Note: Descriptions are shown in the official language in which they were submitted.
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Novel Compounds
Field of Invention
This invention relates to newly identified polypeptides and polynucleotides
encoding such polypeptides, to their use in diagnosis and in identifying
compounds that may
be agonists, antagonists that are potentially useful in therapy, and to
production of such
polypeptides and polynucleotides. The polynucleotides and polypeptides of the
present
invention also relate to proteins with signal sequences which allow them to be
secreted
extracellularly or membrane-associated (hereinafter often referred
collectively as secreted
proteins or secreted polypeptides).
Background of the Invention
The drug discovery process is currently undergoing a fundamental revolution as
it
embraces "functional genomics", that is, high throughput genome- or gene-based
biology.
This approach as a means to identify genes and gene products as therapeutic
targets is
rapidly superseding earlier approaches based on "positional cloning", A
phenotype, that is a
biological function or genetic disease, would be identified and this would
then be tracked
back to the responsible gene, based on its genetic map position.
Functional genomics relies heavily on high-throughput DNA sequencing
technologies and the various tools of bioinformatics to identify gene
sequences of potential
interest from the many molecular biology databases now available. There is a
continuing
need to identify and characterise further genes and their related
polypeptides/proteins, as
targets for drug discovery.
Proteins and polypeptides that are naturally secreted into blood, lymph and
other
body fluids, or secreted into the cellular membrane are of primary interest
for
pharmaceutical research and development. The reason for this interest is the
relative ease to
target protein therapeutics into their place of action (body fluids or the
cellular membrane).
The natural pathway for protein secretion into extracellular space is the
endoplasmic
reticulum in eukaryotes and the inner membrane in prokaryotes (Palade, 1975,
Science, 189,
347; Milstein, Brownlee, Harrison, and Mathews, 1972, Nature New Biol., 239,
117;
Blobel, and Dobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand,
there is no known
natural pathway for exporting a protein from the exterior of the cells into
the cytosol (with
the exception of pinocytosis, a mechanism of snake venom toxin intrusion into
cells).
Therefore targeting protein therapeutics into cells poses extreme
difficulties.
The secreted and membrane-associated proteins include but are not limited
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to all peptide hormones and their receptors (including but not limited to
insulin,
growth hormones, ehemokines, eytokines, neuropeptides, integrins, kallikreins,
lamins, melanins, natriuretic hormones, neuropsin, neurotropins, pituitiary
hormones, pleiotropins, prostaglandins, secretogranins, selectins,
thromboglobulins,
thymosins), the breast and colon cancer gene products, leptin, the obesity
gene
protein and its receptors, serum albumin, superoxide dismutase, spliceosome
proteins, 7TM (transmembrane) proteins also called as G-protein coupled
receptors,
immunoglobulins, several families of serine proteinases (including but not
limited
to proteins of the blood coagulation cascade, digestive enzymes),
deoxyribonuclease
I, etc.
Therapeutics based on secreted or membrane-associated proteins approved
by FDA or foreign agencies include but are not limited to insulin, glucagon,
growth
hormone, chorionic gonadotropin, follicle stimulating hormone, luteinizing
hormone, calcitonin, adrenocorticotropic hormone (ACTH), vasopressin,
interleukines, interferones, immunoglobulins, lactoferrin (diverse products
marketed
by several companies), tissue-type plasminogen activator (Alteplase by
Genentech),
hyaulorindase (Wydase by Wyeth-Ayerst), dornase alpha (Pulmozyme\ by
Genentech), Chymodiactin (chymopapain by Knoll), alglucerase (Ceredase by
Genzyme), streptokinase (Kabikinase by Pharmacia) (Streptase by Astray, etc.
This
indicates that secreted and membrane-associated proteins have an established,
proven history as therapeutic targets. Clearly, there is a need for
identification and
characterization of further secreted and membrane-associated proteins which
can
play a role in preventing, ameliorating or correcting dysfunction or disease,
including but not limited to diabetes, breast-, prostate-, colon cancer and
other
malignant tumors, hyper- and hypotension, obesity, bulimia, anorexia, growth
abnormalities, asthma, manic depression, dementia, delirium, mental
retardation,
Huntington's disease, Tourette's syndrome, schizophrenia, growth, mental or
sexual
development disorders, and dysfunctions of the blood cascade system including
those leading to stroke. The proteins of the present invention which include
the signal
sequences are also useful to further elucidate the mechanism of protein
transport which
at present is not entirely understood, and thus can be used as research tools.
Summary of the Invention
The present invention relates to particular polypeptides and polynucleotides
of the
genes set forth in Table I, including recombinant materials and methods for
their production.
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Such polypeptides and polynucleotides are of interest in relation to methods
of treatment of
certain diseases, including, but not limited to, the diseases set forth in
Tables III and V,
hereinafter referred to as "diseases of the invention". In a further aspect,
the invention
relates to methods for identifying agonists and antagonists (e.g., inhibitors)
using the
materials provided by the invention, and treating conditions associated with
imbalance of
polypeptides and/or polynucleotides of the genes set forth in Table I with the
identified
compounds. In still a further aspect, the invention relates to diagnostic
assays for detecting
diseases associated with inappropriate activity or levels the genes set forth
in Table I.
Another aspect of the invention concerns a polynucleotide comprising any of
the nucleotide
sequences set forth in the Sequence Listing and a polypeptide comprising a
polypeptide
encoded by the nucleotide sequence. In another aspect, the invention relates
to a polypeptide
comprising any of the polypeptide sequences set forth in the Sequence Listing
and
recombinant materials and methods for their production. Another aspect of the
invention
relates to methods for using such polypeptides and polynucleotides. Such uses
include the
treatment of diseases, abnormalities and disorders (hereinafter simply
referred to as diseases)
caused by abnormal expression, production, function and or metabolism of the
genes of this
invention, and such diseases are readily apparent by those skilled in the art
from the homology
to other proteins disclosed for each attached sequence. In still another
aspect, the invention
relates to methods to identify agonists and antagonists using the materials
provided by the
invention, and treating conditions associated with the imbalance with the
identified
compounds. Yet another aspect of the invention relates to diagnostic assays
for detecting
diseases associated with inappropriate activity or levels of the secreted
proteins of the present
invention.
Description of the Invention
In a first aspect, the present invention relates to polypeptides the genes set
forth in
Table I. Such polypeptides include:
(a) an isolated polypeptide encoded by a polynucleotide comprising a sequence
set forth in
the Sequence Listing, herein when refernng to polynucleotides or polypeptides
of the
Sequence Listing, a reference is also made to the Sequence Listing referred to
in the
Sequence Listing;
(b) an isolated polypeptide comprising a polypeptide sequence having at least
95%, 96%,
97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence
Listing;
(c) an isolated polypeptide comprising a polypeptide sequence set forth in the
Sequence
Listing;
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(d) an isolated polypeptide having at least 95%, 96%, 97%, 98%, or 99%
identity to a
polypeptide sequence set forth in the Sequence Listing;
(e) a polypeptide sequence set forth in the Sequence Listing; and
(f) an isolated polypeptide having or comprising a polypeptide sequence that
has an Identity
Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence
set forth in the
Sequence Listing;
(g) fragments and variants of such polypeptides in (a) to (f).
Polypeptides of the present invention are believed to be members of the gene
families set
forth in Table II . They are therefore of therapeutic and diagnostic interest
for the reasons
set forth in Tables III and V. The biological properties of the polypeptides
and
polynucleotides of the genes set forth in Table I are hereinafter referred to
as "the biological
activity" of polypeptides and polynucleotides of the genes set forth in Table
I. Preferably, a
polypeptide of the present invention exhibits at least one biological activity
of the genes set
forth in Table I.
Polypeptides of the present invention also include variants of the
aforementioned
polypeptides, including all allelic forms and splice variants. Such
polypeptides vary from
the reference polypeptide by insertions, deletions, and substitutions that may
be
conservative or non-conservative, or any combination thereof. Particularly
preferred
variants are those in which several, for instance from 50 to 30, from 30 to
20, from 20 to 10,
from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acids are
inserted, substituted,
or deleted, in any combination.
Preferred fragments of polypeptides of the present invention include an
isolated
polypeptide comprising an amino acid sequence having at least 30, 50 or 100
contiguous
amino acids from an amino acid sequence set forth in the Sequence Listing, or
an isolated
polypeptide comprising an amino acid sequence having at least 30, 50 or 100
contiguous
amino acids truncated or deleted from an amino acid sequence set forth in the
Sequence
Listing. Preferred fragments are biologically active fragments that mediate
the biological
activity of polypeptides and polynucleotides of the genes set forth in Table
I, including
those with a similar activity or an improved activity, or with a decreased
undesirable
activity. Also preferred are those fragments that are antigenic or immunogenic
in an animal,
especially in a human.
Fragments of a polypeptide of the invention may be employed for producing the
corresponding full-length polypeptide by peptide synthesis; therefore, these
variants may be
employed as intermediates for producing the full-length polypeptides of the
invention. A
polypeptide of the present invention may be in the form of the "mature"
protein or may be a
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part of a larger protein such as a precursor or a fusion protein. It is often
advantageous to
include an additional amino acid sequence that contains secretory or leader
sequences, pro-
sequences, sequences that aid in purification, for instance multiple histidine
residues, or an
additional sequence for stability during recombinant production.
Polypeptides of the present invention can be prepared in any suitable manner,
for
instance by isolation form naturally occurring sources, from genetically
engineered host
cells comprising expression systems (vide infra) or by chemical synthesis,
using for instance
automated peptide synthesizers, or a combination of such methods. Means for
preparing
such polypeptides are well understood in the art.
In a further aspect, the present invention relates to polynucleotides of the
genes set forth in
Table I. Such polynucleotides include:
(a) an isolated polynucleotide comprising a polynucleotide sequence having at
least 95%,
96%, 97%, 98%, or 99% identity to a polynucleotide sequence set forth in the
Sequence
Listing;
(b) an isolated polynucleotide comprising a polynucleotide set forth in the
Sequence
Listing;
(c) an isolated polynucleotide having at least 95%, 96%, 97%, 98%, or 99%
identity to a
polynucleotide set forth in the Sequence Listing;
(d) an isolated polynucleotide set forth in the Sequence Listing;
(e) an isolated polynucleotide comprising a polynucleotide sequence encoding a
polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a
polypeptide sequence set forth in the Sequence Listing;
(f) an isolated polynucleotide comprising a polynucleotide sequence encoding a
polypeptide set forth in the Sequence Listing;
(g) an isolated polynucleotide having a polynucleotide sequence encoding a
polypeptide
sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide
sequence
set forth in the Sequence Listing;
(h) an isolated polynucleotide encoding a polypeptide set forth in the
Sequence Listing;
(i) an isolated polynucleotide having or comprising a polynucleotide sequence
that has an
Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polynucleotide
sequence set
forth in the Sequence Listing;
(j) an isolated polynucleotide having or comprising a polynucleotide sequence
encoding a
polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or
0.99 compared
to a polypeptide sequence set forth in the Sequence Listing; and
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polynucleotides that are fragments and variants of the above mentioned
polynucleotides or
that are complementary to above mentioned polynucleotides, over the entire
length thereof.
Preferred fragments of polynucleotides of the present invention include an
isolated
polynucleotide comprising an nucleotide sequence having at least 15, 30, 50 or
100
contiguous nucleotides from a sequence set forth in the Sequence Listing, or
an isolated
polynucleotide comprising a sequence having at least 30, 50 or 100 contiguous
nucleotides
truncated or deleted from a sequence set forth in the Sequence Listing.
Preferred variants of polynucleotides of the present invention include splice
variants, allelic variants, and polymorphisms, including polynucleotides
having one or more
single nucleotide polymorphisms (SNPs).
Polynucleotides of the present invention also include polynucleotides encoding
polypeptide variants that comprise an amino acid sequence set forth in the
Sequence Listing
and in which several, for instance from 50 to 30, from 30 to 20, from 20 to
10, from 10 to 5,
from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues are
substituted, deleted or
added, in any combination.
In a further aspect, the present invention provides polynucleotides that are
RNA transcripts
of the DNA sequences of the present invention. Accordingly, there is provided
an RNA
polynucleotide that:.
(a) comprises an RNA transcript of the DNA sequence encoding a polypeptide set
forth in the Sequence Listing;
(b) is a RNA transcript of a DNA sequence encoding a polypeptide set forth in
the
Sequence Listing;
(c) comprises an RNA transcript of a DNA sequence set forth in the Sequence
Listing; or
(d) is a RNA transcript of a DNA sequence set forth in the Sequence Listing;
and RNA polynucleotides that are complementary thereto.
The polynucleotide sequences set forth in the Sequence Listing show homology
with the polynucleotide sequences set forth in Table II. A polynucleotide
sequence set forth
in the Sequence Listing is a cDNA sequence that encodes a polypeptide set
forth in the
Sequence Listing. A polynucleotide sequence encoding a polypeptide set forth
in the
Sequence Listing may be identical to a polypeptide encoding a sequence set
forth in the
Sequence Listing or it may be a sequence other than a sequence set forth in
the Sequence
Listing, which, as a result of the redundancy (degeneracy) of the genetic
code, also encodes
a polypeptide set forth in the Sequence Listing. A polypeptide of a sequence
set forth in the
Sequence Listingis related to other proteins of the gene families set forth in
Table II, having
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homology and/or structural similarity with the polypeptides set forth in Table
II. Preferred
polypeptides and polynucleotides of the present invention are expected to
have, inter alia,
similar biological functionslproperties to their homologous polypeptides and
polynucleotides. Furthermore, preferred polypeptides and polynucleotides of
the present
invention have at least one activity of the genes set forth in Table I.
Polynucleotides of the present invention may be obtained using standard
cloning
and screening techniques from a cDNA library derived from mRNA from the
tissues set
forth in Table IV (see for instance, Sambrook et al., Molecular Cloning: A
Laboratory
Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
(1989)).
Polynucleotides of the invention can also be obtained from natural sources
such as genomic
DNA libraries or can be synthesized using well known and commercially
available
techniques.
When polynucleotides of the present invention are used for the recombinant
production of polypeptides of the present invention, the polynucleotide may
include the
coding sequence for the mature polypeptide, by itself, or the coding sequence
for the mature
polypeptide in reading frame with other coding sequences, such as those
encoding a leader
or secretory sequence, a pre-, or pro- or prepro- protein sequence, or other
fusion peptide
portions. For example, a marker sequence that facilitates purification of the
fused
polypeptide can be encoded. In certain preferred embodiments of this aspect of
the
2,0 invention, the marker sequence is a hexa-histidine peptide, as provided in
the pQE vector
(Qiagen, Inc.) and described in Gentz et al., Proc Natl Acad Sci USA (1989)
86:821-824, or
is an HA tag. A polynucleotide may also contain non-coding 5' and 3'
sequences, such as
transcribed, non-translated sequences, splicing and polyadenylation signals,
ribosome
binding sites and sequences that stabilize mRNA.
Polynucleotides that are identical, or have sufficient identity to a
polynucleotide
sequence set forth in the Sequence Listing, may be used as hybridization
probes for cDNA
and genomic DNA or as primers for a nucleic acid amplification reaction (for
instance,
PCR). Such probes and primers may be used to isolate full-length cDNAs and
genomic
clones encoding polypeptides of the present invention and to isolate cDNA and
genomic
clones of other genes (including genes encoding paralogs from human sources
and orthologs
and paralogs from other species) that have a high sequence similarity to
sequences set forth
in the Sequence Listing, typically at least 95°lo identity. Preferred
probes~and primers will
generally comprise at least 15 nucleotides, preferably, at least 30
nucleotides and may have
at least 50, if not at least 100 nucleotides. Particularly preferred probes
will have between
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30 and 50 nucleotides. Particularly preferred primers will have between 20 and
25
nucleotides.
A polynucleotide encoding a polypeptide of the present invention, including
homologs from other species, may be obtained by a process comprising the steps
of
screening a library under stringent hybridization conditions with a labeled
probe having a
sequence set forth in the Sequence Listing or a fragment thereof, preferably
of at least 15
nucleotides; and isolating full-length cDNA and genomic clones containing the
polynucleotide sequence set forth in the Sequence Listing. Such hybridization
techniques
are well known to the skilled artisan. Preferred stringent hybridization
conditions include
overnight incubation at 42°C in a solution comprising: 50% formamide,
5xSSC (150mM
NaCI, l5mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5x Denhardt's
solution,
10 % dextran sulfate, and 20 microgram/ml denatured, sheared salmon sperm DNA;
followed by washing the filters in O.lx SSC at about 65°C. Thus the
present invention also
includes isolated polynucleotides, preferably with a nucleotide sequence of at
least 100,
obtained by screening a library under stringent hybridization conditions with
a labeled probe
having the sequence set forth in the Sequence Listing or a fragment thereof,
preferably of at
least 15 nucleotides.
The skilled artisan will appreciate that, in many cases, an isolated cDNA
sequence
will be incomplete, in that the region coding for the polypeptide does not
extend all the way
through to the 5'terminus. This is a consequence of reverse transcriptase, an
enzyme with
inherently low "processivity" (a measure of the ability of the enzyme to
remain attached to
the template during the polymerisation reaction), failing to complete a DNA
copy of the
mRNA template during first strand cDNA synthesis.
There are several methods available and well known to those skilled in the art
to
obtain full-length cDNAs, or extend short cDNAs, for example those based on
the method
of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al.,
Proc Nat
Acad Sci USA 85, 8998-9002, 1988). Recent modifications of the technique,
exemplified
by the Marathon (trade mark) technology (Clontech Laboratories Inc.) for
example, have
significantly simplified the search for longer cDNAs. In the Marathon (trade
mark)
technology, cDNAs have been prepared from mRNA extracted from a chosen tissue
and an
'adaptor' sequence ligated onto each end. Nucleic acid amplification (PCR) is
then carried
out to amplify the "missing" 5' end of the cDNA using a combination of gene
specific and
adaptor specific oligonucleotide primers. The PCR reaction is then repeated
using 'nested'
primers, that is, primers designed to anneal within the amplified product
(typically an
adapter specific primer that anneals further 3' in the adaptor sequence and a
gene specific
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primer that anneals further 5' in the known gene sequence). The products of
this reaction
can then be analyzed by DNA sequencing and a full-length cDNA constructed
either by
joining the product directly to the existing cDNA to give a complete sequence,
or carrying
out a separate full-length PCR using the new sequence information for the
design of the 5'
primer.
Recombinant polypeptides of the present invention may be prepared by processes
well known in the art from genetically engineered host cells comprising
expression systems.
Accordingly, in a further aspect, the present invention relates to expression
systems
comprising a polynucleotide or polynucleotides of the present invention, to
host cells which
are genetically engineered with such expression systems and to the production
of
polypeptides of the invention by recombinant techniques. Cell-free translation
systems can
also be employed to produce such proteins using RNAs derived from the DNA
constructs of
the present invention.
For recombinant production, host cells can be genetically engineered to
incorporate
expression systems or portions thereof for polynucleotides of the present
invention.
Polynucleotides may be introduced into host cells by methods described in many
standard
laboratory manuals, such as Davis et al., Basic Methods in Molecular Biology
(1986) and
Sambrook et al.(ibid). Preferred methods of introducing polynucleotides into
host cells
include, for instance, calcium phosphate transfection, DEAF-dextran mediated
transfection,
transvection, micro-injection, cationic lipid-mediated transfection,
electroporation,
transduction, scrape loading, ballistic introduction or infection.
Representative examples of appropriate hosts include bacterial cells, such as
Streptococci, Staphylococci, E. coli, Streptomyces and Bacillus subtilis
cells; fungal cells,
such as yeast cells and Aspergillus cells; insect cells such as Drosophila S2
and Spodoptera
Sf9 cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 and
Bowes
melanoma cells; and plant cells.
A great variety of expression systems can be used, for instance, chromosomal,
episomal and virus-derived systems, e.g., vectors derived from bacterial
plasmids, from
bacteriophage, from transposons, from yeast episomes, from insertion elements,
from yeast
chromosomal elements, from viruses such as baculoviruses, papova viruses, such
as SV40,
vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and
retroviruses, and
vectors derived from combinations thereof, such as those derived from plasmid
and
bacteriophage genetic elements, such as cosmids and phagemids. The expression
systems
may contain control regions that regulate as well as engender expression.
Generally, any
system or vector that is able to maintain, propagate or express a
polynucleotide to produce a
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polypeptide in a host may be used. The appropriate polynucleotide sequence may
be
inserted into an expression system by any of a variety of well-known and
routine
techniques, such as, for example, those set forth in Sambrook et al., (ibic~.
Appropriate
secretion signals may be incorporated into the desired polypeptide to allow
secretion of the
translated protein into the lumen of the endoplasmic reticulum, the
periplasmic space or the
extracellular environment. These signals may be endogenous to the polypeptide
or they
may be heterologous signals.
If a polypeptide of the present invention is to be expressed for use in
screening
assays, it is generally preferred that the polypeptide be produced at the
surface of the cell.
In this event, the cells may be harvested prior to use in the screening assay.
If the
polypeptide is secreted into the medium, the medium can be recovered in order
to recover
and purify the polypeptide. If produced intracellularly, the cells must first
be lysed before
the polypeptide is recovered.
Polypeptides of the present invention can be recovered and purified from
recombinant cell cultures by well-known methods including ammonium sulfate or
ethanol
precipitation, acid extraction, anion or cation exchange chromatography,
phosphocellulose
chromatography, hydrophobic interaction chromatography, affinity
chromatography,
hydroxylapatite chromatography and lectin chromatography. Most preferably,
high
performance liquid chromatography is employed for purification. Well known
techniques
far refolding proteins may be employed to regenerate active conformation when
the
polypeptide is denatured during intracellular synthesis, isolation and/or
purification.
Polynucleotides of the present invention may be used as diagnostic reagents,
through detecting mutations in the associated gene. Detection of a mutated
form of a gene
is characterized by the polynucleotides set forth in the Sequence Listing in
the cDNA or
genomic sequence and which is associated with a dysfunction. Will provide a
diagnostic
tool that can add to, or define, a diagnosis of a disease, or susceptibility
to a disease, which
results from under-expression, over-expression or altered spatial or temporal
expression of
the gene. Individuals carrying mutations in the gene may be detected at the
DNA level by a
variety of techniques well known in the art.
Nucleic acids for diagnosis may be obtained from a subject's cells, such as
from
blood, urine, saliva, tissue biopsy or autopsy material. The genomic DNA may
be used
directly for detection or it may be amplified enzymatically by using PCR,
preferably RT-
PCR, or other amplification techniques prior to analysis. RNA or cDNA may also
be used
in similar fashion. Deletions and insertions can be detected by a change in
size of the
amplified product in comparison to the normal genotype. Point mutations can be
identified
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by hybridizing amplified DNA to labeled nucleotide sequences of the genes set
forth in
Table I. Perfectly matched sequences can be distinguished from mismatched
duplexes by
RNase digestion or by differences in melting temperatures. DNA sequence
difference may
also be detected by alterations in the electrophoretic mobility of DNA
fragments in gels,
with or without denaturing agents, or by direct DNA sequencing (see, for
instance, Myers et
al., Science (1985) 230:1242). Sequence changes at specific locations may also
be revealed
by nuclease protection assays, such as RNase and S 1 protection or the
chemical cleavage
method (see Cotton et al., Proc Natl Acad Sci USA (1985) 85: 4397-4401).
An array of oligonucleotides probes comprising polynucleotide sequences or
fragments thereof of the genes set forth in Table I can be constructed to
conduct efficient
screening of e.g., genetic mutations. Such arrays are preferably high density
arrays or grids.
Array technology methods are well known and have general applicability and can
be used to
address a variety of questions in molecular genetics including gene
expression, genetic
linkage, and genetic variability, see, for example, M. Chee et al., Science,
274, 610-613
(1996) and other references cited therein.
Detection of abnormally decreased or increased levels of polypeptide or mRNA
expression
may also be used for diagnosing or determining susceptibility of a subject to
a disease of the
invention. Decreased or increased expression can be measured at the RNA level
using any
of the methods well known in the art for the quantitation of polynucleotides,
such as, for
example, nucleic acid amplification, for instance PCR, RT-PCR, RNase
protection,
Northern blotting and other hybridization methods. Assay techniques that can
be used to
determine levels of a protein, such as a polypeptide of the present invention,
in a sample
derived from a host are well-known to those of skill in the art. Such assay
methods include
radio-immunoassays, competitive-binding assays, Western Blot analysis and
ELISA assays.
Thus in another aspect, the present invention relates to a diagnostic kit
comprising:
(a) a polynucleotide of the present invention, preferably the nucleotide
sequence set forth in
the Sequence Listing , or a fragment or an RNA transcript thereof;
(b) a nucleotide sequence complementary to that of (a);
(c) a polypeptide of the present invention, preferably the polypeptide set
forth in the
Sequence Listing or a fragment thereof; or
(d) an antibody to a polypeptide of the present invention, preferably to the
polypeptide set
forth in the Sequence Listing .
It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise
a
substantial component. Such a kit will be of use in diagnosing a disease or
susceptibility to
a disease, particularly diseases of the invention, amongst others.
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The polynucleotide sequences of the present invention are valuable for
chromosome
localisation studies. The sequences set forth in the Sequence Listing are
specifically
targeted to, and can hybridize with, a particular location on an individual
human
chromosome. The mapping of relevant sequences to chromosomes according to the
present
invention is an important first step in correlating those sequences with gene
associated
disease. Once a sequence has been mapped to a precise chromosomal location,
the physical
position of the sequence on the chromosome can be correlated with genetic map
data. Such
data are found in, for example, V. Mcl~usick, Mendelian Inheritance in Man
(available on-
line through Johns Hopkins University Welch Medical Library). The relationship
between
genes and diseases that have been mapped to the same chromosomal region are
then
identified through linkage analysis (co-inheritance of physically adjacent
genes). Precise
human chromosomal localisations for a genomic sequence (gene fragment etc.)
can be
determined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, D.,
Thomas, P.,
Weissenbach, J., and Goodfellow, P., (1994) A method for constructing
radiation hybrid
maps of whole genomes, Nature Genetics 7, 22-28). A number of RH panels are
available
from Research Genetics (Huntsville, AL, USA) e.g. the GeneBridge4 RH panel
(Hum Mol
Genet 1996 Mar;S(3):339-46 A radiation hybrid map of the human genome. Gyapay
G,
Schmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D, Muselet D, Prud~-
Iomme JF,
Dib C, Auffray C, Morissette J, Weissenbach J, Goodfellow PN). To determine
the
chromosomal location of a gene using this panel, 93 PCRs are performed using
primers
designed from the gene of interest on RH DNAs. Each of these DNAs contains
random
human genomic fragments maintained in a hamster background (human / hamster
hybrid
cell lines). These PCRs result in 93 scores indicating the presence or absence
of the PCR
product of the gene of interest. These scores are compared with scores created
using PCR
products from genomic sequences of known location. This comparison is
conducted at
http://www.genome.wi.mit.edu/.
The polynucleotide sequences of the present invention are also valuable tools
for
tissue expression studies. Such studies allow the determination of expression
patterns of
polynucleotides of the present invention which may give an indication as to
the expression
patterns of the encoded polypeptides in tissues, by detecting the mRNAs that
encode them.
The techniques used are well known in the art and include in situ
hydridization techniques
to clones arrayed on a grid, such as cDNA microarray hybridization (Schena et
al, Science,
270, 467-470, 1995 and Shalon et al, Genome Res, 6, 639-645, 1996) and
nucleotide
amplification techniques such as PCR. A preferred method uses the TAQMAN
(Trade
mark) technology available from Perkin Elmer. Results from these studies can
provide an
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WO 01/98342 PCT/USO1/19929
indication of the normal function of the polypeptide in the organism. In
addition,
comparative studies of the normal expression pattern of mRNAs with that of
mRNAs
encoded by an alternative form of the same gene (for example, one having an
alteration in
polypeptide coding potential or a regulatory mutation) can provide valuable
insights into the
role of the polypeptides of the present invention, or that of inappropriate
expression thereof
in disease. Such inappropriate expression may be of a temporal, spatial or
simply
quantitative nature.
A further aspect of the present invention relates to antibodies. The
polypeptides of
the invention or their fragments, or cells expressing them, can be used as
immunogens to
produce antibodies that are immunospecific for polypeptides of the present
invention. The
term "immunospecific" means that the antibodies have substantially greater
affinity for the
polypeptides of the invention than their affinity for other related
polypeptides in the prior
art.
Antibodies generated against polypeptides of the present invention may be
obtained
by administering the polypeptides or epitope-bearing fragments, or cells to an
animal,
preferably a non-human animal, using routine protocols. For preparation of
monoclonal
antibodies, any technique which provides antibodies produced by continuous
cell line
cultures can be used. Examples include the hybridoma technique (Kohler, G. and
Milstein,
C., Nature (1975) 256:495-497), the trioma technique, the human B-cell
hybridoma
technique (Kozbor et al., Immunology Today (1983) 4:72) and the EBV-hybridoma
technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96, Alan
R. Liss,
Inc., 1985).
Techniques for the production of single chain antibodies, such as those
described in
U.S. Patent No. 4,946,778, can also be adapted to produce single chain
antibodies to
polypeptides of this invention. Also, transgenic mice, or other organisms,
including other
mammals, may be used to express humanized antibodies.
The above-described antibodies may be employed to isolate or to identify
clones
expressing the polypeptide or to purify the polypeptides by affinity
chromatography.
Antibodies against polypeptides of the present invention may also be employed
to treat
diseases of the invention, amongst others.
Polypeptides and polynucleotides of the present invention may also be used as
vaccines. Accordingly, in a further aspect, the present invention relates to a
method for
inducing an immunological response in a mammal that comprises inoculating the
mammal
with a polypeptide of the present invention, adequate to produce antibody
and/or T cell
immune response, including, for example, cytokine-producing T cells or
cytotoxic T cells,
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WO 01/98342 PCT/USO1/19929
to protect said animal from disease, whether that disease is already
established within the
individual or not. An immunological response in a mammal may also be induced
by a
method comprises delivering a polypeptide of the present invention via a
vector directing
expression of the polynucleotide and coding for the polypeptide ih vivo in
order to induce
such an immunological response to produce antibody to protect said animal from
diseases of
the invention. One way of administering the vector is by accelerating it into
the desired
cells as a coating on particles or otherwise. Such nucleic acid vector may
comprise DNA,
RNA, a modified nucleic acid, or a DNA/RNA hybrid. For use a vaccine, a
polypeptide or a
nucleic acid vector will be normally provided as a vaccine formulation
(composition). The
formulation may further comprise a suitable carrier. Since a polypeptide may
be broken
down in the stomach, it is preferably administered parenterally (for instance,
subcutaneous,
intra-muscular, intravenous, or intra-dermal injection). Formulations suitable
for parenteral
administration include aqueous and non-aqueous sterile injection solutions
that may contain
anti-oxidants, buffers, bacteriostats and solutes that render the formulation
instonic with the
blood of the recipient; and aqueous and non-aqueous sterile suspensions that
may include
suspending agents or thickening agents. The formulations may be presented in
unit-dose or
mufti-dose containers, for example, sealed ampoules and vials and may be
stored in a
freeze-dried condition requiring only the addition of the sterile liquid
carrier immediately
prior to use. The vaccine formulation may also include adjuvant systems for
enhancing the
immunogenicity of the formulation, such as oil-in water systems and other
systems known
in the art. The dosage will depend on the specific activity of the vaccine and
can be readily
determined by routine experimentation.
Polypeptides of the present invention have one or more biological functions
that are
of relevance in one or more disease states, in particular the diseases of the
invention
hereinbefore mentioned. It is therefore useful to identify compounds that
stimulate or
inhibit the function or level of the polypeptide. Accordingly, in a further
aspect, the present
invention provides for a method of screening compounds to identify those that
stimulate or
inhibit the function or level of the polypeptide. Such methods identify
agonists or
antagonists that may be employed for therapeutic and prophylactic purposes for
such
diseases of the invention as hereinbefore mentioned. Compounds may be
identified from a
variety of sources, for example, cells, cell-free preparations, chemical
libraries, collections
of chemical compounds, and natural product mixtures. Such agonists or
antagonists so-
identified may be natural or modified substrates, ligands, receptors, enzymes,
etc., as the
case may be, of the polypeptide; a structural or functional mimetic thereof
(see Coligan et
al., Current Protocols in Immunology 1(2):Chapter 5 (1991)) or a small
molecule. Such
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small molecules preferably have a molecular weight below 2,000 daltons, more
preferably
between 300 and 1,000 daltons, and most preferably between 400 and 700
daltons. It is
preferred that these small molecules are organic molecules.
The screening method may simply measure the binding of a candidate compound to
the polypeptide, or to cells or membranes bearing the polypeptide, or a fusion
protein
thereof, by means of a label directly or indirectly associated with the
candidate compound.
Alternatively, the screening method may involve measuring or detecting
(qualitatively or
quantitatively) the competitive binding of a candidate compound to the
polypeptide against
a labeled competitor (e.g. agonist or antagonist). Further, these screening
methods may test
whether the candidate compound results in a signal generated by activation or
inhibition of
the polypeptide, using detection systems appropriate to the cells bearing the
polypeptide.
Inhibitors of activation are generally assayed in the presence of a known
agonist and the
effect on activation by the agonist by the presence of the candidate compound
is observed.
Further, the screening methods may simply comprise the steps of mixing a
candidate
compound with a solution containing a polypeptide of the present invention, to
form a
mixture, measuring an activity of the genes set forth in Table I in the
mixture, and
comparing activity of the mixture of the genes set forth in Table I to a
control mixture which
contains no candidate compound.
Polypeptides of the present invention may be employed in conventional low
capacity screening methods and also in high-throughput screening (HTS)
formats. Such
HTS formats include not only the well-established use of 96- and, more
recently, 384-well
micotiter plates but also emerging methods such as the nanowell method
described by
Schullek et al, Anal Biochem., 246, 20-29, (1997).
Fusion proteins, such as those made from Fc portion and polypeptide of the
genes set forth
in Table I, as hereinbefore described, can also be used for high-throughput
screening assays
to identify antagonists for the polypeptide of the present invention (see D.
Bennett et al., J
Mol Recognition, 8:52-58 (1995); and K. Johanson etal., J Biol Chem,
270(16):9459-9471
(1995)).
The polynucleotides, polypeptides and antibodies to the polypeptide of the
present
invention may also be used to configure screening methods for detecting the
effect of added
compounds on the production of mRNA and polypeptide in cells. For example, an
ELISA
assay may be constructed for measuring secreted or cell associated levels of
polypeptide
using monoclonal and polyclonal antibodies by standard methods known in the
art. This
can be used to discover agents that may inhibit or enhance the production of
polypeptide
(also called antagonist or agonist, respectively) from suitably manipulated
cells or tissues.
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A polypeptide of the present invention may be used to identify membrane bound
or
soluble receptors, if any, through standard receptor binding techniques known
in the art.
These include, but are not limited to, ligand binding and crosslinking assays
in which the
polypeptide is labeled with a radioactive isotope (for instance, 125,
chemically modified
(for instance, biotinylated), or fused to a peptide sequence suitable for
detection or
purification, and incubated with a source of the putative receptor (cells,
cell membranes, cell
supernatants, tissue extracts, bodily fluids). Other methods include
biophysical techniques
such as surface plasmon resonance and spectroscopy. These screening methods
may also be
used to identify agonists and antagonists of the polypeptide that compete with
the binding of
the polypeptide to its receptors, if any. Standard methods for conducting such
assays are
well understood in the art.
Examples of antagonists of polypeptides of the present invention include
antibodies
or, in some cases, oligonucleotides or proteins that are closely related to
the ligands,
substrates, receptors, enzymes, etc., as the case may be, of the polypeptide,
e.g., a fragment
of the ligands, substrates, receptors, enzymes, etc.; or a small molecule that
bind to the
polypeptide of the present invention but do not elicit a response, so that the
activity of the
polypeptide is prevented.
Screening methods may also involve the use of transgenic technology and the
genes
set forth in Table I. The art of constructing transgenic animals is well
established. For
example, the genes set forth in Table I may be introduced through
microinjection into the
male pronucleus of fertilized oocytes, retroviral transfer into pre- or post-
implantation
embryos, or injection of genetically modified, such as by electroporation,
embryonic stem
cells into host blastocysts. Particularly useful transgenic animals are so-
called "knock-in"
animals in which an animal gene is replaced by the human equivalent within the
genome of
that animal. Knock-in transgenic animals are useful in the drug discovery
process, for target
validation, where the compound is specific for the human target. Other useful
transgenic
animals are so-called "knock-out" animals in which the expression of the
animal ortholog of
a polypeptide of the present invention and encoded by an endogenous DNA
sequence in a
cell is partially or completely annulled. The gene knock-out may be targeted
to specific
cells or tissues, may occur only in certain cells or tissues as a consequence
of the limitations
of the technology, or may occur in all, or substantially all, cells in the
animal. Transgenic
animal technology also offers a whole animal expression-cloning system in
which
introduced genes are expressed to give large amounts of polypeptides of the
present
invention
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Screening kits for use in the above described methods form a further aspect of
the
present invention. Such screening kits comprise:
(a) a polypeptide of the present invention;
(b) a recombinant cell expressing a polypeptide of the present invention;
(c) a cell membrane expressing a polypeptide of the present invention; or
(d) an antibody to a polypeptide of the present invention;
which polypeptide is preferably that set forth in the Sequence Listing.
It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise
a
substantial component.
Glossary
The following definitions are provided to facilitate understanding of certain
terms used
frequently hereinbefore.
"Antibodies" as used herein includes polyclonal and monoclonal antibodies,
chimeric,
single chain, and humanized antibodies, as well as Fab fragments, including
the products of
an
Fab or other immunoglobulin expression library.
"Isolated" means altered "by the hand of man" from its natural state, i.e., if
it occurs
in nature, it has been changed or removed from its original environment, or
both. For
example, a polynucleotide or a polypeptide naturally present in a living
organism is not
"isolated," but the same polynucleotide or polypeptide separated from the
coexisting
materials of its natural state is "isolated", as the term is employed herein.
Moreover, a
polynucleotide or polypeptide that is introduced into an organism by
transformation, genetic
manipulation or by any other recombinant method is "isolated" even if it is
still present in
said organism, which organism may be living or non-living.
"Secreted protein activity or secreted polypeptide activity" or "biological
activity of
the secreted protein or secreted polypeptide" refers to the metabolic or
physiologic function
of said secreted protein including similar activities or improved activities
or these activities
with decreased undesirable side-effects. Also included are antigenic and
immunogenic
activities of said secreted protein.
"Secreted protein gene" refers to a polynucleotide comprising any of the
attached
nucleotide sequences or allelic variants thereof and/or their complements.
"Polynucleotide" generally refers to any polyribonucleotide (RNA) or
polydeoxribonucleotide (DNA), which may be unmodified or modified RNA or DNA.
"Polynucleotides" include, without limitation, single- and double-stranded
DNA, DNA that
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is a mixture of single- and double-stranded regions, single- and double-
stranded RNA, and
RNA that is mixture of single- and double-stranded regions, hybrid molecules
comprising
DNA and RNA that may be single-stranded or, more typically, double-stranded or
a mixture
of single- and double-stranded regions. In addition, "polynucleotide" refers
to triple-
s stranded regions comprising RNA or DNA or both RNA and DNA. The term
"polynucleotide" also includes DNAs or RNAs containing one or more modified
bases and
DNAs or RNAs with backbones modified for stability or for other reasons.
"Modified"
bases include, for example, tritylated bases and unusual bases such as
inosine. A variety of
modifications may be made to DNA and RNA; thus, "polynucleotide" embraces
chemically,
enzymatically or metabolically modified forms of polynucleotides as typically
found in
nature, as well as the chemical forms of DNA and RNA characteristic of viruses
and cells.
"Polynucleotide" also embraces relatively short polynucleotides, often
referred to as
oligonucleotides.
"Polypeptide" refers to any polypeptide comprising two or more amino acids
joined
to each other by peptide bonds or modified peptide bonds, i.e., peptide
isosteres.
"Polypeptide" refers to both short chains, commonly referred to as peptides,
oligopeptides
or oligomers, and to longer chains, generally referred to as proteins.
Polypeptides may
contain amino acids other than the 20 gene-encoded amino acids. "Polypeptides"
include
amino acid sequences modified either by natural processes, such as post-
translational
processing, or by chemical modification techniques that are well known in the
art. Such
modifications are well described in basic texts and in more detailed
monographs, as well as
in a voluminous research literature. Modifications may occur anywhere in a
polypeptide,
including the peptide backbone, the amino acid side-chains and the amino or
carboxyl
termini. It will be appreciated that the same type of modification may be
present to the
same or varying degrees at several sites in a given polypeptide. Also, a given
polypeptide
may contain many types of modifications. Polypeptides may be branched as a
result of
ubiquitination, and they may be cyclic, with or without branching. Cyclic,
branched and
branched cyclic polypeptides may result from post-translation natural
processes or may be
made by synthetic methods. Modifications include acetylation, acylation, ADP-
ribosylation, amidation, biotinylation, covalent attachment of flavin,
covalent attachment of
a heme moiety, covalent attachment of a nucleotide or nucleotide derivative,
covalent
attachment of a lipid or lipid derivative, covalent attachment of
phosphotidylinositol, cross-
linking, cyclization, disulfide bond formation, demethylation, formation of
covalent cross-
links, formation of cystine, formation of pyroglutamate, formylation, gamma-
carboxylation,
glycosylation, GPI anchor formation, hydroxylation, iodination, methylation,
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myristoylation, oxidation, proteolytic processing, phosphorylation,
prenylation,
racemization, selenoylation, sulfation, transfer-RNA mediated addition of
amino acids to
proteins such as arginylation, and ubiquitination (see, for instance, Proteins
- Structure and
Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New
York,
1993; Wold, F., Post-translational Protein Modifications: Perspectives and
Prospects, 1-12,
in Post-translational Covalent Modification of Proteins, B. C. Johnson, Ed.,
Academic Press,
New York, 1983; Seifter et al., "Analysis for protein modifications and
nonprotein
cofactors", Meth Enzymol, 182, 626-646, 1990, and Rattan et al., "Protein
Synthesis: Post-
translational Modifications and Aging", Ann NY Acad Sci, 663, 48-62, 1992).
"Fragment" of a polypeptide sequence refers to a polypeptide sequence that is
shorter than the reference sequence but that retains essentially the same
biological function
or activity as the reference polypeptide. "Fragment" of a polynucleotide
sequence refers to a
polynucleotide sequence that is shorter than the reference sequence set forth
in the Sequence
Listing.
"Variant" refers to a polynucleotide or polypeptide that differs from a
reference
polynucleotide or polypeptide, but retains the essential properties thereof. A
typical variant
of a polynucleotide differs in nucleotide sequence from the reference
polynucleotide.
Changes in the nucleotide sequence of the variant may or may not alter the
amino acid
sequence of a polypeptide encoded by the reference polynucleotide. Nucleotide
changes
may result in amino acid substitutions, additions, deletions, fusions and
truncations in the
polypeptide encoded by the reference sequence, as discussed below. A typical
variant of a
polypeptide differs in amino acid sequence from the reference polypeptide.
Generally,
alterations are limited so that the sequences of the reference polypeptide and
the variant are
closely similar overall and, in many regions, identical. A variant and
reference polypeptide
may differ in amino acid sequence by one or more substitutions, insertions,
deletions in any
combination. A substituted or inserted amino acid residue may or may not be
one encoded
by the genetic code. Typical conservative substitutions include Gly, Ala; Val,
Ile, Leu; Asp,
Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe and Tyr. A variant of a
polynucleotide or
polypeptide may be naturally occurring such as an allele, or it may be a
variant that is not
known to occur naturally. Non-naturally occurring variants of polynucleotides
and
polypeptides may be made by mutagenesis techniques or by direct synthesis.
Also included
as variants are polypeptides having one or more post-translational
modifications, for
instance glycosylation, phosphorylation, methylation, ADP ribosylation and the
like.
Embodiments include methylation of the N-terminal amino acid, phosphorylations
of
serines and threonines and modification of C-terminal glycines.
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"Allele" refers to one of two or more alternative forms of a gene occurring at
a
given locus in the genome.
"Polymorphism" refers to a variation in nucleotide sequence (and encoded
polypeptide sequence, if relevant) at a given position in the genome within a
population.
"Single Nucleotide Polymorphism" (SNP) refers to the occurrence of nucleotide
variability at a single nucleotide position in the genome, within a
population. An SNP may
occur within a gene or within intergenic regions of the genome. SNPs can be
assayed using
Allele Specific Amplification (ASA). For the process at least 3 primers are
required. A
common primer is used in reverse complement to the polymorphism being assayed.
This
common primer can be between 50 and 1500 bps from the polymorphic base. The
other two
(or more) primers are identical to each other except that the final 3' base
wobbles to match
one of the two (or more) alleles that make up the polymorphism. Two (or more)
PCR
reactions are then conducted on sample' DNA, each using the common primer and
one of the
Allele Specific Primers.
"Splice Variant" as used herein refers to cDNA molecules produced from RNA
molecules initially transcribed from the same genomic DNA sequence but which
have
undergone alternative RNA splicing. Alternative RNA splicing occurs when a
primary
RNA transcript undergoes splicing, generally for the removal of introns, which
results in the
production of more than one mRNA molecule each of that may encode different
amino acid
sequences. The term splice variant also refers to the proteins encoded by the
above cDNA
molecules.
"Identity" reflects a relationship between two or more polypeptide sequences
or two
or more polynucleotide sequences, determined by comparing the sequences. In
general,
identity refers to an exact nucleotide to nucleotide or amino acid to amino
acid
correspondence of the two polynucleotide or two polypeptide sequences,
respectively, over
the length of the sequences being compared.
"% Identity" - For sequences where there is not an exact correspondence, a "%
identity" may be determined. In general, the two sequences to be compared are
aligned to
give a maximum correlation between the sequences. This may include inserting
"gaps" in
either one or both sequences, to enhance the degree of alignment. A % identity
may be
determined over the whole length of each of the sequences being compared (so-
called global
alignment), that is particularly suitable for sequences of the same or very
similar length, or
over shorter, defined lengths (so-called local alignment), that is more
suitable for sequences
of unequal length.
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"Similarity" is a further, more sophisticated measure of the relationship
between
two polypeptide sequences. In general, "similarity" means a comparison between
the amino
acids of two polypeptide chains, on a residue by residue basis, taking into
account not only
exact correspondences between a between pairs of residues, one from each of
the sequences
being compared (as for identity) but also, where there is not an exact
correspondence,
whether, on an evolutionary basis, one residue is a likely substitute for the
other. This
likelihood has an associated "score" from which the "% similarity" of the two
sequences can
then be determined.
Methods for comparing the identity and similarity of two or more sequences are
well known in the art. Thus for instance, programs available in the Wisconsin
Sequence
Analysis Package, version 9.1 (Devereux J et al, Nucleic Acids Res, 12, 387-
395, 1984,
available from Genetics Computer Group, Madison, Wisconsin, USA), for example
the
programs BESTFIT and GAP, may be used to determine the % identity between two
polynucleotides and the % identity and the % similarity between two
polypeptide sequences.
BESTFIT uses the "local homology" algorithm of Smith and Waterman (J Mol Biol,
147,195-197, 1981, Advances in Applied Mathematics, 2, 482-489, 1981) and
finds the best
single region of similarity between two sequences. BESTFIT is more suited to
comparing
two polynucleotide or two polypeptide sequences that are dissimilar in length,
the program
assuming that the shorter sequence represents a portion of the longer. In
comparison, GAP
aligns two sequences, finding a "maximum similarity", according to the
algorithm of
Neddleman and Wunsch (J Mol Biol, 48, 443-453, 1970). GAP is more suited to
comparing
sequences that are approximately the same length and an alignment is expected
over the
entire length. Preferably, the parameters "Gap Weight" and "Length Weight"
used in each
program are 50 and 3, for polynucleotide sequences and 12 and 4 for
polypeptide sequences,
respectively. Preferably, % identities and similarities are determined when
the two
sequences being compared are optimally aligned.
Other programs for determining identity and/or similarity between sequences
are
also known in the art, for instance the BLAST family of programs (Altschul S F
et al, J Mol
Biol, 215, 403-410, 1990, Altschul S F et al, Nucleic Acids Res., 25:389-3402,
1997,
available from the National Center for Biotechnology Information (NCBI),
Bethesda,
Maryland, USA and accessible through the home page of the NCBI at
www.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology, 183, 63-
99,
1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85, 2444-2448,1988,
available as part of the Wisconsin Sequence Analysis Package).
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Preferably, the BLOSUM62 amino acid substitution matrix (Henikoff S and
Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) is used in
polypeptide
sequence comparisons including where nucleotide sequences are first translated
into amino
acid sequences before comparison.
Preferably, the program BESTFIT is used to determine the % identity of a query
polynucleotide or a polypeptide sequence with respect to a reference
polynucleotide or a
polypeptide sequence, the query and the reference sequence being optimally
aligned and the
parameters of the program set at the default value, as hereinbefore described.
"Identity Index" is a measure of sequence relatedness which may be used to
compare a candidate sequence (polynucleotide or polypeptide) and a reference
sequence.
