGTGAATCCGTGCATCCTTAAT1-i'TTTTTTCTTTCTSEQ
ID NO:
TTTTfTTCCTGGAGCTGAGGACTGAACCCAGGGCCTTGCGCTTG350
CCTAGGAAGCACAAGGCCCTGGGTTAGGTCCCCAGCTCCAAAAA
AAAGAACCAA AACAATGGCGGCCGCAAGCTT
ATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTGGCCGTCGT
TTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAA
TCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATANCN
AANAGGCCCCCACCGATCGCCCTTCCCAACAGTTGCGCAACCTG
AATGGCGAATGGGACCCCC
TTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCTTGGGGTCAGCA
GCTGCCAATGACTGATGACTCCTCATGCCTTTGCCAAAACGTCAC
CCGTTCCTGGAGGGACAAGCCTGAGCCGCCATTCCCCCTTAATA
TTTATGAAGTGCCTGAGACATCTGCTTGCCTTGCTCAGGAGTCCT
GGCCTGTGCCGTGTAAGTGTCCTGCTCAGGGGTGGCCATTGAGA
CTTCCGTCTCATGCCCAGCCCCTACTGTCCATGGGAGATTTGCA
SEQID NO:
Phase-1 RCT-237 CTTCACGTCTCTCTGCGCACTTTTCCCGTTGGGCACCCACGTGG
~
351
CCCGCGTCTGTACTCCTAGGTTGCACTGTTTGGTGGTGTGTTGG
ATGGAACCTCGGGCCAGAGGTGGCCCCGAATCACTCACTACAGA
AGACAATTGCCAGGCCCCAAGCACCCATTGCCTTCTCCGGTGCT
GGGCAGATCTCAGGGCCTCGTTTGTTTTTTGTTTGTTTGTTTGTTT
GTTTGTTTACGTTAAACCTCTGCCTGGCAGTTTCTGACTGAACTG
CAGAGTTGTTCCGCTCCTCTGGTAAACAGTGACTCAACNCGTCTT
TCTCACAAAAAAAA.4AAAAAAAACACATGCGGC
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGTCAAGTTCCTGCCA
AGATGTCCTGCCAGCAGAGCCAGAAGCAGTGCCAGCCTCCTCCC
AAGTGCCCCTCCCCGAAGTGCTCCCCAAAGTGCCCCCCAAAGAG
CACAGCACAGTGTCTGCCTGCAGCCTCTTCCTGCTGTGCTACAA
GCTCTGGGGGCTGCAGTGTCCCCAGCTCTGAGGGAGGCTGCTG
CCTGAGCCACCACAGGCGCAGGTCCCACAGATGCAGGCGCAGG
Phase-1 RCT-239 AGCTCCAGTTCCTGTGACCGTGGCAGTGGTCAGCAGTCTGGGGSEQ ID NO:
GCTGCTGCTGACTTGTATCACGAGGTTGAGACAAGAGAGTTTTGA352
ATACTGAGCCACCTTGGCTTGTGCTCTCTCAGACATCCTTATCTC
TCTTGAGCTATGTGTTCTTAGACTCTTCTAATGGATTTCCCGAAAG
CCTGGTTGCCTCTCCTTCTCATGGTTCCATCACCTGTGTCTGGGC
ATGTCAGTGAATAAAGTTCTTTCTCAGCATTACCAGTAAAAAAAAA
AAAAAAAAAAAAAAAAATGGAAGCGGCCGCAAGCTTATTCCCTTT
AGTGAGGGTTAATTTTAGCTTGGCATGGCCGTCGTTTTACAACGT
CGTGAATGGGAAAANCCTGGC
_
TTTTTTTTTTTTTTTTTTTTTCTTCGGAGCTGGGGACCGAAGTGCT
CTACCACTGAGCTAAATCCCCAACCCCTCACCGTTACATTTTGTG
TGGAGCATCAGTCGCGTGCCTGAGGGTCTTGCCTATAGAGTCTG
TGGTCATCCTGTTGGCCAACAGGTATTCCTTTTGTTGGACCAATT
GCATTTCCCATCTCTCTGTGGTGTGATGGAGGTGTGAGTCCTGG
Phase-1 RCT-240 ATGTAAGTGCGAAGAGTCCACTGTGGAATGGTGGCTAACATCCASEQ ID NO:
CTTTAGCTAAAATCTCATAATACAGCAAATAAAACACTGGGGTTAT353
TATGCCCACTATCAACATTATCACGACAGCTGTCCACCAACCCAT
CCCCCAGTCTGCGCCGTAATATGGATCCTTTCGGTGAACGCTTTT
GTTATCAGGCTCAAATCGGACCTGTTGTGCTGTTAAGGCGGACA
CTACTTCATTCAGGTTCTCCTTCTTGGTGTCTGTACACTTGACTAT
TTGCTCTATGTCGCG
193
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCNTNACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGAGCATGCTGACC
TTATTAGTCAGGCTCGCCCTGATTGTAGTACCCCTGAGCTTGCCC
TAGGGTAGACGCCAGTCATTTCACAGAGCCCACCTACTCAGAAC
TGCACAACACGGCTCTGGTCCTGGGATTTTGGTTTGCAGTGAGA
AGAAAACATCTTCGTGTAAACTTGACCTCACGCTTAATAGTTTAAG
GGTGAAAACAAGTGGATCAGATGTGTGATGAATGCCACAAGAGA
Phase-1 RCT-241 GTGATTGCTTTTATTGTATAGATTTATCACATTTAATGGAGAGGTTSEQ ID
NO:
ACAAACTAGACTTTGGCCATACCTTGAAATGAGAACTTGTAGTCA354
CTGATAAAGTACAAAGAACTCTCTTCGTGTCTACACTAAACCTAAC
CAGAGATGTAGAAATGGAGAGGAGGCTCTTCACAGGTCTCCCAC
TGTCTAGCTTATGGCAGTAAACCAGGAGAGCAAAGAGCTCCACG
CTTACTGTCCAGGTGACTCTACCCTGTTCAACAGACTTCATTCTT
CTTTAGTTGTTGACTACCTCAGAAGAGAAGAAAAGGACATTTCAC
AGAGTGATGCCTTTTACACATAATATACCCCCCACACACACACAC
ACGCTGTAACTAGAAGG
CATTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGGACCGAGAGCTG
TGGGTTGAAGCAAAGCTGTGAATCGCTCCAGATGGTCCCTGTGT
TCTGTCCACACACAGGTCCCCGCCTTTTTAGAAGCAGCCTCCTG
GTCTCATGCTTAAATCTGTTCCTCACTGCCCGTGTTCACTTTANAA
ATGGCAGAACCACAGAGCTGGACTGTTGAGCAGGCCTGTCTCTC
TCATTAAATAAAAATAAGTAAGTTTGTAAGCTATTCCGACAGAANA
Phase-1 RGT-242 GACAAAGGTTACTGATTGTACAATAGCGCTTTTATATGGAAGACTSEQ ID
NO:
GTACAGCTTTATGGACAAATGTAAAACTTTTTTGTTTTTAATAAAAA355
TGTAGCAGACCCCAANCNTAAAAANAAAATAAAAATGGAAGCGGC
CGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACT
GGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTA
CCCAACTTAATCGCCTTGCACACATCCCCCCTTTCNCCAGCTGGC
GTAATAACNAAGAGGCCCGCACCCGATCNCCCTTCCAACAAGTT
GCNCACCTGAATGNCGAATGGGACCCCCCCCTGTACCGGCCCC
NTTAAACCCGGCGGGGTGG
GNNNNTCTCTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGGGGATTT
CGCCGCGCAGTGGGAGAGAGCACGGGTTCCCAGGTGTGAGCGG
AGCGCGGGAACCGAGTGTGGGACGCGGGAGGCCGGCGATCGG
ACGGCGCGAAGTGACCGTGCGTTAAGAGTGGAGTGGCGGCGTC
CACAAACCCGAAAAGGACATCGGATCCCACTAAAGATGGTTGTG
AACCACCATGTGGTTGCTGGAAATTGAACTCAAGACCTTTGGAAG
Phase-1 RCT-243 ACGGACAAACCCGAAAAGGACATCGGATCCCACATGGTGGCTCASEG2 ID
NO:
CAACCATCTGTAATGAGATCTGGTGCGCTCTTCTGGCCTGCAGTC356
ACATATGAGGCAGAATGCTATACATAAAATAAATAAATAAATCTTT
NANGNANAAAAANAAANAANNAAAGNGGACGGGCCCNAGGTTNT
TNCCTTTNATNNNGGGTNATTTTNACTTGGNCCTNGCCCTCCTTT
TCNACCTNCTGACTNGGAAAACCTGGCGTTTCCCCACTTTATTCC
CTTTGAACCNATTTCCCCTTT'fNCCCNCTTGGGTTAATNACCNAA
AAGGCCCCCNCNNTTNCCCTTTCCCACAATTGCCCCCCNTAATTG
GGCAAATNGGAACCCCCCTNTAACCGNC
CTTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGAGCGGATTTACC
GGAGTTGCTTGGCGGTCTTGAATGATTGGCCTGATGTGTTTTGAT
GTCGGCTGCCGGGTGTCTTATGGACGTGCTGGCAATCTACTAAG
TCGGGACATGACAGTGACTTATGAGGATGTGCATGTGAACTTCAC
GCGGGAAGAGTGGGCTTTGCTGGATCCCTTCCAGAAGAAGCTCT
ACAAAGATGTCATGCTGGAGACCTACAGGAACCTCAATGCTATAG
Phase-1 RCT-244 GCTTTAATTGGGAAGACCAAAATATTGAGGAACACTGTCAAAGATSEQ ID
NO:
CTAGAAGACAGAGAAGGTACTTCTTAAATGCAAGCTCATACAAAT357
ATGCCTCTGAAGAAATTTTAATGTGTTTTGAAAGTTTGAAAGTAAA
GCAACAGTGTAAATAAGAACTGCTTTAAGTATATTGGTGATCAATA
CATTCTAACAAAACCATGGTATTCCATGTGCTTTTATCTTATTTGTT
TTCAATGCAATTTTTTT,qATAAAGTGGACTTTTAAACAGTGCC-f'fA
GTGTATATCAGCATTTGAAACACAGCCCTATTACAACTACTCTGTA
CAACTGGCAGTAAATI-fCTGTTAATTTTTTAAAAGCTCCACATGGT
GAATAGTTG
194
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TCTTTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGTTTTTTTTTTGTT
TATTTCTTTGTTTTTAGGTAAGGCTCAGGTTTTCCTCCAGGTCCGT
CTGATGGGGGCAGTTTCTCAACTGAGGTTTTCTCTTCCCAAATGA
CTCTAGCCTGTGTAAAGTTGACATGAAAACTAGCCTGAACAATCA
CTCAGTTCACCAACTAACACACTGAATCCATGATCCCTATCCACA
CACTAAAGAAACTAGAGAGAAGGCCAGA1T1'GGGATAGAGTTGC
Phase-1 RCT-245 CTGCCTAGCATGACAAGGCCCAGAGTTCTATGCCCACTGCTCAASEQ ID
NO:
GGTGCTGGGCACAGGAGCACACACTGTAATCCCAGCATTCATGA358
GACTGAGGCAGAAGAACCTTGAGCTACACATTGAGTTCCAGACA
ATTTTGAACCACTTGCTGAGATATTATCTCCCAAGAGACTTGGGC
AGTTGAGACTGGAGAACTAGCAGTTCAAGTTCATCCTCAACTGGA
NGCCAACCTGAGCCTTACCTAAAAACAAAGAAATAAACAAAAAAA
AAAAAAAAAAACCTTTGCGGCCCGCAAGCTTATTCCCTTTAGTGA
GGGTTTAATTTTANCTTGGCACTGGCCGTCGTTTTACAACGTCGT
GGACTGGGGAAA
TTTATNACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCATTACTCCTGAAA
TGTGTAATAAGCTGGGTTAGCTCTCTGCAAATAGACCGAGTAAAT
ATTGGCTCTAAAACGGCATTATCTGCCTTAACAGAAAGAATATAG
TTCAGCCAGTGAACATGTAGTTAAACCGTCCCTGGTCTTGAATGG
TGTATGTGGTGTATCTGCGAACAGGAAGGGAAGCCAATCGTCTTT
TCAATTCGAATGTCCCATTGCTAATGCTAGTAGCACAGAAAGGGG
Phase-1 RCT-246 GAAAGGAAATGTCCGGCGGAGAGGGGAGATGCATCCTCCTTTTTSEQ ID
NO:
CCTGGAGCCTGGGAAAGCGGGTCATCTCACTGGCTCATGCATCA359
TAATCACTTGAAAATGATATGGGTATGATTTTATCCTCAAGTGGCC
TCTGC1-fAAAGACAAAGACACACAGCTAGAGAATACCCAGAAGGT
CTGCAACAAGAACCCAAAAAGACAAATTCTGGGTTTTACTTCCTG
TTCCCACATTCATAGATTCTTTCAGATATCCCTCTCTTGAGAGGTC
CTTCCAACGGGGGGTGTCTCAATTAAAAAAAAAAAAAAAAAACCT
TTGCGGNCGCAAGCTTATTCCCTTTAATGAGGGGTAATTTTAGCT
TGGCACTG
TTATGACATGATTACGAATTNAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGCATTATTTACTAC
TCAATTTTGCCTTACCAACCTCACTGATAATAATGAACACCGATTA
GAGAAAGAATGCTAGAGGAAAGATGGTTGTGGCCTCCCCAGTCT
GTCATCTGAACCCTTCATACATGGTGATCTAGAACATTATTAGCC
ACGGTGATCTTCAAGGAGGCAAACAAGTCCTGTCTGCTTCTCTTG
GCATCTGCTGACTCTAACAAGACCGTTTCAGAACTTTCCACTGGA
Phase-1 RCT-248 AGTCCTCTTCCTCTCAGAAGTCAGAAATTCTCCCTAGAAGAATAASEQ ID
NO:
GAAATAAATTCTTTTGGTAACCTG 360
AAAAAATTGGAAGCGGCCGCAAGCTTATTCCCTTTAGTGAGCGTT
AATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGG
GAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCC
CCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCG
CCCTTCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACCCCCC
TGTAGCGGCGCATTAAGCGCGGCGGGGNGTGGNGGNTACCCGC
AGCGGGGACCGCTACCACTTGCCAGCGCCC
CNNNNNNNNNNNNTCTATGACATGATTACGAATTTAATACGACTC
ACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGG
AAAGAAATGCCTTCAAAGACTTGACTATTGGCTAATCTCATGGTG
GCATTTTCTCAATTGTTGCTCCCCTTTCCCAGAAAACCCTCCTTG
GGTCAAGGTGACAAAAACTAACCAGCGTGCCTGATGTCATTGCTA
TGGTGTAGAACAGTATCTGGCACAGAATTCATGATAGACGGCGTT
ATCAGCTGTATCTGCTTTAGAATCACCTGGAATCTCCATGAAGGTSEOID NO:
Phase-1 RCT-251 ATATTTTGATTAGGGCAGCCTCCGAAGATGTTTCTGGGCATTATT361
TTGATTACCTTAACCTGAGGTGGGAAGACATGCTTACTGCTGAGG
GTGACAGTGGGGAACTGTGCTTCTTATACCTGCTCCCCCAAATG
CTGACCATCTGATGGAGAGCACACAGTAGTTACATGCTTCATGTA
ACGTTTTTGTCTCTATTTTATGGATAAAGCATCCAAAGGCCTTTTA
TATTTTGGTATT'fTGAGACAGGGTCCATACCATGTGGCCTAGTCT
GGTCTTAATCTCCAAGTTCCAGACTTAACAGACATGTACTTTAAAG
ATCAGATAAGGAGTCGGAAAGTTCAATGGACTGGTAACC
195
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGCCAATACTCTACTG
GCAAGACCACCTTCATCAGGTACCTGCTGGAACAGGATTTTCCA
GGCATGAGGATTGGGCCTGAGCCAACCACTGATTCCTTCATAGC
AGTGATGCAGGGAGATGTGGAGGGGATCATCCCTGGGAACGCC
CTGGTGGTGGATCCGAAGAAACCCTTCAGAAAGCTCAACGCCTT
CGGCAATGCCTTCTTGAACAGGTTTGTGTGTGCGCAGCTGCCCA
ACGCTGTTCTAGAAAGTATCAGTGTCATGGACACACCGGGGATC
SEQID NO:
Phase-1 RCT-252 CTCTCTGGTGAGAAACAGAGGATCAGCCGAGGGTATGATTTTGC
362
TGCTGTCCTCGAATGGTTTGCTGAGCGGGTGGACCGAATCATCC
TGCTCTTTGACGCCCACAAGCTTGACATCTCTGATGAGTTCTCAG
AAGTCATCAAGGCCCTCAAGAACCACGAGGATGCAGGATCAGCT
GCAGGCCCAGGACTTCAGCAAATTCCAACCACTGAAGAGCAAGC
TGCTAGAAGTGGTTGATGACATGCTGGCCCATGACATTGCCCAG
CTCATGGTGCTGGTACGCCAGGAAAAGACCCACGGCCTGTTCAG
ATGGTGAANGGCGGAGCATTTTGANGGAACCCTCCAAGGGCCCT
TTGGGCATGGGCTTT
TCCNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT
TTGGCCCTCGAGGCCAAGAATTCGGCACGAGGATCCTGAAGATT
GTTGTGTCTGTGGCTTCCCTGGGACTAAGTCTCCGGAGTATGTG
TGGCCGGAACTCCCAGGTCTTGAATGATGAAGAGACAGAGAAGA
AGCTTCTTGGGGGGGATTCGGCACCGGCCTCCCCGACCAAAGA
GAAGATGCCTGTTACCCCATGAGCTGTCCAAACCCACATGTGTCC
CTGTCCAGAGTAATCCAGGGAGAACGGCACTGATCCTAAGGCCT
Phase-1 RCT-253 CTTCTGGCCCCGCAGCACATGCTTACTTCTGATGTAGCCACTGTCSEQ ID
NO:
CAGCCCTTTTTCTCTTCCTCTCTCCCCGCTGTCCTCACACCAATG363
TCCTTTCTTCCATGAACAGATATTATGTCATTTTCTCCAATGCTGA
TAAAGCAGAAACAACTAG TG
GAAGC;GGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGC
TTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCC
TGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGC
CAGCTGGCGTAATAGCGAANAAGNCCGCACCGATCGCCCTTCCA
ACAGTTGCGCAGCCTGAATGGCGAATGG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCTGGAGGCAAGGGG
ATGTCGAATGCCAACGGACCGAGTGCCTCAAACCAGTCGTTCAG
GATGTCCTGACCATCTCCCCATTTCAGAGTGTGTACAAGATTGGG
GAATCCATTGAGCTGACCTGTCCCAGAGGCTTTGTTGTTGCTGG
CCCATCGAGGTATACATGCAAGGGAGACTCCTGGACACCTCACA
TTCCAAATTCACTGAGCTGTGAAAAAGATATTCTGACAAAGTCAAA
GGGCCTTTGTCAACCAGGACAAAAGCAATCAGGATCCGAGTGTG
SEQID NO:
Phase-1 RCT-255 TTTGTATGTCCCCAGAAGAAGACTGTAGCAGTTATTCGGAAGATC
364
TCTGTATATTTGATGAGGGATCCAGTCAGTACTTCACTTCATCTG
CTTGCAAATTTTTGGCTGAAAAATGTTTAAACAGCAACCAGTTCCA
CTTTGTCCATGCTGGTTCCTGCCAAGAAGGCCCACAGTTAGAATG
GGGTCTTGAGAGGCTAAAACTCGCAATGAAGAGCACAAAGAGAG
TGCCCTGTGGATATGATACCTGCTATGACTGGGAAAAATGTTCAG
CCCACACCTCCAACTGTGTCTGCCTATTGCCCCCACAATGCCCC
AAGGATGAAAACCAACTCCACTGTGTCAAAATGGGATCATCAATG
CGT
TCTCNTAANATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGAATTGAGTGACAT
ATCACTCCTGAGTATGCCCACTAGATGCGGTGGAGATGCAGAGG
CATCCGGACCCCACGCCCCACCCCCTCCCCTCACACACTTACTC
TCTGCCTAGTAATGCCACAGAGCTTCCATCCCCATCCAAAGGTCA
TCAGGCATGGCTATCAGTTGGCTCTCAGGGTGGATTTGACATTCT
CAGATGATTAGAAGTTGGCAAGAAGCAACCTTGGTGAATAACTCT
Phase-1 RCT-256 GGTGTCTAAACTCTGTACTTGAGTTACAGTCTCAGTAGAGGAGACSEQ ID
NO:
GCCAAAGCTGTTGCGAGTGACGGCAGGATTATTGAACAGTCATG365
ATGCTTGGCTTTCAAAGGCGATTATCGCTTTAAGGTCTTAGAATTA
GTAAGTGCATCTTTATAACCAGGCATAGCTAGATCATAAACTACT
GATGGCCAAGGACCATAGAACGTGCTTCTTACCTTCCTCTCTAGT
TAGCATTACGACAAACATAATCACCAACGCTCAGGGAAACACTTG
CTGATTCAAGTAAAATGCATGAACCTTGGAAGACCTTTCTAGAAG
TCAGAGATCAAGTTCATCTTGNTCTAGCACTTTCCACATTCATGTT
TGGGTTGTATGCTGCGCCCTAN
196
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TNATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGACCAGTCAGGGAAG
AATGTGATGGTGGAGCCCCATCGGCATGAAGGAGTCTTTATCTG
TCGCGGAAAGGAGGATGCCCTTGTCACAAAGAATCTGGTTCCTG
GAGAATCTGTGTATGGAGAGAAGAGAGTCTCTATCTCCGAAGGA
GATGACAAAATTGAGTACCGAGCCTGGAACCCCTTCCGCTCCAA
GCTGGCCGCAGCAATCCTGGGTGGCGTAGACCAGATCCACATCA
Phase-1 RCT-258 AGCCGGGGGCCAAGGTGCTCTACCTTGGGGCAGCCTCAGGCACSEO ID
NO:
CACCGTCTCCCACGTGTCTGACATTGTTGGCCCGGATGGTCTGG366
TCTACGCAGTTGAGTTCTCCCACCGCTCTGGCCGTGACCTCATC
AACTTGGCCAAGAAGAGGACCAACATTATTCCTGTAATTGAAGAT
GCTCGGCACCCACACAAATACCGCATGCTTATTGCAATGGTGGA
TGTCATCTTTGCCGATGTGGCCCAGCCAGACCAAACCCGAATTG
TGGCCCTGAATGCCCACACCTTCCTGCGGAATGGANGACACTTT
GTGATTTCCATTAANGGCCAACTGCATTGATTCCACAGCCTCAAC
ANAANCTGTGTTTGCATCTGAAGTGAAAA
CAAGGGCAGCCCTCGTTGGGCTNTGAGTCGTTGAGAGATTTTGT
AGAGCTCCATTGTGGCCCTGGCATTTTNTACAGAGCAAGTGGCC
CCCGCCAGTTGTTCTGGATGCTCTTGTGCAGCAGGCGCTTGCAC
AGCAGCCTCAGGGACACACGGCTGTAGCAGTGCAGCTTGGCCT
CGTGCCACAGCAGCATGTCTGTGGACGTGTCGTAGATGGTGTAT
TTTCTCATGTCCTCCTTCAGGGCACTGAAGTCATGCTTCAGGTTA
Phase-1 RCT-259 TGGCCCACCACCAGCTTGCCTTTCAGAAGCTGCAGGATCTCTAGSEQ ID
NO:
CCTGGCTTCAGCAAATGGCGTGGCCCTCGCCATGTGCTGAGGC367
GTGATCCCGCTGACTTGGGTTCTGTAGTCCGTGATCTCTCCCTCA
GGCTGGATGTACTTGTCATAGAGGACTGCGCTGTGGACGTTCAC
AATGCTGCAGCGGGCGAGGCCACTCACCCTTTGAGGCCCGAGC
CCCACCATCTCACAGTCCATGGCTACCACCTCTGGGCTGTCTGC
CATGCTCCTCAGACCCTCAGGAAGTCCTGTCCCAGTGCCCTGGG
TTCTCTTCTGCCTCTGTTTCTAC
GGGGGTGAACATACAAGAAGGTTGNTGTCCTTTGCACANAAAAAT
TTTGT'f-f'GAAACTGTGANTGGNGAGTACACGAGTTTTCTCTAACC
AGTCACCACACTTCTGAAATAACGCGTGCTAACATTCAACTGATA
AAGGGACCGTCCCCTTGGGTAAAGTGTCAAGCAGGGTTAAATAT
GTATAATAGACAAGCACCATGAGGAATCTGCTCCTGCTCGATGG
GTCTGTGTCTCAATGTCCNTGTGTACCCTCTTTTTGTGCAAGTTG
SEOID NO:
Phase-1 RCT-260 ATTACATGGTTTTGGCTGACTCCAAAAGCACATGGTCACAAGACA
368
AACATTTTTTTTI-fAAAAAACATTCTCATGAATGATTTATCTACAGT
ACGGTTTCTAATACACAACGATCCTTCTTTATTGCTGAAACTGGTG
GTACTTAAGTGTCTCCT'fTCCTTTTTCTTGCACAACTAAGCTTCCA
ACCCAGTCCACCAACTCTTTCAAACCTAAAGTCTCCTGTCACAGA
TGACAGGATGCAGAAGAGACCTGCTGGGATCGGCTTTTGCAACC
TGTGCTGCAGCCTTCGCCCTCCTTGGGTGTGAAGTTGAT
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT'(TG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTTTTTTTTTTTTTTT
TTTTTCTGGCTTTACAATTGTTTTATTCAAAACAAACTTAAAACCTA
ATAAATACCTTTTAAATGGGGGATTTAAAATCATTTTATAATTAGTT
CTAATGCTGCTTGTCTTACCTTCAAACAAATATCGATATATTATT-T'
CTGATATCCACGCCATACATTCTAATCCTTTTTAGGTATTCAAATG
TCAACATGACCTCCCTAAGATTTAGAAGAAATGATCTGTGTGCCC
Phase-1 RCT-261 TGCGCAGTTGAAAAATGACACAAGGGATTTAAAAAAAAAAAAAAASEQ ID
NO:
ACCTCCGTGGTCACATGTCAGGGTGTCATTTGTGGCTGTGAGAA369
GTGCTCTGTTTGCTAAGTTCTTGCCCCAGAGCTGTATCTAAAATG
GCTATCAGTGGTTCTGTGGAANAAGCCTTACAAGGCTTCAGCTTG
TGTGGTTTGACTTCCAGATGTCATCACACATGGTTCACAGCAAGT
GATAGCAGCTTCAGAAGCCCAGTGTCACCACTGTGAGAAAGAAT
AAGGTGGAGTGCATTCTATCTGGATACACCCGGTAGTGGGTAAN
GATCCCAAGGACATTATAGTAAAATAAATAACATTTGCACCCTTGA
TCCCCATTCTNAAGCATGACGGG
197
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCTCTATACAAAAACAC
AAGACTTCAGCCTCCACACAACAGAAGTGCCCAGCCCCGAAGCA
ATAGGGGGGCGACTCGCCGTCTCTCACCCAGCCATGGAATACCT
TTCAGCCTTGAGCTCCAATGGCCTGCTAAGGTCAGTGTCTACTAT
GAGCTCCGAGC'fTAGCCGTAGGGTCTGGAACTCGGCTCCTCCAC
CTCAGCGACCCTTCCGTGTCTGTGATCATAAGCGGACAGTCCGG
AAAGGACTAACAGCCGCCACCCGCCAGGAACTGCTAGATAAGGT
SEOfD NO:
Phase-1 RCT-263 AGTGGAGACCTTGCTGCTAAGCGGAGTGCTAACGCTGGTCCTGG
370
AGGAGGATGGGACTGCGGTGGAGACTGAAGACTTCTTCGAGCTG
CTAGAGGATGACACATGCTTGATGGCTCTAGAGCAGGGACAGAG
CTGGAGCCCAAAGAGTGGGATGTTGTCATACGGCCTAGGACGG
GAGAAGCCAAAACATAGCAAGGACATCGCCCGCATCACCTTTGA
TGTGTATAAACAAAATCCTCGAGACTCTTCGGCAGCCTCAACGTG
AAAGCTACATTCTACGGGCTCTACTCCATGAGCTTGCGATTTTCA
AGGAGTTGGCCCTAAAAAAGTACTCAGGGAGCTCCT1'CGTTGGA
CTTCCTCCTGCTGCA
CTANNCCNTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCATCTCG
AGCAGAGAGCCTGTTTCCAGCACCCGTTCTCCTACCACCAAGTC
ACACTCGTGGCTGGCACAGAGAAGGTGCTCACTGTTTGCTTGTT
CAGACCGCGTCACCAAAACATGGAAAACTCATTGAGTTTAATATT
CTGGGCTTAACAGACTGATTATTTTCAGGAGCAAACTGAAGGATA
TTCGTAAGTATGCTGAAGTGACAGGTGGAGAACAATTCCCATTAA
TTATTATGTCTAATTATTCCACTTAATAATGATGAGATGCAAATAA
Phase-1 RCT-264 GACCAACCAATAAAAAATGAGGAAAATACACAAGTATAATGTATASEO ID
NO:
GAAAAAGCACAAAGTATTACCATTCCTTCAGCTTCGAACAAGACC371
ATGATCAACATCAAAGGACAACCTATAGCCCAAGACATGTGCCTG
TCTGCACTCCAGGGTTGCTTACCTTGCTACGGATGATGAGAGGG
AGTGGCAATAAAACCAAAACAGTGGAAAACCACAAGGAGAAAGC
GACGATACACCAAAAGCGTAATTGAGGAGCTTCATGCCTGAGCA
GGTGCTTCAACANTTCCCCCTCACTCTCAGGCAGAAGTTAATAAC
CAGCTGGGATTAATATTTCTCTACCTCATCATCTTTACCTACTGGC
TCAGANAGAACCAACGCTGGTTAAAAATAAATCTCATTTTTATTGG
TTTN
TTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCATATTCCAAGACCT
CACATTTATTACAACAGAGCAGAGACAGACCACATTCCCGTCCTT
CCACCACCTACTCCAGCCCCAGCCCCTTCCCAACACTCAGCTGC
AGCT,CTGAGCTTGGACAAGTTTGAAGAGAGTGTTCGGTGAATAAA
GGCCCCGAGACAGTGGAAAGGCGTAACCGGAAATGAGGAGACC
TGCAGATCGCTTACCATATTCACACCTCCCGAGAAGTCAGGAGAA
Phase-1 RCT-265 CAGATGGAATTCTGAATGGCCATGCCCACCATGGGCCCAGAGAASEO ID
NO:
GGAAGTAACACTGTGGGACAGAGGTGAGAGATCAGTCTAAAGCC372
ATCGTCGGAGCCTCGGGAACAGAAGGGAGGCGCACTCGGCCCT
GACAGGATAGCATCAGGCTCCGAGCGGAGACTGGGATCCTTACG
TCACAAGCTGGGCACTATCATGGGGCAGTCGAGGCAGCAAGTCT
GTCCGGCGCCAGCGGAGGAAGTTGTCTAGCAGGACAGCTGGGT
TGGAGCTCATCTCTATCAGGTCGCGCTGGGTCCATGCCTCTAGG
NCCACAAGTGCTACCCGGACATTCAGGGGCTGGAANAACTGAP,T
GGGCGGANGCTCAAAAAANGGGCNGGGCTTCA
CACCAGTTGCAACCCAANGACAGCAGTGAACAGTCCCCTTGACA
AGAGTTCATTTGGAAAGAAAGTCAAGTAAATTTTGTAACAGATGA
CATAAACCCTTGAGCCAGCAGTGCACTAGGATGCACTACAGCCC
TGCCCCCGGTGCTCTGCCTCCTCCGGGATGGATGCGGAACTTAC
TGCTCACTCTTTGGTGGTTCCTGTTTCCCATTAAGCTCTTGATCAA
CTTGTTTGATGCACTCTGGTATGCCGACGTACTCCCATGGGAACA
SEOID NO:
Phase-1 RCT-266 AGCTCCGCCAGTTCAGCCAAATTAAAGACGTATCTAATCTTCTGA
373
CTGAATTTTGAACTGATAAATGGTCTTGTAACAGCCAGAAGTGTT
CGGATAAACCAAGAGGGGTGCACAATGATTAGAGACTTTAGGTTT
TTCCTTAATCGTCTGTCGATTTGCTGGTAGCATCTCCTGAGCCAT
CCCAGACTGGGCATTTTCCTTCGCGTTGTCGCACCATTTAAGTAA
ATGATCATGTAGTTCTCTGCTACCAACAGCTCTAAAGTGCCAATA
ACATATTTAAAGAGATTGTCCATCAAATATCTATAGTTAGGCTGAC
198
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGGCTGTTCTCCAGGAA
AGATAAGGTTGACTTTGTCCAAAGAATGCTCTTCAACCAACAGGA
GCTCTTTGGAAGGAATGGATTTGAATATAGGATGTTCCAGATGTT
TGAATCCTCACATAAGGACCTGCTTTTCAGTGATGACACAGAATG
CTTGTCTAACCTTCAGAACAAAGCAACCTATAAAACATACCTAGG
GCCACAGTATCTTACCCTGATGGACAACTTTAGACAGTGCTTGTC
CTCAGAACTGCTGGATGCCTGTACATTTCACAAACATTAAACCAT
SEQID NO:
Phase-1 RCT-268 TCAGCTGGGGGGGTAACCCAAGGACTGGGGACCCAACTGCTTG
374
CCTCCATGTGGACCTGTGCCGACATCTCTATAACTCAGTGTCATA
GTGGAAACAAACAAAAAAATGAATAAAAGTATCTTCCCAGAAAAA
AAAAAAAAAAAAACACATGCGGCCGCAAGCTTATTCCCTTTAGTG
AGGGTTAATTTTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGT
GACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGC
ACATCCCCCTTTCCCAGCTGGCGTAATANCGAAAAGCCCGCACC
GATCGCCCTTCCAACAGTTGCCCCACCTGAATGGCGAATGGGAC
NCC
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCCAGCTGGCCTCT
CGGCTCTTCTCCTCTGTCCTGTTCTCTACCCTGTGCTAGTCTCCC
CTCTCACAGATACCCCTGGCCACATTCAGTCTGCTCTCTGAACTC
TTCAGATGCCTCTGCCTGTCCTCTGGTATCTAAAATAAGAACTTC
CCCTCAACCATACCCTGTCTGTCTATAGCTCCCCCAGGGAGCTT
GTGTTTGAAGTCTGCTCAGCTGCATGGTGGAGAGGACTGCATTC
SEQID NO:
Phase-1 RCT-270 GTTTCTCTTGCTCACAATTCCTTTCAAATTGCATTGACAGCCAGAA
375
GACAAAGGAAAGAACTGTTAACTAGCAGAATGCATTTTACAGAGC
TCTGGCTGACAGTCTCCTTGCCCACGGAATCATTTGTCTCAGTTA
GCGTTTAAAGGAGTTTTTGCGAGGCAAATTTTCCGTTTGTGAGAT
CTCTGAAGTGGGATTGTTATTTTCCCACTGCCAAAACACTTTCACT
GATTTCAAATCAGGATGCATTACAGAAACTATTTCCTAGGACTTCC
TCAAAGCTAAGCAAGATGCCCCAGGCCAGTGGCAGGCAAACAGG
ATGG
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCACATTTCTTCAGTC
ATCATGGAGAAGGTGGGCACTACCACTACGATACCACCCCAGAC
ACAGTGGAGTATCTCGGCTACTTCTCGCCTGCACAGTTCCTCTAC
CGAATTGACCAGCCCAAGGAGACCCATGCCTTTGGGAGGGATTA
AAGCAGCTGCTGCTTGATTAGGGGAAAAATGGTTAGCTAAGGTTA
TATTGCTAACCCAGCAATTGACAGTAATTAAAAAATATAGTAGGAC
SEQID NO:
Phase-1 RCT-271 CAAAGAGAGAGAGAGAGAGACCGCAGCCAACAACAGTCATTTCA
376
CTACATTAGCACTGTTTTTATGGCATCCATGTGGATAAGGGACAC
TCGTGTTATTTAGCATCTTTATGTGAAGGAGTCTTGGGAACAAAG
ATAACTAATTGAGATGCTCACTTTACTCAACCAATTTTCTGTCTTT
ATAGCCCAGAAGTCCACCTTCCTTCTCTTCACACCTCAGGTATGG
GCATGGACAGGGACCTTTCATTATCCCTGCTATCGAGTAACATTT'
GGGTCACATTGCTGAATTT1TCAAGTTCATCTCACAAGGCTAAGG
GGTC
CTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCAGTTGAGTAGGT
GGTAGGTCAGAGAGTATGGTGTGTGTAGAGGTAAATCTGTGCTT
GTCACAGCAGTTTTTCCCTATCCCATACAAGCCAACCACTGTACT
TTGGGGTAGCCTGCCTCTTCCAAGTGCCTCTGGGCTCTGTGAGA
GCCTCCCCCCAAGCAGGTAGACCAATTTGTTTCCTCTGCTCTTTG
CTGGACCTCCCCAGAGGTGGTCTCCATGTGGCGGTGATGCGAAA
SEQID NO:
Phase-1RCT-273 GATCAATGTCCTTGTGACCACTGCTCTGACTGTCCAAAATAAGCA
377
CTTTCTGTCCAAGCAAATCCCCAAACTTCCTCACCCTCATTACTCA
ACTACCTCAGTCTCACAGCTCAAGGCACACAAGCACCCACTTGC
CTCACATCATCCTCTCCTGCCCTTGTGTTTATGGGCTTGGAGCAA
ATGCAAAGTCCTCAGTTTCAAAACTCAAGCTGCTCTTCCTGGATC
TGCGCCTTCTCTAGTGACACTGGCCCCCAATCACCTACTGGGGG
CTTTANAGAGTGACTCTCCAGNTTGGTCCCTGTACGACAAGCAG
GNAGC
199
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCGGCAGCAGAGCCAA
GTCCTAGATGCTATGCAGGACAGCTTCACTCGGGCGTCTGGCAT
CATAGATACGCTTTTCCAGGACCGGTTCTTCACCCATGAGCCCCA
GGACATCCACCATTTCTCCCCCATGGGCTTCCCACACAAGCGGC
CTCATTTCTTGTACCCCAAGTCCCGCTTGGTCCGCAGCCTCATGC
CTCTCTCCCACTACGGGCCTCTGAGCTTCCACAACATGTTCCAGC
CTTTCTTTGATATGATACACCAGGCTCAACAGGCCATGGACGTCCSEQID NO:
Phase-1 RCT-274 AGCTCCATAGCCCAGCTTTACAGTTCCCGGATGTGGATTTCTTAA378
AAGAAGGTGAAGATGACCGCACAGTGTGCAAGGAGATCCGCCAT
AACTCCACAGGATGCCTGAAGATGAAGGGCCAGTGTGAGAAGTG
CCAAGAGATCTTGTCTGTGGACTGTTCGACCAACAATCCTGCCCA
GGCTAACCTGCGCCAGGAGCTAAACGACTCGCTNCAGGTGGCT
GAGAGCTGACCCAGCAATACAACGAGCTGCTTCATTCCTCCAGT
CCCAGATGCTCAACACCTCATCCTGCTGGAACAGCTGAACGACC
AGTTCAGCTGGGTGTCCAGCTGGCTAACCTCACACAGGGCGATG
ACCAGTACCTTCGGTCTCCACAGTGACAACCATTCTTTN
ANNNNNGNNNCCNCTATGACATGATTACGAATTTAATACGACTCA
CTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGC
TGACCCGTGTGCAGAGGCATTTTCGTTCCCCTTTGTCTTTATTTCT
ACCTACACGTACTATTTACCTTCCGTGTCCTAGCCCTGCCACCTG
TGTATTTTTGGGGTGCTATGGAAACAATGAAGAGAAACGGGGGTT
TCAGAAGAAAATTGTAACCAAATTCATATGCTTTGTATAAGTTTTT
GATATCATGATCACAGGTGATTCACACGCATACACATCCACACCCSEQID NO:
Phase-1 RCT-276 ACACGTGCAGCCTGAAGTGATGTCCATGGAACCCATCGTCTTTGT379
ACAGCGTATGTACATGGCAATCATTTCATACTTTTGACTGGTCAG
AAAAAAAAAACTAATTGTGATTTCTAGTCTTGCAAAGCTGTATGTA
GTTAGATGATGTGACCTCTAATATTTATCTAATAAATATGTATTCA
GATGAAACCTGTAAAAAACAAAAGTTGCNTAACANAAAAAAAAAA
AGGGNGNGCGGCCGCAAGCTTATTCCCTTTAGTGAGGGTTAATT
TTANCTTGGCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAA
CCCTGGCGT
TTCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGCTGAGAATCTGTA
TTGTGGTGTATAAAGTGTCTTCCTAAGAGCAGTAAAAGGACAAAT
TAAGCAGACTTTCTTTTCAAGCTTATGACTTAGATTCTTTTAGAAA
TATAGTTCTTAATCTTTAAAGATGAGATT'CTAAGCCTAGAATTTTAA
ACCACATTTCATTATGGTGGCTTACTGATCTCAAATTTTCTACAAT
.
