NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF COLON CANCER

NOUVEAUX NUCLEOTIDES ET SEQUENCES D'ACIDES AMINES, ET LEURS DOSAGES ET PROCEDES D'UTILISATION POUR LE DIAGNOSTIC DU CANCER DU COLON

English Abstract

Novel markers for colon cancer that are both sensitive and accurate. These
markers are overexpressed in colon cancer specifically, as opposed to normal
colon tissue. The measurement of these markers, alone or in combination, in
patient samples provides information that the diagnostician can correlate with
a probable diagnosis of colon cancer. The markers of the present invention,
alone or in combination, show a high degree of differential detection between
colon cancer and non-cancerous states.

French Abstract

La présente invention a trait à de nouveaux marqueurs qui sont à la fois sensibles et précis. Ces marqueurs sont surexprimés dans le cancer du côlon de manière spécifique, par opposition au tissu de côlon normal. La mesure de ces marqueurs, seuls ou en combinaison, dans des échantillons de patients fournit une information dont le diagnosticien peut établir la corrélation avec un diagnostic probable du cancer du côlon. Les marqueurs de la présente invention, seuls ou en combinaison, présentent un degré élevé de la détection différentielle entre des états de cancer du côlon et non cancéreux.

Claims

1841
WHAT IS CLAIMED IS:
1. ~An isolated polynucleotide comprising a polynucleotide having a sequence
of
R11723-PEA_1_T5.
2. ~The isolated polynucleotide of claim 1, comprising a node having a
sequence of:
R11723_PEA_1_node_13.
3. ~An isolated polypeptide comprising a polypeptide having a sequence of:
R11723_PEA_1_P_13.
4. ~The isolated of claim 3, comprising a chimeric polypeptide encoding for
R11723_PEA_1_P_13, comprising a first amino acid sequence being at least 95 %
homologous
to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV
MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to
amino
acids 1 - 63 of R11723_PEA_1_P_13, and a second amino acid sequence being at
least about
95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT
corresponding to amino acids 64 - 84 of R11723_PEA_1_P_13, wherein said first
and second
amino acid sequences are contiguous and in a sequential order.
4. ~The isolated polypeptide of claim 4, comprising a tail of
R11723_PEA_1_P_13,
comprising a polypeptide being at least about 95% homologous to the sequence
DTKRTNTLLFEMRHFAKQLTT in R11723_PEA_1_P_13.
5.~The isolated oligonucleotide of claim 1, comprising an amplicon according
to
SEQ ID NO: 1297.~
6. ~A primer pair, comprising a pair of isolated oligonucleotides capable of
amplifying said amplicon of claim 5.

1842~
7. ~The primer pair of claim 6, comprising a pair of isolated
oligonucleotides: SEQ
NOs 1295 and 1296.
8. ~An antibody capable of specifically binding to an epitope of an amino acid
sequence of
claim 3.
9. ~The antibody of claim 8, wherein said amino acid sequence comprises said
tail of claim
4.
10. ~The antibody of claim 8, wherein said antibody is capable of
differentiating between
a splice variant having said epitope and a corresponding known protein PSEC.
11. ~A kit for detecting colon cancer, comprising a kit detecting
overexpression of a
splice variant according to claim 1.
12. ~The kit of claim 11, wherein said kit comprises a NAT-based technology.
13. ~The kit of claim 11, wherein said kit further comprises at least one
primer pair
capable of selectively hybridizing to a nucleic acid sequence according to
claim 1.
14. ~The kit of claim 11, wherein said kit further comprises at least one
oligonucleotide capable of selectively hybridizing to a nucleic acid sequence
according to claim
1.
12. ~A kit for detecting colon cancer, comprising a kit detecting
overexpression of a
splice variant according to claim 3, said kit comprising an antibody according
to claim 8.
13. ~The kit of claim 12, wherein said kit further comprises at least one
reagent for
performing an ELISA or a Western blot.

1843
14. ~A method for detecting colon cancer, comprising detecting overexpression
of a
splice variant according to claim 1.
15. ~The method of claim 14, wherein said detecting overexpression is
performed
with a NAT-based technology.
16. ~A method for detecting colon cancer, comprising detecting overexpression
of a
splice variant according to claim 3, wherein said detecting overexpression is
performed with an
immunoassay.
17. ~The method of claim 16, wherein said immunoassay comprises an antibody
according to claim 8.
18. ~A biomarker capable of detecting colon cancer, comprising a nucleic acid
sequence according to claim 1 or a fragment thereof, or an amino acid sequence
according to
claim 3 or a fragment thereof.
19. ~A method for screening for colon cancer, comprising detecting colon
cancer cells
with a biomarker according to claim 18.
20. ~A method for diagnosing colon cancer, comprising detecting colon cancer
cells
with a biomarker according to claim 18.
21. ~A method for monitoring disease progression and/or treatment efficacy
and/or
relapse of colon cancer, comprising detecting colon cancer cells with a
biomarker according to
claim 18.
22. ~A method of selecting a therapy for colon cancer, comprising detecting
colon
cancer cells with a biomarker according to claim 18 and selecting a therapy
according to said
detection.

Description

DEMANDE OU BREVET VOLUMINEUX
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NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND
METHODS OF USE THEREOF FOR DIAGNOSIS OF COLON CANCER
FIELD OF THE INVENTION
The present invention is related to novel nucleotide and protein sequences
that are
diagnostic markers for colon cancer, and assays and methods of use thereof.
BACKGROUND OF THE INVENTION
Colon and rectal cancers are malignant conditions which occur in the
corresponding
segments of the large intestine. These cancers are sometimes refereed to
jointly as "colorectal
cancer", and, in many respects, the diseases are considered identical. The
major differences
between them are the sites where the malignant growths occur and the fact that
treatments may
differ based on the location of the tumors.
More than 95 percent of cancers of the colon and rectum are adenocarcinomas,
which
develop in glandular cells lining the inside (lumen) of the colon and rectum.
In addition to
adenocarcinomas, there are other rarer types of cancers of the large
intestine: these include
carcinoid tumors usually found in the appendix and rectum; gastrointestinal
stromal tumors
found in connective tissue in the wall 'of the colon and rectum; and
lymphomas, which are
malignancies of immune cells in the colon, rectum and lymph nodes. As with
other malignant
conditions, a number of genetic abnormalities have been associated with colon
tumors (Bos et
al, (1987) Nature 327:293-297; Baker et al, (1989) 244:217-221; Nishisho et
al, (1991) 253:665-
669).
Colorectal cancer is the second most common cause of cancer death in the
United States
and the third most prevalent cancer in both men and women. Approximately
100,000 patients
every year suffer from colon cancer and approximately half that number die of
the disease. In
large part this death rate is due to the inability to diagnose the disease at
an early stage (Wanebo
(1993) Col~rectal Cancer; Mosby, St. Louis Mo.). In fact, the prognosis for a
case of colon
cancer is vastly enhanced when malignant tissue is detected at the early stage
known as polyps.
Polyps are usually benign growths protruding from the mucous membrane. Nearly
all cases of

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colorectal cancer arise from adenomatous polyps, some of which mature into
large polyps,
undergo abnormal growth and development, and ultimately progress into cancer.
This
progression would appear to take at least 10 years in most patients, rendering
it a readily
treatable form of cancer if diagnosed early, when the cancer is localized.
Simple removal of
malignant polyps (polypectomy) through colonoscopy is now routine, and curing
the condition
from this procedure is effectively guaranteed. However, early detection of
polyps and tumors
depends on diligent and ongoing examination of patients at risk. The most
reliable detection
procedures to date include fecal occult blood tests, sigmoidoscopy, barium
enema X-ray, digital
rectal exam, and colonoscopy. Normally a malignant colon cancer will not cause
noticeable
symptoms (e.g., bowel obstruction, abdominal pain, anemia) until it has
reached an advanced
and far more serious stage of malignancy. At these stages, only risky,
traumatic and/or invasive
procedures are available, including chemotherapy, radiation therapy, and
colonectomy.
Although current understanding of the etiology of colon cancer is undergoing
continual
refinement, extensive research in this area points to a combination of
factors, including age,
hereditary and non-hereditary conditions, and environmental/dietary factors.
Age is a key risk
factor in the development of colorectal cancer, since men and women over 40
years of age
become increasingly susceptible to that cancer. Incidence rates increase
considerably in each
subsequent decade of life. A number of hereditary and nonhereditary conditions
have also been
linked to a heightened risk of developing colorectal cancer, including
familial adenomatous
polyposis (FAP), hereditary nonpolyposis colorectal cancer (Lynch syndrome or
HNPCC), a
personal and/or family history of colorectal cancer or adenomatous polyps,
inflammatory bowel
disease, diabetes mellitus, and obesity.
In the case of FAP, the tumor suppressor gene APC (adenomatous polyposis
coli),
located at Sq2l, has been either mutationally inactivated or deleted (Alberts
et al., Molecular
Biology of the Cell 1288 (3d ed. 1994)). The APC protein plays a role in a
number of functions,
including cell adhesion, apoptosis, and repression of the c-myc oncogene. Of
those patients with
colorectal cancer who have normal APC genes, over 65% have such mutations in
the cancer
cells but not in other tissues. In the case of HPNCC, patients manifest
abnormalities in the tumor
suppressor gene HNPCC, but only about 15% of tumors contain the mutated gene.
A host of
other genes have also been implicated in colorectal cancer, including the K-
ras, c-Ki-ras, N-ras,

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H-ras and c-myc oncogenes, and the tumor suppressor genes DCC (deleted in
colon carcinoma),
Wg/Wnt signal transduction pathway components and p53.
Some tyrosine kinases have been shown up-regulated in colorectal tumor tissues
or cell
lines like HT29. Focal adhesion kinase (FAK) and its up-stream kinase c-src
and c-yes in
colonic epithelial cells may play an important role in the promotion of
colorectal cancers
through the extracellular 1 5 matrix (ECM) and integrin-mediated signaling
pathways. The
formation of c-src/FAK complexes may coordinately deregulate VEGF expression
and
apoptosis inhibition.
Recent evidences suggest that a specific signal-transduction pathway for cell
survival
that implicates integrin engagement leads to FAK activation and thus activates
PI-3 kinase and
akt. In turn, akt phosphorylates BAD and blocks apoptosis in epithelial cells.
The activation of
c-sre in colon cancer may induce VEGF expression through the hypoxia pathway.
Other genes
that may be implicated in colorectal cancer include Cox enzymes (Ota, S. et
al. Aliment
Pharmacol. Ther. 16 (Suppl 2): 102-106 (2002)), estrogen (alAzzawi, F, and
Wahab, M.
Climacteric 5: 3-14 (2002)), peroxisome proliferator-activated receptor-y
(PPAR-y) (Gelman, L.
et aI. CeII Mol. Life Sci. 5 5: 932-943 (I999)), IGF-I (Giovannucci (2001)),
thymine DNA
glycosylase (TDG) (Hardeland, U. et al. Prog. Nucleic Acid Res. Mol. Biol. 68:
235-253
(2001)) and EGF (Mendelsohn, J. EndocrineRelated Cancer 8: 3-9 (2001)).
Procedures used for detecting, diagnosing, monitoring, staging, and
prognosticating
colon cancer are of critical importance to the outcome of the patient. For
example, patients
diagnosed with early colon cancer generally have a much greater five-year
survival rate as
compared to the survival rate fox patients diagnosed with distant metastasized
colon cancer.
Because colon cancer is highly treatable when detected at an early, localized
stage, screening
should be a part of routine care for all adults starting at age 50, especially
those with first-degree
relatives with colorectal cancer. One major advantage of colorectal cancer
screening over its
counterparts in other types of cancer is its ability to not only detect
precancerous lesions, but to
remove them as well. The key colorectal cancer screening tests in use today
are fecal occult
blood test, sigmoidoscopy, colonoscopy, double-contrast barium enema, and the

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carcinoembryonic antigen (CEA) test. New diagnostic methods which are more
sensitive and
specific for detecting early colon cancer are clearly needed.
Visual examination of the colon for abnormalities can be performed through
endoscopic
or radiographic techniques such as rigid proctosigmoidoscopy, flexible
sigmoidoscopy,
colonoscopy, and barium-contrast enema. These methods enable one to detect,
biopsy, and
remove adenomatous polyps. Despite the advantages of these procedures, there
are
accompanying downsides: they are expensive, and uncomfortable, and also carry
with them a
risk of complications. Sigmoidoscopy, by definition, is limited to the sigmoid
colon and below,
colonoscopy is a relatively expensive procedure, and both share the risk of
possible bowel
perforation and hemorrhaging. Double-contrast barium enema (DCBE) enables
detection of
lesions better than FOBT, and almost as well a colonoscopy, but it may be
limited in evaluating
the winding rectosigmoid region.
Another method of colon cancer diagnosis is the detection of carcinoembryonic
antigen
(CEA) in a blood sample from a subject, which when present at high levels, may
indicate the
presence of advanced colon cancer. But CEA levels may also be abnormally high
when no
cancer is present. Thus, this test is not selective for colon cancer, which
limits the test's value as
an accurate and reliable diagnostic tool. In addition, elevated CEA levels are
not detectable until
late-stage colon cancer, when the cure rate is low, treatment options limited,
and patient
prognosis poor.
Several classification systems have been devised to stage the extent of
colorectal cancer,
including the Dukes' system and the more detailed International Union against
Cancer-American
Joint Committee on Cancer TNM staging system, which is considered by many in
the field to be
a more useful staging system. These most widely used staging systems generally
use at least one
of the following characteristics for staging: the extent of tumor penetration
into the colon wall,
with greater penetration generally correlating with a more dangerous tumor;
the extent of
invasion of the tumor through the colon wall and into other neighboring
tissues, with greater
invasion generally correlating with a more dangerous tumor; the extent of
invasion of the tumor
into the regional lymph nodes, with greater invasion generally correlating
with a more

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dangerous tumor; and the extent of metastatic invasion into more distant
tissues, such as the
liver, with greater metastatic invasion generally correlating with a more
dangerous disease state.
"Dukes A" and "Dukes B" colon cancers are neoplasia that have invaded into the
wall of
the colon but have not spread into other tissues. Dukes A colon cancers are
cancers that have not
5 invaded beyond the submucosa. Dukes B colon cancers are subdivided into two
groups: Dukes
B1 and Dukes B2. "Dukes BI" colon cancers are neoplasias that have invaded up
to but not
through the muscularis propria. Dukes B2 colon cancers are cancers that have
breached
completely through the muscularis propria. Over a five year period, patients
with Dukes A
cancer who receive surgical treatment (i.e. removal of the affected tissue)
have a greater than
90% survival rate. Over the same period, patients with Dukes B 1 and Dukes B2
cancer
receiving surgical treatment have a survival rate of about 85% and 75%
respectively. Dukes A,
Bl and B2 cancers are also referred to as Tl, T2 and T3-T4 cancers,
respectively. "Dukes C"
colon cancers are cancers that have spread to the regional lymph nodes, such
as the lymph nodes
of the gut. Patients with Dukes C cancer who receive surgical treatment alone
have a 35%
survival rate over a five year period, but this survival rate is increased to
60% in patients that
receive chemotherapy. "Dukes D" colon cancers are cancers that have
metastasized to other
organs. The liver is the most common organ in which metastatic colon cancer is
found. Patients
with Dukes D colon cancer have a survival rate of less than 5% over a five
year period,
regardless of the treatment regimen.
The TNM system, which is used for either clinical or pathological staging, is
divided
into four stages, each of which evaluates the extent of cancer growth with
respect to primary
tumor (T), regional lymph nodes (N), and distant metastasis (M). The system
focuses on the
extent of tumor invasion into the intestinal wall, invasion of adjacent
structures, the number of
regional lymph nodes that have been affected, and whether distant metastasis
has occurred.
Stage 0 is characterized by in situ carcinoma (Tis), in which the cancer cells
are located inside
the glandular basement membrane (intraepithelial) or lamina propria,
(intramucosal). In this
stage, the cancer has not spread to the regional lymph nodes (NO), and there
is no distant
metastasis (N40). In stage l, there is still no spread of the cancer to the
regional lymph nodes
and no distant metastasis, but the tumor has invaded the submucosa (T I) or
has progressed
further to invade the muscularis propria (T2). Stage R also involves no spread
of the cancer to
the regional lymph nodes and no distant metastasis, but the tumor has invaded
the subserosa, or

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the nonperitonealized pericolic or perirectal tissues (T3), or has progressed
to invade other
organs or structures, and/or has perforated the visceral peritoneum (T4).
Stage 3 is characterized
by any of the T substages, no distant metastasis, and either metastasis in 1
to 3 regional lymph
nodes (Nl) or metastasis in four or more regional lymph nodes (N2). Lastly,
stage 4 involves any
of the T or N substages, as well as distant metastasis.
Currently, pathological staging of colon cancer is preferable over clinical
staging as
pathological staging provides a more accurate prognosis. Pathological staging
typically involves
examination of the resected colon section, along with surgical examination of
the abdominal
cavity.
SUMMARY OF THE INVENTION
The baclcground art does not teach or suggest markers for colon cancer that
are
sufficiently sensitive and/or accurate, alone or in combination. From the
foregoing, it is clear
that procedures used for detecting, diagnosing, monitoring, staging,
prognosticating, and
preventing the recurrence of colorectal cancer are of critical importance to
the outcome of the
patient. Moreover, current procedures, while helpful in each of these
analyses, are limited by
their specificity, sensitivity, invasiveness, and/or their cost. It would
therefore be desirable to
provide more sensitive and accurate methods and reagents for the early
diagnosis, staging,
prognosis, monitoring, and treatment of diseases associated with colon cancer,
or to indicate a
predisposition to such for preventative measures, as well as to determine
whether or not such
cancer has metastasized and for monitoring the progress of colon cancer in a
human which has
not metastasized for the onset of metastasis.
The present invention overcomes the deficiencies of the background art by
providing
novel markers for colon cancer that are both sensitive and accurate.
Furthermore, these markers
are able to distinguish between different stages of colon cancer, such as
adenocarcinoma
(mucinous or signet ring cell originating); leiomyocarcomas; carcinoid.
Furthermore, at least
some of these markers are able to distinguish, alone or in combination,
between colon cancer
between non-cancerous polyps. These markers are overexpressed in colon cancer
specifically, as
opposed to normal colon tissue. The measurement of these markers, alone or in
combination, in
patient samples provides information that the diagnostician can correlate with
a probable

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diagnosis of colon cancer. The markers of the present invention, alone or in
combination, show
a high degree of differential detection between colon cancer and non-cancerous
states.
According to preferred embodiments of the present invention, examples of
suitable
biological samples include but are not limited to blood, serum, plasma, blood
cells, urine,
sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external
secretions of the skin,
respiratory, intestinal, and genitourinary tracts, tears, mills, neuronal
tissue, colon tissue or
mucous and any human organ or tissue. In a preferred embodiment, the
biological sample
comprises colon tissue and/or a senun sample and/or a urine sample and/or a
stool sample
and/or any other tissue or liquid sample. The sample can optionally be diluted
with a suitable
eluant before contacting the sample to an antibody and/or performing any other
diagnostic
assay.
Information given in the text with regard to cellular localization was
determined
according to four different software programs: (i) tmhmm (from Center for
Biological Sequence
Analysis, Technical University of Denmark DTU,
1.ittp:/hwww.cbs.dtu.dk/services/TM.HMM/TMtl_MM.2.Ob.guide.php) or (ii) tmpred
(from
EMBnet, maintained by the ISREC Bionformatics group and the LICR Information
Technology
Office, Ludwig Institute for Cancer Research, Swiss Institute of
Bioinformatics,
http:/huww.ch.embnct.org/software/TMPRED fomn.htznl) for transmembrane region
prediction; (iii) signalp hmm or (iv) signalp nn (both from Center for
Biological Sequence
Analysis, Technical University of Denmark DTU,
http://'vww.cbs.dtu.dk/services/Signal.P/baclc.ground/prediction.ph.p) for
signal peptide
prediction. The terms "signalp hmm" and "signalp nn" refer to two modes of
operation for the
program SignalP: hmrn refers to Hidden Markov Model, while nn refers to neural
networks.
Localization was also determined through manual inspection of known protein
localization
and/or gene structure, and the use of heuristics by the individual inventor.
In some cases for the
manual inspection of cellular localization prediction inventors used the
ProLoc computational
platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit
Novik;
(2004) "Evolution of multicellularity in metazoa: comparative analysis of the
subcellular
localization of proteins in Saccharomyces, Drosophila and Caenorhabditis."
Cell Biology
International 2004;28(3):171-8.], which predicts protein localization based on
various
parameters including, protein domains (e.g., prediction of trans-membranous
regions and

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s
localization thereof within the protein), pI, protein length, amino acid
composition, homology to
pre-annotated proteins, recognition of sequence patterns which direct the
protein to a certain
organelle (such as, nuclear localization signal, NLS, mitochondria
localization signal), signal
peptide and anchor modeling and using unique domains from Pfam that are
specific to a single
compartment.
Information is given in the text with regard to SNPs (single nucleotide
polymorphisms).
A description of the abbreviations is as follows. "T - > C", for example,
means that the SNP
results in a change at the position given in the table from T to C. Similarly,
"M - > Q", for
example, means that the SNP has caused a change in the corresponding amino
acid sequence,
from methionine (M) to glutamine (Q). If, in place of a letter at the right
hand side for the
nucleotide sequence SNP, there is a space, it indicates that a frameshift has
occurred. A
frameshift may also be indicated with a hyphen (-). A stop codon is indicated
with an asterisk at
the right hand side (*). As part of the description of an SNP, a comment may
be found in
parentheses after the above description of the SNP itself. This comment may
include an FTId,
which is an identifier to a SwissProt entry that was created with the
indicated SNP. An FTId is
a unique and stable feature identifier, which allows construction of links
directly from position-
specific annotation in the feature table to specialized protein-related
databases. The FTId is
always the last component of a feature in the description field, as follows:
FTId=XXX number,
in which XXX is the 3-letter code for the specific feature key, separated by
an underscore from
a 6-digit number. In the table of the amino acid mutations of the wild type
proteins of the
selected splice variants of the invention, the header of the first column is
"SNP positions) on
amino acid sequence", representing a position of a known mutation on amino
acid sequence.
SNPs may optionally be used as diagnostic markers according to the present
invention, alone or
in combination with one or more other SNPs andlor any other diagnostic marker.
Preferred
embodiments of the present invention comprise such SNPs, including but not
limited to novel
SNPs on the known (WT or wild type) protein sequences given below, as well as
novel nucleic
acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a
variant
amino acid andlor nucleic acid sequence described herein.
Information given in the text with regard to the Homology to the known
proteins was
determined by Smith-Waterman version 5.1.2 using special (non default)
parameters as follows:
-model=sw.model

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9
-GAPEXT=0
-GAPOP=100.0
-MATRIX=blosum 100
Information is given with regard to overexpression of a cluster in cancer
based on ESTs.
A key to the p values with regard to the analysis of such overexpression is as
follows:
- library-based statistics: P-value without including the level of expression
in cell-
lines (P 1 )
- library based statistics: P-value including the level of expression in cell-
lines (P2)
- EST clone statistics: P-value without including the level of expression in
cell-lines
(SP 1 )
- EST clone statistics: predicted overexpression ratio without including the
level of
expression in cell-lines (R3)
- EST clone statistics: P-value including the level of expression in cell-
lines (SP2)
- EST clone statistics: predicted overexpression ratio including the level of
expression in cell-lines (R4)
Library-based statistics refer to statistics over an entire library, while EST
clone statistics
refer to expression only for ESTs from a particular tissue or cancer.
Information is given with regard to overexpression of a cluster in cancer
based on
microarrays. As a microarray reference, in the specific segment paragraphs,
the unabbreviated
tissue name was used as the reference to the type of chip for which expression
was measured.
There are two types of microarray results: those from microarrays prepared
according to a
design by the present inventors, for which the microarray fabrication
procedure is described in
detail in Materials and Experimental Procedures section herein; and those
results from
microarrays using Affymetrix technology. As a microarray reference, in the
specific segment
paragraphs, the unabbreviated tissue name was used as the reference to the
type of chip for
which expression was measured. For microarrays prepared according to a design
by the present
inventors, the probe name begins with the name of the cluster (gene), followed
by an identifying
number. Oligonucleotide microarray results taken from Affymetrix data were
from chips
available from Affymetrix Inc, Santa Clara, CA, USA (see for example data
regarding the
Human Genome U133 (HG-U133) Set at