Thus, for instance, a candidate polynucleotide sequence having, for example,
an Identity
Index of 0.95 compared to a reference polynucleotide sequence is identical to
the reference
sequence except that the candidate polynucleotide sequence may include on
average up to
five differences per each 100 nucleotides of the reference sequence. Such
differences are
selected from the group consisting of at least one nucleotide deletion,
substitution, including
transition and transversion, or insertion. These differences may occur at the
5' or 3'terminal
positions of the reference polynucleotide sequence or anywhere between these
terminal
positions, interspersed either individually among the nucleotides in the
reference sequence
or in one or more contiguous groups within the reference sequence. In other
words, to
obtain a polynucleotide sequence having an Identity Index of 0.95 compared to
a reference
polynucleotide sequence, an average of up to 5 in every 100 of the nucleotides
of the in the
reference sequence may be deleted, substituted or inserted, or any combination
thereof, as
hereinbefore described. The same applies mutatis mutandis for other values of
the Identity
Index, for instance 0.96, 0.97, 0.98 and 0.99.
Similarly, for a polypeptide, a candidate polypeptide sequence having, for
example,
an Identity Index of 0.95 compared to a reference polypeptide sequence is
identical to the
reference sequence except that the polypeptide sequence may include an average
of up to
five differences per each 100 amino acids of the reference sequence. Such
differences are
selected from the group consisting of at least one amino acid deletion,
substitution,
including conservative and non-conservative substitution, or insertion. These
differences
may occur at the amino- or carboxy-terminal positions of the reference
polypeptide
sequence or anywhere between these terminal positions, interspersed either
individually
among the amino acids in the reference sequence or in one or more contiguous
groups
within the reference sequence. In other words, to obtain a polypeptide
sequence having an
Identity Index of 0.95 compared to a reference polypeptide sequence, an
average of up to 5
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in every 100 of the amino acids in the reference sequence may be deleted,
substituted or
inserted, or any combination thereof, as hereinbefore described. The same
applies nzutatis
mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98
and 0.99.
The relationship between the number of nucleotide or amino acid differences
and
the Identity Index may be expressed in the following equation:
na~xa-~xa~na
in which:
na is the number of nucleotide or amino acid differences,
xa is the total number of nucleotides or amino acids in a sequence set forth
in the
Sequence Listing,
I is the Identity Index,
~ is the symbol for the multiplication operator, and
in which any non-integer product of xa and I is rounded down to the nearest
integer prior to
subtracting it from xa.
"Homolog" is a generic term used in the art to indicate a polynucleotide or
polypeptide sequence possessing a high degree of sequence relatedness to a
reference
sequence. Such relatedness may be quantified by determining the degree of
identity and/or
similarity between the two sequences as hereinbefore defined. Falling within
this generic
term are the terms "ortholog", and "paralog". "Ortholog" refers to a
polynucleotide or
polypeptide that is the functional equivalent of the polynucleotide or
polypeptide in another
species. "Paralog" refers to a polynucleotideor polypeptide that within the
same species
which is functionally similar.
"Fusion protein" refers to a protein encoded by two, often unrelated, fused
genes or
fragments thereof. In one example, EP-A-0 464 533-A discloses fusion proteins
comprising
various portions of constant region of immunoglobulin molecules together with
another
human protein or part thereof. In many cases, employing an immunoglobulin Fc
region as
a part of a fusion protein is advantageous for use in therapy and diagnosis
resulting in, for
example, improved pharmacokinetic properties [see, e.g., EP-A 0232 262]. On
the other
hand, for some uses it would be desirable to be able to delete the Fc part
after the fusion
protein has been expressed, detected and purified.
All publications and references, including but not limited to patents and
patent
applications, cited in this specification are herein incorporated by reference
in their entirety
as if each individual publication or reference were specifically and
individually indicated to
be incorporated by reference herein as being fully set forth. Any patent
application to which
23
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
this application claims priority is also incorporated by reference herein in
its entirety in the
manner described above for publications and references.
Table I.
GSI~ Nucleic Acid Corresponding
Gene Name Gene SEQ ID NO's Protein
ID
SEQ ID NO's
sb 237163LIPASE 237163 SEQ ID NO:1 SE ID N0:23
sbg251170CEAa 251170 SEQ ID N0:2 SEQ ID N0:24
SEQ ID N0:3 SEQ ID N0:25
sbg389686WNT15a 389686 SEQ ID N0:4 SEQ ID N0:26
SE ID NO:S SEQ ID N0:27
sbg236015LIPASE 236015 SEQ ID N0:6 SEQ ID N0:28
SEQ ID N0:7 SEQ ID N0:29
sbg417005LAMII~tIN_AL417005 SEQ ID N0:8 SEQ ID N0:30
PHA SEQ ID N0:9 SEQ ID N0:31
sb 425649KINASEa425649 SEQ ID NO:10 SEQ ID N0:32
sbg419582PROTOCADH419582 SEQ ID NO:11 SEQ ID N0:33
ERIN SEQ ID N0:12 SEQ ID N0:34
sb 453915TECTORINa453915 SEQ ID N0:13 SEQ ID NO:35
SBh385630.antiinflam385630 SEQ ID N0:14 SEQ ID N0:36
SE ID NO:15 SEQ ID N0:37
sb 471005nAChR 471005 SEQ ID N0:16 SEQ ID N0:38
sbg442445PROa 442445 SEQ ID N0:17 SEQ ID N0:39
sbg456548CytoRa 456548 SEQ ID N0:18 SEQ ID N0:40
SE ID N0:19 SEQ ID N0:41
sb 456548C toga 456548bSE ID N0:20 SEQ ID N0:42
sbg442358PROa 442358 SEQ ID N0:21 SEQ ID N0:43
SE ID N0:22 SEQ ID N0:44
24
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Table II
Gene Gene Closest PolynuclotideClosest PolypeptideCell
Name by
Family by homology homology Localization
(by
homology)
sbg237163PancreaticGB:AC011328 Mouse pancreatic Secreted
lipase
LIPASE lipase Direct submittedrelated protein
(06- 1, gi:
OCT-1999) Genome9256628
Therapeutics Remington,S.G.,
Corporation, Lima,P.H. and
100 Nelson,J.D.
Beaver Street, Invest. Ophthalmol.
Vis.
Waltham, MA Sci. 40 (6), 1081-1090
02453,
USA (1999)
sbg251170CCarcinoemGB:AC020914 Mouse putative Secreted
protein,
EAa bryonic Submitted (12-JAN-gi:12842545
antigen 2000) ProductionCarninci,P., Shibata,Y.,
Sequencing Facility,Hayatsu,N., Sugahara,Y.,
DOE Joint Shibata,K., Itoh,M.,
Genome Institute,Konno,H., Okazaki,Y.,
2800
Mitchell Drive,Muramatsu,M. and
Walnut
Creek, CA 94598,Hayashizaki,Y.
USA
Genome Res. 10
(10),
1617-1630 (2000).
sbg389686WNT15 GB:AC015855 Chicken WNT14 Secreted
protein,
WNTlSa Directly submittedgi:3915306
(17-
NOV-1999) WhiteheadBergstein I, Eisenberg
LM,
Institute/MIT Bhalerao J, Jenkins
Center NA,
for Genome Research,Copeland NG, Osborne
320 Charles MP, Bowcock AM,
Street, Brown
Cambridge, MA AM; 1997; Genomics
02141,
USA. 46:450-8.
sbg236015LLysosomaGB:AL358532 Rat lingual lipase,Secreted
IPASE 1 acid Directly submittedgi:126307
(15-
lipase DEC-2000) by Docherty,A.J.,
Sanger
Centre, Hinxton,Bodmer,M.W., Angal,S.,
Cambridgeshire,Verger,R., Riviere,C.,
CB 10
1SA, UK. Lowe,P.A., Lyons,A.,
Emtage,J.S. and
Harris,T.J.
Nucleic Acids
Res. 13 (6),
1891-1903 (1985)
sbg417005LLaminin GB:AL354836 Human laminin Secreted
alpha 5,
AMININ_Aalpha Direct submittedgi:12274842
(02-
LPHA MAY-2000) SangerSubmitted (14-FEB-2001)
Centre, Hinxton,by Sanger Centre,
Hinxton,
Cambridgeshire,Cambridgeshire,
CB10 CB10
1SA 1SA, UK.
sbg425649KC GB:AL356107 Human casein kinaseCytosolic
I-
INASEa Submitted (16-MAY-alpha,
asein 2000) by gi:2134872
kinase Sanger Centre, Fish,K.J.,
I-
alpha Hinxton, Cegielska,A.,
Cambridgeshire,
CB 10
1SA, UK. Getman,M.E.,
Landes,G.M. and
Virshup,D.M.
J. Biol. Chem.
270 (25),
14875-14883 (1995)
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WO 01/98342 PCT/USO1/19929
sbg419582PProtocadhGB:AL355593 Human protocadherinSecreted
ROTOCAD erin Direct submitted68
HERIN (17- gi:11433373
MAY-2000) SangerSubmitted (16-NOV-2000)
Centre, Hinxton,by National Center
Cambridgeshire,for
CB 10 Biotechnology
1SA, UK. Information, NIH,
Bethesda, MD 20894,
USA
sbg453915TTectorinSC:AL157786 Mouse tectorin Secreted
beta,
ECTORINaBeta Submitted (04-MAY-gi:7363457
2001) by SangerLegan,P.K., Rau,A.,
Centre, Hinxton,Keen,J.N. and
Cambridgeshire,Richardson,G.P.
CB10
1SA, UK. J. Biol. Chem.
272 (13),
8791-8801 (1997)
SBh385630.Lipase GB:AC015525 Rabbit lacrimal Secreted
lipase,
antiinflam Submitted (16-NOV-gi:13560884
1999) by WhiteheadSubmitted (20-FEB-2001)
Institute/MIT Ophthalmology,
Center Regions
for Genome Research,Hospital, 640
Jackson
320 Charles Street, St. Paul,
Street, MN 55101,
Cambridge, MA USA
02141,
USA
26
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Table II (cont).
Gene Gene FamilyClosest Closest PolypeptideCell
Nam by
Polynuclotidehomology Localization
by homology (by homology)
sbg47100Nicotinic GB:AC060812Human cholinergicMembrane-
SnAChR acetylcholineDirect submittedreceptor, nicotinic,bound
alpha
receptor (20-APR-2000)polypeptide 10,
Whitehead gi:11138123
Institute/MITLustig,L.R.,
Peng,H.,
Center for Hiel,H., Yamamoto,T.
Genome and Fuchs,P.A.
Research, Genomics 73 (3),
320 272-
Charles 283 (2001)
Street,
Cambridge,
MA
02141, USA
sbg44244Leucine GB:AC060234RIKEN cDNA mouseCytosolic
rich
SPROa repeat Submitted 4930442L21 gene
protein
(20-APR-2000)Carninci,P.,
Shibata,Y.,
Genome Hayatsu,N.,
TherapeuticsSugahara,Y.,
Shibata,K.,
Corporation,Itoh,M., Konno,H.,
100
Beaver Street,Okazaki,Y.,
Waltham, Muramatsu,M.
and
MA 02453, Hayashizaki,Y.
USA
Genome Res. 10
(10),
1617-1630(2000)
sbg45654Cytokine GB:AL158138Human IL20 receptor,Membrane-
8CytoRareceptor Submitted gi:7657691 bound
(20-
JAN-2001) Xie MH, Aggarwal
by S,
Sanger Centre,Ho WH, Foster
J, Zhang
Hinxton, Z, Stinson J,
Wood WI,
Cambridgeshire,Goddard AD and
Gurney
CB 10 1 AL.
SA, UK.
J. Biol. Chem.
275 (40),
31335-31339(2000)
sbg44235Leucine GB:AL139099Human EXMAD-9 Membrane-
rich
8PROa repeat Submitted geneseqp: AAB27231bound
protein (23-
MAY-2000) Submitted by
by INCYTE
Genoscope GENOMICS INC
-
Centre NationalApplication and
de Sequencagepublication date:
:
BP 191 91006W0200068380-A2,
16-
EVRY cedex NOV-00
-
FRANCE
27
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Table III
Gene Uses Associated
Name
Diseases
sbg237163An embodiment of the invention Cancer, infection,
is the use of sbg237163
LIPASE LIPASE as replacement enzymes for autoimmune
patients with chronic
pancreatitis. A close homologue disorder,
of sbg237163 LIPASE
is pancreatic lipase. Pancreatic hematopoietic
lipase hydrolyzes dietary
long chain triacylglycerol to freedisorder,
fatty acids and wound
monoacylglycerols in the intestinalhealing disorders,
lumen (Lowe ME,
Rosenblum JL, and Strauss AW; 1989;inflammation.
J Biol Chem
264:20042-8). Pancreatic steatorrhea
and pancreatic
diabetes are the dominant symptoms
of patients in a
certain stage of chronic pancreatitis.
In this stage, the
nutritional state is greatly disturbed
and hypoglycemia and
labile infection are involved.
Pancreatic enzyme
replacement therapy is the principal
treatment method for
pancreatic steatorrhea (Nakamura
T, Takeuchi T, and
Tando Y; 1998; Pancreas 16:329-36.
sbg251170CAn embodiment of the invention Cancer,
is the use of
EAa sbg251170CEAa as cell-surface moleculesautoimmune
mediating
cell-specific interactions in normaldisorders,
and neoplastic cells. A wound
close homologue of sbg251170CEAa healing disorders,
is
carcinoembryonic antigen-related hematopoietic
cell adhesion molecule .
6. Carcinoembryonic antigen-relateddisorders
cell adhesion and
molecule 6 is claimed to function infection
as a cell-surface
molecules mediating cell-specific
interactions in normal '
and neoplastic cells (1. Barnett
T, Goebel SJ, Nothdurft
MA, Elting JJ, Carcinoembryonic
antigen family:
characterization of cDNAs coding
for NCA and CEA and
suggestion of nonrandom sequence
variation in their
conserved loop-domains. Genomics
1988 Jul;3(1):59-66.
2. Inazawa J, Abe T, moue K, Misawa
S, Oikawa S,
Nakazato H, Yoshida MC. Regional
assignment of
nonspecific cross-reacting antigen
(NCA) of the CEA
gene family to chromosome 19 at
band q13.2. Cytogenet
Cell Genet 1989;52(1-2):28-31).
sbg389686An embodiment of the invention Cancer, infection,
is the use of
WNTlSa sbg389686WNT15a in regulation of autoimmune
cell growth and
differentiation. Close homologues disorder,
of
sbg389686WNT15a are Wnt proteins. hematopoietic
Wnt proteins are
involved in critical developmentaldisorder,
processes in both wound
vertebrates and invertebrates and healing disorders,
are implicated in
regulation of cell growth and differentiationand inflammation
in certain
adult mammalian tissues (Bergstein
I, Eisenberg LM,
Bhalerao J, Jenkins NA, Copeland
NG, Osboxne MP,
Bowcock AM, Brown AM; 1997; Genomics
46:450-8).
The Wnt gene family consists of
at least 15 structurally
related genes that encode secreted
extracellular
signaling factors. Wnt signaling
is involved in many
mammalian developmental processes,
including cell
proliferation, differentiation
and epithelial-mesenchymal
interactions, thxough which they
contribute to the
development of tissues and organs
such as the limbs, the
brain, the reproductive tract and
the kidney. Evidence
from tumor expression studies and
transgenic animals
experiments suggests that inappropriate
activation of the
Wnt signaling pathway is a major
feature in human
neoplasia and that oncogenic activation
of this pathway
can occur at man levels. Ina ro
riate ex ression of
28
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
the Wnt ligand and Wnt binding
proteins have been
found in a variety of human tumors
(Smalley MJ, Dale
TC;1999; Cancer Metastasis Rev
18:215-30).
sbg236015LAn embodiment of the invention Cancer, infection,
is the use of
IPASE sbg236015LIPASE for treating lipaseautoimmune
deficiency. A
close homologue of sbg236015LIPASEdisorder,
is lysosomal
acid lipase. The lysosomal acid hematopoietic
lipase catalyzes the
deacylation of triacylglyceryl disorder,
and cholesteryl ester core wound
lipids of endocytosed low density healing disorders,
lipoproteins. This
activity is deficient in patients inflammation,
with Wolman disease and
cholesteryl ester storage disease,Wolman disease,
which are caused by a
deficiency of lysosomal acid lipaseand cholesteryl
activity, resulting in
massive accumulation of cholesterylester storage
ester and
triglycerides (Anderson RA, Sando disease
GN; 1991;J Biol
Chem 266:22479-84).
sbg417005LAn embodiment of the invention Cancer, infection,
is the use of
AMININ_Asbg417005LAMININ_ALPHA to promote autoimmune
myogenesis
LPHA in skeletal muscle, outgrowth of disorder,
neurites from central
and peripheral neurons, and mesenchymalhematopoietic
to epithelial
transitions in kidney. A close disorder,
homologue of wound
sbg417005LAMININ_ALPHA is laminin.healing disorders,
Laminins
trimers, composed of alpha, beta, inflammation,
and gamma chains, are
components of all basal laminae congenital
(BLs) throughout the
bodies. In mammals they play at muscular
least three essential
roles. First, they are major structuraldystrophy,
elements of BLs, and
forming one of two self assemblingfunctional
networks to which
other glycoproteins and proteoglycansepidermolysis
of the BL attach.
Second, they interact with cell bullosa
surface components such
as dystroglycan to attach cells
to the extracellular
matrix. Third, they are signaling
molecules that interact
with cellular receptors such as
the integrins to convey
important information to the cell
interior. The alpha
chains are ligands for most cellular
laminin receptors.
(Miner JH, Patton BL, Lentz SI,
Gilbert DJ, Snider WD,
Jenkins NA, Copeland NG, Sanes
JR; 1997; J Cell Biol
137:685-701).
sbg425649KAn embodiment of the invention Cancer, wound
is the use of
INASEa sbg425649KINASEa in DNA replicationhealing disorders,
and repair,
membrane trafficking, neuroprotective,autoimmune
cytostatic,
cardioactive, immunomodulatory, disorders,
muscular, vulnerary,
gastrointestinal, nephrotropic, hematopoietic
anti-infective,
gynaecological and antibacterial disorders
activities, and can be and
used in gene therapy. Close homologuesinfection
of
sbg425649KINASEa is mammalian casein
kinases I
(CKI) and human prostate cancer
associated protein.
CKI belongs to a family of serine/threonine
protein
kinases involved in diverse cellular
processes including
DNA replication and repair, membrane
trafficking,
circadian rhythms and Wnt signaling.
Human prostate
cancer associated proteins have
neuroprotective,
cytostatic, cardioactive, immunomodulatory,
muscular,
vulnerary, gastrointestinal, nephrotropic,
anti-infective,
gynaecological and antibacterial
activities, and can be
used in ene them
29
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WO 01/98342 PCT/USO1/19929
Table III (coat).
Gene Uses Associated
Name
Diseases
sbg419582PAn embodiment of the invention Cancer, infection,
is the use of
ROTOCAD sbg419582PROTOCADHERIN in functionalautoimmune
systems of
HERIN the nervous system, and may be disorder,
involved in the
formation of the neural network. hematopoietic
A close homologue of
sbg419582PROTOCADHERIN is protocadherin.disorder,
The wound
expression of protocadherin is healing disorders,
developmentally
regulated in a subset of the functionalinflammation,
systems of the
nervous system, and may be involvedParkinson's
in the formation
of the neural network by segregationdisease,
of the brain nuclei
and mediation of the axonal connectionsHuntington's
(Hirano S, Yan
Q, Suzuki ST; 1999; J Neurosci chorea, and
19:995-1005). The
members of the cadherin superfamilymultiple
are divided into sclerosis
two groups: classical cadherin
type and protocadherin
type. The current cadherins appear
to have evolved from
protocadherin (Suzuki ST; 1996;
J Cell Sci 109:2609-
11).
sbg453915TAn embodiment of the invention Infection,
is the use of cancer,
ECTORINasbg453915TECTORINa, a secreted wound healing
protein, in cellular
adhesion. A close homologue of disorders,
sbg453915TECTORINa is mouse tectorinhemotopoietic
beta. The
beta-tectorin is a protein of 36,074disorders
Da that contains 4 and
consensus N glycosylation sites autoimmune
and a single zona
pellucida domain. It is similar disorders.
to components of the
sperm-egg adhesion system, and,
as such may have a
similar functional role (Legan
PK, Rau A, Keen JN,
Richardson GP, The mouse tectorins.
Modular matrix
proteins of the inner ear homologous
to components of
the sperm-egg adhesion system.
J Biol Chem 1997 Mar
28;272(13):8791-801).
SBh385630.An embodiment of the invention Lematopoietic
is the use of
antiinflamSBh385630.antiinflam in gene therapydisorders,
and are also wound
suggested to have cytokine and healing disorders,
cell
proliferation/differentiation activity,viral and
immune bacterial
stimulating (e.g.vaccines) or suppressinginfections,
activity, cancer,
haematopoiesis regulating activity,and autoimmune
tissue growth
activity, activin/inhibinactivity,diseases
chemotacticlchemokinetic activity,
haemostatic and
thrombolytic activity, receptor/ligand
activity,anti-
inflammatory activity, cadherin/tumour
invasion
suppressor activity, and tumour
inhibition activity.
Lipases are also reported to be
useful for gene therapy
(W09957132-Al;.Agostino, M.J.,
filed by GENETICS
INST INC.). Close homologues of
SBh385630.antiinflam include 1i
ases.
sbg471005nAn embodiment of the invention Cancer, infection,
is the use of
AChR sbg471005nAChR in physiological autoimmune
and behavioural
processes of the brain. A close disorder,
homologue of
sbg471005nAChR is neuronal nicotinichematopoietic
acetylcholine
receptors. Neuronal nicotinic acetylcholinedisorder,
receptors wound
are a family of ion channels whichhealing disorders,
are widely
distributed in the human brain. inflammation,
There are many
subtypes, and each has individual Alzheimer's
pharmacological and
functional profiles. They mediate disease,
the effects of nicotine,
and are involved in a number of Parkinson's
physiological and
behavioural processes. Additionallydisease,
they may be and
im licated in a number of atholo schizo hrenia
ical conditions such
CA 02414005 2002-12-20
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as Alzheimer's disease, Parkinson's
disease and
schizophrenia (Paterson D, Nordberg
A; 2000; Prog
Neurobiol 61:75-111).
sbg442445PAn embodiment of the invention Inflammation,
is the use of
ROa sbg442445PROa which may be involvedautoimmune
in protein-
protein interation and signal transductiondisorders,
in immune asthma,
system. sbg442445PROa was expressedallergies
predominantly
in lung and spleen/lymph. It encodesand
a protein with
leucine rich repeats which may sbg442445PROa-
be involved in protein-
protein interation and signal transductionassociated
in immune
s stems. disorders
sbg456548CThe present gene has been cloned. Chronic and
Sybrman data acute
ytoRa showed its high expression levels inflammation,
in placenta and
moderate levels in spleen and lymph.allergy,
A close arthritis
homologue of sbg456548CytoRa is (including
another Class II
cytokine receptor, ZCYTOR7. An rheumatoid
embodiment of the
invention is the use of sbg456548CytoRa,arthritis),
a decoy
receptor, in the identification septicemia,
of other ligands, the
promotion of anti-microbial activationautoimmune
of these cells,
and/or potentiate the effectivenessdiseases
of the natural ligand. (e.g.,
Growth factors are known to promoteinflammatory
the progression of
cancer. A decoy receptor could bowel disease,
interfere with that
process. Proliferation, survival psoriasis),
and differentiation can
be transduced from activated cytokinetransplant
receptors (Cell
Signal. 1998. 10(9):619-628). Blockingrejection,
these events graft vs.
could be crucial in modulating host disease,
various diseases.
The decoy receptor could potentiallyinfection,
interfere with stroke,
binding of these or other putativeischemia,
ligands, preventing acute
downstream effects (Blood. 1999. respiratory
94(6):1943-1951). disease
GM-CSF also has anti-apoptotic syndrome,
activity. A decoy asthma,
receptor might then be able to restenosis,
block GM-CSF's anti- brain
apoptotic actions when appropriateinjury, AIDS,
(Mol Biol Cell. bone
1999. 10(11):3959-3970). Roles diseases,
for blocking the cancer,
activity of the decoy receptor atheroschlerosis,
can be envisioned. GM-
CSF promotes anti-microbial functionsAlzheimers
of mature
neutrophils. Inhibiting the activitydisease,
of an interfering ,
decoy receptor could promote anti-microbialhematopoietic
activation
of these cells. Furthermore, rhGM-CSFdisorder,
is in wide and
clinical use to fight acute myeloidwound healing
leukemia
(Haematologica. 1991. 82(2): 239-245).disorder
Inhibition of a
decoy receptor could potentiate
the effectiveness of the
natural 1i and.
sbg442358PAn embodiment of the invention Cancer,
is the use of
ROa sbg442358PROa useful in the preventionautoimmune
and treatment
of cancers, cell proliferation, disorders,
cardiovascular,
reproductive, immune, musculoskeletal,hemotopoietic
developmental
and gastrointestinal disorders disorders,
and inflammation. Close wound
homologues of sbg442358PROa are healing disorders
human protein
B27231 and Drosophila LRR47 that and infections
also contains
leucine-rich repeats (LRRs) motifs.
LRR has been
found in a variety of extracellular,
membrane and
cytoplasmic proteins.and are believed
to mediate
specific protein-protein interactions
and to function in
cellular adhesion (Ntwasa,M., Buchanan,S.G.
and
Gay,N.J. Biochim. Biophys. Acta
1218 (2), 181-186
(1994)).
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Table IV. Quantitative, Tissue-specific mRNA expression detected using SybrMan
Quantitative, tissue-specific, mRNA expression patterns of the genes were
measured using SYBR-
Green Quantitative PCR (Applied Biosystems, Foster City, CA; see Schmittgen
T.D. et al.,
Analytical Biochemistry 285:194-204, 2000) and human cDNAs prepared from
various human
S tissues. Gene-specific PCR primers were designed using the first nucleic
acid sequence listed in the
Sequence List for each gene. Results are presented as the number of copies of
each specific gene's
mRNA detected in lng mRNA pool from each tissue. Two replicate mRNA
measurements were
made from each tissue RNA.
Gene Name sbg237163LIPASE
Tissue-Specific
mltNA
Expression
Gene (copies
per
ng
mRNA;
avg.
range
for
2
data
points
per
tissue)
Name BrainHeartLung LiverKidneySkeletalIntestine
muscle
sbg237165 g 7 -6 5 5 4
3LIPASE
0 2 2 1 1 2 6
Gene Name sbg237I63LIPASE cont.
Tissue-Specific
mRNA Expression
Gene (copies
per ng
mRNA; av
. t range
for 2 data
points
per tissue)
Name Spleen/lymphPlacentaTestis
sbg237163 1 47
3LIPASE
2 1 1
Gene Name sbg251170CEAa
Tissue-Specific
mRNA
Expression
Gene (copies
per
ng
mRNA;
av
.
range
for
2
data
points
per
tissue)
Name BrainHeartLung LiverKidneySkeletalIntestine
muscle
sbg251173 19 30 -5 3 5 21
OCEAa 1 1 5 3 1 5 2
Gene Name sbg251170CEAa cont.
Tissue-Specific
mRNA Expression
Gene (copies
per ng
mRNA; av
. range
for 2 data
points
per tissue)
Name Spleen/lymphPlacentaTestis
sbg2371633 22 14
3LIPASE
4 3 0
Table IV (cont).
In each gene's first subset table, two replicate measurements of gene of
identification (GOI) mRNA
were measured from various human tissues (column 2 and 3). The average GOI
mRNA copies of
the two replicates were made from each tissue RNA (column 4). The average
amount of 18S rRNA
from each tissue RNA was measured (column 5) and used for normalization. To
make each tissue
32
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WO 01/98342 PCT/USO1/19929
with the same amount of 50 ng of 18S rRNA, the normalization factor (column 6)
was calculated
by dividing 50 ng with the amount of 18S rRNA measured from each tissue
(column 5). The
mRNA copies per 50 ng of total RNA were obtained by multipling each GOI
normalization factor
and average mRNA copies (column7).
Fold changes shown in each gene's second subset table were only calculated for
disease tissues
which have a normal counterpart. There are blanks in the fold change column
for all samples that
do not have counterparts. In addition, the fold change calculations are the
fold change in the disease
sample as compared to the normal sample. Accordingly, there will not be a fold
change calculation
next to any of the normal samples. For patient matched cancer pairs (colon,
lung, and breast), each
tumor is compared to its specific normal counterpart. When patient-matched
normal/disease pairs
do not exist, each disease sample was compared back to the average of all the
normal samples of
that same tissue type. For example, normal brain from the same patient that
provided Alzheimer's
brain is not applicable . Three normal brain samples and 4 Alzheimer's brain
samples are used in the
fold change. Three normal samples were averaged, and each of the Alzheimer's
samples was
compared back to that average.
Abbreviations
ALZ Alzheimer's Disease
CT CLONTECH ( 1020 East Meadow Circle Palo Alto, CA 94303-4230, USA)
KC Sample prepared by GSK investigator
COPD chronic obstructive pulmonary disease
endo endothelial
VEGF vascular endothelial growth factor
bFGF basic fibroblast growth factor
BM bone marrow
osteo osteoblast
OA osteoarthritis
RA rheumatoid arthritis
PBL peripheral blood lymphocytes
PBMNC peripheral blood mononuclear cells
HIV human immunodeficiency virus
HSV Herpes simplex virus
HPV human papilloma virus
Gene Name sbg389686WNT15a
Strong expression in Brain and dendritic cells. Brain expression may be from
presence of glial cells.
Expression in RA and OA synovium along with dendritic cells suggests a role
for this protein in
these diseases. Down regulation in ischemic and dilated heart indicates that
replacement of protein
could be therapeutic.
Sample Mean Mean Average18S 50 ng/18Scopies
GOI GOI of
sbg389686WNT15acopies copies GOI rRNA rRNA mRNA
(sample (sampleCopies (ng) (ng) detected/
1) 2)
50
ng
total
RNA
Subcutaneous 0.00 0.00 0.00 3.06 16.34 0.00
Adi oc tes
Zenbio
Subcutaneous 0.00 1.71 0.86 0.96 52.36 44.76
Adipose
Zenbio
Adrenal Gland 2.29 4.18 3.24 0.61 81.97 265.16
Clontech
Whole Brain 698.52 625.01 661.77 7.24 6.91 4570.20
Clontech
Fetal Brain 4.14 6.78 5.46 0.48 103.95 567.57
Clontech
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Cerebellum 2.02 3.63 2.83 2.17 23.04 65.09
Clontech
Cervix 3.16 10.14 6.65 2.42 20.66 137.40
Colon 2.48 3.44 2.96 2.71 18.45 54.61
Endometrium 2.69 5.20 3.95 0.73 68.21 269.10
Eso ha us 10.67 3.24 6.96 1.37 36.50 253.83
Heart Clontech9.26 6.07 7.67 1.32 37.88 290.34
H othalamus 7.10 5.16 6.13 0.32 155.28 951.86
Ileum 2.04 10.37 6.21 2.58 19.38 120.25
Je'unum 36.78 27.16 31.97 6.60 7.58 242.20
Kidney 16.46 16.55 16.51 2.12 23.58 389.27
Liver 14.07 3.34 8.71 1.50 33.33 290.17
Fetal Liver 4.60 8.89 6.75 10.404.81 32.43
Clontech
Lun 3.11 10.49 6.80 2.57 19.46 132.30
Mammary Gland 3.28 10.61 6.95 13.003.85 26.71
Clontech
M ometrium 1.79 13.84 7.82 2.34 21.37 166.99
Omentum 1.96 2.65 2.31 3.94 12.69 29.25
Ov 4.50 1.71 3.11 4.34 11.52 35.77
Pancreas 3.40 2.41 2.91 0.81 61.80 179.54
Head of Pancreas2.22 4.63 3.43 1.57 31.85 109.08
Parotid Gland 5.48 2.07 3.78 5.48 9.12 34.44
Placenta Clontech15.15 12.80 13.98 5.26 9.51 132.84
Prostate 3.39 7.44 5.42 3.00 16.67 90.25
Rectum 2.98 3.94 3.46 1.23 40.65 140.65
Salivary Gland3.24 1.61 2.43 7.31 6.84 16.59
Clontech
Skeletal Muscle2.01 1.55 1.78 1.26 39.68 70.63
Clontech
Skin 2.69 3.45 3.07 1.21 41.32 126.86
Small Intestine5.39 1.67 3.53 0.98 51.07 180.29
Clontech
S Teen 3.96 2.52 3.24 4.92 10.16 32.93
Stomach 1.08 5.33 3.21 2.73 18.32 58.70
Testis Clontech3.27 2.88 3.08 0.57 87.87 270.21
Th mus Clontech5.43 4.42 4.93 9.89 5.06 24.90
Th roid 2.32 3.01 2.67 2.77 18.05 48.10
Trachea Clontech1.64 4.25 2.95 9.71 5.15 15.16
Urinary Bladder3.63 6.81 5.22 5.47 9.14 47.71
Uterus 31.55 11.10 21.33 5.34 9.36 199.67
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Sample Reg Mean copies Sample Fold Change
sbg389686WNT15anumber GOI of in
(GSK copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 36.16 72.32 colon
GW98-167 normal
colon tumor 21940 71.5 143.00 colon 1.977323009
GW98-166 tumor
colon normal 22080 2.09 4.18 colon
GW98-178 normal
colon tumor 22060 9.84 19.68 colon 4.708133971
GW98-177 tumor
colon normal 23514 13.09 26.18 colon
GW98-561 normal
colon tumor 23513 15.11 30.22 colon 1.154316272
GW98-560 tumor
colon normal 24691 8.62 17.24 colon
GW98-894 normal
colon tumor 24690 5.76 11.52 colon -1.496527778
GW98-893 tumor
lung normal 20742 140.19280.38 lung normal
GW98-3
lung tumor GW98-220741 1.67 3.34 lung tumor-83.94610778
lung normal 20677 60.54 121.08 lung normal
GW97-179
lung tumor GW97-17820676 135.62271.24 lung tumor2.240171787
lung normal 21922 257.96515.92 lung normal
GW98-165
lung tumor GW98-16421921 61.69 123.38 lung tumor-4.181552926
lung normal 22584 49.3 98.60 lung normal
GW98-282
lung tumor GW98-28122583 12.39 24.78 lung tumor-3.979015335
breast normal 28750 71.94 71.94 breast
GW00-392 normal
breast tumor 28746 41.4 82.80 breast 1.150959133
GW00-391 tumor
breast normal 28798 19.37 19.37 breast
GW00-413 normal
breast tumor 28797 1.13 2.26 breast -8.57079646
GW00-412 tumor
breast normal 27592-958.19 8.19 breast
GW00- normal
235:238
breast tumor 27588-9138.27 38.27 breast 4.672771673
GW00- tumor
231:234
breast normal 23656 77.26 154.52 breast
GW98-621 normal
breast tumor 23655 37.57 75.14 breast -2.056428001
GW98-620 tumor
brain normal 25507 597.171194.34brain
BB99-542 normal
brain normal 25509 104.34208.68 brain
BB99-406 normal
brain normalBB99-90425546 282.15564.30 brain
normal
brain stage 25502 84.26 168.52 brain -3.891367988
ALZ BB99- stage
874 5
ALZ
brain stage 25503 247.01494.02 brain -1.327422641
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 173.02346.04 brain -1.895079567
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 253.73507.46 brain -1.292266057
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 146.22292.44 CT lung
lung 26 KC normal 150.46150.46 lung 26
lung 27 KC normal 0 0.00 lung 27
lung 24 KC COPD 4.76 4.76 lung 24 -23.36292017
lung 28 KC COPD 10.06 10.06 lung 28 -11.05442346
lung 23 KC COPD 2.75 2.75 lung 23 -40.43909091
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lung 25 KC COPD 1.93 1.93 lung 25
asthmatic lung 29321 20.88 20.88 asthmatic-5.326029693
OD03112 lun
asthmatic lung 29323 133.29266.58 asthmatic2.397140481
OD03433 lun
asthmatic lung 29322 322.77645.54 asthmatic5.804824315
OD03397 lun
asthmatic lung 29325 43.52 87.04 asthmatic-1.277659697
OD04928 lun
endo cells KC control1.89 1.89 endo cells
endo VEGF KC 0 0.00 endo VEGF-1.89
endo bFGF KC 1.17 1.17 endo bFGF-1.615384615
heart Clontech normal 153.9 307.80 heart
heart ( T-1 29417 137.74275.48 heart -1.117322492
) ischemic T-1
heart (T-14) 29422 87.79 175.58 heart -1.753047044
non- T-14
obstructive
DCM
heart (T-3399) 29426 43.68 87.36 heart -3.523351648
DCM T-3399
adenoid GW99-26926162 17.62 35.24 adenoid
tonsil GW98-28022582 52.34 104.68 tonsil
T cells PC0031428453 8.45 16.90 T cells
PBMNC KC 1.99 1.99 PBMNC
monocyte KC 4.74 9.48 monocyte
B cells PC0066528455 7.65 15.30 B cells
dendritic cells 194.97389.94 dendritic
28441 cells
neutrophils 28440 2.13 2.13 neutrophils
eosinophils 28446 7.25 14.50 eosinophils
BM unstim KC 0 0.00 BM unstim
BM stun KC 0 0.00 BM stim 0
osteo dif KC 1.48 1.48 osteo
dif
osteo undif 7.41 7.41 osteo 5.006756757
KC undif
chondrocytes 26.64 66.60 chondrocyte
s
OA Synovium 29462 476.3 476.30 OA
IP12/O1 S novium
OA Synovium 29461 151.36302.72 OA
NP10/Ol S novium
OA Synovium 28464 165.01330.02 OA
NP57/00 S novium
RA Synovium 28466 84.02 168.04 RA
NP03/Ol S novium
RA Synovium 28467 184.75369.50 RA
NP71/00 Synovium
RA Synovium 28475 223.3 446.60 RA
NP45/00 S novium
OA bone (biobank)29217 72.31 72.31 OA bone
(biobank)
OA bone Sample J. Emory10.46 20.92 OA bone
1
OA bone Sample J. Emory111.79223.58 OA bone
2
Cartilage (pool)Normal 215.54431.08 Cartilage
( ool)
Cartilage (pool)OA 81.85 163.70 Cartilage-2.633353696
( ool)
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PBL unifected 28441 2.31 4.62 PBL
unifected
PBL HIV IIIB 28442 2.28 4.56 PBL HIV -1.013157895
IIIB
MRCS uninfected29158 2.37 4.74 MRCS
( 100%) uninfected
(100%)
MRCS HSV strain29178 37.5 75.00 MRCS 15.82278481
F HSV
strain
F
W 12 cells 29179 0.93 1.86 W 12
cells
Keratinocytes 29180 1.33 2.66 Keratinocyte
s
Gene Name sbg389686WNT15a
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 1.98
colon tumor 4.71
colon tumor 1.15
colon tumor -1.50
lun tumor -83.95
lun tumor 2.24
lun tumor -4.18
lun tumor -3.98
breast tumor 1.15
breast tumor -8.57
breast tumor 4.67
breast tumor -2.06
brain sta a 5 ALZ -3.89
brain sta a 5 ALZ -1.33
brain sta a 5 ALZ -1.90
brain sta a 5 ALZ -1.29
lun 24 -23.36
lun 28 -11.05
lun 23 -40.44
asthmatic lun -5.33
asthmatic lun 2.40
asthmatic lun 5.80
asthmatic lun -1.28
endo VEGF -1.89
endo bFGF -1.62
heart T-1 -1.12
heart T-14 -1.75
heart T-3399 -3.52
BM stun ' 0.00
osteo undif 5.01
Cartila a ( ool) -2.63
PBL HIV IIIB -1.01
'~M-C5 HSV strain F 15.82
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Gene Name sbg236015LIPASE
Strongly expressed in neutrophils and eosinophils suggesting an immune system
function.
Additional expression is seen in RA and OA synovium andl/3 OA bone samples.
This suggests an
involvement of 236015 in RA and OA. The high expression in skin when taken
together with
expression in neutrophils and eosinophils suggests possible involvement in
immune pathologies of
the skin ie. Eosinophilia, psoriasis and eczema. The expression in eosinophils
also suggests
involvement in allergic reactions. Expression in neutrophils suggests role in
anti-infectives.
Sample Mean Mean Average18S 50 copies
sbg236015LIPASEGOI GOI GOI rRNA ng/18Sof
copies copies Copies (ng) rRNA mRNA
(sample (sample (ng) detected/
1) 2) 50
ng
total
RNA
Subcutaneous 0.00 11.45 5.73 3.06 16.34 93.55
Adi oc tes
Zenbio
Subcutaneous 0.00 1.33 0.67 0.96 52.36 34.82
Adipose
Zenbio
Adrenal Gland 0.52 5.04 2.78 0.61 81.97 227.87
Clontech
Whole Brain 15.73 14.55 15.14 7.24 6.91 104.56
Clontech
Fetal Brain 1.02 0.94 0.98 0.48 103.95101.87
Clontech
Cerebellum 0.38 0.39 0.39 2.17 23.04 8.87
Clontech
Cervix 16.33 20.03 18.18 2.42 20.66 375.62
Colon 32.41 50.89 41.65 2.71 18.45 768.45
Endometrium 0.40 0.42 0.41 0.73 68.21 27.97
Esophagus 5.45 22.47 13.96 1.37 36.50 509.49
Heart Clontech0.92 0.00 0.46 1.32 37.88 17.42
Hypothalamus 0.50 1.59 1.05 0.32 155.28162.27
Ileum 41.95 1.51 21.73 2.58 19.38 421.12
Jejunum 7.59 15.40 11.50 6.60 7.58 87.08
Kidney 5.32 6.82 6.07 2.12 23.58 143.16
Liver 12.64 19.46 16.05 1.50 33.33 535.00
Fetal Liver 10.02 5.90 7.96 10.40 4.81 38.27
Clontech
Lung 22.86 24.78 23.82 2.57 19.46 463.42
Mammary Gland 1.53 20.56 11.05 13.00 3.85 42.48
Clontech
Myometrium 16.05 1.34 8.70 2.34 21.37 185.79
Omentum 8.33 9.88 9.11 3.94 12.69 115.55
Ovary 8.22 14.40 11.31 4.34 11.52 130.30
Pancreas 0.00 1.58 0.79 0.81 61.80 48.83
Head of Pancreas0.00 1.98 0.99 1.57 31.85 31.53
Parotid Gland 5.30 11.45 8.38 5.48 9.12 76.41
Placenta Clontech11.93 1.22 6.58 5.26 9.51 62.50
Prostate 0.00 0.00 0.00 3.00 16.67 0.00
Rectum 6.96 1.27 4.12 1.23 40.65 167.28
Salivary Gland0.34 0.53 0.44 7.31 6.84 2.98
Clontech
Skeletal Muscle176.88 0.41 88.65 1.26 39.68 3517.66
Clontech
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Skin 95.17 147.16 121.17 1.21 41.32 5006.82
Small Intestine0.35 1.31 0.83 0.98 51.07 4.2.39
Clontech
Spleen 105.73 80.76 93.25 4.92 10.16 947.61
Stomach 0.56 3.73 2.15 2.73 18.32 39.29
Testis Clontech0.79 0.78 0.79 0.57 87.87 68.98
Thymus Clontech22.00 22.48 22.24 9.89 5.06 112.44
Thyroid 0.65 0.48 0.57 2.77 18.05 10.20
Trachea Clontech1.20 0.00 0.60 9.71 5.15 3.09
Urinary Bladder5.59 8.67 7.13 5.47 9.14 65.17
Uterus 19.26 27.10 23.18 5.34 9.36 217.04
Sample Reg Mean copies Sample Fold Change
sbg236015LIPASEnumber GOI of in
(GSK copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 58.7 117.40 colon
GW98-167 normal
colon tumor 21940 300.92601.84 colon 5.126405451
GW98-166 tumor
colon normal 22080 8.78 17.56 colon
GW98-178 normal
colon tumor 22060 23.74 47.48 colon 2.703872437
GW98-177 tumor
colon normal 23514 27.1 54.20 colon
GW98-561 normal
colon tumor 23513 39.16 78.32 colon 1.44501845
GW98-560 tumor
colon normal 24691 10.15 20.30 colon
GW98-894 normal
colon tumor 24690 144.58289.16 colon 14.24433498
GW98-893 tumor
lung normal 20742 165.8 331.60 lung
GW98-3 normal
lung tumor GW98-220741 80.9 161.80 lung -2.049443758
tumor
lung normal 20677 37.81 75.62 lung
GW97-179 normal
lung tumor GW97-17820676 109.72219.44 lung 2.90187781
tumor
lung normal 21922 150.06300.12 lung
GW98-165 normal
lung tumor GW98-16421921 169.73339.46 lung 1.131080901
tumor
lung normal 22584 489.42978.84 lung
GW98-282 normal
lung tumor GW98-28122583 188.22376.44 lung -2.600255021
tumor
breast normal 28750 44.86 44.86 breast
GW00-392 normal
breast tumor 28746 46.35 92.70 breast 2.06642889
GW00-391 tumor
breast normal 28798 16.35 16.35 breast
GW00-413 normal
breast tumor 28797 55.98 111.96 breast 6.847706422
GW00-412 tumor
breast normal 27592-953.84 3.84 breast
GW00- normal
235:238
breast tumor 27588-9135.8 35.80 breast 9.322916667
GW00- tumor
231:234
breast normal 23656 12.14 24.28 breast
GW98-621 normal
breast tumor 23655 44.85 89.70 breast 3.694398682
GW98-620 tumor
brain normal 25507 26.03 52.06 brain
BB99-542 normal
brain normal 25509 14.78 29.56 brain
BB99-406 normal
brain normal 25546 3.39 6.78 brain
BB99-904 normal
brain stage 25502 35.71 71.42 brain 2.423755656
ALZ BB99- stage
874 5
ALZ
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brain stage 25503 9.11 18.22 brain -1.617270399
ALZ BB99- stage
887 5
ALZ
brain stage 25504 8.18 16.36 brain -1.801140994
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 46.37 92.74 brain 3.147285068
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 80.77 161.54 CT lung
lung 26 KC normal 233.65233.65 lung
26
lung 27 KC normal 75.27 75.27 lung
27
lung 24 KC COPD 68.64 68.64 lung -1.876821096
24
lung 28 KC COPD 94.1 94.10 lung -1.369022317
28
lung 23 KC COPD 88.48 88.48 lung -1.455978752
23
lung 25 KC normal 44.84 44.84 lung
25
asthmatic lung 29321 111.42111.42 asthmatic-1.156210734
OD03112 lun
asthmatic lung 29323 566.5 1133.00 asthmatic8.794876771
OD03433 lun
asthmatic lung 29322 262.77525.54 asthmatic4.079487677
OD03397 lun
asthmatic lung 29325 367.52735.04 asthmatic5.70572482
ODO4928 lung
endo cells KC control3.23 3.23 endo
cells
endo VEGF KC 3.41 3.41 endo 1.055727554
VEGF
endo bFGF KC 0 0.00 endo -3.23
bFGF
heart Clontech normal 0 0.00 heart
heart ( T-1 29417 35.96 71.92 heart 71.92
) ischemic T-1
heart (T-14) 29422 18.72 37.44 heart 37.44
non- T-14
obstructive
DCM
heart (T-3399) 29426 37.97 75.94 heart 75.94
DCM T-3399
adenoid GW99-26926162 14.17 28.34 adenoid
tonsil GW98-28022582 51.21 102.42 tonsil
T cells PC0031428453 111.1 222.20 T cells
PBMNC KC 162.01162.01 PBMNC
monocyte KC 90.49 180.98 monocyte
B cells PC0066528455 109.71219.42 B cells
dendritic cells 2.44 4.88 dendritic
28441 cells
neutrophils 28440 1110.911110.91 neutrophils
eosinophils 28446 835.721671.44 eosinophils
BM unstim KC 181.05181.05 BM unstim
BM stim KC 93.96 93.96 BM stun -1.92688378
osteo dif KC 0 0.00 osteo
dif
osteo undif 0.72 0.72 osteo 0.72
KC undif
chondrocytes 2.03 5.08 chondrocyte
s
OA Synovium 29462 27.82 27.82 OA
IP12/O1 Synovium
OA Synovium 29461 84.94 169.88 OA
NP10/Ol S novium
OA Synovium 28464 46.58 93.16 OA
NP57/00 S novium
RA Synovium 28466 248.24496.48 RA
NP03/Ol S novium
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RA Synovium 28467 148.32296.64 RA
NP71/00
S novium
RA Synovium 28475 260.28520.56 RA
NP4S/00
S novium
OA bone (biobank)29217 10.27 10.27 OA bone
(biobank)
OA bone Sample J. Emory17.32 34.64 OA bone
1
OA bone Sample J. Emory657.011314.02 OA bone
2
Cartilage (pool)Normal 59.17 118.34 Cartilage
( ool)
Cartilage (pool)OA 23.33 46.66 Cartilage-2.53621946
( ool)
PBL unifected 28441 23.51 47.02 PBL
unifected
PBL HIV IIIB 28442 5.86 11.72 PBL HIV -4.011945392
IIIB
MRCS uninfected29158 3.79 7.58 MRCS
(100%)
uninfected
(100%)
MRCS HSV strain29178 80.19 160.38 MRCS 21.15831135
F HSV
strain
F
W 12 cells 29179 95.42 190.84 W 12
cells
Keratinocytes 29180 16.18 32.36 Keratinocyte
s
Gene Name sbg23601SLIPASE
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 5.13
colon tumor 2.70
colon tumor 1.45
colon tumor 14.24 .
lun tumor -2.OS
lun tumor 2.90
lun tumor 1.13
lun tumor -2.60
breast tumor 2.07
breast tumor 6.85
breast tumor 9.32
breast tumor 3.69
brain sta a S ALZ 2.42
brain sta a S ALZ -1.62
brain sta a S ALZ -1.80
brain sta a S ALZ 3.15
lun 24 -1.88
lun 28 -1.37
lun 23 -1.46
asthmatic lun -1.16
asthmatic lung 8.79
asthmatic lun 4.08
asthmatic lun 5.71
endo VEGF 1.06
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endo bFGF _ _ -3.23
~
_
heart T-1 __ 71.92
__
heart T-14 37.44
heart T-3399 75.94
BM stun -1.93
osteo undif 0.72
Cartila a ( ooI) -2.54
PBL HIV IIIB -4.01
MRCS HSV strain F 21.16
Gene Name sbg417005LAMIN11V
Expression in adenoid, tonsil and B-cells with corroborating expression in
RA/OA samples and
asthmatic lung (1/4) suggests involvement in these diseases. Strong expression
in brain with
overexpression in Alzheimer's disease indicates a role in AD. Down regulation
in HSV infected
cells suggests potential host cell factor. Expression in colon and lung
normal/tumor pairs without
corroborating expression in normal tissues suggests immune cell infiltrates.