TTGGTTTTTTTAGACTTAAAAACAGCTAAACAAAACCTTCCTTTATSEQID NO:
Phase-1 RCT-277 CTTTCTCATCACATCCAGTGGCAGAGGGGACTGTCTGAGAGTAA380
AGTCCCATGATTCAGAAGGACATAGCAGGTCAGGATGTACCAATA
AAAGTTATGAATGTGATGTTCATTAGAAAGAAACTGAACAACTGA
GTACAGAAATGAATATCAGCAAGAATTTGTTTT'AAGGATTTTCCAG
ATTTTACTTTGTATCTTGAAGTGTGTGCCATATGCCAAGAACTAAC
AGAACTTCCTGTTCCATCTCTGTACCTTCTTCTTTTTTAAAAGTGA
ACTTATGGGTCGGTTCATTNCTGGGGGCCTTATGGGATGGGTTG
GCTTGGACTGGTTGCCACTGGATGCTGCAGTTNCTTTTAAT
TNTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGGCCCCTTGCTGGC
AGTGTGCAGAAAGCAGAGGTCTAGGAGCAGGAAGCTCCTGTGAG
CGGCAGCTTCCAGGACTTCAGGCCTGGGTATACCCCACTGCTCA
CCCCCCTCCAGATCTGCTGATCCTCTGGTCTCAGGTCAAGGACC
CTTTGTGGCCGCGGGAGCACTATGGTCGTTCAGCAGGCACACCT
TGGGTTAGCCAGGAGCCACATCTTTCTGTGTCAGAGCCTTCCACTSEOID NO:
Phase-1 RCT-278 GGGCTGCGCGATGCCCTCTGTAGTTCCTCTGAGACGCCCCTGCC381
CTCAGTTTCCCCTTTCATCTGACTTCGGCTGCCCTCTCCAGCCCC
AGCCTTTGGAACTCACTCTAGCAATACCACCAGACTAGTTAGCCT
TCCCGGCCCCCAAGACACTTGCGGTTTCATGCCTTTGTGCCTTTC
GCTCACGCGGTTTCTTCAGCTGGAATGCCTTCCCGCTCCTCCCG
CCTCCTCTGCCTGGCAAGCCCCTATTAGCCTCTCCCAGGCCCCT
CCCTCCCCCAGGAAGGCACCTCCACCCCTCTCTTCCGGGCTACT
CTGCAC
200
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
ATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTGTGACTGATGGTG
GAAGCAGGCCTTTCTTTTATTATCCAAACCTTCTGCCACTGAACC
ATATCTCCTTTAGTACCAACTTCAAACACCTTTTCTGCTTTTATTTT
CAGTTTCTAGATTTTGTTTTTTTCTGAGTCTTACTTTCTCACTGAAA
CTTTTGTTTCCTCATGATAAGGTACCCTGTTGTCACCTCCCCTTCC
CCTCCTCCCCCTCCAGAGCACAGCTCACTGGCCGCTTCAAGCCT
TGTGCTGGCTTACTTTGTTTGTAGGGGCTATTATAAAAGCTAATTC
SEOID NO:
Phase-1 RCT-279 TTCAAAATTAAAAATTTAAATTAGGAAGTGTTGTATTCCAGCCCAA
382
CAAAATGCATGTCTATAACCCCAGCCTCTAGGAGGCAAGGCTAA
CTGGGGCCCAAGGATTGCCAGGAATTGACAGCCAGCCCGAGCT
ACATAACAAGATGGAAAGAAAACACTGGTGATATTTTAATCTGATA
CATTGGTTGGAGGAGTATTTATATGAACATGTATCTGTGGATTAA
GAAGTTATTTTATTGGCTATGATACAGAATATCTAAGCCCCNTGGT
TACTTNAATGAGCCGGCTCTTACTTTCTTATCTCGGCAGANAACC
CTGGTGGTAAGTGGATTTTTTGGCAGNAAAGCTCAAAATCTCTGG
CTGAATAATTGGGAAAANATTCTTCTAAGCGNGGGGAA
ATCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGTCCTCTCCCACGC
CATCTGCGCATCCTTCTTGCCCTTGTCCACTCCCTTTCCTCCTGC
CTCTTTCTGCCCCTGAAATTTGCACTATGTCTCTGGAGGGGAACA
CTGGGCAGAGGGCGTGTGATGTGGGGTTACAGCCCCCCACCCC
ATTTAGACACAAGGATGCTGGGTCTCTATGCGGATGGGGACAAT
GTTTACAGGCACCCAGTCACACATTCACGTGTGCACACAGGCAC
Phase-1 RCT-280 ACGACGAGAGGCACCCCAGCACATAGCTTGTAGTTTT-fGCAATTGSEQ ID
NO:
TCTTCTCCAGGTAATAGGATGGACACAAAGGGGCCACACCCCCC383
AGTTTAAGAAAAGAGTCCATCCCAACCCCCTCCCTGCTCCTCCCC
TGGAGCAGGGCACCCATCCCTCCTGCACACCCTTGCCTGGTGGT
GAGCAGGGTTTTACTGTGAGGTGAATTGGGATTACTTTCTTTCTA
TTTGGTTTGTGGTGAGCTTGTCTGTCTGAGTCTTGTGTCTACCCC
TAGACCAGTAATGGCTAATGAATCTTAGAAATTTCTGATTGATCTT
GGGGTCCCTCTGTGATATTTCTTTGTGCCCAAAAGATATTAAAAA
AAAGACCAAAATATGTGAAT
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGTTGGATGAAGAGA
ACATATGAGCTTGTGAGAGAAGACCGTGACCAGCAGCGATTTTT
GTGACGTGGAGCACTGCTGACTCATAAAGGGAAGACAGAGAATC
TTTTAGAGATCGCATGTTTTTCAGAAAGGCTTGGCCCCATACAGC
CTGTTGTTGTTGGACATTCATAGTAGAACTCCTGTGTGGCTTGTT
GTATTTGAAAGAAAGAAAAAAAGCATATTGCTAAAAAATCTGGCT
SEOID NO:
Phase-1 RCT-281 GAAAATACCTTAATGAATGGCAGGATGTGGGAAAAATGGATGGTT
384
GGTCATTCAGATGTCTAGTGATACAAAGACAGATGAGTGTGGCC
CCAAGCGCTGGCACTTGCTGTGTTTTAGGGGAATCGTATTGGTG
GCACATTGGATATTTCTAATATGTATTAAAGCTGTGTATCTTGACT
CACCTTTATCCTTTGCTATGTCTGCGTATCTCTCTTAAAATGCCAA
GAACCTCTCTTTTGCTGTCATCGATCCTTTGGAAACAATTTTGCTT
CTTTAGTTACAGGTTGTCATTGACCTTTAGGAATTAAATCTGAGG
GGT
ACANNANNNNGTCTATGGACATGATTACGAATTTGAATACGACTC
ACTATAGGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGG
GAAATATTTGTTAAGGAACAGGCTGAAGTTGGTGGAATGGGTGCT
TTGTTTTTCTAAATGTTCATCTAT7-fGTGTGTGTGAAAGGGAAATA
TTTTGGCATACTGTTTCTGTCAAATGATGCTGGTTCCCCTTTCTTC
CCACAGTTTGTTGTTTTCAGTGCTAAGCACCCCGTTTCTGGAGTG
GGCGGAGCTAAGCCTGTGCGCAGCATCAGTACCAGCTGCCTTAA
SEQfD N0:
Phase-1RCT-282 AACTCAAGTTTACATTCTTTGTCGACACTGTCCATCTAGTGTTAGC
385
CATGACGCTGGGAAGCCGTGGACCTGCCTGGCTGTTGGTCAGA
CAGCGAGACTGGCATGGGTCAGCTTTGCACACGACATTGAGAAC
ACGGAGTACCCCTTGTTTAAAGATAAATGCAGTGCAGATTGCCAC
TTTCCAGTGTTTTGAGCTTCCCCAATGAGTTATGGACATTTATATC
TAATGTATATTTTAGATAATTTTTATACTTTTTTAACTCATATCCATG
TTCTCTCTCTTCCCTCACCAGCCCCACCCCTTTCTTNATTCATCCT
ATCCCCAAACTGC
201
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CNNCCCGNCANAATNATCCGNCCCNGNNNNNCAAANAATAANGC
CCCCNCCAAAAANAAAAANNNNNGGCNGNCCNNCNCTGTTCGCN
CACTGTATTTTCGAAGCCAAGGTCAGCTGAANCACTTATTTANTT
GGTCNAATAAATCAAGATCNNCNANAAANCAAACANACAANAAAA
CCCNCNATNACCTCTANACATAAGATAAGANACCTCTAACATNAN
CATTCTTCAATTTTGAGTAAGCTCTGCAGNACGGAAAATATACAAA
CTTCAAATAGCTGCAAAAATAGTGTCTTTGGGTGAAAATAGAGTTT
Phase-1 RCT-283 CTACATCAATACAAGAAAAATAGGCATTTTTCTAATTGAATCCAACSEO ID
NO:
CCTGGGGTGGGTAGAGGATATGGAGNTGCTATGTGTCCCCTGG386
GGCAGGTGGAGGGTATGTGGCTGTTACATGCCCCCTGGAGGAG
TGCCAGATCCTTCTTCCCACTCTTGATTTTGGGCCGGGATGCTGC
TTAAGACAATCTTCAGTCAGGGTAAAACTGAGATGAAAATGCCAC
TTGGGAAATCTCGTGGTCCCCTGCCAACAGACGATTGGTCAAGT
GTTCTGGCNCCGAGGACCACTCTGGCCTCGTGCCGAATTCTTGG
CCTCGAGGGCCAAATTCCCTATAGTGAGTCGTATTAAATTCGTAA
TCATGTCATANCNNGGGNNTNNAANNNNNNNNNNNCTCT
TNCTAACATGATTACGANTTTAATACGACTCACTATAGGGAAT'iTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGGGTTACTCCATTCAA
AATAACATACTTTGAAAGCAAGTATAGGAAAGCCTTTTCCTATTAT
TTTTCTTCTTAGCTTCCCCATTGTCTGAATTGGGAAAACAGGAAA
GCATTGCTTTGTAGCACCTGCAAAATGGTTTAATGCCCCTGCATA
GTTCCATATCTTTCAACAATAGATTTAGCATGGGAATCTAAACTAG
ACACCCTGAGAACATCTGTCCTGTCCCCAGCTCCTAAACCCAGG
CTTTGATTATGTGTGGCTTGTGAATCCTATCAACCAAAACAGGGG
Phase-1 RCT-284 GACAGACATACCTCACCAACTGTATACCCTGATGACTCCTTACTCSEQ ID
NO:
AAGGGCTTTTTGAGTACCTGTTCTTGATAGTACGTGTCTATTTCAG387
ATGGGGACCCTGGAGCTTTCATCCTTCCCATCTTACTTGCAGGG
CGGCAAGTGGCTCCTCTTTGCATTTTACCGAGCCCCCCTCCAAG
CTTAAGTTCATTTGCGGATCAGGGATTAAGCCTGGAATTGTCTTG
TCCCTGGTGTCAGGGGTTATTGTAAAATGGTAGTAATCTCACCCC
AAGCCCTCAGTAAGAACATAAATATTTAAAAAATATGNGCATTTGN
AATCTGGTTCTGGATCCTGGAACTGTGGGCTGNTCANGCAGGAG
TGGACTTTAATCTTCTAGTGAATAATTGCCCACTTTGNGGGAAGG
N
GNNNNNTNCTATGACATGATTACGAATTTAATACGACTCACTATA
GGGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGATCGTG
GTTCTTTCAGATGCCTTCCTCAGACGTCCCTGGTGTAGCCAGAG
CTTCCGGGAGGGACTGTGCCGCCTACTGGAGCTCACCCGCAGA
CCTATCTTTATCACCTTCGAGGGCCAGAGGCGTGAGCCCATTCA
CCCTGCTCTCCGTCTCCTGCGCCAGCACCGCCACCTCGTGACCC
TGCTGCTTTGGAAGCCTGGCTCCGTGACACCTTCCTCTGATTTTT
SEQID NO:
Phase-1 RCT-285 GGAAAGAGCTACAGTTGGCACTACCACGGAAGGTGCAATACAGA
388
CCCGTGGAGGGAGACCCCCAAACCCGACTTCAGGATGACAAAGA
TCCCATGCTAATCGTGAGAGGACGTGCTGCCCAGGGCCGGGCC
ATGGAGTCAGAGCTGGATCCAGACCCTGAGGGAGACCTGGGTG
TCCGTGGACCTGTCTTTGGGGAGCCACCAACTCCACTACACGAA
AGCAAGGTCTCCATAGGAGAGGGCCATGCCAGTGAAATGGATGT
CTCTGACCTTGGCTCTCGAAACTACAGTGCGCGAACAGACTTCTA
CTGCCTTGTGTCTGAGGATGACGTG
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGACTATGGCGAGTCCCA
CTTCACGGTGAACCAGCAGCCCTTCCTCTACTTCCAAGTGCTGTT
CCTGACTGCACAGTTTGAAGCTGCCATTGCCTTTCTCTTCCGCAT
GGAGCGGCTGCGCTGCCATGCTGTCCATGTGGCCCTGGTGCTG
TTTGAGCTAAAGCTGCTTTTAAAGTCCTCCGGGCAGAGTGGTCAG
CTCCTCAGCCACGAGCCTGGTGACCCTCCCTGCATGCGACGGCT
Phase-1 RCT-286 GAACTTTGTGCGTCTACTCATGCTCTACACCCGCAAGTTTGAGTCSEQ ID
NO:
CACGGACCCAAGAGAAGCCCTGCAGTACTTTTACTTCCTCAGGG389
ATGAGAAAGACAGTCAAGGAGAAAACATGTTTCTGCGCTGTGTGA
GTGAGCTTGTGATAGAAAGTCGAGAGTTTGATATGATTCTTGGGA
AGCTAGAGAATGACGGAAGTAGAAAGCCTGGAGTCATAGATAAG
TTTACCAGTGACACAAAGCCTATTATCAACAAAGTTGCTTCCGTG
GCAGAAAATAAAGGACTATTTGAAGAAGCAGCCAAGCTTTATGAC
CTTGCCAAGAATGCNGACAANGTGCTGGAGCTGATGAACAAGCT
GCTAAGCCCTGGGGTCCCACAGATCAGCGNCC
202
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGCCAAAACCTGACGGA
CAGATCAGTTTTGACCTCTTATCCTCTGTGGCTCTGAGTGGTACT
AATCATGAACATGACCAGCCAGCACATTTAACCTTGAAGGATGAC
AGCATACCTGTTAATAGAAATCTGTCAATATATGATGGGCCTGAG
CAGCGATTCTGCCCTGCAGGAGTTTATGAATTTGTTCCTCTGGAA
CAAGGTGATGGATTTCGGTTACAGATAAATGCTCAGAACTGTGTG
CATTGTAAAACATGTGATATCAAAGACCCAAGTCAAAATATTAACTSEQ ID
NO:
Phase-1 RCT-287 GGGTGGTCCCAGAAGGTGGAGGAGGACCTGCTTACAATGGCAT390
GTAAAGCCCAAGTGCCTCCACTTACTGGCACACTTGACAGCCAG
TTTCTAGAATACTGTAAATGTATGCCAAACTAACCTCCCATATGTT
TGGATAACTTCTGAACAAGTGTCCTTCAAACACTGAAGTAP,AAAA
CTTTGTATCTAACGTCCCATAAAATCATGAAATATTTGTCATTAATA
AAACTTTATAAATAAATAAA TCTCGCGGCCG
CAAGCTTATTCCTTTAGTGAGGGTTAATTTTAGCTTGGCCTGGCC
GTCGTTTTTCAACGTCC
TCCTNATNAGATGATNACGAATTTAATACGACTCACTATAGGGAA
TTTGGCCCTCGAGGCAAGAATTCGGCACGAGGAATTAAAACTATA
TAAATAAGAATAATAGAAAATAAGTTAAGGAAATAAACAGTAGTAA
AACACCTCTGGTTTATCAAACGTTTAATCATAGAAGGAAACCCTG
ATGTCACTTTCTTTACGTATGACTCTGTGAAGGAATGTAATGGTAC
ATTACAATAGGAGCTAATGTTTTAAATGTGTACAGTAGTGAAATAA
TTAACAATAAACTGGAGTTCAAAATGCCAGTCAATGTAAGTACATT
CTATGATGGGGCTTTGAAAGTGTTTATTCCATGAAGCAATTCTACSEO ID
NO:
Phase-1 RCT-288 AAAGAACATTGATGAGCAATATGGGTAAACTGTTTGGAAGGTGCT391
GGGCAAATAACTGGAATTGTCTAAGTGGCTTCACCGCACTGTACC
AGAAACATATTCTGAAAGTCAGATCCATCAGTGCTCACTGTGCTG
CCGAACTTCACAGTAATTTACTTTACTGTTGTGAAAAATAAACATC
GCTCTTGTAAACTGTGGTGTTAACATTTTTTCTAAAATGTAAAGGA
GGCATTC'>TfTTACAAAAGAGAAATGCTTTATCTTTCAGAAAAAAA
ATGAAGCAAAAACATCTTATCCATTATCTGAATGTTGATTCCTTTG
CTTATAAGTTTTAGGTGCAGGTGGCTTCTCCTATTGCTTCTCTT
GTTACTTGTGGTGGCACAAACNTCAAACAACCAATATACAAGTGT
TCTGGGGTTGGATCAGGGGTCGGGGAAGTCCCAAGTTTTAACTC
TGTGGGGTTTGGGGAGACAAGGTGGGGNAATTGAACGAATGGG
GAAATCAATTTATTTTTNTTAATTCTGTCCATATAAATATATTCATG
AAGACCAAAAGAGGGAAGGGCAGTTGGGNTGGTGATGAAGTGG
GAGAAGGGNAGGCAGAGCCCTCTCAACTCTACTCAGCCAAAAAT
ATNAAACANATTAATTTCATGGTGGGAGAAGAGATTTAAANAATGSEOID NO:
Phase-1 RCT-289 ATAGAAGATGGGAAGGAGGGGGAGACAGAAGGGGACCAACCAG3g2
GGAAAAGGGGGACCCATGGCAAGGGAGTCCCATGTCAAGGAGT
CCTGTGCCGGTGTGAGAATCTGTCTGCTTCTCTCNTCAGCCATAA
TGTGGTAAGCTCTGGCCCAATCCGCCTTCGGCTCCCGGCTT'GGC
CCTTGCTCCTATTGTGCCAGCCCCTCCCGCCTCCAGCTATTGAG
AGCTAGCTCGCTCCAGGCCTCGTGCCGAATTCTTGGCCTCGAGG
GCCAAATTCCCTATAGTGAGTCGTATTAAATTCGTAATCATGTCAT
ACCNNNC
CTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGTCTGAAGTGGGAGT
CTGTGAGTTCTAAGCCAGCCAGGGATACAAACTGAGACCTAGTTT
TAAAATAAAATATAGACATCTTCTTCGCAGGTGGGACGGTGAAGC
CTTGACTCCTGTCTAAATTAGTAGGGCACAAGAAAGTGAGACCTT
GGCAGTCCTTACTGGCTCCTGCTACAGGCTTAGCTGAAGTATCT
GTTCCAAGGGAATTACCTTCCGAAGCCAGCCAGGACAGGAGCTGSEOID NO:
Phase-1 RCT-290 CTAGCCCCACAACTGTTTCCCACAGCCTCTGTGGGGCTGATTAAA393
CCTTCCATTCCACGGTCTGCTTCCATTGTTCCTCGGAAACCTCCA
CTTGGATCTGGAGTTTCAGATTCCTGCTGACTATCTTCCTCTTCAC
CCCCGCCACCACCAATGCGGCCGCAAGCTTATTCCCTTTAGTGA
GGGTTAATT-fTAGCTTGGCACTGGCCGTCGTTTTACAACGTCGTG
ACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCA
CATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCAC
CGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAA
203
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GTCATCTTCAGCTATGCAGTGAATATGAGGCCAGTCTGGACTACA
GGAAACCNTGTATTGGACAGAGCTAGAAGATCATACAATCAGGAA
TGTGGGTGTAACAGCACTTACTTTTAAGGATAATGGATAAAACTC
GAAAGAACATGAATTCGGAATGGTCTAGTTTTAGTGGTGTCTGTT
GGAACATTTTGTAGAGCGGCTCTAAGATGACATTTAAAACGAAAA
TACTGCTGACTTTAAAAGGGAGGGAAAATATGGAAAGTTACATGT
AATAAACCAATTAAGAGGTAGTGTTGGGGCTGCCTCTACACAGTG
SEQID NO:
Phase-1 RCT-291 CCACGTTCTGGCCAAGAATGTTCTCTACTCATTTAAGGTCAGTTC
3g4
CAGTACAGTCAGAATCCAACTGCCTCATGACCTCCTCTGCCACTT
CACTCACATATAACTAAAGCATGACAAACACTATGGTCCTGAAAA
GTGTGAAATCTACTGTCTGTTTCATGTGCTTATAAAAAATCAACTC
CCCTGTGTATCCCACACGCTCCAGATTCAGTTGTCCAAATCAGTC
CAGAATTTCAGAGGAACACACCTCGTGCCGAATTCTTGGCCTCG
AGGGCCAAATTCCCTATAGGAGTCGTATTAAATTCGNATCANGTN
AATCNNNNG
TCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTT
GGCCCTCGAGGCCAAGAATTCGGCACGAGGCACGTACTAAGCA
GACCGCTCGAAAGTCCACGGGCGGCAAAGCCCCGCGCAAGCAG
CTCGCCACCAAGGCCGCCCGCAAGAGCGCTCCGGCCACCGGCG
GCGTGAAGAAGCCCCACCGCTACCGTCCCGGCACCGTGGCTCT
GCGCGAGATCCGGCGCTACCAGAAGTCCACCGAGCTGCTGATC
CGCAAGCTGCCGTTCCAGCGCCTGGTGCGCGAAATCGCGCAGG
ACTTCAAGACCGACCTTCGCTTCCAGAGCTCGGCGGTCATGGCC
SEQID NO:
Phase-1 RCT-292 CTTCAGGAGGCCAGCGAGGCCTACCTTGTGGGTCTGTTTGAGGA
3g5
CACCAACCTGTGCGCCATCCACGCCAAGCGTGTGACCATCATGC
CCAAGGACATCCAGCTGGCCCGCCGCATTCGTGGAGAGAGAGC
TTAAACGGTCCTACGAGCAGTTAACCCAAAGGCTCTTTTCAGAGC
CACACNANTNNATNANTAGNAANNNNAANAAAACAATTGCGGCC
GCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGTTGGCACTGG
CCGTCGTTTTACAACGTCGTGACTGGGAAAACCTGGCGTTACCC
AATTTATCCCTTGCAGCACATCCCCCTTTCGCCAGCTGGNGTAAT
AAC
GNNNTGTCTATGACATGATTACGAATTTAATACGACTCACTATAG
GGAATTTGGCCCTCGAGGCCAAGAATTCGGCACGAGGCCTCGCT
CCTCAACTTGGCAAAAATGCCTACAGAGACTGAGAGATGCATCG
AGTCCCTGATTGCTGTTTTCCAGAAGTACAGTGGGAAGGATGGA
AATAGCTGTCATCTCTCCAAAACTGAGTTCCTTTCCTTCATGAACA
CGGAGCTGGCCGCCTTCACGAAGAACCAGAAGGACCCCGGTGT
CCTCGACCGCATGATGAAGAAGCTGGACCTCAACAGTGATGGGC
SEOID NO:
Phase-1 RCT-293 AGCTAGATTTCCAAGAGTTTCTCAACCTTATTGGTGGCTTAGCTAT
396
AGCATGCCATGAGTCCTTCCTCCAGACTTCCCAGAAGCGTATCTA
ACCCTCTCCATTCCCTTCCAGCCACCAAGTCATCGCCTCCTCCAC
TCCTTCCCCCATCCACACCTGCACTGAGCCCACCACACCTACCA
CACATGCAGCCCACGCCTGAGAGGGAAAATAAAACAATGTCATTT
TTTTAAATGT TGGAAGCGGCC
GCAAGCTTATTCCCTTTAGTGAGGGTTAATTTTAGCTTGGCACTG
GCCGNCGTTT
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAAT1TGG
CCCTCGAGGCCAAGAATTCGGCACGAGGGTTCTCAGGCCTCTAT
TCCTGCTGTCCTCTGGTGCACAAGCAGGAGAGGTGGCCATGCTA
GGCTGGGTGCCCACTTCCCGTGAAGCAGCATTTCATTCTGCAGA
ACCATCCTTCCTTTCCCTTGCCCATTTCCCACGTTTCCTTCGTGCT
GCCTCAGGGCAGGACTGAAGAGCTGGAAGGAAGCAGTCAGTGT
ACCCTCCCAACGTTCCCTGAAGGTCTCCACTAGACTCTGGGCTT
Phase-1 RCT-294 CCCTTTGCCTAGTGCAGGGGTCACCGCTGGAGAAGAACCAACACSEQ ID NO:
TGTCCTTGGTGTGCTCCAAGCCTGGAGCCAATTTACCCTGTTGG397
CCCACCCAGCCCCAGCGGGGGATTATTTCCTGGGTTTCTGTCCC
TCCAAGGCTTACCAGGTGTAGTTGGCTTTGTTCTTCTGGGGGTGT
TAGTCCTTCTACTTTCTTTCTCACTTCACCCTGGACCCCCTTCTGT
GTCTCTGCAGTCTTCTGTCCCTCCCACCCATGTGCATGAGCAAAT
ATGCAACTTACCTTGGGATCTGCAGTCAGTTGAAGCCAAGCTTCC
CACATCCTCTTTGTTTGCCATGAAGTGATGTGGGGTTTCCATTGT
GTCTGTCATTACCACCGTGTCTTTCCTAACCAGTCTCN
204
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TATGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTGG
CCCTCGAGGCCAAGAATTCGGCACGAGGATAACATTAATCTTTTT
AACAAAAATATGGTCACTTTATCTAAACCCATCCTATCCCCAAGTT
TAACCAGGATAAGCTATTTTCATTGCCAAACTATCTATTCTCCACA
CGTTTCTGTTCTGATTTTCTGATATTCCTCCCTGTAAATCTGAATA
AATTCAGCAAGTAATAACAATGCCACAATTTAAATAATGTTTTCTT
Phase-1 RCT-296 GAAAGGAATCATCCAGGGAATACCTTTCCCTCTAACTTCTTTTACTSEQ !D
NO:
TCACCCTGAACAGGCAGGTGAACCTATACATCCCGAAATTCTCCA398
TATCTGATACCTATGACCTTAAAGACATGCTGGAAGACCTGAACA
TTAAGGACTTGCTCACCAACCAATCAGATTTCTCAGGCAACACCA
AAGATGTTCCCTTGACATTAACGATGGTCCACAAGGCCATGCTAC
AACTGGATGAAGGGAATGTGTTGCCTAATTCTACCAACGGGGCT
CCCCTACACCTGCGCTCTGAACCACTTGACATCAAGTTCAACAAG
CCCTTCATCCTCCTGGTCTTTGACAAGTTCACATGGAGCAGCC
TCCTATGACATGATTACGAATTTAATACGACTCACTATAGGGAATT
TGGCCCTCGAGGCCAAGAATTCGGCACGAGGTGATGTTGGAGAA
GGCTGCCGGGGTGTTGCTAGGGGCGGCTTTCCCAGCACCCAGA
TTCTTCTACGGCCCGGATTCCTTCCTACTGAGCACCTGCTACTGG
TGACAAAGGACCGTTTATAGCTGGACGAGCGGACATCGTAGTAT
ACAGCAACATTCGCACCCCTCTGCCCAGTACAGACCGACCTACC
TGTCCATTAGTTGGCTGAATGAAGAAGTGTGTAATCAGGAGCCGT
SEQID NO:
Phase-1 RCT-297 TGAGTAGGCGGGTTTTAAATGCTGCATTTTAAGATCTGGACAACT
399
TAAGATACATTTGTACTCTCAATGATTTP,AAAAACTGATCTCATCT
GACTCGTGATCCTAAAACTATTGACCGGAAGGAGTTCGGCAGGT
CTCCCGGACCCCCTTTGTGAACTACATTTTGGGTAGAACATTTTA
ATCACCGAAACCCTTCTGAGGAAAAAAAGACTCCCACTGCCCCCT
GCAAAAAAACAAAAAA CACATGCGGCCGCAAGC
TTATTCCCTTTAGTGAGGGTTAATTTTACTTGGCACTGGCCGTCG
TTTT
CTATTGACAAATATGTTTTGGGTAGACACTACAAGCACTGGCTAA
CACAGGTGCTGGTTGTAGAGCCACTATTATGAGTGGACAGTACC
Phase-1 RCT-289 TGACGTTATGTTTGTCCCTCATAGGGGATAGTGAGTTTCCTCTTG
SEQ ID
novel TATCAAGTGTTGCTATAGTTCCTTTGCAATCGTTGTCTTCCAGTGGNO:
400
GGAACAAGGATAAAAGAGCAAGGTATAAAAACAACTACTAGAGAA
CAATGATATGCTAATTACACATCATAATTTAGCTTGGCTTACGTAC
GAAGCTT
AGGTTGACAAATGCTGTCAGATTTTTATTGGATATTTTCTTTTTAC
ATTTCAAATGTAGTTCCCATTCACAGTTTTCATTCCAGAAACCCCA
Phase-1 RCT-290 TAACCCATTACCTGCTACTCTTGCCCGTCTGAGGGTGCCTCTCCASEQ ID
NO:
novel CCCTCTAACCAAATCATGACTCCCAGCATTGACATTACCCCTACA401
ATAGGGCTTTGAGCCTTCACAAAACCAAGGGCCTCTCCTGCCATT
GTTGCTCAACAAGGCCATCCTCTGCTTGATATGCCTCTAAGCTT
Genes with
some known
cell function
determined
to be toxicologically
responsive
TGGNGAATTGGGCCCTCTAGATGCATGC.TCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCAAAAAG
CAGCAGATGGCTCGAGAATACAGAGAGAAGATCGAGACGGAGCT
GAGGGACATCTGCAACGACGTACTGTCTCTTTTGGAAAAGTTCTT
GATCCCCAATGCTTCGCAGCCAGAAAGCAAAGTCTTCTATTTGAA
AATGAAGGGTGACTACTACCGCTACTTGGCTGAGGTTGCTGCTG
GTGATGACAAGAAAGGAATTGTGGACCAGTCACAGCAAGCATAC
SEQID NO:
14-3-3 zeta D17615 CAAGAAGCATTTGAAATCAGCAAAAAGGAGATGCAGCCGACACA
402
CCCCATCAGACTGGGTCTGGCCCTCAACTTCTCTGTGTTCTACTA
TGAGATCCTGAACTCCCCAGAGAAAGCCTGCTCTCTTGCAAAAAC
AGCTTTTGATGAAGCCATTGCTGAACTTGATACATTAAGTGAAGA
GTCGTACAAAGACAGCACGCTAATAATGCAGTTACTGAGAGACAA
CTTGACATTGTGGACATCGGATACCCAAGGAGACGAAGCAGAAA
AGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGGCCGNACT
AGTGGATNCGAGCTCNGTACCCAGCTTTGATGCATA
205
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGCGATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
.