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to
www.affymetrix.com/products/arrays/specific/hgul33.affx; GeneChip Human Genome
U133A
2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133av2.affx; and
Human
Genome U 133 Plus 2.0 Array at
www.affymetrix.com/products/arrays/specific/hgu133plus.affx). The probe names
follow the
Affymetrix naming convention. The data is available from NCBI Gene Expression
Omnibus
(see www.ncbi.nhn.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids
Research, 2002, Vol.
30, No. 1 207-210). The dataset (including results) is available from
www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1133 for the Series GSE1133
database
(published on March 2004); a reference to these results is as follows: Su et
al (Proc Natl Acad
Sci U S A. 2004 Apr 20;101 (16):6062-7. Epub 2004 Apr 09). A list of probes is
given below.
>M85491 0 0 25999
GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC
>M85491 0 14 0
GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG
>H53626 0 16 0
ATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTTC
>H53626 0 0 8391
GGGTCTGGGGTGCTCTCCTGGTCTTTGTGTCGGCGTTCCCCTCCCTACCT
>HSENA78 0 1 0
TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC
>HUMGROGS 0 0 16626
GCAGAAACTTTGCAGTAACACCTTCAGTGAGTTCAAGGCTAGGATCCCTG
>R00299 0 8 0
CCAAGGCTCGTCTGCGCACCTTGTGTCTTGTAGGGTATGGTATGTGGGAC
>567314 0 0 741
CACAGAGCCAGGATGTTCTTCTGACCTCAGTATCTACTCCAGCTCCAGCT
>567314 0 0 744
TGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTG
>Z44808 0 8 0
AAAAGCATGAGTTTCTGACCAGCGTTCTGGACGCGCTGTCCACGGACATG
>Z44808 0 0 72347

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11
ATGTTCTTAGGAGGCAAGCCAGGAGAAGCCGGGTCTGACTTTTCAGCTCA
>Z44808 0 0 72349
TCCTCCAGACCCAAAGCCACAACCCATCGCAAGTCAAGAACACTTTGCAG
>Z25299 0 3 0
AACTCTGGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTG
>HUMCA 1 XIA 0 0 14909
GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG
>HUMCA1XIA 0 18 0
TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG
>HSSl00PCB 0 0 12280
CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGGTCTAAAA
>HUMPHOSLIP 0 0 18458
AAGGAAGCAGGACCAGTGGATGTGAGGCGTGGTCGAAGAACAACAGAAAG
>HUMPHOSLIP 0 0 18487
ACAGGGGCCAGATGGTGACCCATGACCCAGCCTAAAAGGCAGCCAGAGGG
>D11853 0 0 0
GAGGCCCCTGGGTGGGAATGGGGACAGGAATTGACAGTGGAAGGGGTTCT
>D11853 0 0 3085
TGACTCCCTACATACTCCAGGACTAGCTTAGGTCCCAACCCAATAGTTCC
>D11853 0 0 3082
TGGTCCCCATGTGATTCTCCGAGGATCCTGAGGGTCGTGGTTTATGGAGA
>M77903 0 0 21402
ACGTGATGGTTGGAACGCGTACCTTAGAGCTTCCAGTTCCGTCTTAGGAC
>AA583399 0 12 0
ATCCCCACTGAACCCAGTGCTTTCACCAGCCATATTAGCTCCCAGTCACC
>AA583399 0 0 1681
CACCGCATGCTGCCAATCTGATGGTGGAGACAGAACAGCAGTCCCGGATG
>AA583399 0 1 1687
TTTCCACACTCAGTGCCACGAAGTGCAGCTCTAAGCTGGGGATTTCTGTG
>HUMCACH1A 0 12 0
ACCCAGCTCCATGTGCG'Z'TCTCAGGGAATGGACGCCAGTGTACTGCCAAT

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12
>HUMCACH1A 0 3 14917
AGAGAATATCACTCCGATGGTCGGTTTCTGACTGTCACGCTAAGGGCAAC
>HUMCACH1A 0 0 14922
GAACACAGAGAACGTCAGCGGTGAAGGCGAGAACCGAGGCTGCTGTGGAA
>HUMCACH 1 A 0 0 14913
GACTCAGGAGATGAACAGCTCCCAACTATTTGCCGGGAAGACCCAGAGAT
>HUMCACHlA 0 0 14924
GGCCCAGCATTGGGAACCTTGAGCATGTGTCTGAAAATGGGCATCATTCT
>HUMCEA 0 0 96
CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC
>HUMCEA 0 0 15183
CCTGGTGGGAGCCCATGAGAAGCGAGTTCTCTGTGCAACGGACTTAGTAA
>HUMCEA 0 0 15182
GCTCCCTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCT
>HUMCEA 0 0 15168
TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC
>HUMCEA 0 0 15180
TTTAACACAGGATTGGGACAGGATTCAGAGGGACACTGTGGCCCTTCTAC
>M78035 0 0 21693
CCATCCACATTTATGGAAACACTTGCTGTATATCTGGTGATTTACGTGTG
>M78035 0 0 21691
CCTTTCACCACTGTGTGCAAGCGAATACACGCGGAACAATCCTAGTGAAT
>M78035 0 1 21707
TTTGCTAGAAATCTGGTGTGGTGCAGGAGCGACTCCAGGATTCACTCTGT
>T23657 0 18 0
TCCGTGACCCTCAGAGATCCTTTGCCCTGGGAATCCAGTGGATTGTAGTT
>T51958 0 0 50903
CCCATGGTGGCCAGAGTGTCAGGTCTCATCGTGACGCTCTTGTCCTCCTC
>T51958 0 0 50916
GGGGCTGTGCCCAGTCCCCCTGTCAGACCCTCAATGACTGAGGCCTGGGG
>Z17877 0 4 0

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13
ACTTTGCACTGGAACTTACAACACCCGAGCAAGGACGCGACTCTGCCGAC
>HSHCGI 0 0 10611
GCCTACTGATTCATCCACATACAATTCTCAGCGTATATCCAAATGCAGTC
>HSHCGI 0 0 10620
GGACCTCTAAGTCTACAGGTGGTCAAAATGCTGTATCCACCCAATTCCAC
The following list of abbreviations for tissues was used in the TAA
histograms. The teen
"TAA" stands for "Tumor Associated Antigen", and the TAA histograms, given in
the text,
represent the cancerous tissue expression pattern as predicted by the
biomarkers selection
engine, as described in detail in examples 1-5 below:
"BONE" for "bone";
"COL" for "colon";
"EPI" for "epithelial";
"GEN" for "general";
"LIVER" for "liver";
"LUN" for "lung";
"LYMPH" for "lymph nodes";
"MARROW" for "bone marrow";
"OVA" for "ovary";
"PANCREAS" for "pancreas";
"PRO" for "prostate";
"STOMACH" for "stomach";
"TCELL" for "T cells";
"THYROID" for "Thyroid";
"MAM" for "breast";
"BRAIN" for "brain";
"UTERUS" for "uterus";
"SKIN" for "skin";
"KIDNEY" for "kidney";
"MUSCLE" for "muscle";
"ADREN" for "adrenal' ;

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l4
"HEAD" for "head and neck";
"BLADDER" for "bladder";
It should be noted that the terms "segment", "seg" and "node" are used
interchangeably
in reference to nucleic acid sequences of the present invention; they refer to
portions of nucleic
acid sequences that were shown to have one or more properties as described
below. They are
also the building blocks that were used to construct complete nucleic acid
sequences as
described in greater detail below. Optionally and preferably, they are
examples of
oligonucleotides which are embodiments of the present invention, for example
as amplicons,
hybridization units and/or from which primers and/or complementary
oligonucleotides may
optionally be derived, and/or for any other use.
As used herein the phrase "colon cancer" refers to cancers of the colon or
colorectal
cancers.
The term "marker" in the context of the present invention refers to a nucleic
acid
fragment, a peptide, or a polypeptide, which is differentially present in a
sample taken from
subjects (patients) having colon cancer as compared to a comparable sample
taken from subjects
who do not have colon cancer.
The phrase "differentially present" refers to differences in the quantity of a
marker
present in a sample taken from patients having colon cancer as compared to a
comparable
sample taken from patients who do not have colon cancer. For example, a
nucleic acid fragment
may optionally be differentially present between the two samples if the amount
of the nucleic
acid fragment in one sample is significantly different from the amount of the
nucleic acid
fragment in the other sample, for example as measured by hybridization and/or
NAT-based
assays. A polypeptide is differentially present between the two samples if the
amount of the
polypeptide in one sample is significantly different from the amount of the
polypeptide in the
other sample. It should be noted that if the marker is detectable in one
sample and not detectable
in the other, then such a marker can be considered to be differentially
present.
As used herein the phrase "diagnostic" means identifying the presence or
nature of a
pathologic condition. Diagnostic methods differ in their sensitivity and
specificity. The
"sensitivity" of a diagnostic assay is the percentage of diseased individuals
who test positive
(percent of "true positives"). Diseased individuals not detected by the assay
are "false

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negatives." Subjects who are not diseased and who test negative in the assay
are termed "true
negatives." The "specificity" of a diagnostic assay is 1 minus the false
positive rate, where the
"false positive" rate is defined as the proportion of those without the
disease who test positive.
While a particular diagnostic method may not provide a definitive diagnosis of
a condition, it
5 suffices if the method provides a positive indication that aids in
diagnosis.
As used herein the phrase "diagnosing" refers to classifying a disease or a
symptom,
determining a severity of the disease, monitoring disease progression,
forecasting an outcome of
a disease and/or prospects of recovery. The term "detecting" may also
optionally encompass any
of the above.
10 Diagnosis of a disease according to the present invention can be effected
by determining
a level of a polynucleotide or a polypeptide of the present invention in a
biological sample
obtained from the subject, wherein the level determined can be correlated with
predisposition to,
or presence or absence of the disease. It should be noted that a "biological
sample obtained from
the subject" may also optionally comprise a sample that has not been
physically removed from
15 the subject, as described in greater detail below.
As used herein, the term "level" refers to expression levels of RNA and/or
protein or to
DNA copy number of a marker of the present invention.
Typically the level of the marker in a biological sample obtained from the
subject is
different (i.e., increased or decreased) from the level of the same variant in
a similar sample
obtained from a healthy individual (examples of biological samples are
described herein).
Numerous well known tissue or fluid collection methods can be utilized to
collect the
biological sample from the subject in order to determine the level of DNA, RNA
and/or
polypeptide of the variant of interest in the subject.
Examples include, but are not limited to, fine needle biopsy, needle biopsy,
core needle
biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the
procedure
employed, once a biopsy/sample is obtained the level of the variant can be
determined and a
diagnosis can thus be made.
Determining the level of the same variant in normal tissues of the same origin
is
preferably effected along-side to detect an elevated expression and/or
amplification and/or a
decreased expression, of the variant as opposed to the normal tissues.

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16
A "test amount" of a marker refers to an amount of a marker in a subject's
sample that is
consistent with a diagnosis of colon cancer. A test amount can be either in
absolute amount
(e.g., microgram/ml) or a relative amount (e.g., relative intensity of
signals).
A "control amount" of a marker can be any amount or a range of amounts to be
compared against a test amount of a marker. For example, a control amount of a
marker can be
the amount of a marker in a patient with colon cancer or a person without
colon cancer. A
control amount can be either in absolute amount (e.g., microgram/ml) or a
relative amount (e.g.,
relative intensity of signals).
"Detect" refers to identifying the presence, absence or amount of the object
to be
detected.
A "label" includes any moiety or item detectable by spectroscopic, photo
chemical,
biochemical, immunochemical, or chemical means. For example, useful labels
include 32P, 355,
fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in
an ELISA),
biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or
monoclonal
antibodies are available, or nucleic acid molecules with a sequence
complementary to a target.
The label often generates a measurable signal, such as a radioactive,
chromogenic, or
fluorescent signal, that can be used to quantify the amount of bound label in
a sample. The label
can be incorporated in or attached to a primer or probe either covalently, or
through ionic, van
der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides,
or biotinylated
nucleotides that are recognized by streptavadin. The label may be directly or
indirectly
detectable. Indirect detection can involve the binding of a second label to
the first label, directly
or indirectly. For example, the label can be the ligand of a binding partner,
such as biotin, which
is a binding partner for streptavadin, or a nucleotide sequence, which is the
binding partner for a
complementary sequence, to which it can specifically hybridize. The binding
partner may itself
be directly detectable, for example, an antibody may be itself labeled with a
fluorescent
molecule. The binding partner also may be indirectly detectable, for example,
a nucleic acid
having a complementary nucleotide sequence can be a part of a branched DNA
molecule that is
in turn detectable through hybridization with other labeled nucleic acid
molecules (see, e.g., P.
D. Fahrlander and A. I~lausner, Bio/Technology 6:1165 (1988)). Quantitation of
the signal is
achieved by, e.g., scintillation counting, densitometry, or flow cytometry.

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17
Exemplary detectable labels, optionally and preferably for use with
immunoassays,
include but are not limited to magnetic beads, fluorescent dyes, radiolabels,
enzymes (e.g., horse
radish peroxide, alkaline phosphatase and others commonly used in an ELISA),
and calorimetric
labels such as colloidal gold or colored glass or plastic beads.
Alternatively, the marker in the
sample can be detected using an indirect assay, wherein, for example, a
second, labeled antibody
is used to detect bound marker-specific antibody, andlor in a competition or
inhibition assay
wherein, for example, a monoclonal antibody which binds to a distinct epitope
of the marker are
incubated simultaneously with the mixture.
"Immunoassay" is an assay that uses an antibody to specifically bind an
antigen. The
immunoassay is characterized by the use of specific binding properties of a
particular antibody
to isolate, target, and/or quantify the antigen.
The phrase "specifically (or selectively) binds" to an antibody or
"specifically (or
selectively) immunoreactive with," when referring to a protein or peptide (or
other epitope),
refers to a binding reaction that is determinative of the presence of the
protein in a
heterogeneous population of proteins and other biologics. Thus, under
designated immunoassay
conditions, the specified antibodies bind to a particular protein at least two
times greater than the
background (non-specific signal) and do not substantially bind in a
significant amount to other
proteins present in the sample. Specific binding to an antibody under such
conditions may
require an antibody that is selected for its specificity for a particular
protein. For example,
polyclonal antibodies raised to seminal basic protein from specific species
such as rat, mouse, or
human can be selected to obtain only those polyclonal antibodies that are
specifically
immunoreactive with seminal basic protein and not with other proteins, except
for polymorphic
variants and alleles of seminal basic protein. This selection may be achieved
by subtracting out
antibodies that cross-react with seminal basic protein molecules from other
species. A variety of
irmnunoassay formats may be used to select antibodies specifically
immunoreactive with a
particular protein. For example, solid-phase ELISA immunoassays are routinely
used to select
antibodies specifically immunoreactive with a protein (see, e.g., Harlow &
Lane, Antibodies, A
Laboratory Manual (1988), for a description of immunoassay formats and
conditions that can be
used to determine specific irrununoreactivity). Typically a specific or
selective reaction will be
at least twice background signal or noise and more typically more than 10 to
100 times
background.

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18
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NOs: 1 and 2.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 89, 90, 91, 92, 93,
94, 95, 96, 97,
98 and 99.According to preferred embodiments of the present invention, there
is provided an
isolated polypeptide comprising SEQ ID NOs 534 and 535.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NOs: 3, 4, 5 and 6.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 100, 101, 102, 103,
104, 105, 106
and 107.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 536, 537, 538 and 539.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 7.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 108, 109, 110, 111,
112, 113, 114,
115, 116, 117, 118, 119, 120 ,121 and 122.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 540.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript selected from the group
consisting of SEQ ID
NO. 8 and 9.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment selected from the group
consisting of SEQ ID
NOs: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,
137, 138, 139, 140,
141 and 142.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 541, 542.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 10.

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19
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: I43, I44, 145, 146,
147, 148 and
149.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 543.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 1 l, 12, 13 and 14.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 150, 151, 152, 153,
154, 155, 156,
157, 158, 159, 160, 161, 162, 163, 164, 165, 166 and 167.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 544, 545, 546 and 547.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 15.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 168, 169, 170, 171,
172, 173, 174,
175, 176, 177, 178, 179, 180, 181, 182, 183 and 184.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NO. 548.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 16.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 185, 186, 187, 188,
189, 190, 191,
192, 193, 194, 195 and 196.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 549.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 17 and 18.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 197, 198, 199, 200,
201, 202, 203,
204, 205, 206, 207, 208, 209, 210 and 211.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 550 and 551.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 19, 20, 21 and 22.
5 According to preferred embodiments of the present invention, there is
provided an
isolated polynucleotide comprising a segment SEQ ID NOs: 212, 213, 214, 215,
216, 217, 218
and 219.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 552, 553, SS4 and SSS.
10 According to preferred embodiments of the present invention, there is
provided an
isolated polynucleotide comprising a transcript SEQ ID NO. 23, 24, 25, 26 and
27.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 220, 221, 222, 223,
224, 225, 226,
227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239 and 240.
15 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide comprising SEQ ID NOs 556, SS7, SS8 and SS9.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 28, 29, 30, 31 and
32.
According to preferred embodiments of the present invention, there is provided
an
20 isolated polynucleotide comprising a segment SEQ ID NOs: 241, 242, 243,
244, 245, 246, 247,
248, 249, 2S0 and 2S 1.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 560, 561, 562 and 563.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 33, 34, and 35.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 252, 253, 254, 255,
256, 257, 258,
259, 260, 261, 262, 263, 264, 265, 266, 267, 267, 269, 270, 271, 272, 273,
274, 275, 276, 277,
278, 279, 280, 281, 282, 283, 284.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 564, 565, and 566.

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21
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 36, 37, 38, 39, 40,
41, 42 and 43.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 285, 286, 287, 288,
289, 290, 291,
292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305 and 306.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 567, 568, 569, 570, 571, 572, 573
and 574.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 44.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 307, 308, 309, 310,
31 l, 312, 313,
314, 315 and 316.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NO. 575.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 45, 46, 47 and 48.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 317, 318, 319, 320,
321, 322, 323,
324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,
339, 340, 341, 342,
343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357,
358, 359, 360, 361
and 362.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 576, 577, 578 and 579.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 49.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 363, 364 and 365.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NO, 580.
~ According to preferred embodiments of the present invention, there is
provided an
isolated polynucleotide comprising a transcript SEQ ID NO. 50, 51, 52, 53, 54,
55 and 56.

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22
According to prefen-ed embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 366, 367, 368, 369,
370, 371, 372,
373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387,
388, 389, 390, 391,
392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,
407, 408, 409, 410,
411,412,413,414,415,416,417and418.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 581, 582, 583, 584, 585, 586 and
587.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 57, 58, 59, 60, 61,
62, 63, 64, 65,
66, 67, 68, 69, 70, 71, 72 , 73 and 74.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 419, 420, 421, 422,
423, 424, 425,
426, 427, 428, 429, 43, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441,
442, 443, 444,
445, 446, 447, 448 and 449.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 588, 589, 590, 591, 592, 593, 594,
595, 596, 597,
598, 599, 600, 601 and 602.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 75, 76, 77, 78, 79
and 80.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 450, 451, 452, 453,
454, 455, 456,
457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471,
472, 473, 474 and
475.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 603, 604, 605, 606 and 607.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 81, 82, 83 and 84.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 476, 477, 478, 479,
480, 481, 482,
483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497,
498, 499, 500, 501,
502, 503 and 504.

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23
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs 608, 609, 610 and 611.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a transcript SEQ ID NO. 85, 86, 87 and 88.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a segment SEQ ID NOs: 505-532 and 533.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising SEQ ID NOs: 612, 613, 614 and 615.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encodings from clusters M85491, T10888, H14624,
H53626,
HSENA78, HUMGROGS, HUMODCA, 800299, 219178, 567314, 244808, 225299,
HUMFSA, HUMANK, 239818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853,
811723, M77903 and HSKITCR.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 608, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 207 of SSRA HUMAN,
which
also corresponds to amino acids 1 - 207 of SEQ ID NO. 608, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide corresponding
to amino
acids 208 - 214 of SEQ ID NO. 608, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 608, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to acids 208 - 214
in SEQ ID
NO. 608.
_ According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. 609, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 207 of SSRA HUMAN,
which
also corresponds to amino acids 1 - 207 of SEQ ID NO. 609.

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24
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 610, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 181 of SSRA HUMAN,
which
also corresponds to amino acids 1 - 181 of SEQ ID NO. 610, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide corresponding
to amino
acids 182 - 192 of SEQ ID NO. 610, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 610, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to acids 182 - 192
in SEQ ID
NO. 610.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 611, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 93 of SSRA HUMAN,
which also
corresponds to amino acids 1 - 93 of SEQ ID NO. 61 l, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide corresponding to
amino acids 94 -
104 of SEQ ID NO. 611, wherein said first amino acid sequence and second amino
acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 611, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 94 -
104 in SEQ
ID NO. 611.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
corresponding to
amino acids 1 - 110 of SEQ ID NO. 604, and a second amino acid sequence being
at least 90

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homologous to amino acids 1 - 112 of Q8IXM0, which also corresponds to amino
acids 111 -
222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are
contiguous and
in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
5 isolated polypeptide encoding for a head of SEQ ID NO. 604, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 110 of
SEQ ID NO. 604.
According to preferred embodiments of the present invention, there is provided
an
10 isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 83 of Q96AC2, which
also
corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide corresponding to
amino acids 84 -
15 222 of SEQ ID NO. 604, wherein said first and second amino acid sequences
are contiguous and
in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at Ieast about 85%, more
preferably at least
20 about 90% and most preferably at least about 95% homologous to amino acids
84 - 222 in SEQ
ID NO. 604.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first
amino acid
25 sequence being at least 90 % homologous to amino acids 1 - 83 of Q8N2G4,
which also
corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amino acid
sequence being
at Ieast 70%, optionally at Ieast 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide corresponding to
amino acids 84 -
222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are
contiguous and
in a sequential order.

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26
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 84 -
222 in SEQ
ID NO. 604.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 24 - 106 of BAC85518,
which also
corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide corresponding to
amino acids 84 -
222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are
contiguous and
in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 84 -
222 in SEQ
ID NO. 604.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 64 of Q96AC2, which
also
corresponds to amino acids 1 - 64 of SEQ ID NO. 605, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide corresponding to
amino acids 65 - 93
of SEQ ID NO. 605, wherein said first and second amino acid sequences are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 65 -
93 in SEQ
ID NO. 605.