Sample Mean GOI Mean Average18S 50 copies
sbg417005LAMININcopies GOI GOI rRNA ng/18Sof
(sample copies Copies (ng) rRNA mRNA
1) (sample (ng) detecte
2) d/50
ng
total
RNA
Subcutaneous 60.278530373.5967995566.94 3.06 16.34 1093.75
Adi oc tes
Zenbio
Subcutaneous 3.0325729651.9858621532.51 0.96 52.36 131.37
Adipose
Zenbio
Adrenal Gland0.9657034970.9657034970.97 0.61 81.97 79.16
Clontech
Whole Brain 4131.5579926997.8790785564.727.24 6.91 3$430.3
Clontech 8
Fetal Brain 0.9657034973.2682113252.12 0.48 103.95220.06
Clontech
Cerebellum 3.30105786717.396666510.35 2.17 23.04 238.45
Clontech
Cervix 5.9204840497.5178915716.72 2.42 20.66 138.83
Colon 35.4896268422.5318060529.01 2.71 18.45 535.25
Endometrium 11.597574920.9657034976.28 0.73 68.21 428.49
Esophagus 7.0985288573.5232164755.31 1.37 36.50 193.83
Heart Clontech0.9657034975.3689772873.17 1.32 37.88 119.98
Hypothalamus 0.9657034970.9657034970.97 0.32 155.28149.95
Ileum 30.8100684714.1503229622.48 2.58 19.38 435.66
Jejunum 44.0899405830.2938631437.19 6.60 7.58 281.76
Kidney 9.42497398115.6852912512.56 2.12 23.58 296.11
Liver 3.7422881610.9657034972.35 1.50 33.33 78.47
fetal Liver 94.4594948493.896225294.18 10.404.81 452.78
Clontech
Lung 13.8478244419.9536756616.90 2.57 19.46 328.81
Mammary Gland107.795616195.02632495101.41 13.003.85 390.04
Clontech
Myometrium 12.5011786614.9374280413.72 2.34 21.37 293.15
Omentum 13.99821322.0381635718.02 3.94 12.69 228.66
Ovary 0.9657034970.9657034970.97 4.34 11.52 11.13
Pancreas 2.2547504250.9657034971.61 0.81 61.80 99.52
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Head of Pancreas0.9657034970.9657034970.97 1.57 31.85 30.75
Parotid Gland25.893089214.8566817320.37 5.48 9.12 185.90
Placenta Clontech83.8402966895.0263249589.43 5.26 9.51 850.13
Prostate 8.04738673315.1824526211.61 3.00 16.67 193.58
Rectum 10.5357288220.0638501115.30 1.23 40.65 621.94
Salivary Gland62.4302433157.1962335259.81 7.31 6.84 409.12
Clontech
Skeletal Muscle1.3767462140.9657034971.17 1.26 39.68 46.48
Clontech
Skin 0.9657034970.9657034970.97 1.21 41.32 39.91
Small Intestine0.9657034970.9657034970.97 0.98 51.07 49.32
Clontech
Spleen 0.9657034975.7401474923.35 4.92 10.16 34.07
Stomach 0.9657034970.9657034970.97 2.73 18.32 17.69
Testis Clontech0.9657034970.9657034970.97 0.57 87.87 84.86
Thymus Clontech258.7386545207.7169358233.23 9.89 5.06 1179.11
Thyroid 12.5684978519.0948934315.83 2.77 18.05 285.77
Trachea Clontech24.3533087831.8704764128.11 9.71 5.15 144.76
Urinary Bladder51.8183109157.5303587154.67 5.47 9.14 499.77
Uterus ' 13.1209955914.6171897113.87 5.34 9.36 129.86
I i I I
Sample Reg Mean copies Sample Fold Change
sbg417005LAMININnumberGOI of in Disease
(GSK copies mRNA Population
identifier detected/50
ng total
RNA
colon normal 21941 15446.9272830893.85colon
GW98-167 normal
colon tumor 21940 23910.9041547821.81colon 1.547939193
GW98-166 tumor
colon normal 22080 14621.9732129243.95colon
GW98-178 normal
colon tumor 22060 2058.303964116.61 colon -7.10389403
GW98-177 tumor
colon normal 23514 5590.90047411181.80colon
GW98-561 normal
colon tumor 23513 12318.1036224636.21colon 2.203241442
GW98-560 tumor
colon normal 24691 4478.6924038957.38 colon
GW98-894 normal
colon tumor 24690 7546.10094415092.20colon 1.684889308
GW98-893 tumor
lung normal 20742 23910.9041547821.81lung
GW98-3 normal
lung tumor GW98-220741 35021.2331770042.47lung 1.464655328
tumor
lung normal 20677 23341.6142146683.23lung
GW97-179 normal
lung tumor GW97-17820676 24103.9025248207.81lung 1.032657909
tumor
lung normal 21922 18374.4127336748.83lung
GW98-165 normal
lung tumor GW98-16421921 34735.1972669470.39lung 1.890411289
tumor
lung normal 22584 3002.2984676004.60 lung
GW98-282 normal
lung tumor GW98-28122583 3519.5609557039.12 lung 1.172288829
tumor
breast normal 28750 5978.6719375978.67 breast
GW00-392 normal
breast tumor 28746 5674.72118611349.44breast 1.898321649
GW00-391 tumor
breast normal 28798 1523.6432581523.64 breast
GW00-413 normal
breast tumor 28797 956.09029141912.18 breast 1.255005444
GW00-412 tumor
breast normal 27592-95760.6128764760.61 breast
GW00- I
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235:238 normal
breast tumor 27588-914192.500034192.50 breast 5.51200244
GW00- tumor
231:234
breast normal 23656 5674.72118611349.44breast
GW98-621 normal
breast tumor 23655 8017.20207116034.40breast 1.412792243
GW98-620 tumor
brain normal 25507 791.78182891583.56 brain
BB99-542 normal
brain normal 25509 524.9900011049.98 brain
BB99-406 normal
brain normal 25546 396.8655236793.73 brain
BB99-904 normal
brain stage 25502 3203.4986456407.00 brain 5.608243725
ALZ BB99- stage
874 5
ALZ
brain stage 25503 3925.5059177851.01 brain 6.872234505
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 1502.6519423005.30 brain 2.630635833
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 1555.7113253111.42 brain 2.723524884
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal3730.2498747460.50 CT lung
lung 26 KC normal286.3143862286.31 lung
26
lung 27 KC normal72.3056094172.31 lung
27
lung 24 KC COPD 28.4777137428.48 lung -69.25877363
24
lung 28 KC COPD 66.9800687566.98 lung -29.44654382
28
lung 23 KC COPD 57.5303587157.53 lung -34.28331708
23
lung 25 KC COPD 70.2063740270.21 lung
25
asthmatic lung 29321 2304.9153852304.92 asthmatic1.168624722
OD03112 lun
asthmatic lung 29323 3112.3770186224.75 asthmatic3.156038395
OD03433 lun
asthmatic lung 29322 21892.207143784.41asthmatic22.19931768
OD03397 lun
asthmatic lung 29325 5268.43836410536.88asthmatic5.34234563
OD04928 lun
endo cells KC control396.8655236396.87 endo
cells
endo VEGF KC 157.1987188157.20 endo -2.524610421
VEGF
endo bFGF KC 518.1542863518.15 endo 1.305616778
bFGF
heart Clontech normal1865.3029573730.61 heart
heart ( T-1 29417 3757.5054567515.01 heart 2.014421005
) ischemic T-1
heart (T-14) 29422 1633.3335433266.67 heart -1.142022072
non- T-14
obstructive
DCM
heart (T-3399) 29426 2938.2264925876.45 heart 1.575200683
DCM T-3399
adenoid GW99-26926162 1238.7251052477.45 adenoid
tonsil GW98-28022582 2288.6252364577.25 tonsil
T cells PC0031428453 61.34444995122.69 T cells
PBMNC KC 5.3414929575.34 PBMNC
monocyte KC 3.5766866927.15 monocyte
B cells PC0066528455 716.26015361432.52 B cells
dendritic cells 32.2324331464.46 dendritic
28441 cells
neutrophils 28440 32.969399632.97 neutrophils
eosinophils 28446 1.4441443122.89 eosinophils
BM unstim KC 5.9511157955.95 BM unstim
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BM stim KC 11.7223323511.72 BM stun 1.969770503
osteo dif KC 10.2049546510.20 osteo
dif
osteo undif 8.5260980788.53 osteo -1.196907959
KC undif
chondrocytes 14621.9732136554.93chondrocyte
s
OA Synovium 29462 5549.4801425549.48 OA
IP12/Ol
S novium
OA Synovium 29461 3545.1971277090.39 OA
NP10/O1
S novium
OA Synovium 28464 4223.3254548446.65 OA
NP57/00
Synovium
RA Synovium 28466 1221.8453092443.69 RA
NP03/Ol
S novium
RA Synovium 28467 4892.678729785.36 RA
NP71/00
S novium
RA Synovium 28475 1080.3967392160.79 RA
NP45/00
S novium
OA bone (biobank)29217 995.7612933995.76 OA bone
(biobank)
OA bone Sample J. 982.34839141964.70 OA bone
1 Emory
OA bone Sample J. 472.8535333945.71 OA bone
2 Emory
Cartilage (pool)Normal1213.4964342426.99 Cartilage
( ool)
Cartilage (pool)OA 697.43021731394.86 Cartilage-1.73995391
( ool)
PBL unifected 28441 161.1142664322.23 PBL
unifected
PBL HIV IIIB 28442 191.5686557383.14 PBL HIV 1.189023542
IIIB
MRCS uninfected29158 5934.22059311868.44MRCS
(100%) uninfected
(100%)
MRCS HSV strain29178 50.63206269101.26 MRCS -117.2028213
F HSV
strain
F
W 12 cells 29179 13843.295527686.59W 12
cells
Keratinocytes 29180 11849.915623699.83Keratinocyte
s
Gene Name sbg417005LAMIN1N
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 1.55
colon tumor -7.10
colon tumor 2.20
colon tumor 1.68
lun tumor 1.46
lun tumor 1.03
lun tumor 1.89
lun tumor 1.17
breast tumor 1.90
breast tumor 1.26
breast tumor 5.51
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breast tumor _ 1.41
brain sta a 5 ALZ ~~5.61
brain sta a 5 ALZ 6.87
brain sta a 5 ALZ 2.63
brain sta a 5 ALZ 2.72
lun 24 -69.26
lun 28 -29.45
lun 23 -34.28
asthmatic lun 1.17
asthmatic lun 3.16
asthmatic lun 22.20
asthmatic lun 5.34
endo VEGF -2.52
endo bFGF 1.31
heart T-1 2.01
heart T-14 -1.14
heart T-3399 1.58
BM stim 1.97
osteo undif -1.20
Cartila a ( ool) -1.74
PBL HIV IIIB 1.19
MRCS HSV strain F -117.20
Gene Name sbg425649KINASEa
Strongly expressed in neutrophils and eosinophils suggesting function in
immume system such as
involvement in allergic reactions and anti-infective. Lower expression in T-
cells. Expression in 2/3
OA bone samples indicate a role in OA. Strongly expressed in rectum and
skeletal muscle,
unknown function.
Sample Mean Mean Average18S 50 copies
sbg425649KINASEaGOI GOI GOI rRNA ng/18Sof
copies copies Copies (ng) rRNA mRNA
(sample(sample (ng) detected/
1) 2) 50
ng
total
RNA
Subcutaneous 0.00 0.03 0.02 3.06 16.34 0.25
Adi ocytes
Zenbio
Subcutaneous 0.00 0.00 0.00 0.96 52.36 0.00
Adipose
Zenbio
Adrenal Gland 0.23 0.00 0.12 0.61 81.97 9.43
Clontech
Whole Brain 163.64 47.63 105.64 7.24 6.91 729.52
Clontech
Fetal Brain 0.47 0.00 0.24 0.48 103.9524.43
Clontech
Cerebellum 0.00 0.00 0.00 2.17 23.04 0.00
Clontech
Cervix 5.54 0.00 2.77 2.42 20.66 57.23
Colon 0.70 0.00 0.35 2.71 18.45 6.46
Endometrium 0.33 0.06 0.20 0.73 68.21 13.30
Esophagus 0.35 0.47 0.41 1.37 36.50 14.96
Heart Clontech0.00 0.00 0.00 1.32 37.88 0.00
Hypothalamus 0.00 0.00 0.00 0.32 155.280.00
Ileum 0.00 4.49 2.25 2.58 19.38 43.51
Jejunum 0.29 0.73 0.51 6.60 7.58 3.86
Kidney 0.00 0.00 0.00 2.12 23.58 0.00
Liver 10.48 5.64 8.06 1.50 33.33 268.67
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Fetal Liver 8.56 0.00 4.28 10.40 4.81 20.58
Clontech
Lung 0.00 0.00 0.00 2.57 19.46 0.00
Mammary Gland 0.00 0.00 0.00 13.00 3.85 0.00
Clontech
Myometxium 8.61 5.00 6.81 2.34 21.37 145.41
Omentum 0.23 10.99 5.61 3.94 12.69 71.19
Ovary 4.48 4.62 4.55 4.34 11.52 52.42
Pancreas 0.27 0.00 0.14 0.81 61.80 8.34
Head of Pancreas0.11 0.04 0.08 1.57 31.85 2.39
Parotid Gland 0.69 4.51 2.60 5.48 9.12 23.72
Placenta Clontech10.58 0.14 5.36 5.26 9.51 50.95
Prostate 9.74 6.18 7.96 3.00 16.67 132.67
Rectum 225.51 76.99 151.25 1.23 40.65 6148.37
Salivary Gland60.93 67.22 64.08 7.31 6.84 438.27
Clontech
Skeletal Muscle749.28 29.78 389.53 1.26 39.68 15457.54
Clontech
Skin 0.00 4.46 2.23 1.21 41.32 92.15
Small Intestine0.73 0.00 0.37 0.98 51.07 18.64
Clontech
Spleen 4.10 8.60 6.35 4.92 10.16 64.53
Stomach 4.24 19.28 11.76 2.73 18.32 215.38
Testis Clontech10.11 6.34 8.23 0.57 87.87 722.76
Thymus Clontech2.79 5.35 4.07 9.89 5.06 20.58
Thyroid 0.00 0.06 0.03 2.77 18.05 0.54
Trachea Clontech5.24 14.14 9.69 9.71 5.15 49.90
Urinary Bladder0.09 0.00 0.05 5.47 9.14 0.41
Uterus 27.26 7.61 117.44 5.34 9.36 163.25
Sample Reg Mean copies Sample Fold Change
sbg425649KINASEanumber GOI of in Disease
(GSK copiesmRNA Population
identifier) detected/50
ng total
RNA
colon normal 21941 11.11 22.22 colon
GW98-167 normal
colon tumor 21940 7.3 14.60 colon -1.521917808
GW98-166 tumor
colon normal 22080 0 0.00 colon
GW98-178 normal
colon tumor 22060 2.57 5.14 colon 5.14
GW98-177 tumor
colon normal 23514 0 0.00 colon
GW98-561 normal
colon tumor 23513 0 0.00 colon 0
GW98-560 ~ tumor
colon normal 24691 2.71 5,42 colon
GW98-894 normal
colon tumor 24690 8.51 17.02 colon 3.140221402
GW98-893 tumor
lung normal 20742 1.78 3.56 lung
GW98-3 normal
lung tumor GW98-220741 0 0.00 lung -3.56
tumor
lung normal 20677 3.18 6.36 lung
GW97-179 normal
lung tumor GW97-17820676 2.64 5.28 lung -1.204545455
tumor
lung normal 21922 6.46 12.92 lung
GW98-165 normal
lung tumor GW98-16421921 19.99 39.98 lung 3.094427245
tumor
lung normal 22584 31.56 63.12 lung
GW98-282 normal
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lung tumor GW98-28122583 7.47 14.94 lung -4.224899598
tumor
breast normal 28750 5.68 5.68 breast
GW00-392 normal
breast tumor 28746 2.87 5.74 breast l.OlOS6338
GW00-391 tumor
breast normal 28798 1.66 1.66 breast
GW00-413 normal
breast tumor 28797 1.99 3.98 breast 2.397590361
GW00-412 tumor
breast normal 27592-950 0.00 breast
GW00- normal
235:238
breast tumor 27588-912.19 2.19 breast 2.19
GW00- tumor
231:234
breast normal 23656 4.72. 9.44 breast
GW98-621 normal
breast tumor 23655 0 0.00 breast -9.44
GW98-620 tumor
brain normal 25507 28.9 57.80 brain
BB99-542 normal
brain normal 25509 24.84 49.68 brain
BB99-406 normal
brain normal 25546 6.92 13.84 brain
BB99-904 normal
brain stage 25502 23.65 47.30 brain 1.169634026
S ALZ BB99- stage
874 5
ALZ
brain stage 25503 28.68 57.36 brain 1.418397626
ALZ BB99- stage
887 5
ALZ
brain stage 25504 18.18 36.36 brain -1.112211221
S ALZ BB99- stage
862 5
ALZ
brain stage 25542 14.18 28.36 brain -1.42S9S2045
5 ALZ BB99- stage
927 S
ALZ
CT lung KC normal 29.45 58.90 CT lung
lung 26 KC normal 2.47 2.47 lung
26
lung 27 KC normal 0 0.00 lung
27
lung 24 KC COPD 0 0.00 lung -15.3425
24
lung 28 KC COPD 0.3 0.30 lung -S 1.14166667
28
lung 23 KC COPD 0 0.00 lung -15.3425
23
lung 2S KC COPD 0 0.00 lung
2S
asthmatic lung 29321 3.24 3.24 asthmatic-4.73S339S06
OD03112 lun
asthmatic lung 29323 88.32 176.64 asthmatic11'.S
OD03433 lun 1311716
asthmatic lung 29322 SS.6S 111.30 asthmatic7.254358807
OD03397 lun
asthmatic lung 29325 50.64 101.28 asthmatic6.601270979
OD04928 lun
endo cells KC control0 0.00 endo
cells
endo VEGF KC 0 0.00 endo 0
VEGF
endo bFGF KC 0 0.00 endo 0
bFGF
heart Clontech normal 15.26 30.52 heart
heart ( T-1 29417 0 0.00 heart -30.52
) ischemic T-1
heart (T-14) 29422 3.69 7.38 heart -4.135S013S5
non- T-14
obstructive
DCM
heart (T-3399) 29426 0 0.00 heart -30.52
DCM T-3399
adenoid GW99-26926162 0 0.00 adenoid
tonsil GW98-28022582 3.65 7.30 tonsil
T cells PC0031428453 167.51335.02 T cells
PBMNC KC 2.S 2.50 PBMNC
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monocyte KC 2.37 4.74 monocyte
B cells PC0066528455 0 0.00 B cells
dendritic cells 0 0.00 dendritic
28441 cells
neutrophils 28440 1576.761576.76 neutrophils
eosinophils 28446 755.1 1510.20 eosinophils
BM unstim KC 14.87 14.87 BM unstim
BM stim KC 45.45 45.45 BM stim 3.056489576
osteo dif KC 0 0.00 osteo
dif
osteo undif 0 0.00 osteo 0
KC undif
chondrocytes 7.48 18.70 chondrocyte
s
OA Synovium 29462 17.79 17.79 OA
IP12/O1 S novium
OA Synovium 29461 14.09 28.18 OA
NP10/O1 S novium
OA Synovium 28464 11.97 23.94 OA
NP57/00 Synovium
RA Synovium 28466 6.84 13.68 RA
NP03/Ol S novium
RA Synovium 28467 22.88 45.76 RA
NP71/00 S novium
RA Synovium 28475 1.64 3.28 RA
NP45/00 S novium
OA bone (biobank)29217 370.22370.22 OA bone
(biobank)
OA bone Sample J. Emory3.21 6.42 OA bone
1
OA bone Sample J. Emory311.65623.30 OA bone
2
Cartilage (pool)Normal 32.23 64.46 Cartilage
( ool)
Cartilage (pool)OA 2.87 5.74 Cartilage-11.22996516
( ool)
PBL unifected 28441 4.18 8.36 PBL
unifected
PBL HIV IIIB 28442 0 0.00 PBL HIV -8.36
IIIB
MRCS uninfected29158 4.4 8.80 MRCS
( 100%) uninfected
(100%)
MRCS HSV strain29178 11.46 22.92 MRCS HSV 2.604545455
F strain
F
W 12 cells 29179 0 0.00 W 12 cells
Keratinocytes 29180 0 0.00 Keratinocyte
s
Gene Name sbg425649KINASEa
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor -1.52
colon tumor 5.14
colon tumor 0.00
colon tumor 3.14
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lun tumor -3.56
lun tumor -1.20
lun tumor 3.09
lun tumor -4.22
breast tumor 1.01
breast tumor 2.40
breast tumor 2.19
breast tumor ~ -9.44
brain sta a 5 ALZ 1.17
brain sta a 5 ALZ 1.42
brain sta a 5 ALZ -1.11
brain sta a 5 ALZ -1.43
lun 24 -15.34
lun 28 -51.14
lun 23 -15.34
asthmatic lun -4.74
asthmatic lun 11.51
asthmatic lun 7.25
asthmatic lun 6.60
endo VEGF 0.00
endo bFGF 0.00
heart T-1 -30.52
heart T-14 -4.14
heart T-3399 -30.52
BM stun 3.06
osteo undif 0.00
Cartila a ( ool) -11.23
PBL HIV IIIB -8.36
MRCS HSV strain F 2.60
Gene Name sbg419582PROTOCADHERIN
Brain specific expression. No correlation with Alzheimer's disease. Low
expression in RA and OA
synovium but no corroborating expression in immune cells. Slightly upregulated
in heart disease.
Overexpressed in lung (1l4) and breast (1/4) tumors.
Sample Mean Mean Average18S 50 copies
sbg419582PROTOCAGOI GOI GOI rRNA ng/18Sof
DHERIN copies copies Copies (ng) rRNA mRNA
(sample(sample (ng) detected/
1) 2) 50
ng
total
RNA
Subcutaneous 18.18 23.43 20.81 3.06 16.34 339.95
Adi oc tes
Zenbio
Subcutaneous 0.11 0.33 0.22 0.96 52.36 11.52
Adipose
Zenbio
Adrenal Gland 1.8 1.06 1.43 0.61 81.97 117.21
Clontech
Whole Brain 10913.9210314.4210614.177.24 6.91 73302.28
Clontech
Fetal Brain 0.31 4.68 2.50 0.48 103.95259.36
Clontech
Cerebellum 0.1 4.58 2.34 2.17 23.04 53.92
Clontech
Cervix 0.22 1.22 0.72 2.42 20.66 14.88
Colon 0.31 13.73 7.02 2.71 18.45 129.52
Endometrium 0.1 0.58 0.34 0.73 68.21 23.19
Esophagus 2.21 1.96 2.09 1.37 36.50 76.09
Heart Clontech0.32 0 0.16 1.32 37.88 6.06
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Hypothalamus 0.15 1.2 0.68 0.32 155.28104.81
Ileum 2.77 1.03 1.90 2.58 19.38 36.82
Jejunum 0.26 1.18 0.72 6.60 7.58 5.45
Kidney 1.99 0.28 1.14 2.12 23.58 26.77
Liver 7.59 12.42 10.01 1.50 33.33 333.50
Fetal Liver 18.75 11.04 14.90 10.40 4.81 71.61
Clontech
Lung 7.19 0.71 3.95 2.57 19.46 76.85
Mammary Gland 88.14 97.88 93.01 13.00 3.85 357.73
Clontech
Myometrium 0.51 4.8 2.66 2.34 21.37 56.73
Omentum 7.52 2.19 4.86 3.94 12.69 61.61
Ovary 13.46 4.84 9.15 4.34 11.52 105.41
Pancreas 0.49 1.02 0.76 0.81 61.80 46.66
Head of Pancreas0.29 0.15 0.22 1.57 31.85 7.01
Parotid Gland 6.09 6.19 6.14 5.48 9.12 56.02
Placenta Clontech10.67 2.35 6.51 5.26 9.51 61.88
Prostate 2.02 3.59 2.81 3.00 16.67 46.75
Rectum 0.54 7.25 3.90 1.23 40.65 158.33
Salivary Gland20.51 13.73 17.12 7.31 6.84 117.10
Clontech
Skeletal Muscle1.06 0.79 0.93 1.26 39.68 36.71
Clontech
Skin 13.09 0.6 6.85 1.21 41.32 282.85
Small Intestine0.11 2.47 1.29 0.98 51.07 65.88
Clontech
Spleen 1.05 11 6.03 4.92 10.16 61.23
Stomach 0.95 1.3 1.13 2.73 18.32 20.60
Testis Clontech2.82 3.19 3.01 0.57 87.87 264.06
Thymus Clontech117.82 118.81 118.32 9.89 5.06 598.15
Thyroid 2.34 2.29 2.32 2.77 18.05 41.79
Trachea Clontech8.72 9.37 9.05 9.71 5.15 46.58
Urinary Bladder14.23 16.82 15.53 5.47 9.14 141.91
Uterus 1.49 27.26 14.38 5.34 9.36 134.60
Sample Reg Mean copies Sample Fold Change
sbg419582PROTOCAnumber GOI of in
DHERIN (GSK copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 464.48928.96 colon
GW98-167 normal
colon tumor 21940 84.22 168.44 colon -5.515079554
GW98-166 tumor
colon normal 22080 32.8 65.60 colon
GW98-178 normal
colon tumor 22060 44.71 89.42 colon 1.363109756
GW98-177 tumor
colon normal 23514 135.5 271.00 colon
GW98-561 normal
colon tumor 23513 78.51 157.02 colon -1.72589479
GW98-560 tumor
colon normal 24691 454.16908.32 colon
GW98-894 ~ normal
colon tumor 24690 51.37 102.74 colon -8.840957757
GW98-893 tumor
lung normal 20742 60.35 120.70 lung
GW98-3 normal
lung tumor GW98-220741 101.98203.96 lung 1.689809445
I tumor
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lung normal 20677 264 528.00 lung
GW97-179 normal
lung tumor GW97-17820676 78.49 156.98 lung -3.363485794
tumor
lung normal 21922 88.19 176.38 lung
GW98-165 normal
lung tumor GW98-16421921 7554.5815109.16lung 85.66254677
tumor
lung normal 22584 344.2 688.40 lung
GW98-282 normal
lung tumor GW98-28122583 45.51 91.02 lung -7.563172929
tumor
breast normal 28750 132.43132.43 breast
GW00-392 normal
breast tumor 28746 98.14 196.28 breast 1.482141509
GW00-391 tumor
breast normal 28798 154.37154.37 breast
GW00-413 normal
breast tumor 28797 1289.092578.18 breast 16.70130207
GW00-412 tumor
breast normal 27592-9518.63 18.63 breast
GW00- normal
235:238
breast tumor 27588-91133.52133.52 breast 7.166935051
GW00- tumor
231:234
breast normal 23656 1334.912669.82 breast
GW98-621 normal
breast tumor 23655 212.39424.78 breast -6.285182918
GW98-620 tumor
brain normal 25507 6816.4713632.94brain
BB99-542 normal
brain normal 25509 1984.483968.96 brain
BB99-406 normal
brain normal 25546 2805.825611.64 brain
BB99-904 normal
brain stage 25502 467.59935.18 brain -8.274178946
ALZ BB99- stage
874 5
ALZ
brain stage 25503 3104.226208.44 brain -1.24634315
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 1889.813779.62 brain -2.047255191
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 2902.295804.58 brain -1.333058837
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 103.32206.64 CT lung
lung 26 KC normal 1.13 1.13 lung
26
lung 27 KC normal 1.51 1.51 lung
27
lung 24 KC COPD 1.47 1.47 lung -35.82312925
24
lung 28 KC COPD 0 0.00 lung -52.66
28
lung 23 KC COPD 1.91 1.91 lung -27.57068063
23
lung 25 KC COPD 1.36 1.36 lung
25
asthmatic lung 29321 2.68 2.68 asthmatic-19.64925373
OD03112 lun
asthmatic lung 29323 3.25 6.50 asthmatic-8.101538462
OD03433 lun
asthmatic lung 29322 26.23 52.46 asthmatic-1.003812429
OD03397 lung
asthmatic lung 29325 7.15 14.30 asthmatic-3.682517483
OD04928 lun
endo cells KC control15.9 15.90 endo
cells
endo VEGF KC 8.26 8.26 endo -1.924939467
VEGF
endo bFGF KC 2.01 2.01 endo -7.910447761
bFGF
heart Clontech normal 7.9 15.80 heart
heart ( T-1 29417 67.47 134.94 heart 8.540506329
) ischemic T-1
heart (T-14) 29422 106.83213.66 heart 13.52278481
non- T-14
obstructive
DCM
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heart (T-3399) 29426 425.28 850.56 heart 53.83291139
DCM T-3399
adenoid GW99-26926162 15.98 31.96 adenoid
tonsil GW98-28022582 17.95 35.90 tonsil
T cells PC0031428453 3.I8 6.36 T cells
PBMNC KC 0 0.00 PBMNC
monocyte KC 0.81 I.62 monocyte
B cells PC0066528455 2.74 5.48 B cells
dendritic cells 0 0.00 dendritic
28441 cells
neutrophils 28440 0 0.00 neutrophils
eosinophils 28446 0 0.00 eosinophils
BM unstim KC 0 0.00 BM unstim
BM stim KC 0 0.00 BM stun 0
osteo dif KC 2.34 2.34 osteo
dif
osteo undif 0 0.00 osteo -2.34
KC undif
chondrocytes 145.14 362.85 chondrocyte
s
OA Synovium 29462 320.78 320.78 OA
IP12/O1 S novium
OA Synovium 29461 396.85 793.70 OA
NPI0101 S novium
OA Synovium 28464 329.87 659.74 OA
NP57/00 S novium
RA Synovium 28466 103.85 207.70 RA
NP03/Ol S novium
RA Synovium 28467 617.72 1235.44 RA
NP71/00 S novium
RA Synovium 28475 63.13 126.26 RA
NP45/00 S novium
OA bone(biobank)29217 3.19 3.19 OA bone
(biobank)
OA bone Sample J. 126.87 253.74 OA bone
1 Emory
OA bone Sample J. 44.76 89.52 OA bone
2 Emory
Cartilage (pool)Normal502.66 1005.32 Cartilage
( ool)
Cartilage (pool)OA 206.76 413.52 Cartilage-2.431127878
( ool)
PBL unifected 28441 0 0.00 PBL
unifected
PBL HIV IIIB 28442 0 0.00 PBL HIV 0
IIIB
MRCS uninfected29158 0 0.00 MRCS
( I00%) uninfected
(100%)
MRC5 HSV strain29178 17.73 35.46 MRCS 35.46
F HSV
strain
F
W12 cells 29179 0.62 1.24 W12 cells
Keratinocytes 29180 22.63 45.26 Keratinocyte-
s
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Gene Name sbg419582PROTOCADHER1N
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor -5.52
colon tumor 1.36
colon tumor -1.73
colon tumor -8.84
lun tumor 1.69
lun tumor -3.36
lun tumor 85.66
lun tumor -7.56
breast tumor 1.48
breast tumor 16.70
breast tumor 7.17
breast tumor -6.29
brain sta a 5 ALZ -8.27
brain sta a 5 ALZ -1.25
brain sta a 5 ALZ -2.05
brain sta a 5 ALZ -1.33
lun 24 -35.82
lun 28 -52.66
lun 23 -27.57
asthmatic lun -19.65
asthmatic lun -8.10
asthmatic lun -1.00
asthmatic lun -3.68
endo VEGF -1.92
endo bFGF -7.91
heart T-1 8.54
heart T-14 13.52
heart T-3399 53.83
BM stun 0.00
osteo undif -2.34
Cartila a ( ool) -2.43
PBL HIV IIIB 0.00
MRCS HSV strain F 35.46
Gene Name sbg453915TECTORINa
Very low expression overall. Expression in female reproductive tissues
suggests a
protein that may be secreted by these tissue types.
Sample Mean Mean Average18S 50 ng/18Scopies
GOI GOI of
sbg453915TECTORINcopies copies GOI rRNA rRNA mRNA
a (sample(sample Copies (ng) (ng) detected/
1) 2)
50
ng
total
RNA
Subcutaneous 2.70 5.41 4.06 3.06 16.34 66.26
Adi ocytes
Zenbio
Subcutaneous 0.00 0.00 0.00 0.96 52.36 0.00
Adipose
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Zenbio
Adrenal Gland 3.75 5.67 4.71 0.61 81.97 386.07
Clontech
Whole Brain 22.57 27.88 25.23 7.24 6.91 174.21
Clontech .
Fetal Brain 2.42 1.80 2.11 0.48 103.95 219.33
Clontech
Cerebellum 0.00 1.93 0.97 2.17 23.04 22.24
Clontech
Cervix 2.90 2.10 2.50 2.42 20.66 51.65
Colon 11.19 2.68 6.94 2.71 18.45 127.95
Endometrium 4.79 19.31 12.05 0.73 68.21 821.96
Esophagus 2.06 2.93 2.50 1.37 36.50 91.06
Heart Clontech5.42 7.31 6.37 1.32 37.88 241.10
Hypothalamus 0.00 3.70 1.85 0.32 155.28 287.27
Ileum 3.72 18.75 11.24 2.58 19.38 217.73
Jejunum 28.49 49.80 39.15 6.60 7.58 296.55
Kidney 2.12 4.37 3.25 2.12 23.58 76.53
Liver 15.74 39.80 27.77 1.50 33.33 925.67
Fetal Liver 27.96 26.14 27.05 10.404.81 130.05
Clontech
Lung 0.00 2.37 1.19 2.57 19.46 23.05
Mammary Gland 19.68 19.22 19.45 13.003.85 74.81
Clontech
Myometrium 3.40 1.71 2.56 2.34 21.37 54.59
Omentum 14.33 138.99 76.66 3.94 12.69 972.84
Ovary 46.55 37.80 42.18 4.34 11.52 485.89
Pancreas 4.26 2.19 3.23 0.81 61.80 199.32
Head of Pancreas1.93 1.52 1.73 1.57 31.85 54.94
Parotid Gland 4.04 5.93 4.99 5.48 9.12 45.48
Placenta Clontech3.69 15.48 9.59 5.26 9.51 91.11
Prostate 7.94 28.75 18.35 3.00 16.67 305.75
Rectum 11.09 3.41 7.25 1.23 40.65 294.72
Salivary Gland0.00 1.45 0.73 7.31 6.84 4.96
Clontech
Skeletal Muscle4.76 0.00 2.38 1.26 39.68 94.44
Clontech
Skin 0.00 1.39 0.70 1.21 41.32 28.72
Small Intestine2.20 1.41 1.81 0.98 51.07 92.19
Clontech
Spleen 7.15 8.12 7.64 4.92 10.16 77.59
Stomach 1.98 0.00 0.99 2.73 18.32 18.13
Testis Clontech6.83 2.61 4.72 0.57 87.87 414.76
Thymus Clontech0.00 0.00 0.00 9.89 5.06 0.00
Thyroid 2.38 1.88 2.13 2.77 18.05 38.45
Trachea Clontech1.71 9.25 5.48 9.71 5.15 28.22
Urinary Bladder3.72 8.22 5.97 5.47 9.14 54.57
Uterus 74.31 73.54 73.93 5.34 9.36 692.18
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Sample Reg Mean copies Sample Fold Change
sbg453915TECTORINanumber GOI of in
(GSI~ copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 131.15262.30 colon
GW98-167 normal
colon tumor 21940 85.76 171.52 colon -1.529267724
GW98-166 tumor
colon normal 22080 1.82 3.64 colon
GW98-178 normal
colon tumor 22060 10.14 20.28 colon 5.571428571
GW98-177 tumor
colon normal 23514 14.25 28.50 colon
GW98-561 normal
colon tumor 23513 9.89 19.78 colon -1.440849343
GW98-560 tumor
colon normal 24691 32.05 64.10 colon
GW98-894 normal
colon tumor 24690 53.06 106.12 colon 1.655538222
GW98-893 tumor
lung normal 20742 6.9 13.80 lung
GW98-3 normal
lung tumor GW98-220741 0.81 1.62 lung -8.518518519
tumor
lung normal 20677 1.19 2.38 lung
GW97-179 normal
lung tumor GW97-17820676 0 0.00 lung -2.38
tumor
lung normal 21922 0.91 1.82 lung
GW98-165 normal
lung tumor GW98-16421921 5.99 11.98 lung 6.582417582
tumor
lung normal 22584 5.93 11.86 lung
GW98-282 normal
lung tumor GW98-28122583 1.54 3.08 lung -3.850649351
tumor
breast normal 28750 6.88 6.88 breast
GW00-392 normal
breast tumor 28746 4.24 8.48 breast 1.23255814
GW00-391 tumor
breast normal 28798 0 0.00 breast
GW00-413 normal
breast tumor 28797 13.96 27.92 breast 27.92
GW00-412 tumor
breast normal 27592-9514.42 14.42 breast
GW00- normal
235:238
breast tumor 27588-910 0.00 breast -14.42
GW00- tumor
231:234
breast normal 23656 5.81 11.62 breast
GW98-621 normal
breast tumor 23655 0 0.00 breast -11.62
GW98-620 tumor
brain normal 25507 20.59 41.18 brain
BB99-542 normal
brain normal 25509 15.98 31.96 brain
BB99-406 normal
brain normal 25546 2.38 4.76 brain
BB99-904 normal
brain stage 25502 25.45 50.90 brain 1.960205392
ALZ BB99- stage
874 5
ALZ
brain stage 25503 35.78 71.56 brain 2.755840822
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 13.83 27.66 brain 1.06521181
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 21.67 43.34 brain 1.669062901
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 6.52 13.04 CT lung
lung 26 KC normal 2.1 2.10 lung
26
lung 27 KC normal 0.84 0.84 lung
27
lung 24 KC COPD 1.25 1.25 lung -3.432
24
lung 28 KC COPD 0 0.00 lung -4.29
28
Flung 23 KC COPD 1.16 1.16 lung -3.698275862
23
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lung 25 KC COPD 1.18 1.18 lung
25
asthmatic lung 29321 4.9 4.90 asthmatic1.142191142
OD03112 lun
asthmatic lung 29323 0.83 1.66 asthmatic-2.584337349
OD03433 lung
asthmatic lung 29322 2.46 4.92 asthmatic1.146853147
OD03397 lun
asthmatic lung 29325 6 12.00 asthmatic2.797202797
OD04928 lun
endo cells KC control2.52 2.52 endo
cells
endo VEGF KC 1.28 1.28 endo -1.96875
VEGF
endo bFGF KC 0 0.00 endo -2.52
bFGF
heart Clontech normal 0 0.00 heart
heart ( T-1 29417 3.58 7.16 heart 7.16
) ischemic T-1
heart (T-14) 29422 0 0.00 heart 0
non- T-14
obstructive
DCM
heart (T-3399)DCM29426 0 0.00 heart 0
T-3399
adenoid GW99-26926162 2.29 4.58 adenoid
tonsil GW98-28022582 1.85 3.70 tonsil
T cells PC0031428453 4.29 8.58 T cells
PBMNC KC 0 0.00 PBMNC
monocyte KC 3.39 6.78 monocyte
B cells PC0066528455 6.04 12.08 B cells
dendritic cells 0.83 1.66 dendritic
28441 cells
neutrophils 28440 34.69 34.69 neutrophils
eosinophils 28446 2.86 5.72 eosinophils
BM unstim KC 0 0.00 BM unstim
BM stim KC 12.8 12.80 BM stun 12.8
osteo dif KC 0 0.00 osteo
dif
osteo undif 0 0.00 osteo 0
KC undif
chondrocytes 4.78 11.95 chondrocyte
s
OA Synovium 29462 18.31 18.31 OA
IP12/O1 Synovium
OA Synovium 29461 0 0.00 OA
NP10/O1 S novium
OA Synovium 28464 11.46 22.92 OA
NP57/00 S novium
RA Synovium 28466 0.87 1.74 RA
NP03/Ol S novium
RA Synovium 28467 26.95 53.90 RA
NP71/00 S novium
RA Synovium 28475 18.91 37.82 RA
NP45/00 S novium
OA bone (biobank)29217 0 0.00 OA bone
(biobank)
OA bone Sample J. Emory8.66 17.32 OA bone
1
OA bone Sample J. Emory7.8 15.60 OA bone
2
Cartilage (pool)Normal 16.93 33.86 Cartilage
( ool)
Cartilage (pool)OA 6.39 12.78 Cartilage-2.649452269
( ool)
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PBL unifected 28441 0 0.00 PBL
unifected
PBL HIV IIIB 28442 1.15 2.30 PBL HIV 2.3
IIIB
MRCS uninfected 29158 0 0.00 MRCS
(100%)
uninfected
(100%)
MRCS HSV strain 29178 70.84 141.68 MRCS 141.68
F HSV
strain
F
W 12 cells 29179 5.59 11.18 W 12
cells
Keratinocytes 29180 0 0.00 Keratinocyte
s
Gene Name sbg453915TECTORINa
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor -1.53
colon tumor 5.57
colon tumor -1.44
colon tumor 1.66
lun tumor -8.52
lun tumor -2.38
lun tumor 6.58
lun tumor -3.85
breast tumor 1.23
breast tumor 27.92
breast tumor -14.42
breast tumor -11.62
brain sta a 5 ALZ 1.96
brain sta a 5 ALZ 2.76
__
brain sta a 5 ALZ 1.07
brain sta a 5 ALZ . 1.67
lun 24 -3.43
lun 28 -4.29
lun 23 -3.70
asthmatic lun 1.14
asthmatic lun -2.58
asthmatic lun 1.15
asthmatic lun 2.80
endo VEGF -1.97
endo bFGF -2.52
heart T-1 7.16
heart T-14 0.00
heart T-3399 0.00
BM stim 12.80
osteo undif 0.00
Cartila a ( ool) -2.65
PBL HIV IIIB 2.30
MRCS HSV strain F 141.68
Gene Name SBh385630.antiinflam
Some expression in adenoid, tonsils and T-cells suggesting a role in the
immune
system. Expression in GI tissues suggests a role in the digestive system and
potential role in
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diseases of the GI system such as IBD. Overexpression in lung (1/4) and colon
tumors (1/4)
suggesting a role in lung and colon cancer. Increased expression in ischemic
and dilated
heart samples indicating a role in Cardiovascular diseases that are consistent
With cardiac
hypertrophy. Expression in whole brain but not localized to hypothalamus,
cerebellum or
cortex.