GATGGATATCTGCAGAATTCGCCCTTACACACACAGTGGCCCCA
AATGGTCAATGTACTAAGAATGAAGAGAGAAGGTCTTAGCCATGC
TATAGTCTGAAAACAAGCCCATTTTACCCAACAGACTTAACTGCAT
GATTTTTGTTTTATCTACCTCTAAAGCAAAACTGCAGTGTTCCAAA
GTCTGTGGTATTGATTCAAAACAGAAGTCCAGTAACAAAATGAAA
ACTCAATAATGGGTTTAGTTGGGGCAAACACATTGCCTGTGTTCA
TGGACTGATTTATCATCCCTGTCCCCACGTGGACACTCCCACACASEQID NO:
25-DX U63315 CAGTAACTCTCACACACCTGGTAATTGGCAGTTGGAACTACAACA403
GAATCTGAAAATTCAAGGTAGAACTTTGCAAAAGAAAAATCTGTT
GCATGTAGCAGGGCAATGGTTATGTGGTTATTGGCCAAATGTAAA
ATTTGAGAGCAATATACAGGACAGGAACAGGTGTGCGCTAAGGG
CGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTC
GGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGGCACCT
AAATAGCTTGGCGTAATCATGGNCATAGCTGTTTCCTGTGTGAAA
TTGGTATTCCGCTCACAATTCCACACAACATCCGAGCCGGAAAGC
ATTAAGTGT
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTAACTAACAGCCCCAGGCA
GCCTGGGCAGGGATCCCCCACTGATCCTTCCATGCTTACAGTGT
TCACTGACAGCTGTCTAAGCATCCATTGCAGCACAAACTAAGTGA
CTGTGCACCTGGTCTGCACCTGGTCTGCACCTGGTTGCGTCTCT
GCCTGACCATGTGAGCTCTTTGAGAAGAGTGATGACTACTGGGC
TTTTAGCTCTTTTCCTTTTTGGGACACAGTCTTGCTATTGTACTCC
25-hydroxyvitamin ATGCTGTCCTTGAACCCACAAGCCCTCACCTCACCTTCCCAAGTGSEQ ID
NO:
D3-
1 alpha-hydroxylaseAg001992 TTGGGTTACGGACATTAGCTATGGCTTCCAGCTTTATTAGTCTTTC404
TATCTCCTGCCATGGTCTATCCCCGGCTATTT'GATACTATATATTC
TCAGATTGAATCTGGACCATGTGGTAGAAGGGATGACCACTCAC
CAGGCTCTACCCACCACTTTATCTTAATCTTTTCTCTAGGAAAGTG
AATCTCTCCTTGCCl-fACAGCATTTTAAAGCTCCCCTTGGCTGTTC
TGCTCTAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTG
GATCCGAGCTCGGNACCAACTTGATGCATAAGCTTGAGTATTCTA
TAGGNCACCTAAATAGCT
AATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATG
GATATCTGCAGAATTCGCCCTTGACAGGTCCTTGTCCGGCGACTT
GCTGATGGAACAGAACTCCGTGGGCGCATTGTAGAGACTGAGGC
ATACTTGGGGCCAGAAGACGAAGCTGCCCACTCAAGGGGTGGC
CGGCAGACCCCCCGTAACCGTGGCATGTTCATGAAACCTGGAAC
TCTGTACGTGTACCTCATCTATGGCATGTACTTCTGCTTGAATGT
CTCCAGTCAAGGGGCTGGGGCTTGTGTCTTGCTAAGAGCACTAG
3-methyladenine AGCCATTGGAGGGCCTAGAGACCATGCGGCAGCTTCGAAACTCCSEQ ID NO:
DNA
glycosylase X56420 CTCCGGAAAAGCACTGTCGGCCGTTCCCTCAAGGACCGCGAGCT405
CTGTAATGGTCCCTCCAAACTGTGCCAGGCCCTAGCCATTGATAA
GAGCTTTGACCAGCGAGACCTGNCCCAAGATGAGGCTGGGTGG
CTGGAGCATGGCCCTCTGGAGTCCAGCAGCCCAGCTGTGGTGG
CGGCAGCCCGCATAGGTATTGGCCATGCACGGGAATGGACACA
CAAGCCCAGGGCGAATTCCAGCACACTGNCGGGCGNTACTAATG
GATCCAACTCGGNACCAANCTTGATGCATANCTTGGGATTCTATA
TGGCACCTAAAAACTTGGNGAATATGGGATACT
ANCGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTCGCGGGATCCGGTGAAGCTTC
GAAAAATGCCTAGGTATTACCCTACTGAAGACGTGCCTCGGAAG
CTGCTGAGCCACGGCAAGAAGCCCTTCAGCCAGCACGTGAGGA
GGCTGCGCTCCAGCATCACTCCCGGGACTGTCCTGATCATCCTC
ACTGGGCGCCGCAGGGGCAAGAGAGTGGTTTTCCTCAAGCAGC
60S ribosomal TGGGCAGTGGCTTGCTACTTGTGACTGGACCTCTTGCCCCCAACSEQ ID NO:
protein
X$7107 AGAGTTCCTCTGCGTAGGACACACCAGAAGTTTGTCATCGCCAC406
L6 CTCTACAAAAGTTGATATCAGCAAGGTTAAAATTCCCAAACACCT
GACTGATGCTTACTTCAAGAAGAAGCCACTTCGCAAGCCCAGGC
ATCAGGAGGGTGAGATCTTCGACACAGAGAAGGAGAAATACGAA
ATTACAGAGCAGCGAAAGGCTGATCAGAAAGCTGTGGACTCGCA
GATTTTGCCAAAGATCAAAAGCTGTCCCCCAGCTTCAGGGCTACC
TGCTTGCANGGCCAANGGCGAATTCAGCACACTTGGCGGGCGG
TACTAGTGGGATNCCN
206
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
NAGTGNCTCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTTGCAGCAGCTTCGAGTGGCCT
CTTATGAAGAGGCCCACAAGGCCCTCTGCACCCTGCCTGGAGTG
GGCACCAAGGTGGCTGACTGCATCTGCTTAATGGCCCTGGACAA
ACCCCAGGCTGTGCCTGTAGACATCCATGTGTGGCAGATTGCCC
ATCGTGACTACGGCTGGCAGCCTAAGACATCGCAGACTAAGGGC
CCGAGCCCTCTGGCCAACAAAGAACTGGGAAACTTTTTCCGGAA
8-oxoguanine AF029690 TCTGTGGGGACCTTATGCTGGCTGGGCCCAAGCAGTGCTGTTCASEQ ID N0:
DNA GT
glycos
lase
y GCTGACCTTCGTCAACAAAACCTGTCTCGGGAGCCACCAGCA407
AAGCGCAAAAAGGGATCTAAGAAGACAGAAGGCTAGGTAGGGCC
CAGGGGACAAAAGATGTCACTGATATTTTCCCCTTTGTTCTCCAT
TTCTCTCCCTTGTCCTCACCCAAGTCAGAAAGGCTTAACATTCCT
ACCTCCAAGGCAAACATCCCAAATCAAAGGGCGAATTCCAGCAC
ACTGGCGGCCGGT/lCT.AG7GGATGCGAGCTCGGTACC.QAGCTTG
ATGCATAGCTTGAGTATTCTATAGTGTCACCTAAATAGTTGGCGT
AATCATGGCATAGCTGGTTCCTGTGTGAAATTGTAN
AGCTATGNCCATGATTACGCCAAGCTATTTAGGTGCCACTATAGA
ATACTCAAGTATGCATCAAGTTGGTACCGAGCTCGGATCCACTAG
TAACGGCCGCAGTGTGCTGGAATTCGCCCTTTGCGGCTGACAAC
ATCCCTCCTAGGGAAGATGGAGTGAGAACATTCATCATTGAAGTT
GTCCAATGGCCAGGGTATGCTTTCTAGAAACTATGCTGTTCTGTC
CTAGACTGACTGTGCATAGGGCATTCGTTTCTGAGCCTGGTGTTG
TGCTATTTAGATGTTTGTCTTGCACAACATTGGCGTGATTTTTTTC
Activating M63282 CGGGAGTTTCATCAGACCTGATTTCCGAGAGTTTGGGGGTCTGCSEQ ID N0:
transcription CACTGTGGACAATATCCCCCAAAAGTGTTTGGGTGGCCATGTAAA408
factor 3
CTGGCTGATGACCAGCTGTGCTACTCTGTGCTGACCGAGGACTG
ATGCCTCCTTCCCCTGTACCCACTGCTGAGGAAGAACCCGGGCA
CAGCAGCTGTCCTTGGCTACAAACTGTTACAATGTCACAGAACGA
AGGCRCAAAGTCCCGCTTTCAAAGGGCGTAGGACTCCACACTCA
GTGACAGGGCAGGAAGAGCCAAGGGCGAATTCTGCAGATATCCA
TCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTC
GCAA
TGNGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCACACGC
AGGAATGGCAATGGTCTGTGAAACGATAGAAGAATGCTGGGATC
ATGATGCAGAAGCCAGGTTATCAGCTGGATGTGTAGGTGAAAGA
ATTACTCAGATGCAAAGACTAACAAATATAATTACTACAGAGGACA
TTGTAACAGTGGTCACAATGGTGACAAATGTTGACTTTCCTCCCA
AAGAATCTAGTCTATGATGGTTGCACCATCTGTCCACACTGAGAA
Activin receptorS48190 TCGGGACTCTGAACTGGAGCTGCTAAGCTAAGGAAACTGCTTAGSEQ iD
N0:
type II
TTTATTTTCTGTGTGAAATGAGTAGGGTGCCTCCGGGACACGTAT409
GCAAGCAGCCCCTTGTGGAAAGCATGGATTGGGAGACTTCCTGC
AGCGTCTGCAACACGGATATGAAGGGGGTCTAAGGGGAAACTGC
GAACTGTAAAGAACTTCTGAAAACTTACACGAAGAATGTGGCCCT
CTCCAAATCAAGGATCTTTTGGACCTGGCTAATCAAGTAAGCTTG
GCCAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGAT
CCGAGCTCGGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAG
TGCACCTA
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTTCGCTGGTAACCTGGCCTC
TGGTGGGGCAGCTGGGGCTACCTCCCTCTGCTTCGTCTACCCAC
TGGACTTTGCTAGGACCAGGCTGGCTGCCGACGTGGGCAAGGG
ATCTTCCCAGCGTGAGTTCAATGGGCTGGGTGACTGTCTCACCA
AGATGTTCAAGTCTGATGGCCTGAAGGGTCTCTACCAGGGTTTCA
Adenine nucleotide GTGTCTCTGTGCAGGGCATCATCATCTACAGAGCTGCCTACTTCG
SEQ ID N0:
transiocator D12770 GAGTCTATGACACTGCCAAGGGGATGCTGCCAGACCCCAAGAAT
1
410
GTGCACATTATTGTGAGCTGGATGATTGCCCAGAGTGTGACAGC
CGTGGCGGGGCTAGTGTCCTATCCATTTGACACTGTCCGTCGTA
GGATGATGATGCAGTCTGGCCGGAAAGGGGCTGATATTATGTAC
ACGGGGACAGTTGACTGCTGGAGGAAGATTGCAAAAGATGAAGG
AGCCAAAGCTTTCTTCAAAGGTGCTTGGTCCAACGTACTGAGAG
GCATGGGGGGTGCTAAGGGCGAATTNCAACACACTNGCGGGCG
GTACTAATGGATCCCANCTCNG
207
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTACAGACAAAGACAAGGAC
GGCATGGCCCCCAGAAACAAGATCAGCCCTCAAGGCTATGGCCG
CCGGCGCCGGCGTTCCCTGCCAGAGGTCCTCCGAGCCCGGACT
GTGGAGTCCTCCCAGGAGCAGACACACTCAGCTCCAGCCTCCCC
GGCGCACCAAGACATCTCCAGAGTCTCTAGGTTATAGGTGCGGG
TGGCAGCATTGAACAGTCGGGCGAGTATCCCATTGGCGCCTGCGSEO ID NO:
AdrenomedullinU15419 GAATCAGAGAGCTTCGCACCCTGAGCGGACTGAGACAATCTTGC411
AGAGATCTGCCTGGCTGCCCCTAGGGGAGGCAGAGGAATCCAA
GATCAAGCCAGGCTCACGTCAGAAACCGAGAATTACAGGCTGAT
ACTCTCTCCGGGCAGGGGTCTGAGCCACTGCCTTGCCCGCTCAT
AAACTGGTTTTTCTCACGGGGCATACGCCTCATTACTACTTGAAC
TTTTCCAAAACCTATNCGAGGAAAAAGTGCAAAGGGCGAATTCCA
CCACACTGGCGGCCGNTACTNAGTGNG
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTACCCTCTGCAAGAAAAATGGC
TGGATCATGCCAACTGTGTACCAGGGCATGTACAACGCCATCAC
CAGGCAGGTGGAGACTGAGCTCTTCCCCTGCCTCAGACACTTCG
GACTAAGGTTCTACGCCTTCAACCCTTTGGCTGGGGGCCTGCTG
ACTGGCAGATATAAATACCAGGATAAGGATGGGAAGAATCCTGA
GAGCCGCTTCTTTGGGAATCCATTTTCTCAACTGTACATGGACCG
Aflatoxin CTACTGGAAGGAGGAACACTTCAATGGCATCGCCTTGGTGGAGASEO ID NO:
B1 aldehyde
reductase X74673 AGGCTCTGAAGACTACCTATGGCCCCACTGCCCCCAGTATGATC412
TCAGCTGCCGTACGGTGGATGTACCATCACTCACAGCTCAAGGG
CACCCAAGGGGATGCAGTCATTCTGGGCATGTCCAGTCTGGAAC
AACTGGAGCAGAACTTGGCCTTGGTCGAGGAAGGGCCTCTGGA
GCCAGCTGTTGTGGATGCCTTTGACCAAGAAGGGCGAATTCCAG
CACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGC
TTGATGCATAGCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGG
CGTAATCATGGNCATAAGCTGGTTTCCTGTGGTGAAATTG
TGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTCGCGGAATTCTCTAAGGG
CTACATGGGCGAGTGCGGGTTTCGTGGTGGCTATGTGGAGGTG
GTAAACATGGATGCTGAGGTGCAGAAACAGATGGGGAAGCTGAT
GAGTGTGCGGCTGTGTCCACCAGTGCCAGGCCAGGCCTTGATG
GACATGGTGGTCAGTCCGCCAACACCCTCCGAGCCGTCCTTCAA
GCAGT1-fCAAGCAGAGAGACAGGAGGTGCTGGCTGAACTGGCA
Alanine GCCAAGGCTAAGCTCACGGAGCAGGTCTTCAATGAGGCTCCCGGSEQ ID NO:
aminotransferaseD10354 GATCCGCTGCAACCCAGTGCAGGGCGCCATGTATTCCTTCCCTC413
AAGTGCAGCTGCCCTTGAAAGCGGTGCAGCGTGCTCAGGAACTG
GGCCTGGCCCCTGACATGTTCTTCTGCCTGTGCCTCCTGGAAGA
GACTGGCATCTGCGTTGTGCCCGGGAGTGGCTTTGGGCAGCAG
GAGGGCACCTATCATTTCCGGATGACCATTCTGCCCCCATGGAG
AAACTGCGGCTTGCAAGCTTGGCCAANGGCGAATTCAACACACT
GCGGNCGNTACTAGTGGATCCGAGCTCGGTACCAAACTTGATGC
ATAGCTTGAGTATTCTATAGNGN
TAGGTGACACTATAGAATACTCAAGCTATGCATCAAGCTTGGACC
GAGCTCGGATCCACTAGTACCGCCCGCCAGTGTGCTGGAATNCC
CCTTTCGCGGGGATCCAGTCGCCAAGGTGACCCCAGGCTCCAC
CTGTGCCGTGTTTGGCCTGGGAGGTGTTGGTCTGTCTGTCGTCA
TTGGCTGTAAAACAGCAGGAGCAGCCAAGATCATTGCCGTGGAC
ATCAACAAAGACAAGTTTGCGAAGGCCAAAGAGTTAGGTGCCAC
TGACTGTATCAACCCTCAAGACTACACCAAACCCATCCAGGAAGT
Alcohol TCTCAGGAGATGACTGATGGAGGGGTGGACTTTTCATTTGAAGTCSEQ ID NO:
dehydrogenaseM15327 ATTGGCCGTCTTGATACCATGACTTCTGCCCTGTTAAGCTGCCAT414
1
TCAGCATGCGGTGTAAGCGTCATTGTCGGGGTGCCTCCCAGTGC
CCAAAGCCTCTCCGTTAACCCCATGTCGCTGCTGCTGGGACGCA
CCTGGAAAGGAGCAATATTCGGCGGGTTTAAGAGTAAAGATGCC
GTCCCCAAACTTGTCGCTGACTTCATGGCTAAGAAGTTTCCGTTG
GAGCCGCTGATTACTCATGAAGCTTGGCCAAGGGCGAATTCTGC
AGATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGG
GCCCAATTCTCCAA
208
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AGAATACTGAAGCTATGCATCAAGTTGGTNCNGAGCTCGGATCCA
CTTAGTAACGGCCGCCAGTGTGTTGGAATTCGCCCTTCGCGGGA
TCCTGTTAGGAGGAGTGTGGAGCGGGCTAAGAAATACGTTCTAG
GAGATCCTCTGGACTCAGGAATAAGTCAAGGTCCTCAGATTGACA
AGGAGCAACATGCTAAAATCCTTGATCTCATTGAGAGTGGGAAGA
AAGAAGGCGCCAAACTGGAGTGTGGTGGAGGACGCTGGGGGAA
Aldehyde CAAAGGCTTCTTTGTCCAGCCTACAGTCTTCTCCAATGTGACCGA
SEQ ID
dehydrogenaseM23995 TGAGATGCGCATTGCCAAAGAGGAGATATTTGGACCAGTGCAACNO:
1
415
AAATCATGAAGTTTAAGTGCATAGATGATGTGATCAAGAGAGCCA
ACAATACTCCCTATGGTCTAGCAGCAGGAGTCTTCACAAAAGACC
TGGAGAGGGCCATGACTGTGTCTTCTGCTCTGCAGGCCGGGACA
GTGTGGGTGAATTGTTATTTGACTCTTTCTGTCCAGTGCCCATTT
GGTGGGTTCAAGATGTCTGGAAATGGGCGAGAAATGGGTGAACA
GGGTAAGCTTGGCCAAGGGCGAATTCTGCAGATATCCATCACAC
TGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTC
GCGAATTGGCCCTCTAGATGCATGCTCGAGGGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTACAAGAAGGGGCGAAGCTG
CTGTGCGGTGGGGGCGCCGCCGCAGACCGTGGTTACTTCATCC
AGCGCACCGTGTTCGGAGACGTCAAAGATGGCATGACCATCGCC
AAGGAGGAGATCTTGGGACCAGTGATGCAGATCCTCAAATTCAA
GACCATTGAGGAGGCTGTGGGGCGAGCCAATAATTCCAAGTACG
GGCTGGCTGCCGCTGTCTTCACAAAGGACCTGGACAAGGCCAAT
Aldehyde X14977 TACCTGTCCCAAGCTGTGCAGGCTGGGACTGTGTGGATCAACTGSEQ ID
NO:
dehydrogenase CTACGATGTGTTTGGGGCCCAGTCCCCATTTGGTGGCTATAAGAT416
2
GTCGGGGAGCGGCAGGGAGCTGGGCGAGTATGGCCTGCAGGC
CTACACGGAAGTGAAGACGGTCACCGTCAAAGTGCCACAGAAGA
ACTCGTAAAGTGGCGTGCAGGGTTCCTCAGCCAGCGCCCAAAAA
CCCAACAAGATCCTGAGAAAAGCCACCACCAAGCACACTGCAAG
GGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGC
TCGGTACCAAGCTTTGATGCATAGCTTGAGTATTCTATATGGCAC
CTAA
GAAATNGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTATCGGGGGATGGACCGTCAG
TGTGTCAGGGGAAGGATGTGTGTATGCTCAGACCATGCTGAGAT
ACAACATGCCCTTGGAGAAGCAGCAGCCTGCATTTGCTCTAAAG
GTGCAGACAGTACCCCTGACTTGTAACAACCCCAAAGGCCAGAA
CAGCTTCCAGATCTCACTAGAAATCAGTTACACGGGGAGCCGTC
CAGCCTCCAACATGGTGATTGCTGATGTGAAGATGCTCTCTGGCT
Alpha 1 - J03552 TCATCCCATTGAAACCAACAGTGAAGAAGCTTGAAAGATTAGAGCSEQ ID
inhibitor NO:
III
ACGTAAGCAGAACAGAAGTGACCACCAACAACGTCCTGTTATATT417
TGGACCAGGTAACCAATCAGACACTGTCCTTCTCGTTCATCATTC
AACAAGACATCCCAGTAAAGAACCTGCAGCCTGCCATTGTGAAA
GTGTATGACTACTATGAGACAGATGAAGTGGCTTTTGCTGAATAC
AGCAGCCCCTGCAGCTCAGACGACCACAAGGGGGAATTCCAGCA
CACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTT
TGATGCATAGCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGG
CGTAATCATGGC
ATACTCAAGCTATGCATCAAGCTTGGTAGCGAGCTCGGATCCACT
AGTAACGGCCGCAGTGTGGTGGAATTCGCCCTTCGCGGGATCCT
CACGTAGACAAGTCCACCACAGTGAAGGTGCCCATGATGAACCG
CCTGGGCATGTTTGACATGCACTATTGCAGCACACTGTGGAGCT
GGGTGCTGATGATGGATTACCTGGGCAACGGCACTGCCATCTTC
CTCCTGCCCGATGATGGCAAGATGCAGCATCTGGAGCAAACTCT
CACCAAGGATCTCA'fTfCCCGGTTCCTGCTAAACAGGCAAACAAG
gEQID NO:
Alpha 1-antitrypsinM32247 GTCAGCCATTCTCTAGTTCCCCAAACTGTCCATCTCTGGAACCTA
41$
TAACTTGAAGACACTCCTGAGCTCACTGGGCATCACCCGGGTCT
TCAACAATGATGCTGATCTCTCTGGAATCACAGAGGATGCCCGCC
TGAAGGTTAGCCAGGCTGTGCATAAGGCTGTGCTGACCTTAGAT
GAGAGGGGAACAGAGGCTGCAGGAGCCACTGTGGTGGAGGCCG
TCCCCATGTCTCTGCCCCCTCAAGTGAAGTTCGACCACCCTTTCA
TTTTCATGCTCGAGGGCCAAGGGCGAATTCTGCAGATATCCATCA
CACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCNATTC
209
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTTGGCCCCA
GAGAAACTTCAAAGACTTTTATTTAGGGTGGGCTAAAAGTGGGCT
AGAGGAGAGAACCGCTGTTGAAATGCTCCTTAAGGAGCAATGTC
TAAGGTGCTCTTTP~AAAAPJaAAAATTCTAGAAACTTTTTTAAAAAA
GAGAGCTTAAAAGTTAAAGAATTATACAAATTAGTCCTGAATTTAG
GATCGAGAAGGTTTCTTCTTCTGAAGATGCTATAAGGGATCTGGGSEO ID NO:
alpha-1,2- AB015637 ATCTGTGTTCTGGAGGTAACCAGGCCTCCAGAAAAGAAGGGTAT419
fucosyltransferase ACCCCTGGGCTCACAAAATCTTAAATCCGGCATTGAGAAGGTCAA
GGGTGAAGGATCAGAAGGTGTTCCAGAACTGTGAGCTCAGCCTA
AGTCCCTATAAAACACGGGCTGGAAGCAAAGATGGGACATTTGG
CTGACATCAGGTATACTTGATGCTTTTTCAAGAACGGAGAAAGTT
TCCTCAGATAGCATTTAACCTAATTGTATTCCCTTCCAAGACCAAC
TAAGCTTGGCCAAGGGCGAATTNCAGACACTGGCGGNCGTTCTA
GTGGATCCGAGCTCGGACCAAGCTTGATG
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTGCCGACTGTGCCTGGGGA
TTACACCGTGAAGGTGACAGGAGAAGGCTGTGTCTACCTCCAGA
CATCCTTGAAATACAGTGTTCTCCCGAGAGAGGAGGAGTTCCCC
TTCGCTGTGGTGGTGCAGACTCTGCCTGGGACATGTGAGGATCC
CAAAGCTCACACCAGCTTCCAGATCTCACTCAACATCAGTTACAC
TGGAAGCCGTTCTGAATCCAACATGGCAATTGCTGACGTGAAGAT
GGTGTCCGGCTTCATCCCCTTGAAACCAACAGTGAAAATGCTTGASEO ID NO:
Alpha-2-macroglobulinJ02635 AAGATCTGTGCATGTGAGCCGAACAGAAGTCAGCAATAACCATGT420
CTTGATTTACCTGGATAAGGTGTCAAATCAGACGGTGAACTTGTC
CTTCACGGTTCAGCAAGATATTCCAATAAGAGACCTGAAGCCAGC
CGTAGTGAAAGTCTACGATTACTATGAGAAAGATGAGTTTGCAGT
TGCAAAATACAGCGCTCCCTGCAAGGGCGAATTCCAGCACACTG
GCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGC
ATAGCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATC
ATGGGCATAGCTGGTTNCTGTGTGAAATTG
GAAACGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTTCAGCAGAGCTGATAGACCTGA
CAGGGAAGATGGTGAGCATTGCCTCAACGTGCTGTCAGCTCAGT
GAGGAGAAACGGTCCGCCTGCGGTGAGGGACTGGCCGACATTT
ACATTGGACACTTGTGTTTAAGACATGAGGCAAACCCTGTGAACT
CCGGTATCAACCACTGCTGCAGTTCCTCGTATTCCAACAGGAGG
CTCTGCATCACCAGCTTTCTGAGGGACGAAACCTACGTCCCTCC
ACCATTCTCTGAAGACAAATTCATCTTCCACAAGGATCTGTGCCASEO ID NO:
Alpha-fetoproteinX02361 AGCTCAGGGCCGAGCGCTACAGACCATGAAACAAGAGCTTCTCA421
TTAACCTGGTGAAACAAAAGCCTGAAATGACAGAGGAGCGGCAC
GCGGCTGTCACTGCTGATTTCTCTGGCCTCTTGGAGAAGTGCTG
CAAAGACCAGGATCAGGAAGCCTGTTTCGCAAAAGAGGGTCCAA
AGTTGATTTCCAAAACTCGTGAGGCTTTGGGGGTTTAAACATCTC
CAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCC
GAGCTCGGTACCCAGCTTGATGCATAGCTTGAGTATTCTATAGTG
CACCTAAATAGCTTGGCGTAATCATGGC
GGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTGCGCGGATCCTGATGTG
GTCCCCAAAGATGTCAATGCTGCCATTGCCACCATCAAGACCAA
GCGCAGCATCCAGTTTGTGGACTGGTGCCCCACTGGCTTCAAGG
TTGGCATTAATTACCAGCCTCCCACTGTGGTACCTGGTGGCGAC
CTGGCCAAGGTCCAGAGAGCTGTGTGTATGCTGAGCAACACCAC
AGCCATTGCTGAGGCTTGGGCTCGCCTGGATCACAAGTTTGATCSEOID NO:
Alpha-tubulinJ00798 TGATGTATGCCAAGCGTGCCTTTGTGCACTGGTACGTGGGTGAG422
GGAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGTT
ACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTGA
GTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCATA
GCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAA
CATACGAGCCGGAAGCATAAAAGTGTAAAGCCTGGGGTGCCTAA
TGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCT
TTNCAATCGGGAAACCTGCGTGCCAACTGCATTAATGAATCGC
210
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GTGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCGGGGGAC
GGATGAAGAGAAGTTCATCACCATCCTTGGGACACGCAGTGTGT
CTCATTTAAGAAGAGTGTTTGACAAGTACATGACAATATCAGGATT
TCAGATTGAGGAAACCATTGACCGAGAGACCTCAGGGAACTTGG
AGAACTTACTCCTGGCTGTCGTGAAGTCTATTCGGAGCATACCTG
CCTACCTTGCAGAGACCCTCTACTATGCTATGAAGGGTGCTGGG
Annexin V M21730 ACGGACGATCACACCCTCATCAGAGTCATAGTGTCGAGGAGTGASQ ID NO.