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27
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first
amino acid
sequence being at Least 90 % homologous to amino acids 1 - 64 of Q8N2G4, which
also
corresponds to amino acids 1 - 64 of SEQ ID NO. 605, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at Least 95% homologous to a polypeptide corresponding to
amino acids 65 - 93
of SEQ ID NO. 605, wherein said first and second amino acid sequences are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ TD NO. 605, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 65 -
93 in SEQ
ID NO. 605.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MWVLG corresponding to amino acids 1 - 5 of SEQ ID NO. 605, second amino acid
sequence
being at least 90 % homologous to amino acids 22 - 80 of BAC85273, which also
corresponds
to amino acids 6 - 64 of SEQ ID NO. 605, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at Least 95% homologous to a polypeptide sequence corresponding to
amino acids 65
- 93 of SEQ ID NO. 605, wherein said first, second and third amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 605, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 5 of
SEQ ID NO. 605.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a
polypeptide being at

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28
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 6S -
93 in SEQ
ID NO. 605.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 24 - 87 of BAC8SS18,
which also
corresponds to amino acids 1 - 64 of SEQ ID NO. 605, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 9S% homologous to a polypeptide sequence
corresponding to amino
acids 65 - 93 of SEQ ID NO. 605, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a
polypeptide being at
Least 70%, optionally at least about 80%, preferably at Least about 8S%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 65 -
93 in SEQ
ID NO. 605.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 63 of Q96AC2, which
also
corresponds to amino acids 1 - 63 of SEQ ID NO. 606, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at Least 9S% homologous to a polypeptide sequence
corresponding to amino
acids 64 - 84 of SEQ ID NO. 606, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
2S According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of SEQ ID NO. 606, comprising a
polypeptide being at
Least 70%, optionally at least about 80%, preferably at least about 8S%; more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 64 -
84 in SEQ
ID NO. 606.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first
amino acid

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29
sequence being at least 90 % homologous to amino acids 1 - 63 of Q96AC2, which
also
corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid
sequence being
at least 70%, optionally at Ieast 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 64 - 90 of SEQ ID NO. 607, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 64 -
90 in SEQ
ID NO. 607.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids I - 63 of Q8N2G4, which
also
corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 64 - 90 of SEQ ID NO. 607 wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at Ieast about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 64 -
90 in SEQ
ID NO. 607.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 5 of SEQ ID NO. 607, second amino acid
sequence being at
least 90 % homologous to amino acids 22 - 79 of BAC85273, which also
corresponds to amino
acids 6 - 63 of SEQ ID NO. 607, and a third amino acid sequence being at least
70%, optionally

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at least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide sequence corresponding to amino acids 64 - 90
of SEQ ID
NO. 607, wherein said first, second and third amino acid sequences are
contiguous and in a
sequential order.
5 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a head of SEQ ID NO. 607, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - S of
SEQ ID NO. 607.
10 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 64 -
90 in SEQ
ID NO. 607.
15 According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 24 - 86 of BAC855I8,
which also
corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid
sequence being
at Least 70%, optionally at Least 80%, preferably at least 85%, more
preferably at least 90% and
20 most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 64 - 90 of SEQ ID NO. 607, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a
polypeptide being at
25 least 70%, optionally at least about 80%, preferably at Least about 85%,
more preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 64 -
90 in SEQ
ID NO. 607.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first
amino acid
30 sequence being at Least 70%, optionally at least 80%, preferably at least
85%, more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence

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31
corresponding to amino acids 1 - 26 of SEQ ID NO. 588, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 201 of SEQ ID NO. 588, a bridging amino acid A corresponding
to amino acid
202 of SEQ ID NO. 588, and a third amino acid sequence being at least 90 %
homologous to
amino acids 189 - 342 of SEQ ID NO. 639, which also corresponds to amino acids
203 - 356 of
SEQ ID NO. 588, wherein said first amino acid sequence, second amino acid
sequence, bridging
amino acid and third amino acid sequence axe contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 588, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence amino
acids 1 - 26 of SEQ ID NO. 588.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 588, a second amino acid
sequence being
at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also
corresponds to
amino acids 1 IO - 268 of SEQ ID NO. 588, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
269 - 356 of SEQ ID NO. 588, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 588, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 588.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 588, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least

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32
about 90% and most preferably at least about 95% homologous to amino acids 269
- 356 in SEQ
ID NO. 588.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 588, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 588, and a second amino acid
sequence being
at least 90 % homologous to amino acids 130 - 356 of SEQ ID NO. 638, which
also corresponds
to amino acids 130 - 356 of SEQ ID NO. 588, wherein said first amino acid
sequence, bridging
amino acid and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to amino acids 1 - 26 of
SEQ ID NO.
589, a second amino acid sequence being at least 90 % homologous to amino
acids 13 - 187 of
SEQ ID NO. 639, which also corresponds to amino acids 27 - 201 of SEQ ID NO.
589, a
bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 589, a
third amino acid
sequence being at least 90 % homologous to amino acids 189 - 297 of SEQ ID NO.
639, which
also corresponds to amino acids 203 - 311 of SEQ ID NO. 589, and a fourth
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first
amino acid
sequence, second amino acid sequence, bridging amino acid, third amino acid
sequence and
fourth amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at

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33
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 312
- 315 in SEQ
ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at Least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence to amino
acids 1 - 109 of SEQ ID NO. 589, a second amino acid sequence being at least
90
homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to
amino acids
110 - 268 of SEQ ID NO. 589, and a third amino acid sequence being at least
70%, optionally at
least 80%, preferably at Least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide sequence corresponding to amino acids 269 -
315 of SEQ ID
NO. 589, wherein said first amino acid sequence, second amino acid sequence
and third amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 269
- 315 in SEQ
ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 589, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 31 I of SEQ ID NO. 638, which also
corresponds to
amino acids 130 - 311 of SEQ ID NO. 589, and a third amino acid sequence being
at Least 70%,

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34
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
312 - 3I5 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated poIypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 312
- 315 in
SEQ ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 311 of Q9UJZ1,
which also
corresponds to amino acids 1 - 311 of SEQ ID NO. 589, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 3I2
- 315 in SEQ
ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeiic polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 589, a second amino acid
sequence being
at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also
corresponds to
amino acids I 10 - 268 of SEQ ID NO. 589, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most

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preferably at Least 95% homologous to a polypeptide sequence con-esponding to
amino acids
269 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
5 isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a
polypeptide being
at least 70%, optionally at Least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to amino
acids 1 - 109 of
SEQ ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
10 isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 269
- 315 in SEQ
ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
15 isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, Which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 589, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 311 of SEQ ID NO. 638, which also
corresponds to
20 amino acids 130 - 311 of SEQ ID NO. 589, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
25 order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 312
- 315 in SEQ
30 ID NO. 589.

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36
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 311 of Q9UJZ1,
which also
corresponds to amino acids 1 - 311 of SEQ ID NO. 589, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 312
- 315 in SEQ
ID NO. 589.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 590, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 187 of Q9P042, which also
corresponds to amino
acids 27 - 201 of SEQ ID NO. 590, a bridging amino acid A corresponding to
amino acid 202 of
SEQ ID NO. 590, a third amino acid sequence being at least 90 % homologous to
amino acids
189 - 254 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 268
of SEQ ID NO.
590, and a fourth amino acid sequence being at least 70%, optionally at least
80%, preferably at
least 85%, more preferably at least 90% and most preferably at least 95%
homologous to a
polypeptide sequence corresponding to amino acids 269 - 290 of SEQ ID NO. 590,
wherein said
first amino acid sequence, second amino acid sequence, bridging amino acid,
third amino acid
sequence and fourth amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 590, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at

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37
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 590.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding fox a tail of SEQ ID NO. 590, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 269
- 290 in SEQ
ID NO. 590.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 590, and a second amino
acid sequence
being at Ieast 90 % homologous to corresponding to amino acids 1 - 181 of SEQ
ID NO. 640,
which also corresponds to amino acids 110 - 290 of SEQ ID NO. 590, wherein
said first amino
acid sequence and second amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 590, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at Ieast about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 590.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first
amino acid
sequence being at least ~90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 590, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 590, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 268 of SEQ ID NO. 638, which also
corresponds to
amino acids 130 - 268 of SEQ ID NO. 590, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
269 - 290 of SEQ ID NO. 590, wherein said first amino acid sequence, bridging
amino acid,

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38
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 269
- 290 in SEQ
ID NO. 590.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZI,
which also
corresponds to amino acids 1 - 268 of SEQ ID NO. 590, and a second amino acid
sequence
1S being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 269 - 290 of SEQ ID NO. 590, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at Ieast about 9S% homologous to amino acids 269
- 290 in SEQ
ID NO. 590.
According to preferred embodiments of the present invention, there is provided
an
2S isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a
first amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 591, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 201 of SEQ ID NO. 591, a bridging amino acid A corresponding
to amino acid
202 of SEQ ID NO. 591, a third amino acid sequence being at least 90 %
homologous to amino

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39
acids 189 - 226 of SEQ ID NO. 639, which also con-esponds to amino acids 203 -
240 of SEQ
ID NO. 591, a fourth amino acid sequence being at least 70%, optionally at
least 80%,
preferably at least 8S%, more preferably at least 90% and most preferably at
least 9S%
homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of
SEQ ID NO.
591, and a fifth amino acid sequence being at least 90 % homologous to amino
acids 227 - 342
of SEQ ID NO. 639, which also corresponds to amino acids 282 - 397 of SEQ ID
NO. 591,
wherein said first amino acid sequence, second amino acid sequence, bridging
amino acid, third
amino acid sequence, fourth amino acid sequence and fifth amino acid sequence
are contiguous
and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 591, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 8S%,
more preferably at
least about 90% and most preferably at Ieast about 9S% homologous to amino
acids 1-26 of
SEQ ID NO. 591.
1S According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 591,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 8S%,
more preferably at least about 90% and most preferably at least about 9S%
homologous to the
sequence encoding amino acids 241 - 28I corresponding to SEQ ID NO. S91.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 591, a second amino acid
sequence being
2S at least 90 % homologous to amino acids 1 - 131 of SEQ ID NO. 640, which
also corresponds to
amino acids 110 - 240 of SEQ ID NO. 591, a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 8S%, more preferably at least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
241 - 281 of SEQ ID NO. 591, a fourth amino acid sequence being at least 90 %
homologous to
amino acids 132 - 1S9 of SEQ ID NO. 640, which also corresponds to amino acids
282 - 309 of
SEQ ID NO. 591, and a fifth amino acid sequence being at least 70%, optionally
at least 80%,

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preferably at least 85%, more preferably at least 90% and most preferably at
least 95%
homologous to a polypeptide sequence corresponding to amino acids 310 - 397 of
SEQ ID NO.
591, wherein said first amino acid sequence, second amino acid sequence, third
amino acid
sequence, fourth amino acid sequence and fifth amino acid sequence are
contiguous and in a
5 sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 591, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
10 SEQ ID NO. 591.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 591,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
15 sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO.
591.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 591, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 310
- 397 in
20 SEQ ID NO. 591.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2,
which also
corresponds to amino acids 1 - 128 of SEQ ID NO. 591, a bridging amino acid L
corresponding
25 to amino acid 129 of SEQ ID NO. 591, a second amino acid sequence being at
least 90
homologous to amino acids 130 - 240 of SEQ ID NO. 638, which also corresponds
to amino
acids 130 - 240 of SEQ ID NO. 591, a third amino acid sequence being at least
70%, optionally
at least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide sequence corresponding to amino acids 241 -
281 of SEQ ID
30 NO. 591, and a fourth amino acid sequence being at least 90 % homologous to
amino acids 241
- 356 of SEQ ID NO. 638, which also corresponds to amino acids 282 - 397 of
SEQ ID NO.

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4l
591, wherein said first amino acid sequence, bridging amino acid, second amino
acid sequence,
third amino acid sequence and fourth amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 591,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 591.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 240 of Q9UJZ1,
which also
corresponds to amino acids 1 - 240 of SEQ ID NO. 591, a second amino acid
sequence being at
least 70%, optionally at least 80%, preferably at Least 85%, more preferably
at Least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 241 - 281 of SEQ ID NO. 591, and a third amino acid sequence being at
least 90
homologous to amino acids 241 - 356 of Q9UJZ1, which also corresponds to amino
acids 282
397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino
acid sequence
and third amino acid sequence axe contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 591,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at Least about 90% and most preferably at least about 95%
homologous to the
sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 591.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 592, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 201 of SEQ ID NO. 592, a bridging amino acid A corresponding
to amino
acid 202 of SEQ ID NO. 592, a third amino acid sequence being at least 90 %
homologous to to

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42
amino acids 189 - 254 of SEQ ID NO. 639, which also corresponds to amino acids
203 - 268 of
SEQ ID NO. 592, and a fourth amino acid sequence being at least 90 %
homologous to amino
acids 298 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 269 -
313 of SEQ
ID NO. 592, wherein said first amino acid sequence, second amino acid
sequence, bridging
amino acid, third amino acid sequence and fourth amino acid sequence are
contiguous and in a
sequential order.
According to prefeiTed embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids I - 26 of
SEQ ID NO. 592.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in Length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise HA, having a
structure as follows: a
sequence starting from any of amino acid numbers 268-x to 268; and ending at
any of amino
acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence amino acids
1 - I09 of SEQ ID NO. 592, a second amino acid sequence being at least 90 %
homologous to
amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids
110 - 268 of
SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally
at least 80%,
preferably at least 85%, more preferably at least 90% and most preferably at
least 95%
homologous to a polypeptide sequence corresponding to amino acids 269 - 313 of
SEQ ID NO.
592, wherein said first amino acid sequence, second amino acid sequence and
third amino acid
sequence are contiguous and in a sequential order.

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43
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 592.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 592, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 269
- 313 in SEQ
ID NO. 592.
According to prefen-ed embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 592, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 268 of SEQ ID NO. 638, which also
corresponds to
amino acids 130 - 268 of SEQ ID NO. 592, and a third amino acid sequence being
at least 90
homologous to amino acids 312 - 356 of SEQ ID NO. 638, which also corresponds
to amino
acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence,
bridging amino
acid, second amino acid sequence and third amino acid sequence are contiguous
and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise HA, having a
structure as follows: a
sequence starting from any of amino acid numbers 268-x to 268; and ending at
any of amino
acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid

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44
sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZ1,
which also
corresponds to amino acids 1 - 268 of SEQ ID NO. 592, and a second amino acid
sequence
being at least 90 % homologous to amino acids 312 - 356 of Q9UJZ1, which also
corresponds to
amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise HA, having a
structure as follows: a
sequence starting from any of amino acid numbers 268-x to 268; and ending at
any of amino
acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence amino acids
1 - 109 of SEQ ID NO. 592, a second amino acid sequence being at least 90 %
homologous to
amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids
110 - 268 of
SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally
at least 80%,
preferably at least 85%, more preferably at least 90% and most preferably at
least 95%
homologous to a polypeptide sequence corresponding to amino acids 269 - 313 of
SEQ ID NO.
592, wherein said first amino acid sequence, second amino acid sequence and
third amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 592.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 592, comprising a
polypeptide being at

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least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 269
- 313 in SEQ
ID NO. 592.
According to preferred embodiments of the present invention, there is provided
an
5 isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 592, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 268 of SEQ TD NO. 638, which also
corresponds to
10 amino acids 130 - 268 of SEQ ID NO. 592, and a third amino acid sequence
being at Least 90
homologous to amino acids 312 - 356 of SEQ ID NO. 638, which also corresponds
to amino
acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence,
bridging amino
acid, second amino acid sequence and third amino acid sequence are contiguous
and in a
sequential order.
15 Accoxding to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
20 acids in length, wherein at least two amino acids comprise HA, having a
structure as follows: a
sequence starting from any of amino acid numbers 268-x to 268; and ending at
any of amino
acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first
amino acid
25 sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZ1,
which also
corresponds to amino acids 1 - 268 of SEQ ID NO. 592, and a second amino acid
sequence
being at least 90 % homologous to amino acids 312 - 356 of Q9UJZ1, which also
corresponds to
amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
30 According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592,
comprising a

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46
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at Least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise HA, having a
structure as follows: a
sequence starting from any of amino acid numbers 268-x to 268; and ending at
any of amino
acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 593, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 20I of SEQ ID NO. 593, a bridging amino acid A corresponding
to amino acid
202 of SEQ ID NO. 593, a third amino acid sequence being at least 90 %
homologous to amino
acids 189 - 226 of SEQ ID NO. 639, which also corresponds to amino acids 203 -
240 of SEQ
ID NO. 593, a fourth amino acid sequence being at Least 70%, optionally at
least 80%,
preferably at least 85%, more preferably at least 90% and most preferably at
least 95%
homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of
SEQ ID NO.
593, a fifth amino acid sequence being at least 90 % homologous to amino acids
227 - 254 of
SEQ ID NO. 639, which also corresponds to amino acids 282 - 309 of SEQ ID NO.
593, and a
sixth amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%,
more preferably at least 90% and most preferably at least 95% homologous to a
polypeptide
sequence corresponding to amino acids 310 - 331 of SEQ ID NO. 593, wherein
said first amino
acid sequence, second amino acid sequence, bridging amino acid, third amino
acid sequence,
fourth amino acid sequence, fifth amino acid sequence and sixth amino acid
sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 593, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids I - 26 of
SEQ ID NO. 593.

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47
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 593,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 310
- 331in SEQ
ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at Least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 593, a second amino acid
sequence being
at least 90 % homologous to amino acids 1 - 13I of SEQ ID NO. 640, which also
corresponds to
amino acids 110 - 240 of SEQ ID NO. 593, a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at Least 95% homologous to a polypeptide sequence corresponding to
amino acids
241 - 281 of SEQ ID NO. 593, and a fourth amino acid sequence being at least
90
homologous to amino acids 132 - 181 of SEQ ID NO. 640, which also corresponds
to amino
acids 282 - 331 of SEQ ID NO. 593, wherein said first amino acid sequence,
second amino acid
sequence, third amino acid sequence and fourth amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 593, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to anun~
acids 1 - 109 of
SEQ ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 593,
comprising an amino

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48
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 8S%,
more preferably at least about 90% and most preferably at least about 9S%
homologous to the
sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
S isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 593, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 593, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 240 of SEQ ID NO. 638, which also
corresponds to
amino acids 130 - 240 of SEQ ID NO. 593, a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 8S%, more preferably at least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
241 - 281 of SEQ ID NO. 593, a fourth amino acid sequence being at Least 90 %
homologous to
amino acids 241 - 268 of SEQ ID NO. 638, which also corresponds to amino acids
282 - 309 of
1S SEQ ID NO. 593, and a fifth amino acid sequence being at least 70%,
optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most preferably at
least 9S%
homologous to a polypeptide sequence corresponding to amino acids 310 - 331 of
SEQ ID NO.
593, wherein said first amino acid sequence, bridging amino acid, second amino
acid sequence,
third amino acid sequence, fourth amino acid sequence and fifth amino acid
sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 593,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 8S%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
2S sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO.
593.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a
polypeptide being at
Least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 310
- 331 in SEQ
ID NO. 593.

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49
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric poIypeptide encoding for SEQ ID NO. 593, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 240 of Q9UJZ1,
Which also
corresponds to amino acids 1 - 240 of SEQ ID NO. 593, a second amino acid
sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more preferably
at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 241 - 281 of SEQ ID NO. 593, a third amino acid sequence being at least
90
homologous to amino acids 241 - 268 of Q9UJZ1, which also corresponds to amino
acids 282 -
309 of SEQ ID NO. 593, and a fourth amino acid sequence being at least 70%,
optionally at
least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at Least
95% homologous to a polypeptide sequence corresponding to amino acids 310 -
331 of SEQ ID
NO. 593, wherein said first amino acid sequence, second amino acid sequence,
third amino acid
sequence and fourth amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 593,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
Least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 310
- 331 in
SEQ ID NO. 593.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 594, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 134 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 148 of SEQ ID NO. 594, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most

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preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
I49 - 183 of SEQ ID NO. 594, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
5 isolated polypeptide encoding for a head of SEQ ID NO. 594, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 594.
According to preferred embodiments of the present invention, there is provided
an
10 isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 149
- 183 in SEQ
ID NO. 594.
According to preferred embodiments of the present invention, there is provided
an
I5 isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids I - I28 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 594, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 594, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 148 of SEQ ID NO. 638, which also
corresponds to
20 amino acids 130 - 148 of SEQ ID NO. 594, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
149 - 183 of SEQ ID NO. 594, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
25 order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 149
- 183 in
30 SEQ ID NO. 594.

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51
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 148 of Q9UJZ1,
which also
corresponds to amino acids 1 - 148 of SEQ ID NO. 594, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 149 - 183 of SEQ ID NO. 594, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 149
- 183 in SEQ
ID NO. 594.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first
amino acid
sequence being at Least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 595, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 180 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 194 of SEQ ID NO. 595, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
195 - 220 of SEQ ID NO. 595, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 595, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 595.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a
polypeptide being at

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52
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at Ieast about 95% homologous to amino acids 195
- 220 in
SEQ ID NO. 595.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 595, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 595, a second amino acid
sequence being at
least 90 % homologous to amino acids 130 - 194 of SEQ ID NO. 638, which also
corresponds to
amino acids 130 - 194 of SEQ ID NO. 595, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
195 - 220 of SEQ ID NO. 595, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 195
- 220 in
SEQ ID NO. 595.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 194 of Q9UJZ1,
which also
corresponds to amino acids 1 - 194 of SEQ ID NO. 595, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 195 - 220 of SEQ ID NO. 595, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least

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53
about 90% and most preferably at least about 95% homologous to amino acids 195
- 220 in
SEQ ID NO. 595.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 596, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 134 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 148 of SEQ ID NO. 596, a third amino acid sequence being at
least 90
homologous to amino acids 180 - 187 of SEQ ID NO. 639, which also corresponds
to amino
acids 149 - 156 of SEQ ID NO. 596, a bridging amino acid A corresponding to
amino acid 157
of SEQ ID NO. 596, and a fourth amino acid sequence being at least 90 %
homologous to
amino acids 189 - 342 of SEQ ID NO. 639, which also corresponds to amino acids
I58 - 311 of
SEQ ID NO. 596, wherein said first amino acid sequence, second amino acid
sequence, third
amino acid sequence, bridging amino acid and fourth amino acid sequence are
contiguous and in
a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 596, comprising a
polypeptide being
at least 70%, optionally at Ieast about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 596.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise RV, having a
structure as follows: a
sequence starting from any of amino acid numbers 148-x to 148; and ending at
any of amino
acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first
amino acid

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54
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 109 of SEQ ID NO. 596, a second amino acid
sequence being
at least 90 % homologous to amino acids 1 - 39 of SEQ ID NO. 640, which also
corresponds to
amino acids 110 - 148 of SEQ ID NO. 596, a third amino acid sequence being at
least 90
homologous to amino acids 85 - 159 of SEQ ID NO. 640, which also corresponds
to amino
acids 149 - 223 of SEQ ID NO. 596, and a fourth amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
224 - 311 of SEQ ID NO. 596, wherein said first amino acid sequence, second
amino acid
sequence, third amino acid sequence and fourth amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 596, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 109 of
SEQ ID NO. 596.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, pxeferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise RV, having a
structure as follows: a
sequence starting from any of amino acid numbers 148-x to 148; and ending at
any of amino
acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 596, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 224
- 311 in
SEQ ID NO. 596.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2,
Which also
corresponds to amino acids 1 - 128 of SEQ ID NO. 596, a bridging amino acid L
corresponding
5 to amino acid 129 of SEQ ID NO. 596, a second amino acid sequence being at
least 90
homologous to amino acids 130 - 148 of SEQ ID NO. 638, which also corresponds
to amino
acids 130 - 148 of SEQ ID NO. 596, and a third amino acid sequence being at
least 90
homologous to corresponding to amino~acids 194 - 356 of SEQ ID NO. 638, which
also
corresponds to amino acids 149 - 311 of SEQ ID NO. 596, wherein said first
amino acid
10 sequence, bridging amino acid, second amino acid sequence and third amino
acid sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
15 at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise RV, having a
structure as follows: a
sequence starting from any of amino acid numbers 148-x to 148; and ending at
any of amino
acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2.
20 According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 148 of Q9UJZ1,
which also
corresponds to amino acids 1 - 148 of SEQ ID NO. 596, and a second amino acid
sequence
being at least 90 % homologous to amino acids 194 - 356 of Q9UJZ1, which also
corresponds to
25 amino acids 149 - 311 of SEQ ID NO. 596, wherein said first amino acid
sequence and second
amino acid sequence axe contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
30 at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino

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56
acids in length, wherein at least two amino acids comprise RV, having a
stuucture as follows: a
sequence starting from any of amino acid numbers 148-x to 148; and ending at
any of amino
acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 597, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 143 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 1S7 of SEQ ID NO. 597, and a third amino acid sequence being
at Least 90
homologous to amino acids 295 - 342 of SEQ ID NO. 639, which also corresponds
to amino
acids 1S8 - 205 of SEQ ID NO. 597, wherein said first amino acid sequence,
second amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
1 S isolated polypeptide encoding for a head of SEQ ID NO. 597, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at Least about 8S%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to amino
acids 1 - 26 of
SEQ ID NO. 597.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about SO amino
acids in length, wherein at least two amino acids comprise IV, having a
structure as follows: a
2S sequence starting from any of amino acid numbers 1 S7-x to 1 S7; and ending
at any of amino
acid numbers 1S8+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2,
which also
corresponds to amino acids 1 - 128 of SEQ ID NO. 597, a bridging amino acid L
corresponding
to amino acid 129 of SEQ ID NO. 597, a second amino acid sequence being at
least 90

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S7
homologous to amino acids 130 - 157 of SEQ ID NO. 639" which also con-esponds
to amino
acids 130 - I57 of SEQ ID NO. 597, and a third amino acid sequence being at
least 90
homologous to amino acids 309 - 356 of ID NO. 639, which also corresponds to
amino acids
158 - 205 of SEQ ID NO. 597, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at Least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise TV, having a
structure as follows: a
sequence starting from any of amino acid numbers 157-x to I57; and ending at
any of amino
acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 157 of Q9UJZ1,
which also
corresponds to amino acids 1 - 157 of SEQ ID NO. 597, and a second amino acid
sequence
being at Least 90 % homologous to amino acids 309 - 356 of Q9UJZ1, which also
corresponds to
amino acids 158 - 205 of SEQ ID NO. 597, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
Length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise IV, having a
structure as follows: a
sequence starting from any of amino acid numbers 157-x to 157; and ending at
any of amino
acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first
amino acid