Sample Mean Mean Average18S 50 ng/18Scopies
SBh385630.antiinflamGOI GOI GOI rRNA rRNA of
copies copies Copies(ng) (ng) mRNA
(sample(sample detected/
1) 2) 50
ng
total
RNA
Subcutaneous 0.00 6.41 3.21 3.06 16.34 52.37
Adi oc tes Zenbio
Subcutaneous 0.00 0.00 0.00 0.96 52.36 0.00
Adipose
Zenbio
Adrenal Gland 8.40 0.00 4.20 0.61 81.97 344.26
Clontech
Whole Brain 817.17 466.76 641.977.24 6.91 4433.46
Clontech
Fetal Brain 3.80 0.00 1.90 0.48 103.95 197.51
Clontech
Cerebellum Clontech6.66 0.00 3.33 2.17 23.04 76.73
Cervix 11.99 12.30 12.15 2.42 20.66 250.93
Colon 55.51 211.32 133.422.71 18.45 2461.53
Endometrium 0.00 0.00 0.00 0.73 68.21 0.00
Esophagus 11.75 30.29 21.02 1.37 36.50 767.15
Heart Clontech 0.00 0.00 0.00 1.32 37.88 0.00
Hypothalamus 0.00 0.00 0.00 0.32 155.28 0.00
Ileum 40.37 42.85 41.61 2.58 19.38 806.40
Jejunum 200.19 263.82 232.016.60 7.58 1757.61
Kidney 18.38 34.53 26.46 2.12 23.58 623.94
Liver 11.00 17.20 14.10 1.50 33.33 470.00
Fetal Liver 150.74 123.93 137.3410.404.81 660.26
Clontech
Lung 82.73 77.24 79.99 2.57 19.46 1556.13
Mammary Gland 161.37 155.19 158.2813.003.85 608.77
Clontech
Myometrium 5.79 9.38 7.59 2.34 21.37 162.07
Omentum 36.14 46.80 41.47 3.94 12.69 526.27
Ovary 59.25 44.29 51.77 4.34 11.52 596.43
Pancreas 6.29 6.70 6.50 0.81 61.80 401.42
Head of Pancreas0.00 26.25 13.13 1.57 31.85 417.99
Parotid Gland 8.77 52.96 30.87 5.48 9.12 281.61
Placenta Clontech4.11 0.00 2.06 5.26 9.51 19.53
Prostate 100.91 49.99 75.45 3.00 16.67 1257.50
Rectum 180.24 305.61 242.931.23 40.65 9875.00
Salivary Gland 49.36 70.01 59.69 7.31 6.84 408.24
Clontech
Skeletal Muscle0.00 0.00 0.00 1.26 39.68 0.00
Clontech
Skin 18.00 3.22 10.61 1.21 41.32 438.43
Small Intestine3.90 2.55 3.23 0.98 51.07 164.71
Clontech
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Spleen 9.67 5.60 7.64 4.92 10.16 77.59
Stomach 32.34 83.60 57.97 2.73 18.32 1061.72
Testis Clontech3.53 0.00 1.77 0.57 87.87 155.10
Thymus Clontech73.66 60.02 66.84 9.89 5.06 337.92
Thyroid 15.87 12.31 14.09 2.77 18.05 254.33
Trachea Clontech98.68 187.11 142.909.71 5.15 735.81
Urinary Bladder118.92 101.91 110.425.47 9.14 1009.28
Uterus 1 9.03 24.21 16.62 5.34 9.36 155.62
1 I 1
Sample Reg Mean copies Sample Fold Change
SBh385630.antiinflamnumber GOI of in
(GSK copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 6479.7712959.54colon
GW98-167 normal
colon tumor 21940 7824.0215648.04colon 1.207453351
GW98-166 tumor
colon normal 22080 343.81687.62 colon
GW98-178 normal
colon tumor 22060 3011.936023.86 colon 8.760449085
GW98-177 tumor
colon normal 23514 5457.3810914.76colon
GW98-561 normal
colon tumor 23513 4017.148034.28 colon -1.358523726
GW98-560 tumor
colon normal 24691 14903.6829807.36colon
GW98-894 normal
colon tumor 24690 4814.199628.38 colon -3.095781429
GW98-893 tumor
lung normal 20742 3731.847463.68 lung
GW98-3 normal
lung tumor GW98-220741 719.6 1439.20 lung -5.185992218
tumor
lung normal 20677 1090.562181.12 lung
GW97-179 normal
lung tumor GW97-17820676 6187.2212374.44lung 5.673433832
tumor
lung normal 21922 8416.8216833.64lung
GW98-165 normal
lung tumor GW98-16421921 4405.148810.28 lung -1.910681613
tumor
lung normal 22584 2033.264066.52 lung
GW98-282 normal
lung tumor GW98-28122583 1785.693571.38 lung -1.138641086
tumor
breast normal 28750 1583.491583.49 breast
GW00-392 normal
breast tumor 28746 1334.892669.78 breast 1.686010016
GW00-391 tumor
breast normal 28798 1225.921225.92 breast
GW00-413 normal
breast tumor 28797 1213.712427.42 breast 1.980080266
GW00-412 tumor
breast normal 27592-95862.26862.26 breast
GW00- normal
235:238
breast tumor 27588-911766.081766.08 breast 2.048198919
GW00- tumor
231:234
breast normal 23656 1420.572841.14 breast
GW98-621 normal
breast tumor 23655 760.051520.10 breast -1.869048089
GW98-620 tumor
brain normal 25507 679.481358.96 brain
BB99-542 normal
brain normal 25509 423.69847.38 brain
BB99-406 normal
brain normal 25546 401.34802.68 brain
BB99-904 normal
brain stage 25502 264.51529.02 brain -1.895971167
ALZ BB99- stage
874 5
ALZ
brain stage 25503 648.881297.76 brain 1.293869765
5 ALZ BB99- stage
887 5
ALZ
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brain stage 25504 234.97469.94 brain -2.134329205
ALZ BB99- stage
862 5
ALZ
brain stage 25542 404.55809.10 brain -1.239657232
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 6620.8513241.70CT lung
lung 26 KC normal 320.43320.43 lung
26
lung 27 KC normal 164.59164.59 lung
27
lung 24 KC COPD 141.57141.57 lung -25.25392032
24
lung 28 KC COPD 323.8 323.80 lung -11.04137585
28
lung 23 KC COPD 363.35363.35 lung -9.839541764
23
lung 25 KC COPD 574.07574.07 lung
25
asthmatic lung 29321 6073.996073.99 asthmatic1.698924325
OD03112 lun
asthmatic lung 29323 4568.419136.82 asthmatic2.555612662
OD03433 lung
asthmatic lung 29322 17389.1134778.22asthmatic9.727636026
OD03397 lun
asthmatic lung 29325 4719.279438.54 asthmatic2.640005203
OD04928 lun
endo cells KC control0 0.00 endo
cells
endo VEGF KC 0 0.00 endo 0
VEGF
endo bFGF KC 0 0.00 endo 0
bFGF
heart Clontech normal 10.63 21.26 heart
heart ( T-1 29417 599.011198.02 heart 56.3508937
) ischemic T-1
heart (T-14) 29422 666.411332.82 heart 62.69143932
non- T-14
obstructive
DCM
heart (T-3399) 29426 142.85285.70 heart 13.43838194
DCM T-3399
adenoid GW99-26926162 1138 2276.00 adenoid
tonsil GW98-28022582 561.571123.14 tonsil
T cells PC0031428453 736.271472.54 T cells
PBMNC KC 0 0.00 PBMNC
monocyte KC 30.38 60.76 monocyte
B cells PC0066528455 204.15408.30 B cells
dendritic cells 57.66 115.32 dendritic
28441 cells
neutrophils 28440 13.3 13.30 neutrophils
eosinophils 28446 5.71 11.42 eosinophils
BM unstim KC 0 0.00 BM unstim
BM stim KC 50.38 50.38 BM stun 50.38
osteo dif KC 8.62 8.62 osteo
dif
osteo undif 0 0.00 osteo -..8.62
KC undif
chondrocytes 14.98 37.45 chondrocyte
s
OA Synovium 29462 134.63134.63 OA
IP12/O1 S novium
OA Synovium 29461 73.89 147.78 OA
NP10/O1 S novium
OA Synovium 28464 106.98213.96 OA
NP57/00 S novium
RA Synovium 28466 26.59 53.18 RA
NP03/Ol S novium
Synovium NP71/0028467 60.88 121.76 RA
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Synovium
RA Synovium 28475 60.81 121.62 RA
NP45100
S novium
OA bone (biobank)29217 98.18 98.18 OA bone
(biobank)
OA bone Sample J. Emory78.3 156.60 OA bone
1
OA bone Sample J. Emory107.7 215.40 OA bone
2
Cartilage (pool)Normal 72.21 144.42 Cartilage
( ool)
Cartilage (pool)OA 48.61 97.22 Cartilage-1.485496811
( ool)
PBL unifected 28441 30.22 60.44 PBL
unifected
PBL HIV IIIB 28442 21.89 43.78 PBL HIV -1.380539059
IIIB
MRCS uninfected29158 10.74 21.48 MRCS
(100%) uninfected
(100%)
MRC5 HSV strain29178 171.23342.46 MRCS 15.94320298
F HSV
strain
F
W12 cells 29179 1143.852287.70 W12 cells
Keratinocytes 29180 388.06776.12 Keratinocyte
s
Gene Name SBh385630.antiinflam
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 1.21
colon tumor 8.76
colon tumor -1.36
colon tumor -3.10
lun tumor -5.19
lun tumor 5.67
lun tumor -1.91
lun tumor -1.14
breast tumor 1.69
breast tumor 1.98
breast tumor 2.05
breast tumor -1.87
brain sta a 5 ALZ -1.90
brain sta a 5 ALZ 1.29
brain stage 5 ALZ -2.13
brain sta a 5 ALZ -1.24
lun 24 -25.25
lun 28 -11.04
lun 23 -9.84
asthmatic lun 1.70
asthmatic lun 2.56
asthmatic lun 9.73
asthmatic lun 2.64
endo VEGF 0.00
endo bFGF 0.00
heart T-1 56.35
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heart T-14 62.69
heart T-3399 _ 13.44
~
BM stun 50.38
osteo undif -8.62
Cartila a ( ool) -1.49
PBL HIV IIIB -1.38
MRCS HSV strain F 15.94
Gene Name sbg471005nAChR
Expressed in immune cells with corroborating expression in OA and RA synovium
suggesting a role in this disease.
High expression in whole brain but not present in cortex, cerebellum, or
hypothalamus suggesting
localized brain expression.
Sample Mean Mean Average185 50 ng/18Scopies
sbg471005nAChRGOI GOI GOI rRNA rRNA of
copies copies Copies (ng) (ng) mRNA
(sample (sample detecte
1) 2) d/50
ng
total
RNA
Subcutaneous 32.42 2.90 17.66 3.06 16.34 288.56
Adi oc tes
Zenbio
Subcutaneous 0.00 0.00 0.00 0.96 52.36 0.00
Adipose
Zenbio
Adrenal Gland 0.00 0.00 0.00 0.61 81.97 0.00
Clontech
Whole Brain 1606.00 1058.071332.047.24 6.91 9199.14
Clontech
Fetal Brain 0.00 6.34 3.17 0.48 103.95 329.52
Clontech
Cerebellum 10.65 0.00 5.33 2.17 23.04 122.70
Clontech
Cervix 0.00 0.00 0.00 2.42 20.66 0.00
Colon 0.00 0.00 0.00 2.71 18.45 0.00
Endometrium 0.00 0.00 0.00 0.73 68.21 0.00
Esophagus 0.00 2.52 1.26 1.37 36.50 45.99
Heart Clontech4.05 0.00 2.03 1.32 37.88 76.70
Hypothalamus 2.24 0.00 1.12 0.32 155.28 173.91
Ileum 0.00 0.00 0.00 2.58 19.38 0.00
Jejunum 20.32 41.44 30.88 6.60 7.58 233.94
Kidney 14.56 0.00 7.28 2.12 23.58 171.70
Liver 3.55 10.72 7.14 1.50 33.33 237.83
Fetal Liver 127.95 116.81 122.38 10.404.81 588.37
Clontech
Lung 12.79 0.00 6.40 2.57 19.46 124.42
Mammary Gland 30.53 24.12 27.33 13.003.85 105.10
Clontech
Myometrium 0.00 7.10 3.55 2.34 21.37 75.85
Omentum 8.15 0.00 4.08 3.94 12.69 51.71
Ovary 18.27 7.02 12.65 4.34 11.52 145.68
Pancreas 0.00 0.00 0.00 0.81 61.80 0.00
Head of Pancreas0.00 0.00 0.00 1.57 31.85 0.00
Parotid Gland 0.00 0.00 0.00 5.48 9.12 0.00
Placenta Clontech9.17 0.00 4.59 5.26 9.51 43.58
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Prostate 0.00 1.35 0.68 3.00 16.67 11.25
Rectum 0.00 0.00 0.00 1.23 40.65 0.00
Salivary Gland0.00 11.84 5.92 7.31 6.84 40.49
Clontech
Skeletal Muscle6.09 7.36 6.73 1.26 39.68 266.87
Clontech
Skin 0.00 0.00 0.00 1.21 41.32 0.00
Small Intestine0.00 0.00 0.00 0.98 51.07 0.00
Clontech
Spleen 5.20 7.36 6.28 4.92 10.16 63.82
Stomach 12.85 6.38 9.62 2.73 18.32 176.10
Testis Clontech0.00 2.25 1.13 0.57 87.87 98.86
Thymus Clontech177.85 168.23 173.04 9.89 5.06 874.82
Thyroid 6.44 0.00 3.22 2.77 18.05 58.12
Trachea Clontech5.07 0.00 2.54 9.71 5.15 13.05
Urinary Bladder0.00 0.00 0.00 5.47 9.14 0.00
Uterus 29.20 10.39 19.80 5.34 9.36 185.35
Sample Reg Mean copies Sample Fold
sbg471005nAChR number GOI of Change
(GSK copiesmRNA in Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 1530.093060.18 colon
GW98-167 normal
colon tumox 21940 617.151234.30 colon -2.479283805
GW98-166 tumor
colon normal 22080 406.03812.06 colon
GW98-178 normal
colon tumor 22060 1231.532463.06 colon 3.033101002
GW98-177 tumor
colon normal 23514 844.371688.74 colon
GW98-561 normal
colon tumor 23513 633.991267.98 colon -1.331834887
GW98-560 tumor
colon normal 24691 1130.512261.02 colon
GW98-894 normal
colon tumor 24690 721.291442.58 colon -1.567344619
GW98-893 tumor
lung normal 20742 2433.654867.30 lung normal
GW98-3
lung tumor GW98-220741 334.04668.08 lung tumor-7.28550473_
lung normal 20677 823.511647.02 lung normal
GW97-179
lung tumor GW97-17820676 1492 2984.00 lung tumor1.811756991
lung normal 21922 829.651659.30 lung normal
GW98-165
lung tumor GW98-16421921 595.311190.62 lung tumor-1.393643648
lung normal 22584 357.69715.38 lung normal
GW98-282
lung tumor GW98-28122583 256.76513.52 lung tumor-1.393090824
breast normal 28750 357.44357.44 breast
GW00-392 normal
breast tumor 28746 280.98561.96 breast 1.572179946
GW00-391 tumor
breast normal 28798 286.18286.18 breast
GW00-413 normal
breast tumor 28797 195.5 391.00 breast 1.366272975
GW00-412 tumor
breast normal 27592-95161.68161.68 breast
GW00- normal
235:238
breast tumor 27588-91217.83217.83 breast 1.347290945
GW00- tumor
231:234
breast normal 23656 531.531063.06 breast
GW98-621 normal
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breast tumor 23655 556.171112.34 breast 1.046356744
GW98-620 tumor
brain normal 25507 143.72287.44 brain
BB99-542 normal
brain normal 25509 569.171138.34 brain
BB99-406 normal
brain normal 25546 106.85213.70 brain
BB99-904 normal
brain stage 25502 286.37572.74 brain 1.048027423
ALZ BB99- stage
874 5
ALZ
brain stage 25503 746.741493.48 brain 2.732842121
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 382.97765.94 brain 1.401554151
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 367.49734.98 brain 1.344902042
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 175.41350.82 CT lung
lung 26 KC normal 20.66 20.66 lung
26
lung 27 KC normal 13.06 13.06 lung
27
lung 24 KC COPD 15.89 15.89 lung -6.182662052
24
lung 28 KC COPD 7.34 7.34 lung -13.38453678
28
lung 23 KC COPD 22.3 22.30 lung -4.405493274
23
lung 25 KC COPD 8.43 8.43 lung
25
asthmatic lung 29321 264.47264.47 asthmatic2.692012113
OD03112 lun
asthmatic lung 29323 442.3 884.60 asthmatic9.004249688
OD03433 lun
asthmatic lung 29322 670.041340.08 asthmatic13.64053236
OD03397 lun
asthmatic lung 29325 414.13828.26 asthmatic8.430770797
OD04928 lung
endo cells KC control66.94 66.94 endo
cells
endo VEGF KC 18.49 18.49 endo -3.620335316
VEGF
endo bFGF KC 15.93 15.93 endo -4.202134338
bFGF
heart Clontech normal 180.76361.52 heart
heart ( T-1 29417 161.9 323.80 heart -1.116491662
) ischemic T-1
heart (T-14) 29422 141.03282.06 heart -1.281713111
non- T-14
obstructive
DCM
heart (T-3399) 29426 321.32642.64 heart 1.777605665
DCM T-3399
adenoid GW99-26926162 193.61387.22 adenoid
tonsil GW98-28022582 625.4 1250.80 tonsil
T cells PC0031428453 140.44280.88 T cells
PBMNC KC 0 0.00 PBMNC
monocyte KC 0 0.00 monocyte
B cells PC0066528455 476.72953.44 B cells
dendritic cells 205.79411.58 dendritic
28441 cells
neutrophils 28440 1366.991366.99 neutrophils
eosinophils 28446 316.57633.14 eosinophils
BM unstim KC 29.41 29.41 BM unstim
BM stun KC 46.03 46.03 BM stun 1.565113907
osteo dif KC 17.47 17.47 osteo
dif
osteo undif 1.87 1.87 osteo -9.342245989
KC undif
chondrocytes 735.881839.70 chondrocyte
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OA Synovium 29462 686.8 686.80 OA
IP12/O1
Synovium
OA Synovium 29461 4887.169774.32 OA
NP10/O1
S novium
OA Synovium 28464 721.491442.98 OA
NP57/00
S novium
RA Synovium 28466 383.33766.66 RA
NP03/Ol
S novium
RA Synovium 28467 780.941561.88 RA
NP71/00
S novium
RA Synovium 28475 543.621087.24 RA
NP45/00
S novium
OA bone (biobank)29217 780.12780.12 OA bone
(biobank)
OA bone Sample J. Emory361.65723.30 OA bone
1
OA bone Sample J. Emory197.57395.14 OA bone
2
Cartilage (pool)Normal 220.7 441.40 Cartilage
( ool)
Cartilage (pool)OA 75.52 151.04 Cartilage-2.922404661
( ool)
PBL unifected 28441 1745.813491.62 PBL
unifected
PBL HIV IIIB 28442 832.4 1664.80 PBL HIV -2.097321
IIIB
MRCS uninfected29158 147.92295.84 MRCS
(100%) uninfected
(100%)
MRCS HSV strain29178 146 292.00 MRCS -1.013150685
F HSV
strain
F
W12 cells 29179 304.27608.54 W12 cells
Keratinocytes 29180 139.44278.88 Keratinocyte
s
Gene Name sbg471005nAChR
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor -2.48
colon tumor 3.03
colon tumor -1.33
colon tumor -1.57
lun tumor -7.29
lun tumor 1.81
lun tumor -1.39
lun tumor -1.39
breast tumor 1.57
breast tumor 1.37
breast tumor 1.35
breast tumor 1.05
brain sta a 5 ALZ 1.05
brain sta a 5 ALZ 2.73
brain sta a 5 ALZ 1.40
brain sta a 5 ALZ 1.34
lung 24 -6.18
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lun 28 -13.38
lun 23 -4.4
1
____ _
asthmatic lun _____
2.69
asthmatic lun 9.00
asthmatic lun 13.64
asthmatic lun 8.43
endo VEGF -3.62
endo bFGF -4.20
heart T-1 -1.12
heart T-14 -1.28
heart T-3399 1.78
BM stun 1.57
osteo undif -9.34
Cartila a ( ool) -2.92
PBL HIV IIIB -2.10
MRCS HSV strain F -1.01
Gene Name sbg442445PROa
Strong expression in B-cells with expression in other immune cell types
indicate function in immune
system.Corroborating expression in RA and OA samples indicate role in disease.
2X increase in
cells infected with HIV suggests possible marker in HIV infection. Expression
in whole brain but
not cortex or cerebellum suggests localized expression in brain.
Sample Mean Mean Average18S 50 ng/18Seopies
sbg442445PROa GOI GOI GOI rRNA rRNA of
copies copies Copies (ng) (ng) mRNA
(sample (sample deteete
1) 2) 4150
ng
total
RNA
Subcutaneous 1.13 3.82 2.48 3.06 16.34 40.44
Adi oc tes
Zenbio
Subcutaneous 0.63 0 0.32 0.96 52.36 16.49
Adipose
Zenbio
Adrenal Gland 0.64 0.74 0.69 0.61 81.97 56.56
Clontech
Whole Brain 368.87 396.51 382.69 7.24 6.91 2642.89
Clontech
Fetal Brain 1.57 2.5 2.04 0.48 103.95 211.54
Clontech
Cerebellum 1.63 0 0.82 2.17 23.04 18.78
Clontech
Cervix 4.57 5.6 5.09 2.42 20.66 105.06
Colon 18.13 7.38 12.76 2.71 18.45 235.33
Endometrium 4.23 0 2.12 0.73 68.21 144.27
Esophagus 6.85 12.66 9.76 1.37 36.50 356.02
Heart Clontech12.83 1.44 7.14 1.32 37.88 270.27
Hypothalamus 0.58 7.26 3.92 0.32 155.28 608.70
Ileum 22.89 6.34 14.62 2.58 19.38 283.24
Jejunum 6.67 36.71 21.69 6.60 7.58 164.32
Kidney 2.82 6.28 4.55 2.12 23.58 107.31
Liver 11.21 1.24 6.23 1.50 33.33 207.50
Fetal Liver 118 135.81 126.91 10.404.81 610.12
Clontech
Lung 13.95 37.87 25.91 2.57 19.46 504.09
Mammary Gland 15.77 11.19 13.48 13.003.85 51.85
Clontech
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Myometrium 16.26 49.21 32.74 2.34 21.37 699.47
Omentum 16.64 25.59 21.12 3.94 12.69 267.96
Ovary 4.98 7.48 6.23 4.34 11.52 71.77
Pancreas 1.23 0 0.62 0.81 61.80 38.01
Head of Pancreas3.57 0 1.79 1.57 31.85 56.85
Parotid Gland 0.59 0 0.30 5.48 9.12 2.69
Placenta Clontech2.67 2.75 2.71 5.26 9.51 25.76
Prostate 9.23 7.92 8.58 3.00 16.67 142.92
Rectum 2.62 4.28 3.45 1.23 40.65 140.24
Salivary Gland1.02 14.59 7.81 7.31 6.84 53.39
Clontech
Skeletal Muscle0 0.98 0.49 1.26 39.68 19.44
Clontech
Skin 2.72 0 1.36 1.21 41.32 56.20
Small Intestine0.99 1 1.00 0.98 51.07 50.82
Clontech
Spleen 31.29 42.16 36.73 4.92 10.16 373.22
Stomach 15.74 7.87 2.73 18.32 144.14
Testis Clontech4.63 2.77 3.70 0.57 87.87 325.13
Thymus Clontech503.91 615.6 559.76 9.89 5.06 2829.90
Thyroid 0.75 10.38 5.57 2.77 18.05 100.45
Trachea Clontech65.95 52.98 59.47 9.71 5.15 306.20
Urinary Bladder9.1 3.76 6.43 5.47 9.14 58.78
Uterus I 13.884.35 9.12 5.34 9.36 85.35
I I I - I
Sample Reg Mean copies Sample Fold Change
sbg442445PROa numberGOI of in Disease
(GSK copies mRNA Population
identifier) .
detected/SO
ng total
RNA
colon normal 21941 392.89 785.78 colon
GW98-167 normal
colon tumor 21940 466.75 933.50 colon 1.18799155
GW98-166 tumor
colon normal 22080 113.54 227.08 colon
GW98-178 normal
colon tumor 22060 43.88 87.76 colon -2.587511395
GW98-177 tumor
colon normal 23514 335.16 670.32 colon
GW98-561 normal
colon tumor 23513 173.85 347.70 colon -1.927868852
GW98-560 tumor
colon normal 24691 288.76 577.52 colon
GW98-894 normal
colon tumor 24690 164.44 328.88 colon -1.756020433
GW98-893 tumor
lung normal 20742 2119.164238.32lung normal
GW98-3
lung tumor GW98-220741 33.63 67.26 lung tumor-63.01397562
lung normal 20677 1213.422426.84lung normal
GW97-179
lung tumor GW97-17820676 2011.794023.58lung tumor1.657950256
lung normal 21922 2088.934177.86lung normal
GW98-165
lung tumor GW98-16421921 862.54 1725.08lung tumor-2.421835509
lung normal 22584 499.54 999.08 lung normal
GW98-282
lung tumor GW98-28122583 946.36 1892.72lung tumor1.894462906
breast normal 28750 208.96 208.96 breast
GW00-392 normal
breast tumor 28746 259.34 518.68 breast 2.48219755
GW00-391 tumor
breast normal 28798 65.02 65.02 breast
GW00-413 I normal
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breast tumor 28797 493.02 986.04 breast 15.16517994
GW00-412 tumor
breast normal 27592-9524.18 24.18 breast
GW00- normal
235:238
breast tumor 27588-91126.63 126.63 breast 5.236972705
GW00- tumor
231:234
breast normal 23656 536.09 1072.18breast
GW98-621 normal
breast tumor 23655 203.7 407.40 breast -2.631762396
GW98-620 tumor
brain normal 25507 88.47 176.94 brain
BB99-542 normal
brain normal 25509 147.87 295.74 brain
BB99-406 normal
brain normal 25546 35.13 70.26 brain
BB99-904 normal
brain stage 25502 75.02 150.04 brain -1.206211677
ALZ BB99- stage
874 5
ALZ
brain stage 25503 189 378.00 brain 2.088628578
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 131.38 262.76 brain 1.451873135
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 36.77 73.54 brain -2.46097362
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal1441.162882.32CT lung
lung 26 KC normal69.7 69.70 lung 26
lung 27 KC normal59.95 59.95 lung 27
lung 24 KC COPD 5.33 5.33 lung 24 -142.0727017
lung 28 KC COPD 30.24 30.24 lung 28 -25.04125331
lung 23 KC COPD 52.96 52.96 lung 23 -14.29847998
lung 25 KC COPD 17.02 17.02 lung 25
asthmatic lung 29321 309.94 309.94 asthmatic-2.44320675
OD03112 lun
asthmatic lung 29323 532.32 1064.64asthmatic1.405933991
OD03433 lun
asthmatic lung 29322 1159.052318.10asthmatic3.061218426
OD03397 lun
asthmatic lung 29325 873.73 1747.46asthmatic2.307647103
OD04928 lung
endo cells KC control0 0.00 endo cells
endo VEGF KC 0.93 0.93 endo VEGF0.93
endo bFGF KC 5.16 5.16 endo bFGF5.16
heart Clontech normal43.01 86.02 heart
heart ( T-1 29417 81.55 163.10 heart 1.896070681
) ischemic T-1
heart (T-14) 29422 51.64 103.28 heart 1.200651011
non- T-14
obstructive
DCM
heart (T-3399) 29426 90.27 180.54 heart 2.098814229
DCM T-3399
adenoid GW99-26926162 982.05 1964.10adenoid
tonsil GW98-28022582 3981.717963.42tonsil
T cells PC0031428453 265.95 531.90 T cells
PBMNC KC 40.89 40.89 PBMNC
monocyte KC 62.92 125.84 monocyte
B cells PC0066528455 9045.5818091.16B cells
dendritic cells 267.47 534.94 dendritic
28441 cells
neutrophils 28440 1212.1 1212.10neutrophils
eosinophils 28446 1563.763127.52eosinophils
BM unstim KC 56.55 56.55 BM unstim
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BM stim KC 27.4 27.40 BM stun -2.063868613
osteo dif KC 0 0.00 osteo
dif
osteo undif 0 0.00 osteo 0
KC undif
chondrocytes 0.92 2.30 chondrocytes
OA Synovium 29462 524.44524.44 OA
IP12/O1 Synovium
OA Synovium 29461 191.8 383.60 OA
NP10/Ol S novium
OA Synovium 28464 461.09922.18 OA
NP57/00 S novium
RA Synovium 28466 484.63969.26 RA Synovium
NP03/Ol
RA Synovium 28467 698.081396.16RA Synovium
NP71100
RA Synovium 28475 1034.782069.56RA Synovium
NP45/00
OA bone (biobank)29217 547.68547.68 OA bone
(biobank)
OA bone Sample J. Emory286.6 573.20 OA bone
1
OA bone Sample J. Emory604.861209.72OA bone
2
Cartilage (pool)Normal 224.68449.36 Cartilage
( ool)
Cartilage (pool)OA 113.78227.56 Cartilage-1.974687994
( ool)
PBL unifected 28441 966.681933.36PBL
unifected
PBL HIV IIIB 28442 1353.872707.74PBL HIV 1.400535855
IIIB
MRCS uninfected29158 1.28 2.56 MRCS
(100%) uninfected
(100%)
MRCS HSV strain29178 34.07 68.14 MRCS HSV 26.6171875
F strain
F
W 12 cells 29179 3.55 7.10 W 12 cells
Keratinocytes I 291805.64 11.28 Keratinocytes
I
Gene Name sbg442445PROa
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 1.19
colon tumor -2.59
colon tumor -1.93
colon tumor -1.76
lun tumor -63.01
lun tumor 1.66
lun tumor -2.42
lun tumor 1.89
breast tumor 2.48
breast tumor 15.17
breast tumor 5.24
breast tumor -2.63
brain sta a 5 ALZ -1.21
brain sta a 5 ALZ 2.09
brain stage 5 ALZ 1.45
brain sta a 5 ALZ -2.46
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lun 24 -142.07
_
lun 28 -25.04
lun 23 -14.30
asthmatic lun -2.44
asthmatic lun 1.41
asthmatic lun 3.06
asthmatic lun 2.31
endo VEGF 0.93
endo bFGF 5.16
heart T-1 1.90
heart T-14 ~ 1.20
heart T-3399 2.10
BM stun -2.06
osteo undif 0.00
Cartila a ( ool) -1.97
PBL HIV IIIB 1.40
MRCS HSV strain F 26.62
Gene Name sbg456548CytoRa
Strongly expressed in adenoid/tonsils and dendritic cells. Overexpressed in
stimulated bone marrow. Taken together, these data suggest a role in immune
function.
Expression in GI tract suggests potential role in diseases of the GI system
like IBD,
Chron's, etc.
Sample Mean Mean Average18S 50 ng/18Scopies
sbg456548CytoRaGOI GOI GOI rRNA rRNA of
copies copies Copies (ng) (ng) mRNA
(sample (sample detected/
1) 2) 50
ng
total
RNA
Subcutaneous 0.00 5.06 2.53 3.06 16.34 41.34
Adi oc tes
Zenbio
Subcutaneous 0.00 0.00 0.00 0.96 52.36 0.00
Adipose
Zenbio
Adrenal Gland 0.00 0.00 0.00 0.61 81.97 0.00
Clontech
Whole Brain 0.00 0.00 0.00 7.24 6.91 0.00
Clontech
Fetal Brain 0.00 0.00 0.00 0.48 103.95 0.00
Clontech
Cerebellum 0.00 0.00 0.00 2.17 23.04 0.00
Clontech
Cervix 0.00 7.86 3.93 2.42 20.66 81.20
Colon 9.12 37.61 23.37 2.71 18.45 431.09
Endometrium 0.00 0.00 0.00 0.73 68.21 0.00
Esophagus 0.00 0.00 0.00 1.37 36.50 0.00
Heart Clontech0.00 0.00 0.00 1.32 37.88 0.00
Hypothalamus 0.00 0.00 0.00 0.32 155.28 0.00
Ileum not done39.63 39.63 2.58 19.38 768.02
Jejunum 9.16 33.67 21.42 6.60 7.58 162.23
Kidney 0.00 0.00 0.00 2.12 23.58 0.00
Liver 0.00 13.75 6.88 1.50 33.33 229.17
Fetal Liver 0.00 0.00 0.00 10.404.81 0.00
Clontech
Lung 0.00 0.00 0.00 2.57 19.46 0.00
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Mammary Gland 136.73 106.34 121.54 13.003.85 467.44
Clontech
Myometrium 27.33 17.56 22.45 2.34 21.37 479.59
Omentum 0.00 12.61 6.31 3.94 12.69 80.01
Ovary 16.46 17.90 17.18 4.34 11.52 197.93
Pancreas 0.00 0.00 0.00 0.81 61.80 0.00
Head of Pancreas0.00 0.00 0.00 1.57 31.85 0.00
Parotid Gland 21.25 23.72 22.49 5.48 9.12 205.16
Placenta Clontech101.11 73.40 87.26 5.26 9.51 829.42
Prostate 8.55 0.00 4.28 3.00 16.67 71.25
Rectum 0.00 0.00 0.00 1.23 40.65 0.00
Salivary Gland0.00 0.00 0.00 7.31 6.84 0.00
Clontech
Skeletal Muscle0.00 0.00 0.00 1.26 39.68 0.00
Clontech
Skin 0.00 0.00 0.00 1.21 41.32 0.00
Small Intestine0.00 0.00 0.00 0.98 51.07 0.00
Clontech
Spleen 31.60 14.66 23.13 4.92 10.16 235.06
Stomach 0.00 7.01 3.51 2.73 18.32 64.19
Testis Clontech0.00 0.00 0.00 0.57 87.87 0.00
Thymus Clontech51.70 103.21 77.46 9.89 5.06 391.58
Thyroid 0.00 0.00 0.00 2.77 18.05 0.00
Trachea Clontech0.00 0.00 0.00 9.71 5.15 0.00
Urinary Bladder0.00 7.29 3.65 5.47 9.14 33.32
Uterus 5.98 21.02 13.50 15.3419.36 126.40
Sample Reg Mean copies Sample Fold Change
sbg456548CytoRanumber GOI of in
(GSK copiesmRNA Disease
identifier) detected/50 Population
ng total
RNA
colon normal 21941 54.19 108.38 colon
GW98-167 normal
colon tumor 21940 242.87485.74 colon 4.481823215
GW98-166 tumor
colon normal 22080 24.61 49.22 colon
GW98-178 normal
colon tumor 22060 17.37 34.74 colon -1.416810593
GW98-177 tumor
colon normal 23514 120.13240.26 colon
GW98-561 normal
colon tumor 23513 43.05 86.10 colon -2.79047619
GW98-560 tumor
colon normal 24691 81.35 162.70 colon
GW98-894 normal
colon tumor 24690 16.94 33.88 colon -4.802243211
GW98-893 tumor
lung normal 20742 12.83 25.66 lung
GW98-3 normal
lung tumor GW98-220741 94.41 188.82 lung 7.358534684
tumor
lung normal 20677 519.7 1039.40 lung
GW97-179 normal
lung tumor GW97-17820676 46.83 93.66 lung -11,09758702
tumor
lung normal 21922 7.95 15.90 lung
GW98-165 normal
lung tumor GW98-16421921 237.54475.08 lung 29.87924528
tumor
lung normal 22584 251.04502.08 lung
GW98-282 normal
lung tumor GW98-28122583 28.16 56.32 lung -8.914772727
tumor
breast normal 28750 138.99138.99 breast
GW00-392 normal
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breast tumor 28746 147.66295.32 breast 2.124757177
GW00-391 tumor
breast normal 28798 30.39 30.39 breast
GW00-413 normal
breast tumor 28797 37.64 75.28 breast 2.477130635
GW00-412 tumor
breast normal 27592-95218.09218.09 breast
GW00- normal
235:238
breast tumor 27588-9114.68 14.68 breast -14.85626703
GW00- tumor
231:234
breast normal 23656 1888.33776.60 breast
GW98-621 normal
breast tumor 23655 877.2 1754.40 breast -2.152644779
GW98-620 tumor
brain normal 25507 0 0.00 brain
BB99-542 normal
brain normal 25509 0 0.00 brain
BB99-406 normal
brain normal 25546 0 0.00 brain
BB99-904 normal
brain stage 25502 0 0.00 brain 0
ALZ BB99- stage
874 5
ALZ
brain stage 25503 7.32 14.64 brain 14.64
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 0 0.00 brain 0
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 0 0.00 brain 0
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 10.31 20.62 CT lung
lung 26 KC normal 49.79 49.79 lung
26
lung 27 KC normal 4.11 4.11 lung
27
lung 24 KC COPD 0.67 0.67 lung -38.10074627
24
lung 28 KC COPD 19.24 19.24 lung -1.326793139
28
lung 23 KC COPD 3.15 3.15 lung -8.103968254
23
lung 25 KC COPD 27.59 27.59 lung
25
asthmatic lung 29321 2.95 2.95 asthmatic-8.653389831
OD03112 lun
asthmatic lung 29323 9.86 19.72 asthmatic-1.294497972
OD03433 lun
asthmatic lung 29322 24.39 48.78 asthmatic1.910880423
OD03397 lun
asthmatic lung 29325 53.84 107.68 asthmatic4.218196063
OD04928 lun
endo cells KC control0 0.00 endo
cells
endo VEGF KC 14.65 14.65 endo 14.65
VEGF
endo bFGF KC 0 0.00 endo 0
bFGF
heart Clontech normal 0 0.00 heart
heart ( T-1 29417 21.18 42.36 heart 42.36
) ischemic T-1
heart (T-14) 29422 27.4 54.80 heart 54.8
non- T-14
obstructive
DCM
heart (T-3399) 29426 93.27 186.54 heart 186.54
DCM T-3399
adenoid GW99-26926162 579.691159.38 adenoid
tonsil GW98-28022582 3780.087560.16 tonsil
T cells PC0031428453 5.86 11.72 T cells
PBMNC KC 0 0.00 PBMNC
monocyte KC 0 0.00 monocyte
B cells PC0066528455 19.6 39.20 B cells .
dendritic cellsI 580.671161.34 dendritic
28441
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cells
neutrophils 28440 19.76 19.76 neutrophils
eosinophils 28446 15.12 30.24 eosinophils
BM unstim KC 0 0.00 BM unstim
BM stim KC 296.72296.72 BM stun 296.72
osteo dif KC 0 0.00 osteo
dif
osteo undif 0 0.00 osteo 0
KC undif
chondrocytes 15.31 38.28 chondrocyte
s
OA Synovium 29462 39.57 39.57 OA
IP12/O1 S novium
OA Synovium 29461 0 0.00 OA
NP10/O1 S novium
OA Synovium 28464 70.08 140.16 OA
NP57/00 Synovium
RA Synovium 28466 23.73 47.46 RA
NP03/Ol S novium
RA Synovium 28467 24.13 48.26 RA
NP71/00 S novium
RA Synovium 28475 51.88 103.76 -RA
NP45/00 S novium
OA bone (biobank)29217 0 0.00 OA bone
(biobank)
OA bone Sample J. Emory0 0.00 OA bone
1
OA bone Sample J. Emory5.45 10.90 OA bone
2
Cartilage (pool)Normal 0 0.00 Cartilage
( ool)
Cartilage (pool)OA 0 0.00 Cartilage0
( ooI)
PBL unifected 28441 76.67 153.34 PBL
unifected
PBL HIV IIIB 28442 13.77 27.54 PBL HIV -5.567901235
IIIB
MRCS uninfected29158 0 0.00 MRCS
(100%) uninfected
(100%)
MRCS HSV strain29178 0 0.00 MRCS 0
F HSV
strain
F
W 12 cells 29179 0 0.00 W 12
cells
Keratinocytes 29180 0 0.00 Keratinocyte
s
Gene Name sbg456548CytoRa
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 4.48
colon tumor -1.42
colon tumor -2.79
colon tumor -4.80
lung tumor 7.36
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lung tumor -11.10
lung tumor 29.88
lung tumor -8.91
breast tumor 2.12
breast tumor 2.48
breast tumor -14.86
breast tumor -2.15
brain stage 5 ALZ 0.00
brain stage 5 ALZ 14.64
brain stage 5 ALZ 0.00
brain stage 5 ALZ 0.00
lung 24 -38.10
lung 28 -1.33
lung 23 -8.10
asthmatic lung -8.65
asthmatic lung -1.29
asthmatic lung 1.91
asthmatic lung 4.22
endo VEGF 14.65
endo bFGF 0.00
heart T-1 42.36
heart T-14 54.80
heart T-3399 186.54
BM stim 296.72
osteo undif 0.00
Cartilage (pool) 0.00
PBL HIV IIIB -5.57
MRCS HSV strain F ( 0.00
Gene Name sbg442358PROa
Expression in multiple immune cell types as well as stimulated bone marrow and
thymus strongly suggests function in immune system. Overexpressed in breast
tumors (1/4).
Expression in RA and OA with corroborating expression in immune cells suggests
role in
these diseases. Overexpressed in heart disease suggesting role in CV diseases.
Downregulated in HSV infected cells suggesting possible host cell factor.
Sample Mean Mean Average18S 50 ng/18Scopies
GOI GOI
sbg442358PROa copies copies GOI rRNA rRNA of
(sample (sampleCopies (ng) (ng) mRNA
1) 2)
detecte
d/50
ng
total
RNA
Subcutaneous 1.86 1.71 1.79 3.06 16.34 29.17
Adi ocytes
Zenbio
Subcutaneous 0.71 0.73 0.72 0.96 52.36 37.70
Adipose
Zenbio
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Adrenal Gland 3.45 1.89 2.67 0.61 81.97 218.85
Clontech
Whole Brain 406.27 496.60 451.44 7.24 6.91 3117.65
Clontech
Fetal Brain 3.82 1.68 2.75 0.48 103.95 285.86
Clontech
Cerebellum 5.84 30.51 18.18 2.17 23.04 418.78
Clontech
Cervix 2.50 0.48 1.49 2.42 20.66 30.79
Colon 18.45 18.77 18.61 2.71 18.45 343.36
Endometrium 4.93 0.30 2.62 0.73 68.21 178.38
Esophagus 8.97 6.99 7.98 1.37 36.50 291.24
Heart Clontech5.26 16.53 10.90 1.32 37.88 412.69
Hypothalamus 2.10 2.41 2.26 0.32 155.28 350.16
Ileum 18.94 12.62 15.78 2.58 19.38 305.81
Jejunum 65.51 95.24 80.38 6.60 7.58 608.90
Kidney 2.60 3.81 3.21 2.12 23.58 75.59
Liver 7.19 7.05 7.12 1.50 33.33 237.33
Fetal Liver 1252.221363.06 1307.6410.404.81 6286.73
Clontech
Lung 27.57 6.97 17.27 2.57 19.46 335.99
Mammary Gland 79.83 72.99 76.41 13.003.85 293.88
Clontech
Myometrium 2.46 10.62 6.54 2.34 21.37 139.74
Omentum 10.40 3.27 6.84 3.94 12.69 86.74
Ovary 17.71 31.15 24.43 4.34 11.52 281.45
Pancreas 3.33 1.74 2.54 0.81 61.80 156.67
Head of Pancreas3.82 6.17 5.00 1.57 31.85 159.08
Parotid Gland 22.77 22.54 22.66 5.48 9.12 206.71
Placenta Clontech14.71 53.83 34.27 5.26 9.51 325.76
Prostate 16.71 19.39 18.05 3.00 16.67 300.83
Rectum 6.71 3.49 5.10 1.23 40.65 207.32
Salivary Gland55.38 9.30 32.34 7.31 6.84 221.20
Clontech
Skeletal Muscle3.79 4.16 3.98 1.26 39.68 157.74
Clontech
Skin 4.51 14.47 9.49 1.21 41.32 392.15
Small Intestine8.12 7.87 8.00 0.98 51.07 408.32
Clontech
Spleen 14.88 17.12 16.00 4.92 10.16 162.60
Stomach 21.85 11.68 16.77 2.73 18.32 307.05
Testis Clontech22.77 11.54 17.16 0.57 87.87 1507.47
Thymus Clontech1990.821374.71 1682.779.89 5.06 8507.41
Thyroid 16.85 2.86 9.86 2.77 18.05 177.89
Trachea Clontech29.69 82.85 56.27 9.71 5.15 289.75
Urinary Bladder2.32 13.42 7.87 5.47 9.14 71.94
uterus 8.86 11.18 10.02 5.34 9.36 93.82
Sample Reg Mean copies Sample Fold
of Change
sbg442358PROa number GOI mRNA in Disease
(GSK copiesdetected/50 Population
identifier) ng total
RNA
colon normal 21941 1232.322464.64 colon
GW98-167 normal
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colon tumor 21940 2940.175880.34 colon 2.385881914
GW98-166 tumor
colon noxmal 22080 221.26442.52 colon
GW98-178 normal
colon tumor 22060 709.521419.04 colon 3.20672512
GW98-177 tumor
colon normal 23514 985.521971.04 colon .
GW98-561 normal
colon tumor 23513 829.671659.34 colon -1.18784577
GW98-560 tumor
colon normal 24691 2738.175476.34 colon
GW98-894 normal
colon tumor 24690 3022.066044.12 colon 1.103678734
GW98-893 tumor
lung normal 20742 536.821073.64 lung normal
GW98-3
lung tumor GW98-220741 594.2 1188.40 lung tumor1.106888715
lung normal 20677 4382.618765.22 lung normal
GW97-179
lung tumor GW97-17820676 359.07718.14 lung tumor-12.20544741
lung normal 21922 622.061244.12 lung normal
GW98-165
lung tumor GW98-16421921 1299.852599.70 lung tumor2.089589429
lung normal 22584 1782.093564.18 lung normal
GW98-282
lung tumor GW98-28122583 470.51941.02 lung tumor-3.787570934
breast normal 28750 429 429.00 breast
GW00-392 normal
breast tumor 28746 417.99835.98 breast 1.948671329
GW00-391 tumor
breast normal 28798 16.03 16.03 breast
GW00-413 normal
breast tumor 28797 1048.112096.22 breast 130.768559
GW00-412 tumor
breast normal 27592-952.17 2.17 breast
GW00- normal
235:238
breast tumor 27588-9169.91 69.91 breast 32.21658986
GW00- tumor
231:234
breast normal 23656 1037.082074.16 breast
GW98-621 normal
breast tumor 23655 1010.592021.18 breast -1.026212411
GW98-620 tumor
brain normal 25507 299.28598.56 brain
BB99-542 normal
brain normal 25509 250.85501.70 brain
BB99-406 normal
brain normal 25546 97.7 195.40 brain
BB99-904 normal
brain stage 25502 125 250.00 brain -1.727546667
ALZ BB99- stage
874 5
ALZ
brain stage 25503 850.011700.02 brain 3.936264143
5 ALZ BB99- stage
887 5
ALZ
brain stage 25504 347.91695.82 brain 1.611117114
5 ALZ BB99- stage
862 5
ALZ
brain stage 25542 147.11294.22 brain -1.467903836
5 ALZ BB99- stage
927 5
ALZ
CT lung KC normal 130.37260.74 CT lung
lung 26 KC normal 159.19159.19 lung 26
lung 27 KC normal 0.49 0.49 lung 27
lung 24 KC COPD 2.37 2.37 lung 24 -47.89873418
lung 28 KC COPD 45.72 45.72 lung 28 -2.482939633
lung 23 KC COPD 20.36 20.36 lung 23 -5.575638507
lung 25 KC COPD 33.66 33.66 lung 25
asthmatic lung 29321 65.46 65.46 asthmatic-1.734188818
OD03112 ' lun
asthmatic lung 29323 532.421064.84 asthmatic9.380197322
OD03433 lung
asthmatic lung 29322 2865.675731.34 asthmatic50.48749119
OD03397 lun
asthmatic lung 29325 494.27988.54 asthmatic8.708069063
OD04928 lun
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endo cells KC control62.77 62.77 endo cells
endo VEGF KC 22.41 22.41 endo VEGF-2.800981705
endo bFGF KC 33.16 33.16 endo bFGF-1.892943305
heart Clontech normal 74.18 148.36 heart
heart ( T-1 29417 270.07540.14 heart 3.640738744
) ischemic T-1
heart (T-14) 29422 680.121360.24 heart 9.168509032
non- T-14
obstructive
DCM
heart (T-3399) 29426 414 828.00 heart 5.581019143
DCM T-3399
adenoid GW99-26926162 781.461562.92 adenoid
tonsil GW98-28022582 2279.134558.26 tonsil
T cells PC0031428453 1129.272258.54 T cells
PBMNC KC 27.98 27.98 PBMNC
monocyte KC 3.55 7.10 monocyte
B cells PC0066528455 872.581745.16 B cells
dendritic cells 1055.222110.44 dendritic
28441 cells
neutrophils 28440 740.39740.39 neutrophils
eosinophils 28446 1081.832163.66 eosinophils
BM unstim KC 50.91 50.91 BM unstim
BM stun KC 391.11391.11 BM stim 7.682380672
osteo dif KC 161.31161.31 osteo
dif
osteo undif 40.01 40.01 osteo -4.031742064
KC undif
chondrocytes 2250.595626.48 chondrocytes
OA Synovium 29462 229.19229.19 OA
IP12/O1 S novium
OA Synovium 29461 152.3 304.60 OA
NP10/O1 S novium
OA Synovium 28464 413.06826.12 OA
NP57/00 S novium
RA Synovium 28466 611.021222.04 RA Synovium
NP03/Ol
RA Synovium 28467 385.94771.88 RA Synovium
NP71/00
RA Synovium 28475 1701.683403.36 RA Synovium
NP45/00
OA bone(biobank)29217 225.69225.69 OA bone
(biobank)
OA bone Sample J. Emory306.63613.26 OA bone
1
OA bone Sample J. Emory1811.323622.64 OA bone
2
Cartilage (pool)Normal 384.44768.88 Cartilage
( ool)
Cartilage (pool)OA 174.53349.06 Cartilage-2.202715865
( ool)
PBL unifected 28441 9016.8218033.64PBL
unifected
PBL HIV IIIB 28442 4331.768663.52 PBL HIV -2.081560382
IIIB
MRCS uninfected29158 2232.484464.96 MRCS
(100%) ' uninfected
(100%)
MRCS HSV strain29178 419.67839.34 MRCS HSV -5.319608264
F strain
F
W12 cells 29179 3336.076672.14 W12 cells
~Keratinocytes 129180 5568.9111137.82Keratinocytes
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Gene Name sbg442358PROa
Disease tissues Fold Change in
Disease
Population Relative
to
Normal
colon tumor 2.39
colon tumor 3.21
colon tumor -1.19
colon tumor 1.10
lun tumor 1.11
lung tumor -12.21
lun tumor 2.09
lun tumor -3.79
breast tumor 1.95
breast tumor 130.77
breast tumor 32.22
breast tumor -1.03
brain sta a 5 ALZ -1.73
brain stage 5 ALZ 3.94
brain sta a 5 ALZ 1.61
brain sta a 5 ALZ -1.47
lun 24 -47.90
lung 28 -2.48
lun 23 -5.58
asthmatic lun -1.73
asthmatic lun 9.38
asthmatic lun 50.49
asthmatic lung ' 8.71
endo VEGF -2.80
endo bFGF -1.89
heart T-1 3.64
heart T-14 9.17
heart T-3399 5.58
BM stun 7.68
osteo undif -4.03
Cartila a ( ool) -2.20
PBL HIV IIIB -2.08
MRCS HSV strain F I -5.32
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Table V. Additional diseases based on mRNA expression in specific tissues
Tissue Additional Diseases
Expression
Brain Neurological and psychiatric diseases, including
Alzheimers, parasupranuclear
palsey, Huntington's disease, myotonic dystrophy,
anorexia, depression,
schizophrenia, headache, amnesias, anxiety
disorders, sleep disorders, multiple
sclerosis
Heart Cardiovascular diseases, including congestive
heart failure, dilated
cardiomyopathy, cardiac arrhythmias, Hodgson's
Disease, myocardial
infarction, cardiac arrh thmias
Lung Respiratory diseases, including asthma, Chronic
Obstructive Pulmonary
Disease, c stic fibrosis, acute bronchitis,
adult res irator distress s ndrome
Liver Dyslipidemia, hypercholesterolemia, hypertriglyceridemia,
cirrhosis, hepatic
encephalopathy, fatty hepatocirrhosis, viral
and nonviral hepatitis, Type II
Diabetes Mellitis, im aired lucose tolerance
Kidney Renal diseases, including acute and chronic
renal failure, acute tubular necrosis,
cystinuria, Fanconi's Syndrome, glomerulonephritis,
renal cell carcinoma,
renovascular h ertension
Skeletal Eulenburg's Disease, hypoglycemia, obesity,
tendinitis, periodic paralyses,
muscle mali nant h erthermia, aram otonia con enita,
m otonia con enita
Intestine Gastrointestinal diseases, including Myotonia
congenita, Ileus, Intestinal
Obstruction, Tro ical S rue, Pseudomembranous
Enterocolitis
Spleen/lymphLymphangiectasia, hypersplenism, angiomas,
ankylosing spondylitis, Hodgkin's
Disease, macro lobulinemia, mali nant 1 m homas,
rheumatoid arthritis
Placenta Choriocarcinoma, hydatidiform mole, placenta
previa
Testis Testicular cancer, male reproductive diseases,
including low testosterone and
male infertility
Pancreas Diabetic ketoacidosis, Type 1 & 2 diabetes,
obesity, impaired glucose tolerance
CA 02414005 2002-12-20
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SEQUENCE LISTING
<110> SMITHKLINE BEECHAM CORPORATION
SMITHKLINE BEECHAM p.l.c.
GLAXO GROUP LTD.