GATTGATCTGTTTAACATCAGGAAGGAGTTTAGGAAGAACTTCGC423
CACGTCCCTGTACTCTATGATCAAGGGCGACACATCi'GGAGACT
ATAAGAAGGCCCTGCTGCTCCTCTGTGGAGGCGAGGATGACTGA
GGAGCTGCCTGGAGTGCCCTGGGCCCGCCTGCTGCCCACCATC
AGCTTCCTTCAGCACCACGCCTACTTACGTTCAATGCCTGCCTGA
AGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGA
GCTCGGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGNC
ACCTAAATAGCTTGGCGTAAT
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTGCGCGGATCCTAGCCTGG
AAGGAGCTTTGGTTCGGAGACAGGCAGCGGAGACGGATGTGCA
GACCCTGTTCAGCCAGTATCTTCAGAGTTTAACTGACTATGGCAA
GGATTTGATGGAGAAGGCCCAGCCCTCAGAGATTCAGAACCAAG
CCAAGGCTTACTTTCAGAATGCACAGGAGAGACTGACACCCTTTG
TCCAGAGAACTGGGACGAATCTGATGGACTTCTTAAGCCGTTTAA
ApolipoproteinM28615 TGAGCCCCGAGGAGAAACCAGCTCCTGCAAGCTTGGCCAAGGGSEO ID
All NO:
CGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTC424
GGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCACCT
AAATAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAA
TTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCAT
AAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATT
AATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGT
CGTGCCAGCTGCATTAATGAATCGGNCAACGCGCGGGGAGANG
CGGNTTGCGTATTGGGCG
GCAAACCGCTTCTCCCGGGGCGTTGGCCGATTCATTAATGCAGT
GGCACGACAGGTTTCCCGACTGAAAAGCGGGCAGTGAGCGCAA
CGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTT
ACACTTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCG
GATACCAATTTCACACAGGAAACAGCTATGACCATGATTACGCCA
AGCTATTTAGGTGACACTATAGAATACTCAAGCTATGCATCAAGC
TTGGTACCGAGCTCGGATCCACTAGTAACGGCCGCCAGTGTGCT
SEOID NO:
ApoiipoprofeinJ02596 GGAATTCGCCCTTGCGCGGATCCTCACGGCTCAAGAGTTGGTGT
Clli
425
TGTTAGTTGGTCCTCAGGGCCAGACTCCCAGAGGCCAGTGAACT
TATCAGTGAACTTGCTCCAGTAGCCTTTCAGGGATTTGAAGCGAT
TGTCCATCCAGCCCCTGGCCACCACAGCTATATCAGACTCCTGC
ATGCTGCTTAGTGCATCCTGGACCGTCTTGGAGGCTTGTTCCATG
TAGCCCTGCATAGAGCCCAGCAGCAAGGATCCCTCTCCCTCATC
AGGGAAGCTTGGCCAAGGGCGAATTCTGCAGATATCCATCACAC
TGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTC
TGAGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTGCGCGGATCCAGGCTTT
GAGTGACCGCATCCGAGGGCGGCTGGAGGAAGTGGGCAACCAG
GCCCGAGACCGCCTAGAGGAGGTGCGTGAGCAGATGGAGGAGG
TGCGCTCCAAGATGGAGGAGCAGACCCAGCAGATACGCCTGCA
GGCCGAGATCTTCCAGGCCCGCATCAAGGGCTGGTTCGAGCCG
CTAGTGGAAGACATGCAGCGCCAGTGGGCAAACCTAATGGAGAA
ApolipoproteinJ02582 GATACAGGCCTCTGTGGCTACCAACTCGATTGGCTCCACCACAGSEO ID
E NO:
TGCAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGTT426
ACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTGA
GTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCATA
GCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAA
CATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAAT
GAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT
TCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGCC
AACGCCCCGGGAGAAGCGGTTTGC
211
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GAGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCCATCATCGGCTCCGTCCT
CTACAACTACCTGCTGTTCCCCTCGGCAAAGAGCCTGCAGGAGC
GCTTGGCAGTGCTCAAGGGCCTGGAGCCCGACACCGACTGGGA
GGAACGTGRAGTGCGGCGGCGGCAGTCGGTGGAGCTCCACTCT
CCTCAGAGCCTGCCTCGCGGCAGCAAGGCCTGAGCTCCCCTGC
AGCGCACCGCAGCTCAGCCGACCGACGGCTCGCCCCCTCCTTC
Aquaporin-2 D13906 CCCCTGACCCGTCGTCGGTTCCCAGTGCAGAGTAGCTGCTCCAGSEQ ID
NO:
CGAGTGCAGTGAGCCTCAAGAAGGGGCTCGCCCGGGAGCCTGA427
CAGTACCTCCGCCCGGAAGCCTTGAGCTACCCTCGAGCTCGCCC
CTTGCAGGGAACCAGACACTTGGGGACCGAGGCGTGGGGAGGG
AAGGCAGGCCGGCGAGAGACGGAGAGCTCTGGAGAGCCCGCTC
TGGTGCCTGGGGAGAAGTGCATAGAGTCCCTTCTGGGGGACTGT
GCTTAGTGCATAAGGGCGAATTCCAGCACACTGCGGCCGTTACT
AGTGGATCCGACTTCGGTACCAAGCTTGATGCATACTTTGAGTAT
TCTATAGTGTC
ATAGCTTTTTTTCCGGTTTNTAGGGGANTGCACAGGAGTTTCCCT
ACAAGTCANAGTGGACAGTATGCNTTACACACAGAACTTTGCTCC
CTGCAACCAGTCATTGCTACCAGAACATTCCAAGGGTACACAGTT
GGACTTTCCCTGGAAGGGATTTTGAACGATCCCTACACCCTAACG
CTTTTAATTTAGAAGACTTTGTCAGTTGTTTACAAGTTCNTGAAAA
Aryl hydrocarbon CCAAAGACACGGGATAAACTCACAGTCAGCCATGGTCAGTCCTCSEQ ID
NO:
receptor U09000 AGGCGTACTACGCTGGGGCCATGTCCATGTACCAGTGCCAGGCA
428
GGGCCTCAGCACACCCCTGTGGACCAGATGCAGTACAGCCCTGA
GATTCCAGGCTCCCAGGCGTTCCTAAGCAAGTTTCAGAGTCCGA
GCATTTTAAATGAAGCCTACTCGGCAGACTTGAGCAGCATTGGCC
ACCTTCAGACTGCTGCTAAGCTTGGCCAAGGGCGAATTCTGCAG
ATATCCATNACACTGNCGGCCGATCGAGCAGCATCTAGAGGGCC
NTTACCTTNAANNTN
CTATGCATCAAGTTGGACCGAGTCGGATCCACTAGTAACGGCCG
CCAGTGTGCTGNAATTCGCCCTTCGCGGGATCCCCTGTCCTTGC
TCCCTCAGAGTCTGCTGGATCAGAAGGTCAAGGTGATCTTACATT
GCCCGAAATGCAAAGGATGTGGTTGTCTCCTATTATAACTTCTAC
AACATGGCCAAGCTGCACCCTGATCCAGGCACCTGGGACAGCTT
CTTGGAGAACTTCATGGATGGGGAAGTGTCCTATGGGTCGTGGT
ACCAGCGCGTGAAGGAGTGGTGGGAGCTGAGACACACTCACCC
SEQID NO:
Aryl sulfotransferaseX52883 TGTTCTCTATCTCTTCTATGAAGACATAAAGGAGAACCCCAAAAG
429
GGAGATCAAGAAGATTCTAGAGTTTTTGGGGCGCTCTCTACCCG
AGGAGACTGTGGATTCCATTGTTCACCACACATCTTTCAAGAAAA
TGAAAGAGAACTGCATGGCTAACTACACAACCATCCCCACTGAGA
TTATGGACCAGAATGTTTCTCCCTTCATGAGGAAAGGTACTACTG
GGGACTGGAAAAATACCTTCACTGTAGCCCAGAATGAGCGCAAG
CTTGGCCAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGC
CGCTCGAGCATGCATCTAGAGGGCCGTTCACAAGNACAGANCNC
_
NTATGCATCAAGTTGGGTCCGAGTCGNATCCCACTAGAACGCCC
CGCCAGTGGCTGGAATTCGCCCTTCGCGGNATCCCACCCCGGTA
GAGCCTCTCATATTAGAGGCTGTAAGAGAAGAATAACTAGTTCTG
TCATTAACAGTTGTCGAGTGTGTCCTCGTGGTGTGGAGCAACTGT
GTCAGCAGACCCNCATTATGGAAATTATGCTTTACAAAAACCAAC
AGGGCAGTAGAAGATGTAATGTCTTTGTCATGGCTGTTCTGTAGC
Aspartate CTGGAGTTTCATCCCATTCTACTGCTCGGTTGACCATCAACCTCA
SEQ ID
aminotransferase,M18467 TCCTTAGGAGTGATCTAAGAATAAAGAATGTAGTTTTTCTGTTCATNO:
'
43
mitochondrial GCCATAACCTTCTGTCTCAGCAAAGAGCCGGGGAGAGTGGGACC0
CTGCCCTTGATTTCAGAGTCCTCTTCAGTGATTGATTGGCTCCTA
CGGGGGTGGGGCCTCTGCCCAGCTGGACGTCCTCATTCATCCT
GACTGCAGCCTGTCTTCACATGAGTCAGACATGCAGGGTAGGAT
CGGAAGGAGCTATTCTGGGGTTTGTATGCTACCAGCCCGGAAGC
TTGGCCAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCC
GCTCGAGCATGCATCTAGAGGGCCCGNTCCAATGACANATNAC
212
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
NATAGAATACTCCAAGCTATGCATCAAGCTTGGACCCGAGNCGG
ATCCCACTAGTAACGGCCGGCCAGTGTGCTGGAATTCGCCC1-fC
ACAGAGGAGGTCTTTCGAAGCTACGTTTTTTACCTCCACCAGCAG
GAACAAGAGACCCAGGGGGCAGCCGCCCCTGCTTAACCCTGAG
ATGGACAACTTGTCCCTAGAACCCAACAGTGTCTTGGGTCAGGT
GGGTCGGNAGCTTGCTCTCATCGGAGACGATATTAATCGGCGCT
ACGACACGGAGTTCCAGAATTTACTGGAACAGCTTCAGCCCACC
SEQID NO:
BAlf AF259504 GCTGGGAATGCCTACGAACTCTTCACCAAGATCGCCTCCAGCCT
431
ATTTAAGAGCGGCATCAGCTGGGGCCGTGTGGTGGCTCTCCTGG
GCTTTGGCTACCGTCTGGCCCTGTATGTCTACCAGCGTGGTTTG
ACTGGCTTCCTGGGCCAGGTGACCTGCTTTTTGGCTGATATCATA
CTACACCATTACATTGCCAGATGGATTGCACAGAGAGGTGGTTG
GGTGGCAGCCCTGAGTTTGCGTAGAGACCCCATCCTGAGTGTAG
TGGTAAAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCC
GCTCGAGCATGCATCTAGAGGGCCATGTC
CTCAAGTTATGCATCAAGTTTGGTACCGAGTTGGATCCACTAGTA
ACGGCCGCAGTGTGCTGAATTCGCCCTTCGCGGAATTCGGGGC
CTTTTTGTTACAGGGTTTCATCCAGGATCGAGCAGAGAGGATGG
CTGGGGAGACACCTGAGCTGACCTTGGAGCAGCCGCCCCAGGA
CGCATCCACCAAGAAGCTGAGCGAGTGTCTCAGGCGAATTGGCG
ATGAACTGGACAACAACATGGAGCTGCAGAGGATGATTGCTGAT
GTGGATACAGACTCCCCCCGAGAGGTCTTCTTCCGTGTGGCAGC
SEOID NO:
Bax (alpha) U49729 TGACATGTTTGCAGACGGCAACTTCAACTGGGGCCGGGTGGTTG
432
CCCTTTTCTACTTTGCTAGCAAACTGGTGCTCAAGGCCCTGTGCA
CTAAAGTGCCCGAGCTGATCAGAACCATCATGGGCTGGACACTG
GACTTCCTCCGGGAGGGGCTGGTTGTCTGGATCCAAGACCAGGG
TGGCTGGGATGGCCTCCTTTCCTACTTCGGGACCCCCACATGGC
AGACAGTGACCATCTTTGTGGCTGGAGTCCTCACTGCCTCGCTC
ACCATCTGGAAGAAGCTTGGCCAAGGGCGAATTCTGCAGATATC
CATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCGN
TTGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGAATTCCAGCCT
GAGAGCAACCGAACGCCCGCTGTGCACCGAGACACGGCTGCCA
GGACGTCGCCTCTACGGCCCCTTGTCGCCAACGCTGGGCCTGC
GCTCAGCCCTGTGCCACCTGTGGTCCACCTGACCCTCCGCCGG
GCTGGGGATGACTTCTGTCGTCGCTACCGTCGCGACTTTGCAGA
GATGTCCAGTCAGCTGCACCTGACGCCCTTCACCGCGAGGGGA
Bcl-2 L14680 CGCTTTGCCACGGTGGTGGAGGAACTCTTCAGGGATGGGGTGAASEO ID NO:
CTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGT433
GTGTGGAGAGCGTCAACAGGGAGATGTCACCCCTGGTGGACAA
CATCGCTCTGTGGATGACTGAGTACCTGAACCGGCATCTGCACA
CCTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAACTA
TATGGCCCCAGCATGCGACCTCTGTTTGATT1'CTCCTGGCTGTCT
CTGAAGACAAAGCTTGGCCAAGGGCGAATTNCAACACACTGGCN
GGCCGTACTAGTGGATCCAACTCGGTACCAACTTGATGCATACTT
GAGT
TTGNNNNGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTACCGGGAGCTGGTGGTTG
ACTTTCTCTCCTACAAGCTCTCCCAGAAAGGATACAGCTGGAGTC
AGTTTAGCGATGTCGAAGAGAACAGGACTGAAGCCCCAGAAGAA
ACTGAACCAGAAAGGGAGACCCCCAGTGCCATCAATGGCAACCC
ATCCTGGCACCTGGCGGATAGCCCCGCGGTGAATGGAGCCACT
GGCCACAGCAGCAGTTTGGATGCGCGGGAGGTAATCCCCACGG
Bcl-xL AF136230 CAGCAGTGAAGCAAGCGCTGAGAGAGGCTGGCGATGAGTTTGAASEQ ID NO:
CTGCGGTACCGGAGAGCATTCAGTGATCTAACATCCCAGCTTCAT434
ATAACCCCAGGGACAGCATATCAGAGCTTTGAACAGGTAGTGAAT
GAACTCTTTCGGGATGGGGTAAACTGGGGTCGCATTGTGGCCTT
CTTCTCCTTTGGCGGGGCACTGTGCGTGGAAAGCGTAGACAAGG
AGATGCACGTATTGGTGAGTCGGATTGCAAGTTGGATGGCCACC
TACCTGAATGACCACCTAGAGCCTTGGATCCAGGAGAACGGCGG
NTGGGACACTTTTGTGGATNTTTACGGAACAATGCACANCCGAAA
CCCGAAAGGGCAGACCGTTTCAACCGTTGGTTCT
213
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGNGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTGCGCGGATCCCCGGGA
CCTGACAGACTACCTCATGAAGATCCTGACTGAAAGGGGCTACA
GCTTCACCACCACAGCTGAGAGGGAAATCGTGCGTGACATTAAA
GAGAAGCTGTGCTATGTTGCCCTAGACTTCGAGCAAGAGATGGC
CACTGCCGCATCCTCTTCCTCCCTGGAGAAGAGCTATGAGCTGC
CTGACGGTCAGGTCATCACTATCGGCAGTGAGCGGTTCCGATGC
Beta-actin V01217 CCCGAGGCTCTCTTCCAGCCTTCCTTCCTGGGTATGGAATCCTGTSEQ ID NO:
GGCATCCATGAAACTACATTCAATTCCATCATGAAGTGTGACGTT435
GACATCCGTAAAGACCTCTATGCCAACACAGTGCTGTCTGGTGG
CACCACCATGTACCCAGGCATTGCTGACAGGATGCAGAAGGAGA
TTACTGCCCTGGCTCCTAGCACCATGAAGATCAAGATCATTGCTC
CTCCTGAGCGAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGC
GGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCAT
AGCTTGAGTATTCTATAGTGGCACCTAAATAGCTTGGCGTAATCA
TGGGCATAGCTGGTTCCTGTGTG
CAAGCTATTTAGGTGNCCTATAGAATACTCAAGCTATGCATCAAG
CTTGGTACCGAGCTCGGATCCACTAGTAACGGCCGCCAGTGTGC
TGGAATTCGCCCTTATCGCGGAATTCGGAGGGCTGTGGGTTTTT
GTAGCCATTTAGAGAATTATTAATGCTTTACAGACAGAAGTATCCA
CTGGGATCTAAAGTAATTTTGAGTGACTTTCAGTAATAATTTCAGT
TTGAAATGTCTATGTAGAAAGGAGAGAGCCCAGAGTCAGCATGA
Bile salt GTCAAAG'TTCAAAGTCCAAGGTCAAGTAGCTGCTTATCTGCCAGC
export pump
(sister of AF010597 CAGTGCTGCTCTGGGTAGAAACTGGTCACTGTCTCCATCGAGGASEO ID NO:
p-
glycoprotein) CGCCGCGGTGAGAGCAAGGAGTCCTCCTTCAGGACAGAGGGTT436
ATCTCTTGCATCTGGGAAAGCTCCCTGCGCACTGAGCCTGCTCT
GTAATCTGCACTCAACTGTTTGAGCCAGTTCAAGGCCAAGAGCTA
AGGACCCAAGGCTACTGGTATTTCTTAACTAAGTTTAGTTTGTTTA
CTATAAGGAAGCAAATTTATTTACCTTTAACTCCTGTGAGTAGGGT
GGGGAGCCCTTTCCCATTCTGGCATAAGCTAAGGGCGAATTCTG
CAGATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAG
GGCCCAATTCGCA
GTGTNAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGTCAA
ATGGCTACCCCAAAACGATCTGCTTGGTCATCCAAAGGCTCGGG
CGTTCATCACACACTCCGGTTCCCATGGTATTTATGAAGGAATAT
GCAATGGGGTTCCAATGGTGATGATGCCCTTGTTTGGTGATCAG
ATGGACAACGCCAAGCGCATGGAAACTCGGGGAGCTGGGGTGA
Bilirubin CCCTGAATGTCCTGGAAATGACTGCCGATGATTTGGAAAATGCCC
UDP-
SEO ID NO:
glucuronosyitransferaM34007 TTAAAACTGTCATCAATAACAAGAGTTACAAGGAGAACATCATGC
437
seisozymel GCCTCTCCAGCCTTCACAAGGACCGTCCTATCGAGCCTCTGGAC
CTGGCTGTGTTCTGGGTGGAGTACGTGATGAGGCACAAGGGGG
CGCCACACCTGCGCCCCGCCGCCCACGACCTCACCTGGTACCA
GTACCACTCCTTGGACGTGATTGGCTTTCTCCTGGCCATCGTGTT
GACGGTGGTCTTCATTGTCTATAAAAAGTGTGCCTATGGCTGCCA
AGCTTGGCCAAGGGCGAATTCCAGCCACTTGCGGNCGNTACTAN
TGGATCCGAGCTCGGACCAACTTGATGCATNCTTGAGTATTTAT
AACTCAAGCTATGCATCAAGGTTGGGACCGAGCTCGGATCCACT
AGTACCGCCCNGCCAGTGTGCTGGAATTCGCCCTTCGCGTCTAG
ATTGGTGTTGGCAGAGCTGGCTCGGTGAGGCTGAGGGACTCGA
AGGATCCACGCTCTGCAGCATTCCTGAACCTGATTGGATTTGTGT
CCAGACGAGAGCTTGGGAGCCTTGATGAAGTACGGCAGATTTCT
TTGGAAGATGCTCTCCGAAGCCAAGAGATTGATGTCGCCTATATT
TGCAGTGAGAGTTCCAGCCATGAAGACTATATACGGCAGTTTCTG
Biliverdin M81681 CAGGCTGGCAAGCATGTCCTCGTGGAATACCCCATGACACTGTCSEQ ID NO:
reductase
ATTTGCGGCGGCCCAGGAGCTGTGGGAGCTGGCCGCACAGAAA438
GGGAGAGTCCTGCATGAGGAGCACGTGGAACTCTTGATGGAGG
AATTCGAATTCCTGAGAAGAGAAGTGTTGGGGAAAGAGCTACTG
AAAGGGTCTCTTCGCTTCACAGCTAGCCCACTGGAAGAAGAGAG
ATTTGGCTTCCCTGCGTTCAGCGGCATTTCTCGCCTGACCTGGCT
GGTCTCCCTCTTCAAGCTTGGCCAAGGGCGAATTCTGCAGATAT
CCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCAAT
TCGCAA
214
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCAATATTT
TCTGGGCATTGCAGGAGGAAAGTGGATAGTTAGCTATTCTTGGG
TGATCAAGTCTATCCAAGAAAGAAAACTTCTGAGTGTGCATGAAT
TTGAAGTCAAAGGAGACGTTGTGACTGGAAGCAACCACCAAGGT
CCAAGGCGATCCAGAGAATCCCAGGAAAAGCTCTTTGAAGGCCT
ACAGATCTATTGTTGTGAGCCCTTCACCAACATGCCCAAAGGGTG
BRCA1 AF036760 CTCATCCAATTGTGCTCGTGCAGCCAAGTGCCTGGACAGAAGACSEQ ID NO:
AACGACTGCCCTGATATTGGGCAGCTGTGCAAGGGACGTCTAGT439
GATGTGGGACTGGGTGTTGGACAGTATATCCGTCTACCGGTGTC
GGGATCTGGATGCCTACCTGGTACAGAATATCACCTGTGGCCGT
GAAAGCTTGGCAAGGGCGAATTCCAGCACACTGGCGGCCGTTAC
TAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTGAGT
ATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCATAG
CTGTTTCCTGTGTGAAATTGGTATCCGGTCACAATTTCACACAAC
ATACGACCGGAACATAAAGTGTAAAAGCCTG
CCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATGGATATCT
GCAGAATTCGCCCTTGACGAAGTGTCATACACATGTCAAAATGAT
ATAATGCTTACAGCTACTTGCAAGTCAGATGGCACCTGGCATCCC
CGGACACCATCATGTCATCAGAGTTGTGATTTTCCGCCTGCCATT
GCTCACGGACGTTATACAAAATCTI'CTTCATACTACGTCAGAACT
CAGGTTACATATGAATGTGAAGAAGGATACAGACTGGTTGGAGA
GGCAACCATCTCCTGCTGGTATTCACAATGGACACCAGCAGCTC
C4b-binding NM 012516CACAGTGTAAAGCTCTATGTCGGAAACCAGAGATAGGAAATGGASEQ ID NO:
protein
GTACTGTCTACCAATAAAGATCAATATGTCGAAACTGAAAATGTCA440
CCATCCAATGTGACTCGGGCTTTGTCATGCTAGGTTCCCAAAGCA
TCACTTGTTCGGAGAATGGAACCCGGTACCCAAAGGTGCCCAGA
TGTGAGCAGGAGGTCCCTAAAGACTGTGAGCACGTGTTNGCAGG
CAAGAAGCTCATGCAATGTNTGCAANTTCAAGGGCGAATTCCAG
CNCACTGGCGGNCGTTNCTAGTGGATCCGAGCTCGGNCCANCN
TGATGCATAGCTTGAGTATTNTATANTGCANCTNAATAGCTT
TGCGAATTGGGCCCTGTAGATGCATGCTCGAGCGGGCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCAGCGC
TAAGAAATCTCCCGAAGAAATGAAGAGCATTTTTCAAAAATATGCA
GCCAAAGAAGGCGATCCAAACCAGCTGTCCAAGGAGGAGCTGAA
GCTGCTGATTCAGTCAGAGTTGCCCAGCCTCCTGAAGCAGGCTT
CAAGTACTCTAGACAATCTCTTTAAAGAGCTGGATAAGAACGGTG
ATGGAAGCTTGGCCAAAAGGGCGAATTCCAGCACACTGGCGGCC
Caibindin-D J02954 G~ACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTSEO ID NO:
(9K)
GAGTATTCTATAGTGTCACCTAAATAGC1'TGGCGTAATCATGGTC441
ATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACAC
AACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTA
ATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGC
TTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCG
GCCAACGCGCGGGGAGAGGCGGTTTGCGTA1?GGGCGCTCTTN
CGCTTNCTCGCTCACTTGACTCGCTGCGCTTCGGTCGTTCGGCT
GCGGCGAGCGGTATCAGCT
_
ACACTATAGAATACTCAAGCTATGCATCAAGCTTGGTNCCGAGCT
CGGATCCACTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTT
CGCGGGATCCTGAGGCGAGTTACCCTTTGGAAATGTGCTCACAC
TTCGATGCTGATGAGATTAAAAGGCTAGGAAAGAGATTCAAGAAG
CTTGACTTGGACAACTCTGGTTCTTTGAGCGTGGAGGAGTTGATG
TCTCTGCCTGAGTTACAACGGAACCCTTTAGTACAGCGGGTCATA
GATATATTCGACACAGACGGGAATGGAGAAGTGGACTTCAAAGA
Calcineurin-BL03554 A~CATTGAAGGAGTCTCTCGGTTCAGTGTCAAAGGCGATAAGGASEQ ID NO:
ACAGAAGTTGAGGTTCGCTTTCCGTATCTACGACATGGATAAAGA442
CGGCTATATTTCCAATGGAGAGCTCTTCCAGGTGTTGAAGATGAT
GGTGGGCAACAACCTGAAAGATACGCAGTTACAGCAGATTGTAG
ACAAAACCATAATAGACGCAGATAAGGACGGGGACGGGAGAATA
TCCTTTGAGGAGTTCTGTGCTGTTGTAGGTGGCCTAGATATCCAC
AAAAGATGGTGGTAGATGCTGCAGGGCCAAGGGCGAATTCTGCA
GATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGG
GCCAATTC
215
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATAGAATACTCAAGCTTATGCATCAAGCTTGGTACCGAGCTCG
GATCCACTAGTACCGGCCGCCAGTGTGCTGGAATTCGCCCTTCG
CGGGATCCCCAGATTTCTTTGATGACCTGGAACCTTTTAGGATAA
CTCCTTTCAGCGCTATTGGTTTGGAGCTCTGGTCCATGACATCCG
ACATCTTTTTTGACAACTTTATCATTAGTGGTGACCGAAGAGTAGT
TGATGACTGGGCCAATGATGGGTGGGGCCTGAAGAAAGCTGCTG
ATGGGGCTGCAGAGCCAGGTGTAGTGGGGCAGATGCTGGAGGC
SEQID NO:
Calnexin L18889 AGCTGAAGAGCGTCCATGGCTTTGGGTGGTCTACATTCTGACTG
443
TAGCGTTGCCAGTGTTCCTTGTGATCCTCTI'CTGCTGTTCTGGAA
AGAAACAGTCCAATGCTATGGAGTACGAGAAGACAGATGCTCCC
CAGCCAGATGTGAAGGACGAAGAAGGGAAGGAAGAAGAGTAGA
ACAAGGGAGATGAAGAGGAAGAAGAGGAGAAGCTTGAAGAGAAA
CAGAAGAGTGATGCTGAAGAAGATGGTGGCACTGGCAGTCAAGA
TGAGGAGATAGCCTCGAGGGCAAGGGCGAATTCTGCAGATATCC
ATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCNATTC
TGGGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAG
TGTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGATG
ACCCCACAGATTCCAAGCCTGAGGACTGGGACAAGCCAGAGCAC
ATCCCTGACCCTGATGCTAAGAAGCCTGAGGACTGGGACGAAGA
GATGGATGGAGAGTGGGAACCACCAGTGATTCAAAATCCTGAAT
ACAAGGGCGAATGGAAGCCACGTCAAATTGACAACCCAGATTAC
AAGGGTACCTGGATACACCCAGAGATTGACAATCCTGAATACTCC
Calreticulin D78308 CCCGATGCGAATATCTATGCCTATGATAGTTTTGCTGTACTGGGCSEQ ID
NO: '
TTAGACCTCCGGCAGGTCAAGTCTGGCACAATTTTTGACAACTTC444
CTCATCACCAATGATGAGGCCTATGCAGAGGAGTTTGGCAATGA
GACCTGGGGTGTCACCAAGGCTGCAGAGAAGCAGATGAAGGAC
AAGCAGGATGAGGAGCAGAGGCTTAAGGAAGAAGAAGAAGACAA
GAAGCGTAAAGAGGAAGAGGAGGCCGAGGATAAAGAGGATGAG
GAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGTTAC
TAGTGGATCCGAGCTCGGTACCAAACTTGATGCATAGCTTGAGTA
TTCTATAGTGTCACGTAAATAGCTTGGCGTA
NTGNCNATGATTACGCCAAGCTATTTAGGTGACACTATAGAATAC
TCAAGCTATGCATCAAAGCTTGGTACCGAGCTCGGATCCACTAGT
AACGCCCGCCAGTGTGCTGGAATTCGCCCTTTAGATGTTGCCTC
CATTGGACTGCACGACCTTCGAGAGAGGCTGACCATCATTCCCC
AGGACCCCATTTTGTTCTCGGGGAGTCTGAGGATGAATCTCGAC
CCTTTCAACAAATAT'1'CAGATGAGGAGGTTTGGAGGGCCCTGGA
Canaiicular GTTGGCTCACCTCAGATCCTTTGTGTCTGGCCTACAGCTTGGGTT
multispecificD86086 GTTATCCGAAGTGACAGAGGGTGGTGACAACCTGAGCATAGGGCSEQ ID
organic NO:
anion transporter AGAGGCAGCTCCTATGCCTGGGCAGGGCTGTGCTTCGAAAATCC445
AAAATCCTGGTCCTGGATGAAGCCACGGCTGCAGTGGATCTCGA
GACGGATAGCCTCATTCAGACGACCATCCGAAAGGAGTTCTCCC
AGTGCACGGTCATCACCATCGGTCACAGGCTGCACACCATCATG
GACAGTGACAAGATAATGGTCCTAGACAACGGGAAGATTGTCGA
GTATGGCAGTCGTGAAGAACTGCTGTGCAACAGAGGTTCCTTCTA
AAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGA
GCATGCATCTAGAGGGCCA
NNGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATG
GATATCTGCAGAATTCGCCCTTCAGGGCTCTGAGCACACCGTGA
ACAAAAAAAAATATGCTGCAGAGCTTCACTTGGTTCACTGGAACA
CCAAATATGGGGATTTTGGAAAAGCTGTGGAGCACCCAGATGGA
CTGGCTGTTTTGGGTATTTTTTTGAAGATTGGACCTGCCTCACAA
GGCCTTCAGAAAATCACTGAAGCACTGCATTCCATTAAAACAAAG
GGGAAACGTGCAGCCTTTGCTAACTTTGATCCTTGCTCCCTTCTT
SEQID NO:
Carbonic anhydraseX58294 CCTGGAAACTTGGACTACTGGACATATCCTGGCTCTCTGACCACT
II
446
CCGCCCCTGCTGGAATGTGTGACCTGGATAGTGCTCAAGGAACC
CATTACTGTCAGCAGTGAGCAGATGTCTCATTTCCGTAAACTGAA
CTTCAATTCGGAGGGGGAGGCTGAAGAACTGATGGTGGACAACT
GGCGTCCAGCTCAACCGCTGAAGAACAGAAAGATCAAGGGCGG
GTTTCCCCTTTTTTAAAAATTAAAAAAAATGGGACCCCCCCTTGGC
CAAGCCTTGGGGGGGGGTCCCCAAAAAAAAAAAAGGGGGGCGG
AAAATTTTCCCAAGCCACCAACCTTGGGGCGGGGGG
216
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCAGGTCCA
TGCTGAGAGGTGGCCCTCTCTCTGGACCCTACCGACTTCGCCAA
TTCCATCTTCACTGGGGCTCCTCGGATGACCATGGCTCTGAGCA
CACAGTGGATGGAGTGAAGTATGCTGCTGAGCTTCACCTGGTTC
ACTGGAACCCGAAGTATAACACCTTCGGAGAGGCTCTGAAGCAG
CCCGATGGGATTGCTGTGGTTGGCATTTTTCTGAAGATAGGACG
Carbonic anhydraseM22413 GGAGAAAGGCGAGTTCCAGATTCTCCTTGATGCCCTGGACAAAASEQ ID
NO:
III TTAAGACTAAGGGCAAGGAGGCTCCTTTTAATCACTTCGACCCAT447
CGTGCCTGTTCCCTGCTTGCCGGGACTATTGGACCTACCATGGC
TCCTTCACCACGCCACCCTGCGAGGAGTGCATTGTGTGGCTGCT
ACTGAAAGAGCCCATGACAGTGAGCTCAGACCAGATGGCCAAGC
TGCGCAGCCTGTTCGCCAGTGCAGAAAATGAGCCCCCGGTGCCT
CTGGTGGGGAATTAAGCTTGGCCAAGGGCGAATTCCAGCACACT
GGCGGNCGGTACTAGTGGATCCGAGCTCGGACCAAGCTTGATG
CATAGCTTGAGTATTCTATAGTG
TGCGAATTGGCCCTCTAGATGCATGCTCGAGCGGGCGCCAGTGT
GATGGATATCTGCAGAATTGGCCCTTTGACCCCACCCCCTTCCAC
ATTCAAGCAGAGGTGACAATGAAAACCAACTTTTTTGGTACCCAA
GATGTCTGCAAGGAGCTACTCCCTATAATAAAACCCCAAGGCAGA
GTGGTGAATGTATCAAGCAGCGTGAGTCTCAGGGCCCTGAAAAG
CTGCAGCCCGGAGCTGCAGCAGAAGTTTCGAAGTGAGACCATCA
CTGAGGAAGAGCTGGTGGGGCTCATGAACAAGTTTGTAGAGGAT
Carbonyl reduetaseX84349 GCAAAGAAAGGAGTCCATGCGAAAGAAGGCTGGCCCAATAGTGCSEQ ID
NO:
ATATGGGGTCACCAAGATAGGGGTGACAGTCCTGTCCAGAATCT448
ATGCCAGGAAACTCACTGAGGAGAGGAGAGAGGACAAGATCCTC
CTGAATGCCTGCTGCCCTGGGTGGGTCAGAACCGACATGGCAG
GACCAAAAGCCACCAAAAGCCCAGAAGAAGGAGCAGAGACCCC
CGTGTACTTGGCCCTTTTGCCTCCAGGTGCAGAGAAGGGCGAAT
TCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTAC
CAAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCACCTAAATA
GCTTGGCGTAATCATGGGCATAGCTGGTTNCTGTGTGAAAT
ANTTGAGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCA
GTGTGATGGATATCTGCAGAATTCGCCCTTGCGCGGATCCCCTG
CACTATGGAGTCCTGCAACTTTGTGCAGGCCATGATGGACCCCA
AGTCAACGGCAGAGCAGAGGCTCAAGCTGTTCAAGATAGCTTGT
GAGAAGCACCAGCACCTGTACCGCCTCGCCATGACGGGCGCCG
GCATCGACCGCGATCTCTTCTGCCTCTATGTGGTGTCCAAGTATC
TTGCAGTCGACTCACCTTTCCTGAAGGAGGTATTGTCTGAGCCAT
Carnitine L07736 GGAGGTTGTCTACGAGCCAGACTCCTCAGCAGCAGGTGGAGCTCSEO ID
palmitoyl- NO:
CoA transferase TTTGAAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCG449
TTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTG
AGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCAT
AGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACA
ACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAA
TGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCGCTT
TCCAGTCGGGAAACCTGTCGNGGCCAGCTTGCATTAATGAATCG
GCCAACGCCCCGGGGAGAGGCGGTTTG
TGCGAATTGCGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTAATTCAAAGAATTTGCTG
CCTGGCCAGAGCACAAGACTTCTGACAGTACCTTCCTTGTATTCA
TGTCTCATGGTCTCCAGGAGGGAATATGTGGGATCACATACTCTA
ATGAAGTTGCAGATATTTTAAAGGTTGACACAATCTTTCAAATGAT
GAACACATTGAAGTGCCCAAGCTTGAAAGACAAGCCCAAGGTTAT
CATTATTCAGGCATGCCGTGGAGAGAAACAAGGAGTGGTGTTGT
Caspase 1 U14647 T~GATTCAGTAGGAAACTCCGAAGAGGGATTCTTAP,CAGATGSEQ ID
NO:
CAATTTTTGAAGATGATGGCATTAAGAAGGCCCATATAGAGAAAG450
ATTTTATTGCTTTCTGCTCTTCAACACCAGATAATGTGTCCTGGAG
ACATCCTGTCCGGGGATCTCTCTTCATTGAGTCACTCATCAAACA
CATGAAAGAATATGCCTGGTCTTGTGACTTGGAGGACATTTTCAG
AAAGGTTCGATTTTCTTTCGAACAACCACTGCAGGGCCAANGGC
GAATTCCACACACTGGCGGCCGGTACTAGTGGATCCGACTCGGT
CCAACTTGATGCATAGCTTGAGTATTCTATAGTGCCCTAAATAGC
TTGCGTAATC
217
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GCCTCTTGACCGTGATGTTGATGAAGTAAGTCTTCTGTACCTCCT
TAGGATGGCATCATGTTGGTCCTTGTGCTTACTGCAGGTTGTAAT
GGCACGTTTCACTTGCTCCCTCCAAAGCTGAAGGCTCCAAGAGA
GCAGGACTGTACTCCTTAGTTATTGGCTATTCAGTACGGCACTTA
CTAGGTCTTCAATGAATGTTTCCTGAGTAAAGGAAGGAGACAAGC
Caspase 2 077933 AGCTAACTTTAGTTAGAGCCTATCTTTTGCGATTTCTAAATTGCTASEQ ID
NO:
TTATAGTACTCAGTTTAATTAGTATTTGTACTCTTGTGGGGGTTTT457
TTTCCAGGTGTTTTATTTTTATCCACTGTTTTGTTGTTTTTTTACAT
TGTTTGAAGATGTATCACGTGTGAGACAACTTCTTTCACATCTCCA
TGGTGCCCCGCAAATTTGAGGCCTATGGTAGTTGAGGTGCTCAA
TTAATGTTTGTCGTATGAACCAGGTGGTTTGAAGACTTGCTGCCA
AATTCTGCCTTT
TTGGCGAATTGGGCCCTGTAGATGCATGCTCGAGCGGCCGCCAG
TGTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGGCC
CTGAAATACGAAGTCAGGAATAAAAATGACCTTACTCGTGAAGAA
ATTATGGAATTGATGGATAGTGTTTCTAAGGAAGATCACAGCAAA
AGGAGCAGTTTTGTGTGTGTGATTCTAAGTCATGGAGATGAAGGA