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sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
Least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 598, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 128 of SEQ ID NO. 639, which also
con-esponds to
S amino acids 27 - 142 of SEQ ID NO. 598, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
143 - 161 of SEQ ID NO. 598, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 598, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 8S%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to amino
acids 1 - 26 of
SEQ ID NO. 598.
1 S According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 143
- 161 in
SEQ ID NO. 598.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first
amino acid
sequence being at Least 90 % homologous to amino acids 1 - 128 of SEQ ID NO.
638, which
also corresponds to amino acids 1 - 128 of SEQ ID NO. 598, a bridging amino
acid L
corresponding to amino acid 129 of SEQ ID NO. 598, a second amino acid
sequence being at
2S least 90 % homologous to amino acids 130 - 142 of SEQ ID NO. 638, which
also corresponds to
amino acids 130 - 142 of SEQ ID NO. 598, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 8S%, more preferably at least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
143 - 161 of SEQ ID NO. 598, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 143
- 161 in
SEQ ID NO. 598.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 142 of Q9UJZ1,
which also
corresponds to amino acids 1 - 142 of SEQ ID NO. 598, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 143 - 161 of SEQ ID NO. 598, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at Least
about 90% and most preferably at least about 95% homologous to amino acids 143
- 161 in
SEQ ID NO. 598.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 61 of SEQ ID NO.
638, which also
corresponds to amino acids 1 - 6I of SEQ ID NO. 600, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 62 - 102 of SEQ ID NO. 600, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 600, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to the sequence
amino acids 62 -
102 in SEQ ID NO. 600.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 61 of Q9UJZ1, which
also
corresponds to amino acids 1 - 61 of SEQ ID NO. 600, and a second amino acid
sequence being
5 at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 62 - 1Q2 of SEQ ID NO. 600, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
10 isolated polypeptide encoding for a tail of SEQ ID NO. 600, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 62 -
102 in SEQ
ID NO. 600.
According to preferred embodiments of the present invention, there is provided
an
15 isolated chimeric poIypeptide encoding for SEQ ID NO. 601, comprising a
first amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ TD NO. 601, a second amino acid
sequence being at
Least 90 % homologous to amino acids 13 - 47 of SEQ ID NO. 639, which also
corresponds to
20 amino acids 27 - 61 of SEQ ID NO. 601, and a third amino acid sequence
being at least 70%,
optionally at least 80%, preferably at Least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids 62
- 72 of SEQ ID NO. 601, wherein said first amino acid sequence, second amino
acid sequence
and third amino acid sequence axe contiguous and in a sequential order.
25 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a head of SEQ ID NO. 601, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 601.
30 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a
polypeptide being at

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least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 62 -
72 in SEQ
ID NO. 601.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 61 of Q96FY2, which
also
corresponds to amino acids 1 - 61 of SEQ ID NO. 601, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence con-
esponding to amino
acids 62 - 72 of SEQ ID NO. 601, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 60I, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 62 -
72 in SEQ
TD NO. 601.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first
amino acid
sequence being at Least 90 % homologous to amino acids 1 - 61 of Q9UJZ1, which
also
corresponds to amino acids 1 - 61 of SEQ ID NO. 601, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
coiTesponding to amino
acids 62 - 72 of SEQ ID NO. 601, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at Least about 85%, more
preferably at Least
about 90% and most preferably at least about 95% homologous to amino acids 62 -
72 in SEQ
ID NO. 601.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first
amino acid

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sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 26 of SEQ ID NO. 602, a second amino acid
sequence being at
least 90 % homologous to amino acids 13 - 80 of SEQ ID NO. 639, which also
corresponds to
amino acids 27 - 94 of SEQ ID NO. 602, and a third amino acid sequence being
at least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids 95
- 111 of SEQ ID NO. 602, wherein said first amino acid sequence, second amino
acid sequence
and third amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 602, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at Least about 95% homologous to amino
acids 1 - 26 of
SEQ ID NO. 602.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a
polypeptide being at
least 70°l0, optionally at least about 80%, preferably at least about
85%, more preferably at least
about 90% and most preferably at least about 95% homologous to amino aeids 95 -
111 in SEQ
ID NO. 602.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 94 of SEQ ID NO.
638, which also
corresponds to amino acids 1 - 94 of SEQ ID NO. 602, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 95 - 111 of SEQ ID NO. 602, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least

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about 90% and most preferably at least about 95% homologous to amino acids 95 -
111 in SEQ
ID NO. 602.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 94 of Q9UJZ1, which
also
corresponds to amino acids I - 94 of SEQ ID NO. 602, and a second amino acid
sequence being
at least 70%, optionally at Least 80%, preferably at least 85%, more
preferably at Least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 95 - 111 of SEQ ID NO. 602, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 95 -
111 in SEQ
ID NO. 602.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding fox SEQ ID NO. 581, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 67 of PLTP HUMAN,
which also
corresponds to amino acids 1 - 67 of SEQ ID NO. 58I, and a second amino acid
sequence being
at least 90 % homologous to amino acids 163 - 493 of PLTP~HUMAN, which also
corresponds
to amino acids 68 - 398 of SEQ ID NO. 581, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 58I,
comprising a
polypeptide having a Length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise EI~, having a
structure as follows: a
sequence starting from any of amino acid numbers 6~7-x to 67; and ending at
any of amino acid
numbers 68+ ((n-2) - x), in which x varies from 0 to n-2.

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According to prefen-ed embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 582, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 427 of PLTP HUMAN,
which also
corresponds to amino acids 1 - 427 of SEQ ID NO. 582, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 428 - 432 of SEQ ID NO. 582, wherein said Erst amino acid sequence
and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 582, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and mast preferably at least about 95% homologous to amino acids 428
- 432 in
SEQ ID NO. 582.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 584, comprising a Erst
amino acid
sequence being at least 90 % homologous to amino acids 1 - 67 of PLTP HUMAN,
which also
corresponds to amino acids 1 - 67 of SEQ ID NO. 584, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at Ieast 95% homologous to a polypeptide sequence
corresponding to amino
acids 68 - 98 of SEQ ID NO. 584, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 584, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 68 -
98 in SEQ
ID NO. 584.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 585, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 183 of PLTP'HLTMAN,
which also
corresponds to amino acids 1 - 183 of SEQ ID NO. 585, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least

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90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 184 - 200 of SEQ ID NO. 585, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
5 isolated polypeptide encoding for a tail of SEQ ID NO. 58S, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 184
- 200in SEQ
ID NO. 585.
According to preferred embodiments of the present invention, there is provided
an
10 isolated chimeric polypeptide encoding for SEQ ID NO. 586, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 205 of PLTP HUMAN,
which also
corresponds to amino acids 1 - 205 of SEQ ID NO. 586, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at Least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
15 amino acids 206 - 217 of SEQ ID NO. 586, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 586, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at Least about 85%, more
preferably at least
20 about 90% and most preferably at least about 95% homologous to amino acids
206 - 217 in
SEQ ID NO. 586.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 587, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 109 of PLTP HUMAN,
Which also
25 corresponds to amino acids I - 109 of SEQ ID NO. 587, a second amino acid
sequence bridging
amino acid sequence comprising of L, a third amino acid sequence being at
least 90
homologous to amino acids 163 - 183 of PLTP HUMAN, which also corresponds to
amino
acids 11I - 13I of SEQ TD NO. 587, and a fourth amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
30 preferably at least 95% homologous tb a polypeptide sequence corresponding
to amino acids
132 - 148 of SEQ ID NO. 587, wherein said first amino acid sequence, second
amino acid

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sequence, third amino acid sequence and fourth amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 587,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
Least about 50 amino
acids in length, wherein at least three amino acids comprise FLK having a
structure as follows
(numbering according to SEQ ID NO. 587): a sequence starting from any of amino
acid
numbers 109-x to 109; and ending at any of amino acid numbers 111 + ((n-2) -
x), in which x
varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 587, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 132
- 148 in
SEQ ID NO. 587.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 576, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 1056 of SEQ ID NO.
634, which
also corresponds to amino acids 1 - 1056 of SEQ ID NO. 576, and a second amino
acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least. 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1057 - 1081 of SEQ ID NO. 576, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 576, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at Least
about 90% and most preferably at least about 95% homologous to amino acids
1057 - 1081 in
SEQ ID NO. 576.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 577, comprising a first
amino acid

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sequence being at least 90 % homologous to amino acids 1 - 714 of SEQ ID NO.
634, which
also corresponds to amino acids 1 - 714 of SEQ ID NO. 577, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 715 - 729 of SEQ ID NO. 577, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 577, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 715
- 729 in SEQ
ID NO. 577.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 578, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 648 of SEQ ID NO.
634, which
also corresponds to amino acids 1 - 648 of SEQ ID NO. 578, a second amino acid
sequence
being at least 90 % homologous to amino acids 667 - 7I4 of SEQ ID NO. 634,
which also
corresponds to amino acids 649 - 696 of SEQ ID NO. 578, and a third amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 697 - 738 of SEQ ID NO. 578, wherein said first amino acid
sequence, second
amino acid sequence and third amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 578,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise AG, having a
structure as follows: a
sequence starting from any of amino acid numbers 648-x to 648; and ending at
any of amino
acid numbers 649+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 578, comprising a
polypeptide being at

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least 70%, optionally at Least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at Least about 95% homologous to amino acids 697
- 738 in SEQ
ID NO. 578.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 579, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 260 of SEQ ID NO.
634, which
also corresponds to amino acids 1 - 260 of SEQ ID NO. 579, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 261 - 273 of SEQ ID NO. 579, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 579, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 261
- 273 in SEQ
ID NO. 579.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 575, comprising a first
amino acid
sequence being at Least 90 % homologous to amino acids 1 - 13 of GFR2 HUMAN,
Which also
corresponds to amino acids 1 - 13 of SEQ ID NO. 575, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 14 - 30 of SEQ ID NO. 575, wherein said first amino acid sequence and
second amino
acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 575, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 14 -
30 in SEQ
ID NO. 575.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first
amino acid

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sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO.
631, which
also corresponds to amino acids 1 - 123 of SEQ ID NO. 567, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 124 - 156 of SEQ ID NO. 567, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 567, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 124
- I56 in
SEQ ID NO. 567.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 73 of SEQ ID NO. 567, and a second amino acid
sequence
being at least 90 % homologous to amino acids 1799 - 1881 of SEQ ID NO. 629,
which also
corresponds to amino acids 74 - 156 of SEQ ID NO. 567, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 567, comprising a
polypeptide being
at least 70%, optionally at Ieast about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence amino
acids 1 - 73 of SEQ ID NO. 567.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first
amino acid
sequence being at least 90 % homologous to to amino acids 1 - 52 of SEQ ID NO.
630, which
also corresponds to amino acids 1 - 52 of SEQ ID NO. 567, a bridging amino
acid G
corresponding to amino acid 53 of SEQ ID NO. 567, a second amino acid sequence
being at
least 90 % homologous to amino acids 54 - 124 of SEQ ID NO. 630, which also
corresponds to
amino acids 54 - 124 of SEQ ID NO. 567, and a third amino acid sequence being
at least 70%,

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optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
125 - 156 of SEQ ID NO. 567, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
5 order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 567, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 125
- 156 in
10 SEQ ID NO. 567.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 568, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO.
631, which
also corresponds to amino acids 1 - 123 of SEQ ID NO. 568, and a second amino
acid sequence
15 being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at Least 95% homologous to a polypeptide sequence
corresponding to
amino acids 124 - 169 of SEQ ID NO. 568, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
20 isolated polypeptide encoding for a tail of SEQ ID NO. 568, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 124
- 169 in
SEQ ID NO. 568.
According to preferred embodiments of the present invention, there is provided
an
25 isolated chimeric polypeptide encoding for SEQ ID NO. 568, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - 52 of SEQ ID NO. 568, a bridging amino acid G
corresponding
to amino acid 53 of SEQ ID NO. 568, a second amino acid sequence being at
least 90
homologous to amino acids 54 - 122 of SEQ ID NO. 630, which also corresponds
to amino
30 acids 54 - 122 of SEQ ID NO. 568, a third amino acid sequence being at
least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least

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71
95% homologous to a polypeptide sequence corresponding to amino acids 123 -
136 of SEQ ID
NO. 568, and a fourth amino acid sequence being at least 90 % homologous to
amino acids 123
- 155 of SEQ ID NO. 630, which also corresponds to amino acids 137 - 169 of
SEQ ID NO.
568, wherein said first amino acid sequence, bridging amino acid, second amino
acid sequence,
third amino acid sequence and fourth amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptidE encoding for an edge portion of SEQ ID NO. 568,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence encoding for amino acids 123 - 136, corresponding to SEQ ID NO. 568.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 569, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO.
631, which
also corresponds to amino acids 1 - 123 of SEQ ID NO. 569, and a second amino
acid sequence
being at Least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 124 - 180 of SEQ ID NO. 569, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 569, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to the sequence
amino acids 124
- 180 in SEQ ID NO. 569.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 569, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - 52 of SEQ ID NO. 569, a bridging amino acid G
corresponding
to amino acid 53 of SEQ ID NO. 569, a second amino acid sequence being at
least 90
homologous to amino acids 54 - 123 of SEQ ID NO. 630, which also corresponds
to amino
acids 54 - 123 of SEQ ID NO. 569, a third amino acid sequence being at least
70%, optionally at

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72
least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
9S% homologous to a polypeptide sequence corresponding to amino acids 124 -
148 of SEQ ID
NO. 569, and a fourth amino acid sequence being at least 90 % homologous to
amino acids 124
- 1S5 of SEQ ID NO. 630, which also corresponds to amino acids 149 - 180 of
SEQ ID NO.
569, wherein said first amino acid sequence, bridging amino acid, second amino
acid sequence,
third amino acid sequence and fourth amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 569,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 8S%,
more preferably at least about 90% and most preferably at least about 9S%
homologous to the
sequence encoding for amino acids 124 - 148, corresponding to SEQ ID NO. 569.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a Erst
amino acid
sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO.
631, which
also corresponds to amino acids I - I23 of SEQ ID NO. 570, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% arid most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 124 - 14S of SEQ ID NO. 570, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 570, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 124
- 148 in SEQ
2S ID NO. 570.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - S2 of SEQ ID NO. 570, a bridging amino acid G
corresponding
to amino acid S3 of SEQ ID NO. 570, a second amino acid sequence being at
least 90
homologous to amino acids S4 - 124 of SEQ ID NO. 630, which also corresponds
to amino

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73
acids 54 - 124 of SEQ ID NO. 570, and a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
125 - 145 of SEQ ID NO. 570, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 570, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 125
- 145 in
SEQ ID NO. 570.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 101 of SEQ ID NO.
631, which
also corresponds to amino acids 1 - 101 of SEQ ID NO. 571, and a second amino
acid sequence
being at Least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 102 - 122 of SEQ ID NO. 571, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 571, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 102
- 122 in SEQ
ID NO. 571.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids I - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - 52 of SEQ ID NO. 571, a bridging amino acid G
corresponding
to amino acid 53 of SEQ ID NO. 571, a second amino acid sequence being at
least 90
homologous to amino acids 54 - 101 of SEQ ID NO. 630, which also corresponds
to amino
acids 54 - 101 of SEQ ID NO. 571, and a third amino acid sequence being at
least 70%,

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74
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
102 - 122 of SEQ ID NO. 571, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 571, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 102
- 122 in SEQ
I0 ID NO. 571.
According to preferred embodiments of the present invention, there is provided
an
isolated chirneric polypeptide encoding for SEQ ID NO. 572, comprising a first
amino acid
sequence being at Least 90 % homologous to amino acids I - 62 of SEQ ID NO.
631, which also
corresponds to amino acids 1 - 62 of SEQ ID NO. 572, a bridging amino acid P
corresponding
to amino acid 63 of SEQ ID NO. 572, a second amino acid sequence being at
least 90
homologous to amino acids 64 - 123 of SEQ ID NO. 63I, which also corresponds
to amino
acids 64 - 123 of SEQ ID NO. 572, and a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
124 - 155 of SEQ ID NO. 572, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 572, comprising a
polypeptide being at
Least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 124
- 155 in SEQ
ID NO. 572.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 572, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - 52 of SEQ ID NO. 572, a bridging amino acid G
corresponding

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to amino acid S3 of SEQ ID NO. 572, a second amino acid sequence being at
least 90
homologous to LSDDEETIS corresponding to amino acids S4 v 62 of SEQ ID NO.
630, which
also corresponds to amino acids S4 - 62 of SEQ ID NO. 572, a bridging amino
acid P
corresponding to amino acid 63 of SEQ ID NO. 572, and a third amino acid
sequence being at
S least 90 % homologous to amino acids 64 - 1 SS of SEQ ID NO. 630, which also
corresponds to
amino acids 64 - 155 of SEQ ID NO. 572, wherein said first amino acid
sequence, bridging
amino acid, second amino acid sequence, bridging amino acid and third amino
acid sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
10 isolated chimeric polypeptide encoding for SEQ ID NO. 573 comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 62 of SEQ ID NO.
631 which also
corresponds to amino acids 1 - 62 of SEQ ID NO. 573, a bridging amino acid P
corresponding
to amino acid 63 of SEQ ID NO. 573, a second amino acid sequence being at
Least 90
homologous to amino acids 64 - 101 of SEQ ID NO. 631, which also corresponds
to amino
1 S acids 64 - 101 of SEQ ID NO. 573, and a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at Least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
102 - 109 of SEQ ID NO. 573, wherein said first amino acid sequence, bridging
amino acid,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
20 order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 573, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 102
- 109 in SEQ
25 ID NO. 573.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 573, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - S2 of SEQ ID NO.
630 which also
corresponds to amino acids 1 - S2 of SEQ ID NO. 573, a bridging amino acid G
corresponding
30 to amino acid S3 of SEQ ID NO. 573, a second amino acid sequence being at
least 90
homologous to amino acids 54 - 62 of SEQ ID NO. 630, which also corresponds to
amino acids

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54 - 62 of SEQ ID NO. 573, a bridging amino acid P corresponding to amino acid
63 of SEQ
ID NO. 573, a third amino acid sequence being at least 90 % homologous to
amino acids 64 -
101 of SEQ ID NO. 630, which also corresponds to amino acids 64 - 101 of SEQ
ID NO. 573,
and a fourth amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
S 8S%, more preferably at least 90% and most preferably at least 95%
homologous to a
polypeptide sequence corresponding to amino acids 102 - 109 of SEQ ID NO. 573,
wherein said
first amino acid sequence, bridging amino acid, second amino acid sequence,
bridging amino
acid, third amino acid sequence and fourth amino acid sequence are contiguous
and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 573, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 102
- 109 in SEQ
ID NO. 573.
1S According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 62 of SEQ ID NO.
631, Which also
corresponds to amino acids 1 - 62 of SEQ ID NO. 574, a bridging amino acid P
corresponding
to amino acid 63 of SEQ ID NO. 574, a second amino acid sequence being at
least 90
homologous to amino acids 64 - 101 of SEQ ID NO. 631, which also corresponds
to amino
acids 64 - 101 of SEQ ID NO. 574, and a third amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 8S%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
102 - 133 of SEQ ID NO. 574, wherein said first amino acid sequence, bridging
amino acid,
2S second amino acid sequence and third amino acid sequence are contiguous and
in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 574, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 102
- 133 in
SEQ ID NO. 574.

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77
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO.
630, which also
corresponds to amino acids 1 - 52 of SEQ ID NO. 574, a bridging amino acid G
corresponding
to amino acid 53 of SEQ ID NO. 574, a second amino acid sequence being at
least 90
homologous to amino acids 54 - 62 of SEQ ID NO. 630, which also corresponds to
amino acids
54 - 62 of SEQ ID NO. 574, a bridging amino acid P con-esponding to amino acid
63 of SEQ
ID NO. 574, a third amino acid sequence being at least 90 % homologous to
amino acids 64 -
101 of SEQ ID NO. 630, which also corresponds to amino acids 64 - 101 of SEQ
ID NO. 574,
and a fourth amino acid sequence being at least 90 % homologous to amino acids
124 - 155 of
SEQ ID NO. 630, which also corresponds to amino acids 102 - 133 of SEQ ID NO.
574,
wherein said first amino acid sequence, bridging amino acid, second amino acid
sequence,
bridging amino acid, third amino acid sequence and fourth amino acid sequence
are contiguous
and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 574,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at Least about 40 amino acids in length and most preferably at
least about 50 amino
acids in length, wherein at least two amino acids comprise KV, having a
structure as follows: a
sequence starting from any of amino acid numbers 101-x to 101; and ending at
any of amino
acid numbers I02+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptid a encoding for SEQ ID NO. 564, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 1617 of SEQ ID NO.
627, which
also corresponds to amino acids 1 - 1617 of SEQ ID NO. 564, and a second amino
acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1618 - 1645 of SEQ ID NO. 564, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 564, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids
1618 - 1645 in
SEQ ID NO. 564.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 565, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 2062 of SEQ ID NO.
627, which
also corresponds to amino acids 1 - 2062 of SEQ ID NO. 565, and a second amino
acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 2063 - 2074 of SEQ ID NO. 565, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
1 S isolated polypeptide encoding for a tail of SEQ ID NO. 565, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids
2063 - 2074 in
SEQ ID NO. S6S.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 566, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - S87 of SEQ ID NO.
627, which
also corresponds to amino acids 1 - 587 of SEQ ID NO. 566, and a second amino
acid sequence
ZS being at least 70%, optionally at Least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids S88 - 603 of SEQ ID NO. 566, wherein said first amino acid
sequence and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 566, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least

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about 90% and most preferably at least about 9S% homologous to amino acids 588
- 603 in
SEQ TD NO. 566.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 560, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 131 of SEQ ID NO.
625, which
also corresponds to amino acids 1 - 131 of SEQ ID NO. 560, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 132 - 139 of SEQ ID NO. 560, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 560, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 132
- 139 in SEQ
ID NO. 560.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding fox SEQ ID NO. 561, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids I - 131 of SEQ ID NO.
625, which
also corresponds to amino acids 1 - 13I of SEQ ID NO. 561, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 132 - 156 of SEQ ID NO. 561, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 561, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids I32
- I56 in SEQ
ID NO. 561.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 562, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 81 of SEQ ID NO.
625, which also

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corresponds to amino acids 1 - 81 of SEQ ID NO. 562, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 82 - 89 of SEQ ID NO. 562, wherein said first and second amino acid
sequences are
5 contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 562, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 82 -
89 in SEQ
10 ID NO. 562.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 563, comprising a first
amino acid
sequence being at Ieast 90 % homologous to amino acids 1 - 82 of SEQ ID NO.
62S which also
corresponds to amino acids 1 - 82 of SEQ ID NO. 563.
1 S According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. SS2, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 116 of FABH HUMAN, which also corresponds to
amino
20 acids 1 - 116 of SEQ ID NO. SS2, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at Ieast 9S% homologous to a polypeptide sequence corresponding to
amino acids
117 - 21S of SEQ ID NO. SS2, wherein said firstand second amino acid sequences
are
contiguous and in a sequential order.
2S According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of SEQ ID NO. SS2, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at Ieast
about 90% and most preferably at least about 9S% homologous to amino acids 117
- 21S in SEQ
ID NO. 552.
30 According to preferred embodiments of the present invention, there is
provided an
isolated chimeric polypeptide encoding for SEQ ID NO. SS2, comprising a first
amino acid

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sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373,
which also
corresponds to amino acids 1 - 116 of SEQ ID NO. 552, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least $5%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 117 - 215 of SEQ ID NO. 552, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 552, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 117
- 215 in SEQ
ID NO. 552.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence amino acids
1 - 116 ofFABH HUMAN, which also corresponds to amino acids 1 - 116 of SEQ ID
NO. 553,
and a second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90% and most preferably at least 95% homologous
to a
polypeptide sequence corresponding to amino acids 117 - 178 of SEQ ID NO. 553,
wherein said
first and second amino acid sequences are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 117
- 178 in SEQ
ID NO. 553.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373,
which also
corresponds to amino acids 1 - 116 of SEQ ID NO. 553, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to

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amino acids 117 - 178 of SEQ ID NO. 553, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a
polypeptide being at
S least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least
about 90% and most preferably at least about 9S% homologous to acids 117 - 178
in SEQ ID
NO. 553.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. SS3, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 1 - I16 of FABH HUMAN, which also corresponds to
amino
acids 1 - 116 of SEQ ID NO. 553, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 8S%, more preferably at least 90%
and most
preferably at least 9S% homologous to a polypeptide sequence corresponding to
amino acids
117 - 178 of SEQ ID NO. 553, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 117
- 178 in SEQ
ID NO. 553.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids I - II6 of AAP35373,
which also
corresponds to amino acids 1 - 116 of SEQ ID NO. SS3, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 117 - 178 of SEQ ID NO. SS3, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids I
I7 - 178 in SEQ
ID NO. 553.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding far SEQ ID NO. 554, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
coiTesponding to amino acids 1 - 116 of FABH HUMAN, which also corresponds to
amino
acids 1 - 116 of SEQ ID NO. 554, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at Least 95% homologous to a polypeptide sequence corresponding to
amino acids
117 - 126 of SEQ ID NO. 554, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 554, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 117
- 126 in SEQ
ID NO. 554.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding fox SEQ ID NO. 554, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 116 of AAP3S373,
which also
corresponds to amino acids 1 - 116 of SEQ ID NO. 554, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 117 - 126 of SEQ ID NO. 554, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 554, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least