<120> NOVEL COMPOUNDS
<130> GP50029
<140> TO BE ASSIGNED
<141> 2001-06-22
<150> 60/213,161
<151> 2000-06-22
<150> 60/213,156
<151> 2000-06-22
<160> 44
<170> FastSEQ for Windows Version 4.0
<210> 1
<211> 1383
<212> DNA
<213> Homo Sapiens
<400> 1
atgcttggaa tttggattgt tgcattcttg ttctttggca catcaagagg aaaagaagtt 60
tgctatgaaa ggttagggtg tttcaaagat ggtttaccat ggaccaggac tttctcaaca 120
gagttggtag gtttaccctg gtctccagag aagataaaca ctcgtttcct gctctacact 180
atacacaatc ccaatgccta tcaggagatc agtgcggtta attcttcaac tatccaagcc 240
tcatattttg gaacagacaa gatcacccgt atcaacatag ctggatggaa aacagatggc 300
aaatggcaga gagacatgtg caatgtgttg ctacagctgg aagatataaa ttgcattaat 360
ttagattgga tcaacggttc acgggaatac atccatgctg taaacaatct ccgtgttgtt 420
ggtgctgagg tggcttattt tattgatgtt ctcatgaaaa aatttgaata ttccccttct 480
aaagtgcact tgattggcca cagcttggga gcacacctgg ctggggaagc tgggtcaagg 540
ataccaggcc ttggaagaat aactgggttg gacccagctg ggccattttt ccacaacact 600
ccaaaggaag tcaggctaga cccctcggat gccaactttg ttgacgttat tcatacaaat 660
gcagctcgca tcctctttga gcttggtgtt ggaaccattg atgcttgtgg tcatcttgac 720
ttttacccaa atggagggaa gcacatgcca ggatgtgaag acttaattac acctttactg 780
aaatttaact tcaatgctta caaaaaagaa atggcttcct tctttgactg taaccatgcc 840
cgaagttatc aattttatge tgaaagcatt cttaatcctg atgcatttat tgcttatcct 900
tgtagatcct acacatcttt taaagcaggt acatgtgtag gatgtgcaga tttgttacat 960
aggatagata agataggaag tcatacttcc catgtgtttt taaccctttc tctccctttc 1020
cttcttgttt ccttatatct aggttggagg cacaaattgt ctgttaaact cagtggaagc 1080
gaagtcactc aaggaactgt ctttcttcgt gtaggcgggg cagttaggaa aactggggag 1140
tttgccattg tcagtggaaa acttgagcca ggcatgactt acacaaaatt aatcgatgca 1200
gatgttaacg ttggaaacat tacaagtgtt cagttcatct ggaaaaaaca tttgtttgaa 1260
gattctcaga ataagttggg agcagaaatg gtgataaata catctgggaa atatggatat 1320
aaatctacct tctgtagcca agacattatg ggacctaata ttctccagaa cctgaaacca 1380
tgc 1383
<210> 2
<211> 927
<212> DNA
<213> Homo Sapiens
1/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
<400> 2
atgccgttcc tgcagctgaa agggagagca acacctccat cctggagaca cgatagccgc 60
tcacttgttc acctgctgga cggcaaggag ggcgtgtggg acaccacggg ctatgcctta 120
gggagcagag aatcattgaa tcctgacatg gggattggtg acccacatgg acacagcact 180
gtccacacca gggaagcagg cactgcctgt ccattacagc ttctaggtgc tcgggaggcc 240
agtctgctgg cctgtgggat ctgccaggcc tctggccaaa tcttcatcac ccaaaccctg 300
gggatcaagg gatatcggac tgtcgtggcc ctggataagg tccctgagga tgttcaggaa 360
tacagctggt actggggtgc aaacgacagc gcaggaaaca tgattatcag ccacaaaccg 420
cccagtgccc agcagcctgg gcccatgtac actggcaggg agagagtgaa cagagaaggc 480
agcctgttga tcaggccgac tgcattaaat gacacgggaa actacactgt tcgggtggtt 540
gcaggcaatg agacccaaag agcaaccggc tggctggagg ttctagatgg gcccgactat 600
gtgctgctga ggagcaatcc tgatgatttc aacggcattg tgacagctga gatcggctcc 660
caagtggaaa tggagtgtat ctgctattcc ttcctggatc tcaagtacca ctggatccac 720
aatggctccc tcctgaactt ctcagatgca aagatgaacc tctcgagtct tgcctgggag 780
cagatgggcc gttaccgatg cactgtggag aaccccgtga cacagctgat catgtacatg 840
gacgtcagga tccaggcccc ccatgagtgc agcagctccc ctccaggctc atgctttgca 900
CatCtCCCtg CCtCCatgCC ctgctag 927
<210> 3
<211> 1374
<212> DNA
<213> Homo Sapiens
<400> 3
atggaccttt ccagacccag atggagcctg tggaggaggg tcttcctcat ggccagtctg 60
ctggcctgtg ggatctgcca ggcctctggc caaatcttca tcacccaaac cctggggatc 120
aagggatatc ggactgtcgt ggccctggat aaggtccctg aggatgttca ggaatacagc 180
tggtactggg gtgcaaacga cagcgcagga aacatgatta tcagccacaa accgcccagt 240
gcccagcagc ctgggcccat gtacactggc agggagagag tgaacagaga aggcagcctg 300
ttgatcaggc cgactgcatt aaatgacacg ggaaactaca ctgttcgggt ggttgcaggc 360
aatgagaccc aaagagcaac cggctggctg gaggttctag agttgggaag caatctgggc 420
atctccgtca atgccagctc cctggtggag aacatggatt ctgtggctgc tgactgcctc 480
acaaatgtca ccaacatcac gtggtatgtg aatgatgtgc ctacctctag tagtgaccgg 540
atgacaattt ccccagacgg caagaccctc gtcatcctca gggtcagccg ctatgacaga 600
acaattcagt gcatgataga gagtttccca gagatctttc agagaagtga acgcatctct 660
ctgactgtgg cctatgggcc cgactatgtg ctgctgagga gcaatcctga tgatttcaac 720
ggcattgtga cagctgagat cggctcccaa gtggaaatgg agtgtatctg ctattccttc 780
ctggatctca agtaccactg gatccacaat ggctccctcc tgaacttctc agatgcaaag 840
atgaacctct cgagtcttgc ctgggagcag atgggccgtt accgatgcac tgtggagaac 900
cccgtgacac agctgatcat gtacatggac gtcaggatcc aggcccccca tgagtgtcct 960
cttccttcag ggatcttacc tgttgtccac agagatttct ccatctcagg atccatggtg 1020
atgttcctca tcatgctgac agtgctgggt ggcgtttaca tctgtggagt cctgatccat 1080
gctctgatca accactactc aatcaggtgc cctcattgct ctgggacaag ggtgggatgt 1140
tggctggggg ctgggactca ggagccagcc ctccctccag aggggaagca gagccagaag 1200
gggagggata agccaggaac taggttgtca gggatcatct ggggcagaca gatcagcccc 1260
caggacctga agctgatggg agcaagagag ggtttagagt cggccatggt tctaaatagc 1320
tgtggggttt cttctagcaa cttcccttct ctttgtgttt ataagggata ttaa 1374
<210> 4
<211> 2115
<212> DNA
<213> Homo Sapiens
<400> 4
atgctccatg atgggttgac tgcacctgat gggtgtggaa tctacagcct gaccgggcgg 60
gaagtcctga cgcccttccc aggattgggc actgcggcag ccccggcaca gggcggggcc 120
cacctgaagc agtgtgacct gctgaagctg tcccggcggc agaagcagct ctgccggagg 180
gagcccggcc tggctgagac cctgagggat gctgcgcacc tcggcctgct tgagtgccag 240
2/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
tttcagttcc ggcatgagcg ctggaactgt agcctggagg gcaggatggg cctgctcaag 300
agaggcttca aagagacagc tttcctgtac gcggtgtcct ctgccgccct cacccacacc 360
ctggcccggg cctgcagcgc tgggcgcatg gagcgctgca cctgtgatga ctctccgggg 420
ctggagagcc ggcaggcctg gcagtggggc gtgtgcggtg acaacctcaa gtacagcacc 480
aagtttctga gcaacttcct ggggtccaag agaggaaaca aggacctgcg ggcacgggca 540
gacgcccaca atacccacgt gggcatcaag gctgtgaaga gtggcctcag gaccacgtgt 600
aagtgccatg gcgtatcagg ctcctgtgcc gtgcgcacct gctggaagca gctctccccg 660
ttccgtgaga cgggccaggt gctgaaactg cgctatgact cggctgtcaa ggtgtccagt 720
gccaccaatg aggccttggg ccgcctagag ctgtgggccc ctgccaggca gggcagcctc 780
accaaaggcc tggccccaag gtctggggac ctggtgtaca tggaggactc acccagcttc 840
tgccggccca gcaagtactc acctggcaca gcaggtaggg tgtgctcccg ggaggccagc 900
tgcagcagcc tgtgctgcgg gcggggctat gacacccaga gccgcctggt ggccttctcc 960
tgccactgcc aggtgcagtg gtgctgctac gtggagtgcc agcaatgtgt gcaggaggag 1020
cttgtgtaca cctgcaagca ctagatgggc cctgtggggt tcccgaggca gtgccaggga 1080
gccttctttg agagcagccc tgggcagacc agggcccgcc tgaccgggcg ggaagtcctg 1140
acgcccttcc caggattggg cactgcggca gccccggcac agggcggggc ccacctgaag 1200
cagtgtgacc tgctgaagct gtcccggcgg cagaagcagc tctgccggag ggagcccggc 1260
ctggctgaga ccctgaggga tgctgcgcac ctcggcctgc ttgagtgcca gtttcagttc 1320
cggcatgagc gctggaactg tagcctggag ggcaggatgg gcctgctcaa gagaggcttc 1380
aaagagacag ctttcctgta cgcggtgtcc tctgccgccc tCaCCCaCaC CCtggCCCgg 1440
gcctgcagcg ctgggcgcat ggagcgctgc acctgtgatg actctccggg gctggagagc 1500
cggcaggcct ggcagtgggg cgtgtgcggt gacaacctca agtacagcac caagtttctg 1560
agcaacttcc tggggtccaa gagaggaaac aaggacctgc gggcacgggc agacgcccac 1620
aatacccacg tgggcatcaa ggctgtgaag agtggcctca ggaccacgtg taagtgccat 1680
ggcgtatcag gctcctgtgc cgtgcgcacc tgctggaagc agctctcccc gttccgtgag 1740
acgggccagg tgctgaaact gcgctatgac tcggctgtca aggtgtccag tgccaccaat 1800
gaggccttgg gccgcctaga gctgtgggcc cctgccaggc agggcagcct caccaaaggc 1860
ctggccccaa ggtctgggga cctggtgtac atggaggact cacccagctt ctgccggccc 1920
agcaagtact cacctggcac agcaggtagg gtgtgctccc gggaggccag ctgcagcagc 1980
ctgtgctgcg ggcggggcta tgacacccag agccgcctgg tggccttctc ctgccactgc 2040
caggtgcagt ggtgctgcta cgtggagtgc cagcaatgtg tgcaggagga gcttgtgtac 2100
acctgcaagc actag 2115
<210> 5
<211> 1086
<212> DNA
<213> Homo Sapiens
<400> 5
atgaagcccc tgaggaggcc ccttcccttc atttgcccct caccaccatc cccaaggctc 60
acctgtctcc ctcctctcgc tctctctagc ctgaccgggc gggaagtcct gacgcccttc 120
ccaggattgg gcactgcggc agccccggca cagggcgggg cccacctgaa gcagtgtgac 180
ctgctgaagc tgtcccggcg gcagaagcag ctctgccgga gggagcccgg cctggctgag 240
accctgaggg atgctgcgca cctcggcctg cttgagtgcc agtttcagtt ccggcatgag 300
cgctggaact gtagcctgga gggcaggatg ggcctgctca agagaggctt caaagagaca 360
gctttcctgt acgcggtgtc ctctgccgcc ctcacccaca ccctggcccg ggcctgcagc 420
gctgggcgca tggagcgctg cacctgtgat gactctccgg ggctggagag ccggcaggcc 480
tggcagtggg gcgtgtgcgg tgacaacctc aagtacagca ccaagtttct gagcaacttc 540
ctggggtcca agagaggaaa caaggacctg cgggcacggg cagacgccca caatacccac 600
gtgggcatca aggctgtgaa gagtggcctc aggaccacgt gtaagtgcca tggcgtatca 660
ggctcctgtg ccgtgcgcac ctgctggaag cagctctccc cgttccgtga gacgggccag 720
gtgctgaaac tgcgctatga ctcggctgtc aaggtgtcca gtgccaccaa tgaggccttg 780
ggccgcctag agctgtgggc ccctgccagg cagggcagcc tcaccaaagg cctggcccca 840
aggtctgggg acctggtgta catggaggac tcacccagct tctgccggcc cagcaagtac 900
tcacctggca cagcaggtag ggtgtgctcc cgggaggcca gctgcagcag cctgtgctgc 960
gggcggggct atgacaccca gagccgcctg gtggccttct cctgccactg ccaggtgcag 1020
tggtgctgct acgtggagtg ccagcaatgt gtgcaggagg agcttgtgta cacctgcaag 1080
cactag 1086
3153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
<210> 6
<211> 1098
<212> DNA
<213> Homo Sapiens
<400> 6
atgtggctgc ttttaacaac aacttgtttg atctgtggaa ctttaaatgc tggtggattc 60
cttgatttgg aaaatgaagt gaatcctgag gtgtggatga atactagtga aatcatcatc 120
tacaatggct accccagtga agagtatgaa gtcaccactg aagatgggta tatactcctt 180
gtcaacagaa ttccttatgg gcgaacacat gctaggagca cagcagatgc aggttatgat 240
gtatggatgg gaaacagtcg gggaaacact tggtcaagaa gacacaaaac actctcagag 300
acagatgaga aattctgggc ctttagtttt gatgaaatgg ccaaatatga tctcccagga 360
gtaatagact tcattgtaaa taaaactggt caggagaaat tgtatttcat tggacattca 420
cttggcacta caatagggtt tgtagccttt tccaccatgc ctgaactggc acaaagaatc 480
aaaatgaatt ttgccttggg tcctacgatc tcattcaaat atcccacggg catttttacc 540
aggttttttc tacttccaaa ttccataatc aaggctgttt ttggtaccaa aggtttcttt 600
ttagaagata agaaaacgaa gatagcttct accaaaatct gcaacaataa gatactctgg 660
ttgatatgta gcgaatttat gtccttatgg gctggatcca acaagaaaaa tatgaatcag 720
agtcgaatgg atgtgtatat gtcacatgct cccactggtt catcagtaca caacattctg 780
catataaaac agctttacca ctctgatgaa ttcagagctt atgactgggg aaatgacgct 840
gataatatga aacattacaa tcagagtcat ccccctatat atgacctgac tgccatgaaa 900
gtgcctactg ctatttgggc tggtggacat gatgtcctcg taacacccca ggatgtggcc 960
aggatactcc ctcaaatcaa gagtcttcat tactttaagc tattgccaga ttggaaccac 1020
tttgattttg tctggggcct cgatgcccct caacggatgt acagtgaaat catagcttta 1080
atgaaggcat attcctaa 1098
<210> 7
<211> 1194
<212> DNA
<213> Homo Sapiens
<400> 7
atgtggcagc ttttagcagc agcatgctgg atgcttcttc ttggatctat gtatggttat 60
gacaagaaag gaaacaatgc aaaccctgaa gctaatatga atattagcca gattatttct 120
tactggggtt atccttatga agagtatgat gttacaacaa aagatggtta tatccttgga 180
atttatagga ttccacatgg aagaggatgc ccagggagga cagctccaaa gcctgctgtg 240
tatttgcagc atggcttaat tgcatctgcc agtaactgga tttgcaacct gcccaacaac 300
agtttggctt tccttctggc agatagtggt tatgacgtgt ggttggggaa cagccgagga 360
aacacttggt ccagaaaaca ccttaaattg tcaccgaaat caccggaata ctgggccttc 420
agtttggatg agatggctaa atatgacctt ccagccacaa tcaattttat catagagaaa 480
actggacaga agcgactcta ctacgtgggc cactcacaag gcaccaccat agcttttata 540
gcattttcta caaacccaga actggctaaa aagattaaga tattttttgc actggctcca 600
gttgtcacag ttaaatacac ccaaagtcct atgaaaaaac taacaaccct ttccaggcga 660
gtagttaagg tgttgtttgg tgacaaaatg ttccaccctc atacattgtt tgaccaattc 720
attgccacca aagtgtgcaa tcgaaagcta ttccgtcgta tttgcagcaa cttcctattt 780
actctgagtg gatttgatcc gcaaaactta aatatgagtc gcttggatgt ttatttgtca 840
cacaatcctg cgggaacatc tgttcagaat atgctgcact gggctcagct ttaccactct 900
gatgaattca gagcttatga ctggggaaat gacgctgata atatgaaaca ttacaatcag 960
agtcatcccc ctatatatga cctgactgcc atgaaagtgc ctactgctat ttgggctggt 1020
ggacatgatg tcctcgtaac accccaggat gtggccagga tactccctca aatcaagagt 1080
cttcattact ttaagctatt gccagattgg aaccactttg attttgtctg gggcctcgat 1140
gcccctcaac ggatgtacag tgaaatcata gctttaatga aggcatattc ctaa 1194
<210> 8
<211> 11118
<212> DNA
<213> Homo Sapiens
<400> 8
4153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
atggcgaagc ggctctgcgc ggggagcgca ctgtgtgttc gcggcccccg gggccccgcg 60
ccgctgctgc tggtcgggct ggcgctgctg ggcgcggcgc gggcgcggga ggaggcgggc 120
ggcggcttca gcctgcaccc gccctacttc aacctggccg agggcgcccg catcgccgcc 180
tccgcgacct gcggagagga ggccccggcg cgcggctccc cgcgccccac cgaggacctt 240
tactgcaagc tggtaggggg ccccgtggcc ggcggcgacc ccaaccagac catccggggc 300
cagtactgtg acatctgcac ggctgccaac agcaacaagg cacaccccgc gagcaatgcc 360
atcgatggca cggagcgctg gtggcagagt ccaccgctgt cccgcggcct ggagtacaac 420
gaggtcaacg tcaccctgga cctgggccag gtcttccacg tggcctacgt cctcatcaag 480
tttgccaact caccccggcc ggacctctgg gtgctggagc ggtccatgga cttcggccgc 540
acctaccagc cctggcagtt ctttgcctcc tccaagaggg actgtctgga gcggttcggg 600
ccacagacgc tggagcgcat cacacgggac gacgcggcca tctgcaccac cgagtactca 660
cgcatcgtgc ccctggagaa cggagagatc gtggtgtccc tggtgaacgg acgtccgggc 720
gccatgaatt tctcctactc gccgctgcta cgtgagttca ccaaggccac caacgtccgc 780
ctgcgcttcc tgcgtaccaa cacgctgctg ggccatctca tggggaaggc gctgcgggac 840
cccacggtca cccgccggta ttattacagc atcaaggata tcagcatcgg aggccgctgt 900
gtctgccacg gccacgcgga tgcctgcgat gccaaagacc ccacggaccc gttcaggctg 960
cagtgcacct gccagcacaa cacctgcggg ggcacctgcg accgctgctg ccccggcttc 1020
aatcagcagc cgtggaagcc tgcgactgcc aacagtgcca acgagtgcca gtcctgtaac 1080
tgctacggcc atgccaccga ctgttactac gaccctgagg tggaccggcg ccgcgccagc 1140
cagagcctgg atggcaccta tcagggtggg ggtgtctgta tcgactgcca gcaccacacc 1200
accggcgtca actgtgagcg ctgcctgccc ggcttctacc gCCCtCCCaa CCaCCCtCtC 1260
gactcgcccc acgtctgccg ccgctgcaac tgcgagtccg acttcacgga tggcacctgc 1320
gaggacctga cgggtcgatg ctactgccgg cccaacttct ctggggagcg gtgtgacgtg 1380
tgtgccgagg gcttcacggg cttcccaagc tgctacccga cgccctcgtc ctccaatgac 1440
accagggagc aggtgctgcc agccggccag attgtgaatt gtgactgcag cgcggcaggg 1500
acccagggca acgcctgccg gaaggaccca agggtgggac gctgtctgtg caaacccaac 1560
ttccaaggca cccattgtga gctctgcgcg ccagggttct acggccccgg ctgccagccc 1620
tgccagtgtt CCagCCCtgg agtggccgat gaccgctgtg accctgacac aggccagtgc 1680
aggtgccgag tgggcttcga gggggccaca tgtgatcgct gtgcccccgg ctactttcac 1740
ttccctctct gccagttgtg tggctgcagc cctgcaggaa ccttgcccga gggctgcgat 1800
gaggccggcc gctgcctatg ccagcctgag tttgctggac ctcattgtga ccggtgccgc 1860
cctggctacc atggtttccc caactgccaa gcatgcacct gcgaccctcg gggagccctg 1920
gaccagctct gtggggcggg aggtttgtgc cgctgccgcc ccggctacac aggcactgcc 1980
tgccaggaat gcagccccgg ctttcacggc ttccccagct gtgtcccctg ccactgctct 2040
gctgaaggct ccctgcacgc agcctgtgac ccccggagtg ggcagtgcag ctgccggccc 2100
cgtgtgacgg ggctgcggtg tgacacatgt gtgcccggtg cctacaactt cccctactgc 2160
gaagctggct cttgccaccc tgccggtctg gccccagtgg atcctgccct tcctgaggca 2220
caggttccct gtatgtgccg ggctcacgtg gaggggccga gctgtgaccg ctgcaaacct 2280
gggttctggg gactgagccc cagcaacccc gagggctgta cccgctgcag ctgcgacctc 2340
aggggcacac tgggtggagt tgctgagtgc cagccgggca ccggccagtg cttctgcaag 2400
ccccacgtgt gcggccaggc ctgcgcgtcc tgcaaggatg gcttctttgg actggatcag 2460
gctgactatt ttggctgccg cagctgccgg tgtgacattg gcggtgcact gggccagagc 2520
tgtgaaccga ggacgggcgt ctgccggtgc cgccccaaca cccagggccc cacctgcagc 2580
gagcctgcga gggaccacta cctcccggac ctgcaccacc tgcgcctgga gctggaggag 2640
gctgccacac ctgagggtca cgccgtgcgc tttggcttca accccctcga gttcgagaac 2700
ttcagctgga ggggctacgc gcagatggca cctgtccagc ccaggatcgt ggccaggctg 2760
aacctgacct cccctgacct tttctggctc gtcttccgat acgtcaaccg gggggccatg 2820
agtgtgagcg ggcgggtctc tgtgcgagag gagggcaggt cggccacctg cgccaactgc 2880
acagcacaga gtcagcccgt ggccttccca cccagcacgg agcctgcctt catcaccgtg 2940
ccccagaggg gcttcggaga gccctttgtg ctgaaccctg gcacctgggc cctgcgtgtg 3000
gaggccgaag gggtgctcct ggactacgtg gttctgctgc ctagcgcata ctacgaggcg 3060
gcgctcctgc agctgcgggt gactgaggcc tgcacatacc gtccctctgc ccagcagtct 3120
ggcgacaact gcctcctcta cacacacctc cccctggatg gcttcccctc ggccgccggg 3180
ctggaggccc tgtgtcgcca ggacaacagc ctgccccggc cctgccccac ggagcagctc 3240
agcccgtcgc acccgccact gatcacctgc acgggcagtg atgtggacgt ccagcttcaa 3300
gtggcagtgc cacagccagg ccgctatgcc ctagtggtgg agtacgccaa tgaggatgcc 3360
cgccaggagg tgggcgtggc cgtgcacacc ccacagcggg ccccccagca ggggctgctc 3420
tccctgcacc cctgcctgta cagcaccctg tgccggggca ctgcccggga tacccaggac 3480
cacctggctg tcttccacct ggactcggag gccagcgtga ggctcacagc cgaacaggca 3540
5/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
cgcttcttcc tgcacggggt cactctggtg cccattgagg agttcagccc ggagttcgtg 3600
gagccccggg tcagctgcat cagcagccac ggcgcctttg gccccaacag tgccgcctgt 3660
ctgccctcgc gcttcccaaa gccgccccag cccatcatcc tcagggactg ccaggtgatc 3720
ccgctgccgc ccggcctccc gctgacccac gcgcaggatc tcactccagc catgtcccca 3780
gctggacccc gacctcggcc ccccaccgct gtggaccctg atgcagagcc caccctgctg 3840
cgtgagcccc aggccaccgt ggtcttcacc acccatgtgc ccacgctggg ccgctatgcc 3900
ttcctgctgc acggctacca gccagcccac cccaccttcc ccgtggaagt cctcatcaac 3960
gccggccgcg tgtggcaggg ccacgccaac gccagcttct gtccacatgg ctacggctgc 4020
cgcaccctgg tggtgtgtga gggccaggcc ctgctggacg tgacccacag cgagctcact 4080
gtgaccgtgc gtgtgcccaa gggccggtgg ctctggctgg attatgtact cgtggtccct 4140
gagaacgtct acagctttgg ctacctccgg gaggagcccc tggataaatc ctatgacttc 4200
atcagccact gcgcagccca gggctaccac atcagcccca gcagctcatc cctgttctgc 4260
cgaaacgctg ctgcttccct ctccctcttc tataacaacg gagcccgtcc atgtggctgc 4320
cacgaagtag gtgctacagg ccccacgtgt gagcccttcg ggggccagtg tccctgccat 4380
gcccatgtca ttggccgtga ctgctcccgc tgtgccaccg gatactgggg cttccccaac 4440
tgcaggccct gtgactgcgg tgcccgcctc tgtgacgagc tcacgggcca gtgcatctgc 4500'
ccgccacgca ccatcccgcc cgactgcctg ctgtgccagc cccagacctt tggctgccac 4560
cccctggtcg gctgtgagga gtgtaactgc tcagggcccg gcatccagga gctcacagac 4620
cctacctgtg acacagacag cggccagtgc aagtgcagac ccaacgtgac tgggcgccgc 4680
tgtgatacct gctctccggg cttccatggc taCCCCCgCt gCCgCCCCtg tgaCtgtCaC 4740
gaggcgggca ctgcgcctgg cgtgtgtgac cccctcacag ggcagtgcta ctgtaaggag 4800
aacgtgcagg gccccaaatg tgaccagtgc agccttggga ccttctcact ggatgctgcc 4860
aaccccaaag gttgcacccg ctgcttctgc tttggggcca cggagcgctg ccggagctcg 4920
tcctacaccc gccaggagtt cgtggatatg gagggatggg tgctgctgag cactgaccgg 4980
caggtggtgc cccacgagcg gcagccaggg acggagatgc tccgtgcaga cctgcggcac 5040
gtgcctgagg ctgtgcccga ggctttcccc gagctgtact ggcaggcccc accctcctac 5100
ctgggggacc gggtgtcatc ctacggtggg accctccgtt atgaactgca ctcagagacc 5160
cagcggggag atgtctttgt ccccatggag agcaggccgg atgtggtgct gcagggcaac 5220
cagatgagca tcacattcct ggagccggca taccccacgc ctggccacgt tcaccgtggg 5280
cagctgcagc tggtggaggg gaacttccgg catacggaga cgcgcaacac tgtgtcccgc 5340
gaggagctca tgatggtgct ggccagcctg gagcagctgc agatccgtgc cctcttctca 5400
cagatctcct cggctgtctt cctgcgcagg gtggcactgg aggtggccag cccagcaggc 5460
cagggggccc tggccagcaa tgtggagctg tgcctgtgcc ccgccagcta ccggggggac 5520
tcatgccagg aatgtgCCCC CggCttCtat cgggacgtca aaggtctctt cctgggccga 5580
tgtgtccctt gtcagtgcca tggacactca gaccgctgcc tccctggctc tggcgtctgt 5640
gtggactgcc agcacaacac cgaaggggcc cactgtgagc gctgccaggc tggcttcgtg 5700
agcagcaggg acgaccccag cgccccctgt gtcagctgcc cctgccccct ctcagtgcct 5760
tccaacaact tcgccgaggg ctgtgtcctg cgaggcggcc gcacccagtg cctctgcaaa 5820
cctggttatg caggtgcctc ctgcgagcgg tgtgcgcccg gattctttgg gaacccactg 5880
gtgctgggca gctcctgcca gccatgcgac tgcagcggca acggtgaccc caacttgctc 5940
ttcagcgact gcgaccccct gacgggcgcc tgccgtggct gcctgcgcca caccactggg 6000
ccccgctgcg agatctgtgc ccccggcttc tacggcaacg ccctgctgcc cggcaactgc 6060
acccggtgcg actgtacccc atgtgggaca gaggcctgcg acccccacag cgggcactgc 6120
ctgtgcaagg cgggcgtgac tgggcggcgc tgtgaccgct gccaggaggg acattttggt 6180
ttcgatggct gcgggggctg ccgcccgtgt gcttgtggac cggccgccga gggctccgag 6240
tgccaccccc agagcggaca gtgccactgc cgaccaggga ccatgggacc ccagtgccgc 6300
gagtgtgccc ctggctactg ggggctccct gagcagggct gcaggcgctg ccagtgccct 6360
gggggccgct,gtgaccctca cacgggccgc tgcaactgcc ccccggggct cagcggggag 6420
cgctgcgaca cctgcagcca gcagcatcag gtgcctgttc caggcgggcc tgtgggccac 6480
agcatccact gtgaagtgtg tgaccactgt gtggtcctgc tcctggatga cctggaacgg 6540
gccggcgccc tCCtCCCCgC CattCaCgag caactgcgtg gcatcaatgc cagctccatg 6600
gcctgggccc gtctgcacag gctgaacgcc tccatcgctg acctgcagag ccagctccgg 6660
agccccctgg gcccccgcca tgagacggca cagcagctgg aggtgctgga gcagcagagc 6720
acaagcctcg ggcaggacgc acggcggcta ggcggccagg caggagcccc aagacccccc 6780
agggccccgg gaggctttca cctgtaccag gcgagccaat tgctggccgg caccgaggcc 6840
acactgggcc atgcgaagac gctgttggcg gccatccggg ctgtggaccg caccctgagc 6900
gagctcatgt cccagacggg ccacctgggg ctggccaatg cctcggctcc atcaggtgag 6960
cagctgctcc ggacactggc cgaggtggag cggctgctct gggagatgcg ggcccgggac 7020
ctgggggccc cgcaggcagc agctgaggct gagttggctg cagcacagag attgctggcc 7080
6153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
cgggtgcagg agcagctgag cagcctctgg gaggagaacc aggcactggc cacacaaacc 7140
cgcgaccggc tggcccagca cgaggccggc ctcatggacc tgcgagaggc tttgaaccgg 7200
gcagtggacg ccacacggga ggcccaggag ctcaacagcc gcaaccagga gcgcctggag 7260
gaagccctgc aaaggaagca ggagctgtcc cgggacaatg ccaccctgca ggccactctg 7320
catgcggcta gggacaccct ggccagcgtc ttcagattgc tgcacagcct ggaccaggct 7380
aaggaggagc tggagcgcct cgccgccagc ctggatgggg ctcggacccc actgctgcag 7440
aggatgcaga ccttctcccc ggcgggcagc aagctgcgtc tagtggaggc cgccgaggcc 7500
cacgcacagc agctgggcca gctggcactc aatctgtcca gcatcatcct ggacgtcaac 7560
caggaccgcc tcacccagag ggccatcgag gcctccaacg cctacagccg catcctgcag 7620
gccgtgcagg ctgccgagga tgctgctggc caggccctgc agcaggcgga ccacacgtgg 7680
gcgacggtgg tgcggcaggg cctggtggac cgagcccagc agctcctggc caacagcact 7740
gcactagaag aggccatgct ccaggaacag cagaggctgg gccttgtgtg ggctgccctc 7800
cagggtgcca ggacccagct ccgagatgtc cgggccaaga aggaccagct ggaggcgcac 7860
atccaggcgg cgcaggccat gcttgccatg gacacagacg agacaagcaa gaagatcgca 7920
catgccaagg ctgtggctgc tgaagcccag gacaccgcca cccgtgtgca gtcccagctg 7980
caggccatgc aggagaatgt ggagcggtgg cagggccagt acgagggcct gcggggccag 8040
gacctgggcc aggcagtgct tgacgcaggc cactcagtgt ccaccctgga gaagacgctg 8100
ccccagctgc tggccaagct gagcatcctg gagaaccgtg gggtgcacaa cgccagcctg 8160
gccctgtccg ccagcattgg ccgcgtgcga gagctcattg cccaggcccg gggggctgcc~8220
agtaaggtca aggtgcccat gaagttcaac gggcgctcag gggtgcagct gcgcacccca 8280
cgggatcttg ccgaccttgc tgcctacact gccctcaagt tctacctgca gggcccagag 8340
cctgagcctg ggcagggtac cgaggatcgc tttgtgatgt acatgggcag ccgccaggcc 8400
actggggact acatgggtgt gtctctgcgt gacaagaagg tgcactgggt gtatcagctg 8460
ggtgaggcgg gccctgcagt cctaagcatc gatgaggaca ttggggagca gttcgcagct 8520
gtcagcctgg acaggactct ccagtttggc cacatgtccg tcacagtgga gagacagatg 8580
atccaggaaa ccaagggtga cacggtggcc cctggggcag aggggctgct caacctgcgg 8640
ccagacgact tcgtcttcta cgtcgggggg taccccagta ccttcacgcc ccctcccctg 8700
cttcgcttcc ccggctaccg gggctgcatc gagatggaca cgctgaatga ggaggtggtc 8760
agcctctaca acttcgagag gaccttccag ctggacacgg ctgtggacag gccttgtgcc 8820
cgctccaagt cgaccgggga cccgtggctc acggacggct cctacctgga cggcaccggc 8880
ttcgcccgca tcagcttcga cagtcagatc agcaccacca agcgcttcga gcaggagctg 8940
cggctcgtgt cctacagcgg ggtgctcttc ttcctgaagc agcagagcca gttcctgtgc 9000
ttggccgtgc aagaaggcag cctcgtgctg ttgtatgact ttggggctgg cctgaaaaag 9060
gccgtcccac tgCagCCCCC aCCgCCCCtg acctcggcca gcaaggcgat ccaggtgttc 9120
ctgctggggg gcagccgcaa gcgtgtgctg gtgcgtgtgg agcgggccac ggtgtacagc 9180
gtggagcagg acaatgatct ggagctggcc gacgcctact acctgggggg cgtgccgccc 9240
gaccagctgc ccccgagcct gcgacggctc ttccccaccg gaggctcagt ccgtggctgc 9300
gtcaaaggca tcaaggccct gggcaagtat gtggacctca agcggctgaa cacgacaggc 9360
gtgagcgccg gctgcaccgc cgacctgctg gtggggcgcg ccatgacttt ccatggccac 9420
ggcttccttc gcctggcgct ctcgaacgtg gcaccgctca ctggcaacgt ctactccggc 9480
ttcggcttcc acagcgccca ggacagtgcc ctgctctact accgggcgtc cccggatggg 9540
ctatgccagg tgtccctgca gcagggccgt gtgagcctac agctcctgag gactgaagtg 9600
aaaactcaag cgggcttcgc cgatggtgcc ccccattacg tcgccttcta cagcaatgcc 9660
acgggagtct ggctgtatgt cgatgaccag ctccagcaga tgaagcccca ccggggacca 9720
ccccccgagc tccagccgca gcctgagggg cccccgaggc tcctcctggg aggcctgcct 9780
gagtctggca ccatttacaa cttcagtggc tgcatcagca acgtcttcgt gcagcggctc 9840
ctgggcccac agcgcgtatt tgatctgcag cagaacctgg gcagcgtcaa tgtgagcacg 9900
ggctgtgcac ccgccctgca agcccagacc ccgggcctgg ggcctagagg actgcaggcc 9960
accgcccgga aggcctcccg ccgcagccgt CagCCCgCCC ggcatcctgc ctgcatgctg 10020
cccccacacc tcaggaccac ccgagactcc taccagtttg ggggttccct gtccagtcac 10080
ctggagtttg tgggcatcct ggcccgacat aggaactggc ccagtctctc catgcacgtc 10140
ctcccgcgaa gctcccgagg cctcctcctc ttcactgccc gtctgaggcc cggcagcccc 10200
tccctggcgc tcttcctgag caatggccac ttcgttgcac agatggaagg cctcgggact 10260
cggctccgcg cccagagccg ccagcgctcc cggcctggcc gctggcacaa ggtctccgtg 10320
cgctgggaga agaaccggat cctgctggtg acggacgggg cccgggcctg gagccaggag 10380
gggccgcacc ggcagcacca gggggcagag cacccccagc cccacaccct ctttgtgggc 10440
ggcctcccgg ccagcagcca cagctccaaa cttccggtga ccgtcgggtt cagcggctgt 10500
gtgaagagac tgaggctgca cgggaggccc ctgggggccc ccacacggat ggcaggggtc 10560
acaccctgca tcttgggccc cctggaggcg ggcctgttct tcccaggcag cgggggagtt 10620
7/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
atcactttag aCCtCCCagg agctacactg cctgatgtgg gcctggaact ggaggtgcgg 10680
cccctggcag tcaccggact gatcttccac ttgggccagg cccggacgcc cccctacttg 10740
cagttgcagg tgaccgagaa gcaagtcctg ctgcgggcgg atgacggagc aggggagttc 10800
tccacgtcag tgacccgccc ctcagtgctg tgtgatggcc agtggcaccg gctagcggtg 10860
atgaaaagcg ggaatgtgct ccggctggag gtggacgcgc agagcaacca caccgtgggc 10920
cccttgctgg cggctgcagc tggtgcccca gcccctctgt acctcggggg cctgcctgag 10980
cccatggccg tgcagccctg gccccccgcc tactgcggct gcatgaggag gctggcggtg 11040
aaccggtccc ccgtcgccat gactcgctct gtggaggtcc acggggcagt gggggccagt 11100
ggctgcccag ccgcctag 11118
<210> 9
<211> 11091
<212> DNA
<213> Homo Sapiens
<400> 9
atggcgaagc ggctctgcgc ggggagcgca ctgtgtgttc gcggcccccg gggccccgcg 60
ccgctgctgc tggtcgggct ggcgctgctg ggcgcggcgc gggcgcggga ggaggcgggc 120
ggcggcttca gcctgcaccc gccctacttc aacctggccg agggcgcccg CatCCJCCgCC 180
tccgcgacct gcggagagga ggccccggcg cgcggctccc cgcgccccac cgaggacctt 240
tactgcaagc tggtaggggg ccccgtggcc ggcggcgacc ccaaccagac catccggggc 300
cagtactgtg acatctgcac ggctgccaac agcaacaagg cacaccccgc gagcaatgcc 360
atcgatggca cggagcgctg gtggcagagt ccaccgctgt cccgcggcct ggagtacaac 420
gaggtcaacg tcaccctgga cctgggccag gtcttccacg tggcctacgt cctcatcaag 480
tttgccaact caccccggcc ggacctctgg gtgctggagc ggtccatgga cttcggccgc 540
acctaccagc cctggcagtt ctttgcctcc tccaagaggg actgtctgga gcggttcggg 600
ccacagacgc tggagcgcat cacacgggac gacgcggcca tctgcaccac cgagtactca 660
cgcatcgtgc ccctggagaa cggagagatc gtggtgtccc tggtgaacgg acgtccgggc 720
gccatgaatt tctcctactc gccgctgcta cgtgagttca ccaaggccac caacgtccgc 780
ctgcgcttcc tgcgtaccaa cacgctgctg ggccatctca tggggaaggc gctgcgggac 840
cccacggtca cccgccggta ttattacagc atcaaggata tcagcatcgg aggccgctgt 900
gtctgccacg gccacgcgga tgcctgcgat gccaaagacc ccacggaccc gttcaggctg 960
cagtgcacct gccagcacaa cacctgcggg ggcacctgcg accgctgctg ccccggcttc 1020
aatcagcagc cgtggaagcc tgcgactgcc aacagtgcca acgagtgcca gtcctgtaac 1080
tgctacggcc atgccaccga ctgttactac gaccctgagg tggaccggcg ccgcgccagc 1140
cagagcctgg atggcaccta tcagggtggg ggtgtctgta tcgactgcca gcaccacacc 1200
accggcgtca actgtgagcg ctgcctgccc ggcttctacc gctctcccaa ccaccctctc 1260
gactcgcccc acgtctgccg ccgctgcaac tgcgagtccg acttcacgga tggcacctgc 1320
gaggacctga cgggtcgatg ctactgccgg cccaacttct ctggggagcg gtgtgacgtg 1380
tgtgccgagg gcttcacggg cttcccaagc tgCtaCCCga CgCCCtCgtC CtCCaatgaC 1440
accagggagc aggtgctgcc agccggccag attgtgaatt gtgactgcag cgcggcaggg 1500
acccagggca acgcctgccg gaaggaccca agggtgggac gctgtctgtg caaacccaac 1560
ttccaaggca cccattgtga gctctgcgcg ccagggttct acggccccgg ctgccagccc 1620
tgccagtgtt ccagccctgg agtggccgat gaccgctgtg accctgacac aggccagtgc 1680
aggtgccgag tgggcttcga gggggccaca tgtgatcgct gtgcccccgg ctactttcac 1740
ttccctctct gccagttgtg tggctgcagc cctgcaggaa ccttgcccga gggctgcgat 1800
gaggccggcc gctgcctatg ccagcctgag tttgctggac ctcattgtga ccggtgccgc 1860
cctggctacc atggtttccc caactgccaa gcatgcacct gcgaccctcg gggagccctg 1920
gaccagctct gtggggcggg aggtttgtgc cgctgccgcc ccggctacac aggcactgcc 1980
tgccaggaat gcagccccgg ctttcacggc ttccccagct gtgtcccctg ccactgctct 2040
gctgaaggct ccctgcacgc agcctgtgac ccccggagtg ggcagtgcag ctgccggccc 2100
cgtgtgacgg ggctgcggtg tgacacatgt gtgcccggtg cctacaactt cccctactgc 2160
gaagctggct cttgccaccc tgccggtctg gccccagtgg atcctgccct tcctgaggca 2220
caggttccct gtatgtgccg ggctcacgtg gaggggccga gctgtgaccg ctgcaaacct 2280
gggttctggg gactgagccc cagcaacccc gagggctgta cccgctgcag ctgcgacctc 2340
aggggcacac tgggtggagt tgctgagtgc cagccgggca ccggccagtg cttctgcaag 2400
ccccacgtgt gcggccaggc ctgcgcgtcc tgcaaggatg gcttctttgg actggatcag 2460
gctgactatt ttggctgccg cagctgccgg tgtgacattg gcggtgcact gggccagagc 2520
tgtgaaccga ggacgggcgt ctgccggtgc cgccccaaca cccagggccc cacctgcagc 2580
x/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
gagcctgcga gggaccacta cctcccggac ctgcaccacc tgcgcctgga gctggaggag 2640
gctgccacac ctgagggtca cgccgtgcgc tttggcttca accccctcga gttcgagaac 2700
ttcagctgga ggggctacgc gcagatggca cctgtccagc ccaggatcgt ggccaggctg 2760
aacctgacct cccctgacct tttctggctc gtcttccgat acgtcaaccg gggggccatg 2820
agtgtgagcg ggcgggtctc tgtgcgagag gagggcaggt cggccacctg cgccaactgc 2880
acagcacaga gtcagcccgt ggccttccca cccagcacgg agcctgcctt catcaccgtg 2940
ccccagaggg gcttcggaga gccctttgtg ctgaaccctg gcacctgggc cctgcgtgtg 3000
gaggccgaag gggtgctcct ggactacgtg gttctgctgc ctagcgcata ctacgaggcg 3060
gcgctcctgc agctgcgggt gactgaggcc tgcacatacc gtccctctgc ccagcagtct 3120
ggcgacaact gcctcctcta cacacacctc cccctggatg gcttcccctc ggccgccggg 3180
ctggaggccc tgtgtcgcca ggacaacagc ctgccccggc cctgccccac ggagcagctc 3240
agcccgtcgc acccgccact gatcacctgc acgggcagtg atgtggacgt ccagcttcaa 3300
gtggcagtgc cacagccagg ccgctatgcc ctagtggtgg agtacgccaa tgaggatgcc 3360
cgccaggagg tgggcgtggc cgtgcacacc ccacagcggg ccccccagca ggggctgctc 3420
tccctgcacc cctgcctgta cagcaccctg tgccggggca ctgcccggga tacccaggac 3480
cacctggctg tcttccacct ggactcggag gccagcgtga ggctcacagc cgaacaggca 3540
cgcttcttcc tgcacggggt cactctggtg cccattgagg agttcagccc ggagttcgtg 3600
gagccccggg tcagctgcat cagcagccac ggcgcctttg gccccaacag tgccgcctgt 3660
ctgccctcgc gcttcccaaa gccgccccag cccatcatcc tcagggactg ccaggtgatc 3720
ccgctgccgc ccggcctccc gctgacccac gcgcaggatc tcactccagc catgtcccca 3780
gctggacccc gaCCtCggCC CCCCaCCgCt gtggaCCCtg atgcagagcc caccctgctg 3840
cgtgagcccc aggccaccgt ggtcttcacc acccatgtgc ccacgctggg ccgctatgcc 3900
ttcctgctgc acggctacca gccagcccac cccaccttcc ccgtggaagt cctcatcaac 3960
gccggccgcg tgtggcaggg ccacgccaac gccagcttct gtccacatgg ctacggctgc 4020
cgcaccctgg tggtgtgtga gggccaggcc ctgctggacg tgacccacag cgagctcact 4080
gtgaccgtgc gtgtgcccaa gggccggtgg ctctggctgg attatgtact cgtggtccct 4140
gagaacgtct acagctttgg ctacctccgg gaggagcccc tggataaatc ctatgacttc 4200
atcagccact gcgcagccca gggctaccac atcagcccca gcagctcatc cctgttctgc 4260
cgaaacgctg ctgcttccct ctccctcttc tataacaacg gagcccgtcc atgtggctgc 4320
cacgaagtag gtgctacagg ccccacgtgt gagcccttcg ggggccagtg tccctgccat 4380
gcccatgtca ttggccgtga ctgctcccgc tgtgccaccg gatactgggg cttccccaac 4440
tgcaggccct gtgactgcgg tgcccgcctc tgtgacgagc tcacgggcca gtgcatctgc 4500
ccgccacgca ccatcccgcc cgactgcctg ctgtgccagc cccagacctt tggctgccac 4560
cccctggtcg gctgtgagga gtgtaactgc tcagggcccg gcatccagga gctcacagac 4620
cctacctgtg acacagacag cggccagtgc aagtgcagac ccaacgtgac tgggcgccgc 4680
tgtgatacct gctctccggg cttccatggc tacccccgct gccgcccctg tgactgtcac 4740
gaggcgggca ctgcgcctgg cgtgtgtgac cccctcacag ggcagtgcta ctgtaaggag 4800
aacgtgcagg gccccaaatg tgaccagtgc agccttggga ccttctcact ggatgctgcc 4860
aaccccaaag gttgcacccg ctgcttctgc tttggggcca cggagcgctg ccggagctcg 4920
tcctacaccc gccaggagtt cgtggatatg gagggatggg tgctgctgag cactgaccgg 4980
caggtggtgc cccacgagcg gcagccaggg acggagatgc tccgtgcaga cctgcggcac 5040
gtgcctgagg ctgtgcccga ggctttcccc gagctgtact ggcaggcccc accctcctac 5100
ctgggggacc gggtgtcatc ctacggtggg accctccgtt atgaactgca ctcagagacc 5160
cagcggggag atgtctttgt ccccatggag agcaggccgg atgtggtgct gcagggcaac 5220
cagatgagca tcacattcct ggagccggca taccccacgc ctggccacgt tcaccgtggg 5280
cagctgcagc tggtggaggg gaacttccgg catacggaga cgcgcaacac tgtgtcccgc 5340
gaggagctca tgatggtgct ggccagcctg gagcagctgc agatccgtgc cctcttctca 5400
cagatctcct cggctgtctt cctgcgcagg gtggcactgg aggtggccag cccagcaggc 5460
cagggggccc tggccagcaa tgtggagctg tgcctgtgcc ccgccagcta ccggggggac 5520
tcatgccagg aatgtgcccc cggcttctat cgggacgtca aaggtctctt cctgggccga 5580
tgtgtccctt gtcagtgcca tggacactca gaccgctgcc tccctggctc tggcgtctgt 5640
gtggactgcc agcacaacac cgaaggggcc cactgtgagc gctgccaggc tggcttcgtg 5700
agcagcaggg acgaccccag cgccccctgt gtcagctgcc cctgccccct ctcagtgcct 5760
tccaacaact tcgccgaggg ctgtgtcctg cgaggcggcc gcacccagtg cctctgcaaa 5820
cctggttatg caggtgcctc ctgcgagcgg tgtgcgcccg gattctttgg gaacccactg 5880
gtgctgggca gctcctgcca gccatgcgac tgcagcggca acggtgaccc caacttgctc 5940
ttcagcgact gcgaccccct gacgggcgcc tgccgtggct gcctgcgcca caccactggg 6000
ccccgctgcg agatctgtgc ccccggcttc tacggcaacg CCCtgCtgCC CggCaaCtgC 6060
acccggtgcg actgtacccc atgtgggaca gaggcctgcg acccccacag cgggcactgc 6120
9/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
ctgtgcaagg cgggcgtgac tgggcggcgc tgtgaccgct gccaggaggg acattttggt 6180
ttcgatggct gcgggggctg ccgcccgtgt gcttgtggac cggccgccga gggctccgag 6240
tgccaccccc agagcggaca gtgccactgc cgaccaggga ccatgggacc ccagtgccgc 6300
gagtgtgccc ctggctactg ggggctccct gagcagggct gcaggcgctg ccagtgccct 6360
gggggccgct gtgaccctca cacgggccgc tgcaactgcc ccccggggct cagcggggag 6420
cgctgcgaca cctgcagcca gcagcatcag gtgcctgttc caggcgggcc tgtgggccac 6480
agcatccact gtgaagtgtg tgaccactgt gtggtcctgc tcctggatga cctggaacgg 6540
gccggcgccc tcctccccgc cattcacgag caactgcgtg gcatcaatgc cagctccatg 6600
gcctgggccc gtctgcacag gctgaacgcc tccatcgctg acctgcagag ccagctccgg 6660
agccccctgg gcccccgcca tgagacggca cagcagctgg aggtgctgga gcagcagagc 6720
acaagcctcg ggcaggacgc acggcggcta ggcggccagg cagccgtggg gacccgagac 6780
caggcgagcc aattgctggc cggcaccgag gccacactgg gccatgcgaa gacgctgttg 6840
gcggccatcc gggctgtgga ccgcaccctg agcgagctca tgtcccagac gggccacctg 6900
gggctggcca atgcctcggc tccatcaggt gagcagctgc tccggacact ggccgaggtg 6960
gagcggctgc tctgggagat gcgggcccgg gacctggggg ccccgcaggc agcagctgag 7020
gctgagttgg ctgcagcaca gagattgctg gcccgggtgc aggagcagct gagcagcctc 7080
tgggaggaga accaggcact ggccacacaa acccgcgacc ggctggccca gcacgaggcc 7140
ggcctcatgg acctgcgaga ggctttgaac cgggcagtgg acgccacacg ggaggcccag 7200
gagctcaaca gccgcaacca ggagcgcctg gaggaagccc tgcaaaggaa gcaggagctg 7260
tcccgggaca atgccaccct gcaggccact ctgcatgcgg ctagggacac cctggccagc 7320
gtcttcagat tgctgcacag cctggaccag gctaaggagg agctggagcg cctcgccgcc 7380
agcctggatg gggctcggac cccactgctg cagaggatgc agaccttctc cccggcgggc 7440
agcaagctgc gtctagtgga ggccgccgag gcccacgcac agcagctggg ccagctggca 7500
ctcaatctgt ccagcatcat cctggacgtc aaccaggacc gcctcaccca gagggccatc 7560
gaggcctcca acgcctacag ccgcatcctg caggccgtgc aggctgccga ggatgctgct 7620
ggccaggccc tgcagcaggc ggaccacacg tgggcgacgg tggtgcggca gggcctggtg 7680
gaccgagccc agcagctcct ggccaacagc actgcactag aagaggccat gctccaggaa 7740
cagcagaggc tgggccttgt gtgggctgcc ctccagggtg ccaggaccca gctccgagat 7800
gtccgggcca agaaggacca gctggaggcg cacatccagg cggcgcaggc catgcttgcc 78~60
atggacacag acgagacaag caagaagatc gcacatgcca aggctgtggc tgctgaagcc 7920
caggacaccg ccacccgtgt gcagtcccag ctgcaggCCa tgcaggagaa tgtggagcgg 7980
tggcagggcc agtacgaggg cctgcggggc caggacctgg gccaggcagt gcttgacgca 8040