GTAATTTTTGGAACGAACGGACCTGTGGACCTGAAAAAACTAACT
AGTTTCTTCAGAGGCGACTACTGCCGGAGTCTGACTGGAAAGCC
SEOID NO:
Caspase 3 084410 GAAACTCTTCATCATTCAGGCCTGCCGAGGTACAGAGCTGGACT
452
GCGGTATTGAGACAGACAGTGGAACTGACGATGATATGGCATAC
CAGAAGATACCAGTGGAGGCGGACTTCCTGTATGCTTACTCTACC
GCACCCGGTTACTATTCCTGGAGGAATTCAAGGGACGGGTCATG
GTTCATCCAGTCACTTTGCGCCATGCTGAAACTGTACGCGCACAA
GCTGGAATTCATGCACATCCTCACTCGTGTTAACCGGAAGGTGG
CCATGGAATTTAAGCTTGGCCAAGGGCGAATTCCAGCACACTGC
GGCCGTTACTAGTGGATCCGACTCGGTCCAACT
TTGGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCATGCCG
ATTGCTTCCTGTGTCTTCCTGAGCCACGGGGAAGGCAACCACAT
TTACGCATACGATGCCAAAATTGAAATTCAGACCTTGACTGGCTT
GTTCAAAGGAGACAAGTGTCAGAGCCTGGTTGGAAAACCCAAGA
TATTCATCATCCAGGCCTGTCGGGGCAGCCAGCATGACGTGCCC
GTGGTTCCTCTGGACGTGGTGGATCATCAGACAGACAAGCTGGA
Caspase 6 AF025670 CGACAACGTGACCCAGGTGGATGCTGCCTCGGTGTACACTCTGCSEQ ID
NO:
CTGCGGGGGCGGACTTCCTCATGTGTTACTCTGTTGCAGAAGGG453
TATTACTCTCACCGAGAGACTGTGAACGGCTCCTGGTACATTCAG
GATTTGTGCGAGATGCTGGCCAGGCACGGCAGTTCCCTGGAGTT
CACCGAGCTGCTCACGCTGGTGAACAGGAAGGTCTCTCAGCGCC
GTGTGGATTTCTGCAAAGACCCAGGTGCAATTGGCAAGAAGCAA
GCTTGGCCAAGGGCGAATTCCAGCACACTGDCGGCCGTTACTAG
TGGATCCGAGCTCGGTACCAACTTGATGCATACTTGAGTATTCTA
TAGTGTCACCTAAATAGCTTGCGTAATCATGN
TTGGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAG
TGTGATGGATATCTGCAGAATTCGCCCTTCGCGGAATTCGATGCA
GGATCTGCTTAGACGAGCCTCTGAAGAGGACCACAGCAACTCAG
CCTGCTTCGCCTGCGTCCTGCTGAGCCACGGAGAAGAGAATCTG
ATTTATGGGAAAGACGGCGTGACACCGATAAAGGATCTGACAGC
TCATTTTAGGGGAGACCGATGCAAAACCCTGCTAGAGAAACCCA
AGCTCTTCTTCATCCAGGCGTGCCGAGGGACGGAGCTGGATGAC
Caspase 7 AF072124 GGGATCCAGGCTGACTCGGGGCCTATCAACGACACCGACGCTAASEQ ID
NO:
TCCCCGCTACAAGATCCCGGTGGAAGCTGACTTTCTCTTTGCTTA454
CTCCACGGTTCCAGGCTATTATTCGTGGAGGAACCCAGGAAAGG
ACTCCTGGTTTGTGCAGGCCCTCTGCTCCATCCTGAATGAGCAT
GGCAAGGACCTGGAGATCATGCAGATCCTGACCAGGGTGAACGA
CAGGGTGGCCAGACACTTCGAGTCCCAGTCTGATGACCCCCGCT
TCAATGAGAAGAAAAGCTTGGCCAAGGGCGAATTCCAGCACACT
GCGGGCGNTACTAGTGGATCCGAGCTCGGTACCAACTTGATGCA
TAACTTGAGTAl-fCTATAGTGNCACCT
218
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGTGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTATCGCGCCGACGAGATG
GCACACTTTGACAGAGAGCGGATTCCTGAGAGAGTGGTACATGC
AAAGGGAGCAGGTGCTTTTGGATACTTTGAGGTCACCCACGATAT
TACCAGATACTCCAAGGCAAAGGTGTTTGAGCATATTGGGAAGA
GGACTCCTATTGCCGTCCGATTCTCCACAGTCGCTGGAGAGTCA
GGCTCAGCTGACACAGTTCGTGACCCTCGTGGGTTTGCAGTGAA
SEOID NO:
Catalase M11670 ATTCTACACTGAAGATGGTAACTGGGACCTTGTGGGAAACAACAC
455
CCCTATTTTCTTCATCAGGGATGCCATGTTGTTTCCATCCTTTATC
CATAGCCAGAAGAGAAACCCACAAACTCACCTGAAGGACCCTGA
CATGGTCTGGGACTTCTGGAGTCTTTGTCCAGAGTCTCTCCATCA
GGTTACTTTCTTGTTCAGCGACCGAGGGATTCCAGATGGACATC
GGCACATGAATGGCTATGGCTCACACACCTTCAAGCTGGTTAATG
CGAATGGAGAGGCAGTGTACTGCAAGTTCCATTACAAAGACTGA
CCAGGGCATCAAAAACTTGCCTGTTGAANAGCANGGAAGACT
AGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTCGCGGGATCCGACCCTTTCTA
TGCTCCTGGGGCTTGTCCTCGGGGGCTGTGGTTCCAGACTGTCA
TACACTGGCACATTTTAAAGGTAGTGAGCCCACTATGCAAAATCA
CTTCAATAACCCTGAAAAGCACCTATGGATGAAGGGCTGAATTGA
GGCCAAAGGTACAATAGATCACAGCCTGCCCAGCATGCAAGAGG
CCTCAAGGTTAATCCTCTACACCCGAGCCTCATGGTCTCGCTAAC
Catechol-O- M60753 TAGAAGAGGAGATCTTCACGGGGTTTCAGTGTGGGATCCCTAGGSEQ ID
NO:
methyltransferase CACTGCATCACCAGTTAGGCCCAGCAGGAAGTCAGCAAACTGTA456
AATGTCCAGACGCCAAATAACAGCAGAGGCTCAGAGACAGTACT
GTCACTCGCTGTCCCCAGCAGCTCACACCACATCTCATCTGAAG
AATGAGTCACAAGCTTTCCAGGTATGGTGGTGCACGCCTGTCAT
CCCCAGTATCCAGGAGGCAGAGGCATCGGAGTTCAGCTGCAGG
GCCAAGGGCGAATTCCACACACTGGCGGCCGTTACTAGTGGATC
CCAGCTCGGTACCAACTTTGATGCATAGCTTGAGTATTCTATANT
GTCACCTAAATAC
NNAGGGATACCAATTTCACACAGGAACCAGCTATGNCCATGATTA
CGCCAAGCTATTTAGGTGNCACTATAGAATACTCAAGCTATGCAT
CAAGTTGGTACCGAGCTCGGATCCACTAGTAACGGCCGCCAGTG
TGCTGGAATTCGCCCTTTGCAGGCAGGGAGTGAGGCAGATAGGA
GTCTTTGATTCTTTGAGTTCACCTAACATGCATGAAGCTTTCAGCA
AGGTTTGGGTGACTGGACCAGAGCTGCCCCCCATCAGAGCCACC
CTACCTGGCTCCCTTCTAGCCTATCCCATGACAGTGATCACAGCC
Cathepsin X82396 TACATCCTAGCCTCTCCCTAGACTAGTGCTGTGTGTAGCGCCTGCSEO ID
B NO:
TGCTGTGGCTCTGTCTGCCATCCCTCCCACCCCCACCTCAGCAT457
CCCCAGACCAAGGGCTTTGGCTGCAGGATTTCCAAAGGAATGAA
CACCAACTACATGATGAGAGGACAGATGCCACCCGCCAGCTGCA
CCTTGAAGCTAGTCACTTCTAGGACTGTGGCAGGCTTTGATGGC
CCAATGCAGTTCTCTGGAGAAAACTACCTTTCCCCAAGGCATCTG
CACCCATTGACAATGGTAATGTGCCCATCTCTCCTTGGTCCTGCC
CAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCG
AGCATGCATCTAGAGGGCCCAATTCGC
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCGATCTAGG
CAATCAGGGCTGTAATGGAGGCCTGATGGATTTTGCTTTCCAGTA
CATTAAGGAAAATGGAGGTCTGGACTCAGAGGAGTCTTATCCCTA
TGAAGCAAAGGATGGATCTTGTAAATACAGAGCTGAGTATGCTGT
GGCTAACGACACAGGGTTTGTGGATATCCCTCAGCAAGAGAAAG
CCCTCATGAAGGCTGTAGCGACGGTGAGGCCTATTTCTGTTGCC
Cathepsin Y00697 ATGGATGCAAGCCATCCGTCTCTCCAGTTCTATAGTTCAGGTATCSEQ ID
L NO:
TACTATGAACCCAACTGTAGCAGCAAGGACCTCGACCATGGGGT458
TCTGGTGGTTGGCTATGGTTATGAAGGAACAGATTCAAATAAGGA
TAAATACTGGCTTGTCAAAAACAGCTGGGGTAAAGAATGGGGTAT
GGATGGCTACATCAAAATAGCCAAAGACCGGAACAACCACTGCG
GACTTGCCACCGCAGCCAGCTATCCTATCGTGAATTGATGGACA
GCGATAAAGCTTGGCCAAAAGGGCGAATTCCAGCACACTGGCGG
NCGTTACTAGTGGATCCGAGCTCGGTCCAAGCTTGATGCATAGC
TTGAGTATTCTATAGTG
219
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GAATGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTGGTACATTGAGCTCCCCTTCGG
CGATGAAGAAGCTCTGAAAGAAGCAGTGGCCACTAAAGGGCCTG
TCTCTGTGTGCATCGACGCCAGCCATTCCTCCTTCTTCCTCTACC
AAAGTGGTGTCTATGATGACCCCTCCTGTACCGAGAATGTGAATC
ATGGTGTTCTCGTGGTTGGCTATGGGACTCTTGATGGGAAAGAC
TACTGGCTTGTGAAAAACAGTTGGGGCCTTCACTTTGGTGATCAA
GGATATATTCGGATGGCGAGAAATAACAAAAATCACTGCGGGATT5E0 ID
NO:
Cathepsin L03201 GCTAGCTATTGCTCTTACCCAGAAATCTAAACCGTTTCTTCTTTTT459
S
CTAATGGGTCACAAAGACGGAATACACTCTAATTTAATTTTGTCTG
CTCCATCCGGAGGACCCAAGTGTGTCGTGATCAGTGTGTACATA
CTGTGCTAACTGGCTTACAGCTTGTTTGTTTTATAACCTTACCTCT
' CTCTGAAAAGTCTGTAAGCAAGGACGCGCTGAGGAAGGGCGAAT
TCCAGCACACTGGCGGGCGTTACTAGTGGATCCGAGCTCGGACC
AAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCCCTAAATAGCT
TGGCGTAATCATGGNCATAGCTGGTTCCTGTGTGAAAT
GACCGAGCTCGGGATCCACCTAGAACCGNCCCGGCCAGTGGCT
GGAATTCGCCCTTCGGTCCACAGGAGACCAGGAAGTTTCTACTG
GTTTATGAACTAGGTTGAGTTTTGTGTATCACTTAGTTTTTTATGTA
GCTTGAGGGTAGAGATGGTTCTT-t'TAGAAAAGAAATTAATATAGA
GGGCCTAAGGTACGTGCATTGTTTT'AATATTTATTTGAGATAGATT
GGGTCTTTGAAAGCTGAGTAGTTTTATAAACGTGAATGAGAATGT
ATTGATGAGACAGTAATTTCTGGCTTCATTCCTATTTAACTACAATSEOID NO:
CCR-5 077350 TATTCCCAAACTCTTCT1'fAGCCACAAAAGTTCACTATTAAAAAAT460
ACTGAGCATTGGGATTTT'i-fTTTAGAGCTCGAGTATCTGACCAAA
AATAACATCATTTTTTCCCTATATAAAGCAAAATTCAGGCTACTTA
AATCAGGTCTTTGTCTTGCCCTGAGAAGAAAGGATGAGACCATGA
CTAGTTAGGGAATAGATAACCAAGCTATATGAATTGCT1-1'ATAGAC
TTGTATGATCAGTAAGTGCTCTGTGGCCTGAGAAGGAAGGGCGA
ATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCAT
CTAGAGGGCCCAATTCGC
TGNGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCGGTGCA
TTTGGTGAACAAGGAACCAACAGAGACTCCGGACCAGTTTATGA
CAGCTGATGAGACCCGGAATCTGCAGAGTGTGGATATGAAGATT
GGGGTGTAGTGCCTATGCCACTAACTTGAAAAGACACAACAATTG
GAGACATGTCATTACTGGGAGCTGGGACCCTTAACAGATGCAAT
GTGCTACTGATTATT'fT>-ATTGGGGATTATTTTGGGCATAAAATTT
CD44 metastasis CCCTTTTTTTTGT'ITfTTAAAAGTTTGTTTTCCAATTTATGAAAATASEQ ID
NO:
suppressor M61875 GCATTGCTTTCTGAAATGAGGGTCTCTTCCAGTTCCTCCTTAGAG461
gene
GCCTTGCATTACCAGGGTATGCTACCATAGGCTTCTACCAAATGA
ATACTCTTGGTCCCGATTGAACCCAAAGTCCCAGGTAACATCCAC
CAGCTAAGGATTTCCCCAGAACTTAGAGAGATTGGTCTCTGGGA
GGAAATTTGAATGGGTCCATATTGCCTCCCAGCAGTCCAATCTGT
AAGCTTGGCCAAAGGGCGAATTCCACACACTGGCGGGCGTACTA
GTGGATCCGAGCTCGGACCAAACTTGATGCATAACT1-1'GAGTATT
CT
GCTATGCCATGATTACGCCAAGCTATTTAGGTGNCCTATAGAATA
CTCAAGCTATGCATCAAGCTTGGTCCGAGCTCGGATCCACTAGTA
ACGGCCGCCAGTGTGCTGGAATTCGCCCTTATCGCGGATCCCCC
AGGCCAGTGAGCTTTACTTGCAGTGTAAAAGGAGGAAAGGGGTG
GAAAAAAAACCGAATTTCTGCATTTAACTACAAAAAAAAGTTTATG
TTTAGTTTGGTAGAGGTGTTATGTATAATGCTTTGTTAAAGAACCC
CCTTTCCGTGCCACTGGTGAATAGGGATTAATGAATGGGAAGAG
Cellular nucleic ~CAGTCAGACCAGTAAGCCCTTCTGGGTTTGAGTGTGTTCCCATSEQ ID
acid NO:
binding proteinD45254 GTAGGAGGTAAAACCAATTCTGGATGCATCTAAGCTTCCATGAAT462
(CNBP) AACTTTAATTCTTAGCATAATGATGGCCTTGGA1-fGTCTGACCTCA
GTAGCTATTAAATAACATCGAGTAACATCTGCATCAGGCCCTCAT
AGAACATTCAGTTGAGTTGGGAGTAAACTGAAAAGACAAATGTGT
TGAAGGATATGCCAGGGAATCTGGCTAAAGCCTAATACAGGAGC
ATCTTCATCCCAGTGTTGATGCTGGACGTACCTCAAGGGCGAATT
CTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTA
GAGGGCCCAATTCGC
220
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTAGCCTCCAAGCCAGCAGT
GGAGGTCAAACAGGAGAATGATGACACTTTCTACATCAAAACCTC
CACCACTGTTCGAACCACGGAGATTAACTTCAAGATCGGGGAGG
AATTTGAGGAGCAGACTGTGGATGGGAGACCCTGTAAGAGTTTG
GTGAAATGGGAGAGTGAAAACAAAATGGTGTGCGAACAGAGGCT
TCTGAAGGGGGAGGGCCCCAAAACCTCCTGGAGCCGAGAACTG
Cellular retinoic ACCAATGATGGAGAGCTAATCCTGACCATGACAGCAGACGACGTSEQ ID
NO:
acid
binding proteinX23407 TGTATGCACCAGGGTCTACGTCCGAGAGTGAGTGCCTATGTCCA463
2
AGAACTTCTTCTGGAGGCCACAAACCTCCCTCCCATGTCCATTTT
ACAAACTAGCTCTCCCCTTACTCCTGAGGGTCACTCTCTATGCCA
GAGAGGGGCAGACTACCAAAGCTCAGAACCCTTCCATTTGCCTG
GTCAGAAGTCCCAGCTCCAAAGGGCGAATTCCAGCACACTGGCG
GCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATA
GCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCAT
GGTCATAGCTGTTTCCTGTGTGAAATTGGTATNCCG
AAACAGCTATGCCAATGATTACGCCAAGNTATTTAGGTGCACTAT
AGAATACTCAAGTATGCATCAAGCTTGGACCGAGCTCGGATCCA
CTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTCCCAGCCC
GAGTATGTGAACCAATCAGAGGTTCAGCCTCAGCCTCCTTTAACC
CCAGAGGGTCCTCTGCCTCCTGTCCGGCCTGCTGGTGCTACTCT
AGAAAGACCCAGGACTCTCTCTCCTGGGAAGAATGGGGTTGTCA
AAGACGTTTTTGCCTTCGGGGGTGCTGTGGAGAACCCTGAATAC
TTAGTACCGAGAGAAGGCACTGCCTCTCCGCCCCACCCTTCTCCSEQ ID NO:
c-erb B-2 X03362 TGCCTTCAGCCCAGCCTTTGACAACCTCTATTACTGGGACCAGAA464
CTCATCGGAGCAGGGGCCTCCACCAAGTAACTTTGAAGGGACCC
CCACTGCAGAGAACCCTGAGTACCTAGGCCTGGATGTACCTGTA
TGAGACGTGTGCAGACGTCTTGTGCTTTCAGAGTGGGGAAGGCC
TGACTTGTGGTCTCCATCGCCACAAAGCAGGGAGAGGGTCCTCT
GGCCACATTACATCCAGGGCAGACGGCTCTACCAGGAACCTGCC
AAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGA
GCATGCATCTAGAGGGCCCAATTCCA
GANAACCGTTCGTATAAANCCNTGCTCGANTCGGCCGGCAGNGT
GATGGATCTNNGCAGANTTCGCCCTTATNGNGGGANCCCAACCG
AGGATCNAGTCAACNGATCTNTATNTTGGGCTAGGGAGGCCCAT
TGATTGATCNTTGGAAATCTNANGTGNAAGTTTTCANTCCTAAANSEO ID NO:
CeruloplasminL33869 NGAANATGNATTTCTCCCTTCTGTTNCTANNACCTTGNTTACAAN465
GNTTCCTTGNCACTCTNNATGAGTANCGNCAGTNCNTACATTTGG
ANCNCNGCTGGNNNANAGNTTTCCTCTCACAACNATGGNACNCA
TANANNGGNGANTAAACCGCACC
TCCAGGGAAAGGATATAGGCAAAATTCGCNCTTATCGCGGGATC
CGNGTTTCTACGCNNATAAACGAGGGGTCATTCCTTCTNTTCCAA
GTAGNGCNTCNCTGNCGGGNGGCAANCNTTTCCTNCTTAGNATT
CCCCAAGATGACNTCCTTTCTCNAGCATGGGNTTCNCCNGTCTC
NCCCACAGGATTTTTGGCGCAGATCTGCNGGTNTCTAGTGCCAT
TTTTATCNNATTGGTGCANCTATTTCTANCAGCCAANACTGCAGT
GGCTGGNGCNGCNCACTCTGGTCTCNNCNGTGGCCCCATCGCASEOID NO:
c-fos X06769 GACNAGAGCGCCCCATCCTTCGGNCNTCCCCACCCCGTCGCCG466
GGNGCTTAGNCCATANNGNNAGTGGTGAANNCNATGTCAGGCAG
CAGAGCNCANAGCATCGGCAGAAGGGGCAAAGTAGAGCAGCTA
TNTCCTGAAGAGGAAGANNNTCGCAGNATCCNNAGGGAAAGNAA
TAAGATGGCTGCAGTCTAGTGCCGAAATCGGAGNAGGANANTGA
CAGATACGCTCCAANNGGAGNCNGATCNNCTNTNNTAGTAGAAG
TGTGNGTTGCAGACCGNGATTGCCNATCTNCAGAAAGAGAAGGA
AAATTGAGTTTTNTNNCAGCCTCNACCTCTT
221
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GAAATTGNGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTCATAGCTGGGGCCAGAGCT
TCATCACTTTCAGAAAGCAATGTCCTTTGTATTTATTTTCAAAATG
AAGATATTCCAATTGGCAGGATATTTTTCCTAAGGAAATTGCTTTA
TATTTTTATGAAAACTACCAATTAATTATGAAAGGGCTTGAAATTC
ACGTTTTAGTGAAATTACTGATTTTTCACTAGTAAGGTTCTTCAGG
Cholesterol TGTGAAACTGTATTATAAAAATGTTGTAATGGGTCACACTGTGCTT
7-alpha-
hydroxylase J05509 TGCATAAAGGTAAAGGAAACTATGTTTCAGCCTTTTCTGTGTCTATSEQ ID
(P450 NO:
VII) GAGCTTCGAAAATAATCTTACTGTTCTAGAAACACTGGGGAGGCT467
TCGACATGCTCTCGCTATATTTTATTTTACTGGTGCTAGAAATTTT
CATTTCAGTTTTCAACTACCTTATCTTTCCCCCATTTTGACATGCA
TGCCAATGAGAAGAGTATTTTTTAGGAATTAACAAGGCACCTCCC
AGAACCCTACCCTGAGACTAAGGGCGAATTCCAGCACACTGGCG
GCCGTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAG
CTTGAGTATTCTATAGTGTCCCTAAATAGCTTGGCGTAATCATGG
GCATAGCTGNTTCCTGTGTGAAATTGNTATCCGCTCAC
AATACTCAAGCTATGCATCAAGCTTGGTCCGAGTTCGGATCCACT
AGAACGGCCGCCAGTGTGTNGAATTCGCCCCTTCGCGGGATCTT
GGAAGTCCTACCCAACACTGAAAATCTCTGAGAAAATGATTCCAG
TGGTTGCTGAGAAGTACTTCGGAGGGACAGATGACCCTGCCAAA
AGGAAAGACCTGTTCGAGGACTTGGTTGCAGATGTGATATTTGGT
GTCCCATCAGTGATGGTGTCTCGAAGCCACAGAGATGCTGGAGC
CCCCACCTTCATGTATGAATTTGAGTATCGCCCAAGCTTTGTATC
Cholesterol L_46791 AGCCATGAGGCCCAAGACAGTGATCGGAGACCATGGTGATGAACSEQ ID
esterase NO:
TCTTCTCAGTATTTGGATCTCCATTTTTAAAAGATGGTGCCTCAGA468
' AGAGGAGACCAATCTCAGCAAAATGGTGATGAAATACTC~GGCCA
ACTTTGCTCGGAATGGGAGCCCTAATGGGGGAGGGCTGCCCCAT
TGGCCAGAATATGACCAGAAGGAAGGGTACCTGAAGATTGGTGC
CTCAACTCAGGCAGCCCAGAGGCTGAAGGACAAAGAAGTGGCTT
TTTGGTCTGAGCTCACTGCAGGGCCAAGGGCGAATTCTGCAGAT
ATCCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCC
AATTCT
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCTCGAGCTTGAGAACCTGA
GGTCATTGCTGCAGTATACTAGATCCCCAGTTGTGTTTTGTCATA
ATGACTGTCAAGAAGGTAATATCTTATTGTTGGAAGGCCAAGAGA
ATTCTGAAAAGCAGAAGTTGATGCTCATTGACTTTGAATACAGCA
GTTACAATTACAGGGGATTTGACATTGGAAATCATTTCTGTGAAT
GGATGTATGATTATACCTATGAAAAGTATCCTTTCTTCAGAGCAAA
Choline kinaseD10262 CATTCAGAAGTATCCTACCCGAAAACAACAGCTCCATTTTATTTGASEQ !D
NO:
AGTTACTTGACTACATTCCAAAATGATTTTGAAAGCCTCAGCAGT469
GAAGAGCAGTCTGCTACAAAAGAAGACATGTTGCTTGAAGTCAAC
AGATTTGCCCTTGCCTCTCATTTCCTCTGGGGACTTTGGTCCATT
GTACAGGCCAAGATCTCATCCATTGAATTTGGGTACATGGAATAT
GCCCAAGCCAGGTTCGATGCCTACTTTGACAAGGGCGAATTCCA
GCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAG
CTTGATGCATAGCTTGAGTATTCTATAGGNCACCTAAATAGCTTG
GCGTAATCATGGNCATAGCTGN
CCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATGGATATCT
GCAGAATTCGCCCTTATCCAGCTGATCCAGAACCATTTTGTGGAC
GAGTATGATCCCACTATAGAGGACTCCTACCGGAAACAGGTAGT
CATTGATGGGGAGACGTGTTTACTGGACATCTTAGACACAGCAG
GTCAAGAAGAGTATAGTGCCATGCGGGACCAGTACATGCGCACA
GGGGAGGGCTTCCTCTGTGTATTTGCCATCAACAACACCAAGTC
CTTTGAAGACATCCATCAGTACAGGGAGCAGATCAAGCGGGTGA
c-N-ras M13011 ~GATTCAGATGATGTGCCAATGGTGCTGGTGGGCAACAAGTGT5EQ ID
NO:
GACCTGGCCGCTCGCACTGTTGAGTCTCGGCAGGCCCAGGACC470
TTGCCCGCAGCTATGGCATCCCCTACATTGAAACATCAGCCAAGA
CCCGGCAGGGTGTGGAGGATGCCTTCTACACACTAGTACGTGAG
ATTCGGCAGCATAAACTGCGGAAACTGAACCCGCCTGATGAGAG
TGGCCCTGGCTGCATGAGCTGCAAGTGTGTGCTGTAAGGGCGAA
TTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTA
CCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCACCTAAATA
GCTTGGCGT
222
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTACTCAGTGGATGGTGTACCAGT
GGCAAGCACTGATCGTTGGAGTGAGATGACTGAGGCAGAGCGA
CTCCAAGAGAACCTCCAGGCTTACCGTACCTTCCGAGGGATGTT
AACCAAGCTCTTAGAAGACCAGAGAGTACATTTCACCCCAACTGA
AGGTGACTTCCATCAGGCAATACATACTCTTATGCTCCAAGTTTC
TGCCTTTGCCTACCAGCTAGAGGAGTTAATGGTGCTTCTGGAACA
Ciliary neurotrophic GAAGATCCCTGAAAATGAGGCTGATGGGATGCCTGCCACAGTTG
SEQ ID NO:
factor X17457 GAGATGGTGGTCTCTTTGAGGAGAAGCTATGGGGCTTGAAGGTC
471
CTTCAAGAGCTCTCACAGTGGACTGTGAGGTCTATCCATGACCTT
CGTGTCATTTCTTCTCATCAGATGGGAATCTCAGCACTTGAGAGC
CATTATGGGGCCAAAGATAAGCAGATGTAGCCAAGGGCGAAT1'C
CAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTCCAA
GCTTGATGCATAGCTTGAGTATTCTATAAGTGCACCTAAATAGCTT
GGCGGTAATCATGGCATAGCTGTTTCCTGTGTGAAATTGGTATTC
CGCTCACAATTNCACACAACATACGAGCCCGGAAGCATAAAAGT
GG
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTCGTTCC
TCCAGTCCGAGAGTGGCGCCTACGGCTACAGTAACCCTAAGATT
CTGAAGCAGAGCATGACCTTGACCCTGGCCGACCCGGTGGGCA
ATCTGAAGCCGCACCTCCGAGCCAAGAACTCGGACCTTCTCACG
TCGCCCGACGTCGGGCTGCTCAAGCTGGCGTCGCCGGAGCTGG
AGCGCCTGATCATCCAGTCCAGCAATGGGCACATCACCACTACA
c-jun X17163 CCGACCCCCACTCAGTTCTTGTGCCCCAAGAACGTGACCGACGASEQ ID NO:
GCAGGAGGGCTTCGCCGAAGGCTTCGTGCGCGCCCTAGCTGAA472
CTGCATAGCCAGAATACGCTGCCCAGTGTCACCTCCGCGGCACA
ACCTGTCAGTGGGGCGGGCATGGTCGCTCCCGCTGTGGCCTCA
GTAGCTGGCGCTGGCGGCGGCGGCGGCTACAGCGCCAGCCTG
CACAGTGAGCCTCCGGTGTACGCCAACCTCAGCAAAGCTTGGCC
AAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCG
AGCTCGGTACCAAACTTGATGCATAGCTTGAGTATTCTATAGTGT
CACCTAA
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTCGCGGGATCCACCAGGCTCA
ACAGGCCATGGACGTCCAGCTCCATAGCCCAGCTTTACAGTTCC
CGGATGTGGATi'TCTfAAAAGAAGGTGAAGATGACCGCACAGTG
TGCAAGGAGATCCGCCATAACTCCACAGGATGCCTGAAGATGAA
GGGCCAGTGTGAGAAGTGCCAAGAGATCTTGTCTGTGGACTGTT
CGACCAACAATCCTGCCCAGGCTAACCTGCGCCAGGAGCTAAAC
Clusterin M64723 GACTCGCTCCAGGTGGCTGAGAGGCTGACCCAGCAGTACAACGSEQ ID NO:
AGCTGCTTCATTCCCTCCAGTCCAAGATGCTCAACACCTCATCCC473
TGCTGGAACAGCTGAACGACCAGTTCAGCTGGGTGTCCCAGCTG
GCTAACCTCACACAGGGCGATGACCAGTACCTTCGGGTCTCCAC
AGTGACAACCCATTCTTCTGACTCAGAAGTCCCCTCTCGTGTCAC
TGAGGTGGTGGTGAAGCTGTT-T'GACTCTGACCCATCACAGTGGT
GAAGCTTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGGT
ACTAGTGGATCCGACTCGGTACCAAGCTTGATGCATAGCTTGAGT
ATTCTATATGTC
NTNCNNANGNGCCCTNTANATGCTGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGGAGAAG
AGGCAAACCCCTGCCAAGAGGTCCGAGTCAGGGTCATCCCCATC
AAGAGGCCACAGCAAACCTCCACACAGCCCACTGGTCCTCAAGA
GGTGCCATGTCTCTACTCACCAGCACAATTATGCAGCACCCCCCT
CCACAAGGAAGGACTATCCGGCTGCCAGGAGGGCCAAGTTGGA
CAGTGGCAGGGTCCTGAAACAGATCAGCAACAACCGCAAATGCT
c-myc X01023 CCAGCCCCAGGTCCTCAGACACCGAGGAAAACGACAAGAGGCGSEO fD NO:
GACACACAACGTCTTGGAACGTCAGAGGAGAAACGAGCTGAAGC474
GTAGCTT'~fll'GCCCTGCGCGACCAGATCCCTGAGTTGGAAAACA
ACGAAAAGGCCCCCAAGGTAGTTATCCTCAAAAAAGCCACCGCC
TACATCCTGTCCGTTCAAGCAGATGAGCACAAACTCATCTCAGAA
AAGGACTTACTGAGGAAACGACGAGAACAGTTGAAACACAAAAG
CTTGGCCAAGGGCGAATTCCAGCACACTGGCGGGCCGGTACTA
GTGGATCCGAGCTCGGTCCAAACTTGATGCATTAGCTTGAGTATT
CTATAGTGTCACCTAAATAGCTTGGGGTA
223
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGCGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCGGAGCA
GCAAGAGCAAGGAGAAGAAGCACATCTGGTTTGGAGAGACCATG
AACGGCGGCTTCCACTTCAGCTACGGCGACGGCAACCTGGCTCC
CAACACCGCTAACGTCCAGATGACTTTCCTCCGTCTACTGTCCAC
TGAGGGCTCCCAGAACATCACCTACCACTGTAAGAACAGCATTG
CCTACCTGGACGAAGCAGCCGGCAACCTCAAGAAGGCCTTGCTC
Collagen TypeL48440 ATCCAGGGCTCCAATGATGTGGAGATGAGGGCCGAGGGCAACASEQ ID NO:
II
GCAGGTTCACGTACACTGCCCTGAAGGATGGCTGCACGAAACAC475
ACCGGTAAGTGGGGCAAGACCATCATCGAGTACCGATCACAGAA
GACCTCACGCCTTCCCATTGTTGACATTGCACCCATGGACATCG
GAGGGCCTGATCAGGAATTTGGTGTGGACATAGGGCCTGTCTGT
TTCTTGTAAAACCCTGAACCCCAAAACAACAAAGCTTGGCCAAAG
GGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGC
TCGGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCAC
CTAAATAGCTTGGCGTAAT
TAGATGCATGCTCGAGCGGCCGCCAGTGTGATGGATATCTGCAG
AATTCGCCCTTATCGCGGAATTCGTCTGTGGTGACCTGGGCATG
GGTGACAGGGCTCTTACTTGCTCCTTGGTCTCTTTATGCTGCTGC
CCCGCCTCCCCCCTTTCCTGCCCTCCCTGGCTACTGGGTCGCTA
ATCTTTCAGGCCATGGATCCGGAGGAGAGTGGTCTATAGGCTCC
ACCAGCCCTGTCCTGAGACAACAGAGGGGGTGAGGACACTGGA
GACTTTCCCGTGGGGCTTACTTAGCCTTCTAGTTACAGACTATTT
Colony-stimulatingMg4361 CCACACTAGAAAATACGTATTTTTAAATAGAAGAAAAACACAGAAASEQ
ID NO:
factor-1 CAAACAAAAGGCATTCTCCTACCCCTCCATCTTAAACATACATTAT476
TAAAGACAGAAGAACAAATCCAACCCATTGCAAGAGGCTCTTTGT
GGGTGCCTGGTTGCATAAGAACAGGAGGAGCCCCAAACCCACCT
TTGGAGCTTCCCTGCACAGGAACCCCTTCTTCCCTCCAAGAAAG
CTCAGAGGGAGCACTGCCAAGCTTGGCCAAGGGCGAATTCCAG
CACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAAC
TTGATGCATACTTGAGTATTCTATAGTGNCACCTAAATAGCTTGG
CGTAATCATGGCAT
AATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATG
GATATCTGCAGAATTCGCCCTTATCGCGGGATCCGGACTTATCCA
GCCGGGGTCGGTCAAGGTCTACTCCTACTACAATCTAGAGGAGT
CATGCACCCGGTTCTATCATCCGGAGAAGGACGATGGAATGCTG
AGCAAGCTGTGCCACAATGAAATGTGCCGCTGTGCCGAGGAGAA
CTGCTTCATGCATCAGTCACAGGATCAGGTCAGCCTGAATGAAC
GACTAGACAAGGCTTGTGAGCCTGGAGTGGACTACGTGTACAAG
Complement X52477 ACCAAGCTAACGACGATAGAGCTGTCGGATGATTTTGATGAGTACSEO ID NO:'
componentC3 ATCATGACCATCGAGCAGGTCATCAAGTCAGGCTCAGATGAGGT477
GCAGGCAGGTCAGGAACGAAGGTTCATCAGCCACGTCAAGTGCA
GAAACGGCCTAAAGCTGCAGAAAGGGAAGCAGTACCTCATGTGG
GGCCTCTCCTCCGACCTCTGGGGAGAAAAGCCCAATACCAGCTA
TATCATTGGGAAGGACACGTGGGTGGAGCAAGCTTGGCCAAAAG
GGCGAATTCCAGCACACTGGCGGCCGTTCTAGTGGATCCGAGCT
CGGTCCAAGCTTGATGCATACTTGAGTATTCTATATGGCACCTAA
ATAACT
TGCGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCAGGCCTCTGCCTCCTAG
GGATTACTCCATCAAACCTTCCCTCCCTCCCTACTCCCCTTCCTC
AGAGAGTCTTCTGTCAAAGACCTGCCGGCTTGGGAGTGGGGAGC
CACTTCTGCACCAGGGCTCAAGGTTATTGAGGGTGTGGGCAATT
CTTTCTGCCTATACCCTTTCCTCTTCCCTCTCCCTGAGATGAGGG
ATGAGATGTTCTGAAGGTGTTTCCAATTAGGAAACTAATCTTAACC
SEQID NO:
Connexin-32 X04070 CCCATGCTGTCAGGTACCCCACTTTGGGAGTCATGTCAAGTGGG
478
GAGGGCTGTGAGCAAGCAGAGTGGAGGAGGGGCTCTGCACTGT
GGATGGAGAAGGGAGGGGAGCTTGCCTTGCTGCCTGCTACAAG
GAAAANGANGACACATCTANGGTGGGGGAAGTTCTTGGAGGGAG
AAACAGGCAGATAAATCAAAATGGGGGTTGGNCAAGGGCTTGCC
CCCATCCCCCCCCAAANTTTTCCCCCAAAAGGGGGCCCTTNTTTT
TTTTTTTTTTTGGAAAAAAATGGGTNAAAGGGGGCGGAAAATTTC
N
224
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCCAAAGA
AGCCACTGGAAGCCTTCACTGTGTGTCTCTATGCCCACGCTGAT
GTGAGCCGAAGCTTCAGCATCTTCTCTTACGCTACCAAGACGAG
CTTTAACGAGATTCTTCTGTTTTGGACTAGGAGTCAAGGGTTTAG
TATTGCAGTAGGTGGGCCTGAAATACTGTTCAGTGCTTCAGAAAT
TCCTGAGGTACCAACACACATCTGTGCCACCTGGGAGTCTACTASEQID NO:
'
C-reactive M83176 CAGGAG
protein rfGTAGAGCTTTGGCTTGACGGGAAACCCAGGGTGCG
479
GAAAAGTCTGCAGAAGGGCTACATTGTGGGGACAAATGCAAGCA
TCATCTTGGGGCAGGAGCAGGACTCGTATGGCGGTGGCTTTGAC
GCGAATCAGTCTTTGGTGGGAGACATTGGAGATGTGAACATGTG
GGACTTTGTGCTATCTCCAGAACAGATCAATGCAGTCTATGTTGG
TAGGGTATTCAGCCCCAATATTTTGAACTGGCGGGCACTGAAGTA
CTCGAGGGCCAAGGGCGAATTCCAGCACACTGGCGGGGGTACT
AATGGATCCGAGCTCGGACCAAGCTTGATGCATAACTTGA
TATCAGATAGANCGTAACTGNTNNACTGCAGNNGCGTNAANTNC
AATGGCCGANNCGNCCTTNCGNNAGNNGANNGNCTAACNGGNA
AAACNNGTCNNGAANNNANGTCACTCANNATTAANNNANGAAAN
NTNAGNGGNAGCNTNNNGCGCNNTGATNNAGTGAAANTACGNCT
NGNANNCNNNGACAGCNCCGNCNGNACNTNNANATTGNGTNAN
CNNANNGNNGTCNNGCAATNANNTCCGANCCATNNCCNCNNNTT
CAANNNNAGTNNNNANCNNCGNGTGTCANAGAGNTGNNAAANAN
NGNAGNNNGTNGTNGAGAAGTANTNTCTNNGCNGTCCAAACNAA
ANNNATNNNGNNAGNNAGCTNNANTANCCTGCNNGAGANCGGN
CNTCAAGNGNCGGNNCNGGTCTACTCAGTNANNGCCCNCNNCN
NNCNGGNNGNCNANACGAACNl-f'CCAAGNNGNGATGGAATATNN
CXCR4 090610 NCANNGGATTTCNGCCCCTTNNANAGNNTCCATCCATTNTTCGCCSEOID NO:
CAATNTTNACCCAAAGGGGNCGGGCNNANGANNTCTTNTGGCCC480
GNCT1-fTCCCCANNCAGCCTTTTGGATGGTGGTGTTNCAGTTNCN
GGACANCATGGTGGGTTTCATNCTGCCNNGGCATTNGTCATCCT
NTCCTGTTACTGCATCATCATCTTCAAGCTGTCACGNNTGCAAGG
GCCCCCNGGNAGCGCAAGGNCCTCCAAGNCTACGGTCATCCNT
ATCCTGGCTTTCTTTGCCTGCTGGGTACCGTNTTACGTGGGGATC
NGCATCGANTGCTTCATCCTT1?GGAGGTCATCAAGCAAGGATGT
GAGTTNGANAGCGTCGTGCNCNAGTGGATGTTCCATCACGGAGG
NCCTCGCCTTGCTTCCACTGTTGCAGTGAACCCCAGTCCTNCTN
CGNCTTNATCGGGGCCAAATACAATAACTCCGCGCAGCATGCAT
GCATTTCCNAANCAGAGNCACCAGGTTTCAANNCCCTAATTGGN
NNTNNNGGGNNN
GCCCTCTAGATGCATGCTCNAGCGGCCGCCAGNGTGATGGATAT
CTGCAGAATTCGCCCTTCGCGGAATTCCTGCTGGGGACATGCTG
TCATGCTGGGCCTTCATTTGATCTGGGACATAGCATCACAGCAGT
CAGGGCAACTGTGTTCTGTTAGTTATCAATATTGTTACTTGTAGC
GGCCTGTTGTGCATGCCACCATGCTGCTGGACCCGGAGAGATTT
GTTCTGAGTCTCTGGTGCATCATTTAATCTGTTAGGTTCTAGTGTT
CTGTCTTGTTTTGTGTTACTCACAGCATTGTGCTAATGTAAAGCCA
Cyclin D1 D14014 GCCGCAATGCTGTAGGCCCCAGGTTCCCTAGCAAGCTGCCAAACSEQ ID
NO:
CAAAAGGGTCACCACCAGCTTAGCTGAGGCGTCCCAACCAGGCA481.