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about 90% and most preferably at least about 9S% homologous to amino acids 117
- 126 in SEQ
ID NO. SS4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 555, comprising a first
amino acid
S sequence being at least 90 % homologous to amino acids 1 - 24 of FABH HUMAN,
which also
corresponds to amino acids 1 - 24 of SEQ ID NO. SSS, second amino acid
sequence being at
least 70%, optionally at Least 80%, preferably at least 8S%, more preferably
at least 90% and
most preferably at least 9S% homologous to a polypeptide sequence
corresponding to amino
acids 2S - 35 of SEQ ID NO. 555, and a third amino acid sequence being at
least 90
homologous to amino acids 25 - 133 of FABH HUMAN, which also corresponds to
amino
acids 36 - 144 of SEQ ID NO. SSS, wherein said first, second, third and fourth
amino acid
sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding fox an edge portion of SEQ ID NO. SSS,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 9S%
homologous to the
sequence encoding for amino acids 25 - 35 corresponding to SEQ ID NO. SSS.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. SSS, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 24 of AAP3S373,
which also
corresponds to amino acids 1 - 24 of SEQ ID NO. 555, second amino acid
sequence being at
least 70%, optionally at least 80%, preferably at least 8S%, more preferably
at least 90% and
most preferably at least 9S% homologous to a polypeptide sequence
corresponding to amino
acids 25 - 35 of SEQ ID NO. 555, and a third amino acid sequence being at
least 90
2S homologous to
GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI
VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding
to amino acids 2S - 133 of AAP3S373, which also corresponds to amino acids 36 -
144 of SEQ
ID NO. SSS, wherein said first, second and third amino acid sequences are
contiguous and in a
sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 555,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
5 sequence encoding for amino acids 25 - 35 corresponding to SEQ ID NO. 555.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 534, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 476 of EPB2 HUMAN,
which also
corresponds to amino acids 1 - 476 of SEQ ID NO. 534, and a second amino acid
sequence
10 being at least 70%, optionally at Least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 477 - 496 of SEQ ID NO. 534, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
15 isolated polypeptide encoding for a tail of SEQ ID NO. 534, comprising a
polypeptide being at
Least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 477
- 496 in SEQ
ID NO. 534.
According to preferred embodiments of the present invention, there is provided
an
20 isolated chimeric polypeptide encoding for SEQ ID NO. 535, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 270 of EPBZ HUMAN,
which also
corresponds to amino acids 1 - 270 of SEQ ID NO. 535, and a second amino acid
sequence
being at least 70%, optionally at Least 80%, preferably at Least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
25 amino acids 271 - 301 of SEQ ID NO. 535, wherein said first and second
amino acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 535, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
30 about 90% and most preferably at least about 95% homologous to amino acids
271 - 301 in SEQ
ID NO. 535.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding fox SEQ ID NO. 536, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 319 of CEA6 HUMAN,
which
also corresponds to amino acids 1 - 319 of SEQ ID NO. 536, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 320 - 324 of SEQ ID NO. 536, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 536, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 320
- 324in SEQ
ID NO. 536.
According to preferred embodiments of the present invention, there is provided
an
1S isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 234 of CEA6 HUMAN,
which
also corresponds to amino acids 1 - 234 of SEQ ID NO. 537, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 23S - 256 of SEQ ID NO. 537, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 537, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
2S about 90% and most preferably at least about 9S% homologous to amino acids
23S - 2S6 in SEQ
ID NO. 537.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 234 of Q13774,
which also
corresponds to amino acids 1 - 234 of SEQ ID NO. 537, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least

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s7
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 235 - 256 of SEQ ID NO. 537, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 537, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to acids 235 - 256
in SEQ ID
NO. 537.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 538, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 320 of CEA6 HUMAN,
which
also corresponds to amino acids 1 - 320 of SEQ ID NO. 538, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 321 - 390 of SEQ ID NO. 538, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 538, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 321
- 390 in SEQ
ID NO. 538.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 539, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 141 of CEA6 HUMAN,
which
also corresponds to amino acids 1 - 14I of SEQ ID NO. 539, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids I42 - 183 of SEQ ID NO. 539, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 539, comprising a
polypeptide being at

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least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 142
- 183 in SEQ
ID NO. 539.
According to prefen~ed embodiments of the present invention, there is provided
an
S isolated chimeric polypeptide encoding for SEQ ID NO. 540, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 167 of Q9HAPS,
which also
corresponds to amino acids 1 - 167 of SEQ ID NO. 540, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 168 - 180 of SEQ ID NO. 540, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 540, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
1S about 90% and most preferably at least about 9S% homologous to amino acids
168 - I80 in SEQ
ID NO. 540.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding fox SEQ ID NO. 541, comprising a first
amino acid
sequence being at Ieast 90 % homologous to amino acids 1 - 3S7 of Q8N441,
Which also
corresponds to amino acids 1 - 3S7 of SEQ ID NO. 541, second amino acid
sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more preferably
at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
acids 3S8 - 437 of SEQ ID NO. 541, and a third amino acid sequence being at
least 90
homologous to amino acids 3S8 - 504 of Q8N44I, which also corresponds to amino
acids 438
2S S84 of SEQ ID NO. 541, wherein said first, second and third amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of SEQ ID NO. 541,
comprising an amino
acid sequence being at least 70%, optionally at least about 80%, preferably at
least about 8S%,
more preferably at least about 90% and most preferably at least about 9S%
homologous to the
sequence encoding for acids 3S8 - 437 corresponding to SEQ ID NO. 541.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 269 of Q9H4D7,
which also
corresponds to amino acids I - 269 of SEQ ID NO. 542, and a second amino acid
sequence
S being at least 70%, optionally at least 80%, preferably at least 8S%, more
preferably at least
90% and most preferably at least 9S% homologous to a polypeptide sequence
corresponding to
amino acids 270 - 490 of SEQ ID NO. 542, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 542, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 9S% homologous to amino acids 270
- 490 in SEQ
ID NO. 542.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 269 of Q8N44I,
which also
corresponds to amino acids 1 - 269 of SEQ ID NO. 542, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at Least 8S%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 270 - 490 of SEQ ID NO. 542, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 542, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at Least about 85%, more
preferably at least
2S about 90% and most preferably at least about 95% homologous to amino acids
270 - 490 in SEQ
ID NO. 542.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 543, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 81 of SZOS HUMAN,
which also
corresponds to amino acids I - 81 of SEQ ID NO. 543.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 544, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 74 of MI2B_HUMAN,
which also
corresponds to amino acids 1 - 74 of SEQ ID NO. 544.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 545, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids I - 103 of MI2B HUMAN,
which also
corresponds to amino acids 1 - 103 of SEQ ID NO. 545.
According to preferred embodiments of the present invention, there is provided
an
10 isolated chimeric polypeptide encoding for SEQ ID NO. 546, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 61 of MI2B_HUMAN,
which also
corresponds to amino acids 1 - 61 of SEQ ID NO. 546, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide sequence
corresponding to amino
15 acids 62 - 98 of SEQ ID NO. 546, wherein said first and second amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is pxovided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 546, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
20 about 90% and most preferably at least about 95% homologous to amino acids
62 - 98 in SEQ
ID NO. 546.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 547, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
25 least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - I03 of SEQ ID NO. 547, and a second amino
acid sequence
being at least 90 % homologous to amino acids 34 - 107 of MI2B HUMAN, which
also
corresponds to amino acids 104 - 177 of SEQ ID NO. 547, wherein said first and
second amino
acid sequences are contiguous and in a sequential order.
30 According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a head of SEQ ID NO. 547, comprising a
polypeptide being

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at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 103 of
SEQ ID NO. 547.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 29 of SEQ TD NO. 548, and a second amino acid
sequence
being at least 90 % homologous to amino acids 151 - 461 of DCOR HUMAN, which
also
corresponds to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and
second amino
acid sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 29 of
SEQ ID NO. 548.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% . homologous to a polypeptide
sequence
corresponding to amino acids 1 - 29 of SEQ ID NO. 548, and a second amino acid
sequence
being at least 90 % homologous to amino acids 40 - 350 of AAA59968, which also
corresponds
to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and second amino
acid
sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a
polypeptide being
at Least 70%, optionally at Least about 80%, preferably at Least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 29 of
SEQ ID NO. 548.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first
amino acid

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sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
Least 90% and most preferably at least 9S% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 29 of SEQ ID NO. 548, and a second amino acid
sequence
being at least 90 % homologous to amino acids 86 - 396 of AAH14562, which also
corresponds
to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and second amino
acid
sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 29 of
SEQ ID NO. 548.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
1S least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 44 of SEQ ID NO. 549, second amino acid
sequence being at
least 90 % homologous to amino acids 74 - 191 of Q9NWT9, which also
corresponds to amino
acids 45 - 162 of SEQ ID NO. 549, and a third amino acid sequence being at
least 70%,
optionally at Least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide sequence corresponding to
amino acids
163 - 238 of SEQ ID NO. 549, wherein said first, second and third amino acid
sequences are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 549, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 8S%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to amino
acids 1 - 44 of
SEQ ID NO. 549.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 549, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least

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about 90% and most preferably at least about 95% homologous to amino acids 163
- 238 in SEQ
ID NO. 549.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids I - 44 of SEQ ID NO. 549, and a second amino acid
sequence
being at least 90 % homologous to amino acids 21 - 214 of TESC HUMAN, which
also
corresponds to amino acids 45 - 238 of SEQ ID NO. 549, wherein said first and
second amino
acid sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 549, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 44 of
SEQ ID NO. 549.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids I - 130 of SEQ ID NO. 550, and a second amino
acid sequence
being at least 90 % homologous to amino acids 1 - 172 of Q96C98, which also
corresponds to
amino acids I3I - 302 of SEQ ID NO. 550, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 550, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to amino
acids I - 130 of
SEQ ID NO. 550.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at

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least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 74 of SEQ ID NO. 550, and a second amino acid
sequence
being at least 90 % homologous to amino acids 53 - 280 of Q9BVA2, which also
corresponds to
amino acids 75 - 302 of SEQ ID NO. 550, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 550, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 74 of
SEQ ID NO. 550.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first
amino acid
sequence being at least 70%, optionally at Least 80%, preferably at Least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 34 of SEQ ID NO. 551, and a second amino acid
sequence
being at least 90 % homologous to corresponding to amino acids 60 - 172 of
Q96C98, which
also corresponds to amino acids 35 - 147 of SEQ ID NO. 551, wherein said first
and second
amino acid sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 551 comprising a
polypeptide being at
least 70%, optionally at Least about 80%, preferably at least about 85%, more
preferably at Least
about 90% and most preferably at least about 95% homologous to amino acids 1 -
34 of SEQ ID
NO. 551.
Accoxding to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at Least 95% homologous to a polypeptide
sequence
corresponding to amino acids 1 - 34 of SEQ ID NO. 551, and a second amino acid
sequence
being at least 90 % homologous to corresponding to amino acids 168 - 280 of
Q9BVA2, which
also corresponds to amino acids 35 - 147 of SEQ ID NO. 551, wherein said first
and second
amino acid sequences are contiguous and in a sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 551, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to amino
acids 1 - 34 of
5 SEQ ID NO. 551.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 1 -
29 of SEQ ID
10 NO. 548.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 556, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 441 of SMO2 HUMAN,
which
also corresponds to amino acids 1 - 441 of SEQ ID NO. 556, and a second amino
acid sequence
15 being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 442 - 464 of SEQ ID NO. 556, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an An
20 isolated polypeptide encoding for a tail of SEQ ID NO. 556, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 442
- 464 in SEQ
ID NO. 556.
According to preferred embodiments of the present invention, there is provided
an
25 isolated chimeric polypeptide encoding for SEQ ID NO. 557, comprising a
first amino acid
sequence being at least 90 % homologous to amino acids 1 - 428 of SMO2 HUMAN,
which
also corresponds to amino acids 1 - 428 of SEQ ID NO. 557, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
30 amino acids 429 - 434 of SEQ ID NO. 557, wherein said first and second
amino acid sequences
are contiguous and in a sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 557, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to amino acids 429
- 434 in SEQ
ID NO. 557.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 558, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 441 of SMO2 HUMAN,
which
also corresponds to amino acids 1 - 441 of SEQ ID NO. 558, and a second amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide sequence
corresponding to
amino acids 442 - 454 of SEQ ID NO. 558, wherein said first and second amino
acid sequences
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of SEQ ID NO. 558, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous amino acids 442 -
454 in SEQ
ID NO. 558.
According to prefen-ed embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for SEQ ID NO. 559, comprising a first
amino acid
sequence being at least 90 % homologous to amino acids 1 - 170 of SM02 HUMAN,
which
also corresponds to amino acids 1 - 170 of SEQ ID NO. 559, and a second amino
acid sequence
being at least 90 % homologous to amino acids 188 - 446 of SM02 HUMAN, which
also
corresponds to amino acids 171 - 429 of SEQ ID NO. 559, wherein said first and
second amino
acid sequences are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chiineric polypeptide encoding for an edge portion of SEQ ID NO. 559,
comprising a
polypeptide having a length "n", wherein n is at least about 10 amino acids in
length, optionally
at least about 20 amino acids in length, preferably at least about 30 amino
acids in length, more
preferably at least about 40 amino acids in length and most preferably at
least about 50 amino

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acids in length, wherein at least two amino acids comprise TD, having a
structure as follows: a
sequence starting from any of amino acid numbers 170-x to 170; and ending at
any of amino
acid numbers 171+ ((n-2) - x), in which x varies from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
antibody capable of specifically binding to an epitope of an amino acid
sequence from clusters
of M85491, T10888, H14624, H53626, HSENA78, HUMGROGS, HUMODCA, 800299,
219178, 567314, 244808, 225299, HUMFSA, HUMANK, 239818, HUMCA1XIA,
HSS100PCB, HUMPHOSLIP, D11853, 811723, M77903 and HSI~ITCR. Optionally said
amino acid sequence corresponds to a bridge, edge portion, tail, head or
insertion.
Optionally the antibody is capable of differentiating between a splice variant
having said
epitope and a corresponding known protein.
According to preferred embodiments of the present invention, there is provided
a kit for
detecting colon cancer, comprising a kit detecting overexpression of a splice
variant from
clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROGS, HUMODCA,
800299, 219178, 567314, 244808, 225299, HUMFSA, HUMANK, 239818, HUMCA1XIA,
HSSl00PCB, HUMPHOSLIP, D11853, 811723, M77903 and HSKITCR.
Optionally the kit comprises a NAT-based technology.
Optionally the kit further comprises at least one primer pair capable of
selectively
hybridizing to a nucleic acid sequence.
Optionally the kit further comprises at least one oligonucleotide capable of
selectively
hybridizing to a nucleic acid sequence.
Optionally the kit comprises an antibody.
Optionally the kit further comprises at least one reagent for performing an
ELISA or a
Western blot.
According to preferred embodiments of the present invention, there is provided
an
method for detecting colon cancer, comprising detecting overexpression of a
splice variant from
clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROGS, HUMODCA,
800299, 219178, 567314, 244808, 225299, HUMFSA, HUMANK, 239818, HUMCA1XIA,
HSS100PCB, HUMPHOSLIP, D11853, Rl 1723, M77903 and HSI~ITCR.
Optionally detecting overexpression is performed with a NAT-based technology.
Optionally said detecting overexpression is performed with an immunoassay.

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Optionally the immunoassay comprises an antibody.
According to preferred embodiments of the present invention, there is provided
a
biomarlcer capable of detecting colon cancer, comprising nucleic acid
sequences or a fragment
thereof, or amino acid sequences or a fragment thereof from clusters of
M85491, T10888,
H14624, H53626, HSENA78, HUMGROGS, HUMODCA, 800299, 219178, 567314, 244808,
225299, HUMFSA, HUMANK, 239818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP,
Dl 1853, 811723, M77903 and HSKITCR.
According to preferred embodiments of the present invention, there is provided
a method
for screening for colon cancer, comprising detecting colon cancer cells with a
biomarlcer or an
antibody or a method or assay.
According to preferred embodiments of the present invention, there is provided
a method
for diagnosing colon cancer, comprising detecting colon cancer cells with a
biomarker or an
antibody or a method or assay.
According to preferred embodiments of the present invention, there is provided
a method
for monitoring disease progression of colon cancer, comprising detecting colon
cancer cells with
a biomarker or an antibody or a method or assay.
According to preferred embodiments of the present invention, there is provided
a method
of selecting a therapy for colon cancer, comprising detecting colon cancer
cells with a
biomarker or an antibody or a method or assay and selecting a therapy
according to said
detection.
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
Transcript Name
AA583399 PEA 1 TO
AA583399 PEA 1 T1
AA583399 PEA 1 T2
AA583399 PEA 1 T3
AA583399 PEA 1 T4
AA583399 PEA 1 TS

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AA583399 1 T6
PEA
AA583399 PEA 1 T7
AA583399 PEA 1 T8
AA583399 1 T9
PEA
AA583399 PEA 1 T10
AA583399 PEA 1 T11
AA583399 PEA 1 T12
AA583399 PEA 1 T15
AA583399 PEA 1 T16
AA583399 PEA 1 T17
a nucleic acid sequence comprising a sequence selected from the table below:
Segment Narrie
AA583399 PEA 1 node0
AA583399 PEA 1 node3
AA583399 PEA 1 node9
AA583399 PEA 1 node10
AA583399 PEA 1 node12
AA583399 PEA 1 node14
AA583399 PEA 1 node21
AA583399 PEA 1 node24
AA583399 PEA 1 node25
AA583399 PEA 1 node29
AA583399 PEA 1 node1
AA583399 PEA 1 node2
AA583399 PEA 1 node4
AA583399 PEA 1 node5
AA583399 PEA 1 node6
AA583399 PEA 1 node7

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AA583399 PEA 1 8
node
AA583399 PEA 1 11
node
AA583399 PEA 1 19
node
AA583399 PEA_1 27
node
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below
Protein Name
AA583399 PEA l P3
AA583399 PEA 1 P2
AA583399 PEA 1 P4
AA583399 PEA 1 PS
AA583399 PEA 1 P6
AA583399 PEA 1 P8
AA583399 PEA 1 P10
AA583399 PEA 1 P11
AA583399 PEA 1 P12
AA583399 PEA 1 P14
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
Transcript Narrie _
AI684092 PEA 1 T2
AI684092 PEA_l T3
a nucleic acid sequence comprising a sequence in the table below:
~Segnaent Tl'ame

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AI684092 PEA 1 node 0
AI684092 PEA I node 2
AI684092 PEA 1 node 4
AI684092 PEA 1 node 5
AI684092 PEA 1 node 6
AI684092 PEA I node 7
AI684092 PEA l node 8
AI684092 PEA 1 node 9
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below:
prateirt-Name
AI684092 PEA 1 Pl
~AI684092'PEA~l P3
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
Transcript Name.
HUMCACH I A PEA I TO
HUMCACH 1 A PEA 1 T 1
HUMCACHIA PEA 1 T2
HUMCACH I A PEA I T3
HUMCACH1A PEA 1 T4
HUMCACH1A PEA l T6
HUMCACH1A PEA 1 T7
HUMCACH1A PEA 1 T8
HUMCACH1A PEA I TI2
~HUMCACHIA PEA 1 T13

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HUMCACH 1 A PEA 1 T14
HUMCACHlA PEA 1 T15
HUMCACH 1 A PEA 1 T I 6
HUMCACHlA PEA 1 T17
HUMCACH 1 A PEA 1 T 18
HUMCACH 1 A PEA I T 19
HUMCACH1A PEA 1 T20
HUMCACHlA PEA 1 T22
a nucleic acid sequence comprising a sequence in the table below:
Sement.Natne
HUMCACH 1 A PEA 1 node 2
HUMCACHIA PEA 1 node 5
HUMCACH1A PEA 1 node 9
HUMCACH1A PEA 1 node 11
HUMCACH 1 A PEA 1 node 14
HUMCACH1A PEA 1 node 16
HUMCACH 1 A PEA 1 node 27
HUMCACH 1 A PEA 1 node 30
HUMCACH1A PEA 1 node 33
HUMCACH1A PEA 1 node 41
HUMCACH 1 A PEA 1 node 43
HUMCACH1A PEA 1 node 45
HUMCACH1A PEA 1 node 47
HUMCACH1A PEA 1 node 55
HUMCACH1A PEA 1 node 57
HUMCACHIA PEA 1 node 70
HUMCACH1A PEA I node 72
~UMCACH1A PEA 1 node 74

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HUMCACHlA PEA I node 86
HUMCACH 1 A PEA 1 node 92
HUMCACH1A PEA 1 node 94
HUMCACH 1 A PEA 1 node 103
HUMCACH1A PEA 1 node 104
HUMCACH 1 A PEA 1 node 106
HUMCACH 1 A PEA 1 node 109
HUMCACH1A PEA 1 node 113
HUMCACH 1 A PEA I node 114
HUMCACHIA PEA 1 node 116
HUMCACH I A PEA 1 node 119
HUMCACH 1 A PEA 1 node 121
HUMCACH 1 A PEA 1 node 123
HUMCACHlA PEA 1 node 125
HUMCACHIA PEA 1 node 128
HUMCACH1A PEA 1 node 0
HUMCACHIA PEA I node 3
HUMCACHlA PEA 1 node 7
HUMCACH1A PEA 1 node 23
HUMCACHlA PEA 1 node 26
HUMCACH1A PEA 1 node 32
HUMCACH1A PEA 1 node 35
HUMCACH1A PEA 1 node 37
HUMCACH1A PEA 1 node 39
HUMCACH1A PEA 1 node 49
HUMCACH1A PEA 1 node 51
HUMCACH1A PEA 1 node 53
HUMCACHlA PEA 1 node 58
HUMCACH 1 A PEA 1 node 60
HUMCACH 1 A PEA 1 node 62

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HUMCACH1A PEA 1 64
node
HUMCACH 1 A PEA 1 66
node
HUMCACH1A PEA 1 68
node
HUMCACH 1 A PEA 1 76
node
HUMCACH 1 A PEA 1 77
node
HUMCACH1A PEA 1 79
node
HUMCACH1A PEA 1 81
node
HUMCACHlA PEA 1 84
node
HUMCACHlA PEA 1 88
node
HUMCACH1A PEA 1 90
node
HUMCACH 1 A PEA 1 96
node
HUMCACH1A PEA 1 98
node
HUMCACH1A PEA 1 100
node
HUMCACH1A PEA 1 1Ol
node
HUMCACH 1 A PEA 1 107
node
HUMCACH l A PEA 1 111
node
HUMCAGH 1 A PEA 1 117
node
HUMCACHlA PEA 1 124
node
HUMCACHlA PEA 1 126
node
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below:
~,rotein Name
HUMCACHlA PEA 1 P2
HUMCACH1A PEA 1 P3
HUMCACH1A PEA 1 P4
HUMCACHlA PEA 1 PS
HUMCACHlA PEA_ l P7

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HUMCACH1A PEA 1 P8
HUMCACHlA PEA 1 P9
HUMCACH 1 A PEA 1 P 10
HUMCACH1A PEA 1 P11
HUMCACH 1 A PEA 1 P 12
HUMCACH 1 A PEA 1 P 13
HUMCACHlA PEA 1 P14
HUMCACH1A PEA 1 P15
HUMCACH 1 A PEA- 1 P 17
According to prefen-ed embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
andlor:
Tratzscript-~laye~
u
HUMCEA PEA 1 T8
HUMCEA PEA 1 T9
HUMCEA PEA 1 T12
HUMCEA PEA 1 T14
HUMCEA PEA 1 T16
HUMCEA PEA 1 T20
HUMCEA PEA 1 T25
HUMCEA PEA 1 T26
HUMCEA PEA 1 T29
HUMCEA PEA- 1 T30
a nucleic acid sequence comprising a sequence in the table below:
Segment Name
HUMCEA PEA 1 node 0
HUMCEA PEA 1 node 2
HUMCEA PEA 1 node 6