ggccactcag tgtccaccct ggagaagacg ctgccccagc tgctggccaa gctgagcatc 8100
ctggagaacc gtggggtgca caacgccagc ctggccctgt ccgccagcat tggccgcgtg 8160
cgagagctca ttgcccaggc ccggggggct gccagtaagg tcaaggtgcc catgaagttc 8220
aacgggcgct caggggtgca gctgcgcacc ccacgggatc ttgccgacct tgctgcctac 8280
actgccctca agttctacct gcagggccca gagcctgagc ctgggcaggg taccgaggat 8340
cgctttgtga tgtacatggg cagccgccag gccactgggg actacatggg tgtgtctctg 8400
cgtgacaaga aggtgcactg ggtgtatcag ctgggtgagg cgggccctgc agtcctaagc 8460
atcgatgagg acattgggga gcagttcgca gctgtcagcc tggacaggac tctccagttt 8520
ggccacatgt ccgtcacagt ggagagacag atgatccagg aaaccaaggg tgacacggtg 8580
gcccctgggg cagaggggct gctcaacctg cggccagacg acttcgtctt ctacgtcggg 8640
gggtacccca gtaccttcac gccccctccc ctgcttcgct tccccggcta ccggggctgc 8700
atcgagatgg acacgctgaa tgaggaggtg gtcagcctct acaacttcga gaggaccttc 8760
cagctggaca cggctgtgga caggccttgt gcccgctcca agtcgaccgg ggacccgtgg 8820
ctcacggacg gctcctacct ggacggcacc ggcttcgccc gcatcagctt cgacagtcag 8880
atcagcacca ccaagcgctt cgagcaggag ctgcggctcg tgtcctacag cggggtgctc 8940
ttcttcctga agcagcagag ccagttcctg tgcttggccg tgcaagaagg cagcctcgtg 9000
ctgttgtatg actttggggc tggcctgaaa aaggccgtcc cactgcagcc cccaccgccc 9060
ctgacctcgg ccagcaaggc gatccaggtg ttcctgctgg ggggcagccg caagcgtgtg 9120
ctggtgcgtg tggagcgggc cacggtgtac agcgtggagc aggacaatga tctggagctg 9180
gccgacgcct actacctggg gggcgtgccg cccgaccagc tgcccccgag cctgcgacgg 9240
ctcttcccca ccggaggctc agtccgtggc tgcgtcaaag gcatcaaggc cctgggcaag 9300
tatgtggacc tcaagcggct gaacacgaca ggcgtgagcg ccggctgcac cgccgacctg 9360
ctggtggggc gcgccatgac tttccatggc cacggcttcc ttcgcctggc gctctcgaac 9420
gtggcaccgc tcactggcaa cgtctactcc ggcttcggct tccacagcgc ccaggacagt 9480
gccctgctct actaccgggc gtccccggat gggctatgcc aggtgtccct gcagcagggc 9540
cgtgtgagcc tacagctcct gaggactgaa gtgaaaactc aagcgggctt cgccgatggt 9600
gccccccatt acgtcgcctt ctacagcaat gccacgggag tctggctgta tgtcgatgac 9660
10153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
cagctccagc agatgaagcc ccaccgggga ccaccccccg agctccagcc gcagcctgag 9720
gggcccccga ggctcctcct gggaggcctg cctgagtctg gcaccattta caacttcagt 9780
ggctgcatca gcaacgtctt cgtgcagcgg ctcctgggcc cacagcgcgt atttgatctg 9840
cagcagaacc tgggcagcgt caatgtgagc acgggctgtg cacccgccct gcaagcccag 9900
accccgggcc tggggcctag aggactgcag gccaccgccc ggaaggcctc ccgccgcagc 9960
cgtcagcccg cccggcatcc tgcctgcatg ctgcccccac acctcaggac cacccgagac 10020
tcctaccagt ttgggggttc cctgtccagt cacctggagt ttgtgggcat cctggcccga 10080
cataggaact ggcccagtct ctccatgcac gtcctcccgc gaagctcccg aggcctcctc 10140
ctcttcactg cccgtctgag gcccggcagc ccctccctgg cgctcttcct gagcaatggc 10200
cacttcgttg cacagatgga aggcctcggg actcggctcc gcgcccagag ccgccagcgc 10260
tcccggcctg gccgctggca caaggtctcc gtgcgctggg agaagaaccg gatcctgctg 10320
gtgacggacg gggcccgggc ctggagccag gaggggccgc accggcagca ccagggggca 10380
gagcaccccc agccccacac cctctttgtg ggcggcctcc cggccagcag ccacagctcc 10440
aaacttccgg tgaccgtcgg gttcagcggc tgtgtgaaga gactgaggct gcacgggagg 10500
cccctggggg cccccacacg gatggcaggg gtcacaccct gcatcttggg ccccctggag 10560
gcgggcctgt tcttcccagg cagcggggga gttatcactt tagacctccc aggagctaca 10620
ctgcctgatg tgggcctgga actggaggtg cggcccctgg cagtcaccgg actgatcttc 10680
cacttgggcc aggcccggac gcccccctac ttgcagttgc aggtgaccga gaagcaagtc 10740
ctgctgcggg cggatgacgg agcaggggag ttctccacgt cagtgacccg cccctcagtg 10800
ctgtgtgatg gccagtggca ccggctagcg gtgatgaaaa gcgggaatgt gctccggctg 10860
gaggtggacg cgcagagcaa ccacaccgtg ggccccttgc tggcggctgc agctggtgcc 10920
ccagcccctc tgtacctcgg gggcctgcct gagcccatgg ccgtgcagcc ctggcccccc 10980
gcctactgcg gctgcatgag gaggctggcg gtgaaccggt CCCCCgtCgC CatgaCtCgC 11040
tctgtggagg tccacggggc agtgggggcc agtggctgcc cagccgccta g 11091
<210> 10
<211> 1014
<212> DNA
<213> Homo sapiens
<400> 10
atgacaaaca acagcggctc caaagccgaa ctcgttgtgg gagggaaata caaactggtg 60
cggaagatcg ggtctggctc ctttggagac gtttatctgg gcatcaccac caccaacggc 120
gaggacgtag cagtgaagct ggaatctcag aaggtcaagc acccccagtt gctgtatgag 180
agcaaactct acacgattct tcaaggtggg gttggcatcc cccacatgca ctggtatggt 240
caggaaaaag acaacaatgt gctagtcatg gaccttctgg gacccagcct cgaagacctc 300
tttaatttct gttcaagaag gttcaccatg aaaactgtac ttatgttagc cgaccagatg 360
atcagcagaa ttgaatacgt gcatacaaag aattttctac accgagacat taaaccagat 420
aacttcctga tgggtactgg gcgtcactgt aataagttgt tccttattga ttttggtttg 480
gccaaaaagt acagagacaa caggaccagg caacacatac cgtacagaga agataaacac 540
ctcattggca ctgtccgata tgccagcatc aatgcacatc ttggtattga gcagagccgc 600
cgagatgaca tggaatcctt aggctacgtt ttcatgtatt ttaatagaac cagcctgccg 660
tggcaaggac taagggctat gacaaaaaaa caaaaatatg aaaagattag tgagaagaag 720
atgtccaccc ctgttgaagt tttatgtaag gggtttcctg cagaattcgc catgtacttg 780
aactactgtc gtgggctgcg ctttgaggaa gtcccagatt acatgtatct gaggcagcta 840
ttccgcattc ttttcaggac cctgaaccac caatatgact acacatttga ttggacgatg 900
ttaaagcaga aagcagcaca gcaggcagcc tcttccagtg ggcagggtca gcaggcccaa 960
acccagacag gcaagcaaac tgaaaaaaac aagaataatg tgaaagataa ctaa 1014
<210> 11
<211> 2667
<212> DNA
<213> Homo sapiens
<400> 11
atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggac gcaggctgcc 60
gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggac ggtgattgcc 120
aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggca ggcttcagcc 180
tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccag ctctggcctg 24O
11/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccc caagtgcatc 300
atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggt ggagatcaag 360
gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctgga gatctcggag 420
gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccaga ctcaggaagc 480
tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctgga gatcaagacg 540
cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctgga ccgcgagacg 600
cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgcc gcgcctgggc 660
accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggt gtttagcgag 720
tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgt catccgcctc 780
aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactcctt ctatggctac 840
gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcct ggtcactgtc 900
actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgca ggctaaggac 960
ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgct ggacaccaat 1020
gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtgga ggtcagcgag 1080
agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcga ctcaggcctc 1140
aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgca ggaatatgag 1200
agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacga ccaatacaac 1260
ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaa gtcctttacc 1320
gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagcccta ctaccaggtc 1380
attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgc tcgcgacccc 1440
gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggt gcgggacatg 1500
cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgc gctgcgatcc 1560
tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaagga cggcggcctt 1620
ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaa cgacaacacc 1680
ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacat accccgcaac 1740
tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatga gggcgaaaat 1800
ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaat agaccaggtc 1860
aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctc ctatgagctt 1920
atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctct cgtcctaatc 1980
tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaactt gtccttgatt 2040
ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgat cttcgtggca 2100
atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagtaa ttgtttaacc 2160
atcacttgtc tcctcggctg ttttataaaa ggacaaaaca gcaagtgtct gcattgcatc 2220
tcggtttctc ccattagcga ggagcaagac aaaaagacag aggagaaagt gagcctaagg 2280
ggaaagagaa ttgctgagta ctcctatggg catcaaaaga aatcaagcaa gaagaaaaaa 2340
atcagtaaga atgacatccg cctggtaccc cgggatgtgg aggagacaga caagatgaac 2400
gttgtcagtt gctcttccct gacctcctcc ctcaactatt ttgactacca ccagcagacg 2460
ctgcccctgg gctgccgccg ctctgagagc actttcctga atgtggagaa ccagaatacc 2520
cgcaacacca gtgctaacca catctaccat cactctttca acagccaggg gccccagcag 2580
cctgacctga ttatcaacgg tgtgcctctg cctgaggtga gtgcagctaa gtggctctgt 2640
gaggttctcc caggtctcct tctttag 2667
<210> 12
<211> 2568
<212> DNA
<213> Homo sapiens
<400> 12
atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggac gcaggctgcc 60
gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggac ggtgattgcc 120
aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggca ggcttcagcc 180
tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccag ctctggcctg 240
ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccc caagtgcatc 300
atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggt ggagatcaag 360
gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctgga gatctcggag 420
gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccaga ctcaggaagc 480
tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctgga gatcaagacg 540
cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctgga ccgcgagacg 600
cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgcc gcgcctgggc 660
12/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggt gtttagcgag 720
tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgt catccgcctc 780
aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactcctt ctatggctac 840
gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcct ggtcactgtc 900
actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgca ggctaaggac 960
ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgct ggacaccaat 1020
gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtgga ggtcagcgag 1080
agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcga ctcaggcctc 1140
aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgca ggaatatgag 1200
agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacga ccaatacaac 1260
ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaa gtcctttacc 1320
gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagcccta ctaccaggtc 1380
attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgc tcgcgacccc 1440
gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggt gcgggacatg 1500
cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgc gctgcgatcc 1560
tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaagga cggcggcctt 1620
ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaa cgacaacacc 1680
ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacat accccgcaac 1740
tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatga gggcgaaaat 1800
ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaat agaccaggtc 1860
aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctc ctatgagctt 1920
atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctct cgtcctaatc 1980
tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaactt gtccttgatt 2040
ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgat cttcgtggca 2100
atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagaat tgctgagtac 2160
tcctatgggc atcaaaagaa atcaagcaag aagaaaaaaa tcagtaagaa tgacatccgc 2220
ctggtacccc gggatgtgga ggagacagac aagatgaacg ttgtcagttg CtCttCCCtg 2280
acctcctccc tcaactattt tgactaccac cagcagacgc tgcccctggg ctgccgccgc 2340
tctgagagca ctttcctgaa tgtggagaac cagaataccc gcaacaccag tgctaaccac 2400
atctaccatc actctttcaa cagccagggg ccccagcagc ctgacctgat tatcaacggt 2460
gtgcctctgc ctgagactga aaactattct tttgactcca actacgtgaa tagccgagcc 2520
catttaatca agaggtatgt tggtttgctt gcttattgct gcaactaa 2568
<210> 13
<211> 990
<212> DNA
<213> Homo Sapiens
<400> 13
atggtgacga aggcctttgt cttgttggcc atctttgcag aagcctctgc aaaatcgtgt 60
gctccaaata aagcagatgt cattcttgtg ttttgctatc ccaaaaccat catcaccaaa 120
atccccgagt gtccctatgg atgggaagtt catcagctgg ccctcggagg gctgtgttac 180
aatggggtcc acgaaggagg ttactaccaa tttgtgatcc cagatttatc acctaaaaac 240
aagtcctatt gtggaaccca gtctgagtac aagccaccta tctatcactt ctacagtcac 300
atcgtttcca atgacaccac agtgattgta aaaaaccagc ctgtcaacta ctccttctcc 360
tgcacctacc actccaccta cttggtgaac caggctgcct ttgaccagag agtggccact 420
gttcacgtga agaacgggag catgggcaca tttgagagcc aactgtctct caacttctac 480
actaatgcca agttctccat caagaaagaa gctccctttg tcctggaggc atccgaaatc 540
ggttcagatc tgtt,tgcagg agtggaagcc aaagggttaa gcattaggtt taaagtggtc 600
ttgaacagct gttgggccac cccctcggct gacttcatgt atcccttgca gtggcagctg 660
atcaacaagg gctgccccac ggatgaaacc gtcctcgtgc atgagaatgg gagagatcac 720
agggcaacct tccaattcaa tgctttccgg ttccagaaca tccccaaact ctccaaggtg 780
tggttacact gtgagacgtt catctgcgac agtgagaaac tctcctgccc agtgacctgc 840
gataaacgga agcgcctcct gcgagaccag accgggggag tcctggtcgt ggagctctcc 900
ctgcggagca ggggattttc cagtctctat agcttctcag atgttctcca ccacctcatc 960
atgatgttgg ggatttgtgc cgtgttatag 990
<210> 14
<211> 699
13/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
<212> DNA
<213> Homo sapiens
<400> 14
atgctctaca caaggaaaaa cctgacctgc gcacaaacca tcaactcctc agcttttggg 60
aacttgaatg tgaccaagaa aaccaccttc attgtccatg gattcaggcc aacaggctcc 120
cctcctgttt ggatggatga cttagtaaag ggtttgctct ctgttgaaga catgaacgta 180
gttgttgttg attggaatcg aggagctaca actttaatat atacccatgc ctctagtaag 240
accagaaaag tagccatggt cttgaaggaa tttattgacc agatgttggc agaaggagct 300
tctcttgatg acatttacat gatcggagta agtctaggag cccacatatc tgggtttgtt 360
ggagagatgt acgatggatg gctggggaga attacaggcc tcgaccctgc aggcccttta 420
ttcaacggga aacctcacca agacagatta gatcccagtg atgcgcagtt tgttgatgtc 480
atccattccg acactgatgg taacgctcct ttccttgtgg cactgggcta caaggagcca 540
ttaggaaaca tagacttcta cccaaatgga ggattggatc aacctggctg ccccaaaaca 600
atattgggag gaaatgttaa ggaaatgata caggcttcct atatcttttt ccttaaaaac 660
gactctatgg acttaagttc accgaaggaa gtggaatga 699
<210> 15
<211> 1359
<212> DNA
<213> Homo Sapiens
<400> 15
atgttgagat tctacttatt catcagtttg ttgtgcttgt caagatcaga cgcagaagaa 60
acatgtcctt cattcaccag gctgagcttt cacagtgcag tggttggtac gggactaaat 120
gtgaggctga tgctctacac aaggaaaaac ctgacctgcg cacaaaccat caactcctca 180
gcttttggga acttgaatgt gaccaagaaa accaccttca ttgtccatgg attcaggcca 240
acaggctccc ctcctgtttg gatggatgac ttagtaaagg gtttgctctc tgttgaagac 300
atgaacgtag ttgttgttga ttggaat~ga ggagctacaa ctttaatata tacccatgcc 360
tctagtaaga ccagaaaagt agccatggtc ttgaaggaat ttattgacca gatgttggca 420
gaaggagctt ctcttgatga catttacatg atcggagtaa gtctaggagc ccacatatct 480
gggtttgttg gagagatgta cgatggatgg ctggggagaa ttacaggcct cgaccctgca 540
ggccctttat tcaacgggaa acctcaccaa gacagattag atcccagtga tgcgcagttt 600
gttgatgtca tccattccga cactgatgca ctgggctaca aggagccatt aggaaacata 660
gacttctacc caaatggagg attggatcaa cctggctgcc ccaaaacaat attgggagga 720
tttcagtatt ttaaatgtga ccaccagagg tctgtatacc tgtacctgtc ttccctgaga 780
gagagctgca ccatcactgc gtatccctgt gactcctacc aggattatag gaatggcaag 840
tgtgtcagct gcggcacgtc acaaaaagag tcctgtcccc ttctgggcta ttatgctgat 900
aattggaaag accatctaag ggggaaagat cctccaatga cgaaggcatt ctttgacaca 960
gctgaggaga gcccattctg catgtatcat tactttgtgg atattataac atgggacaag 1020
aatgtaagaa gaggggacat taccatcaaa ttgagagaca aagctggaaa cacccacaga 1080
tccaaaatca tcagtaatga acccaccaca tttcagaaat atcaccaagt gagtctactt 1140
gcaagattta atcaagatct ggataaagtg gctgcaattt ccttgatgtt ctctacagga 1200
tctctaatag gcccaaggta caagctcagg attctccgaa tgaagttaag gtcccttgcc 1260
catccggaga ggcctcagct gtgtcggtat gatcttgtcc tgatggaaaa cgttgaaaca 1320
gtcttccaac ctattctttg cccagagttg cagttgtaa 1359
<210> 16
<211> 1353
<212> DNA
<213> Homo Sapiens
<400> 16
atggggctcc ggagccacca cctcagcctg ggccttctgc ttctgtttct actccctgca 60
gagtgcctgg gagctgaggg ccggctggct ctcaagctgt tccgtgacct ctttgccaac 120
tacacaagtg ccctgagacc tgtggcagac acagaccaga ctctgaatgt gaccctggag 180
gtgacactgt cccagatcat cgacatggat gaacggaacc aggtgctgac cctgtatctg 240
tggatacggc aggagtggac agatgcctac ctacgatggg accccaatgc ctatggtggc 300
ctggatgcca tccgcatccc cagcagtctt gtgtggcggc cagacatcgt actctataac 360
14153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
aaagccgacg cgcagcctcc aggttccgcc agcaccaacg tggtcctgcg ccacgatggc 420
gccgtgcgct gggacgcgcc ggccatcacg cgcagctcgt gccgcgtgga tgtagcagcc 480
ttcccgttcg acgcccagca ctgcggcctg acgttcggct cctggactca cggcgggcac 540
caactggatg tgcggccgcg cggcgctgca gccagcctgg cggacttcgt ggagaacgtg 600
gagtggcgcg tgctgggcat gccggcgcgg cggcgcgtgc tcacctacgg ctgctgctcc 660
gagccctacc ccgacgtcac cttcacgctg ctgctgcgcc gccgcgccgc cgcctacgtg 720
tgcaacctgc tgctgccctg cgtgctcatc tcgctgcttg cgccgctcgc cttccacctg 780
cctgccgact caggcgagaa ggtgtcgctg ggcgtcaccg tgctgctggc gctcaccgtc 840
ttccagttgc tgctggccga gagcatgcca ccggccgaga gcgtgccgct catcgggaag 900
tactacatgg ccactatgac catggtcaca ttctcaacag cactcaccat ccttatcatg 960
aacctgcatt actgtggtcc cagtgtccgc ccagtgccag cctgggctag ggccctcctg 1020
ctgggacacc tggcacgggg cctgtgcgtg cgggaaagag gggagccctg tgggcagtcc 1080
aggccacctg agttatctcc tagcccccag tcgcctgaag gaggggctgg ccccccagcg 1140
ggcccttgcc acgagccacg atgtctgtgc cgccaggaag ccctactgca ccacgtagcc 1200
accattgcca ataccttccg cagccaccga gctgcccagc gctgccatga ggactggaag 1260
cgcctggccc gtgtgatgga ccgcttcttc ctggccatct tcttctccat ggccctggtc 1320
atgagcctcc tggtgctggt gcaggccctg tga 1353
<210> 17
<211> 768
<212> DNA
<213> Homo Sapiens
<400> 17
atggttaagg gtgagaaagg ccccaagggc aagaagatca ccctcaaggt ggccaggaat 60
tgcatcaaaa tcacttttga tgggaaaaag cgccttgact tgagcaagat gggaattacc 120
,accttcccca agtgtattct gcgccttagt gacatggacg agctggacct tagccggaat 180
cttatcagga agatccctga ctccatctcc aagttccaga acctccggtg gctggacctg 240
cacagcaact acatagacaa gctgcctgag tccattggcc agatgaccag cctgctctac 300
ctcaacgtca gcaacaaccg gctgaccagc aacgggctgc ccgtggagct gaagcaactc 360
aagaacatcc gcgctgtgaa cctaggcttg aaccacctgg acagcgtgcc caccacactg 420
ggggccctga aggagctcca cgaggtaggg ctccatgaca acctactgaa caacatcccc 480
gtgagcatct ccaagctccc caagctgaaa aagctcaaca taaagcggaa cccctttcca 540
aagccaggtg agtcggaaat attcatagac tccatcagga ggctggagaa cttgtatgtt 600
gtggaggaga aggatctgtg tgcggcttgc ctgagaaaat gccaaaacgc ccgggacaac 660
ctgaatagaa tcaagaacat ggccacgacg acaccgagaa agaccatctt tcccaatctg 720
atctcaccca attccatggc caaggactcc tgggaagact ggaggtga 768
<210> 18
<211> 645
<212> DNA
<213> Homo Sapiens
<400> 18
atgcaggcag gaactcagtc aacgcatgag tctctgaagc ctcagagggt acaatttcag 60
tcccgaaatt ttcacaacat tttgcaatgg cagcctggga gggcacttac tggcaacagc 120
agtgtctatt ttgtgcagta caaaatatat ggacagagac aatggaaaaa taaagaagac 180
tgttggggta ctcaagaact ctcttgtgac cttaccagtg aaacctcaga catacaggaa 240
ccttattacg ggagggtgag ggcggcctcg gctgggagct actcagaatg gagcatgacg 300
ccgcggttca ctccctggtg ggaaacaaaa atagatcctc cagtcatgaa tataacccaa 360
gtcaatggct ctttgttggt aattctccat gctccaaatt taccatatag ataccaaaag 420
gaaaaaaatg tatctataga agattactat gaactactat accgagtttt tataattaac 480
aattcactag aaaaggagca aaaggtttat gaaggggctc acagagcggt tgaaattgaa 540
gctctaacac cacactccag ctactgtgta gtggctgaaa tatatcagcc catgttagac 600
agaagaagtc agagaagtga agagagatgt gtggaaattc catga 645
<210> 19
<211> 696
<212> DNA
15/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
<213> Homo Sapiens
<400> 19
atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttac tggtgtagca 60
ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttca gtcccgaaat 120
tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacag cagtgtctat 180
tttgtgcagt acaaaatata tggacagaga caatggaaaa ataaagaaga ctgttggggt 240
actcaagaac tctcttgtga ccttaccagt gaaacctcag acatacagga accttattac 300
gggagggtga gggcggcctc ggctgggagc tactcagaat ggagcatgac gccgcggttc 360
actccctggt gggaaacaaa aatagatcct ccagtcatga atataaccca agtcaatggc 420
tctttgttgg taattctcca tgctccaaat ttaccatata gataccaaaa ggaaaaaaat 480
gtatctatag aagattacta tgaactacta taccgagttt ttataattaa caattcacta 540
gaaaaggagc aaaaggttta tgaaggggct cacagagcgg ttgaaattga agctctaaca 600
ccacactcca gctactgtgt agtggctgaa atatatcagc ccatgttaga cagaagaagt 660
cagagaagtg aagagagatg tgtggaaatt ccatga 696
<210> 20
<211> 792
<212> DNA
<213> Homo Sapiens
<400> 20
atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttac tggtgtagca 60
ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttca gtcccgaaat 120
tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacag cagtgtctat 180
tttgtgcagt acaaaatcat gttctcatgc agcatgaaaa gctctcacca gaagccaagt 240
ggatgctggc agcacatttc ttgtaacttc ccaggctgca gaacattggc taaatatgga 300
cagagacaat ggaaaaataa agaagactgt tggggtactc aagaactctc ttgtgacctt 360
accagtgaaa cctcagacat acaggaacct tattacggga gggtgagggc ggcctcggct 420
gggagctact cagaatggag catgacgccg Cggttcactc cctggtggga aacaaaaata 480
gatcctccag tcatgaatat aacccaagtc aatggctctt tgttggtaat tctccatgct 540
ccaaatttac catatagata ccaaaaggaa aaaaatgtat ctatagaaga ttactatgaa 600
ctactatacc gagtttttat aattaacaat tcactagaaa aggagcaaaa ggtttatgaa 660
ggggctcaca gagcggttga aattgaagct ctaacaccac actccagcta ctgtgtagtg 720
gctgaaatat atcagcccat gttagacaga agaagtcaga gaagtgaaga gagatgtgtg 780
gaaattccat ga 792
<210> 21
<211> 780
<212> DNA
<213> Homo Sapiens
<400> 21
atgtatgtat tatctccagt ggaatttata attctacaac ttttatttat tcaggccatt 60
tccagcagtt taaaaggttt cctttcagct atgagactgg ctcatagagg ctgtaatgtt 120
gatacaccag tttcaacgct cacaccagtg aagacttcag aatttgaaaa ctttaaaact 180
aaaatggtta tcacatccaa aaaagactat cctctaagta agaattttcc atattccttg 240
gaacatcttc agacttctta ctgtgggctt gtccgagttg atatgcgtat gctttgctta 300
aaaagcctta ggaaattaga cttgagtcac aaccatataa aaaagcttcc agctacaatt 360
ggagacctca tacaccttca agaacttaac ctgaatgaca atcacttgga gtcatttagt 420
gtagccttgt gtcattctac actccagaag tcacttcgga gtttggacct cagcaagaac 480
aaaatcaagg cactccctgt gcagttttgc cagctccagg aacttaagaa tttaaaactt 540
gacgataatg aattgattca atttccttgc aagataggac aactaataaa ccttcgcttt 600
ttgtcagcag ctcgaaataa gcttccattt ttgcctagtg aatttagaaa tttatccctt 660
gaatacttgg atctttttgg aaatactttt gaacaaccaa aagtccttcc agtaataaag 720
ctgcaagcac cattaacttt attggaatct tctgcacgaa ccatattaca taataggtaa 780
<210> 22
16/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
<211> 1251
<212> DNA
<213> Homo Sapiens
<400> 22
atgaagctac actgtgaggt ggaggtgatc agccggcact tgcccgcctt ggggcttagg 60
aaccggggca agggcgtccg agccgtgttg agcctctgtc agcagacttc caggagtcag 120
ccgccggtcc gagccttcct gctcatctcc accctgaagg acaagcgcgg gacccgctat 180
gagctaaggg agaacattga gcaattcttc accaaatttg tagatgaggg gaaagccact 240
gttcggttaa aggagcctcc tgtggatatc tgtctaagta aggccatttc cagcagttta 300
aaaggtttcc tttcagctat gagactggct catagaggct gtaatgttga tacaccagtt 360
tcaacgctca caccagtgaa gacttcagaa tttgaaaact ttaaaactaa aatggttatc 420
acatccaaaa aagactatcc tctaagtaag aattttccat attccttgga acatcttcag 480
acttcttact gtgggcttgt ccgagttgat atgcgtatgc tttgcttaaa aagccttagg 540
aaattagact tgagtcacaa ccatataaaa aagcttccag ctacaattgg agacctcata 600
caccttcaag aacttaacct gaatgacaat cacttggagt catttagtgt agccttgtgt 660
cattctacac tccagaagtc acttcggagt ttggacctca gcaagaacaa aatcaaggca 720
ctccctgtgc agttttgcca gctccaggaa cttaagaatt taaaacttga cgataatgaa 780
ttgattcaat ttccttgcaa gataggacaa ctaataaacc ttcgcttttt gtcagcagct 840
cgaaataagc ttccattttt gcctagtgaa tttagaaatt tatcccttga atacttggat 900
ctttttggaa atacttttga acaaccaaaa gtccttccag taataaagct gcaagcacca 960
ttaactttat tggaatcttc tgcacgaacc atattacata ataggaatag gattccatat 1020
ggctctcata tcattccatt ccatctctgc caagatttgg ataccgcaaa aatttgtgtt 1080
tgtggaagat tctgtctgaa ctctttcatt caaggaacta ctaccatgaa tctgcattct 1140
gttgcccaca ctgtggtctt agtagataat ttgggtggta ctgaagcacc tattatctct 1200
tatttctgtt ctctaggctg ttatgttaat tcctctgata tgttaaagta a 1251
<210> 23
<211> 461
<212> PRT
<213> Homo Sapiens
<400> 23
Met Leu Gly Ile Trp Ile Val Ala Phe Leu Phe Phe Gly Thr Ser Arg
1 5 10 15
Gly Lys Glu Val Cys Tyr Glu Arg Leu Gly Cys Phe Lys Asp Gly Leu
20 25 30
Pro Trp Thr Arg Thr Phe Ser Thr Glu Leu Val Gly Leu Pro Trp Ser
35 40 45
Pro Glu Lys Ile Asn Thr Arg Phe Leu Leu Tyr Thr Ile His Asn Pro
50 55 60
Asn Ala Tyr Gln Glu Ile Ser Ala Val Asn Ser Ser Thr Ile Gln Ala
65 70 75 80
Ser Tyr Phe Gly Thr Asp Lys I1e Thr Arg Ile Asn I1e Ala Gly Trp
85 90 95
Lys Thr Asp Gly Lys Trp Gln Arg Asp Met Cys Asn Val Leu Leu Gln
100 105 110
Leu Glu Asp Ile Asn Cys Ile Asn Leu Asp Trp Ile Asn Gly Ser Arg
115 120 125
Glu Tyr Ile His Ala Val Asn Asn Leu Arg Val Val Gly Ala Glu Val
130 135 140
Ala Tyr Phe Ile Asp Val Leu Met Lys Lys Phe Glu Tyr Ser Pro Ser
145 150 155 160
Lys Val His Leu Ile Gly His Ser Leu Gly Ala His Leu Ala Gly Glu
165 170 175
Ala Gly Ser Arg Ile Pro Gly Leu Gly Arg Ile Thr Gly Leu Asp Pro
180 185 190
Ala Gly Pro Phe Phe His Asn Thr Pro Lys Glu Val Arg Leu Asp Pro
195 200 205
17/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
Ser Asp Ala Asn Phe Val Asp Val Ile His Thr Asn Ala Ala Arg Ile
210 215 220
Leu Phe Glu Leu Gly Val Gly Thr Ile Asp Ala Cys Gly His Leu Asp
225 230 235 240
Phe Tyr Pro Asn Gly Gly Lys His Met Pro Gly Cys Glu Asp Leu Ile
245 250 255
Thr Pro Leu Leu Lys Phe Asn Phe Asn Ala Tyr Lys Lys Glu Met Ala
260 265 270
Ser Phe Phe Asp Cys Asn His Ala Arg Ser Tyr Gln Phe Tyr Ala Glu
275 280 285
Ser Ile Leu Asn Pro Asp Ala Phe Ile Ala Tyr Pro Cys Arg Ser Tyr
290 295 300
Thr Ser Phe Lys Ala Gly Thr Cys Val Gly Cys Ala Asp Leu Leu His
305 310 315 320
Arg Ile Asp Lys Ile Gly Ser His Thr Ser His Val Phe Leu Thr Leu
325 330 335
Ser Leu Pro Phe Leu Leu Val Ser Leu Tyr Leu Gly Trp Arg His Lys
340 345 350
Leu Ser Val Lys Leu Ser Gly Ser Glu Val Thr Gln Gly Thr Val Phe
355 360 ' 365
Leu Arg Val Gly Gly Ala Val Arg Lys Thr Gly Glu Phe Ala Ile Val
370 375 380
Ser Gly Lys Leu Glu Pro Gly Met Thr Tyr Thr Lys Leu Ile Asp Ala
385 390 395 400
Asp Val Asn Val Gly Asn Ile Thr Ser Val Gln Phe Ile Trp Lys Lys
405 410 415
His Leu Phe Glu Asp Ser Gln Asn Lys Leu Gly Ala Glu Met Val Ile
420 425 430
Asn Thr Ser Gly Lys Tyr Gly Tyr Lys Ser Thr Phe Cys Ser Gln Asp
435 440 445
Ile Met Gly Pro Asn Ile Leu Gln Asn Leu Lys Pro Cys
450 455 460
<210> 24
<211> 308
<212> PRT
<213> Homo sapiens
<400> 24
Met Pro Phe Leu Gln Leu Lys Gly Arg.Ala Thr Pro Pro Ser Trp Arg
1 5 10 15
His Asp Ser Arg Ser Leu Val His Leu Leu Asp Gly Lys Glu Gly Val
20 25 30
Trp Asp Thr Thr Gly Tyr Ala Leu Gly Ser Arg Glu Ser Leu Asn Pro
35 40 45
Asp Met Gly Ile Gly Asp Pro His Gly His Ser Thr Val His Thr Arg
50 55 60
Glu Ala Gly Thr Ala Cys Pro Leu Gln Leu Leu Gly Ala Arg Glu Ala
65 70 75 80
Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala Ser Gly Gln Ile Phe Ile
85 90 95
Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg Thr Val Val Ala Leu Asp
100 105 110
Lys Val Pro Glu Asp Val Gln Glu Tyr Ser Trp Tyr Trp Gly Ala Asn
115 120 125
Asp Ser Ala Gly Asn Met Ile Ile Ser His Lys Pro Pro Ser Ala Gln
130 135 140
Gln Pro Gly Pro Met Tyr Thr Gly Arg Glu Arg Val Asn Arg Glu Gly
1153
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
145 150 155 160
Ser Leu Leu Ile Arg Pro Thr Ala Leu Asn Asp Thr Gly Asn Tyr Thr
165 170 175
Val Arg Val Val Ala Gly Asn Glu Thr Gln Arg Ala Thr Gly Trp Leu
180 185 190
Glu Val Leu Asp Gly Pro Asp Tyr Val Leu Leu Arg Ser Asn Pro Asp
195 200 205
Asp Phe Asn Gly Ile Val Thr Ala Glu Ile Gly Ser Gln Val Glu Met
210 215 220
Glu Cys Ile Cys Tyr Ser Phe Leu Asp Leu Lys Tyr His Trp Ile His
225 230 235 240
Asn Gly Ser Leu Leu Asn Phe Ser Asp Ala Lys Met Asn Leu Ser Ser
245 250 255
Leu Ala Trp Glu Gln Met Gly Arg Tyr Arg Cys Thr Val Glu Asn Pro
260 265 270
Val Thr Gln Leu Ile Met Tyr Met Asp Val Arg Ile Gln Ala Pro His
275 280 285
Glu Cys Ser Ser Ser Pro Pro Gly Ser Cys Phe Ala His Leu Pro Ala
290 295 300
Ser Met Pro Cys
305
<210> 25
<211> 457
<212> PRT
<213> Homo Sapiens
<400> 25
Met Asp Leu Ser Arg Pro Arg Trp Ser Leu Trp Arg Arg Val Phe Leu
1 5 10 15
Met Ala Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala Ser Gly Gln Ile
20 25 30
Phe Ile Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg Thr Val Val Ala
35 40 45
Leu Asp Lys Val Pro Glu Asp Val Gln Glu Tyr Ser Trp Tyr Trp Gly
50 55 60
Ala Asn Asp Ser Ala Gly Asn Met Ile Ile Ser His Lys Pro Pro Ser
65 70 75 80
Ala Gln Gln Pro Gly Pro Met Tyr Thr Gly Arg Glu Arg Val Asn Arg
85 90 95
Glu Gly Ser Leu Leu Ile Arg Pro Thr Ala Leu Asn Asp Thr Gly Asn
100 105 110
Tyr Thr Val Arg Val Val Ala Gly Asn Glu Thr Gln Arg Ala Thr Gly
115 120 125
Trp Leu Glu Val Leu Glu Leu Gly Ser Asn Leu Gly Ile Ser Val Asn
130 135 140
Ala Ser Ser Leu Val Glu Asn Met Asp Ser Val Ala Ala Asp Cys Leu
145 150 155 160
Thr Asn Val Thr Asn Ile Thr Trp Tyr Val Asn Asp Val Pro Thr Ser
165 170 175
Ser Ser Asp Arg Met Thr Ile Ser Pro Asp Gly Lys Thr Leu Val Ile
180 185 190
Leu Arg Val Ser Arg Tyr Asp Arg Thr Ile Gln Cys Met Ile Glu Ser
195 200 205
Phe Pro Glu Ile Phe Gln Arg Ser Glu Arg Ile Ser Leu Thr Val Ala
210 215 220
Tyr Gly Pro Asp Tyr Val Leu Leu Arg Ser Asn Pro Asp Asp Phe Asn
225 230 235 240
19/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
Gly Ile Val Thr Ala Glu Ile Gly Ser Gln Val Glu Met Glu Cys Ile
245 250 255
Cys Tyr Ser Phe Leu Asp Leu Lys Tyr His Trp Ile His Asn Gly Ser
260 265 270
Leu Leu Asn Phe Ser Asp Ala Lys Met Asn Leu Ser Ser Leu Ala Trp
275 280 285
Glu Gln Met Gly Arg Tyr Arg Cys Thr Val Glu Asn Pro Val Thr Gln
290 295 300
Leu Ile Met Tyr Met Asp Val Arg Tle Gln Ala Pro His Glu Cys Pro
305 310 315 320
Leu Pro Ser Gly Ile Leu Pro Val Val His Arg Asp Phe Ser Ile Ser
325 330 335
Gly Ser Met Val Met Phe Leu Ile Met Leu Thr Val Leu Gly Gly Val
340 345 350
Tyr Ile Cys Gly Val Leu Ile His Ala Leu Ile Asn His Tyr Ser Ile
355 360 365
Arg Cys Pro His Cys Ser Gly Thr Arg Val Gly Cys Trp Leu Gly Ala
370 375 380
Gly Thr Gln Glu Pro Ala Leu Pro Pro Glu Gly Lys Gln Ser Gln Lys
385 390 395 400
Gly Arg Asp Lys Pro Gly Thr Arg Leu Ser Gly Ile Ile Trp Gly Arg
405 410 415
Gln Ile Ser Pro Gln Asp Leu Lys Leu Met Gly Ala Arg Glu Gly Leu
420 425 430
Glu Ser Ala Met Val Leu Asn Ser Cys Gly Val Ser Ser Ser Asn Phe
435 440 445
Pro Ser Leu Cys Val Tyr Lys Gly Tyr
450 455
<210> 26
<211> 704
<212> PRT
<213> Homo Sapiens
<400> 26
Met Leu His Asp Gly Leu Thr Ala Pro Asp Gly Cys Gly IIe Tyr Ser
1 5 10 15
Leu Thr Gly Arg Glu Val Leu Thr Pro Phe Pro Gly Leu Gly Thr Ala
20 25 30
Ala Ala Pro Ala Gln Gly Gly Ala His Leu Lys Gln Cys Asp Leu Leu
35 40 45
Lys Leu Ser Arg Arg Gln Lys Gln Leu Cys Arg Arg Glu Pro Gly Leu
50 55 60
Ala Glu Thr Leu Arg Asp Ala Ala His Leu Gly Leu Leu Glu Cys Gln
65 70 75 80
Phe Gln Phe Arg His Glu Arg Trp Asn Cys Ser Leu Glu GIy Arg Met
85 90 95
GIy Leu Leu Lys Arg Gly Phe Lys GIu Thr Ala Phe Leu Tyr Ala Val
100 105 110
Ser Ser Ala Ala Leu Thr His Thr Leu Ala Arg Ala Cys Ser Ala Gly
115 120 125
Arg Met Glu Arg Cys Thr Cys Asp Asp Ser Pro Gly Leu Glu Ser Arg
130 135 140
Gln Ala Trp Gln Trp Gly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr
145 150 155 160
Lys Phe Leu Ser Asn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu
165 170 175
Arg Ala Arg Ala Asp Ala His Asn Thr His Val Gly Ile Lys Ala Val
20/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
180 185 190
Lys Ser Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser
195 200 205
Cys Ala Val Arg Thr Cys Trp Lys Gln Leu Sex Pro Phe Arg Glu Thr
210 215 220
Gly Gln Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser
225 230 235 240
Ala Thr Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro Ala Arg
245 250 255
Gln Gly Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly Asp Leu Val
260 265 270
Tyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser Lys Tyr Ser Pro
275 280 285
Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala Ser Cys Ser Ser Leu
290 295 300
Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser Arg Leu Val Ala Phe Ser
305 310 315 320
Cys His Cys Gln Val Gln Trp Cys Cys Tyr Val Glu Cys Gln Gln Cys
325 330 335
Val Gln Glu Glu Leu Val Tyr Thr Cys Lys His Ala Met Gly Pro Val
340 345 350
Gly Phe Pro Arg Gln Cys Gln Gly Ala Phe Phe Glu Ser Ser Pro Gly
355 360 365
Gln Thr Arg Ala Arg Leu Thr Gly Arg Glu Val Leu Thr Pro Phe Pro
370 375 380
Gly Leu Gly Thr Ala Ala Ala Pro Ala Gln Gly Gly Ala His Leu Lys
385 390 395 400
Gln Cys Asp Leu Leu Lys Leu Ser Arg Arg Gln Lys Gln Leu Cys Arg
405 410 415
Arg Glu Pro Gly Leu Ala Glu Thr Leu Arg Asp Ala Ala His Leu Gly
420 425 430
Leu Leu Glu Cys Gln Phe Gln Phe Arg His Glu Arg Trp Asn Cys Ser
435 440 445
Leu Glu Gly Arg Met Gly Leu Leu Lys Arg Gly Phe Lys Glu Thr Ala
450 455 460
Phe Leu Tyr Ala Val Ser Ser Ala Ala Leu Thr His Thr Leu Ala Arg
465 470 475 480
Ala Cys Ser Ala Gly Arg Met Glu Arg Cys Thr Cys Asp Asp Ser Pro
485 490 495
Gly Leu Glu Ser Arg Gln Ala Trp Gln Trp Gly Val Cys Gly Asp Asn
500 505 510
Leu Lys Tyr Ser Thr Lys Phe Leu Ser Asn Phe Leu Gly Ser Lys Arg
515 520 525
Gly Asn Lys Asp Leu Arg Ala Arg Ala Asp Ala His Asn Thr His Val
530 535 540
Gly Ile Lys Ala Val Lys Ser Gly Leu Arg Thr Thr Cys Lys Cys His
545 550 555 560
Gly Val Ser Gly Ser Cys Ala Val Arg Thr Cys Trp Lys Gln Leu Ser
565 570 575
Pro Phe Arg Glu Thr Gly Gln Val Leu Lys Leu Arg Tyr Asp Ser Ala
580 585 590
Val Lys Val Ser Ser Ala Thr Asn Glu Ala Leu Gly Arg Leu Glu Leu
595 600 605
Trp Ala Pro Ala Arg Gln Gly Ser Leu Thr Lys Gly Leu Ala Pro Arg
610 615 620
Ser Gly Asp Leu Val Tyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro
625 630 635 640
Ser Lys Tyr Ser Pro Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala
645 650 655
21/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
Ser Cys Ser Ser Leu Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser Arg
660 665 670
Leu Val Ala Phe Ser Cys His Cys Gln Val Gln Trp Cys Cys Tyr Val
675 680 685
Glu Cys Gln Gln Cys Val Gln Glu Glu Leu Val Tyr Thr Cys Lys His
690 695 700
<210> 27
<211> 361
<212> PRT
<213> Homo sapiens
<400> 27
Met Lys Pro Leu Arg Arg Pro Leu Pro Phe Ile Cys Pro Ser Pro Pro
1 5 10 15
Ser Pro Arg Leu Thr Cys Leu Pro Pro Leu Ala Leu Ser Ser Leu Thr
20 25 30
Gly Arg Glu Val Leu Thr Pro Phe Pro Gly Leu Gly Thr Ala Ala Ala
35 40 45
Pro Ala Gln Gly Gly Ala His Leu Lys Gln Cys Asp Leu Leu Lys Leu
50 55 60
Ser Arg Arg Gln Lys Gln Leu Cys Arg Arg Glu Pro Gly Leu Ala Glu
65 70 75 80
Thr Leu Arg Asp Ala Ala His Leu Gly Leu Leu Glu Cys Gln Phe Gln
85 90 95
Phe Arg His Glu Arg Trp Asn Cys Ser Leu Glu Gly Arg Met Gly Leu
100 105 110
Leu Lys Arg Gly Phe Lys Glu Thr Ala Phe Leu Tyr Ala Val Ser Ser
115 120 125
Ala Ala Leu Thr His Thr Leu A1a Arg Ala Cys Ser Ala Gly Arg Met
130 135 140
Glu Arg Cys Thr Cys Asp Asp Ser Pro Gly Leu Glu Ser Arg Gln A1a
145 150 155 160
Trp Gln Trp Gly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr Lys Phe
165 170 175
Leu Ser Asn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu Arg Ala
180 185 190
Arg Ala Asp A1a His Asn Thr His Val Gly Ile Lys Ala Val Lys Ser
195 200 205
Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser Cys Ala
210 215 220
Val Arg Thr Cys Trp Lys Gln Leu Ser Pro Phe Arg Glu Thr Gly Gln
225 230 235 240
Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser Ala Thr
245 250 255
Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro Ala Arg Gln Gly
260 265 270
Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly Asp Leu Val Tyr Met
275 280 285
Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser Lys Tyr Ser Pro Gly Thr
290 295 300