GGACCCTTGAGGGCTGCTGTGTCCATGGTGATGGGGTGAAGTT'T
TGGCCAAAGGGCCAAAGGCTGGTGGATCCACACAGTCTGCCCTG
TGACATGAATGGCT'T-fGAGGGGCTCTGGCTGGTGGTCAGGTTGG
CTTTTGTGTATTCTGGTTGACACACCATGGCAAGCTTGGCCAAGG
GCGAATTCCAGCACACTGGCGGGCCGNTACTAAGTGGATCCGAA
CTTCGGTACCAAGGTTGATGCATAGCTTTGAGTAI-t'CTATAGTGN
CACCTAAATAGCTTGGCGTAATCATGGCATAACTTGTT
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCCGCCCC
AGTACCTTCCAAAGGTGTTGTTGCCCCTCGCAGGGTCACTGCATT
TGGATCTGGGTCCTTCAGAAATCCCGATAGACGCCTATGAGGAG
CCAACCTAGATGGCTGCTGTGTAATCCCTACTCCAGCTGCTCTTA
GCGGGAACAGCCTAGGCCTTGGCTAGAAGAGCAAGCGCCCGTA
AACTGi'TGCTTTGCTTCCTGCTATGCTTCTGTGGTTGAGGGTCTTSEQID NO:
Cyclin D3 D16309 GAGGGTGCTGATGGTCATTTTAATTTATTGCTTTGAATACAACCGT
482
AAGAGGGTACAGTGAGGCCTGTACCCCACAAGTGGTGGTAACCC
TGGCGGTTGCTCTTTCCCTCCCCTCTGCTACCGCTTTGTGGCCCA
GGAGCGGCTACAGCCTGGGAGGGGGTCCTGCCTTCCTCTCCGT
AGCCCTCCAGCTCATCTTCAGCGGGGAGGGTTTAATAGGGATGG
ATGCCCGTGGAGGTGACTGGACTATCCGGAGAGAGGGCGAGAA
GCTTGGCCAAAAGGGGCGAATTCNANCACACTGGCGGCCGTTAC
TACT
225
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AGTTGGGTACCGAGTTGGNATCCCACTAGTANCGGCCNGCCAGT
GTGTTGNAATTCGCCCTTATCGCGGGATCCCNTTTGGAGTCCCT
GTCCGTACTTACACTCATGAGGTGGTGACCCTCTGGTACCGAGC
ACCGGAGATTCTTCTGGGCTGCAAGTACTACTCCACAGCCGTGG
ACATCjGGAGCCTGGGCTGCATCTTTGCCGAAATGGTGACCCGC
AGGGCCCTATTCCCTGGAGACTCTGAGATTGACCAACTCTTCCG
Cyclin dependent GATCTTTCGGACTCTGGGGACCCCAGATGAGGTGGTTTGGCCAG
gE0 ID
kinase 2 D28753 GAGTTACTTCTATGCCTGATTATAAGCCAAGTTTCCCCAAGTGGGNO:
483
CTCGGCAGGATTTTAGCAAGGTTGTGCCTCCCCTGGATGAAGAC
GGACGGAGCTTGTTATCTCAAATGCTGCACTATGACCCCAACAAG
CGGATTTCAGCCAAAGCAGCCCTGGCTGACCCTTTCTTCCAGGA
TGTGACTAAACCAGTGCCCCACCTTGGACTCTGATGTCCTTCCCA
AAGCCCTCTTCACCTGTGGTCTGACCTGATGCTGGGCCTTTTGGA
CACAAGCTTGGCCAAAAGGGCGAATTCTGCAGATATCCATCACA
CTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTCNCNA
TTGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCAGGATCT
GATGCGCCAGTTTCTAAGCGGCCTAGATTTCCTTCATGCAAACTG
CATTGTTCACCGGGACCTGAAGCCAGAGAACATTCTAGTGACAA
GTAATGGGACAGTTAAGCTGGCCGACTTTGACCTAGCCAGAATC
TACAGCTACCAGATGGCCCTCACGCCTGTGGTTGTTACGCTCTG
Cyclin dependent GTACCGGGCTCCTGAAGTTCTTCTGCAGTCTACATATGCAACGCC
gE0 ID
kinase 4 L11007 TGTGGATATGTGGAGTGTTGGCTGTATCTTCGCAGAGATGTTTCGNO:
484
CCGGAAGCCTCTCTTCTGTGGGAACTCTGAGGCTGACCAGCTGG
GCAAAATCTTTGATCTCATTGGATTGCCTCCAGAAGACGACTGGC
CTCGAGAGGTCTCTCTTCCTCGAGGAGCCTTTTCCCCCAGAGGA
CCTCGGCCAGTGCAGTCAGTGGTGCCGGAGATGGAGGAATCTG
GAGCGCAGTTGCTGCTGGAAATGCTGACCTTTAATCCACTTAAGC
GAAGCTTGGGCAAGGGCGAATTCCAACACACTGGCGGGCGGTA
CTAATGGATCCGAGCTCGNACCAACTTGATGCATAGCTTGAGTN
TGNGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGGAACT
GATGATGATGAAGGCCCTTAAGTGGCGTTCAAGCCCCCTGACCA
TTGTGTCCTGGCTGAATGTTTATGTCCAAGTGGCCTACGTCAAGG
ACACGGGAGAAGTGCTGATGCCTCAGTACCCACAGCAGGTCTTC
GTGCAAATCGCAGAGCTTTTAGACCTGTGCGTCCTGGATGTTGG
CTGCTTAGAATTTCCTTATGGTGTCCTCGCTGCCTCTGCTTTGTAT
gEQID NO:
Cyclin E D14015 CATTTTTCCTCGTTGGAGTTGATGCAGAAGGTCTCAGGTTATCAG
485
TGGTGTGATATAGAGAAGTGTGTCAAGTGGATGGTTCCATTCGCC
ATGGTTATCCGGGAGATGGGAAGTTCCAAGCTCAAGCACTTCCG
GGGAGTTCCCATGGAAGACTCCCACAACATCCAGGCCCACACCA
ACAGCTTGGACTTGCTGGACAAAGCCCAAGCAAAGAAAGCCATA
TTGTCAGAACAAAATAGGATTTCTCCTCCTTCGAGTGGGAAACTT
GGCCAAGGGCGAATTNCANCACACTGGCGGGCGGTACTAATGG
ATNCCAGCTCGGACCAAACTTGATGCATAACTTGAGTATTCTAT
GNNTTCCNNGGGGATGGATATNTGCAGAATTCGCCNNNATCCNC
GGGATCCNATGGCCTCAGGAATNACNGCAAGACTCCCAGGTCTT
NTNAAAGNCAGAGATTTCCGGAGNCCTAACTCAGTNATGGGCTT
NGACACANAAACATTTTCCCTTTGCTGTGAATTTTACTGCAGAGAT
TGGTTGTCTAAAATAAGGACAGGNGNAGCATCTCGGATGTGTCG
GCCTTGAGNNGTNTTATTTGGCTGTGGNAATNNATTNAAGAGGNA
AGGNANTGTCCCNGCTGGCNNACTTNNTNTGNTCCGNATNAGNC
NGTANNGGTTCNCAGTTTCAGACGTGATNAGAATGCAAAAAGATT
gEQID NO:
Cyclin G X70871 GTGTTNNANANAGTGTGNTGCANAGTCNAAGCTATTACNNCCTTC
486
CANTTTCTNCAGNTCTATCANTCGCTCATTNGGGAGCCCNTGCCA
TTTGAAAGGAGNNACNNTNNGAATTNTGANAGNGTACNAGCCCT
NNTNAAGGNGTGCCACNGCNGGATCATATTTTCTAAGNCAAAGC
CNTCTGNGATGGNNCTNGCGATCATTNNTTTGGAGATCCAANCN
GTNCAGTATGTGNAGNNCACNGAAGGAGNANNATGTNTTCAAGC
NCATTCCCAGATAAGTGGCCNGTATNTNNCCTTCTGGCAAGAGC
CNGNNTCCTAGTGTGTTCCGAGATCTTCNTATCCGAGTGGCGCG
NNGNTNNNNANNNNNNC
226
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCGGACGCC
AGACAAACCGAGCACCCCAAGCCTTCCGCCTGCAGAAACCTCTT
CGGCCCGGTCAATCATGAAGAACTAACCCGGGACTTGGAGAAGC
ACTGCCGAGATATGGAAGAAGCGAGCCAGCGCAAGTGGAATTTC
GACTTTCAGAATCATAAGCCCCTGGAGGGCAGATACGAGTGGCA
Cyclin-dependent GGAGGTGGAGAGGGGCAGCTTGCCCGAGTTCTACTACAGACCC
kinase 4 D86924 CCGCGCCCCCCCAAGAGCGCCTGCAAGGTGCCGGCGCAGGAGASEQ ID NO:
inhibitor
P27kip1 GCTTGGATGTCAGCGGGAGCCGCCAGGCGGTGCCTTCAATTGG487
GTCTCAGGCAAACTCTGAGGACCGGCATTTGGTGGACCAAATGC
CTGACTCGTCAGACAGTCCGGCTGGGTTAGCGGAGCAGTGTCCA
GGATGAGGAAGCGACCTGCGGCAGAAGATTCTTCTTCGCAAAAC
AAAAGGGCCAACAGAACAGAAGAAAATGTTTCAGACGGTTCCCG
AATAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGTT
ACTAGTGGATCCCAGCTCGGTACCAACTTGATGCATACTTGAGTA
TTCTATATGNCACC
GCGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCGTTGCTGGG
GGAAGGAATGTTCCAATCGCTGTACAAGCAGTGGCAAAGGCCTC
CATTGACCAGAGCAGAGAGATGAAATACCAGTCACTCAATGAGTA
CCGCAAACGCTTCTCCCTGAAACCTTACACATCGTTTGAAGAACT
TACAGGTGAGAAACGGTTGCTGAAATTTCTAAAATGACCAAGGAT
TAAATGAGAAAAGAGAAGGTGAGAGGGAATTTAGTGAAGGAATAA
SEQID NO:
CyclooxygenaseU04300 ACTGTCTTCCTCCTCTTCCTCTTTTTCGTCTTCTTCTGGAAACAGA
2
488
AAAGGATTGAGTTTATTGAGAAAGGGGAGCAGGAATGGGGGTCG
GCTAGTGAATGTGTACTCGTCATCCAGGGCTATTGTCGGCAATTC
CCAGTTTGATATAGCCATATTGTCTGTACCTTCCAGGAGAGAAAG
AAATGGCTGCAGAGTTTGAAAGCCCTCTACCATGACATCGATGCC
ATGGAACTGTATCCCGCCCTGCTGGTGGAAAAGCCTCGTCCAGA
TGCTATCTTTGGGGAGACCATGGTAGAACCTTGGAGCT'1'CATTCT
TCTTTGAAAGGCCTTATGGGTAATCCCATCTGGTC
CCGGCTCGTATGTTGGGGGAATTGTGAGCGNATACCAATTTCAC
NCAGNAACCAGCTATGNCCATGATTACGCCAAGCTATTTAGGTGA
CACTATAGAATACTCAAGCTATGCATCAAGCTTGGTACCGAGCTG
GGATCCACTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTC
ACACAAGCACAATAGACGCCCATGAAGTAGAAACAATTTGAACAA
TTCTCCCAGCTGTCATTCTTATTCTAATTGCCCTTCCCTCCCTACG
AATTCTATACATAATAGACGAGATTAATAACCCAGTTCTAACAGTA
Cytochrome M64496 ~CTATAGGACACCAATGATACTGAAGCTATGAATATACTGAC5EQ ID NO:
c oxidase
subunitll TATAAAGACCTATGCTTTGACTCCTACATAATCCCAACCAATGACC489
TAAAACCAGGTGAACTTCGTCTATTAGAAGTTGATAATCGGGTAG
TCTTACCAATAGAACTTCCAATTCGTATACTAATCTCATCCGAAGA
CGTCCTGCACTCATGAGCCATCCCTTCAGTAGGGTTAAAAACCGA
CGCAATCCCCGGCCGCCTAAACCAAGCTACAGTCACATCAAACC
GACCAGGTCTATTCTATGGCCAATGCTCTGAAATTTGCAAGGGCG
AATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCA,
TCTAGAGGGCCCAATTCGC
AACACGANTATNGNNTTNTNTAGNGTACNNNTTNANNGNNGNAN
NNNTNNATANAAGNGATANNTGTNCGAAANNGNACNGNANGNTA
NNGAAGCCNAGCANTTNACTTGAAGACNCNCGNAANTCGCGNNG
GTNTAAACCTNANNGNNNNTAAAANNNANGNTAATAANTANNNAG
GNNNCTNGNTAGGANGNAGNNANCNTNGAGTNANATATATTTTN
GNGNANTNNANACGTNGAANGACTNANNGNCCGTGAAAATNANN
TGTGAATNATCAAANGANCANCCTTCANNGANCNANANANTGNAN
ATTTANCTCCAAGNTNNGNATNAAAGGTTGNGTCCNNNGCTCNG
Cytochrome GATNCNTCTTAGTAAGGGCCNNCCAGTGTCNNTGGAATTNGCCCSEQ ID NO:
c oxidase
subunit IV X14209 TTATCANGGGATCCANTANAATNCGGGTGTGCCTTAGGGCCACA
4g0
TGGGAGTGTTNTAAANAGTGAAGANTATGTCTCCNCGTNATATGN
TGATCGGGCNGTGNCNACCCCTNGCNTGATGTGGCNCACGTCAA
NGTTNATGTCTGCCAGCCAAAAGGCCNNTAAGNAGAAGGAGAAG
NCCCAGTGGAGCAGCCTTTCCAGGNNTNAAAAAGTCCAATTGTN
CCGCATCCAGTTNANCGAGAGCTTNGCTCAGATNAACAAGGGCA
CCAATGAGTGGAAGACANTGGTGGGCCTGGCCATGTTCTTCATC
GGCTTCACTGCGCTTGTGCTGATCTGGGAGAAGAGCTACGTGTA
NGGCCCGTCCCTCATACCTTTNATCGTGNTTGGGACATAAGACN
GCGCANGCNGTNTNAACNTTC
Cytochrome ~p5156 GACCTGGGCTCAACTATGCCCAGAAAAGGCGACACTGTATGAATSEO ID NO:
P450
11 A1 TGCAGG 491
227
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCAGGACATCAGGTGTGTGT
TTCTCCAACTGTCAATCAAAGACTGAAAGACTCCTGGGTAGAACG
CTTGGACTTCAATCCTGACCGCTACCTACAGGACAACCCAGCGT
CGGGAGAGAAGTTTGCCTATGTGCCGTTTGGAGCCGGGCGCCAT
CGTTGTATTGGAGAAAATTTTGCCTATGTTCAAATTAAGACAATTT
GGTCCACTATGCTTCGTTTATATGAATTTGACCTCATCAATGGATA
~CCCAGTGTGAATTATACAACAATGATTCATACCCCAGAAAACSEO ID
NO:
Cytochrome D55681 CCAGTAATCCGTTACAAACGAAGATCAAAATGAAGAAAGGAACAA492
P450
14DM GGAGCCAGTGTGGAGACGGGACTGCAAGCTGCAGCTTGGCAGA
GAATGAAGCTTTGACACAGCTTTCATACTGTACTGTTTTTTAGGTG
TGTGGTTCCGAAAGCCAGTTTGATTTTAATGTTTTATTAACTCGGT
GATTTTTGTCAGACCTAATGGCAAAGGGCGAATTCCAGCACACTG
GCGGNCGTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCA
TAGCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCA
TGGTCATAGCTGTTTCCTGTGTGAAAATGGTATCCGCTCACAATT
N
AGTATGATCAAGCTTGGACCGAGNCGGATCCACTAGTACCGNCC
CGCCAGTGGCTGNAATTCGCCNTTCGCGGGATCCGAAGATCCAA
AAGAGATTGACCAGTACGTAGGTTCAGCCGAACACCAACTTTCAA
TGACCGGTCTCACCTCNTCATGNTGGAGGCCACTATCCGAGAAG
TGCTGCGTATCAGGCCGGTGGCTCCCATGCTCATCCCCCACAAG
GCTAACGTTGACTCCAGCATTGGAGAGTTTACTGTCCCCAAGGA
CACACATGTGGTCGTCAATCTCTGGGCACTGCGTCACGATGAGASEO ID
NO:
Cytochrome M22204 ATGAATGGGACCAGCCAGATCAGTTCATGCCTGAACGCTTCTTAG493
P450
17A ATCCAACGGGAAGCCATCTCATTACACCCACGCAGAGTTACTTGC
CCTTCGGAGCTGGTCCCGATCCTGCATCGGAGGGGCTCTGGCC
CGTCAGGAGCTCTTTGTCTTCACGGCCTTGCTACTGCAGAGGTTT
GACTTGGATGTGTCAGATGATAAACAACTGCCCCGCCTGGAGGG
TGATCCCAAGGTAGTCTTTCTGATCGACCCTTTCAAAAAGCTTGG
CCAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGGCCGCT
CGAGCATGCATCTAGAGNGCCCGNTCACNATNTNCAN
Cytochrome TCTGGTCCTCAGCATCTCCAGGCTTAGACTGTCCTGGATGCTCACSEO ID
P450 NO:
1 A1 X00469 CAGAC 494
Cytochrome K03241 SEQ ID
P450 NO:
1A2 AGGTGGACCTGACACCCAGCTATGGGCTGACCATGAAGCC495
NGGTGACACTATAGAATACTCAAAGNTATGCATCAAGCTTGGTAC
CGAGCTCGGATCCACTAGTAACGGCCGCCAGTGTGCTGGAATTC
GCCCTTATCGCGGGATCCAGCGGAAACCAAGTGGCCTGAAGGT
GAGGCGGGCTTACCAATTCATGGCTCCTCACCGGCCAGCAGCTG
GAGATCCTGAAGTATTTTGAAATTGAAGAGTAACAGGGCCCAAGG
AATTTGCATACTGTTCCCCCCTCACCCCCATTAAACACATGCACA
CAAATCAGCATGTGTGTACAGCTATCCAACAAAATATTTCAGTAACSEO ID
NO:
Cytochrome U09540 TCTGCCTTTTTGGGTCAATTTGAAAGGGAACTTCTATGTGCAGAA4g6
P450
1g1 ATTGGCCCCATAGGAAACCACAGTAAGCAGAGGCTTAGGATATAT
ATTTTCAAGATTCAAAGAAGTGATTTAAGTGTAAAATATAAAGAGC
AGAAATTCTACCAAGAGACAAATGAGGCCACTCCCTTGTGGCCCT
GGACGAGGTTTTCTTTCTGCCTGTAGATGTGCCTCCCACTCTAGA
ACGGACCATAAAGCCGTTTTGCTCCCCCTCAAAAGCTTAAGGGC
GAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGC
ATCTAGAGGGCCCAA
Cytochrome M33190 SEQ ID
P450 NO:
2A3 ATATATATTTCAAAGGTAGAGCCAGAGAAGGGGGAAATA497
Cytochrome CAACATACCAGATCTGCTTCTCAGCTCGGTGATCCGGCTGAGGCSEQ ID
P450 NO:
M19972 498
2B1/2B2 AGCCAT
Cytochrome ACTCTCTAAGCTCTCATCTGTAATGTCTCTTCTGAGGGTCCTGTCTSEQ ID
P450 NO:
2C11 U33173 AC-I-f 4gg
Cytochrome AGCTGTGCTTCATTCCTGTCTAATGAAGACCTAAAAGCAGAAATGSEQ ID
P450 NO:
2C12 50mer .103786 ,qAGAT 500
Cytochrome TTGACCCTAAGGATATCGACCTCAGTCCTGTCACAGTTGGCTTTGSEQ ID
P450 NO:
2E1 50mer M20131 GCAGT 501
228
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGAACGGCCCTCTAGATGCTGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCCTTCGCGGGATCCCCTGGCCACT
CACCCAGATACACAGAAGAAACTGCAGGAGGAGATCGACAGGGC
TCTGCCCAATAAGGCACCTCCCACCTATGATACTGTGATGGAAAT
GGAATACCTGGATATGGTGTTGAATGAAGCCCTCAGATTGTATCC
AATTGGTAATAGACTTGAGAGAGTCTGTAAAAAAGATGTTGAAAT
CAATGGTGTGTTTATGCCCAAAGGGTCAGTGGTCATGATTCCATC
Cytochrome TTATGCTCTTCACCGTGATCCACAGCACTGGCAGAGCCTGAGGASEQ ID NO:
P450
3A1 M10161 ACTTCGCCCAGAAAGGTTCAGCAAGGAGAACAAGGGCAGCATTG502
ATCCTTATGTATATCTGCCCTTTGGAAATGGACCCAGGAACTGCA
TTGGCATGAGGTTTGCTCTCATGAATATGAAACTCGCTCTCACTA
AAGTTCTGCAAAACTTCTCCTTCCAGCCTTGTAAGGAAACACAGA
TACCTCTGAAATTAAGCAGACAAGGACTTCTTCAACCAAAGCTTG
GCCAAGGGCGAATTCCAGCACACTGGCGGNCGTTACTAGTGGAT
CCGAGCTCGGTACCAAACTTGATGCATAGCTTGAGTATTCTATAG
TGTCACCTAAATAGCTTGGCGTAATCATGGGCATAGCTGNT
GCCGTNAANNAANCANTTCCNC'fNGTGNACGNNNCNCGNNCNN
GANGTNGTAGNAAGANANCACTCGNNCCGNNANTNNNGATNGCN
NNCTGNANAGCGNNNTNAGNTNGNNCGNTGNGTAGGTNNCGGT
AGNCNTNGNNAAAAAAGANANGAANNNGNNAAAGNAGNTCCNNN
CNCNTGAACANGNNNNNTCNNGGAGNAGCAGGTCAANACNNNC
NANCCCNNANNNGAAATGNGNNGNNNNTNNANNNNNANNGGNN
ANNANNNNNNNCNCGAAGANNGGAANNNNGAAAAGATANNTNNN
NGNCCNCNNGNANNGGTNANNANNCNNGNNAGACNNNTGGNNN
GNNGGNGGCNGAGNNANGCCANNNNAANTCCGTGNNGNANNGG
GGAANNNTGGNNNGNCCAGCTNNNCCCCNANTANAGANANCAN
NCTNGNAANGTNNCCANGCCGNNANAAGGATAGGNNTTGNTCGNSEO ID NO:
Cytochrome M57718 GACGNNNGANNNNNNAGNAGTNNAGNNNCCNAAAATNCANNNA503
P450
4A1 NNNTAGCTNAAAGNTTGGTNCCGNTNTNNGGNNCCCCTAGTAAA
GGNCGNCNNGNGCGCGNGGGNNCTACCNNGGNNCAGNACACC
GGNTANNNCNANCNATTGCNNCAAGCTTGGTACCGAGCTCGGAT
TCCNCTAGNAACGGCCGCCAGTGTGCTGGANTTCNCCCNTTGCG
CGGGATCCCCGTNAGGCTTTCCCCCCCTGNTCCCAGGGCATTGT
CAGAGAAAACAGGACATCTGTCCCCTTCCCCTGATGGGGCGCTC
CATTACCCAAGNGTATNNCAAGTCCACTCTCCCATTTATGGTCTT
CCCCTCTNANCCNAAGGTGNGGCCAAGCCCAGAAGNGTNTNNTA
ANCCTANCAGTGTATTGCACCAGACTCTCNCCGCCACNGCCACN
NATTNCCTGNTNTTGNCCAGNAGGNAGCNAAGNAGCCGCNTGTN
AAACANNTTATTNNGTANGAACCNNTACNGTGGGGCG
Cytochrome TCCAAAAATGGGATCTACCTGTATCTCAAGAAGCTCCACTAATTCSEQ ID NO:
P450
4A1, 50-mer M57718 CGTTG 504
AGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCATGTCGGCG
TCGGTAGTGTCCGTCATCTCCCGGTTCCTGGAGGAGTACTTGAG
CTCCACTCCACAGCGGCTGAAGTTGCTGGATGCCTATCTCCTTTA
TATATTGCTGACCGGGGCGCTGCAGTTCGGCTACTGTCTCCTCG
TGGGCACCTTCCCCTTCAACTCTTTCCTCTCTGGCTTCATCTCTT
GTGTGGGCAGCCTCATCTTAGCGGTTTGCTTGAGAATACAGATCA
Defender against ACCCCCAGAACAAGGCGGATTTCCAAGGCATCTCTCCTGAGCGASEQ ID
NO:
cell
death-1 Y13336 GCCTTTGCTGATTTTCTCTTTGCCAGCACTATCCTGCACCTCGTC505
GTCATAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCG
TTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTG
AGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCAT
AGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACA
ACATACGAGCCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTA
ATGAAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCG
CTTTCN
229
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGCGATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCTTGCCTCTCTCAACGGCA
GCCTCAGGGATGCAGAGAAACCTGTATTATTTTTTGAACGATCTG
TGTATAGTGACAGGTATATTTTCGCATCTAATTTGTATGAATCTGA
CTGCATGAATGAAACAGAATGGACAATATATCAAGACTGGCATGA
CTGGATGAATAGCCAGTTTGGCCAAAGCCTTGAATTGGATGGAAT
AATTTATCTTCGAGCTACTCCAGAGAAGTGCTTAAATAGAATATAT
DeoxycytidineL33894 ATACGGGGAAGGGATGAAGAGCAAGGCATTCCTCTTGAATATTTASEQ ID NO:
kinase
GAGAAACTTCACTATAAACACGAAAGCTGGCTCCTTCATCGGACT506
CTGAAAACCAACTTTGAATATCTCCAAGAGGTGCCTATCCTGACA
TTGGATGTTAATGAAGACTTTAAAGACAAACACGAAAGTCTGGTT
GAAAAGGTCAAAGAATTTTTGAGTACTTTGTGATTGCACAGGAGA
CAACAGGCAACAAAAGGGGGAATTCCAGCACACTGGCGGCCGTA
CTAGTGGATCCGAGCTCGGTCCAAGCTTGATGCATAACTTGAGTA
TTCTATAGNGGACCTAAATAGCTTGGCGTAATCATGGNCATAGCT
GGTTCCTGNGNGAAA
GAAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTAAGGGGACCATGGATCAAC
GAGGGACACTACCAGAGGACTAGAGCTTTCCTTGGCCATCTCAC
TGCCACATTCCTGTCAGATGGCTATGGGGGGACCCTGTCACAGG
GAAGGAGCCCCGTGCCACCCCCTGAGAAGCCGTTCAGATCTAG
GGCTGGACTCTAAGGAGCTGGACTCTCACCTGTCCCTGGTTTCA
TGGGGAACAGGAAACAAGCTGGGCTGACTGGGTCCCTGCCTTCA
Diacylglycerol GGGCGGCCTCCCCCTCACCACAGCTGATGGAATGGCTGGACAGSEO ID NO:
kinase
zeta D78588 CTCAGTCAGGGAGGCCTGCTCTCAGCAGGACTTTCTAAAGCCAC
507
CTGATCCCTTGGGCTCTTTGGAAGGTTCTGGGTGGCTAGCCCTC
CTCTCTGACCCACACACCTTGGGCATCCCAGAAACTCAAGAGCC
TGCTGTATTTGCCTGCCCGCTGCCCTGCTTGGCAGCTACCCTGG
TGATCCTCCTCATGCACCCAGTCATTTCATTTCCGACTGTATGGC
CTGGGGTGAANGGCGAATTCAACACACTGGCGGCCGTTACTAAT
GGATCCGACTCGGTACCAACTTGATGCATRACTTGAGTATTCTAT
AGTGTCCCTAAAATAGCTTGGCGTAATCATGGCATAGCTGNTTNC
TGTGTGAAATTGTN
TGGAATTGGCCGNNTAAATGATGCTCGAGCGGCCGCCAGTGTGA
TGGATATGTGCAGAATTCGCCCTTATCGCGGGATCCAACAAGGG
ACCAGTCAGGGTGGTAGTGGGGAAGACCTTTGATGCCATTGTGA
TGGACCCCAAAAAGGACGTCCTCATTGAATTCTATGCACCGTGGT
GTGGGCACTGCAAGCAGCTGGAGCCTGTCTACACCAGCCTAGG
Disulfide CAAGATGTACAAGGGCCAGAAGGACTTGGTCATGGCCAAGATGG
isomerase
related proteinM86870 ATGCTACTGCCAATGACATCAGCAACGACCGATACAAGGTGGAGSEQ ID NO:
(ERp72) GGCTTCCCCACCATCTATTTTGCCCCCAGTGGGGACAAAAAGAA508
CCCAATTAAGTTTGAGGGTGGCAACAGAGATCTGGAGCATTTGA
NCAAGTTTATCGATGAACATGCCACAAAGAGGAAGAGGACCAAG
GAAGAGCTTTAAGGCCTGGCTGTGTGCAGAAGGTGGAGGGATCA
GACACTGTAGTGGACAGCTTTGGCCACCAAGCAAAGCAAGCCCG
TCACTTTGAATGGGAGGATCTTTGACCAAACTTTGGGCAAAANGG
CGAATTCAGCACACTTGGCGGGCCGTTT
~NACATTTTCACACAGNANCAGCTATGCCCATGATfiACGCCAAGCT
ATTTAGGTGACACTATAGAATACTCAAGCTATGCATCAAGCTTGG
TACCGAGCTCGGATCCACTAGTAACGGCCGCCAGTGTGCTGGAA
TTCGCCCTTCGCGGGATCCATGAAAGCCTTCAGTCCGGTGAGGT
CCGTTAGGAAAAACAGCCTGTCGGACCAGAGCTTGGGCATCTCC
CGGAGCAAAACCCCGGTGGACGACCCGATGAGTCTGCTCTACAA
DNA binding CATGAACGACTGCTACTCCAAGCTCAAGGAACTGGTGCCCAGCASEQ ID NO:
protein
inhibitor D~0863 TCCCCCAGAACAAGAAGGTGACCAAGATGGAAATCCTGCAGCAC
ID2
509
GTCATCGATTATATCTTGGACCTGCAGATCGCCCTGGACTCGCAC
CCCACTATCGTCAGCCTGCACCACCAGAGACCTGGACAGAACCA
AACGTCCAGGACGCCGCTGACCAGCCTGAACACGGAGATCAGCA
TCCTGTCCTTGCAGGCGTCTGAATTCCCTTCTGAGCTTATGTCGA
ATGACAGCAAAAAGCTTGGCCAAGGGCGAATTCTGCAGATATCC
ATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATT
CGCA
230
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGANTGNCCTNTAGATGCTGCTCNAGCGGCCGCCAGNGTGATG
GATATCTGCAGAATTGGCCCTTCGCGGAATTCTGGATCCCGAGTA
CATCGCTACAGTCTGCGGCAGTTTCCGAAGAGGCGCAGAGTCCA
GTGGAGATATGGACGTTCTGCTGACCCACCCAAACTTCACGTCA
GAATCAAGCAAACAGGCAAAGTTGTTACATCGTGTTGTGGAACAG
TTACAAAAAGTCCGTTTCATTACAGATACTCTGTCAAAGGGTGAG
ACAAAGTTCATGGGTGTTTGCCAGCTTCCCAGCGAGAATGATGAA
DNA polymeraseM13961 ~CGAATATCCACACAGGAGAATCGATATCAGGTTGATCCCCAAASEQ ID
beta NO:
GATCAGTACTACTGTGGTGTTCTCTACTTCACTGGAAGTGACATC510
TTTAATAAGAATATGAGAGCGCATGCCCTGGAAAAGGGCTTCACA
ATCAATGAGTACACCATGGGCCCCCTGGGGGTCACTGGGGTTGC
TGGGGAGCCCCTTCCGGTGGACAGCGAGCAGGACATTTTCGATT
ACATCCAGTGGCGCTCCGGGAGCCCAAGGACAGGAGTGAAAAG
CTTGGGNCAAGGGCAAATTCCAGCACACTGGCGGCGGTACTAGT
GGATCCGAGCTCGGTCCAAACCTTGATGCATAGCTTGAGTATTCT
ATAGTGNCACCTAAATAGCTTGGCGTAATCATGGTCATAGG
AATTGGCCGTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATG
GATATCTGCAGAATTCGCCCTTATCGCGGGATCCTGCAGCAGCA
GTTTAAAGAGCTCACAGCCCCTGATGAGAATGTACCAGCAAAGAT
TCTATCTTATAACCGTGCCAATCGCGCTGTTGCAATTCTTTGTAAC
CACCAGAGGGCGCCACCAAAGACCTTTGAGAAGTCAATGATGAA
CTTGCAGTCTAAGATTGATGCCAAGAAAGATCAGCTAGCAGATGC
TCGAAAGGACCTGAAAAGCGCTAAGGCTGATGCCAAAGTCATGA
gEQID NO:
DNA topoisomeraseAF140782AGGATGCAAAGACCAAGAAGGTAGTAGAGTCAAAAAAGAAGGCT
I
511
GTACAGAGATTAGAAGAGCAGCTGATGAAGCTGGAGGTTCAAGC
CACAGACCGAGAGGAGAACAAACAAATTGCCTTGGGGACCTCCA
AACTCAATTACCTGGACCCTAGGATCACAGTGGCTTGGTGCAAAA
AATGGGGGGTCCCAATCGAGAAGATTTACAACAAAACCCAGAGA
GAGAAGTTTGCTTGGGCCATTGATAAGCTTGGCCAAAAGGGCGA
ATTCCAGCACACTGGCGGCCGNTCTAGTGGATCCGAACTCGGTC
CAAACTTGATGCATACTTGAGTATTCTATAA
TTACTCAAAGCTATGCATGAAGCTTGGTACCGAGCTCGGATCCAC
TAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTACCAGAGAA
GAATGGGCACGCCAAGATTGTCAATCCCAGGATTGCCAAGTTCTT
TGAGATCCAGACCATGCCCAATGGCAAAGCCCGGACCTCCCTTA
AGACGATGAGCCGCAGAAAGCTCTCCCAGCAGAAGGAGAAGAAA
Dopamine receptor GCCACTCAGATGCTTGCCATTGTTCTCGGTGTGTTCATCATCTGC
gEQ ID
D2 X53278 TGGCTGCCCTTCTTCATCACGCACATCCTGAATATACACTGTGATNO:
512
TGCAACATCCCACCAGTCCTCTACAGCGCCTTCACATGGCTGGG
CTATGTCAACAGTGCCGTCAACCCCATCATCTACACCACCTTCAA
CATCGAGTTCCGCAAGGCCTTCATGAAGATCTTGCACTGCTGAGT
CTGCCCCTTGCCTGCACAGCAGCTGCTTCCCACCTCCCTGCCTA
TGCAGGCCAGACCi'CATCCCTGCAAGCTGTGGGCAGAAAGGCC
CAGGGG
AGAATTGGGCTCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCT'f~f'CTTCACTCTTGGCATTGT
CCTGGCTACTTTCCTGCTGTCTCTCTTCTGCGTCACCAACGGTGG
CATCTACGTCTTCACACTGCTGGACCACTTTGCAGCTGGCACATC
TATCCTCTTTGGCGTGCTCATTGAAGCCATTGGGGTGGCCTGGTT
CTACGGCGTCCAGCAATTCAGTGATGACATCAAGCAAATGACAG
GGCAGCGACCCAACCTGTACTGGCGGCTATGCTGGAAGCTGGT
CAGCCCCTGCTTCCTCCTGTATGTGGTCGTGGTCAGCATTGTGA
SEQID NO:
Dopamine transporterM80233 CCTTCAGACCCCCACACTATGGGGCCTACATCTTCCCAGACTGG
513
GCCAATGCCCTGGGCTGGATCATCGCCACATCGTCCATGGCCAT
GGTGCCCATTTATGCGACCTACAAGTTCTGCAGCCTGCCGGGGT
CCTTCCGGGAGAAACTGGCCTATGCCATCACACCTGAGAAAGAC
CATCAGCTAGTGGACAGAGGGGAGGTGCGAAGGGCGAATTCCA
GCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCCAA
GCTTGATGCATAGCTTGAGTATTCTATAGTGTCACCTAAAATAGCT
TTGGCGTAATCATTGGTCATAAGCTTGNTTCCTTGTGTGAAAATT
GGTATC
231
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AGNGAGGCTTGATCAGCGAGCTTCTAGCATTTAGGTGACACTTAT
AGAATAGGGCCCTCTAGATGCATGCTCGAGCGGCCGCGATATCG
AATTCGCCCTTCGCGGGATCCCTGTCGCCTCTGCTGCTTGAGCG
GCGCCAGCACCTTCCCTAGGAGCTCGCAGCAGCCGGCTGGCCC
CTGCTCCACGGTAACCATGTGCGACCGGAAGGCGGTGATCAAAA
ATGCAGACATGTCGGAAGAGATGCAACAGGACTCGGTGGAGTGC
GCTACTCAGGCGTTGGAGAAGTACAACATAGAGAAGGATATCGC
Dynein light 066461 GGCCCATATCAAGAAGGAGTTTGACAAGAAGTACAACCCCACCTSEQ ID NO:
chain 1
GGCACTGCATCGTGGGCCGGAACTTCGGTAGCTACGTGACACAC514
GAGACCAAACACTTCATCTACTTCTACCTGGGTCAGGTGGCCATT