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HUMCEA PEA 1node 11
HUMCEA PEA 1node 12
HUMCEA PEA 1node 31
HUMCEA PEA 1node 36
HUMCEA PEA 1node 42
HUMCEA PEA 1node 43
HUMCEA PEA 1node 44
HUMCEA PEA 1node 46
HUMCEA PEA 1node 48
HUMCEA PEA 1node 63
HUMCEA PEA 1node 65
HUMCEA PEA 1node 67
HUMCEA PEA 1node 3
HUMCEA PEA 1node 7
HUMCEA PEA 1node 8
HUMCEA PEA 1node 9
HUMCEA PEA 1node 10
HUMCEA PEA 1node 15
HUMCEA PEA 1node 16
HUMCEA PEA 1node 17
HUMCEA PEA 1node 18
HUMCEA PEA 1node 19
HUMCEA PEA 1node 20
HUMCEA PEA 1node 21
HUMCEA PEA 1node 22
HUMCEA PEA 1node 23
HUMCEA PEA 1node 24
HUMCEA PEA 1node 27
HUMCEA PEA 1node 29
HUMCEA PEA 1node 30

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HUMCEA PEA 1 33
node
HUMCEA PEA 1 34
node
HUMCEA PEA 1 35
node
HUMCEA PEA 1
node
45
HUMCEA PEA 1 49
node
HUMCEA PEA 1 50
node
HUMCEA PEA 1 51
node
HUMCEA PEA 1 56
node
HUMCEA PEA 1 57
node
HUMCEA PEA 1 58
node
HUMCEA PEA 1 60
node
HUMCEA PEA 1 61
node
HUMCEA PEA 1 62
node
HUMCEA PEA 1 64
node
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below
Prutei~ Name .:
HUMCEA PEA 1 P4
HUMCEA PEA 1 PS
HUMCEA PEA 1 P7
HUMCEA PEA 1 P 10
HUMCEA PEA 1 P 14
HUMCEA PEA 1 P 19
- HUMCEA-PEA_ 1,P20 -
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:

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,hrazxscripl
Naxiie
M78035 TO
M78035 T3
M78035 T4
M78035 T7
M78035 T9
M78035 T11
M78035 T17
M78035 T18
M78035 T19
M78035 T20
M78035 T27
M78035 T28
a nucleic acid sequence comprising a sequence in the table below:
Scgmeht .
Naaa~e
M78035 node 4
M78035 node 6
M78035 node 10
M78035 node l7
M78035 node 18
M78035 node 21
M78035 node 25
M78035 node 33
M78035 node 55
M78035 node 58
M78035 node 60
M78035 node 62
M78035 node 63

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M7803S node64
M78035 node6S
M7803S node69
M78035 node71
M7803S node14
M7803S node1S
M7803S node20
M7803S node24
M7803S node26
M78035 node28
M7803S node29
M7803S node30
M78035 node31
M78035 node34
M7803S node3S
M7803S node37
M78035 node40
M78035 node48
M78035 node49
M7803S nodeSO
M7803S nodeS2
M7803S nodeS3
M7803S node54
M78035 node56
M7803S nodeS7
M7803S nodeS9
According to preferred embodiments of the present invention, thexe is provided
an
isolated polypeptide comprising an amino acid sequence in the fable below:

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Protein
Name
M78035 P2
M78035 P4
M78035 P6
M78035 P8
- M78035 P18 -
M78035 P19
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
-: 'P=anscript Name
R30650~PEA 2 ~T2
830650 PEA 2 T3
830650 PEA 2 T6
830650 PEA 2 T14
830650 PEA 2 TIS
830650 PEA 2 T18
830650 PEA 2 T21
R30650,PEA 2 T23
a nucleic acid sequence comprising a sequence in the table below:
Segment Name
830650 PEA 2 node 0
830650 PEA 2 node 1
830650 PEA 2 node 3
830650 PEA 2 node 5
830650 PEA 2 node 9

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ll2
830650 PEA 2 node 11
830650 PEA 2 node 14
830650 PEA 2 node 20
830650 PEA 2 node 22
830650 PEA 2 node 24
830650 PEA 2 node 26
830650 PEA 2 node 32
830650 PEA 2 node 34
830650 PEA 2 node 36
830650 PEA 2 node 37
830650 PEA 2 node 39
830650 PEA 2 node 4I
830650 PEA 2 node 42
830650 PEA 2 node 44
830650 PEA 2 node 46
830650 PEA 2 node 50
830650 PEA 2 node 56
830650 PEA 2 node 60
830650 PEA 2 node 63
830650 PEA 2 node 67
830650 PEA 2 node 70
830650 PEA 2 node 72
830650 PEA 2 node 73
830650 PEA 2 node 75
830650 PEA 2 node 79
830650 PEA 2 node 86
830650 PEA 2 node 87
830650 PEA 2 node 89
830650 PEA 2 node 93
830650 PEA 2 node 8

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830650 PEA 2 node17
830650 PEA 2 node28
830650 PEA 2 node31
830650 PEA 2 node48
830650 PEA 2 node53
830650 PEA 2 node58
830650 PEA 2 node68
830650 PEA 2 node77
830650 PEA 2 node82
830650 PEA 2 node85
830650 PEA 2 node88
830650 PEA 2 node90
830650 PEA 2 node91
830650 PEA 2 node92
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below
Protein Name
830650 PEA 2~P4
830650 PEA 2 P5
830650 PEA 2 P8
830650 PEA 2 P12
830650 PEA 2 P13
830650 PEA 2 P15
830650 PEA 2 P17
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:

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Transcript
Na~~e
T23657 TO
T23657 T1
T23657 T2
T23657 T3
T23657 T4
T23657 TS
T23657 T6
- T'23657 T7
T23657 T8
T23657 T9
T23657 T10
T23657 T11
T23657 T12
T23657 T13
T23657 T14
T23657 T15
T23657 T16
T23657 T17
T23657 T19
T23657 T20
T23657 T21
T23657 T22
T23657 T23
T23657 T24
T23657 T28
T23657 T30
T23657 T31
T23657 T32
~T23657 T35

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T23657 T37
T23657 T38
a nucleic acid sequence comprising a sequence in the table below:
Segment
Nauze
T23657 node
2y~~
T23657 node3
T23657 node8
T23657 node16
T23657 node18
T23657 node23
T23657 node24
T23657 node27
T23657 node29
T23657 node34
T23657 node37
T23657 node38
T23657 node39
T23657 node40
T23657 node45
T23657 node46
T23657 node49
T23657 node0
T23657 node4
T23657 node6
T23657 node11
T23657 node20
T23657 node22
T23657 node25

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T23657 node26
T23657 node28
T23657 node30
T23657 node31
T23657 node32
T23657 node41
T23657 node42
T23657 node43
T23657 node44
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below:
Protein'l~a~~.a,e
.
T23657 P1
T23657 P2
T23657 P3
.1;23657 P4
- T23657 PS
T23657 P6
T23657 P7
T23657 P8
- T23657 P9
T23657 P10
T23657 P11
T23657 P12
T23657 P16
T23657 P17

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T23657 P19
T23657 P21
T23657 P22
T23657 P23
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
='~'raii~scri~t
Nape
T51958 PEA1 T4
T51958 PEA1 TS
T51958 PEA1 T6
T51958 PEA1 T8
T51958 PEA1 T12
TSI958 PEA1 T16
T51958 PEA1 T33
T51958 PEA1 T35
T51958 PEA1 T37
T51958 PEA1 T39
T51958 PEA1 T40
T51958 PEA1 T41
a nucleic acid sequence comprising a sequence in the table below:
Segment Name
T51958 PEA 1 node0
T51958 PEA 1 node7
T51958 PEA 1 node8
T51958 PEA 1 node9
T51958 PEA 1 node14

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T51958 PEA 1 16
node
T51958 PEA 1 18
node
T51958 PEA 1 21
node
T51958 PEA 1 22
node
T51958 PEA l 24
node
T51958 PEA 1 27
node
T51958 PEA 1 29
node
T51958 PEA l 33
node
T51958 PEA 1 40
node
T51958 PEA l 41
node
T51958 PEA 1 46
node
T51958 PEA 1 SI
node
T51958 PEA 1 55
node
T51958 PEA 1 67
node
T51958 PEA 1 70
node
T51958 PEA 1 74
node
T51958 PEA 1 78
node
T51958 PEA 1 11
node
T51958 PEA 1 15
node
T51958 PEA l 20
node
T51958 PEA l 26
node
T51958 PEA 1 35
node
T51958 PEA 1 36
node
T51958 PEA 1 38
node
T51958 PEA 1 39
node
T51958 PEA 1 42
node
T51958 PEA 1 43
node
T51958 PEA 1 44
node
T51958 PEA l 45
node
T51958 PEA 1 47
node

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TSI958 PEA 1 48
node
T51958 PEA 1 49
node
T51958 PEA 1 50
node
T51958 PEA 1 54
node
T51958 PEA 1 61
node
T51958 PEA 1 71
node
T51958 PEA 1 72
node
T51958 PEA 1 75
node
T51958 PEA 1 76
node
T51958 PEA 1 77
node
T51958 PEA 1 80
node
TSI958 PEA I 82
node
T51958 PEA 1 84
node
According to pz-eferi~ed embodinzerzts of the present inverztion, the>"e is
provided an
isolated polypeptide conzprising arz amino acid sequence irz the table below:
Protein Nani
T51958 PEA 1 P5
T51958 PEA 1 P6
T51958 PEA 1 P28
T51958 PEA 1 P30
T51958 PEA 1 P34
T51958 PEA 1 P35
According to preferred embodiments of the present invention, there is provided
an
isolated polynucleotide comprising a nucleic acid sequence in the table below
and/or:
Transcript Name

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217877 PEA 1 TO
217877 PEA 1 T2
Z 17877 PEA 1 T3
217877 PEA 1 T4
217877 PEA 1 T6
217877 PEA 1 T7
217877 PEA 1 T8
217877 PEA 1 T11
217877 PEA- I~T12
a nucleic acid sequence comprising a sequence in the table below:
. Segment Narne
217877 PEA 1
node
0
217877 PEA 1 3
node
217877 PEA 1 8
node
217877 PEA 1
node
9
217877 PEA l 10
node
217877 PEA 1 11
node
217877 PEA 1 l3
node
217877 PEA l 15
node
217877 PEA 1 16
node
217877 PEA 1 l8
node
217877 PEA 1 1
node
217877 PEA 1
node
2
217877 PEA 1
node
4
217877 PEA 1 5
node
217877 PEA 1 6
node
Z 17877 PEA I 14
node
~Z17877 PEA 1 17
node_

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide comprising an amino acid sequence in the table below
;Protein
wine
217877 PEA 1 P1
217877 PEA 1 P2
217877 PEA 1 P3
- 217877 PEA-1'P6
AccordiyZg to pr-eferf°ed ervibodirnents of the present inverztiofz,
they°e is provided afz
isolated polyaucleotide comp~isiug a nucleic acid sequence in the table below
ayZdlor:
T~anscr'tpt Name
HSHCGI PEA 3 TO
HSHCGI PEA 3 Tl
HSHCGI PEA 3 T2
HSHCGI PEA 3 T3
HSHCGI PEA 3 T4
HSHCGI PEA 3 TS
HSHCGI PEA 3 T6
HSHCGI PEA 3 T7
HSHCGI PEA 3 T8
HSHCGI PEA 3 T9
HSHCGI PEA 3 T10
HSHCGI PEA 3 T11
HSHCGI PEA 3 T12
HSHCGI PEA 3 T13
HSHCGI PEA 3 T14
HSHCGI PEA 3 T15

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HSHCGI PEA 3TI7
HSHCGI PEA 3T18
HSHCGI PEA 3T19
HSHCGI PEA 3T20
HSHCGI PEA 3T21
HSHCGI PEA 3 T22
HSHCGI PEA 3T23
HSHCGI PEA 3T24
a nucleic acid sequence comprising a sequence in the table below:
Segment Name
HSHCGI PEA 3 node0
HSHCGI PEA 3 node
2
HSHCGI PEA 3 node7
HSHCGI PEA 3 node8
HSHCGI PEA 3 node14
HSHCGI PEA 3 node16
HSHCGI PEA 3 node18
HSHCGI PEA 3 node
20
HSHCGI PEA 3 node
26
HSHCGI PEA 3 node28
HSHCGI PEA 3 node30
HSHCGI PEA 3 node32
HSHCGI PEA 3 node33
HSHCGI PEA 3 node34
HSHCGI PEA 3 node36
HSHCGI PEA 3 node1
HSHCGI PEA 3 node
4
HSHCGI PEA 3 node6

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HSHCGI PEA 3 9
node
HSHCGI PEA 3 11
node
HSHCGI PEA 3 13
node
HSHCGI PEA 3 19
node
HSHCGI PEA 3
node
21
HSHCGI PEA 3 node22
HSHCGI PEA 3 23
node
HSHCGI PEA 3
node
24
HSHCGI PEA 3 27
node
HSHCGI PEA 3 31
node
HSHCGI PEA 3
node
35
According to preferred embodinzents of the present invention, there is
provided an
isolated polypeptide comprising an amino acid sequence in the table below:
:: ~,xot~itlE.Naz~ae
':
HSHCGI PEA 3 P17
HSHCGI PEA 3 P18
HSHCGI PEA 3 P19
HSHCGI PEA 3 P1
HSHCGI PEA 3 P4
HSHCGI PEA 3 P6
HSHCGI PEA 3 P7
HSHCGI PEA 3 P8
HSHCGI PEA 3 P9
HSHCGI PEA 3 P12
HSHCGI PEA 3 P 13
HSHCGI PEA 3 P14
HSHCGI PEA 3 P15
HSHCGI_PEA 3 P16

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HSHCGI PEA 3 P20
HSHCGI PEA 3 P21
HSHCGI'PEA 3 P22
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P17, comprising a
i~irst amino
acid sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCPQCITQIGETSCGFFKCPLCKTSVR
RDAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYV corresponding to amino acids
1 - 218 of TM31~HUMAN, which also corresponds to amino acids 1 - 2I8 of
HSHCGI PEA 3 P17, and a second amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence EIPLMPTVERSQEARCYP
corresponding to
amino acids 219 - 236 of HSHCGI PEA 3 P17, wherein said first amino acid
sequence and
second amino acid sequence axe contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P17, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
EIPLMPTVERSQEARCYP in HSHCGI PEA 3 PI7.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P19, comprising a
first amino
acid sequence being at Ieast 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
RDAIRFNSLLRNLVEKIQALQASEVQSKRI~EATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLE corxesponding to amino acids 1 - 248 of TM31 HUMAN V2, which also
corresponds to amino acids 1 - 248 of HSHCGI PEA 3 P19, and a second amino
acid

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sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
NWRKNSVKQNQDTTPSQGA corresponding to amino acids 249 - 267 of
HSHCGI PEA 3 P19, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P19, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
NWRKNSVKQNQDTTPSQGA in HSHCGI PEA 3 P19.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P4, comprising a first
amino acid
sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1 - 256 of TM31 HUMAN V1,
which also corresponds to amino acids 1 - 256 of HSHCGI PEA 3 P4, and a second
amino
acid sequence being at least 70%, optionally at least 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence YDGPPQMYFAY corresponding to amino acids 257 - 267 of
HSHCGI PEA 3 P4, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P4, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
YDGPPQMYFAY in HSHCGI PEA 3 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P6, comprising a first
amino acid

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sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVGRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1 - 256 of TM31 HUMAN V 1,
which also corresponds to amino acids 1 - 256 of HSHCGI PEA 3 P6, and a second
amino
acid sequence being at least 70%, optionally at least 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence PTPG corresponding to amino acids 257 - 260 of HSHCGI PEA 3 P6,
wherein
said first amino acid sequence and second amino acid sequence are contiguous
and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P6, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence PTPG in
HSHCGI PEA 3 P6.
According to preferred embodiments of the present invention, there is provided
an
isolated chiineric polypeptide encoding for HSHCGI PEA 3 P7, comprising a
first amino acid
sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKVVLCRS corresponding to amino acids 1 - 257 of
TM31 HUMAN V 1, which also corresponds to amino acids 1 - 257 of HSHCGI PEA 3
P7,
and a second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90% and most preferably at least 95% homologous
to a
polypeptide having the sequence
SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA

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corresponding to amino acids 258 - 310 of HSHCGI PEA 3 P7, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P7, comprising a
polypeptide
S being at least 70%, optionally at least about 80%, preferably at least about
8S%, more preferably
at least about 90% and most preferably at least about 9S% homologous to the
sequence
SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA in
HSHCGI PEA 3 P7.
According to preferred embodiments of the present invention, there is provided
an
IO isolated chimeric polypeptide encoding for HSHCGI PEA 3 P8, comprising a
first amino acid
sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
1 S KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQ
LQADRI~KDENRFFKSMNI~NDMKSWGLLQKNNHKMNKTSEPGSSSAG corresponding to
amino acids 1 - 342 of TM31 HUMAN Vl, which also corresponds to amino acids 1 -
342 of
HSHCGI PEA 3 P8, and a second amino acid sequence being at least 70%,
optionally at least
20 80%, preferably at least 8S%, more preferably at least 90% and most
preferably at least 9S%
homologous to a polypeptide having the sequence KSPVSEY corresponding to amino
acids 343
- 349 of HSHCGI PEA 3 P8, wherein said first amino acid sequence and second
amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
25 isolated polypeptide encoding for a tail of HSHCGI PEA 3 P8, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
8S%, more preferably
at least about 90% and most preferably at least about 9S% homologous to the
sequence
KSPVSEY in HSHCGI PEA 3 P8.
According to preferred embodiments of the present invention, there is provided
an
30 isolated chimeric polypeptide encoding for HSHCGI PEA 3 P9, comprising a
first amino acid
sequence being at least 90 % homologous to

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MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1 - 256 of TM31 HUMAN V1,
which also corresponds to amino acids 1 - 256 of HSHCGI PEA 3 P9, and a second
amino
acid sequence being at Least 70%, optionally at least 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence TGEKTQ con-esponding to amino acids 257 - 262 of HSHCGI PEA 3 P9,
wherein said first amino acid sequence and second amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P9, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
TGEKTQ in HSHCGI PEA 3 P9.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P12, comprising a
first amino
acid sequence being at least 90 % homologous to
MNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAG
KVTFPVCLLASYDEISGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS
corresponding to amino acids 312 - 425 of TM31 HUMAN, which also corresponds
to amino
acids 1 - 114 of HSHCGI PEA 3 P12.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P14, comprising a
first amino
acid sequence being at Least 90 % homologous to
MASGQFVN.~LQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRI~EATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE
KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK
TKQNMPPRQLLEDIKV VLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQ

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LQADRKKDENRFFKSMNKNDMKS corresponding to amino acids 1 - 319 of
TM31 HUMAN V1, which also corresponds to amino acids 1 - 319 of HSHCGI PEA 3
P14,
and a second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90°lo and most preferably at least 95%
homologous to a
polypeptide having the sequence CK corresponding to amino acids 320 - 321 of
HSHCGI PEA 3 P14, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P16, comprising a
first amino
acid sequence being at least 90 % homologous to
MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR
KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES
KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFT
corresponding to amino acids 1 - 171 of TM31 HUMAN Vl, which also corresponds
to amino
acids 1 - 171 of HSHCGI PEA 3 P16, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide having the sequence
VRKTPSHDLWKQKHLCQSSWNPLLH corresponding to amino acids 172 - 196 of
HSHCGI PEA 3 P16, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HSHCGI PEA 3 P 16, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
VRKTPSHDLWKQKHLCQSSWNPLLH in HSHCGI PEA 3 P16.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P21, comprising a
first amino
acid sequence being at least 70%, optionally at least 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ corresponding to amino acids 1 -
28 of HSHCGI PEA 3 P21, and a second amino acid sequence being at least 90

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homologous to
FLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDV
FTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDL
KKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITG
SLKKFKDQLQADRKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGR
TTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYDEISGQGASSQDTKTFDVALSEEL
HAALSEWLTAIRAWFCEVPSS corresponding to amino acids 112 - 425 of TM31 HUMAN,
which also corresponds to amino acids 29 - 342 of HSHCGI PEA 3 P21, wherein
said first
amino acid sequence and second amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of HSHCGI PEA 3 P21, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at Ieast about 90% and most preferably at least about 95% homologous to the
sequence
MHHSDWGNIMWIFQMSPLQNFRKEERNQ of HSHCGI PEA 3 P21.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HSHCGI PEA 3 P22, comprising a
first amino
acid sequence being at least 90 % homologous to
MPPRQLLEDIKV VLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQAD
RKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAP
SHSLFRASSAGKVTFPVCLLASYDEISGQGASSQDTKTFDVALSEELHAALSEWLTATRA
WFCEVPSS corresponding to amino acids 241 - 425 of TM31~HUMAN, which also
corresponds to amino acids 1 - 185 of HSHCGI PEA 3 P22.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P5, comprising a first
amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPWLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARWLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPS V W

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WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVP
SWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLR1NS
VEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTPPPQPQQCMEFDKEATVPCSATG
REKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIASNGPQGQIRAHVQL
TVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRMHIFQ
NGSLVIHDVAPEDSGRYTCIAGNSCNIKHTEAPLYVV corresponding to amino acids 1 -
682 of PTK7 HUMAN V4, which also corresponds to amino acids 1 - 682 of
T51958 PEA 1 P5, and a second amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence
GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS
cowesponding to amino acids 683 - 733 of T51958 PEA liPS, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA 1 P5, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS in
T51958 PEA I P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P6, comprising a first
amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRR ALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRR.ATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERV TCLPPKGLPEPS V W
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVP
SWLKKPQDSQLEEGKPGYLDCLTQATPKPTWWYRNQMLISEDSRFEVFKNGTLRINS
VEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTPPPQPQQCMEFDKEATVPCSATG

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REKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIASNGPQGQIRAHVQL
TVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRM
con-esponding to amino acids 1 - 641 of PTK7 HUMAN V4, which also corresponds
to amino
acids 1 - 641 of T51958 PEA 1 P6, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide having the sequence APW
corresponding
to amino acids 642 - 644 of T51958 PEA 1 P6, wherein said first amino acid
sequence and
second amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPWLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA
corresponding to amino acids I - 409 of PTK7 HUMAN V 11, which also
corresponds to
amino acids 1 - 409 of T51958 PEAT P28, and a second amino acid sequence being
at least
70%, optionally at least 80%, preferably at least 85%, more preferably at
least 90% and most
preferably at least 95% homologous to a polypeptide having the sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV
corresponding to amino acids 410 - 459 of T51958 PEA 1 P28, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958LPEA 1 P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRWTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA
corresponding to amino acids 1 - 409 of Q8NFA5, which also corresponds to
amino acids 1 -
409 of T51958 PEA'1 P28, and a second amino acid sequence being at least 70%,
optionally
at least 80%, preferably at least 85%, more preferably at Ieast 90% and most
preferably at least
95% homologous to a polypeptide having the sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHWESV
corresponding to amino acids 410 - 459 of T5I958 PEA_I P28, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA_I P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPWLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARWLAPQDW
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR

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NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVN1TVA
corresponding to amino acids 1 - 409 of Q8NFA6, which also corresponds to
amino acids 1
409 of T51958 PEAT P28, and a second amino acid sequence being at least 70%,
optionally
at least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV
corresponding to amino acids 410 - 459 of TS 1958 PEA 1 P28, wherein said
first amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA 1 P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA
corresponding to amino acids 1 - 409 of Q8NFA7, which also corresponds to
amino acids 1 -
409 of T51958 PEA 1 P28, and a second amino acid sequence being at least 70%,
optionally
at least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence .
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV

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corresponding to amino acids 410 - 459 of T51958 PEA 1 P28, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA_l P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA-1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA
corresponding to amino acids 1 - 409 of Q8NFA8, which also corresponds to
amino acids 1 -
409 of T51958 PEA_1 P28, and a second amino acid sequence being at least 70%,
optionally
at least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV
corresponding to amino acids 410 - 459 of T51958 PEA 1 P28, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA 1 P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA~1 P28, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
, VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV
VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR
NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW
WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNTTVA
corresponding to amino acids 1 - 409 of AAN04862, which also corresponds to
amino acids 1 -
409 of T51958 PEA 1 P28, and a second amino acid sequence being at least 70%,
optionally
at least 80%, preferably at Ieast 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV
corresponding to amino acids 410 - 459 of TS 1958 PEA 1 P28, wherein said
first amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T52958~PEA_l P28, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in
T51958 PEA 1 P28.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEAT P30, comprising a first
amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIK corresponding to amino acids 1 - 122 of PTK7 HUMAN V 13, which also
corresponds
to amino acids 1 - 122 of T51958 PEA 1 P30, and a second amino acid sequence
being at least
70%, optionally at least 80%, preferably at least 85%, more preferably at
least 90% and most