Ala Gly Arg Val Cys Ser Arg Glu Ala Ser Cys Ser Ser Leu Cys Cys
305 310 315 320
Gly Arg Gly Tyr Asp Thr Gln Ser Arg Leu Val Ala Phe Ser Cys His
325 330 335
Cys Gln Val G1n Trp Cys Cys Tyr Val Glu Cys Gln Gln Cys Val Gln
340 345 350
Glu Glu Leu Val Tyr Thr Cys Lys His
22/53
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355 360
<210> 28
<211> 365
<212> PRT
<213> Homo sapiens
<400> 28
Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr Leu Asn
1 5 10 15
Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu Val Trp
20 25 30
Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu Glu
35 40 45
Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg Ile
50 55 60
Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Ala Asp Ala Gly Tyr Asp
65 70 75 80
Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His Lys
85 90 95
Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe Asp Glu
100 105 110
Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys
115 120 125
Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr
130 135 140
Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile
145 150 155 160
Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr
165 170 175
Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala
180 185 190
Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile
195 200 205
Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys Ser
210 215 220
Glu Phe Met Ser Leu Trp A1a Gly Ser Asn Lys Lys Asn Met Asn Gln
225 230 235 240
Ser Arg Met Asp Val Tyr Met Ser His Ala Pro Thr Gly Ser Ser Val
245 250 255
His Asn Ile Leu His Ile Lys Gln Leu Tyr His Ser Asp Glu Phe Arg
260 265 270
Ala Tyr Asp Trp Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln
275 280 285
Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala
290 295 300
Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala
305 310 315 320
Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro
325 330 335
Asp Trp Asn His Phe Asp Phe Va1 Trp Gly Leu Asp Ala Pro G1n Arg
340 345 350
Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser
355 360 365
<210> 29
<211> 397
23/53
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<212> PRT
<213> Homo Sapiens
<400> 29
Met Trp Gln Leu Leu Ala Ala Ala Cys Trp Met Leu Leu Leu Gly Ser
1 5 10 15
Met Tyr Gly Tyr Asp Lys Lys Gly Asn Asn Ala Asn Pro Glu Ala Asn
20 25 30
Met Asn Ile Ser Gln Ile Ile Ser Tyr Trp Gly Tyr Pro Tyr Glu Glu
35 40 45
Tyr Asp Val Thr Thr Lys Asp GIy Tyr Ile Leu Gly Ile Tyr Arg Ile
50 55 60
Pro His Gly Arg Gly Cys Pro Gly Arg Thr Ala Pro Lys Pro Ala Val
65 70 75 80
Tyr Leu Gln His Gly Leu Ile Ala Ser Ala Ser Asn Trp Ile Cys Asn
85 90 95
Leu Pro Asn Asn Ser Leu Ala Phe Leu Leu Ala Asp Ser Gly Tyr Asp
100 105 110
Val Trp Leu Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Lys His Leu
115 120 125
Lys Leu Ser Pro Lys Ser Pro Glu Tyr Trp Ala Phe Ser Leu Asp Glu
130 135 140
Met Ala Lys Tyr Asp Leu Pro A1a Thr Ile Asn Phe Ile Ile Glu Lys
145 150 155 160
Thr Gly Gln Lys Arg Leu Tyr Tyr Val Gly His Ser Gln Gly Thr Thr
165 170 175
Ile Ala Phe Ile Ala Phe Ser Thr Asn Pro Glu Leu Ala Lys Lys Ile
180 185 190
Lys Ile Phe Phe Ala Leu Ala Pro Val Val Thr Val Lys Tyr Thr Gln
195 200 205
Ser Pro Met Lys Lys Leu Thr Thr Leu Ser Arg Arg Val Val Lys Val
210 215 220
Leu Phe Gly Asp Lys Met Phe His Pro His Thr Leu Phe Asp Gln Phe
225 230 235 240
Ile Ala Thr Lys Val Cys Asn Arg Lys Leu Phe Arg Arg Ile Cys Ser
245 250 255
Asn Phe Leu Phe Thr Leu Ser Gly Phe Asp Pro Gln Asn Leu Asn Met
260 265 270
Ser Arg Leu Asp Val Tyr Leu Ser His Asn Pro Ala Gly Thr Ser Val
275 280 285
Gln Asn Met Leu His Trp Ala Gln Leu Tyr His Ser Asp Glu Phe Arg
290 295 300
Ala Tyr Asp Trp Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln
305 310 315 320
Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala
325 330 335
Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala
340 345 350
Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro
355 360 365
Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg
370 375 380
Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser
385 390 395
<210> 30
<221> 3705
<212> PRT
24/53
CA 02414005 2002-12-20
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<213> Homo Sapiens
<400> 30
Met Ala Lys Arg Leu Cys Ala Gly Ser Ala Leu Cys Val Arg Gly Pro
1 5 10 15
Arg Gly Pro Ala Pro Leu Leu Leu Val Gly Leu Ala Leu Leu Gly Ala
20 25 30
Ala Arg Ala Arg Glu Glu Ala Gly Gly Gly Phe Ser Leu His Pro Pro
35 40 45
Tyr Phe Asn Leu Ala Glu Gly Ala Arg Ile Ala Ala Ser Ala Thr Cys
50 55 60
Gly Glu Glu Ala Pro Ala Arg Gly Ser Pro Arg Pro Thr Glu Asp Leu
65 70 75 80
Tyr Cys Lys Leu Val Gly Gly Pro Val Ala Gly Gly Asp Pro Asn Gln
85 90 95
Thr Ile Arg Gly Gln Tyr Cys Asp Ile Cys Thr Ala Ala Asn Ser Asn
100 105 110
Lys Ala His Pro Ala Ser Asn Ala Ile Asp Gly Thr Glu Arg Trp Trp
115 120 125
Gln Ser Pro Pro Leu Ser Arg Gly Leu Glu Tyr Asn Glu Val Asn Val
130 135 140
Thr Leu Asp Leu Gly Gln Val Phe His Val Ala Tyr Val Leu Ile Lys
145 150 155 160
Phe Ala Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Met
165 170 175
Asp Phe Gly Arg Thr Tyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys
180 185 190
Arg Asp Cys Leu Glu Arg Phe Gly Pro Gln Thr Leu Glu Arg Ile Thr
195 200 205
Arg Asp Asp Ala Ala Ile Cys Thr Thr Glu Tyr Ser Arg Ile Val Pro
210 215 220
Leu Glu Asn Gly Glu Ile Val Val Ser Leu Val Asn Gly Arg Pro Gly
225 230 235 240
Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu Phe Thr Lys Ala
245 250 255
Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His
260 265 270
Leu Met Gly Lys Ala Leu Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr
275 280 285
Tyr Ser Ile Lys Asp Ile Ser Ile Gly Gly Arg Cys Val Cys His Gly
290 295 300
His Ala Asp Ala Cys Asp Ala Lys Asp Pro Thr Asp Pro Phe Arg Leu
305 310 315 320
Gln Cys Thr Cys Gln His Asn Thr Cys Gly Gly Thr Cys Asp Arg Cys
325 330 335
Cys Pro Gly Phe Asn Gln Gln Pro Trp Lys Pro Ala Thr Ala Asn Ser
340 345 350
Ala Asn Glu Cys G1n Ser Cys Asn Cys Tyr Gly His A1a Thr Asp Cys
355 360 365
Tyr Tyr Asp Pro Glu Val Asp Arg Arg Arg Ala Ser Gln Ser Leu Asp
370 375 380
Gly Thr Tyr Gln Gly Gly Gly Val Cys Ile Asp Cys Gln His His Thr
385 390 395 400
Thr Gly Val Asn Cys Glu Arg Cys Leu Pro Gly Phe Tyr Arg Ser Pro
405 410 415
Asn His Pro Leu Asp Ser Pro His Val Cys Arg Arg Cys Asn Cys Glu
420 425 430
Ser Asp Phe Thr Asp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr
435 440 445
25/53
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Cys Arg Pro Asn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly
450 455 460
Phe Thr Gly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser Asn Asp
465 470 475 480
Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val Asn Cys Asp Cys
485 490 495
Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg Lys Asp Pro Arg Val
500 505 510
Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln Gly Thr His Cys Glu Leu
515 520 525
Cys Ala Pro Gly Phe Tyr Gly Pro Gly Cys Gln Pro Cys Gln Cys Ser
530 535 540
Ser Pro Gly Val Ala Asp Asp Arg Cys Asp Pro Asp Thr Gly Gln Cys
545 550 555 560
Arg Cys Arg Val Gly Phe Glu Gly Ala Thr Cys Asp Arg Cys Ala Pro
565 570 575
Gly Tyr Phe His Phe Pro Leu Cys Gln Leu Cys Gly Cys Ser Pro Ala
580 585 590
Gly Thr Leu Pro Glu Gly Cys Asp Glu Ala Gly Arg Cys Leu Cys Gln
595 600 605
Pro Glu Phe Ala Gly Pro His Cys Asp Arg Cys Arg Pro Gly Tyr His
610 615 620
Gly Phe Pro Asn Cys Gln Ala Cys Thr Cys Asp Pro Arg Gly Ala Leu
625 630 635 640
Asp Gln Leu Cys Gly Ala Gly Gly Leu Cys Arg Cys Arg Pro Gly Tyr
645 650 655
Thr Gly Thr Ala Cys Gln Glu Cys Ser Pro Gly Phe His Gly Phe Pro
660 665 670
Ser Cys Val Pro Cys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala
675 680 685
Cys Asp Pro Arg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly
690 695 700
Leu Arg Cys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro Tyr Cys
705 710 715 720
Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro Val Asp Pro Ala
725 730 735
Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg Ala His Val Glu Gly
740 745 750
Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe Trp Gly Leu Ser Pro Ser
755 760 765
Asn Pro Glu Gly Cys Thr Arg Cys Ser Cys Asp Leu Arg Gly Thr Leu
770 775 780
Gly Gly Val Ala Glu Cys Gln Pro Gly Thr Gly Gln Cys Phe Cys Lys
785 790 795 800
Pro His Val Cys Gly Gln Ala Cys Ala Ser Cys Lys Asp Gly Phe Phe
805 810 815
Gly Leu Asp Gln Ala Asp Tyr Phe Gly Cys Arg Ser Cys Arg Cys Asp
820 825 830
Ile Gly Gly Ala Leu Gly Gln Ser Cys Glu Pro Arg Thr Gly Val Cys
835 840 845
Arg Cys Arg Pro Asn Thr Gln Gly Pro Thr Cys Ser Glu Pro Ala Arg
850 855 860
Asp His Tyr Leu Pro Asp Leu His His Leu Arg Leu Glu Leu Glu Glu
865 870 875 880
Ala Ala Thr Pro Glu Gly His Ala Val Arg Phe Gly Phe Asn Pro Leu
885 890 895
Glu Phe Glu Asn Phe Ser Trp Arg Gly Tyr Ala Gln Met Ala Pro Val
900 905 910
Gln Pro Arg Ile Val Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe
26/53
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915 920 925
Trp Leu Val Phe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly
930 935 940
Arg Val Ser Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala Asn Cys
945 950 955 960
Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser Thr Glu Pro Ala
965 970 975
Phe Ile Thr Val Pro Gln Arg Gly Phe Gly Glu Pro Phe Val Leu Asn
980 985 990
Pro Gly Thr Trp Ala Leu Arg Val Glu Ala Glu Gly Val Leu Leu Asp
995 1000 1005
Tyr Val Val Leu Leu Pro Ser Ala Tyr Tyr Glu Ala Ala Leu Leu Gln
1010 1015 1020
Leu Arg Val Thr Glu A1a Cys Thr Tyr Arg Pro Ser Ala Gln Gln Ser
1025 1030 1035 1040
Gly Asp Asn Cys Leu Leu Tyr Thr His Leu Pro Leu Asp Gly Phe Pro
1045 1050 1055
Ser Ala A1a Gly Leu Glu Ala Leu Cys Arg Gln Asp Asn Ser Leu Pro
1060 1065 1070
Arg Pro Cys Pro Thr G1u Gln Leu Ser Pro Ser Hi5 Pro Pro Leu Ile
1075 1080 1085
Thr Cys Thr Gly Ser Asp Val Asp Val Gln Leu Gln Val Ala Val Pro
1090 1095 1100
Gln Pro Gly Arg Tyr A1a Leu Val Val Glu Tyr Ala Asn Glu Asp Ala
1105 1110 1115 1120
Arg Gln Glu Val Gly Val Ala Val His Thr Pro Gln Arg Ala Pro Gln
1125 1130 1135
Gln Gly Leu Leu Ser Leu His Pro Cys Leu Tyr Ser Thr Leu Cys Arg
1140 1145 1150
Gly Thr Ala Arg Asp Thr Gln Asp His Leu Ala Val Phe His Leu Asp
1155 1160 1165
Ser Glu Ala Ser Val Arg Leu Thr Ala Glu Gln Ala Arg Phe Phe Leu
1170 1175 1180
His Gly Val Thr Leu Val Pro Ile Glu Glu Phe Ser Pro Glu Phe Val
1185 1190 1195 1200
Glu Pro Arg Val Ser Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn
1205 1210 1215
Ser Ala Ala Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro Gln Pro Ile
1220 1225 1230
Ile Leu Arg Asp Cys G1n Val Ile Pro Leu Pro Pro Gly Leu Pro Leu
1235 1240 1245
Thr His Ala Gln Asp Leu Thr Pro Ala Met Ser Pro Ala Gly Pro Arg
1250 1255 1260
Pro Arg Pro Pro Thr A1a Val Asp Pro Asp Ala Glu Pro Thr Leu Leu
1265 1270 1275 1280
Arg Glu Pro Gln Ala Thr Val Val Phe Thr Thr His Val Pro Thr Leu
1285 1290 1295
Gly Arg Tyr Ala Phe Leu Leu His Gly Tyr Gln Pro Ala His Pro Thr
1300 1305 1310
Phe Pro Val Glu Val Leu Ile Asn Ala Gly Arg Val Trp Gln Gly His
1315 1320 1325
Ala Asn Ala Ser Phe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val
1330 1335 1340
Val Cys Glu Gly Gln Ala Leu Leu Asp Val Thr His Ser Glu Leu Thr
1345 1350 1355 1360
Val Thr Val Arg Val Pro Lys Gly Arg Trp Leu Trp Leu Asp Tyr Val
1365 1370 1375
Leu Val Val Pro Glu Asn Val Tyr Ser Phe Gly Tyr Leu Arg Glu Glu
1380 1385 1390
27/53
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Pro Leu Asp Lys Ser Tyr Asp Phe Ile Ser His Cys Ala Ala Gln Gly
1395 1400 1405
Tyr His Ile Ser Pro Ser Ser Ser Ser Leu Phe Cys Arg Asn Ala Ala
1410 1415 1420
Ala Ser Leu Ser Leu Phe Tyr Asn Asn Gly Ala Arg Pro Cys Gly Cys
1425 1430 1435 1440
His Glu Val Gly Ala Thr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln
1445 1450 1455
Cys Pro Cys His Ala His Val Ile Gly Arg Asp Cys Ser Arg Cys Ala
1460 1465 1470
Thr Gly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys Asp Cys Gly Ala
1475 1480 1485
Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys Ile Cys Pro Pro Arg Thr
1490 1495 1500
Ile Pro Pro Asp Cys Leu Leu Cys Gln Pro Gln Thr Phe Gly Cys His
1505 1510 1515 1520
Pro Leu Val Gly Cys Glu Glu Cys Asn Cys Ser Gly Pro Gly Ile Gln
1525 1530 1535
Glu Leu Thr Asp Pro Thr Cys Asp Thr Asp Ser Gly Gln Cys Lys Cys
1540 1545 1550
Arg Pro Asn Val Thr Gly Arg Arg Cys Asp Thr Cys Ser Pro Gly Phe
1555 1560 1565
His Gly Tyr Pro Arg Cys Arg Pro Cys Asp Cys His Glu Ala Gly Thr
1570 1575 1580
Ala Pro Gly Val Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys Lys Glu
1585 1590 1595 1600
Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser Leu Gly Thr~Phe Ser
1605 1610 1615
Leu Asp Ala Ala Asn Pro Lys Gly Cys Thr Arg Cys Phe Cys Phe Gly
1620 1625 1630
Ala Thr Glu Arg Cys Arg Ser Ser Ser Tyr Thr Arg Gln Glu Phe Val
1635 1640 1645
Asp Met Glu Gly Trp Val Leu Leu Ser Thr Asp Arg Gln Val Val Pro
1650 1655 1660
His Glu Arg Gln Pro Gly Thr Glu Met Leu Arg Ala Asp Leu Arg His
1665 1670 1675 1680
Val Pro Glu Ala Val Pro Glu Ala Phe Pro Glu Leu Tyr Trp Gln Ala
1685 1690 1695
Pro Pro Ser Tyr Leu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu
1700 1705 1710
Arg Tyr Glu Leu His Ser Glu Thr Gln Arg Gly Asp Val Phe Val Pro
1715 1720 1725
Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly Asn Gln Met Ser Ile
1730 1735 1740
Thr Phe Leu Glu Pro Ala Tyr Pro Thr Pro Gly His Val His Arg Gly
1745 1750 1755 1760
Gln Leu Gln Leu Val Glu Gly Asn Phe Arg His Thr Glu Thr Arg Asn
1765 1770 1775
Thr Val Ser Arg Glu Glu Leu Met Met Val Leu Ala Ser Leu Glu Gln
1780 1785 1790
Leu Gln Tle Arg Ala Leu Phe Ser Gln Tle Ser Ser Ala Val Phe Leu
1795 1800 1805
Arg Arg Val Ala Leu Glu Val Ala Ser Pro Ala Gly Gln Gly Ala Leu
1810 1815 1820
Ala Ser Asn Val Glu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp
1825 1830 1835 1840
Ser Cys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp Val Lys Gly Leu
1845 1850 1855
Phe Leu Gly Arg Cys Val Pro Cys Gln Cys His Gly His Ser Asp Arg
28/53
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1860 1865 1870
Cys Leu Pro Gly Ser Gly Val Cys Val Asp Cys Gln His Asn Thr Glu
1875 1880 1885
Gly Ala His Cys Glu Arg Cys Gln Ala Gly Phe Val Ser Ser Arg Asp
1890 1895 1900
Asp Pro Ser Ala Pro Cys Val Ser Cys Pro Cys Pro Leu Ser Val Pro
1905 ~ 1910 1915 1920
Ser Asn Asn Phe Ala Glu Gly Cys Val Leu Arg Gly Gly Arg Thr Gln
1925 1930 1935
Cys Leu Cys Lys Pro Gly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala
1940 1945 1950
Pro Gly Phe Phe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys Gln Pro
1955 1960 1965
Cys Asp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu Phe Ser Asp Cys
1970 1975 1980
Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys Leu Arg His Thr Thr Gly
1985 1990 1995 2000
Pro Arg Cys Glu Ile Cys Ala Pro Gly Phe Tyr Gly Asn Ala Leu Leu
2005 2010 2015
Pro Gly Asn Cys Thr Arg Cys Asp Cys Thr Pro Cys Gly Thr Glu Ala
2020 2025 2030
Cys Asp Pro His Ser Gly His Cys Leu Cys Lys Ala Gly Val Thr Gly
2035 2040 2045
Arg Arg Cys Asp Arg Cys Gln Glu Gly His Phe Gly Phe Asp Gly Cys
2050 2055 2060
Gly Gly Cys Arg Pro Cys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu
2065 2070 2075 2080
Cys His Pro Gln Ser Gly Gln Cys His Cys Arg Pro Gly Thr Met Gly
2085 2090 2095
Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp Gly Leu Pro Glu Gln
2100 2105 2110
Gly Cys Arg Arg Cys Gln Cys Pro Gly Gly Arg Cys Asp Pro His Thr
2115 2120 2125
Gly Arg Cys Asn Cys Pro Pro Gly Leu Ser Gly Glu Arg Cys Asp Thr
2130 2135 2140
Cys Ser Gln Gln His Gln Val Pro Val Pro Gly Gly Pro Val Gly His
2145 2150 2155 2160
Ser Ile His Cys Glu Val Cys Asp His Cys Val Val Leu Leu Leu Asp
2165 2170 2175
Asp Leu Glu Arg Ala Gly Ala Leu Leu Pro Ala Ile His Glu Gln Leu
2180 2185 2190
Arg Gly Ile Asn Ala Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu
2195 2200 2205
Asn Ala Ser Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser Pro Leu Gly
2210 2215 2220
Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val Leu Glu Gln Gln Ser
2225 2230 2235 2240
Thr Ser Leu Gly Gln Asp Ala Arg Arg Leu Gly Gly Gln Ala Gly Ala
2245 2250 2255
Pro Arg Pro Pro Arg Ala Pro Gly Gly Phe His Leu Tyr Gln Ala Ser
2260 2265 2270
Gln Leu Leu Ala Gly Thr Glu Ala Thr Leu Gly His Ala Lys Thr Leu
2275 2280 2285
Leu Ala Ala Ile Arg Ala Va1 Asp Arg Thr Leu Ser Glu Leu Met Ser
2290 2295 2300
Gln Thr Gly His Leu Gly Leu Ala Asn Ala Ser Ala Pro Ser Gly Glu
2305 2310 2315 2320
Gln Leu Leu Arg Thr Leu Ala Glu Val Glu Arg Leu Leu Trp Glu Met
2325 2330 2335
29/53
CA 02414005 2002-12-20
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Arg Ala Arg Asp Leu Gly Ala Pro Gln Ala Ala Ala Glu Ala Glu Leu
2340 2345 2350
Ala Ala Ala Gln Arg Leu Leu Ala Arg Val Gln Glu Gln Leu Ser Ser
2355 2360 2365
Leu Trp Glu Glu Asn Gln Ala Leu Ala Thr Gln Thr Arg Asp Arg Leu
2370 2375 2380
Ala Gln His Glu Ala Gly Leu Met Asp Leu Arg Glu Ala Leu Asn Arg
2385 2390 2395 2400
Ala Val Asp Ala Thr Arg Glu Ala Gln Glu Leu Asn Ser Arg Asn Gln
2405 2410 2415
Glu Arg Leu Glu Glu Ala Leu Gln Arg Lys Gln Glu Leu Ser Arg Asp
2420 2425 2430
Asn Ala Thr Leu Gln Ala Thr Leu His Ala Ala Arg Asp Thr Leu Ala
2435 2440 2445
Ser Val Phe Arg Leu Leu His Ser Leu Asp Gln Ala Lys Glu Glu Leu
2450 2455 2460
Glu Arg Leu Ala Ala Ser Leu Asp Gly Ala Arg Thr Pro Leu Leu Gln
2465 2470 2475 2480
Arg Met Gln Thr Phe Ser Pro Ala Gly Ser Lys Leu Arg Leu Val Glu
2485 2490 2495
Ala Ala Glu Ala His Ala Gln Gln Leu Gly Gln Leu Ala Leu Asn Leu
2500 2505 2510
Ser Ser Ile Ile Leu Asp Val Asn Gln Asp Arg Leu Thr Gln Arg Ala
2515 2520 2525
Ile Glu Ala Ser Asn Ala Tyr Ser Arg Ile Leu Gln Ala Val Gln Ala
2530 2535 2540
Ala Glu Asp Ala Ala Gly Gln Ala Leu Gln Gln Ala Asp His Thr Trp
2545 2550 2555 2560
Ala Thr Val Val Arg Gln Gly Leu Val Asp Arg Ala Gln Gln Leu Leu
2565 2570 2575
Ala Asn Ser Thr A1a Leu Glu Glu A1a Met Leu Gln Glu Gln Gln Arg
2580 2585 2590
Leu Gly Leu Val Trp Ala Ala Leu Gln Gly Ala Arg Thr Gln Leu Arg
2595 2600 2605
Asp Val Arg Ala Lys Lys Asp Gln Leu Glu Ala His Ile Gln Ala Ala
2610 2615 2620
Gln Ala Met Leu Ala Met Asp Thr Asp Glu Thr Ser Lys Lys Ile Ala
2625 2630 2635 2640
His Ala Lys Ala Val Ala Ala Glu Ala Gln Asp Thr Ala Thr Arg Val
2645 2650 2655
Gln Ser Gln Leu Gln Ala Met Gln Glu Asn Val Glu Arg Trp Gln Gly
2660 2665 2670
Gln Tyr Glu Gly Leu Arg Gly Gln Asp Leu Gly Gln Ala Val Leu Asp
2675 2680 2685
Ala Gly His Ser Val Ser Thr Leu Glu Lys Thr Leu Pro Gln Leu Leu
2690 2695 2700
Ala Lys Leu Ser Ile Leu Glu Asn Arg Gly Val His Asn Ala Ser Leu
2705 2710 2715 2720
Ala Leu Ser Ala Ser Ile Gly Arg Val Arg Glu Leu Ile Ala Gln Ala
2725 2730 2735
Arg Gly Ala Ala Ser Lys Val Lys Val Pro Met Lys Phe Asn Gly Arg
2740 2745 2750
Ser Gly Val Gln Leu Arg Thr Pro Arg Asp Leu Ala Asp Leu Ala Ala
2755 2760 2765
Tyr Thr Ala Leu Lys Phe Tyr Leu Gln Gly Pro Glu Pro Glu Pro Gly
2770 2775 2780
Gln Gly Thr Glu Asp Arg Phe Val Met Tyr Met Gly Ser Arg Gln Ala
2785 2790 2795 2800
Thr Gly Asp Tyr Met Gly Val Ser Leu Arg Asp Lys Lys Val His Trp
30153
CA 02414005 2002-12-20
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2805 2810 2815
Val Tyr Gln Leu Gly Glu Ala Gly Pro Ala Val Leu Ser Ile Asp Glu
2820 2825 2830
Asp Ile Gly Glu Gln Phe Ala Ala Val Ser Leu Asp Arg Thr Leu Gln
2835 2840 2845
Phe Gly His Met Ser Val Thr Val Glu Arg Gln Met Ile Gln Glu Thr
2850 2855 2860
Lys Gly Asp Thr Val Ala Pro Gly Ala Glu Gly Leu Leu Asn Leu Arg
2865 2870 2875 2880
Pro Asp Asp Phe Val Phe Tyr Val Gly Gly Tyr Pro Ser Thr Phe Thr
2885 2890 2895
Pro Pro Pro Leu Leu Arg Phe Pro Gly Tyr Arg Gly Cys Ile Glu Met
2900 2905 2910
Asp Thr Leu Asn Glu Glu Val Val Ser Leu Tyr Asn Phe Glu Arg Thr
2915 2920 2925
Phe Gln Leu Asp Thr Ala Val Asp Arg Pro Cys Ala Arg Ser Lys Ser
2930 2935 2940
Thr Gly Asp Pro Trp Leu Thr Asp Gly Ser Tyr Leu Asp Gly Thr Gly
2945 2950 2955 2960
Phe Ala Arg Ile Ser Phe Asp Ser Gln Ile Ser Thr Thr Lys Arg Phe
2965 2970 2975
Glu Gln Glu Leu Arg Leu Val Ser Tyr Ser Gly Val Leu Phe Phe Leu
2980 2985 2990
Lys Gln Gln Ser Gln Phe Leu Cys Leu Ala Val Gln Glu Gly Ser Leu
2995 3000 3005
Val Leu Leu Tyr Asp Phe Gly Ala Gly Leu Lys Lys Ala Val Pro Leu
3010 3015 3020
Gln Pro Pro Pro Pro Leu Thr Ser Ala Ser Lys Ala Ile Gln Val Phe
3025 3030 ~ 3035 3040
Leu Leu Gly Gly Ser Arg Lys Arg Val Leu Val Arg Val Glu Arg Ala
3045 3050 3055
Thr Val Tyr Ser Val Glu Gln Asp Asn Asp Leu Glu Leu Ala Asp Ala
3060 3065 3070
Tyr Tyr Leu Gly Gly Val Pro Pro Asp Gln Leu Pro Pro Ser Leu Arg
3075 3080 3085
Arg Leu Phe Pro Thr Gly Gly Ser Val Arg Gly Cys Val Lys Gly Ile
3090 3095 3100
Lys Ala Leu Gly Lys Tyr Val Asp Leu Lys Arg Leu Asn Thr Thr Gly
3105 3110 3115 3120
Val Ser Ala Gly Cys Thr Ala Asp Leu Leu Val Gly Arg Ala Met Thr
3125 3130 3135
Phe His Gly His Gly Phe Leu Arg Leu Ala Leu Ser Asn Val Ala Pro
3140 3145 3150
Leu Thr Gly Asn Val Tyr Ser Gly Phe Gly Phe His Ser Ala Gln Asp
3155 3160 3165
Ser Ala Leu Leu Tyr Tyr Arg Ala Ser Pro Asp Gly Leu Cys Gln Val
3170 3175 3180
Ser Leu Gln Gln Gly Arg Val Ser Leu Gln Leu Leu Afg Thr Glu Val
3185 3190 3195 3200
Lys Thr Gln Ala Gly Phe Ala Asp Gly Ala Pro His Tyr Val Ala Phe
3205 3210 3215
Tyr Ser Asn Ala Thr Gly Val Trp Leu Tyr Val Asp Asp Gln Leu Gln
3220 3225 3230
Gln Met Lys Pro His Arg Gly Pro Pro Pro Glu Leu Gln Pro Gln Pro
3235 3240 3245
Glu Gly Pro Pro Arg Leu Leu Leu Gly Gly Leu Pro Glu Ser Gly Thr
3250 3255 3260
Ile Tyr Asn Phe Ser Gly Cys Ile Ser Asn Val Phe Val Gln Arg Leu
3265 3270 3275 3280
31/53
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Leu Gly Pro Gln Arg Val Phe Asp Leu Gln Gln Asn Leu Gly Ser Val
3285 3290 3295
Asn Val Ser Thr Gly Cys Ala Pro Ala Leu Gln Ala Gln Thr Pro Gly
3300 3305 3310
Leu Gly Pro Arg Gly Leu Gln Ala Thr Ala Arg Lys Ala Ser Arg Arg
3315 3320 3325
Ser Arg Gln Pro Ala Arg His Pro Ala Cys Met Leu Pro Pro His Leu
3330 3335 3340
Arg Thr Thr Arg Asp Ser Tyr Gln Phe Gly Gly Ser Leu Ser Ser His
3345 3350 3355 3360
Leu Glu Phe Val Gly Ile Leu Ala Arg His Arg Asn Trp Pro Ser Leu
3365 3370 3375
Ser Met His Val Leu Pro Arg Ser Ser Arg Gly Leu Leu Leu Phe Thr
3380 3385 3390
Ala Arg Leu Arg Pro Gly Ser Pro Ser Leu Ala Leu Phe Leu Ser Asn
3395 3400 3405
Gly His Phe Val Ala Gln Met Glu Gly Leu Gly Thr Arg Leu Arg Ala
3410 3415 3420
Gln Ser Arg Gln Arg Ser Arg Pro Gly Arg Trp His Lys Val Ser Val
3425 3430 3435 3440
Arg Trp Glu Lys Asn Arg Ile Leu Leu Val Thr Asp Gly Ala Arg Ala
3445 3450 3455
Trp Ser Gln Glu Gly Pro His Arg Gln His Gln Gly Ala Glu His Pro
3460 3465 3470
Gln Pro His Thr Leu Phe Val Gly Gly Leu Pro Ala Ser Ser His Ser
3475 3480 3485
Ser Lys Leu Pro Val Thr Val Gly Phe Ser Gly Cys Val Lys Arg Leu
3490 3495 3500
Arg Leu His Gly Arg Pro Leu Gly Ala Pro Thr Arg Met Ala Gly Val
3505 3510 3515 3520
Thr Pro Cys Ile Leu Gly Pro Leu Glu Ala Gly Leu Phe Phe Pro Gly
3525 3530 3535
Ser Gly Gly Val Ile Thr Leu Asp Leu Pro Gly Ala Thr Leu Pro Asp
3540 3545 3550
Val Gly Leu Glu Leu Glu Val Arg Pro Leu Ala Val Thr Gly Leu Ile
3555 3560 3565
Phe His Leu Gly Gln Ala Arg Thr Pro Pro Tyr Leu Gln Leu Gln Val
3570 3575 3580
Thr Glu Lys Gln Val Leu Leu Arg Ala Asp Asp Gly Ala Gly Glu Phe
3585 3590 3595 3600
Ser Thr Ser Val Thr Arg Pro Ser Val Leu Cys Asp Gly Gln Trp His
3605 3610 3615
Arg Leu Ala Val Met Lys Ser Gly Asn Val Leu Arg Leu Glu Val Asp
3620 3625 3630
Ala Gln Ser Asn His Thr Val Gly Pro Leu Leu Ala Ala Ala Ala Gly
3635 3640 3645
Ala Pro Ala Pro Leu Tyr Leu Gly Gly Leu Pro Glu Pro Met Ala Val
3650 3655 3660
Gln Pro Trp Pro Pro Ala Tyr Cys Gly Cys Met Arg Arg Leu Ala Val
3665 3670 3675 3680
Asn Arg Ser Pro Val Ala Met Thr Arg Ser Val Glu Val His Gly Ala
3685 3690 3695
Val Gly Ala Ser Gly Cys Pro Ala Ala
3700 3705
<210> 31
<211> 3696
<212> PRT
32/53
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<213> Homo Sapiens
<400> 31
Met Ala Lys Arg Leu Cys Ala Gly Ser Ala Leu Cys Val Arg Gly Pro
1 5 10 15
Arg Gly Pro Ala Pro Leu Leu Leu Val Gly Leu Ala Leu Leu Gly Ala
20 25 30
Ala Arg Ala Arg Glu Glu Ala Gly Gly Gly Phe Ser Leu His Pro Pro
35 40 45
Tyr Phe Asn Leu Ala Glu Gly Ala Arg Ile Ala Ala Ser Ala Thr Cys
50 55 60
Gly Glu Glu Ala Pro Ala Arg Gly Ser Pro Arg Pro Thr Glu Asp Leu
65 70 75 80
Tyr Cys Lys Leu Va1 Gly Gly Pro Val Ala Gly Gly Asp Pro Asn Gln
85 90 95
Thr Ile Arg Gly Gln Tyr Cys Asp Ile Cys Thr Ala Ala Asn Ser Asn
100 105 110
Lys Ala His Pro Ala Ser Asn Ala Ile Asp Gly Thr Glu Arg Trp Trp
115 120 125
Gln Ser Pro Pro Leu Ser Arg Gly Leu Glu Tyr Asn Glu Val Asn Va1
130 135 140
Thr Leu Asp Leu Gly Gln Val Phe His Val Ala Tyr Val Leu Ile Lys
145 150 155 160
Phe Ala Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Met
165 170 175
Asp Phe Gly Arg Thr Tyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys
180 185 190
Arg Asp Cys Leu Glu Arg Phe Gly Pro G1n Thr Leu Glu Arg Ile Thr
195 200 205
Arg Asp Asp Ala Ala Ile Cys Thr Thr G1u Tyr Ser Arg Ile Val Pro
210 215 220
Leu Glu Asn Gly Glu Ile Va1 Val Ser Leu Val Asn Gly Arg Pro Gly
225 230 235 240
Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu Phe Thr Lys Ala
245 250 255
Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His
260 265 270
Leu Met Gly Lys Ala Leu Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr
275 280 285
Tyr Ser Ile Lys Asp Ile Ser Ile Gly G1y Arg Cys Val Cys His Gly
290 295 300
His Ala Asp Ala Cys Asp Ala Lys Asp Pro Thr Asp Pro Phe Arg Leu
305 310 315 320
Gln Cys Thr Cys Gln His Asn Thr Cys G1y Gly Thr Cys Asp Arg Cys
325 330 335
Cys Pro Gly Phe Asn Gln Gln Pro Trp Lys Pro Ala Thr Ala Asn Ser
340 345 350
Ala Asn Glu Cys Gln Ser Cys Asn Cys Tyr Gly His Ala Thr Asp Cys
355 360 365
Tyr Tyr Asp Pro Glu Val Asp Arg Arg Arg Ala Ser Gln Ser Leu Asp
370 375 380
Gly Thr Tyr Gln Gly Gly Gly Val Cys Ile Asp Cys Gln His His Thr
385 390 395 400
Thr Gly Val Asn Cys Glu Arg Cys Leu Pro Gly Phe Tyr Arg Ser Pro
405 410 415
Asn His Pro Leu Asp Ser Pro His Val Cys Arg Arg Cys Asn Cys Glu
420 425 430
Ser Asp Phe Thr Asp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr
435 440 445
33/53
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Cys Arg Pro Asn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly
450 455 460
Phe Thr Gly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser Asn Asp
465 470 475 480
Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val Asn Cys Asp Cys
485 490 495
Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg Lys Asp Pro Arg Val
500 505 510
Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln Gly Thr His Cys Glu Leu
515 520 525
Cys Ala Pro Gly Phe Tyr Gly Pro Gly Cys Gln Pro Cys Gln Cys Ser
530 535 540
Ser Pro Gly Val Ala Asp Asp Arg Cys Asp Pro Asp Thr Gly Gln Cys
545 550 555 560
Arg Cys Arg Val Gly Phe Glu Gly Ala Thr Cys Asp Arg Cys Ala Pro
565 570 575
Gly Tyr Phe His Phe Pro Leu Cys Gln Leu Cys Gly Cys Ser Pro Ala
580 585 590
Gly Thr Leu Pro Glu Gly Cys Asp Glu Ala Gly Arg Cys Leu Cys Gln
595 600 605
Pro Glu Phe Ala Gly Pro His Cys Asp Arg Cys Arg Pro Gly Tyr His
610 615 620
Gly Phe Pro Asn Cys Gln Ala Cys Thr Cys Asp Pro Arg Gly Ala Leu
625 630 635 640
Asp Gln Leu Cys Gly Ala Gly Gly Leu Cys Arg Cys Arg Pro Gly Tyr
645 650 655
Thr Gly Thr Ala Cys Gln Glu Cys Ser Pro Gly Phe His Gly Phe Pro
660 665 670
Ser Cys Val Pro Cys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala
675 680 685
Cys Asp Pro Arg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly
690 695 700
Leu Arg Cys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro Tyr Cys
705 710 715 720
Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro Val Asp Pro Ala
725 730 735
Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg Ala His Val Glu Gly
740 745 750
Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe Trp Gly Leu Ser Pro Ser
755 760 765
Asn Pro Glu Gly Cys Thr Arg Cys Ser Cys Asp Leu Arg Gly Thr Leu
770 775 780
Gly Gly Val Ala Glu Cys Gln Pro Gly Thr Gly Gln Cys Phe Cys Lys
785 790 795 800
Pro His Val Cys Gly Gln Ala Cys Ala Ser Cys Lys Asp Gly Phe Phe
805 810 815
Gly Leu Asp Gln Ala Asp Tyr Phe Gly Cys Arg Ser Cys Arg Cys Asp
820 825 830
Ile Gly Gly Ala Leu Gly Gln Ser Cys Glu Pro Arg Thr Gly Val Cys
835 840 845
Arg Cys Arg Pro Asn Thr Gln Gly Pro Thr Cys Ser Glu Pro Ala Arg
850 855 860
Asp His Tyr Leu Pro Asp Leu His His Leu Arg Leu Glu Leu Glu Glu
865 870 875 880
Ala Ala Thr Pro Glu Gly His Ala Val Arg Phe Gly Phe Asn Pro Leu
885 890 895
Glu Phe Glu Asn Phe Ser Trp Arg Gly Tyr Ala Gln Met Ala Pro Val
900 905 910
Gln Pro Arg Ile Val Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe
34/53
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915 920 925
Trp Leu Val Phe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly
930 935 940
Arg Val Ser Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala Asn Cys
945 950 955 960
Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser Thr Glu Pro Ala
965 970 975
Phe.Ile Thr Val Pro Gln Arg Gly Phe Gly Glu Pro Phe Val Leu Asn
980 985 990
Pro Gly Thr Trp Ala Leu Arg Val Glu Ala Glu Gly Val Leu Leu Asp
995 1000 1005
Tyr Val Val Leu Leu Pro Ser Ala Tyr Tyr Glu Ala Ala Leu Leu Gln
1010 1015 1020
Leu Arg Val Thr Glu Ala Cys Thr Tyr Arg Pro Ser A1a Gln G1n Ser
1025 1030 1035 1040
Gly Asp Asn Cys Leu Leu Tyr Thr His Leu Pro Leu Asp Gly Phe Pro
1045 1050 1055
Ser Ala Ala Gly Leu Glu Ala Leu Cys Arg Gln Asp Asn Ser Leu Pro
1060 1065 1070
Arg Pro Cys Pro Thr Glu Gln Leu Ser Pro Ser His Pro Pro Leu Ile
1075 1080 1085
Thr Cys Thr Gly Ser Asp Val Asp Val Gln Leu G1n Val Ala Val Pro
1090 1095 1100
Gln Pro Gly Arg Tyr Ala Leu Val Val Glu Tyr Ala Asn Glu Asp Ala
1105 1110 1115 1120
Arg Gln Glu Val Gly Val Ala Val His Thr Pro Gln Arg Ala Pro Gln
1125 1130 1135
Gln Gly Leu Leu Ser Leu His Pro Cys Leu Tyr Ser Thr Leu Cys Arg
1140 1145 1150
Gly Thr Ala Arg Asp Thr Gln Asp His Leu Ala Val Phe His Leu Asp
1155 1160 1165
Ser Glu Ala Ser Val Arg Leu Thr Ala Glu Gln A1a Arg Phe Phe Leu
1170 1175 1180
His Gly Val Thr Leu Val Pro Ile Glu Glu Phe Ser Pro Glu Phe Val
1185 1190 1195 1200
Glu Pro Arg Val Ser Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn
1205 1210 1215
Ser Ala Ala Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro Gln Pro Ile
1220 1225 1230
Ile Leu Arg Asp Cys Gln Val Ile Pro Leu Pro Pro Gly Leu Pro Leu
1235 1240 1245
Thr His Ala Gln Asp Leu Thr Pro Ala Met Ser Pro Ala Gly Pro Arg
1250 1255 1260
Pro Arg Pro Pro Thr Ala Val Asp Pro Asp Ala G1u Pro Thr Leu Leu
1265 1270 1275 1280
Arg Glu Pro Gln Ala Thr Val Val Phe Thr Thr His Val Pro Thr Leu
1285 1290 1295
Gly Arg Tyr Ala Phe Leu Leu His Gly Tyr Gln Pro Ala His Pro Thr
1300 1305 1310
Phe Pro Val Glu Val Leu Ile Asn Ala Gly Arg Val Trp Gln Gly His
1315 1320 1325
Ala Asn Ala Ser Phe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val
1330 1335 1340
Val Cys Glu Gly Gln Ala Leu Leu Asp Val Thr His Ser Glu Leu Thr
1345 1350 1355 1360
Val Thr Val Arg Val Pro Lys Gly Arg Trp Leu Trp Leu Asp Tyr Val
1365 1370 1375
Leu Val Val Pro Glu Asn Val Tyr Ser Phe Gly Tyr Leu Arg Glu Glu
1380 1385 1390
35/53
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Pro Leu Asp Lys Ser Tyr Asp Phe Ile Ser His Cys Ala Ala Gln Gly
1395 1400 1405
Tyr His Ile Ser Pro Ser Ser Ser Ser Leu Phe Cys Arg Asn Ala Ala
1410 1415 1420
Ala Ser Leu Ser Leu Phe Tyr Asn Asn Gly Ala Arg Pro Cys Gly Cys
1425 1430 1435 1440
His Glu Val Gly Ala Thr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln
1445 1450 1455
Cys Pro Cys His Ala His Val Ile Gly Arg Asp Cys Ser Arg Cys Ala
1460 1465 1470
Thr Gly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys Asp Cys Gly Ala
1475 ~ 1480 1485
Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys Ile Cys Pro Pro Arg Thr
1490 1495 1500
Ile Pro Pro Asp Cys Leu Leu Cys Gln Pro Gln Thr Phe Gly Cys His
1505 1510 1515 1520
Pro Leu Val Gly Cys Glu Glu Cys Asn Cys Ser Gly Pro Gly Ile Gln
1525 1530 1535
Glu Leu Thr Asp Pro Thr Cys Asp Thr Asp Ser Gly Gln Cys Lys Cys
1540 1545 1550
Arg Pro Asn Val Thr Gly Arg Arg Cys Asp Thr Cys Ser Pro Gly Phe
1555 1560 1565
His Gly Tyr Pro Arg Cys Arg Pro Cys Asp Cys His Glu Ala Gly Thr
1570 1575 1580
Ala Pro Gly Val Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys Lys Glu
1585 1590 1595 1600
Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser Leu Gly Thr Phe Ser
1605 1610 1615
Leu Asp Ala Ala Asn Pro Lys Gly Cys Thr Arg Cys Phe Cys Phe Gly
1620 1625 1630
Ala Thr Glu Arg Cys Arg Ser Ser Ser Tyr Thr Arg Gln Glu Phe Val
1635 1640 1645
Asp Met Glu Gly Trp Val Leu Leu Ser Thr Asp Arg Gln Val Val Pro
1650 1655 1660
His Glu Arg Gln Pro Gly Thr Glu Met Leu Arg Ala Asp Leu Arg His
1665 1670 1675 1680
Val Pro Glu Ala Val Pro Glu Ala Phe Pro Glu Leu Tyr Trp Gln Ala
1685 1690 1695
Pro Pro Ser Tyr Leu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu
1700 2705 1710
Arg Tyr Glu Leu His Ser Glu Thr Gln Arg Gly Asp Val Phe Val Pro
1715 1720 1725
Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly Asn Gln Met Ser Tle
1730 1735 1740
Thr Phe Leu Glu Pro Ala Tyr Pro Thr Pro G1y His Val His Arg Gly
1745 1750 1755 1760
Gln Leu Gln Leu Val Glu Gly Asn Phe Arg His Thr Glu Thr Arg Asn
1765 1770 1775
Thr Val Ser Arg Glu Glu Leu Met Met Val Leu Ala Ser Leu Glu Gln
1780 1785 1790
Leu Gln Ile Arg Ala Leu Phe Ser Gln Ile Ser Ser Ala Val Phe Leu
1795 1800 1805
Arg Arg Val Ala Leu Glu Val Ala Ser Pro Ala Gly Gln Gly Ala Leu
1810 1815 1820
Ala Ser Asn Val Glu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp
1825 1830 1835 1840
Ser Cys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp Val Lys Gly Leu
1845 1850 1855
Phe Leu Gly Arg Cys Val Pro Cys Gln Cys His Gly His Ser Asp Arg
3b/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
1860 1865 1870
Cys Leu Pro Gly Ser Gly Val Cys Val Asp Cys Gln His Asn Thr Glu
1875 . 1880 1885
Gly Ala His Cys Glu Arg Cys Gln Ala Gly Phe Val Ser Ser Arg Asp
1890 1895 1900
Asp Pro Ser Ala Pro Cys Val Ser Cys Pro Cys Pro Leu Ser Val Pro
1905 1910 1915 1920
Ser Asn Asn Phe Ala Glu Gly Cys Val Leu Arg Gly Gly Arg Thr Gln
1925 1930 1935
Cys Leu Cys Lys Pro Gly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala
1940 1945 1950
Pro Gly Phe Phe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys Gln Pro
1955 1960 1965
Cys Asp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu Phe Ser Asp Cys
1970 1975 1980
Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys Leu Arg His Thr Thr Gly
1985 1990 1995 2000
Pro Arg Cys Glu Ile Cys Ala Pro Gly Phe Tyr Gly Asn Ala Leu Leu
2005 2010 2015
Pro Gly Asn Cys Thr Arg Cys Asp Cys Thr Pro Cys Gly Thr Glu Ala
2020 2025 2030
Cys Asp Pro His Ser Gly His Cys Leu Cys Lys Ala Gly Val Thr Gly
2035 2040 2045
Arg Arg Cys Asp Arg Cys Gln Glu Gly His Phe Gly Phe Asp Gly Cys
2050 2055 2060
Gly Gly Cys Arg Pro Cys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu
2065 2070 2075 2080
Cys His Pro Gln Ser Gly Gln Cys His Cys Arg Pro Gly Thr Met Gly
2085 2090 2095
Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp Gly Leu Pro Glu Gln
2100 2105 2110
Gly Cys Arg Arg Cys Gln Cys Pro Gly Gly Arg Cys Asp Pro His Thr
2115 2120 2125