CTCCTGTTCAAATCTGGTTAATAGCATGGACTGTGCCAAACACCC
AGTGATCCATCCAAAAACAAGGACTGCATCCTAAATTCCAAATAC
CAGAGACTGAATCTTCAGCCTTGCTAAGGGAACACCTCGTTTGAA
TCTGTTGTGTTTTGTACAGGGCACAAGCTTGGCCAAGGGCGAATT
CCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACC
AAGCTTGGGTCTCAA
TGTGAATTCGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTACATCAGCTTCTGAGCC
GTGGTTACCACTTCGATGAGCGCTCCTTCAGAGAAGTGGTCTTC
CAAAAGAAGGCTGCAGACACGGCTGTCGGCTGGGCGCTGGGCT
ACATGCTGAATTTGACTAACCTGATTCCTGCCGACCTCCCCGGAC
TACGCAAGGGCACCCACTTCAGCTCCTGGGTCCGCTCTCCTGCT
GCTCTTCACAGTCCTGATCTTGGCGGCGCTGGTCCTGCTCCTGC
GCCAGGATGTCAGGTCTCAGCCTGTGACTCAGGGTGAGGTCCAT
SEQID NO:
Ecto-ATPase Y11835 TCGGAGTGGGACTTTTGTTCTGAAGGGCGAATTCCAGCACACTG
515
GCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGC
ATAGCTTGAGTATTCTATAGTGTCACCTAAATAGCTTGGCCGTAAT
CATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCCGCTCACA
ATTCCACACAACATACGAGCCCGGAAGCATAAAAGTGTAAAAGCC
TGGGGTGCCTAATGAAGTGAGCTAACTCACATTAATTGCGTTGCG
CTCACTGGCCGCTTTTCAGTCGGGAAACCTGTCGTGCCAGCTTG
CATTAATGAATTCGGNCAACNCCCCGGGGAGAAGGCGGGTTTGC
GTATTTGGGCCGCT
CACTATAGAATACTCAAGCTATGCATCAAGCTTGGNCCGAGCTCG
GATCCACTAGTACCGGCCGCCAGTGTGTTGGAATTCGCCCTTTG
AAGCTTTTGAGTGAAGCTCTGCCTGGGGACAATGTAGGCTTCAA
CGTAAAGAACGTGTCTGTCAAAGACGTTAGACGTGGCAATGTTG
CTGGGGACAGCAAAAATGACCCACCAATGGAAGCAGCTGGCTTC
ACTGCTCAGGTGATTATCCTGAACCATCCAGGCCAGATCAGTGCT
GGCTATGCCCCTGTTCTGGACTGCCACACGGCCCACATAGCATG
Elongation X61043 C'~~GTTTGCCGAGCTTAAAGAGAAGATCGATCGTCGTTCTGGTAASEQ ID NO:
factor-1
alpha GAAGCTGGAAGATGGCCCCAAATTCTTGAAGTCTGGTGATGCTG516
CCATTGTTGACATGGTCCCTGGCAAGCCCATGTGTGTTGAAAGCT
TCTCTGACTACCCTGCACTTGGTCGTTTTGCTGTTCGTGACATGA
GGCAGACAGTTGCTGTGGGTGTCATCAAAGCCGTGGACAAGAAG
GCTGCAGGAGCTGGCAAAGTCACCAAGTCTGCCCAGAAAGCTCA
GAAGGCTAAATGAATATTATCCCTAACACCTGCCACCCCAGTCTT
AATCAAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCG
CTCGAGCATGCATCTAGAGGGCCCAATTCGC
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCGCAACCTCT
GGGAGCACAACCAAGCCATCATTAAGCATCTGCTGGAAAATTCCA
CGGCCAGCGCGAGCGAGGCAGAGAAAAAGGCGCAAGTGTACTA
CCGTGCGTGTATGAACGAAACTAGGATCGAGGAGCTTCGGGCCA
AGCCCCTGATGGAGCTGATTGAGAAGCTCGGAGGTTGGAATATC
ACAGGACCCTGGGCCAAGGACAACTTCCAGGACACGCTGCAGG
Endothelia D29683 TGGTCACAGCGCACTACCGCACCTCACCCTTCTTCTCTGTCTATGSEQ ID NO:
converting
enzyme TCAGTGCCGACTCCAAGAACTCCAACAGCAATGTGATCCAGGTG517
GACCAGTCCGGCCTTGGCTTGCCCTCCAGAGACTATTACCTGAA
CAAGACGGAAAATGAAAAGGTACTGACTGGCTATCTGAACTACAT
GGCCCAGCTGGGGAAACTGCTGGGTGGTGGGGACGAGGACTCC
ATCCGGCCCCAGATGCAGCAGATCCTGGATTTTGAGACCGCTCT
GGCCAACATCACCATCCCCCAGGAGAAGCGCCCGGGATGAAAA
GCTTATTCTACCACAAAGTCAGGGNTGGTTGAACTTGCAGACCTT
G
232
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AATNGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGAT
GGATATCTGCAGAATTCGCCCTTCGCGGGATCCGAAACAGCTGT
CTTGGGAGCAGAGCTCAGCCCCCGAGCTGAGAAGGAAGTGCAG
AGCTCCCCTCCCAGCACATCCTGGAGACCCCGCAGGTCCAAGC
GTTGCTCCTGCTCCTCCTTGATGGACAAGGAGTGTGTCTACTTCT
GCCACCTGGACATCATCTGGGTCAACACTCCCGAGCGCGTCGTC
CCGTATGGACCAGGAAGCCCTTCTAGGTCTAAGCGATCCTTGAA
Endothelin-1 M64711 AGACTTACTTCCGACAAAGACCACAGACCAAGGGAACAGATGCCSEQ ID NO:
AGTGTGCTCACCAAAAAGACAAGAAGTGCTGGAATTTCTGCCAAG518
CAGACAAAGAACTCCGAGCCCAAAGTACCATGCAGAAAGGCGTA
AAAGACTTCAAGAAGGGAAAACCCTGTCCCAAGCTGGGAAAGAA
GTGTATCTATCAGCAGCTGGTGGAGGGAAGAAAACTAAGAAGGT
TGGAGGCCATCAGCAACAGCATCAAGACCTCCTTTCGAGTTGCA
AGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTA
GTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTGAGTATT
CTATAGTGTCACCTAAATAGCTTGGCGTAATCAT
TAGNTGNCATAATAAATACTCAAGTATGCATCAAAGTTTGGTACC
GAGGTCGGATCCACTAGTACCGGCCCGCCAGTGTGCTGGAATTC
GCCCTTATCGCGGGATCCGCTGCAGGCGAAAGTCCTGCAACTGC
CTGCTGCTCAAAGTGAACCAGATTGGCTCCGTGACCGAGTCTCT
GCAGGCGTGTAAGCTGGCCCAGTCCAATGGCTGGGGTGTCATG
GTGTCCCATCGATCTGGGGAGACTGAGGACACTTTCATTGCCGA
CCTGGTGGTGGGGCTCTGCACTGGGCAGATCAAGACTGGTGCC
SEOID NO:
Enolase alphaX02610 CCCTGCCGATCTGAGCGCCTGGCCAAGTACAATCAGATCCTTAG
519
AATCGAGGAGGAGCTGGGCAGCAAAGCCAAGTTTGCCGGCAGG
TCCTTCAGGAACCCCCTGGCCAAGTAAGGCATGGACCGGAGATC
CCTGGAGCTACCAGATCCTCTGTCTCTGTCATCCAGGCGGCTCA
AGGCTGGCCCAGTGCTTGCCCCTCCCATGTCACTGCTTCCTTAG
ATGTCCACCCCGACCACCTGGAGCCCTGCTGGAGCCCCCAGCTT
TGTAAAAGCTTGGCCAAAAGGGCGAATTCTGCAGATATCCATCAC
ACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTCGC
NGNGGAAGGAGCGCCCAATNANGCAAACCCGCCTTTTCCCCGG
GGGGTTGGGCCGATTCCATTAAATGCAGGTTGGCCACGGACAGG
TTTNCCCGATTGGAAANGCGGNCAGTGAGCGCAACCGCAATTTA
ATGTGAGTTAGCTCACTCCATTAGGCACCCCAGGCTTTTACACTT
TTATGCTTCCGGNTCGTATGTTTGTGTGGAAATTGTGAAGCGGAT
AACCAATTTCCNCACCAGGAAACCAGCTATGACCCATGATTTACG
CCAAGGTTATTTTAGGTGACCATTATAGAATTACTCAAAGCTTATG
CATCCAAGGTTTGGTTACCGAAGNTCGGATCCCACTTAGTAACCG
Enoyl CoA GCCGGCCAGTGTGGTTGGAATTTCGGCCCCTTGGCGGCGGNATSEQ ID NO
hydratase
:
(mitochondrial)K03249 TCCGGCGTTGCTTAATATTCCCTTCCATCAAATGAGGCGTTGCGC
520
ATTCTTGGGAGGAGGGGATGGCTGCTTCGCCCCAGAGCCACATT
GAATGTTCA'iTCTTACTTTGCCACGGGTACGGGTGGCCCAAGGC
CACCAAGGGGGGGGCCCAATGTTTCTTATGCNTGCCTTCAAGTT
GGGTTGGCCCCACCATTTCTTAGAGAAAACTGCAGAAATTATTAC
CAGGCAAGAACCCTTGACANTCCCCCAAGCTGGAAGCCCCCAGT
GATTACCTTCAAGAAGGGTTGGTGGGCCCAGGGAAGCCNTCCTC
TGAAGGAATGGCAAAGCTTGGAAGCTTGGCCAAGGGCGAATTCT
GCAGATATCCATCACACTGGCGGCCGTCGAGCATGCTNTAGAGG
CCCA
ATGCCATGATTACGCCAAGCTATTTAGGTGNCACTATAGAATACT
CAAGCTATGCATCAAGCTTGGTACCGAGCTCGGATCCACTAGTAA
CGGCCGCCAGTGTGCTGGAATTCGCCCTTAAGGGCCTCAGACCT
GCCCCAGCAAACAGAGCCAGTTCCGTAGAAACTGGGAGCAGACA
GAAGGTACCGAAGGTGAAATAGCAAACCAGGCTGAAGGGTGGTA
GAGCGGCAGATCTGGTACTCCTGTCTCCACGGCTAATCACTGCT
CAGGGTCCTGAAGATAACTGCATAGCTGCATAGCTGCATAGCCT
Epidermal U04842 CGACTTCTGCTTCTTGCTTGAAGCAGTCCCGTTGAAGACGATCAASEQ ID NO:
growth
factor AAGAGAAGTGGAGAAAAATCATCAGAAACCGAAGTCAAGACGTT521
CACGTGTTGTAAGCTGTGTCTTCTTCCCTGGACTGTTGGGCTCTT
TTCCTTGTTGTCTCAGAAGAAATGGGTTAAAGCAGGCGATCATAT
GCTTTGTTGATTGCACAGTAGATGATATGATCTACATAGATCTTAG
CTCACTCTCACGGAAAGGCTGGAACATTATAGATGCTGCTAAGAT
ACACTGCAAGTGTGGCCCCTGCTCATAAAGCTTAAGGGCGAATT
CTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTA
GAGGGCCCAATTCCCAA
233
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
CTATGNCATGATTACGCCAAGTATTTAGGTGACATATAGAATACT
CAAGCTATGCATCAAGCTTGGTACCGAGCTCGNATCCACTAGAA
CGGCCGCCAGTGTGCTGGAATTCGCCCTTCACGGTGGCCATCTG
TGAAGTCCCAGGATTGGATCTTCGAGATGCTGTCCTTGCAGAACA
ATTACACTATTAACAACAAAAGAAACGGAGTTGCAAGGCTCAACA
TCTTCTTCAAGGAGCTGAACTATAAAACTAATTCGGAGTCTCCTTC
Epithelial TGTCACGATGGTCAGCCTCCTGTCCAACCTGGGCAGCCAGTGGA
sodium
channel alpha054699 GCCTGTGGTTTGGCTCGTCCGTGCTCTCTGTGGTGGAGATGGCGSEQ ID NO:
subunit
(alpha-ENaC) GAGCTCATCTTCGACCTCCTGGTCATCACACTTCTCATGCTGCTA522
CGCCGGTTCCGGAGCCGGTACTGGTCTCCAGGACGAGGGGCCA
GGGGTGCCAGGGAGGTGGCCTCCACTCCAGCTTCCTCCTTCCC
GTCCCGTTTCTGTCCTCACCCTACATTCCCACCACCTTCTTCGCC
CCAGCAGGGCATGACCCCTCCCCTGGCCCTGACAGCCCCTCCA
CCCGCCTATGCTACTCTAGGCCCCAGTGCCCCTCCACTGGACTC
TGCAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCGCT
CGAGCATGCATCTAGAGGGCCCAATTCGC
TTAATGCAGCTGGCACGACAGGTTTCCCGACTGNAAAGCGGGCA
GTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCAC
CCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAA
TTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATG
ATTACGCCAAGCTATTTAGGTGACACTATAGAATACTCAAGCTAT
GCATCAAGCTTGGTACCGAGCTCGGATCCACTAGTAACGGCCGC
CAGTGTGCTGGAATTCGCCCTTGCGCGAATTCGGGGAATCCTTG
SEQID NO:
Epoxide hydrolaseX65083 TGGGAACTCCAGAAGATCCCAAGGTCAGCAAAATTACTACTGAG
523
GAGGAAATAGAGTATTACATACAGCAGTTCAAGAAGTCTGGCTTC
AGAGGCCCTCTAAACTGGTATCGAAACACAGAAAGAAACTGGAA
GTGGAACTGTAAGGCGTTGGGAAGGAAGATCTTGGTCCCTGCCC
TGATGGTCACAGCTGAGAAGGACATTGTACTCCGTCCTGAAATGT
CCAAGAACATGGAAAACTGGATCCCTTTCCTGAAAAGGGGACAC
ATCGAAAAGCTTGGCCAAGGGCGAATTCTGCAGATATCCATCACA
CTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTC
GTTCCAGTATTGTTGTCACAGGGATAAATAATATTTATCAGCAGTT
TTTGAACAGACAAATTTCTATTTCTATCTTGGAAAAAAAAAGGCAA
ATTTGCCACATTCTCAGGTTATGGCTAGGGGTGTCATTATGGTTC
AAATCCTGCTGAGTATTACATGGTAAGCCTTACTGGCTTTATCCC
TGTGGATTTGGTGGCCTCTGAAGTATTCTTGAACATTGTGTTCTG
E-selectin L25527 TGTCCTGGCATTGAGTCCAGCATAATGTCCGTTATTCTTAGTTCASEQ JD NO:
GTGCAAAAAGACTTAAAAAGTCAGAATCCTGTGGCCCATCACAAG524
GCAAAGGTTATCCTAAATCTCTTTTTGATTAGAAAATCCCAGGATT
ATATCTGCAATAAACCTATTTTCAAGATGAGACATTAATAATCAGT
GTGAAATTCTGAGTATTTAATGGTAGCTGGTTTTCAGACATGGTA
CTATCAAAAGGATAGAAAGTAAAGAGAGTGTATATCTGGGGTTCC
CA
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTGATCCAAATGTGTAGAAGGCA
TGGTGGAGATCTT'fGACATGTTGCTGGCTACGTCAAGTCGATTCC
GCATGATGAACCTGCAGGGAGAAGAGTTTGTGTGCCTCAAATCA
ATCATTTTGCTTAATTCTGGAGTGTACACATTTCTATCCAGCACCT
TGAAGTCTCTGGAAGAGAAGGACCACATCCACCGAGTCCTGGAC
AAGATCACAGACACTTTGATCCACTTGATGGCCAAAGCTGGCCTG
Estrogen receptorY00102 ACTCTGCAGCAACAGCATCGCCGTCTGGCCCAGCTCCTCCTCATSEQ ID
NO:
CCTTTCCCATATCCGGCACATGAGTAACAAAGGCATGGAGCATCT525
CTACAACATGAAATGCAAGAATGTCGTGCCTCCCTATGACCTGCT
GCTGGAGATGCTGGATGCTCATCGTCTTCATGCCCCCGCCAGTC
GCATGGGAGTGCCCCCGGTGGAGCCTAGCCAGAGCCAGCTGAC
CACCACCAGCTCCACTTCAGCACATTCCTTAAGCTTGGCCAAGG
GCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCT
CGGTACCCAACTTGATGCATAGCTTGAGTATTCTATAGTGCACCT
AAATAGCTTGGCG
234
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TGGGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCAGCACGAC
CACACTGGCTTTCTGACCGAGTATGTGGCCACACGCTGGTACCG
AGCCCCAGAGATCATGCTTAACTCCAAGGGCTACACCAAATCCAT
TGACACCTGGTCTGTGGGCTGCATTCTGGCTGAGATGCTCTCCA
ACCGGCCTATCTTCCCCGGCAAGCACTACCTGGACCAGCTCAAC
CACATTCTAGGTATACTGGGTTCCCCATCCCAAGAGGACCTAAATSEQ ID NO:
Extracellular-signal-M61177 TGTATCATTAACATGAAGGCCCGAAACTACCTACAGTCTCTGCCC526
regulated TCTAAAACCAAGGTGGCTTGGGCCAAGCTTTTTCCCAAATCTGAC
kinase 1
TCCAAAGCTCTTGACCTGCTGGACCGGATGTTAACCTTTAACCCA
AACAAGCGCATCACAGTAGAGGAAGCACTGGCTCACCCTTACCT
GGAACAGTACTATGATCCGACAGATGAACCAGTGGCTGAGGAGC
CATTCACCTTTGACATGGAGCTGGATGATCTCCCCAACTGCAGG
GCCAAAGGGCGAATTNCAGCACACTGGCGGNCGNTACTAGTGG
ATCGAGCTCGGTACCAAGCTT
CGGNCAAGNNTANCGATNNTNTAAAACAGTANNATCTATAAAANG
AGATGANCNGTCTNNCACGANNNNGGATTNNNNAANCANNTNCC
ATANANTNGAANGANNGTANNNCNCGANNTNNNNTGGAACAACT
CNCNNNNCTNNACCACAAGATANNCAANATNCCCATATCNANAG
CANANAGAAAGAANNNTCANCANGAAGTNNNNAATTTCNNGNAA
ANGGCANATNATAGNACAANAANGNTCCCAGTGTGATGGATATCT
GCAGAATTCGCCCTTCCCCTGCCCCCTGCAACNACCTTTGCCCA
TTTGGAATGCTACTNACTGTGCTGTCCCGTGCTTATTGCTGAGTT
F1-ATPase GGGCATCTATCCAGCNTGTGGATCCGCTGGACTCCACCTCTCGASEQ ID NO:
beta
subunit M19044 p~T-I-ATGGATCCCAACATCGTTGGCAGTGAGCATTANGATGTTGCT527
CGTGGGGTGCAAAAGATCCTGCAGGACTACAAATCTCTCCAGGA
CATCATTGCCATCTTGGGTATGGATGAACTTTCTGAGGAAGATAA
ATTGACTGTGTCCAGGGCAAGGAAGATACAGCGCTTCTTGTCAC
AGCCATTCCAGGTTGCTGAGGTCTTCACAGGTCACATGGGAAAG
CTGGTGCCCCTGAAGGAGACCATTAAAGGATTCCAGCAGATCTT
AGCAGGTGACTATGACCATCTCCCGGAACAAGCCTTCTACATGG
TGGGACCCATTGAAGAAGCTGTGGCAAAGGCTGACAAGCGGCG
GTNANNANNACACC
TGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTG
GAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCA
CTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTA
TGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACA
GCTATGACCATGATTACGCCAAGCTATTTAGGTGACACTATAGAA
TACTCAAGCTATGCATCAAGCTTGGTACCGAGCTCGGATCCACTA
GTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTGCGCGGATCCSEQID NO:
Farnesol receptorU18374 GGGTTTCAGACACTGGACCACGAAGACCAGATTGCTTTGCTCAA528
AGGGTCCGCAGTCGAGGCCATGTTCCTTCGTTCAGCGGAGATTT
TCAATAAGAAACTTCCTGCCGGACACGCAGACCTGTTGGAAGAA
AGAATTCGAAAGAGCGGCATCTCCGATGAGTACATAACCCCGAT
GTTTAGTTTCTATAAAAGTGTCGGGGAGCTGAAAATGACCCAGGA
AGAGTACGCTCTGCTCACAGCAATTGTCATCCTCTCTCCAGACAG
ACAAAAGCTTGGCCAAGGGCGAATTCTGCAGATATCCATCACACT
GGCGGCCGCTCGAGCATGCATCTAGAGGGCCCAATTCGC
GGNCCAGCTTGGTACCGAGCTCGGATCCACTAGTAACGGCCGC
CAGTGTGCTGGAATTCGCCCTTCGCGGGATCCCTGCACCTCGTG
TGGACTTGAAGACATCCTTGAGCCTTGCACACGAACCAGCAACA
CCAAATGCAAGAAACAAAGTTCCAATTATAAGCTCCTTTGGCTGC
TGATCCTCCCCGGTTTGGCAATTCTATTTGTGTTCATATATAAAAG
GTACCGGAAGAGGCAACCTGGTGACCCTGAATCTGGAATCCCAA
GTCCTGAAAGTGTGCCAATGAATGTCTCAGATGTTAACTTGAATA
~TACATCTGGAGAACTGCCGAAAAAATGAAAATCTGTGACGCTASEQ ID NO:
Fas antigen D26112 AAAAATTTGCTCGGCAGCACAAGATCCCGGAAAGCAAGATCGAT529
GAGATCGAGCACAACAGCCCCCAAGATGCAGCTGAGCAGAAAAT
CCAGCTGCTCCAGTGCTGGTATCAATCTCACGGGAAGACTGGTG
CGTGTCAAGCTTTAATCCAGGGTCTCAGAAAAGCTAACCGCTGC
GACATCGCAGAGGAAATTCAAGCCATGGTCTGGGACTGCAGGGC
CAAGGGCGAATTCGATATCGCGGGCCGCTCGAGCATGCATNTAA
GAGGGCCCTATTCTATAGNGTCACTAAATGCTAAAACTCGCTTGA
TCAACCTCACTGT
235
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
AATACTCAAGTTATGCATCAAGCTTGGTNCCGAGCTCGGATCCAC
TAGTACCGGCCGCCAGTGTGCTGGAATTCGCCCTTCGCGGGATC
CACCTTTAAGTCACCCTGAAGGCATCACCATAGCTACAGCCTCAC
CCAGGGGTAGAGAATAGTACTGTCTACTTGTTGACTACCTGGCA
GTTGGTGCCAGCCCCTATAGAGGAAAACAGCAGTGTGTGGCCTC
TGTGAGAAGCATATCCCTGGAAACAGGTGACCAGAGCAGAGGGC
TAATGCCTACCTGAGTCACACAAAACTGACCAGGCTTGAGTGTCC
SEQID NO:
Fatty acid M76767 AGAAGAGTCTATCAGAAGGCCACAGCATTCAGTCCTATCCACAGA
synthase
530
GAGCAGCAGACTAAGTTGTCTCCTCGCCAGCTTAGAAAACTGCA
GTGCTGGGGTACAGGTAGGGTGTTCAGGAGGTCCGGGCCCCAG
TGATTAGTGTAAGACTGAAGCATCTGGTTGGCTGTGGTCCCACCT
AGAAAATTCTTAAAGCTCTTGTCATGTACTTCCTGGGAAGGACCT
ACCCTGTCTCAATAATGTCTCTAGCTCGTTGGAGTCTACTGACTC
AAAAGCTTGGCCAAGGGCGAATTCTGCAGATATCCATCACACTG
GCGGCCGCTCGAGCATGCATCTAGAGGGCCCNATTCCC
GNGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTCGTTGA
AGATGGCTGAAGATAGTGCAGGCCCTGGGGAGTTTCTCCTTGCT
GAGAGCCGGCTCTGTGGTGAGCCCCTAGCAGCCTTACGAGGCG
GTGAAACGGCCCCTTCAGATGAGGAGCAGCCTCTACAATCATTC
TGAGCTTAAAGGTGAAATATGCACCTTTTGTCCTATAAATGTCCTA
TAAATGCTTGGGGGGAGGGGTAATGTTTTGTTTTTTTTTTCTTGAA
Fatty aryl-CoAJ02752 ACAGGGCCCAGAATGGCCTTGAACTCTGATCCTCACAACCTGGTSEQ ID NO;
oxidase AAATGCTGGGCCTACAGGTGTGCGCCGACATGTCTGGCTGATCG531
GAGCTCTTTATTCTTAAAAGCACAGTGGGGAGATGATTGTAACAT
TAAGTCTGTGTCTGTGGCATTCGCATTGTGAGAGCAGTTCCTTAG
AACAGTTCTGAGAGCACAGCATCAATGTAGTGAAAACGATGTCGA
CGCCTGACATGAAATCACAACCCTCCGGGTCATCGACACAAGCC
TTAAAAGCTTAAGGGCGAATTCCAGCACACTGGCCGGCCGTTCT
AGTGGATCCCAACTCGGTACCAAGCTTGATGCATAACTTGAGTAT
TCTATA
NGCTATGNCCATGATTACGCCAAGCTATTTAGGTGACACTATAGA
ATACTCAAGCTATGCTCAAGCTTGGTACCGAGCTCGGATCCACTA
GTAACGGCCGCCAGTGTGCTGGAATTCGCCCTTATCGCGGGATC
CTGCCATCAACCGCCAGATCAACCTGGAGTTGTATGCCTCCTAC
GTCTATCTGTCCATGTCTTGTTATTTTGACCGGGATGATGTGGCC
CTGAAGAACTTTGCCAAATACTTTCTCCATCAATCTCATGAAGAGA
GGGAGCATGCTGAGAAACTGATGAAGCTGCAGAACCAGCGAGGT
GGACGAATCTTCCTGCAGAATATAAAGAAACCTGACCGTGATGAC
SEQID NO:
Ferritin H-chainU58829 TGGGAGAGCGGGCTGAATGCAATGGAGTGTGCACTGCACTTGGA
532
AAAGAGTGTGAATCAATCACTACTGGAACTTCACAAACTGGCTAC
TGACAAGAATGATCCCTACTTATGTGACTTCATTGAGACGCATTA
CCTGAATGAGCAGGTGAAATCCATTAAAGAACTGGGTGACCACG
TGACCAACTTACGCAAGATGGGAGCCCCTGAATCTGGCATGGCA
GAATATCTCTTTGACAAGCACACCCTGGGACACGGTGATGAGAG
CTAAGCTGACGTCCCCAAGGCCATGTGAAAGCTTGGCCAAAAGG
GCGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCAT
GCTCTAGGNGGCCAATCC
GTATGCATCAAGCTNGGTACCGAGCTCGGATCCACTAGAACGGC
CNGCCAGTGTGCTGGAATTCGCCCTTCGCGGGATCCTTGGGCTG
GGCAATGAGAAGATTCATCTGATAAGCATGCAGTCCACCATCCCA
TACGCACTGAGAATACAGCTCAAAGACTGGAGTGGCAGGACCAG
CACCGCGGACTATGCCATGTTCAGGGTGGGTCCTGAATCCGACA
AATACCGCCTGACCTATGCCTACTTCATTGGCGGAGATGCCGGG
GATGCCTTCGACGGCTACGATTTTGGTGATGATCCCAGTGACAA
Fibrinogen J00734 GTTT1'TCACATCCCACAACGGCATGCACTTCAGTACCTGGGACAASEO ID NO:
gamma
chain TGACAACGACAAGTTCGAAGGCAACTGTGCTGAGCAGGATGGAT533
CTGGCTGGTGGATGAACAAGTGTCACGCTGGCCACCTCAATGGA
GTTTATTACCAAGGTGGCACTTACTCCAAGTCATCTACTCCTAAC
GGTTATGACAATGGCATTATTTGGGCCACCTGGAAAACCCGCTG
GTATTCCATGAAGGAAACCACCATGAAGATAATTCCCTTCAACAG
ACTCTCCATTGGAAAGCTTGGCCAAGGGCGAATTCTGCAGATATC
CATCACACTGGCGGCCGCTCGAGCATGCATCTAGAGGGCCGAAT
TCGCA
236
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTATCGCGTCTAGATGCCC
TTTGGGAGATCTTCTCTAGCATTCCACCAGCAGCGAGGAAGTAAC
CTTGTCCTCGGTCGCCCGCACTCACAGCTCCAACTGATGACAGC
TAGCTGAAAGTCTCTCTTGTATAAGTTTAACTACTTATACATGGTT
TTGATTCTGTTATTTTTCTAAATAGTGTTCAGAAAACTCTGGATCC
AAAATGTGGCATTT'i-I'CTGAGAATGAAGATTGTACATTAAGAAGCT
Focal adhesion ~~'TATACTTGGTGTTCAAATTGGGATGTATGTTCCTAGAAGSEQ ID NO:
kinase
(pp125FAIC) AF020777 TGGTAATTCATACTGACCATGACTTCGAATTGGAAGAGAAGTGTC534
TGAGGAGGGAGGGCTCCCAAGACACTGAGACTGGCTATCCTTCC
TGCCAGAATTCCTGTCCAGACTGAATTGCAATATGCTAATCTCATT
TATAGAGAAAGTGCATAAAAGCTATATTTTGAAGAATGAGTGGTTT
CAAAAGAAAACTTCTGCCCTCCCTGTCAAGGGCGAATTCCAGCA
CACTGGCGGCCGTTACTAGTGGATCCGAGCTCGGGACCAACTTG
ATGCATAACTTGGAGTATTCTATAAGTGNCCCTAAAATAGCTTGG
CGTAATCN
GGGNTCCACTAGTANCGGCCNGCCAGTGTGCTGGAATTCGCCCT
TATCGCGGATCCNTGAGTCTCTGCCTTTCGCCTTTGAGACAGTGT
CCAGCTGGNAGCTGGAAGCNTGGTATGAGGATCTGCAGGAGGT
CCTGTCCTCAGATGAAATTGGGGGCACCTATATCTCATCCCCAG
GAAACGAAGAGGAAGAATCAAAAACCTTCACTACTCTTGACCCTG
CATCCCTAGCTTGGCTGACTGAGGAGCCAGGGCCAGCAGAGGT
CACAAGCACCTCCCAAAGCCCTCGCTCTCCAGATTCCAGTCAGA
GTTCTATGGCTCAGGAGGAAGAAGAGGAAGATCAAGGAAGAACTSEOID NO:
Gadd153 U36994 AGGAAACGGAAACAGAGTGGTCAGTGCGCAGCCCGGGCTGGGA535
AACAGCGCATGAAGGAGAAGGAGCAGGAGAATGAGAGGAAAGT
GGCACAGCTTGCTGAAGAGAACGAGCGGCTCAAGCAGGAAATC
GAGCGCCTGACCAGGGAGGTAGAGACCACACGGCGGGCTCTGA
TCGACCGCATGGTCAGTCTGCACCAAGCATGAACTGTTGGCATC
ACCTCCTGTCTGTCTCTCCCGGAGTGTACCCAGCACCATCACGC
CAGTGCCAAGCATGTAATCTCCAGTGCACATGCTGAGGAGGAAG
CTTGGCCAAAAGGGCGAATTCTGCAGATATCCATCACACTGGCG
GCCGCTCGAGCATGCTTTAGGGGNCCAATC
TTNGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGTCTAGAGACTTTG
GAGGAATTCTCGGCCGCAGAGCAGAAGATCGAAAGGATGGACAC
GGTGGGCGATGCCCTGGAGGAAGTGCTCAGCAAGGCTCGGAGT
CAGCGCACCATAACTGTCGGCGTGTACGAGGCAGCCAAGCTGCT
CAACGTAGACCCGGACAACGTGGTCCTGTGCCTGCTGGCTGCG
GATGAAGATGACGACCGGGACGTGGCTCTGCAGATCCATTTCACSEQID NO:
Gadd45 L32591 CCTCATTCGTGCTTTCTGTTGCGAGAACGACATCAACATCCTGCG536
GGTCAGCAACCCGGGTCGGCTGGCAGAGCTGTTGCTACTGGAG
AACGACAAGAGCCCCGCTGAGAGCGGGGGCGCTGCGCAGACCC
CGGACTTACACTGTGTGCTGGTGACGAACCCACATTCATCACAAT
GGAAGGATCCTGCCTTAAGTCAACTTATTTGTT'ITTGCCGGGAAA
GTCGCTACATGGATCAGTGGGTGCCAGTGATTAATCTCCCCGAA
CGGTGATTCAAGCTTGGCCAAGGCGAATTNCAACACACTGCGGG
CGGTACTATGGATCCAACTCGGACCAACTTGATGCATACTT
GATNANTTCAAGCTCGNCCAANTTCACCAACCAGTTTGGGGTAG
CGCCCTCACCANCCAACTTCATCAAGNCAGGTAAGCANCCGCTT
TCATCCATGTGCCCCTCAATCATCGTGGATAAGAACGGCAAGGTT
CGGATGGTGGTTGGAGCCTCGGAAGGTACCCAGATCACCACGTC
TGTTGCACTGGCCATCATCAACAGCCTGTGGTTCGGGTATGATGTSEQ ID NO:
Gamma-glutamylN133821 GAAGAGAGCTGTGGAGGAGCCCCGTCTTCACAACCAGCTTTTGC537
transpeptidase CCAATACCACAACAGTAGAGAAAAATATTGATCAGGTGGTGACTG
CAGGTCTGAAGACTCGGCACCACCATACAGAGGTCACACCCGAC
TTCATCGCTGTGGTTCAGGCCGTCAAGCTTGGCCAAGGGCGAAT
TCTGCAGATATCCATCACACTGGCGTGCCGCTCGAGCATGCATC
TAGAGGGCCCGTTCANCAGGTAACAAA
237
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTTCACGATTCTTGCTTCC
CAAGCGTGGGTCTGGCCTCCCAAGGGAATGCTTCCTGGACCTTG
CAATGGCCTGGCTTCCCTGGGGGGGACACACCTTCATGGGGAG
GTAACTTCAGCAGTTCGGCCAGACCAGACCCCAGGAGAGTAAGG
GCTGCTAGTCACCCAGACCTGGCTGTTTTCTTGTCTGTGGCTGAA
Glucokinase J04218 GAGGCCGGGGAGCCATGAGAGACTGACTATCCGGCTACATGGASEQ ID
NO:
GAGGACTTTCCAGGCATGAACATGCCAGAGACTGTTGCCTTCATA538
TACCTCCACCCGAGTGGCTTACAGTTCTGGGATGAACCCTCCCA
GGAGATGCCAGAGGTTAGAGCCCCAGAGTCCTTGCTCTAAGGGG
ACCAGAAAGGGGAGGCCTCACTCTGCACTATTCAAGCAGGAATC
ATCTCCAACACTCAGGTCCCTGACCCANGAGGAAGAAGCCACCC
TCAGTGTCCCTCCAGAGACCACCCAGGTAAGGGCGAATTCCAGC
ACACTGGCGGCCGGTACTAGTNGATCCGAGCTCGGACCAA
TGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTGGGC
ACCTTTCTTCAGTCAGCAATGAAGTCCAGAAGAATATTCAGGACT
TTGATGGCTCCAGAATTTTTAATGAAAGCAAGACTGTTGCTCAGA
TCTATTCAGATAAGCAGCAGATTTTATAATTTTTTTATTACTGATTT
TGTTATTATTTTTTTTTTTTATCAGCCACTCTCCTATCTCCACACTG
TAGTCTTCACCTTGATTGGGCTAGTGCCTGAGGGTGGAGACCAC
Glucose transporterM13979 GCCCTGTCCAGACACATGCCTTCTTTGCCAAGCTAATCTGTAGGGSEQ
ID
1 NO:
CTGGACCTTTGGCCAAGGACACACTAATACTGAACAATGAGCTAG539
GAGGCTTTACCGCAGGAGGCGGTAGCTGCCACCCACTTCTGCAG
GCCTGGATCTCGACACCATAGGGGTCCAGGCTCCATTTAGGATT
CGCCCATTCCTGTCTCTTCCAACTCAACCAACCACTCGATTAATC
TTTCCTTGCCTGAGACCAGTTGAAAGCACTGGAGTGCAGGGAGG
AGAGAAGCTTGGCCAAAGGGCGAATTCCAGCACACTGGCGGGC
GGTACTAGTGGATCCGAGCTCGGACCAAACTTTGAGCATAACTT
GAGTATTCTN
NATTCCGCCAAGTATTTAGGGCNCTATAGAATACTCAAGCTATGC
ATCAAGCTGGGTCCGAGCTGGGATCCACTAGTACGCCCGCCAGT
GTGCTGGAATTCGCCCTTGCCACTGTACAAATGGAATTCCTGGG
GTCATCAGAGACTGTGTGAGGATGAGCTGCCTAAAATCCAGGAA
CAGACCAGAAGGGAACCATGTGCTCCCTCTTAACTCGAATCCTTC
ATGAGTGTAGGACTACACCCAGGAGGATCATTTATTCCTTTTGAA
GAATTTGACAGACTCCGATTAGAAACGTCAACATATATCATTACCA
Glucose transporterJ03145 ~G~GTATTTTTTTAACTTAGAGAATCTATTTTGGATGGTAAAASEO ID
2 NO:
CTCTTCAGTAAACCAGAGGCTGCTCTGCTTCTCTACAGGGAAAGC540