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preferably at least 95% homologous to a polypeptide having the sequence
CESQGGCAQSPCQTLND corresponding to amino acids 123 - 139 of T51958~PEA 1 P30,
wherein said first amino acid sequence and second amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T51958 PEA 1 P30, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
CESQGGCAQSPCQTLND in T51958 PEA 1 P30.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P34, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPR corresponding to amino acids 1
- 157 of PTK7 HUMAN V3, which also corresponds to amino acids 1 - 157 of
T51958 PEA 1 P34.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T51958 PEA 1 P35, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP
VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA
SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH
TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIA corresponding to amino
acids 1 - 220 of PTK7 HUMAN V 11, which also corresponds to amino acids 1 -
220 of
T51958 PEA 1 P35, and a second amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence GEPGVGAEGMR corresponding to
amino
acids 221 - 231 of T51958 PEA 1 P35, wherein said first amino acid sequence
and second
amino acid sequence are contiguous and in a sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of TS 1958 PEA-1 P35, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
GEPGVGAEGMR in T51958 PEA 1 P35.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P2, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFWIFF
TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG
QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of
S21C HUMAN, which also corresponds to amino acids 1 - 675 of T23657 P2, and a
second
amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence FQLPEVHHSLNVLNRKFQKQTVHNL corresponding to amino acids 676 - 700
of T23657 P2, wherein said first amino acid sequence and second amino acid
sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P2, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
FQLPEVHHSLNVLNRKFQKQTVHNL in T23657 P2.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P3, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
IO QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF
TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG
QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of
S21C HUMAN, which also corresponds to amino acids I - 675 of T23657 P3, and a
second
amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence TIKHKAF corresponding to amino acids 676 - 682 of T23657 P3,
wherein said
first amino acid sequence and second amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P3, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence TIKHKAF
in
T23657 P3.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P4, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYV SAGQS VACGW WAFAPPCLQVLNTPKGILFFLCAAAFLQG

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MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
S QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFWIFF
TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1 - 625 of
S21C HUMAN, which also corresponds to amino acids 1 - 62S of T236S7 P4, a
second amino
acid sequence being at least 70%, optionally at least 80%, preferably at least
8S%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626 - 646 of
T236S7 P4, a third amino acid sequence being at least 90 % homologous to
GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK
corresponding to amino acids 626 - 675 of S21 C HUMAN, which also corresponds
to amino
acids 647 - 696 of T236S7 P4, and a fourth amino acid sequence being at least
70%, optionally
at least 80%, preferably at least 8S%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence TIKHKAF corresponding to
amino
acids 697 - 703 of T236S7 P4, wherein said first amino acid sequence, second
amino acid
sequence, third amino acid sequence and fourth amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of T23657 P4, comprising an
amino acid
sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%, more
preferably at least about 90% and most preferably at Ieast about 95%
homologous to the
sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T236S7 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T236S7 P4, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 8S%, more
preferably at least about

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90% and most preferably at least about 95% homologous to the sequence TIKHKAF
in
T23657 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P5, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF
TFLSSIPALTATLR corresponding to amino acids 1 - 604 of S21C HUMAN, which also
corresponds to amino acids 1 - 604 of T23657 P5.
According to preferred embodiments of the present invention, thexe is provided
an
isolated chimeric polypeptide encoding for T23657 P6, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLW V GAW W VGFLGSGAAAFFTAVPILGYPRQLPGS QRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKV corresponding to amino acids 1 - 547 of S21C HUMAN, which
also corresponds to amino acids 1 - 547 of T23657 P6, and a second amino acid
sequence being

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at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide having the sequence
SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQL
VRESPSFWFSYSL corresponding to amino acids 548 - 620 of T23657 P6, wherein
said first
amino acid sequence and second amino acid sequence axe contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P6, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
IO SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQL
VRESPSFWFSYSL in T23657 P6.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P7, comprising a first amino
acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA V CADSTS GLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQK corresponding to amino acids 1 - 546 of S21 C HUMAN, which
also corresponds to amino acids 1 - 546 of T23657 P7, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide having the sequence
MCP
corresponding to amino acids 547 - 549 of T23657 P7, wherein said first amino
acid sequence
and second amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P8, comprising a first amino
acid sequence

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being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQK corresponding to amino acids 1 - 546 of S21C HUMAN, which
also corresponds to amino acids 1 - 546 of T23657 P8, and a second amino acid
sequence being
at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and
most preferably at least 95% homologous to a polypeptide having the sequence
QHSCTNGNSTMCP corresponding to amino acids 547 - 559 of T23657 P8, wherein
said first
amino acid sequence and second amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P8, comprising a
polypeptide being at least
70%, optionally at Least about 80%, preferably at Least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
QHSCTNGNSTMCP
in T23657 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P10, comprising a first
amino acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYV SAGQSVACGW WAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES

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QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF
TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1 - 625 of
S21C HUMAN, which also corresponds to amino acids 1 - 625 of T23657 P10, a
second
amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626 - 646 of
T23657 P10, and a third amino acid sequence being at least 90 % homologous to
GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAI
ACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 626 -
722 of S21C HUMAN, which also corresponds to amino acids 647 - 743 of T23657
P10,
wherein said first amino acid sequence, second amino acid sequence and third
amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of T23657 P10, comprising an
amino acid
sequence being at least 70%, optionally at least about 80%, preferably at
least about 85%, more
preferably at least about 90% and mast preferably at least about 95%
homologous to the
sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T23657 P10.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P1 l, comprising a first
amino acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLW VGAW W VGFLGSGAAAFFTAVPILGYPRQLPGS QRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLF corresponding to amino acids 1 - 425 of S21 C HUMAN, Which also
corresponds to amino acids 1 - 425 of T23657 P11, and a second amino acid
sequence being at

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least 70%, optionally at least 80%, preferably at least 85%, more preferably
at least 90% and
most preferably at least 95% homologous to a polypeptide having the sequence
ASCPKAT
corresponding to amino acids 426 - 432 of T23657 Pl l, wherein said first
amino acid sequence
and second amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P11, comprising a
polypeptide being at least
70%, optionally at Ieast about 80%, preferably at Ieast about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence ASCPKAT
in
T23657 P11.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P12, comprising a first
amino acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPIL,GYPRQLPGSQRYAVMRAAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF
TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG
QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of
S21 C HUMAN, which also corresponds to amino acids 1 - 675 of T23657 P 12, and
a second
amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence EEENEFRRL corresponding to amino acids 676 - 684 of T23657 P 12,
wherein
said first amino acid sequence and second amino acid sequence are contiguous
and in a
sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P12, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
EEENEFRRL in
T23657 P12.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P16, comprising a first
amino acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide having the
sequence
MGTSPMADPVPAGRQHGSGLDPTTRLSPLC corresponding to amino acids 1 - 30 of
T23657 P16, and a second amino acid sequence being at least 90 % homologous to
SLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVY
RDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQ
RSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILI
MGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV
corresponding to amino acids 49I - 722 of S21 C'HUMAN, which also corresponds
to amino
acids 31 - 262 of T23657 P16, wherein said first amino acid sequence and
second amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of T23657 P16, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to the sequence
MGTSPMADPVPAGRQHGSGLDPTTRLSPLC of T23657 P16.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P17, comprising a first
amino acid sequence
being at least 90 % homologous to
MYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLV
FIF V VIFFTFLS SIPALTATLRCVRDPQRSFALGIQWIV VRILGGIPGPIAFGW VIDKACLL
WQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCL
PSQSSAPDSATDSQLQSSV corresponding to amino acids 525 - 722 of S21 C HUMAN,
which also corresponds to amino acids 1 - 198 of T23657 P17.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657_P21, comprising a first
amino acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide having the
sequence
MWTAR corresponding to amino acids 1 - 5 of T23657 P21, and a second amino
acid sequence
being at least 90 % homologous to
RCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSA
MSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV
corresponding to amino acids 604 - 722 of S21 C HUMAN, which also corresponds
to amino
acids 6 - 124 of T23657 P21, wherein said first amino acid sequence and second
amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of T23657 P21, comprising a
polypeptide being at
least 70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least
about 90% and most preferably at least about 95% homologous to the sequence
MWTAR of
T23657 P21.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for T23657 P23, comprising a first
amino acid sequence
being at least 90 % homologous to
MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC
QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG
MTVNGF1NTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG
VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG
QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM
GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMR.AAEMH
QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES
QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF
SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC
HAGCPAATETNVDGQKV corresponding to amino acids 1 - 547 of S21C HUMAN, which
also corresponds to amino acids 1 - 547 of T23657 P23, and a second amino acid
sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least

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90% and most preferably at least 95% homologous to a polypeptide having the
sequence
SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNL
SEKAPPSGFHIRCNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS
corresponding to amino acids S48 - 661 of T23657 P23, wherein said first amino
acid sequence
and second amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of T23657 P23, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNL
SEKAPPSGFHIRCNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS in
T23657 P23.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P4, comprising a first
amino acid
sequence being at least 90 % homologous to
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT
VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK
MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV
GMYSPGYSEHIPLGKFYNNRAHSNYR.AGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ
DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD
DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPIN
IQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWF
NQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYA
QMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQT
APAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV
EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCT
ATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVD
GKKYPSSEDGIQVWIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKG
RYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPI

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PVVKKKKL, corresponding to amino acids 126 - 1013 of Q9ULM1, which also
corresponds to
amino acids 1 - 888 of 830650 PEA 2 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P4, comprising a first
amino acid
sequence being at least 90 % homologous to
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT
VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK
MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV
GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ
DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD
DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPIN
IQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGTAFEDVPITSRVFFGEPGPWF
NQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 474 - 977
of Q8WUJ3, which also corresponds to amino acids 1 - 504 of 830650 PEA 2 P4,
and a
second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%,
more preferably at least 90% and most preferably at least 95% homologous to a
polypeptide
having the sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSTLS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVWTDGNQGRVVSHTSFRNSIL
QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPTPVVKKKKT, corresponding to amino acids SOS - 888
of 830650 PEA 2 P4, wherein said first amino acid sequence and second amino
acid sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P4, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence

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NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL1NFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL
QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL, in 830650 PEA 2 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P4, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1 - 91 of
830650 PEA 2 P4, and a second amino acid sequence being at least 90 %
homologous to
VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT
FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL
1NCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN
GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV
WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG
LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH
NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTER.AVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL
QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKK.KKL, corresponding to amino acids 8 - 804 of
Q9NPN9, which also corresponds to amino acids 92 - 888 of 830650 PEA 2 P4,
wherein said
first amino acid sequence and second amino acid sequence are contiguous and in
a sequential
order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650~PEA 2 P4, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of 830650 PEA 2 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P4, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT
VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK
MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV
GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ
DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD
DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1 -
389 of 830650 PEA 2 P4, and a second amino acid sequence being at least 90 %
homologous
to
SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHN-NV
TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL
VRHPDC1NVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH
YQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH
NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYWDEDSGLLFLKLKAQNEREKFAFC
SMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAWDVPMPKKLFGSQLKTKDHFLEV
KMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVWIDGNQGRVVSHTSFRNSILQGI
PWQLFNYVATIPDNSIVLMASKGRWSRGPWTRVLEKLGADRGLKLKEQMAFVGFKG
SFRPIWVTLDTEDHKAKIFQVVPIPWKKKK.L corresponding to amino acids 2 - 500 of
Q9H1K5, which also corresponds to amino acids 390 - 888 of 830650 PEA 2 P4,
wherein
said first amino acid sequence and second amino acid sequence are contiguous
and in a
sequential order.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2'P4, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
8S%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL
GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT
VHGSNGLLIKDVVGWSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK
MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV
GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ
DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD
DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of 830650 PEA 2 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for R306S0 PEA 2 PS, comprising a first
amino acid
sequence being at least 90 % homologous to
MDGVNLSTEVVYKI~GQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEV GLLSRNIIVMGEMEDKGYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL
IKDVVGWSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG
YIPKPRQDCNAVSTFWMANPNNNL1NCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS
EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR
EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN
SLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGP1NIQNCTFRKF
VALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGD
2S KTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWGAICSGCYAQMYIQAYK
TSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL
INFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH
YYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE
RAWDVPMPKKLFGSQLKTKDHFLEVKMES SKQHFFHLWDFAYIEVDGKKYPS SED
GIQVWIDGNQGRWSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRWSRGPW
TRVLEKLGADRGLKLKEQMAFVGFKGSFRPIW V TLDTEDHKAI~IFQV VPIPV VKKKI~I,

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corresponding to amino acids 18 - 1013 of Q9ULM1, which also corresponds to
amino acids 1 -
996 of 830650 PEA 2 P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P5, comprising a first
amino acid
sequence being at least 90 % homologous to
MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL
IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG
YIPKPRQDCNAVSTFWMANPNNNL1NCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS
EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR
EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN
SLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGP1NIQNCTFRKF
VALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGD
KTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 366 - 977 of Q8WUJ3,
which also corresponds to amino acids 1 - 612 of 830650 PEA~2 P5, and a second
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
NWLVRHPDC1NVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL
QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKI~KL corresponding to amino acids 613 - 996
of 830650 PEA 2 P5, wherein said first amino acid sequence and second amino
acid sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P5, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at

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least about 90% and most preferably at least about 95% homologous to the
sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL
QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPIPVVI~KIKKI, in 830650 PEA 2 P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P5, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1 - 199 of
830650 PEA 2 P5, and a second amino acid sequence being at least 90 %
homologous to
VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDWGYNSLGHCFFTEDGPEERNT
FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL
1NCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN
GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV
WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG
LDHSGRTLPIGQNFPTRGIQLYDGP1NIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH
NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND
NWLVRHPDC1NVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYWDEDSGLLFLKLKAQNEREKF
AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTER.AVVDVPMPKKLFGSQLKTKDHF
LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQWVIDGNQGRVVSHTSFRNSIL
QGIPWQLFNWATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF
KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKIKL corresponding to amino acids 8 - 804 of

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Q9NPN9, which also corresponds to amino acids 200 - 996 of 830650 PEA~2 PS,
wherein
said first amino acid sequence and second amino acid sequence are contiguous
and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of R306S0 PEA 2'PS, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
8S%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGD of R306S0 PEA 2'P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for R306S0 PEA 2 P5, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 8S%,
more preferably at
1S least 90% and most preferably at least 9S% homologous to a polypeptide
having the sequence
MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL
IKDWGWSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG
YIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS
EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR
EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN
SLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1 - 497 of
2S R306S0 PEA 2 PS, and a second amino acid sequence being at least 90 %
homologous to
SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV
TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL
VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH
YQQYQPWTLQKGYTIHWDQTAPAELAIWL1NFNKGDWIRVGLCYPRGTTFSILSDVH
NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYWDEDSGLLFLKLKAQNEREKFAFC
SMKGCER TKTK A T .IpKNAGVSDCTATAYPKFTERAV VDVPMPKKLFGSQLKTKDHFLEV

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KMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGI
PWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKG
SFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKI, corresponding to amino acids 2 - 500 of
Q9H1K5, which also corresponds to amino acids 498 - 996 of 830650 PEA 2 P5,
wherein
said first amino acid sequence and second amino acid sequence are contiguous
and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P5, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI
LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE
IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL
IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG
YIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS
EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR
EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN
SLFVGESGNVGTEMMDNRIWGPGGLDH of 830650 PEA 2 P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P8, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRTLSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK
corresponding to amino acids 1 - 348 of 830650 PEA 2 P8, a second amino acid
sequence
being at least 90 % homologous to

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AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKP
VRPKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPN
QVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDT
FGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSI
HHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS
DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIF
HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLS
IISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTL
ASGGTFP'YDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIR
GIQLYDGP1NIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV
FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWR
GAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPV VTLQKG
YTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFV
RTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 1 - 788 of Q9ULM1,
which also corresponds to amino acids 349 - 1136 of 830650 PEA 2 P8, and a
third amino
acid sequence being at least 70%, optionally at Ieast 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence KQRTISWR corresponding to amino acids 1137 - 1144 of 830650 PEA 2
P8,
wherein said first amino acid sequence, second amino acid sequence and third
amino acid
sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P8, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MG.AAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERS WGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERL VQYLNAVPDGRTI;S VAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK of
830650 PEA 2 P8.

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According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P8, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
KQRTISWR in 830650 PEA 2 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P8, comprising a first
amino acid
sequence being at least 90 % homologous to
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVWKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPM~.'LHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDWGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL1NCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGI
QLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF
GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids
1 - 977 of Q8WJ3, which also corresponds to amino acids 1 - 977 of 830650 PEA
2 P8, and
a second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90% and most preferably at least 95% homologous
to a
polypeptide having the sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS

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DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGKQRTISWR
corresponding to amino acids 978 - 1144 of 830650 PEA 2 P8, wherein said first
amino acid
sequence and second amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P8, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGKQRTISWR in
830650 PEA 2 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P8, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTS SATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEY'FNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to ammo acids
1 - 564 of 830650 PEA 2 P8, a second amino acid sequence being at least 90 %
homologous
to
VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT
FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL
1NCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN
GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV

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WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG
LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH
NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL1NFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino
acids 8 - 579 of Q9NPN9, which also corresponds to amino acids 565 - 1136 of
830650 PEA 2 P8, and a third amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence KQRTISWR corresponding to
amino acids
1137 - 1144 of 830650 PEA 2 P8, wherein said first amino acid sequence, second
amino acid
sequence and third amino acid sequence are contiguous and in a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P8, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKTSDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMR.A.EVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of 830650 PEA 2 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P8, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
KQRTISWR in 830650 PEA 2 P8.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P8, comprising a first
amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALGPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPW SFLTVKGNPS S S VEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKA,AHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino
acids 1 - 862 of 830650 PEA 2 P8, a second amino acid sequence being at least
90
homologous to
SGRTLPIGQNFPIRGIQLYDGP1NIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV
TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL
VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH
YQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH
NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids
2 - 275 of Q9H1K5, which also corresponds to amino acids 863 - 1136 of 830650
PEA 2 P8,
and a third amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90% and most preferably at least 95% homologous
to a
polypeptide having the sequence KQRTISWR corresponding to amino acids 1137 -
1144 of

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830650 PEA 2 P8, wherein said first amino acid sequence, second amino acid
sequence and
third amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P8, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
I0 YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL1NCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of 830650 PEA 2 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA 2 P8, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
KQRTISWR in 830650 PEA 2 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P15, comprising a
first amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MG.AAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI

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GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
S SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK
corresponding to amino acids 1 - 348 ofR30650 PEA'2 P15, and a second amino
acid
sequence being at least 90 % homologous to
AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKP
VRPKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPN
IO QVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDT
FGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSI
HHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS
DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFVVMANPNNNLINCAAAGSEETGFWFIF
HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLS
15 IISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTL
ASGGTFPYDDGSKQEII~NSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIR
GIQLYDGP1NIQNCTFRKFVALEGRHT SALAFRLNNAW Q SCPHNNVTGIAFEDVPITSRV
FFGEPGPVdFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWR
GAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKG
20 YTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFV
RTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 1 - 788 of Q9ULM1,
which also corresponds to amino acids 349 - 1 I36 of 830650 PEA 2 PIS, wherein
said first
amino acid sequence and second amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
25 isolated polypeptide encoding for a head of 830650 PEA 2 PIS, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
30 FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV

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NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK of
830650 PEA 2 P15.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P15, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPW SFLTVKGNPS S S VEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDWGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGI
QLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF
GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids
1 - 977 of Q8WUJ3, which also corresponds to amino acids 1 - 977 of 830650 PEA
2 P15,
and a second amino acid sequence being at least 70%, optionally at least 80%,
preferably at least
85%, more preferably at least 90% and most preferably at least 95% homologous
to a
polypeptide having the sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPWTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino

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acids 978 - 1136 of 830650 PEA 2 P 15, wherein said first amino acid sequence
and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of 830650 PEA,2 P 15, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 95% homologous to the
sequence
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL1NFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG in
830650 PEA 2 P15.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P15, comprising a
first amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVTVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEV VYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids
I - 564 of 830650 PEA 2 P15, and a second amino acid sequence being at least
90 %
homologous to
VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT
FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL
INCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN
GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV
WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG

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LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH
NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND
NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT
RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS
DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino
acids 8 - 579 of Q9NPN9, which also corresponds to amino acids 565 - 1136 of
830650 PEA 2 P15, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P 15, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKA.AHLEGTELKHMGQQLVGQYPIHFHLAGD ofR30650 PEA 2_P15.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for 830650 PEA 2 P15, comprising a
first amino acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG

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SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR
PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino
acids 1 - 862 of 830650 PEA 2 P15, and a second amino acid sequence being at
least 90
homologous to
SGRTLPIGQNFPIRGIQLYDGP1NIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV
TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL
VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH
YQQYQPWTLQKGYTIHWDQTAPAELAIWL1NFNKGDWIRVGLCYPRGTTFSILSDVH
NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids
2 - 275 of Q9H1K5, which also corresponds to amino acids 863 - 1136 of 830650
PEA 2 P15,
wherein said first amino acid sequence and second amino acid sequence are
contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of 830650 PEA 2 P15, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTS SATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPW SFLTVKGNPS S SVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH
PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR

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PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV
KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG
GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH
TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR
DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH
VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS
ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS
GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of
R306S0 PEA 2 P1S.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for R306S0 PEA 2 P17, comprising a
first amino acid
sequence being at least 90 % homologous to
MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI
GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN
FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG
YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV
NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG
SAAARVFKLFQTEHGEYFNVSLSSEWVQ corresponding to amino acids 1 - 321 of
Q8WUJ3, which also corresponds to amino acids 1 - 321 of R306S0 PEA 2 P17, and
a second
amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence GEEFQTIW corresponding to amino acids 322 - 329 of R306S0 PEA 2
P17,
wherein said first amino acid sequence and second amino acid sequence are
contiguous and in a
sequential order.
2S According to preferred embodiments of the present invention, there is
provided an
isolated polypeptide encoding for a tail of R306S0 PEA 2 P17, comprising a
polypeptide being
at least 70%, optionally at least about 80%, preferably at least about 85%,
more preferably at
least about 90% and most preferably at least about 9S% homologous to the
sequence
GEEFQTIW in 830650 PEA 2 P17.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for M7803S P4, comprising a first amino
acid sequence

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being at least 90 % homologous to
MPGLMRMRERYSASKPLKGARIAGCLHMTVETAVLIETLVTLGAEVQWSSCNIFSTQD
HAAAAIAKAGIPVYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYP
QLLPGIRGISEETTTGVHNLYKMMANGILKVPAINWDSVTKSKFDNLYGCRESLIDGIK
RATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTT
MDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVN
IKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDK
YPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY
corresponding to amino acids 29 - 432 of SAHH HUMAN, which also corresponds to
amino
I O acids I - 404 of M78035 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for M78035 P6, comprising a first amino
acid sequence
being at least 90 % homologous to
MILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMANGILKVPATNVNDSVT
KSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEI
DP1NALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFD
VEIDVKWLNENAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNS
FTNQVMAQIELWTHPDKYPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLG
MSCDGPFKPDHYRY corresponding to amino acids 127 - 432 of SAHH HUMAN, which
also corresponds to amino acids 1 - 306 of M78035 P6.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for M78035 P8, comprising a first amino
acid sequence
being at least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least
90% and most preferably at least 95% homologous to a polypeptide having the
sequence
MSDKLPYKV corresponding to amino acids 1 - 9 ofM78035 P8, and a second amino
acid
sequence being at least 90 % homologous to
WAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEET
TTGVHNLANGILKVPAlNVNDS VTKSKFDNLYGCRESLIDGIKRATDVMIAGKV
AWAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTTMDEACQEGN1FV
TTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVNIKPQVDRYRLKN
GRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGVHFLPKKL

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DEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino
acids 99 - 432 of SAHH HUMAN, which also corresponds to amino acids 10 - 343
of
M78035 P8, Wherein said first amino acid sequence and second amino acid
sequence are
contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of M78035 P8, comprising a
polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%, more
preferably at least about
90% and most preferably at least about 95% homologous to the sequence
MSDKLPYKV of
M78035 P8.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCEA PEA 1 P4, comprising a first
amino
acid sequence being at least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT
LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVL
corresponding to amino acids 1 - 234 of CEAS HUMAN, which also corresponds to
amino
acids 1 - 234 of HUMCEA PEA 1 P4, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide having the sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKN
RRGGAASVLGGSGSTPYDGRNR corresponding to amino acids 235 - 315 of
HUMCEA PEA 1 P4, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HUMCEA PEA-1 P4, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKN
RRGGAASVLGGSGSTPYDGRNR in HUMCEA PEA 1 P4.