Gly Arg Cys Asn Cys Pro Pro Gly Leu Ser Gly Glu Arg Cys Asp Thr
2130 2135 2140
Cys Ser Gln Gln His Gln Val Pro Val Pro Gly Gly Pro Val Gly His
2145 2150 2155 2160
Ser Ile His Cys Glu Val Cys Asp His Cys Val Val Leu Leu Leu Asp
2165 2170 2175
Asp Leu Glu Arg Ala Gly Ala Leu Leu Pro Ala Ile His Glu Gln Leu
2180 2185 2190
Arg Gly Ile Asn Ala Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu
2195 2200 2205
Asn Ala Ser Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser Pro Leu Gly
2210 2215 2220
Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val Leu Glu Gln Gln Ser
2225 2230 2235 2240
Thr Ser Leu Gly Gln Asp Ala Arg Arg Leu Gly Gly Gln Ala Ala Val
2245 2250 2255
Gly Thr Arg Asp Gln Ala Ser Gln Leu Leu Ala Gly Thr Glu Ala Thr
2260 2265 2270
Leu Gly His Ala Lys Thr Leu Leu Ala Ala Ile Arg Ala Val Asp Arg
2275 2280 2285
Thr Leu Ser Glu Leu Met Ser Gln Thr Gly His Leu Gly Leu Ala Asn
2290 2295 2300
Ala Ser Ala Pro Ser Gly Glu Gln Leu Leu Arg Thr Leu Ala Glu Val
2305 2310 2315 2320
Glu Arg Leu Leu Trp Glu Met Arg Ala Arg Asp Leu G1y Ala Pro Gln
2325 2330 2335
37153
CA 02414005 2002-12-20
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Ala Ala Ala Glu Ala Glu Leu Ala Ala Ala Gln Arg Leu Leu Ala Arg
2340 2345 2350
Val Gln Glu Gln Leu Ser Ser Leu Trp Glu Glu Asn Gln Ala Leu Ala
2355 2360 2365
Thr Gln Thr Arg Asp Arg Leu Ala Gln His Glu Ala Gly Leu Met Asp
2370 2375 2380
Leu Arg Glu Ala Leu Asn Arg Ala Va°1 Asp Ala Thr Arg Glu Ala Gln
2385 2390 2395 2400
Glu Leu Asn Ser Arg Asn Gln Glu Arg Leu Glu Glu Ala Leu Gln Arg
2405 2410 2415
Lys Gln Glu Leu Ser Arg Asp Asn Ala Thr Leu Gln Ala Thr Leu His
2420 2425 2430
Ala Ala Arg Asp Thr Leu Ala Ser Val Phe Arg Leu Leu His Ser Leu
2435 2440 2445
Asp Gln Ala Lys Glu Glu Leu Glu Arg Leu Ala Ala Ser Leu Asp Gly
2450 2455 2460
Ala Arg Thr Pro Leu Leu Gln Arg Met Gln Thr Phe Ser Pro Ala Gly
2465 2470 2475 2480
Ser Lys Leu Arg Leu Val Glu Ala Ala Glu Ala His Ala Gln Gln Leu
2485 2490 2495
Gly Gln Leu Ala Leu Asn Leu Ser Ser Ile Ile Leu Asp Val Asn Gln
2500 2505 2510
Asp Arg Leu Thr Gln Arg Ala Ile Glu Ala Sex Asn Ala Tyr Ser Arg
2515 2520 2525
Ile Leu Gln Ala Val Gln Ala Ala Glu Asp Ala Ala Gly Gln Ala Leu
2530 2535 2540
Gln Gln Ala Asp His Thr Trp Ala Thr Val Val Arg Gln Gly Leu Val
2545 2550 2555 2560
Asp Arg Ala Gln Gln Leu Leu Ala Asn Ser Thr Ala Leu Glu Glu Ala
2565 2570 2575
Met Leu Gln Glu Gln Gln Arg Leu Gly Leu Val Trp Ala Ala Leu Gln
2580 2585 2590
Gly Ala Arg Thr Gln Leu Arg Asp Val Arg Ala Lys Lys Asp Gln Leu
2595 2600 2605
Glu Ala His Ile Gln Ala Ala Gln Ala Met Leu Ala Met Asp Thr Asp
2610 2615 2620
Glu Thr Ser Lys Lys Ile Ala His Ala Lys Ala Val Ala Ala Glu Ala
2625 2630 2635 2640
Gln Asp Thr Ala Thr Arg Val Gln Ser Gln Leu Gln Ala Met Gln Glu
2645 2650 2655
Asn Val Glu Arg Trp Gln Gly Gln Tyr Glu Gly Leu Arg Gly Gln Asp
2660 ~ 2665 2670
Leu Gly Gln Ala Val Leu Asp Ala Gly His Ser Val Ser Thr Leu Glu
2675 2680 2685
Lys Thr Leu Pro Gln Leu Leu Ala Lys Leu Ser Ile Leu Glu Asn Arg
2690 2695 2700
Gly Val His Asn Ala Ser Leu Ala Leu Ser Ala Ser Ile Gly Arg Val
2705 2710 2715 2720
Arg Glu Leu Ile Ala Gln Ala Arg Gly Ala Ala Ser Lys Val Lys Val
2725 2730 2735
Pro Met Lys Phe Asn Gly Arg Ser Gly Val Gln Leu Arg Thr Pro Arg
2740 2745 2750
Asp Leu Ala Asp Leu Ala Ala Tyr Thr Ala Leu Lys Phe Tyr Leu Gln
2755 2760 2765
Gly Pro Glu Pro Glu Pro Gly Gln Gly Thr Glu Asp Arg Phe Val Met
2770 2775 2780
Tyr Met Gly Ser Arg Gln Ala Thr Gly Asp Tyr Met Gly Val Ser Leu
2785 2790 2795 2800
Arg Asp Lys Lys Val His Trp Val Tyr Gln Leu Gly Glu Ala Gly Pro
38!53
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2805 2810 2815
Ala Val Leu Ser Ile Asp Glu Asp Ile Gly Glu Gln Phe Ala Ala Val
2820 2825 2830
Ser Leu Asp Arg Thr Leu Gln Phe Gly His Met Ser Val Thr Val Glu
2835 2840 2845
Arg Gln Met Ile Gln Glu Thr Lys Gly Asp Thr Val Ala Pro Gly Ala
2850 2855 2860
Glu Gly Leu Leu Asn Leu Arg Pro Asp Asp Phe Val Phe Tyr Val Gly
2865 2870 2875 2880
Gly Tyr Pro Ser Thr Phe Thr Pro Pro Pro Leu Leu Arg Phe Pro Gly
2885 2890 2895
Tyr Arg Gly Cys Ile Glu Met Asp Thr Leu Asn Glu Glu Val Val Ser
2900 2905 2910
Leu Tyr Asn Phe Glu Arg Thr Phe Gln Leu Asp Thr Ala Val Asp Arg
2915 2920 2925
Pro Cys Ala Arg Ser Lys Ser Thr Gly Asp Pro Trp Leu Thr Asp Gly
2930 2935 2940
Ser Tyr Leu Asp Gly Thr Gly Phe Ala Arg Ile Ser Phe Asp Ser Gln
2945 2950 2955 2960
Ile Ser Thr Thr Lys Arg Phe Glu Gln Glu Leu Arg Leu Val Ser Tyr
2965 2970 2975
Ser Gly Val Leu Phe Phe Leu Lys Gln Gln Ser Gln Phe Leu Cys Leu
2980 2985 2990
Ala Val Gln Glu Gly Ser Leu Val Leu Leu Tyr Asp Phe Gly Ala Gly
2995 3000 3005
Leu Lys Lys Ala Val Pro Leu Gln Pro Pro Pro Pro Leu Thr Ser Ala
3010 3015 3020
Ser Lys Ala Ile Gln Val Phe Leu Leu Gly Gly Ser Arg Lys Arg Val
3025 3030 3035 3040
Leu Val Arg Val Glu Arg Ala Thr Val Tyr Ser Val Glu Gln Asp Asn
3045 3050 3055
Asp Leu Glu Leu Ala Asp Ala Tyr Tyr Leu Gly Gly Val Pro Pro Asp
3060 3065 3070
Gln Leu Pro Pro Ser Leu Arg Arg Leu Phe Pro Thr Gly Gly Ser Val
3075 3080 3085
Arg Gly Cys Val Lys Gly Ile Lys Ala Leu Gly Lys Tyr Val Asp Leu
3090 3095 3100
Lys Arg Leu Asn Thr Thr Gly Val Ser Ala Gly Cys Thr Ala Asp Leu
3105 3110 3115 3120
Leu Val Gly Arg Ala Met Thr Phe His Gly His Gly Phe Leu Arg Leu
3125 3130 3135
Ala Leu Ser Asn Val Ala Pro Leu Thr Gly Asn Val Tyr Ser Gly Phe
3140 3145 3150
Gly Phe His Ser Ala Gln Asp Ser Ala Leu Leu Tyr Tyr Arg Ala Ser
3155 3160 3165
Pro Asp Gly Leu Cys Gln Val Ser Leu Gln Gln Gly Arg Val Ser Leu
3170 3175 3180
Gln Leu Leu Arg Thr Glu Val Lys Thr Gln Ala Gly Phe Ala Asp Gly
3185 3190 3195 3200
Ala Pro His Tyr Val Ala Phe Tyr Ser Asn Ala Thr Gly Val Trp Leu
3205 3210 3215
Tyr Val Asp Asp Gln Leu Gln Gln Met Lys Pro His Arg Gly Pro Pro
3220 3225 3230
Pro Glu Leu Gln Pro Gln Pro Glu Gly Pro Pro Arg Leu Leu Leu Gly
3235 3240 3245
Gly Leu Pro Glu Ser Gly Thr Ile Tyr Asn Phe Ser Gly Cys Ile Ser
3250 3255 3260
Asn Val Phe Val Gln Arg Leu Leu Gly Pro Gln Arg Val Phe Asp Leu
3265 3270 3275 3280
39/53
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Gln Gln Asn Leu Gly Ser Val Asn Val Ser Thr Gly Cys Ala Pro Ala
3285 3290 3295
Leu Gln Ala Gln Thr Pro Gly Leu Gly Pro Arg Gly Leu Gln Ala Thr
3300 3305 3310
Ala Arg Lys Ala Ser Arg Arg Ser Arg Gln Pro Ala Arg His Pro Ala
3315 3320 3325
Cys Met Leu Pro Pro His Leu Arg Thr Thr Arg Asp Ser Tyr Gln Phe
3330 3335 3340
Gly Gly Ser Leu Ser Ser His Leu Glu Phe Val Gly.Ile Leu Ala Arg
3345 3350 3355 3360
His Arg Asn Trp Pro Ser Leu Ser Met His Val Leu Pro Arg Ser Ser
3365 3370 3375
Arg Gly Leu Leu Leu Phe Thr Ala Arg Leu Arg Pro Gly Ser Pro Ser
3380 3385 3390
Leu Ala Leu Phe Leu Ser Asn Gly His Phe Val Ala Gln Met Glu Gly
3395 3400 3405
Leu Gly Thr Arg Leu Arg Ala Gln Ser Arg Gln Arg Ser Arg Pro Gly
3410 3415 3420
Arg Trp His Lys Val Ser Val Arg Trp Glu Lys Asn Arg Ile Leu Leu
3425 3430 3435 3440
Val Thr Asp Gly Ala Arg Ala Trp Ser Gln Glu Gly Pro His Arg Gln
3445 3450 3455
His Gln Gly Ala Glu His Pro Gln Pro His Thr Leu Phe Val Gly Gly
3460 3465 3470
Leu Pro Ala Ser Ser His Ser Ser Lys Leu Pro Val Thr Val Gly Phe
3475 3480 3485
Ser Gly Cys Val Lys Arg Leu Arg Leu His Gly Arg Pro Leu Gly Ala
3490 3495 3500
Pro Thr Arg Met Ala Gly Val Thr Pro Cys Ile Leu Gly Pro Leu Glu
3505 3510 3515 3520
Ala Gly Leu Phe Phe Pro Gly Ser Gly Gly Val Ile Thr Leu Asp Leu
3525 3530 3535
Pro Gly Ala Thr Leu Pro Asp Val Gly Leu Glu Leu Glu Val Arg Pro
3540 3545 3550
Leu Ala Val Thr Gly Leu Ile Phe His Leu Gly Gln Ala Arg Thr Pro
3555 3560 3565
Pro Tyr Leu Gln Leu Gln Val Thr Glu Lys Gln Val Leu Leu Arg Ala
3570 3575 3580
Asp Asp Gly Ala Gly Glu Phe Ser Thr Ser Val Thr Arg Pro Ser Val
3585 3590 3595 3600
Leu Cys Asp Gly Gln Trp His Arg Leu Ala Val Met Lys Ser Gly Asn
3605 3610 3615
Val Leu Arg Leu Glu Val Asp Ala Gln Ser Asn His Thr Val Gly Pro
3620 3625 3630
Leu Leu Ala Ala Ala Ala Gly Ala Pro Ala Pro Leu Tyr Leu Gly Gly
3635 3640 3645
Leu Pro Glu Pro Met Ala Val Gln Pro Trp Pro Pro Ala Tyr Cys Gly
3650 3655 3660
Cys Met Arg Arg Leu Ala Val Asn Arg Ser Pro Val Ala Met Thr Arg
3665 3670 3675 3680
Ser Val Glu Val His Gly Ala Val Gly Ala Ser Gly Cys Pro Ala Ala
3685 3690 3695
<210> 32
<211> 337
<212> PRT
<213> Homo sapiens
40153
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<400> 32
Met Thr Asn Asn Ser Gly Ser Lys Ala Glu Leu Val Val Gly Gly Lys
1 5 10 15
Tyr Lys Leu Val Arg Lys Ile Gly Ser Gly Ser Phe Gly Asp Val Tyr
20 25 30
Leu Gly Ile Thr Thr Thr Asn Gly Glu Asp Val Ala Val Lys Leu Glu
35 40 45
Ser Gln Lys Val Lys His Pro Gln Leu Leu Tyr Glu Ser Lys Leu Tyr
50 55 60
Thr Ile Leu Gln Gly Gly Val Gly Ile Pro His Met His Trp Tyr G1y
65 70 75 80
Gln Glu Lys Asp Asn Asn Val Leu Val Met Asp Leu Leu Gly Pro Ser
85 90 95
Leu Glu Asp Leu Phe Asn Phe Cys Ser Arg Arg Phe Thr Met Lys Thr
l00 105 110
Val Leu Met Leu Ala Asp Gln Met Ile Ser Arg Ile Glu Tyr Val His
115 120 125
Thr Lys Asn Phe Leu His Arg Asp Ile Lys Pro Asp Asn Phe Leu Met
130 135 140
Gly Thr Gly Arg His Cys Asn Lys Leu Phe Leu Ile Asp Phe Gly Leu
145 150 155 160
Ala Lys Lys Tyr Arg Asp Asn Arg Thr Arg Gln His Ile Pro Tyr Arg
165 170 175
Glu Asp Lys His Leu Ile Gly Thr Val Arg Tyr Ala Ser Ile Asn Ala
180 185 190
His Leu Gly Ile Glu Gln Ser Arg Arg Asp Asp Met Glu Ser Leu Gly
195 200 205 '
Tyr Val Phe Met Tyr Phe Asn Arg Thr Ser Leu Pro Trp Gln Gly Leu
210 215 220
Arg Ala Met Thr Lys Lys Gln Lys Tyr Glu Lys Ile Ser Glu Lys Lys
225 230 235 240
Met Ser Thr Pro Val Glu Val Leu Cys Lys Gly Phe Pro Ala Glu Phe
245 250 255
Ala Met Tyr Leu Asn Tyr Cys Arg Gly Leu Arg Phe Glu Glu Val Pro
260 265 270
Asp Tyr Met Tyr Leu Arg Gln Leu Phe Arg Ile Leu Phe Arg Thr Leu
275 280 285
Asn His Gln Tyr Asp Tyr Thr Phe Asp Trp Thr Met Leu Lys Gln Lys
290 295 300
Ala Ala Gln Gln Ala Ala Ser Ser Ser Gly Gln Gly Gln Gln Ala Gln
305 310 315 320
Thr Gln Thr Gly Lys Gln Thr Glu Lys Asn Lys Asn Asn Val Lys Asp
325 330 335
Asn
<210> 33
<211> 888
<212> PRT
<213> Homo Sapiens
<400> 33
Met Glu Ser Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile Leu Trp
1 5 10 15
Thr Gln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val Glu Glu Glu
20 25 30
Gln Arg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp Ala Arg Glu
35 40 45
41/53
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Ala Gly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe Arg Val Val
50 55 60
Ser Asn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser Ser Gly Leu
65 70 75 80
Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu Cys Arg Gln Ser
85 90 95
Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser Ser Met Glu Ile
100 105 110
Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn Asp Asn Ala Pro Ser
115 120 125
Phe Pro Ala Ala Gln Ile Glu Leu Glu Ile Ser Glu Ala Ala Ser Pro
130 135 140
Gly Thr Arg Ile Pro Leu Asp Ser Ala Tyr Asp Pro Asp Ser Gly Ser
145 150 155 160
Phe Gly Val Gln Thr Tyr Glu Leu Thr Pro Asn Glu Leu Phe Gly Leu
165 170 175
Glu Ile Lys Thr Arg Gly Asp Gly Ser Arg Phe Ala Glu Leu Val Val
180 185 190
Glu Lys Ser Leu Asp Arg Glu Thr Gln Ser His Tyr Ser Phe Arg Ile
195 200 205
Thr Ala Leu Asp Gly Gly Asp Pro Pro Arg Leu Gly Thr Val Gly Leu
210 215 220
Ser Ile Lys Val Thr Asp Ser Asn Asp Asn Asn Pro Val Phe Ser Glu
225 230 235 240
Ser Thr Tyr Ala Val Ser Val Pro Glu Asn Ser Pro Pro Asn Thr Pro
245 250 255
Val Ile Arg Leu Asn Ala Ser Asp Pro Asp Glu Gly Thr Asn Gly Gln
260 265 270
Val Val Tyr Ser Phe Tyr Gly Tyr Val Asn Asp Arg Thr Arg Glu Leu
275 280 285
Phe Gln Ile Asp Pro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu
290 295 300
Asp Tyr Glu Glu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp
305 310 315 320
Leu Gly Pro Asn Ser Ile Pro Ala His Cys Lys Val Thr Val Ser Val
325 330 335
Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu Leu Ser Val Asn
340 345 350
Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro Pro Gly Tyr Val Ile
355 360 365
Ala Leu Val Arg Val Ser Asp Arg Asp Ser Gly Leu Asn Gly Arg Val
370 375 380
Gln Cys Arg Leu Leu Gly Asn Val Pro Phe Arg Leu Gln Glu Tyr Glu
385 390 395 400
Ser Phe Ser Thr Ile Leu Val Asp Gly Arg Leu Asp Arg Glu Gln His
405 410 415
Asp Gln Tyr Asn Leu Thr Ile Gln Ala Arg Asp Gly Gly Val Pro Met
420 425 430
Leu Gln Ser Ala Lys Ser Phe Thr Val Leu Tle Thr Asp Glu Asn Asp
435 440 445
Asn His Pro His Phe Ser Lys Pro Tyr Tyr Gln Val Ile Val Gln Glu
450 455 460
Asn Asn Thr Pro Gly Ala Tyr Leu Leu Ser Val Ser Ala Arg Asp Pro
465 470 ~ 475 480
Asp Leu Gly Leu Asn Gly Ser Val Ser Tyr Gln Ile Val Pro Ser Gln
485 490 495
Val Arg Asp Met Pro Val Phe Thr Tyr Val Ser Ile Asn Pro Asn Ser
500 505 510
Gly Asp Ile Tyr Ala Leu Arg Ser Phe Asn His Glu Gln Thr Lys Ala
42/53
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515 520 525
Phe Glu Phe Lys Val Leu Ala Lys Asp~Gly Gly Leu Pro Ser Leu Gln
530 535 540
Ser Asn Ala Thr Va1 Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr
545 550 555 560
Pro Val Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala Glu Val Tyr
565 570 ' 575
Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr Val Val Lys Ala
580 585 590
Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val Thr Tyr Asp Met Thr
595 600 605
Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp Gln Val Asn Gly Glu Val
610 615 620
Arg Thr Thr Arg Thr Phe Gly Glu Ser Ser Lys Ser Ser Tyr Glu Leu
625 630 635 640
Ile Val Val Ala His Asp His Gly Lys Thr Ser Leu Ser Ala Ser Ala
645 650 655
Leu Val Leu Ile Tyr Leu Ser Pro Ala Leu Asp Ala Gln Glu Ser Met
660 665 670
Gly Ser Val Asn Leu Ser Leu Ile Phe Ile Ile Ala Leu Gly Ser Ile
675 680 685
Ala Gly Ile Leu Phe Val Thr Met Ile Phe Val Ala Ile Lys Cys Lys
690 695 700
Arg Asp Asn Lys Glu Ile Arg Thr Tyr Asn Cys Ser Asn Cys Leu Thr
705 710 715 720
Ile Thr Cys Leu Leu Gly Cys Phe Ile Lys Gly Gln Asn Ser Lys Cys
725 730 735
Leu His Cys Ile Ser Val Ser Pro Ile Ser Glu Glu Gln Asp Lys Lys
740 745 750
Thr Glu Glu Lys Val Ser Leu Arg Gly Lys Arg Ile Ala Glu Tyr Ser
755 760 765
Tyr Gly His Gln Lys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys Asn
770 775 780
Asp Ile Arg Leu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met Asn
785 790 795 800
Val Val Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp Tyr
805 810 815
His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser G1u Ser Thr Phe
820 825 830
Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Ser Ala Asn His Ile
835 840 845
Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln Pro Asp Leu Ile
850 855 860
Ile Asn Gly Val Pro Leu Pro Glu Val Ser Ala Ala Lys Trp Leu Cys
865 870 875 880
G1u Val Leu Pro Gly Leu Leu Leu
885
<210> 34
<211> 855
<212> PRT
<213> Homo Sapiens
<400> 34
Met Glu Ser Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile Leu Trp
1 5 10 15
Thr Gln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val Glu Glu Glu
20 25 30
43/53
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Gln Arg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp Ala Arg Glu
35 40 45
Ala Gly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe Arg Val Val
50 55 60
Ser Asn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser Ser Gly Leu
65 70 75 80
Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu Cys Arg Gln Ser
85 90 95
Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser Ser Met Glu Ile
100 105 110
Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn Asp Asn Ala Pro Ser
115 120 125
Phe Pro Ala A1a G1n Ile Glu Leu Glu Ile Ser Glu Ala Ala Ser Pro
130 135 140
Gly Thr Arg Ile Pro Leu Asp Ser Ala Tyr Asp Pro Asp Ser Gly Ser
145 150 155 160
Phe Gly Val Gln Thr Tyr Glu Leu Thr Pro Asn Glu Leu Phe Gly Leu
165 170 175
Glu Ile Lys Thr Arg Gly Asp Gly Ser Arg Phe Ala Glu Leu Val Val
180 185 190
Glu Lys Ser Leu Asp Arg Glu Thr Gln Ser His Tyr Ser Phe Arg Ile
195 200 205
Thr Ala Leu Asp Gly Gly Asp Pro Pro Arg Leu Gly Thr Val Gly Leu
210 215 220
Ser Ile Lys Val Thr Asp Ser Asn Asp Asn Asn Pro Val Phe Ser Glu
225 230 235 240
Ser Thr Tyr Ala Val Ser Val Pro Glu Asn Ser Pro Pro Asn Thr Pro
245 250 255
Val Ile Arg Leu Asn A1a Ser Asp Pro Asp Glu Gly Thr Asn Gly Gln
260 265 270
Val Val Tyr Ser Phe Tyr Gly Tyr Va1 Asn Asp Arg Thr Arg Glu Leu
275 280 285
Phe Gln Ile Asp Pro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu
290 295 300
Asp Tyr Glu Glu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp
305 310 315 320
Leu Gly Pro Asn Ser I1e Pro Ala His Cys Lys Val Thr Val Ser Val
325 330 335
Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu Leu Ser Val Asn
340 345 350
Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro Pro Gly Tyr Val Ile
355 360 365
Ala Leu Val Arg Val Ser Asp Arg Asp Ser Gly Leu Asn Gly Arg Val
370 375 380
Gln Cys Arg Leu Leu Gly Asn Val Pro Phe Arg Leu Gln Glu Tyr Glu
385 390 395 400
Ser Phe Ser Thr Ile Leu Val Asp Gly Arg Leu Asp Arg Glu Gln His
405 410 415
Asp Gln Tyr Asn Leu Thr Ile Gln Ala Arg Asp Gly Gly Val Pro Met
420 425 430
Leu Gln Ser Ala Lys Ser Phe Thr Val Leu Ile Thr Asp Glu Asn Asp
435 440 445
Asn His Pro His Phe Ser Lys Pro Tyr Tyr Gln Val Ile Val Gln Glu
450 455 460
Asn Asn Thr Pro Gly Ala Tyr Leu Leu Ser Val Ser Ala Arg Asp Pro
465 470 475 480
Asp Leu Gly Leu Asn G1y Ser Val Ser Tyr Gln Ile Val Pro Ser Gln
485 490 495
Val Arg Asp Met Pro Val Phe Thr Tyr Val Ser Ile Asn Pro Asn Ser
44/53
CA 02414005 2002-12-20
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500 505 510
Gly Asp Ile Tyr Ala Leu Arg Ser Phe Asn His Glu Gln Thr Lys Ala
515 520 525
Phe Glu Phe Lys Val Leu Ala Lys Asp Gly Gly Leu Pro Ser Leu Gln
530 535 540
Ser Asn Ala Thr Val Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr
545 550 555 560
Pro Val Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala Glu Val Tyr
565 570 575
Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr Val Val Lys Ala
580 585 590
Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val Thr Tyr Asp Met Thr
595 600 605
Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp Gln Val Asn Gly Glu Val
610 615 620
Arg Thr Thr Arg Thr Phe Gly Glu Ser Ser Lys Ser Ser Tyr Glu Leu
625 630 635 640
Ile Val Val Ala His Asp His Gly Lys Thr Ser Leu Ser Ala Ser Ala
645 650 655
Leu Val Leu Ile Tyr Leu Ser Pro Ala Leu Asp Ala Gln Glu Ser Met
660 665 670
Gly Ser Val Asn Leu Ser Leu Ile Phe Ile Ile Ala Leu Gly Ser Ile
675 680 685
Ala Gly Ile Leu Phe Val Thr Met Ile Phe Val Ala Ile Lys Cys Lys
690 695 700
Arg Asp Asn Lys Glu Ile Arg Thr Tyr Asn Cys Arg Ile Ala Glu Tyr
705 710 715 720
Ser Tyr Gly His Gln Lys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys
725 730 735
Asn Asp Ile Arg Leu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met
740 745 750
Asn Val Val Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp
755 760 765
Tyr His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser Glu Ser Thr
770 775 780
Phe Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Sex A1a Asn His
785 790 795 800
Ile Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln Pro Asp Leu
805 .810 815
Ile Ile Asn Gly Val Pro Leu Pro Glu Thr Glu Asn Tyr Ser Phe Asp
820 825 830
Ser Asn Tyr Val Asn Ser Arg Ala His Leu Ile Lys Arg Tyr Val Gly
835 840 845
Leu Leu Ala Tyr Cys Cys Asn
850 855
<210> 35
<211> 329
<212> PRT
<213> Homo Sapiens
<400> 35
Met Val Thr Lys Ala Phe Va1 Leu Leu Ala Ile Phe Ala Glu Ala Ser
1 5 10 15
Ala Lys Ser Cys Ala Pro Asn Lys Ala Asp Val IIe Leu Val Phe Cys
20 25 30
Tyr Pro Lys Thr Ile Ile Thr Lys Ile Pro Glu Cys Pro Tyr Gly Trp
35 40 45
45/53
CA 02414005 2002-12-20
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Glu Val His Gln Leu Ala Leu Gly Gly Leu Cys Tyr Asn Gly Val His
50 55 60
Glu Gly Gly Tyr Tyr Gln Phe Val Ile Pro Asp Leu Ser Pro Lys Asn
65 70 75 80
Lys Ser Tyr Cys Gly Thr Gln Ser Glu Tyr Lys Pro Pro Ile Tyr His
85 90 95
Phe Tyr Ser His Ile Val Ser Asn Asp Thr Thr Val Ile Val Lys Asn
100 105 110
Gln Pro Val Asn Tyr Ser Phe Ser Cys Thr Tyr His Ser Thr Tyr Leu
115 120 125
Val Asn Gln Ala Ala Phe Asp Gln Arg Val Ala Thr Val His Val Lys
130 135 140
Asn Gly Ser Met Gly Thr Phe Glu Ser Gln Leu Ser Leu Asn Phe Tyr
145 150 155 160
Thr Asn Ala Lys Phe Ser Ile Lys Lys Glu Ala Pro Phe Val Leu Glu
165 170 175
Ala Ser Glu Ile Gly Ser Asp Leu Phe Ala Gly Val Glu Ala Lys Gly
180 185 190
Leu Ser Ile Arg Phe Lys Val Val Leu Asn Ser Cys Trp Ala Thr Pro
195 200 205
Ser Ala Asp Phe Met Tyr Pro Leu Gln Trp Gln Leu Ile Asn Lys Gly
210 215 220
Cys Pro Thr Asp Glu Thr Val Leu Val His Glu Asn Gly Arg Asp His
225 230 235 240
Arg Ala Thr Phe Gln Phe Asn Ala Phe Arg Phe Gln Asn Ile Pro Lys
245 250 255
Leu Ser Lys Val Trp Leu His Cys Glu Thr Phe Ile Cys Asp Ser Glu
260 265 270
Lys Leu Ser Cys Pro Val Thr Cys Asp Lys Arg Lys Arg Leu Leu Arg
275 280 285
Asp Gln Thr Gly Gly Val Leu Val Val Glu Leu Ser Leu Arg Ser Arg
290 295 300
Gly Phe Ser Ser Leu Tyr Ser Phe Ser Asp Val Leu His His Leu Ile
305 310 315 320
Mgt Met Leu Gly Ile Cys Ala Val Leu
325
<210> 36
<211> 232
<212> PRT
<213> Homo sapiens
<400> 36
Met Leu Tyr Thr Arg Lys Asn Leu Thr Cys Ala Gln Thr Ile Asn Ser
1 5 10 15
Ser Ala Phe Gly Asn Leu Asn Val Thr Lys Lys Thr Thr Phe Ile Val
20 25 30
His Gly Phe Arg Pro Thr Gly Ser Pro Pro Val Trp Met Asp Asp Leu
35 40 45
Val Lys Gly Leu Leu Ser Val Glu Asp Met Asn Val Val Val Val Asp
50 55 60
Trp Asn Arg Gly Ala Thr Thr Leu Ile Tyr Thr His Ala Ser Ser Lys
65 70 75 80
Thr Arg Lys Val Ala Met Val Leu Lys Glu Phe Ile Asp Gln Met Leu
85 90 95
Ala Glu Gly Ala Ser Leu Asp Asp Ile Tyr Met Ile Gly Val Ser Leu
100 105 1l0
Gly Ala His Ile Ser Gly Phe Val Gly Glu Met Tyr Asp Gly Trp Leu
46/53
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115 120 125
Gly Arg Ile Thr Gly Leu Asp Pro Ala Gly Pro Leu Phe Asn Gly Lys
130 135 140
Pro His Gln Asp Arg Leu Asp Pro Ser Asp Ala Gln Phe Val Asp Val
145 150 155 160
Ile His Ser Asp Thr Asp Gly Asn Ala Pro Phe Leu Val Ala Leu Gly
165 170 175
Tyr Lys Glu Pro Leu Gly Asn Ile Asp Phe Tyr Pro Asn Gly Gly Leu
180 185 190
Asp Gln Pro Gly Cys Pro Lys Thr Ile Leu Gly Gly Asn Val Lys Glu
195 200 205
Met Ile Gln Ala Ser Tyr Ile Phe Phe Leu Lys Asn Asp Ser Met Asp
210 215 220
Leu Ser Ser Pro Lys Glu Val Glu
225 230
<210> 37
<211> 452
<212> PRT
<213> Homo sapiens
<400> 37
Met Leu Arg Phe Tyr Leu Phe Ile Ser Leu Leu Cys Leu Ser Arg Ser
1 5 10 15
Asp Ala Glu Glu Thr Cys Pro Ser Phe Thr Arg Leu Ser Phe His Ser
20 25 30
Ala Val Val Gly Thr Gly Leu Asn Val Arg Leu Met Leu Tyr Thr Arg
35 40 45
Lys Asn Leu Thr Cys Ala Gln Thr Ile Asn Ser Ser Ala Phe Gly Asn
50 55 60
Leu Asn Val Thr Lys Lys Thr Thr Phe Ile Val His Gly Phe Arg Pro
65 70 75 80
Thr Gly Ser Pro Pro Val Trp Met Asp Asp Leu Val Lys Gly Leu Leu
85 90 95
Ser Val Glu Asp Met Asn Val Val Val Val Asp Trp Asn Arg Gly Ala
100 105 110
Thr Thr Leu Ile Tyr Thr His Ala Ser Ser Lys Thr Arg Lys Val A1a
115 120 125
Met Val Leu Lys Glu Phe Ile Asp Gln Met Leu Ala Glu Gly Ala Ser
130 135 140
Leu Asp Asp Ile Tyr Met Ile Gly Val Ser Leu Gly Ala His Ile Ser
145 150 155 160
Gly Phe Val GIy Glu Met Tyr Asp Gly Trp Leu Gly Arg Ile Thr GIy
165 170 175
Leu Asp Pro Ala Gly Pro Leu Phe Asn Gly Lys Pro His Gln Asp Arg
180 185 ~ 190
Leu Asp Pro Ser Asp Ala Gln Phe Val Asp Val Ile His Ser Asp Thr
195 200 205
Asp Ala Leu Gly Tyr Lys Glu Pro Leu Gly Asn Ile Asp Phe Tyr Pro
210 215 220
Asn Gly Gly Leu Asp Gln Pro Gly Cys Pro Lys Thr Ile Leu Gly Gly
225 230 235 240
Phe Gln Tyr Phe Lys Cys Asp His Gln Arg Ser Val Tyr Leu Tyr Leu
245 250 255
Ser Ser Leu Arg Glu Ser Cys Thr Ile Thr Ala Tyr Pro Cys Asp Ser
260 265 270
Tyr Gln Asp Tyr Arg Asn Gly Lys Cys Val Ser Cys Gly Thr Ser Gln
275 280 285
47/53
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Lys Glu Ser Cys Pro Leu Leu Gly Tyr Tyr Ala Asp Asn Trp Lys Asp
290 295 300
His Leu Arg Gly Lys Asp Pro Pro Met Thr Lys Ala Phe Phe Asp Thr
305 310 315 320
Ala Glu Glu Ser Pro Phe Cys Met Tyr His Tyr Phe Val Asp Ile Ile
325 330 335
Thr Trp Asp Lys Asn Val Arg Arg Gly Asp Ile Thr Ile Lys Leu Arg
340 345 350
Asp Lys Ala Gly Asn Thr His Arg Ser Lys Ile Ile Ser Asn Glu Pro
355 360 365
Thr Thr Phe Gln Lys Tyr His Gln Val Ser Leu Leu Ala Arg Phe Asn
370 375 380
Gln Asp Leu Asp Lys Val Ala Ala Ile Ser Leu Met Phe Ser Thr Gly
385 390 395 400
Ser Leu Ile Gly Pro Arg Tyr Lys Leu Arg Ile Leu Arg Met Lys Leu
405 410 415
Arg Ser Leu Ala His Pro Glu Arg Pro Gln Leu Cys Arg Tyr Asp Leu
420 425 430
Val Leu Met Glu Asn Val Glu Thr Val Phe Gln Pro Ile Leu Cys Pro
435 440 445
Glu Leu Gln Leu
450
<210> 38
<211> 450
<212> PRT
<213> Homo Sapiens
<400> 38
Met Gly Leu Arg Ser His His Leu Ser Leu Gly Leu Leu Leu Leu Phe
1 5 10 15
Leu Leu Pro Ala Glu Cys Leu Gly Ala Glu Gly Arg Leu Ala Leu Lys
20 25 30
Leu Phe Arg Asp Leu Phe Ala Asn Tyr Thr Ser Ala Leu Arg Pro Val
35 40 45
Ala Asp Thr Asp Gln Thr Leu Asn Val Thr Leu Glu Val Thr Leu Ser
50 55 60
Gln Ile Ile Asp Met Asp Glu Arg Asn Gln Val Leu Thr Leu Tyr Leu
65 70 75 80
Trp Ile Arg Gln Glu Trp Thr Asp Ala Tyr Leu Arg Trp Asp Pro Asn
85 90 95
Ala Tyr Gly Gly Leu Asp Ala Ile Arg Ile Pro Ser Ser Leu Val Trp
100 105 110
Arg Pro Asp Ile Val Leu Tyr Asn Lys Ala Asp Ala Gln Pro Pro Gly
115 120 125
Ser Ala Ser Thr Asn Val Val Leu Arg His Asp Gly Ala. Val Arg Trp
130 135 140
Asp Ala Pro Ala Ile Thr Arg Ser Ser Cys Arg Val Asp Val Ala Ala
145 150 155 160
Phe Pro Phe Asp Ala Gln His Cys Gly Leu Thr Phe Gly Ser Trp Thr
165 170 175
His Gly Gly His Gln Leu Asp Val Arg Pro Arg Gly Ala Ala Ala Ser
180 185 190
Leu Ala Asp Phe Val Glu Asn Val Glu Trp Arg Val Leu Gly Met Pro
195 200 205
Ala Arg Arg Arg Val Leu Thr Tyr Gly Cys Cys Ser Glu Pro Tyr Pro
210 215 220
Asp Val Thr Phe Thr Leu Leu Leu Arg Arg Arg Ala Ala Ala Tyr Val
48/53
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225 230 235 240
Cys Asn Leu Leu Leu Pro Cys Val Leu Ile Ser Leu Leu Ala Pro Leu
245 250 255
Ala Phe His Leu Pro Ala Asp Ser Gly Glu Lys Val Ser Leu Gly Val
260 265 270
Thr Val Leu Leu Ala Leu Thr Val Phe Gln Leu Leu Leu Ala Glu Ser
275 280 285
Met Pro Pro Ala Glu Ser Val Pro Leu Ile Gly Lys Tyr Tyr Met Ala
290 295 300
Thr Met Thr Met Val Thr Phe Ser Thr Ala Leu Thr Ile Leu Ile Met
305 310 315 320
Asn Leu His Tyr Cys Gly Pro Ser Val Arg Pro Val Pro Ala Trp Ala
325 330 335
Arg Ala Leu Leu Leu Gly His Leu Ala Arg Gly Leu Cys Val Arg Glu
340 345 350
Arg Gly Glu Pro Cys Gly Gln Ser Arg Pro Pro Glu Leu Ser Pro Ser
355 360 365
Pro Gln Ser Pro Glu Gly Gly Ala Gly Pro Pro Ala Gly Pro Cys His
370 375 380
Glu Pro Arg Cys Leu Cys Arg Gln Glu Ala Leu Leu His His Val Ala
385 390 395 400
Thr Ile Ala Asn Thr Phe Arg Ser His Arg Ala Ala Gln Arg Cys His
405 410 415
Glu Asp Trp Lys Arg Leu Ala Arg Val Met Asp Arg Phe Phe Leu Ala
420 425 430
Ile Phe Phe Ser Met Ala Leu Val Met Ser Leu Leu Val Leu Val Gln
435 440 445
Ala Leu
450
<210> 39
<211> 255
<212> PRT
<213> Homo sapiens
<400> 39
Met Val Lys Gly Glu Lys Gly Pro Lys Gly Lys Lys Ile Thr Leu Lys
1 5 10 15
Val Ala Arg Asn Cys Ile Lys Ile Thr Phe Asp Gly Lys Lys Arg Leu
20 25 30
Asp Leu Ser Lys Met Gly Ile Thr Thr Phe Pro Lys Cys Ile Leu Arg
35 40 45
Leu Ser Asp Met Asp Glu Leu Asp Leu Ser Arg Asn Leu Ile Arg Lys
50 55 60
Ile Pro Asp Ser Ile Ser Lys Phe Gln Asn Leu Arg Trp Leu Asp Leu
65 70 75 80
His Ser Asn Tyr Ile Asp Lys Leu Pro Glu Ser Ile Gly Gln Met Thr
85 90 95
Sex Leu Leu Tyr Leu Asn Val Ser Asn Asn Arg Leu Thr Ser Asn Gly
100 105 110
Leu Pro Val Glu Leu Lys Gln Leu Lys Asn Ile Arg Ala Val Asn Leu
115 120 125
Gly Leu Asn His Leu Asp Ser Val Pro Thr Thr Leu Gly Ala Leu Lys
130 135 140
Glu Leu His Glu Val Gly Leu His Asp Asn Leu Leu Asn Asn Ile Pro
145 150 155 160
Val Ser Ile Ser Lys Leu Pro Lys Leu Lys Lys Leu Asn Ile Lys Arg
165 170 175
49/53
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Asn Pro Phe Pro Lys Pro Gly Glu Ser Glu Ile Phe Ile Asp Ser Ile
180 185 190
Arg Arg Leu Glu Asn Leu Tyr Val Val Glu Glu Lys Asp Leu Cys Ala
195 200 205
Ala Cys Leu Arg Lys Cys Gln Asn Ala Arg Asp Asn Leu Asn Arg Ile
210 215 220
Lys Asn Met Ala Thr Thr Thr Pro Arg Lys Thr Ile Phe Pro Asn Leu
225 230 235 240
Ile Ser Pro Asn Ser Met Ala Lys Asp Ser Trp Glu Asp Trp Arg
245 250 255
<210> 40
<211> 214
<212> PRT
<213> Homo sapiens
<400> 40
Met Gln Ala Gly Thr Gln Ser Thr His Glu Ser Leu Lys Pro Gln Arg
1 5 10 15
Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu Gln Trp Gln Pro
20 25 30
Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr Lys
35 40 45
Ile Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly Thr
50 55 60
Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln Glu
65 70 75 80
Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser Glu
85 90 95
Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile Asp
100 105 110
Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val Ile
115 120 125
Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn Val
130 135 140
Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile Asn
145 150 155 160
Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg Ala
165 170 175
Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val Ala
180 185 190
Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu Glu
195 200 205
Arg Cys Val Glu Ile Pro
210
<210> 41
<211> 231
<212> PRT
<213> Homo Sapiens
<400>
41
Met Met Lys HisCys Phe Leu Gly Phe Ile Ser Phe
Pro Leu Phe Leu
1 5 10 15
Thr Gly Ala GlyThr Gln Ser Thr His Ser Leu Pro
Val Glu Lys Gln
20 25 30
Arg Val Phe GlnSer Arg Asn Phe His Ile Leu Trp
Gln Asn Gln Gln
50/53
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35 40 45
Pro Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr
50 55 60
Lys Ile Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly
65 70 75 80
Thr Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln
85 90 95
Glu Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser
100 105 110
Glu Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile
115 120 125
Asp Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val
130 135 140
Ile Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn
145 150 155 160
Val Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile
165 170 175
Asn Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg
180 185 190
Ala Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val
195 200 205
Ala Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu
210 215 220
Glu Arg Cys Val Glu Ile Pro
225 230
<210> 42
<211> 263
<212> PRT
<213> Homo sapiens
<400> 42
Met Met Pro Lys His Cys Phe Leu Gly Phe Leu Ile Ser Phe Phe Leu
1 5 10 15
Thr Gly Val Ala Gly Thr Gln Ser Thr His Glu Ser Leu Lys Pro Gln
20 25 30
Arg Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu Gln Trp Gln
35 40 45
Pro Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr
50 55 60
Lys Ile Met Phe Ser Cys Ser Met Lys Ser Ser His Gln Lys Pro Ser
65 70 75 80
Gly Cys Trp Gln His Ile Ser Cys Asn Phe Pro Gly Cys Arg Thr Leu
85 90 95
Ala Lys Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly
100 105 110
Thr Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln
115 120 125
Glu Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser
130 135 140
Glu Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile
145 150 155 160
Asp Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val
165 170 175
Ile Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn
180 185 190
Val Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile
195 200 205
51/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
Asn Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg
210 215 220
Ala Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val
225 230 235 240
Ala Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu
245 250 255
Glu Arg Cys Val Glu Ile Pro
260
<210> 43
<211> 259
<212> PRT
<213> Homo Sapiens
<400> 43
Met Tyr Val Leu Ser Pro Val Glu Phe Ile Ile Leu Gln Leu Leu Phe
l 5 10 15
Ile Gln Ala Ile Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg
20 25 30
Leu Ala His Arg Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu Thr
35 40 45
Pro Val Lys Thr Ser Glu Phe Glu Asn Phe Lys Thr Lys Met Val Ile
50 55 60
Thr Ser Lys Lys Asp Tyr Pro Leu Ser Lys Asn Phe Pro Tyr Ser Leu
65 70 75 80
Glu His Leu Gln Thr Ser Tyr Cys Gly Leu Val Arg Val Asp Met Arg
85 90 95
Met Leu Cys Leu Lys Ser Leu Arg Lys Leu Asp Leu Ser His Asn His
100 105 110
Ile Lys Lys Leu Pro Ala Thr Ile Gly Asp Leu Ile His Leu Gln Glu
115 120 125
Leu Asn Leu Asn Asp Asn His Leu Glu Ser Phe Ser Val Ala Leu Cys
130 135 140
His Ser Thr Leu Gln Lys Ser Leu Arg Ser Leu Asp Leu Ser Lys Asn
1'45 150 155 160
Lys Ile Lys Ala Leu Pro Val Gln Phe Cys Gln Leu Gln Glu Leu Lys
165 170 175
Asn Leu Lys Leu Asp Asp Asn Glu Leu Ile Gln Phe Pro Cys Lys Ile
180 185 190
Gly Gln Leu Ile Asn Leu Arg Phe Leu Ser Ala Ala Arg Asn Lys Leu
195 200 205
Pro Phe Leu Pro Ser Glu Phe Arg Asn Leu Ser Leu Glu Tyr Leu Asp
210 215 220
Leu Phe Gly Asn Thr Phe Glu Gln Pro Lys Val Leu Pro Val Ile Lys
225 230 235 240
Leu Gln Ala Pro Leu Thr Leu Leu Glu Ser Ser Ala Arg Thr Ile Leu
245 250 255
His Asn Arg
<210> 44
<211> 416
<212> PRT
<213> Homo Sapiens
<400> 44
Met Lys Leu His Cys Glu Val Glu Val Ile Ser Arg His Leu Pro Ala
52/53
CA 02414005 2002-12-20
WO 01/98342 PCT/USO1/19929
1 5 10 15
Leu Gly Leu Arg Asn Arg Gly Lys Gly Val Arg Ala Val Leu Ser Leu
20 25 30
Cys Gln Gln Thr Ser Arg Ser Gln Pro Pro Val Arg Ala Phe Leu Leu
35 40 45
Ile Ser Thr Leu Lys Asp Lys Arg Gly Thr Arg Tyr Glu Leu Arg Glu
50 55 60
Asn Ile Glu Gln Phe Phe Thr Lys Phe Val Asp Glu Gly Lys Ala Thr
65 70 75 80
Val Arg Leu Lys Glu Pro Pro Val Asp Ile Cys Leu Ser Lys Ala Ile
85 90 95
Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg Leu Ala His Arg
100 105 110
Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu Thr Pro Val Lys Thr
115 120 125
Ser Glu Phe Glu Asn Phe Lys Thr Lys Met Val Ile Thr Ser Lys Lys
130 135 140
Asp Tyr Pro Leu Ser Lys Asn Phe Pro Tyr Ser Leu Glu His Leu Gln
145 150 155 160
Thr Ser Tyr Cys Gly Leu Val Arg Val Asp Met Arg Met Leu Cys Leu
165 170 175
Lys Ser Leu Arg Lys Leu Asp Leu Ser His Asn His Ile Lys Lys Leu
180 185 190
Pro Ala Thr Ile Gly Asp Leu Ile His Leu Gln Glu Leu Asn Leu Asn
195 200 205
Asp Asn His Leu Glu Ser Phe Ser Val Ala Leu Cys His Ser Thr Leu
210 215 220
Gln Lys Ser Leu Arg Ser Leu Asp Leu Ser Lys Asn Lys Ile Lys Ala
225 230 235 240
Leu Pro Val Gln Phe Cys Gln Leu Gln Glu Leu Lys Asn Leu Lys Leu
245 250 255
Asp Asp Asn Glu Leu Ile Gln Phe Pro Cys Lys Tle Gly Gln Leu Ile
260 265 270
Asn Leu Arg Phe Leu Ser Ala Ala Arg Asn Lys Leu Pro Phe Leu Pro
275 280 285
Ser Glu Phe Arg Asn Leu Ser Leu Glu Tyr Leu Asp Leu Phe Gly Asn
290 295 300
Thr Phe Glu Gln Pro Lys Val Leu Pro Val Ile Lys Leu Gln Ala Pro
305 310 315 320
Leu Thr Leu Leu Glu Ser Ser Ala Arg Thr Ile Leu His Asn Arg Asn
325 330 335
Arg Ile Pro Tyr Gly Ser His Ile Ile Pro Phe His Leu Cys Gln Asp
340 345 350
Leu Asp Thr Ala Lys Ile Cys Val Cys Gly Arg Phe Cys Leu Asn Ser
355 360 365
Phe Ile Gln Gly Thr Thr Thr Met Asn Leu His Ser Val Ala His Thr
370 375 380
Val Val Leu Val Asp Asn Leu Gly Gly Thr Glu Ala Pro Ile Ile Ser
385 390 395 400
Tyr Phe Cys Ser Leu Gly Cys Tyr Val Asn Ser Ser Asp Met Leu Lys
405 410 415
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