ACGTTATAAGCTTCCTCGCCTGGTTCTACTGAAATTGGAGAGCTT
TCAACATATCACTGCTCTTAAAAGCACGTGACTAAGAAATCTGAA
GCTACAACTGATATATATATATATTTAAATATAATTCCATTGGAATT
TTCTTAGCCACAGATCTGATGCTGAAGGACCTATGGCTGGCAAG
GCTCACACTCAAACTGACGTCTCTGTTACCCACCTCGGTTAAGGG
CGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATG
CATCTAGAGGGCCCAATTCGC
GCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATGGATAT
CTGCAGAATTCGCCCTTGCGCGGATCCTGGCATGTTCTTCAACC
CTGAGGAGTCTGAGCTGGACCTAACCTATGGCAACAGATACAAG
AATGTGAAGCTCCCTGATGCCTATGAACGCCTCATCCTGGATGTC
TTCTGTGGGAGCCAAATGCACTTTGTCCGTAGTGATGAACTCAGG
GAAGCCTGGCGTATCTTCACACCATTGCTGCACAAGATTGATCGA
Glucose-6-phosphate GAGAAGCCCCAGCCCATCCCGTATGTCTATGGCAGCCGAGGTCCSEQ ID
NO:
dehydrogenaseX07467 CACAGAGGCAGATGAGCTGATGAAGAGAGTGGGCTTCCAGTATG
541
AGGGAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCG
TTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTG
AGTATTCTATAGTGTCACCTAAATAGCTTGGCGTAATCATGGTCAT
AGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACA
ACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAA
TGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGGCCGCT
TTNCAGTCGGGAAACCTGCGTG'CCN
238
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GAATNGGCCCTCTAGATGCATGCTCGAGCGGCCGCGAGTGTGAT
GGATATCTGCAGAATTCGCGCTTNGCGGGANCCCTGACTGGAAT
CGCTCCTGCTNCCCGTGGGGTACCCCANATTGNANNCACCTTNG
ANATACATGTGAATGGNATTCNTNGAGTGGCANNTGAAGACANA
GGGACAGGNAACANNNACNNANTCACCATCACCAATGACGAAAA
CCGCCTGAGCCCTGAANAAATTGAAAGGATGGTCAGTGAGGCCG
Glucose-regulated ANAANTNNGCTGAGGANGACNAAANGCTCANAGAGCGCATNGAC
SEO ID NO:
protein 78 M14050 ACGANGAATGAATTGGAAAGCTATGCTTACTCTCTTAAGAACCAN
542
ATCCGGANATNAAGAGANGCTGGGAGGTAAGCTGNCTNCTGAAN
ATAANNAGACCATGGAGAAAGCTGTAGAGGAAAAGATCGAATGG
CTGGAAAGCCACCAGGATGCAGACATTGAACACTNTAAAGCTNN
NAAGATNGAACTAGACNANATTGTTCANCCAATTATGAGCAAACT
CTATNGAAGTGGAGGCCCTCCCCCAACTGGGGANGAAGAAGCTT
GGCCCAGGGCGAATTGCATCACACTGGCNGGCGGTACTATTGGA
TCGATCTCGNTCCAACCTGANGCATAGCTTGAGTNTTCTATNNTG
GAATNGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTG
ATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTTCTTGTC
GGCACTGTGGGACCCTACTATAAGCTGGAGAGCCGGTGGCTACA
GGTTGCGCTGTGGAGGGACGGCCGAGGAGATCCTGGGTGTGTA
ACAAGGCCTCTGTGGCCGACTGGACAGGATGGAATGGAAGTGTT
ATAGATTATGTTTATAGAGACTTTCCAGGACCTGCCTTCAGTGGC
TCATCCGTGTATGTGTGGTATCCGCTCTTTAATTTATTCGCATGGC
GlucosylceramideAF047707 CCTTGCATGTGTGAAAAGCAAAAAAP,CAAAAGCAAAACATGTCTGSEQ ID
NO:
synthase TAGTCGTGGCCAAACAGTGTATTTTATGGAGGTAGAGAATCAAGA543
CAATTGGTTCTAGGAAGTGGGT1-i'TGTTGTTGTT1'ATTTTTTTAAA
CAAATATATATATATATCTATCAATACACACACACACACACACACA
CACACACACACGAGTGCTCTGCAGCAGACACTATGACAGTATCCT
TCAGTAGGGAAAGTTTCTTACCTGAGTTACTCACTCTGANGTCCC
CACCAAGCTTGGCGAAAAGGGCGAAATTNCACACACTGGCGGGC
GGTACTAGTGGATCCGAGCTCGGNACCCAAAGCTTGATGGATAA
CTTGGAGTATTCTATAGTGGCCCGTAAATAGCTTNGGCGN
GCGAATTGGGCCCTCTAGATGCATGCTGGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCATCCTAT
TCCCTGGGTGCCAAGTTTGAGTGAGGAGCTCGGTGTAGAAGTGA
GGCACTCTTGAGGTAGGGGTGGGGATGCAGTACTGGGAAAGTT
GGTTATCTTGGGGGTTCAGCTTGATTACTACTTAGGGTTTCCCTG
GCCACCCTGCAGGAGCAGATGTTGGACAGGTAGCCAGTGGGAT
GCCACTGCTTGCCGCCACTGTCCCTGGGCTTAGTTTAAGGGGAC
Glutamine M29579 GTGTATACCTAATCCACACACGAGTTAGAAGTATGAGTTGGCTGGSEQ ID NO:
synthetase
TCAACTTGAACATTGTTACAGGCGGGTGGGTGTTAGTGGGGGGT544
TATTTTTTGGTGGGACTAGCATGTCACTAAAGCGGGCGTTTfGAT
ATATTAAATTTTTTAAAGCAAAACAAGTTTAGATTTTAATCAAGTTC
GTAGGGTTCCTAACTTTACAGAATTGCCTGTTTGTTTCAATGACTC
CTTCCACTTGGCTCTTAGGGGAACTGAGGACAGGCCTGGAAAGC
TTAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATC
GGAGCTCGGTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGT
GCACCTAAATAGCTTGCGTAATCATGG
GCCAAGCTATTTAGGTGNCACTATAGAATACTCAAGGTATGCATC
AAGCTTGGTACCGAGCTCGGATCCACTAGTAACGGCCCGCCAGT
GTGCTGGAATTCGCCCTTATCTGCAGAAGCGTCTGGGCCCTCGT
GGCCTGGTGGTGCTCGGTTTCCCGTGCAATCAGTTCGGACATCA
GGAGAATGGCAAGAATGAAGAGATTCTGAATTCCCTCAAGTATGT
CGGACCCGGTGGTGGGTTCGAGCCCAACTTTACATTGTTTGAGA
AGTGCGAGGTGAATGGTGAGAAGGGTCACCCGCTCTTTACCTTC
Glutafhione M21210 CCGCGGAATGCCTTGCCAGCACCCAGTGACGATCCCACTGCGCTSEQ ID NO:
peroxidase CATGACCGACCCCAAGTACATCATTTGGTCCCCGGTGTGCCGCA545
ACGACATTTCCTGGAACTTTGAGAAGTTCCTGGTAGGTCCAGACG
GTGTTCCAGTGCGCAGATACAGCAGGCGCTTTCGCACCATCGAC
ATCGAACCCGATATAGAAGCCCTGCTGTCCAAGCAGCCTAGCAA
CCCCTAAGGCATTCCTGGTATCTGGGCTTGGTGATGGCTGGCTG
CCCTCCGGGGGGAGGTTTTTCCATGACGGTAAGGGCGAATTCTG
CAGATATCCATCACACTGGCGGCCGATCGAGCATGCATCTAGAG
GGCCCAATTT
239
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
ACTCAAGTTATGCATCAAGCTTGGTACCGAGCTCGGATCCACTTA
GTAACGGCCGCCAGTGTGTTGGAATTCGCCCTTTCGCGGGATCC
GGGCCTGAATCTAAATAAACTGGGGATTCAGACTGATGACAAAG
GCCATATCCTAGTGGACGAGTTCCAGAATGCCAATGTCGAAGGC
GTCTATGCCGTGGGCGATGTCTGTGGGAAAGCACTTCTCACCCC
AGTTGCGATCGCTGCTGGCCGGAAACTCGCCCATAGACTTTTTG
AGGGCAAAGAAGATTCCAGGTTGGACTATGACAACATCCCTACC
Glutathione U73174 GTGGTCTTCAGCCACCCGCCTATCGGGACAGTGGGGCTCACTGASEQ 1D
reductase NO:
AGATGAAGCCGTCCATAAGTATGGCAAAGACAATGTGAAAATCTA546
CTCGACCGCCTTCACCCCGATGTATCACGCTGTGACCACGAGGA
AGACGAAATGCGTGATGAAGATGGTTTGTGCCAACAAAGAGGAG
AAGGTGGTTGGCATCCATATGCAGGGGACTGGCTGCGATGAGAT
GCTTCAGGGCTTCGCTGTAGCAGTGAAAATGGGGGCCACCCAG
GCCGACTTCGACAATAGGGTCGCCAAAGCTT.GGCCAAGGGCGAA
TTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCATC
TAGAGGGCCCAATTC
NGCNCTATAGAATACTCAAGCTATCCATCAAGCTTGGTACCGAGC
TCGGATCCACTAGTAACGGCCGCCAGTGTGCTGGAATTCGCCCT
TGTGTGGATGAGTACCTGGCATGGCAGCATACGACCCTTCGGAG
AAGCTGTCTCCGGACCCTGTGGCATAAGGTGATGTTCCCCGTTTT
CCTGGGTGAGCAGATACGCCCGGAGATGCTGGCAGCCACATTG
GCAGATCTGGATGTTAACGTACAGGTGCTGGAAGACCAGTTCCT
Glutathione CCAGGACAAAGACTTCCTTGTCGGACCGGACATCTCCCTGGCTG
S-
SEO ID
transferase X67654 ACGTGGTAGCTATCACAGAGCTGATGCATCCTGTAGGTGGTGGCNO:
theta-1
547
TGCCCAGTCTTTGAAGGGCGTCCCAGGCTGGCTGCATGGTACAG
GAGAGTGGAGGCAGCTGTGGGGAAGGACCTCTTCCTGGAGGCC
CATGAGGTCATCCTGAAGGTGAGAGACTGTCCACCTGCTGACCC
CGTCATAAAGCAAAAGCTGATGCCCAGAGTGCTGACCATGATCC
AGTGACGTCAGAAGCTTCATCCCTGCACCAGCCAGGCCACTCGC
ATTACACGACTGTAAGGGCGAATTCTGCAGATATCCATCACACTG
GCGGCCGCTCGAGCATGCATCTAGAGGGCCCAA
TGGCCCTCTAGATGCATGCTGGAGCGGCCGCCAGTGTGATGGAT
ATCTGCAGAATTCGCCCTTCGCGGGATCCTGGAAAAGCTAAAGA
AAGACGGGAATTTGATGTTTGACCAAGTGCCCATGGTGGAGATT
GACGGGATGAAGCTGGCAGAGACCAGAGCCATTCTCAACTACAT
CGCCACCAAATATGACCTCTATGGGAAGGACATGAAGGAGAGAG
CCCTGATTGACATGTATTCAGAGGGTATTTTAGATCTGACTGAAA
Glutathione TGATTATCCAATTGGTAATATGTCCCCCAGACCAAAGAGAAGCCASEO ID
S- NO:
transferase X00136 AGACCGCCTTGGCAAAAGACAGGACCAAAAACCGGTACTTGCCT
Ya
548
GCCTTTGAAAAGGTGTTGAAGAGCCATGGCCAAGACTACCTTGTA
GGTAACAGGGTGACCCGGGTAGACATCCACCTGCTGGAACTTCT
CCTCTATGTTGAAGAGTTTGATGCCAGCCTTCTGACCTCTTTCCC
TCTGCTGAAGGCCTTCAAGAGCAGAATCAGCAGCCTCCCCAATG
TGAAGAAGTTCCTGCAGCCTGGCAGTCAGAGAAAGCCAAGCTTG
GCCAAGGGCGAATTCCAGCACACTGGCGGGCGTTCTAGTGGATC
CGACTCGGACCAAGCTTGATGCATACTTGAGTATTC
TTNCGACATGATTACGAATTTAATACGACTCACTATAGGGAATTTG
GCCCTCGAGGCCAAGAATTCGGCACGAGGCCAGCACGATGCCT
ATGACACTGGGTTACTGGGACATCCGTGGGCTGGCTCACGCCAT
TCGCCTGTTCCTGGAGTATACAGACACAAGCTATGAGGACAAGA
AGTTCAAACTGGGCCTGGACTTCCCCAATCTGCCCTACTTAATTG
ATGGGTCACACAAGATCACCCAGAGCAATGCCATCCTGCGCTAC
Glutathione CTTGGCCGGAAGCACAACCTTTGTGGGGAGACAGAGGAGGAGA
S-
transferase M13590 GGATTCGTGTGGACGTTTTGGAGAACCAGGCTATGGACACCCGCSEO ID
Yb2 NO:
subunit ** CTACAGTTGGCCATGGTCTGCTACAGCCCTGACTTTGAGAGAAA549
GAAGCCAGAGTACTTAGAGGGTCTCCCTGAGAAGATGAAGCTTT
ACTCCGAATTCCTGGGCAAGCAGCCATGGTTTGCAGGGAACAAG
ATTACGTATGTGGATTTi.'CTTGGTTACGATGTCCTTGATCAACACC
GTATATTTGAACCCAAGTGCCTGGACGCCTTCCCAAACCTGAAG
GACTTCGTGGCTCGGTTTGAGGGCCTGAAAAAGATATCTGACTA
CATGGAAGACGGGCCGCAAGCTTTATTTCCTTTAGTGAGGGGTT
AATTTTAGCTTNGCACTGGGCCGCCGTTTTACAACGTCGTG
240
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGGGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTG
TGATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCACTCTG
CTGGAGCAGGCCTATGCTGTGCAGATGGACTTCAACATCCTGGT
AGATGCTGTCAGCCAGAACTCCGCCTTCCTGGAGCAAACACTGT
CTAGCACCATCAAAAAGGATGAGTATACTGCCCGTCTCTTTGATA
TCTACAAGCAAGTCCTGAAAGAGGGCATAGCCCAGACTGTGTTC
CTGGGCCTCAATCGTTCAGATTACATGTTCCAGTGCAGCGCAGA
Glutathione CGGCTCCAAAGCCCTGAAACAGATTGAGATCAACACTATCTCTGCSEQ ID NO:
synthetase L38615 CAGCTTTGGGGGCCTGGCCTCCCGGACTCCGGCTGTGCACCGA550
CATGTTCTCAATGTCCTGAATAAGACCAACGAAGCTTCCAAGATC
CTGTCCAACAACCCCAGCAAGGGACTGGCCCTGGGGATCGCCA
AAGCCTGGGAGCTCTATGGCTCAGCCAATGCCGTGGTGCTACTG
ATTGCTCAGGAGAAGGAAAGGAACATATTTGACCAGCGTGCCGT
AGAGAACGAGCTGCTAGACAGGAAGATCCATGTAATCCGCCGAA
GATTTGAAGATGTCTCTGAAANGGGGTCTCTAGACCAAAACCGAA
G
AATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATG
GATATCTGCAGAATTCGCCCTTCGCGGGATCCATCCTGCACCAC
CAACTGCTTAGCCCCCCTGGCCAAGGTCATCCATGACAACTTTG
GCATCGTGGAAGGGCTCATGACCACAGTCCATGCCATCACTGGC
ACTCAGAAGACTGTGGATGGCCCCTCTGGAAAGCTGTGGCGTGA
TGGCCGTGGGGCAGCCCAGAACATCATCCCTGCATCCACTGGTG
Glyceraldehyde CTGCCAAGGCTGTGGGCAAGGTCATCCCAGAGCTGAACGGGAASEO ID NO:
3-
phosphate M17701 GCTCACTGGCATGGCCTTCCGTGTTCCTACCCCCAATGTATCCGT551
dehydrogenase TGTGGATCTGACATGCCGCCTGGAGAAACCTGCCAAGTATGATG
ACATCAAGAAGGTGGTGAAGCAGGCGGCCGAGGGCCCACTAAA
GGGCATCCTGGGCTACACTGAGGACCAGGTTGTCTCCTGTGACT
TCAACAGCAACTCCCATTCTTCCACCTTTGATGCTGGGGCTGGCA
TTGCTCTCAATGACAACTTTGTGAAGCTCATTTCCTGGTATGAAAA
GCTTGGCCAANGGCGAATTCCAGCACACTGGCGGGCGGTACTA
GTGGATCCGAACTCGGTCCAAACTTGATGCATAGCTTGAGT
CATTGAAACGGNNNCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCCAAAGC
CACGGCTGTTATGCCCGATGGACAATNCAAAGATATCAGCCTAA
GTGATTACAAAGGAAAATATGTTGTATTCTTTTTTTACCCTCTTGA
CTnACTTfTGTGTGTCCCACGGAGATCATTGCTTTCAGTGATAGSEQ ID NO:
Heme binding D30035 AGCNGAANAATTTAAGAAACTCAACTGCCAAGTGATTGGAGCTTC552
protein
23 TGTGGATNNTCACTTCTGTCATCTGGCATGGATTAACACACCCAA
NAAACAAGGAGGATTGGNACCCATGAACATTCCCTTGGTATCAGA
TCCCAAGCGCACCATTGCTCANGATTATGGAGTCTTAAAAGCTGA
TGAAGGTATCNTCTTTCANGGGCCTNTTTATTATTGATGATAAAG
GTATCCTTCNCANATTAACCGATAAATGATCTTTCTGTTGGG
GGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTCTGCA
CTGCTGTCTGACCATCGAGGTGCCACCTATGCCTTCAGTGGCTC
CCACTACTGGCGTCTGGACTCCAGCCGTGATGGGTGGCATAGCT
GGCCCATTGCTCATCACTGGCCCCAGGGTCCTTCAGCAGTAGAT
GCTGCCTTTTCCTGGGATGAGAAAGTCTATCTGATCCAGGGCACT
CAAGTATATGTCTTCCTGACGAAGGGGGGCAATAACCTAGTAAGT
GGTTATCCAAAGCGGCTGGAGAAGGAACTTGGGAGCCCTCCCGSEQ ID NO:
Hemopexin M62642 GGATCAGCCTTGATACCATAGATGCAGCCTTTTCCTGCCCTGGTT553
CTTCCAAGCTCTACGTCACATCAGGACGGCGGCTTTGGTGGCTG
GACCTGAAGTCAGGAGCCCAGGCGACATGGGCAGAACTTTCCTG
GCCCCATGAGAAAGTTGATGGTGCCCTGTGTTTGGAAAAGTCCC
TTGGTCCCTACTCATGCTCTTCCAATGGTCCAAGCTTGGCCAAGG
GCGAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCT
CGGTACCAAGCTTTGATGCATAGCTTGAGTATTCTATAGTGTCAC
CTAAATAGCTTGGCGTAATCATGGTN
241
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
TTGGGAATTGGCCCTCTAGATGCATGCTCGAGCGGNCGGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCCGTTGC
AACAGTCTGGGCTATGACATCCGCAGGGATCGGCCACGCAAGAG
CAAGACACTCTTCCTCATCACCCAAGCCCAGTCCCCCTTCAAAGT
TTATCATTACCAGTTCAAGATCCAGTTCATCAATCAAATGGAGAAG
CCAATAGAGCCTACTTTTACCATGACACTGCTGGGGACAAAAGAA
GAAATAAAGAAAATTCCCATCACCCTGGGCGAAGGAATTACCAGC
Hepatic VipaseM16235 ~T~CCTATTCCTTACTTATCACACTGGACAAAGACATCGGCSEQ ID
NO:
GAGTTGATCATGCTCAAGTTCAAGTGGGAAAACAGCGCAGTGTG554
GGCCAATGTCTGGAACACAGTGCAGACCATAATGCTATGGGACA
CAGAGCCTCACTACGCGGGCCTCATTCTGAAGACCATCTGGGTC
AAAGCTGGAGAGACGCAGCAAAGAATGACATTTTGCCCTGATAAT
GTGGATGATCTCCAGCTTCACCCCACCCAGGAGAAAGTCTAAGC
TTGGCCAAGGGCGAATTCCAAGCACACTGGCGGCCGTTACTAGT
GGNTCCGAGCTCGGTCCAAGCTTGATGCATAGCTTGGAGTATTC
TATAGTGNCACCCTAAA
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCCTTCAAG
TACTAAGGGCATGAAATATCTTGCCAGCAAAAAGTTTGTGCACAG
AGACTTAGCTGCAAGAAACTGCATGTTGGATGAAAAATTCACTGN
CAAGGGTGCTGATTTCGGTCTTGCCAGAGACATGTACGACAAAG
AGTATTATAGCGTCCACAACAAAACGGGTGCGAAACTACCGGTG
Hepatocyte AAGTGGATGGCTTTGGAGAGTCTGCAGACGCRAAAGTTCACCACSEQ ID
growth ' NO
:
factor receptorX96786 CAAGTCAGACGTGTGGTCCTTCGGTGTGCTT
CTCTGGGAGCTCA
555
TGACGAGAGGAGCCCCTCCTTATCCTGACGTGAACACATTTGATA
TCACTATATACCTGTTGCAAGGCAGAAGACTCTTGCAACGAGAGT
ACTGTCCAGACGCCTTGTATGAAGTGATGCTAAAATGCTGGCACC
CCAAAGCAGAAATGCGCCCA'TCGTTTTCTGAACTGGTCTCCAGG
ATATCCTCAATCTTCTCCACTTTCATTGGCGAGCACTATGTCAAG
CTTGGCCAAAAAGGCGAATTCCAGCACACTGGCGGGCGGTACTA
GTGGATCCGAGCTCCGG
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCCTGCGG
TCACAGGTGCAGGTGAGCCTGGAGGATTACATCAACGACCGGCA
GTATGACTCTCGGGGTCGTTTTGGAGAGCTGCTGCTGCTCCTGC
CCACTCTGCAGAGCATTACCTGGCAGATGATCGAGCAGATCCAG
TTCATCAAGCTCTTTGGCATGGCCAAGATTGACAACCTGCTGCAG
GAGATGCTGCTTGGAGGGTCTGCCAGTGACGCGCCGCACGCCC
Hepatocyte D10554 ACCACGCCCTGCACCCTCACCTGATGCAAGAACACATGGGCACCSEQ ID
nuclear NO:
factor4 AATGTCATAGTTGCCAACACGATGCCCTCTCACCTCAGCAATGGA556
CAGATGTCCACCCCTGAGACTCCACAGCCATCACCACCAAGTGG
CTCTGGATCTGAATCCTACAAGCTCCTGCCAGGAGCCATCACCA
CCATCGTCAAGCCTCCCTCTGCCATCCCCCAGCCAACGATCAAG
CTTGGCCAAAGGGCGAATTCCAGCACACTGGCGGCCGTTACTAG
TGGATCCGAGCTCGGTACCAAGCTTGATGCATAGCTTGAGTATTC
TATAGTGTCACCTAAATAGCTTGGCGTAATCATGGCATAGCTGGT
TCCTGTGTGAAATTGGTATCCGGTCAGA
GCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGATGGATAT
CTGCAGAATTCGCCCTTATCGCGGGATCCCGTCTGCTTTACAAG
GGCAACTCACGAAATCTCTGGCAGACATCACTGCAAAGCTGCAG
AAGGGCAGTCCGCACTTCATCCTTTGCGTCAAGCCTAATACCTCA
CAGCTACCTGGTGTGTTCGATCACTTCTACGTGTCTGCCCAACTG
CAGTACCTCGGTGTCCTAGGGCTGGTGAGGCTGTTCCGCTATGG
GTACCCAGTGCGCCCTTCCTTCGAGGACTTCCTGTCCAGATATG
SEQID NO:
Histone 2A 095113 AGCCACTGGCTTCTGTCCTCCTGGGTGAGAAGAAGGGTCAGCCC
557
GCCGAGGAGAGATGTCGGCTGGTTCTCCAGCGGTGTAAACTACA
AGGTTGGCAGATGGGCGTCCACAAAGTGTTCCTGAAGTACTGGC
AGGTGGACCAGCTGGTGACACAATACGAAGCTTGGCCAAAGGGC
GAATTCCAGCACACTGGCGGCCGTTACTAGTGGATCCGAGCTCG
GTACCAAGCTTGATGCATAGCTTGAGTATTCTATAGTGTCACCTA
AATAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAAA
TTGTATCCGCTCACAATTCCACACAACATN
242
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGGGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGGTTT
GTGAAGCTGTCATTCCAGCCAAGGTGGTGAGAGAAGTATTAAAG
ACGACTACGGAAGCTATGGTTGACGTAAACATTAACAAGAATCTT
GTGGGCTCTGCCATGGCTGGTAGCATAGGAGGCTACAACGCCCA
TGCTGCCAACP,TCGTCAGTGCCATCTACATTGCATGTGGCCAGG
ATGCAGCACAGAATGTGGGGAGTTCAAACTGTATTACGTTAATGG
SEQID NO:
HMG CoA reductaseX55286 AAGCAAGTGGTCCCACAAATGAAGACTTATACATCAGCTGTACCA
558
TGCCGTCTATAGAGATCGGAACCGTGGGTGGTGGGACCAACCTT
CTACCTCAGCAAGCCTGCCTGCAGATGCTAGGTGTTCAAGGGGC
GTGCAAAGACAATCCTGGAGAAAATGCACGGCAGCTTGCCCGAA
TTGTGTGTGGCACTGTGATGGCTGGTGAGTTGTCCTTGATGGCA
GCATTGGCAGCAGGACATCTTGTCAGAAGTCACATGGTTCACAAA
GCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGNTCTAGT
GGATCCGAGCTCGGACCAACTTGATGCATACTT
NCGAAGCTTGGTACCGAGCTCGGATCCACTAGTAACGGCCGCCA
GTGTGCTGGAATTCGCCCTTCGCGGGATCCTTGCCATGCATCTTT
TCTCCAAGTCTCTCTTCAGTTCCAAGGCCAAGGTGATCTATCTCA
TCAGAAATCCCAGAGATGTTCTTGTTTCTGGTTATTATTTCTGGGG
TAAGACAACTCTTGCGAAGAAGCCAGACTCACTGGGAACGTATG
TTGAATGGTTCCTCAAAGGATATGTTGCGTATGGATCATGGTTTG
AGCACATCCGTGCCTGGCTGTCTATGCGAGAATTAGACAACTTCT
HydroxysteroidM33329 TGTTACTGTACTATGAAGACATGAAAAAGGATACAATGGGAACCASEQ ID
NO:
sulfotransferase TAAAGAAGATATGTGACTTCCTAGGGAAAAAATTAGAGCCAGATG559
a
AGCTGGATTTGGTCCTCAAGTACAGTTCCTTCCAAGTCATGAAAG
AAAACAACATGTCCAATTATAATCTCATGGAGAAGGAACTGATTCT
TCCTGGTTTTACTTTCATGAGAAACGGCACTACTGGGGACTGGAA
GAATCACTTCACTGTAGCCCAAGCTGAAGCCTAAGCTTGGCCAA
GGGCGAATTCGATATCGCGGCCGCTCGAGCATGCATCTAGAGG
GCCCTATTCTATAGTGTCACCTAAATGCTAGAGCTCGCTGATCAA
NCCTCGACTGNG
GAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGTGA
TGGATATCTGCAGAATTCGCCCTTCGCGGGATCCTGCTGAAGATT
TGGAAAAGGTGTTTATTCCTCATGGACTGATTATGGACAGGACTG
AAAGACTTGCTCGAGATGTCATGAAGGAGATGGGAGGCCATCAC
ATTGTGGCCCTCTGTGTGCTGAAGGGGGGCTATAAGTTCTTTGGT
Hypoxanthine- GACCTGCTGGATTACATTAAAGCGCTGAATAGAAATAGTGATAGG
uanine TCCATTCCTATGACTGTAGATTTTATCAGACTGAAGAGCTACTGTA
NO:
SEQ
phosphoribosyltransfeX62085 ATGAGCAGTCAACGGGGGACATAAAAGTTATTGGTGGAGATGATO
ras e CTCTCAACTTTAACTGGAAAGAACGTCTTGATCGTTGAAGATATAA
TTGACACTGGTAAAACAATGCAGATTTTGCTTTCCTTGGTCAAGC
AGTACAGCCCCAAAATGGTTAAGGTTGCAAGCTTGCTGGTGAAAA
GGACCTCTCGAAAGTGTTGGATACAGGCCAGACTTTGTTGGATTT
GAAATTCCAGACAAGTTTGTTGTTGGATATGCCCTTGACGCAGGC
CAAGGGCGAATTCCAGACACTGGCGGNCGTACTAGTGGATCCGA
GCTCGGACCAAGCTTGATGCATACTT
GCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTATGCCAGATCACAGCACAT
TCACAGCTCCCCAGCATTTCACCAATGCATTGCTGTAGTGTCGTT
TAAAATGCACCTTTTTATTTATTTATTTTTGGTGAGGGAGTTTGTC
CCTTATTGAATTATTTTTAATGAAATGCCAATATAATTTTTTAAGAA
GGCAGTAAATCTTCATCATGATGATAGGCAGTTGAAAATTTTTTAC
Hypoxia-inducible TCATTTTTTTCATGTTTTACATGAAAATAATGCTTTGCCAGCAGTASEQ 1D
NO:
factor 1 alphaAF057308 CATGGTAGTCACAATTGCACAATATATTTTCTTAAAAATACCAGCA
561
GTTACTCATGCATATATTCTGCATTTATGAAACTAGTTTTTAAGAA
GAAACTTTTTTTGGCCTATGGAATTGTTAAGCCTGGATCATGATG
CTGTTGATCTTATAATGATTCTTAAACTGTATGGTTTCTTTATATGG
GTAAAGCCATTTACATGATATAGAGAGATATGCTTATATCTGGAA
GGTATATGGCATTTATTTGGATAAAATTCTCAATTGAGAAGTTATC
TGGTGTTTCTTTACTTTACCGGCTCAAAAGAAAACAGTCCCTATG
AAGGGCGAATTCCAGCACACTGCGGG
243
CA 02440008 2003-09-03
WO 02/066682 PCT/US02/02935
GGATTTCGCCCTTATCGNGGGATCCAAAGCGTTGCCATCTCGCG
CTTGCGCTTGGNACGNCGCCTGCCCCCCCTTGCTGGGACGAAC
AGGCAGGTGAACGTTCTGCTCTACGACATGAACGGCTGCTACTC
ACGCCTCAAGGAGCTGGTGCCTACCCTGCCTCAGAACCGCAAAG
TGAGCAAGGTGGAGATACTGCAGCATGTTATCGACTACATCAGG
GACCTGCAGCTGGAGCTGAACTCTGAGTCTGAAGTCGCGACCGC
CGGAGGCCGGGGGCTGCCCGTCCGGGCCCCGCTCAGCACCCT
SEQID NO:
ID-1 D10862 GAACGGCGAGATCAGTGCCTTGGCGGCCGAGGCGGCATGTGTT
562
CCAGCCGACGACCGCATCTTGTGTCGCTGAGGCGGCGCACTGA
GGAACCAGATGGACTCCAGCCCTTCAGGAGGCAAGAGGAAAAAA
AGTGCTCTCGGTTCCCCAGAGCAACCCGGGGAAAGACACTACCG
CGGCCACGGGACTCTTGACGGATCTGTCCAGGGGGTAGAGGGT
TGATCAACGGAGTCTCGCCCTCTCCAAGCTTGGCCAAAGGGCGA
ATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCAT
CTAGAGGGCCNGTTTTCCAA
TTGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGT
GTGATGGATATCTGCAGAATTCGCCCTTATCGCGGGATCCTGCC
CGAGAGTGAGGATGAGGAGAGCTATGACACGGAGTGAGAATTCA
CGGAAGATGAGTTGCCCTACGATGACTGTGTGTTTGGAGGCCAG
CGTCTGACGTTATAAGAGGAAAGTGGCCAAAGGAACGTGGACTT
GTATATTTGTACAAATAGAGTTTTATTTTTCTAAAAAAAAAAAAGAA
AAAGAAAAAAAAATAAGAAAGGGTATACTTAGCACCACAGCACAC
SEQID NO:
Ik8-a X63594 AGCGCCTAGCCCCGAGCATTCTATTGTGGTGATTCAGCTGTTGTT
563
CTTGTGAAATTTGGGGAAACAGATCACTGAAATTCAAAGGAAATG
TCTCCTAAGGTTCATGTTTGTGGGATTTTTTTTTTTGAGGTGATTT
TCCAGAATCTGATAAAAGGACCACATTTTATTTATTGTGCTTTTGG
TTGAACCGCCATAGACTGTAGCTGACCCCAGTGTGCCCTCTCAC
GTAAGAACCAGGTGTTCAGTGGTATGTGCTTAAGCACCCCAGCT
GAGAAGCTTAAGGGCGAATTCCAGCACACTGGCGGCCGTACTAG
TGGATCCGAGCTCGGACCCAACTTTGATGCAT
TTGGCGAATTGGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAG
TGTGATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCGGAGC
CTCGACCTCTGCATGCCCTCACCCGTGGCCAGGGAGCCTGTGTA
CTAGAACCTGCCGCACCCGCCACGAGCAGCTTGTCCGGTTCTCA
GCATGAAGAGGCAAAGGCTGCTGTGGCCTCTGAGGATGAGCTTG
CCGAGAGCCCAGAGATGACAGAGGAACAGCTGCTGGATAGCTTC
Insulin-like CACCTCATGGCCCCATCCCGTGAGGACCAGCCCATCCTGTGGAA
growth
factor bindingM89791 TGCCATTAGCACCTACAGCAGCATGCGGGCCCGGGAGATCACTGSEO ID
protein NO:
1 ACCTCAAGAAATGGAAGGAGCCCTGCCAACGGGAACTCTATAAA564
GTGTTAGAGAGATTAGCTGCCGCTCAACAGAAAGCAGGAGATGA
GATCTACAAATTTTATCTGCCAAACTGCAACAAGAATGGATTTTAT
CACAGCAAACAGTGCGAGACATCTCTGGATGGAGAAGCTGGGCT
CTGCTGGTGTGTCTACCCATGGAGTGGGAAGAAGATCCTTGGAT
CAAGCTTGGCCAAGGGCGAATTCCAGCACACTGGCGGCCGGTA
CTAGTGGATCCGAGCTCGGTACCAACTTGATGCATAGCTTGAGTA
TTCTATAGTGNCACCTAAATAGCTTGG
TGCGAATTGGCCCTCTAGATGCATGCTCGAGCGGCCGCCAGTGT
GATGGATATCTGCAGAATTCGCCCTTCGCGGGATCCCTGAAGGC
GCTGCTGAATGGCCGCGGGTTCTGCGCCAACGCCAGCGCCGCC
AGCAACCTGAGTGCCTACCTCCCCTCCCAGCCGTCTCCTGGAAA
CACCACTGAGTCTGAGGAGGACCACAATGCTGGGAGTGTGGAAA
GCCAGGTTGTCCCCAGCACACATCGCGTGACTGATTCCAAGTTC
Insulin-like CATCCACTCCATTCAAAGATGGAGGTCATCATAAAAGGCCAGGCT
growth
factor bindingM33300 AGGGACAGCCAGCGCTACAAAGTTGACTATGAGTCCCAGAGCACSEO ID
protein NO:
3 AGACACCCAGAACTTCTCCTCCGAGTCTAAGCGGGAGACAGAAT565
ATGGTCCCTGCCGCAGAGAAATGGAGGACACACTGAATCATCTG
AAGTTCCTCAATGTGCTGAGTCCCAGGGGCGTCCACATCCCAAA
CTGTGACAAGAAGGGGTTCTATAAGAAGAAACAGTGTCGCCCTT
CCAAAGGCAGAAAGCGGGGCTTCTGCTGGTGCGTGGACAAGTA
CGGGCAGCCATTGAAGCTTGGCCAAGGCGAATTCCAGACACTTG
GCGGCCGTTCTAGTGGATCCGACTCGGTACCCAACTTGATGCAT
AGCTTGAGTATTCTATATGTCACCTAA
244
DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 2
~~ TTENANT LES PAGES 1 A 236
NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
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