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According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCEA_PEA 1 P5, comprising a first
amino
acid sequence being at least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT
LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDA
PTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTC
QAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWV
NNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDD
PTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQ
ANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVN
GQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTP
IISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFV
SNLATGRNNSIVKSITVS corresponding to amino acids 1 - 675 of LEAS~HUMAN, which
also corresponds to amino acids 1 - 675 of HUMCEA PEA 1 P5, and a second amino
acid
sequence being at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at
least 90% and most preferably at least 95% homologous to a polypeptide having
the sequence
GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS corresponding to amino
acids 676 - 719 of HUMCEA PEA 1 P5, wherein said first amino acid sequence and
second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HUMCEA PEA 1 P5, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS in HUMCEA PEA 1 P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCEA PEA 1 P7, comprising a first
amino
acid sequence being at least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT

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LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDA
PTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTC
QAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWV
NNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDD
PTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQ
ANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVN
GQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTP
IISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFV
SNLATGRNNSIVKSITV corresponding to amino acids I - 674 of CEAS HUMAN, which
also
corresponds to amino acids 1 - 674 of HUMCEA PEA-1 P7, and a second amino acid
sequence being at least 90 % homologous to SAGATVGIMIGVLVGVALI corresponding
to
amino acids 684 - 702 of CEAS HUMAN, which also corresponds to amino acids 675
- 693 of
HUMCEA PEA-1 P7, wherein said first amino acid sequence and second amino acid
sequence
are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of HUMCEA PEA 1 P7,
comprising a polypeptide having a length "n", wherein n is at least about 10
amino acids in
length, optionally at Least about 20 amino acids in length, preferably at
least about 30 amino
acids in length, more preferably at least about 40 amino acids in length and
most preferably at
least about 50 amino acids in length, wherein at least two amino acids
comprise VS, having a
structure as follows: a sequence starting from any of amino acid numbers 674-x
to 674; and
ending at any of amino acid numbers 675+ ((n-2) - x), in which x varies from 0
to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCEA PEA 1 P10, comprising a
first amino
acid sequence being at least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT
LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDS corresponding to
amino acids 1 - 228 of CEAS HUMAN, which also corresponds to amino acids 1 -
228 of

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HUMCEA PEA_l P 10, and a second amino acid sequence being at least 90 %
homologous to
VILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNI
TEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEA
QNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPV
TLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITP
NNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
corresponding to amino acids 407 - 702 of LEAS HUMAN, which also corresponds
to amino
acids 229 - 524 of HUMCEA PEA 1 P10, wherein said first amino acid sequence
and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of HUMCEA PEA 1
P10,
comprising a polypeptide having a length "n", wherein n is at least about 10
amino acids in
length, optionally at least about 20 amino acids in length, preferably at
least about 30 amino
acids in length, more preferably at least about 40 amino acids in length and
most preferably at
least about 50 amino acids in length, wherein at least two amino acids
comprise SV, having a
structure as follows: a sequence starting from any of amino acid numbers 228-x
to 228; and
ending at any of amino acid numbers 229+ ((n-2) - x), in which x varies from 0
to n-2.
According to preferred embodiments of the present invention, thexe is provided
an
isolated chimeric polypeptide encoding for HUMCEA PEA 1 P19, comprising a
first amino
acid sequence being at least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT
LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILN
corresponding to amino acids 1 - 232 of CEAS~HUMAN, which also corresponds to
amino
acids 1 - 232 of HUMCEA PEA 1 P19, and a second amino acid sequence being at
least 90
homologous to
VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNN
GTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
corresponding to amino acids 589 - 702 of LEAS HUMAN, which also corresponds
to amino

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acids 233 - 346 of HUMCEA PEA'I P19, wherein said first amino acid sequence
and second
amino acid sequence are contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of HUMCEA PEA_1
P19,
comprising a polypeptide having a length "n", wherein n is at least about 10
amino acids in
length, optionally at Least about 20 amino acids in length, preferably at
least about 30 amino
acids in length, more preferably at least about 40 amino acids in length and
most preferably at
least about 50 amino acids in length, wherein at least two amino acids
comprise NV, having a
structure as follows: a sequence starting from any of amino acid numbers 232-x
to 232; and
IO ending at any of amino acid numbers 233+ ((n-2) - x), in which x varies
from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCEA PEA-1 P20, comprising a
first amino
acid sequence being at Least 90 % homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
IS HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT
LHVIKSDLVNEEATGQFRVYP corresponding to amino acids 1 - 142 of LEAS HUMAN,
which also corresponds to amino acids 1 - 142 of HUMCEA PEA 1 P20, and a
second amino
acid sequence being at least 90 % homologous to
ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLVt~WNGQSLPVSPRLQLSNGNRTLT
20 LFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHS
ASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASG
TSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 499 - 702 of
CEAS HUMAN, which also corresponds to amino acids 143 - 346 of HUMCEA PEA_1
P20,
wherein said first amino acid sequence and second amino acid sequence are
contiguous and in a
25 sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for an edge portion of HUMCEA PEA 1
P20,
30 comprising a polypeptide having a Length "n", wherein n is at Least about
10 amino acids in
length, optionally at least about 20 amino acids in length, preferably at
least about 30 amino

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acids in length, more preferably at least about 40 amino acids in length and
most preferably at
least about 50 amino acids in length, wherein at least two amino acids
comprise PE, having a
structure as follows: a sequence starting from any of amino acid numbers 142-x
to I42; and
ending at any of amino acid numbers I43+ ((n-2) - x), in which x varies from 0
to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCACH1A PEA I P7, comprising a
first
amino acid sequence being at least 90 % homologous to
MPTSETESWTENVSGEGENRGCCGSL corresponding to amino acids 466 - 492 of
CCAD HUMAN V3, which also corresponds to amino acids 1 - 27 of
HUMCACHlA PEA 1 P7, a second amino acid sequence being at Least 70%,
optionally at
least 80%, preferably at least 85%, more preferably at least 90% and most
preferably at least
95% homologous to a polypeptide having the sequence WCWWRRRGAAKAGPSGCRRWG
corresponding to amino acids 28 - 48 of HUMCACH1A PEA I P7, and a third amino
acid
sequence being at least 90 % homologous to
IS QAISKSKLSRRWRRWRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTISSEHWQPDWL
TQIQDIANKVLLALFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGITETILVELEIMS
PLGISVFRCVRLLRIFKVTRHWTSLSNLVASLLNSMKSIASLLLLLFLFIIIFSLLGMQLFG
GKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWAVMYDGIMAYGGPSSSGMIVCIYF
IILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARKESLENKI~PE
VNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVPAGPRPRRISELN
MKEKIAPIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSSAALAAEDPIRSHSFR
NTILGWDYAFTAIFTVEILLKMTTFGAFLHKGAFCRNYFNLLDMLVVGVSLVSFGIQSS
AISWKILRVLRVLRPLRAINRAKGLKHWQCVFVAIRTIGNIMIVTTLLQFMFACIGVQ
LFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSPVVRERIWQNSDFNFDNVLSAMMA
LFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVAFFMMNIFVGFVIVTFQE
QGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWVVNSSPFEYMMFVL
TMT .NTLCLAMQHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFKPKGYFSDAWNT
FDSLIVIGSIIDVALSEADPTESENVPWTATPGNSEESNRISITFFRLFRVMRLVKLLSRGE
GIRTLLWTFIKSFQALP WALLIAMLFFIYAVIGMQMFGKVAMRDNNQINRNNNFQTFP
QAVLLLFRCATGEAWQEIMLACLPGKLCDPESDYNPGEEYTCGSNFAIVYFISFYMLCA
FLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKGRIKHLDWTLLRRI

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QPPLGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKIKTEGNLEQA
NEELRAVIKKIWKKTSMKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFKKRKEQGL
VGKYPAKNTTIALQAGLRTLHDIGPEIRR AISCDLQDDEPEETKREEEDDVFKRNGALLG
NHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCHNHHNHNSI
GKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRT
RYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQN
YGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFN
FECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATP
PATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVP
IO SSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAA
STLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL
corresponding to amino acids 494 - 2161 of CLAD HUMAN V3, which also
corresponds to
amino acids 49 - I7I6 of HUMCACHIA PEA I P7, wherein said first amino acid
sequence,
second amino acid sequence and third amino acid sequence are contiguous and in
a sequential
order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for an edge portion of HUMCACHlA PEA 1 P7,
comprising an
amino acid sequence being at least 70%, optionally at least about 80%,
preferably at least about
85%, more preferably at least about 90% and most preferably at least about 95%
homologous to
the sequence encoding for WCWWRRRGAAKAGPSGCRRWG, corresponding to
HUMCACH1A PEA 1 P7.
According to preferred embodiments of the present invention, there is provided
a bridge
portion of HUMCACH1A PEA 1 P7, comprising a polypeptide having a length "n",
wherein
n is at least about 10 amino acids in length, optionally at least about 20
amino acids in length,
preferably at least about 30 amino acids in length, more preferably at least
about 40 amino acids
in length and most preferably at least about 50 amino acids in length, wherein
at least two amino
acids comprise L, having a structure as follows (numbering according to
HUMCACH1A PEA 1 P7): a sequence starting from any of amino acid numbers 492-x
to 492;
and ending at any of amino acid numbers 28 + ((n-2) - x), in which x varies
from 0 to n-2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCACH1A PEA 1 PI3, comprising a
first

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amino acid sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL
corresponding to amino acids 1 - 47 of HUMCACH1A PEA_1 P13, and a second amino
acid
sequence being at least 90 % homologous to
DDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRR
AISCDLQDDEPEETKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQ
RPSIPPASDTEKPLFPPAGNSVCHNHHNHNSIGKQVPTSTNANLNNANMSKAAHGKRPS
IGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGY
FRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGYHHPQGFLE
DDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLHL
MQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLIQVEQSEALDQ
VNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAVLISEGL
GRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVGPLSHRQDYE
LQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1598 - 2161 of
CCAD HUMAN, which also corresponds to amino acids 48 - 611 of
HUMCACHlA PEA 1 P13, wherein said first amino acid sequence and second amino
acid
sequence axe contiguous and in a sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of HUMCACH1A PEA 1 P13, comprising a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL of
HUMCACH 1 A PEA 1 P 13.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCACH1A PEA 1 P14, comprising a
first
amino acid sequence being at least 90 % homologous to
MSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLP
TICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERP
RGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPI
FPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLI

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QVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSL
VEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVG
PLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids
1763 - 2161 of CCAD HUMAN, which also corresponds to amino acids 1 - 399 of
HUMCACH 1 A PEA 1 P 14.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for HUMCACHIA PEA 1 P17, comprising a
first
amino acid sequence being at least 90 % homologous to
MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQ
AAIDAARQAKAAQTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLN
NPIRRACISIVEWKPFDIFILLAIFANCVALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVET
FLKIIAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVILEQLTKETEGGNHSSGKSGGFDV
KALRAFRVLRPLRLVSGVPSLQWLNSTIKAMVPLLHIALLVLFVIIIYAIIGLELFIGKMH
KTCFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLT
VFQCITMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSG
corresponding to amino acids 1 - 407 of CCAD HUMAN, which also corresponds to
amino
acids 1 - 407 of HUMCACH1A PEA 1 P17, and a second amino acid sequence being
at least
70%, optionally at least 80%, preferably at least 85%, more preferably at
least 90% and most
preferably at least 95% homologous to a polypeptide having the sequence HGGSRL
corresponding to amino acids 408 - 413 of HUMCACH1A PEA 1 P17, wherein said
first
amino acid sequence and second amino acid sequence are contiguous and in a
sequential order.
According to preferred embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a tail of HUMCACH1A PEA-1 P17, comprising a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence HGGSRL in HUMCACH1A PEA_1 P17.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for AA583399 PEA 1 P2, comprising a
first amino
acid sequence being at least 90 % homologous to
MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKG
AQTGAGLSQEAEDVDVSRARRVTDAPQGTLCGTGNRNSGSQSARVVGVAHLGEAFRV

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GVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPD
YERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGGWRMGVRRTGQVGP
TMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59 - 313 of
MYEO HUMAN V1, which also corresponds to amino acids 1 - 255 of
AA583399 PEA 1 P2.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for AA583399 PEA 1 P4, comprising a
first amino
acid sequence being at least 70%, optionally at least 80%, preferably at least
85%, more
preferably at least 90% and most preferably at least 95% homologous to a
polypeptide having
the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG corresponding to amino acids 1 - 27
of
AA583399 PEA 1 P4, and a second amino acid sequence being at least 90 %
homologous to
RNSGSQSARWGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSP
GRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTV
VTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding
to amino acids 150 - 313 of MYEO HUMAN V1, which also corresponds to amino
acids 28 -
191 of AA583399 PEA 1 P4, wherein said first amino acid sequence and second
amino acid
sequence are contiguous and in a sequential order.
According to prefen-ed embodiments of the present invention, there is provided
an
isolated polypeptide encoding for a head of AA583399_PEA 1 P4, comprising a
polypeptide
being at least 70%, optionally at least about 80%, preferably at least about
85%, more preferably
at least about 90% and most preferably at least about 95% homologous to the
sequence
MSDLFIGFLVCSLSPLGTGTRCSCSPG of AA583399 PEA 1 P4.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for AA583399 PEA 1 P5, comprising a
first amino
acid sequence being at least 90 % homologous to
MEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCS
TWGLPLRVAGSWLTWTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLL
LLIIILTC corresponding to amino acids 192 - 313 of MYEO HUMAN V2, which also
corresponds to amino acids 1 - 122 of AA583399 PEA 1 P5.
According to preferred embodiments of the present invention, there is provided
an
isolated chimeric polypeptide encoding for AA583399 PEA 1 P10, comprising a
first amino

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acid sequence being at least 90 % homologous to
MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKG
AQTGAGLSQEAEDVDVSRARRVTDAPQGTLCGTGNRNSGSQSARAVGVAHLGEAFRV
GVEQAISSCPEEVHGRHGLSMEIMWAQMDVALRSPGRGLLAGAGALCMTLAESSCPD
YERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGRWRMGVRRTGQVGPT
MHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59 - 313 of
MYEO HUMAN V3, which also corresponds to amino acids 1 - 255 of
AA583399 PEA 1 P10.
According to preferred embodiments of the present invention, there is provided
an
antibody capable of specifically binding to an epitope of an amino acid
sequence as described
herein.
Optionally the amino acid sequence corresponds to a bridge, edge portion,
tail, head or
insertion as described herein.
Optionally the antibody is capable of differentiating between a splice variant
having said
epitope and a corresponding known protein.
According to preferred embodiments of the present invention, there is provided
a kit for
detecting colon cancer, comprising a kit detecting overexpression of a splice
variant as
described herein.
Optionally the kit comprises a NAT-based technology.
Optionally said the kit further comprises at least one primer pair capable of
selectively
hybridizing to a nucleic acid sequence as described herein. Optionally the kit
further comprises
at least one oligonucleotide capable of selectively hybridizing to a nucleic
acid sequence as
described herein.The kit optionally comprises an antibody as described
herein.The kit optionally
further comprises at least one reagent for performing an ELISA or a Western
blot.
There is optionally provided a method for detecting colon cancer, comprising
detecting
overexpression of a splice variant as described herein. Detecting
overexpression is optionally
performed with a NAT-based technology.
Optionally s detecting overexpression is performed with an immunoassay,
optionally
wherein said immunoassay comprises an antibody as described herein. A
biomarker capable of
detecting colon cancer, comprising any of the above nucleic acid sequences or
a fragment
thereof, or any of the above amino acid sequences or a fragment thereof. A
method for screening

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for colon cancer, comprising detecting colon cancer cells with a biomarker or
an antibody or a
method or assay as described herein. A method for diagnosing colon cancer,
comprising
detecting colon cancer cells with a biomarker or an antibody or a method or
assay as described
herein. A method for monitoring disease progression and/or treatment efficacy
and/or relapse of
colon cancer, comprising detecting colon cancer cells with a biomarker or an
antibody or a
method or assay as described herein. A method of selecting a therapy for colon
cancer,
comprising detecting colon cancer cells with a biomarker or an antibody or a
method or assay as
described herein and selecting a therapy according to said detection.
According to preferred embodiments of the present invention, preferably any of
the
above nucleic acid and/or amino acid sequences further comprises any sequence
having at Ieast
about 70%, preferably at least about 80%, more preferably at least about 90%,
most preferably
at least about 95% homology thereto.
Unless otherwise noted, alI experimental data relates to variants of the
present invention,
named according to the segment being tested (as expression was tested through
RT-PCR as
described).
All nucleic acid sequences andlor amino acid sequences shown herein as
embodiments
of the present invention relate to their isolated form, as isolated
polynucleotides (including for
all transcripts), oligonucleotides (including for all segments, amplicons and
primers), peptides
(including for all tails, bridges, insertions or heads, optionally including
other antibody epitopes
as described herein) and/or polypeptides (including for all proteins). It
should be noted that
oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally
be used
interchangeably.
Unless defined otherwise, all technical and scientific terms used herein have
the meaning
commonly understood by a person skilled in the art to which this invention
belongs. The
following references provide one of skill with a general definition of many of
the terms used in
this invention: Singleton et al., Dictionary of Microbiology and Molecular
Biology (2nd ed.
1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988);
The Glossary
of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and
Hale & Marharn, The
Harper Collins Dictionary of Biology (1991). All of these are hereby
incorporated by reference
as if fully set forth herein. As used herein, the following terms have the
meanings ascribed to
them unless specified otherwise.

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BRIEF DESCRIPTION OF DRAWINGS
Figure 1. is schematic summary of cancer biomarkers selection engine and the
wet
validation stages.
Figure 2. Schematic illustration, depicting grouping of transcripts of a given
cluster
based on presence or absence of unique sequence regions.
Figure 3 is schematic summary of quantitative real-time PCR analysis.
Figure 4 is schematic presentation of the oligonucleotide based microarray
fabrication.
Figure 5 is schematic summary of the oligonucleotide based microarray
experimental
flow.
Figure 6 is a histogram showing Cancer and cell-line vs. normal tissue
expression for
Cluster M85491.
Figure 7 is a histogram showing expression of the Ephrin type-B receptor 2
precursor
(EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491
tr°anscripts which are
detectable by amplieon as depicted in sequence name M85491seg24 irZ
nor°rnal and cancerous
colon tissues.
Figure 8 is a histogram showing the expression of M85491 transcripts which are
detectable by amplicon as depicted in sequence name M85491seg24 in different
normal tissues.
Figure 9 is histogram, showing Cancer and cell-line vs. normal tissue
expression for
Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture
of malignant
tumors from different tissues, pancreas carcinoma and gastric carcinoma..

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Figure 10 is a histogram showing expression of the CEA6'HUMAN Carcinoembryonic
antigen-related cell adhesion molecule 6 (T10888) transcripts which are
detectable by amplicon
as depicted in sequence name T10888 juncl 1-17, in normal and cancerous colon
tissues.
Figure 11 is a the histogram showing the expression of T10888 transcripts,
which are
detectable by amplicon as depicted in sequence name T10888juncll-I7, in
different normal
tissues.
Figure IZ is a histogram showing Cancer and cell-Iine vs. normal tissue
expression fox
Cluster H14624.
Figure 13 is a histogram, showing Cancer and cell-Line vs. normal tissue
expression for
Cluster H53626, demonstrating overexpression in the epithelial malignant
tumors, a mixture of
malignant tumors from different tissues and myosarcoma.
Figure 14 is a histogram showing expression of the above-indicated Homo
Sapiens
fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which
are detectable by
amplicon as depicted in sequence name H53626 junc24-27F1R3, in normal and
cancerous colon
tissues.
Figure 15 is the expression of Homo Sapiens fibroblast growth factor receptor-
like 1
(FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in
sequence name
H53626seg25, in normal and cancerous colon tissues.
Figure 16 is a a histogram, showing Cancer and cell-Iine vs. normal tissue
expression for
Cluster HSENA78, demonstrating overexpression in the epithelial malignant
tumors and lung
malignant tumors.
Figure 17 is a histogram, showing Cancer and cell-Iine vs. normal tissue
expression for
the Cluster HUMODCA, demonstrating overexpression in the brain malignant
tumors,

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colorectal cancer, epithelial malignant tumors and a mixture of malignant
tumors from different
tissues.
Figure 18 is a histogram, showing Cancer and cell-line vs. normal tissue
expression for
the cluster 800299, demonstratin overexpression in the lung malignant tumors.
Figure 19 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster 244808, demonstrating overexpression in the colorectal cancer,
lung cancer and
pancreas carcinoma.
Figure 20 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster 225299, demonstrating overexpression in the brain malignant
tumors, a mixture of
malignant tumors from different tissues and ovarian carcinoma.
Figure 21 is a histogram showing expression of 225299 transcripts, which are
detectable by
amplicon as depicted in sequence name Z2S299seg20, in normal and cancerous
colon tissues.
Figure 22 is a histogram showing the expression of Secretory leukocyte
protease inhibitor
Acid-stable proteinase inhibitor with strong affinities for trypsin,
chymotrypsin, elastase, and
cathepsin G. May prevent elastase-mediated damage to oral and possibly other
mucosal tissues
225299 transcripts which are detectable by amplicon as depicted in sequence
name
Z25299seg20 in different normal tissues.
Figure 23 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster HUMANK, demonstrating overexpression in epithelial malignant
tumors.
Figure 24 is the histograms showing Cancer and cell-line vs. normal tissue
expression fox the cluster HUMCA1XIA, demonstrating overexpression in the bone
malignant

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tumors, epithelial malignant tumors, a mixture of malignant tumors from
different tissues and
lung malignant tumors.
Figure 25 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster HSS100PCB, demonstrating overexpression in the mixture of
malignant tumors from
different tissues.
Figure 26 is the histograms showing Cancer and cell-line vs. normal tissue
expression
for the cluster D11853, demonstrating overexpression in the brain malignant
tumors, colorectal
cancer and a mixture of malignant tumors from different tissues.
Figure 27 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster Rl I723, demonstrating overexpression in the epithelial malignant
tumors, a mixture
of malignant tumors from different tissues and kidney malignant tumors
Figure 28 is the histogram showing expression of the 811723 transcripts, which
are
detectable by amplicon as depicted in sequence name 811723 segl3 in normal and
cancerous
colon tissues.
Figure 29 is the histogram showing expression of the 811723 transcripts, which
are
detectable by amplicon as depicted in sequence name 811723 juncll-18 in normal
and
cancerous colon tissues.
Figure 30 is the histogram showing the expression of 811723 transcripts,
detectable by
amplicon depicted in sequence name Rl 1723seg13 in different normal tissues.
Figure 31 is the histogram showing the expression of 811723 transcripts,
detectable by
amplicon in sequence name Rl 1723 juncl 1-18 in different normal tissues.
Figure 32 is a histogram showing over expression of the SM02 HUMAN SPARC
related modular calcium-binding protein 2 precursor (Secreted modular calcium-
binding protein

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zs5
2) (SMOC-2) (Smooth muscle-associated protein 2) 244808 transcripts which are
detectable by
amplicon as depicted in sequence name Z44808junc8-11 in cancerous colon
samples relative to
the normal samples
Figure 33 is the histograms showing Cancer and cell-line vs. normal tissue
expression for
the cluster M77903, demonstrating overexpression in ovarian carcinoma and
uterine
malignancies.
Figure 34 is the histogram showing expression of the SSR-alpha M77903
transcripts,
which are detectable by amplicon, as depicted in sequence name M77903seg18 in
normal and
cancerous colon tissues.
Figure 35 is the histogram showing low over expression for amplicon M77903
junc20-
34-35 in the experiment carried out with colon.
Figure 36 is the histogram showing low over expression for amplicon M77903
junc20-
28 in the experiment earned out with colon
Figures 37-38 are histograms showing differential expression of 6 sequences:
(M85491seg24, M77903 segl8, M77903junc20-28, 244808 junc8-11, 225299 seg 20
and
HSKITCR seg3 in normal and cancerous colon tissues, in different combinations.
Figure 39 is a histogram showing the expression of SM02 HUMAN SPARC related
modular calcium-binding protein 2 precursor (Secreted modular calcium-binding
protein 2)
(SMOC-2) (Smooth muscle-associated protein 2) 244808 transcripts which are
detectable by
amplicon as depicted in sequence name 244808 junc8-11 in different normal
tissues.
Figure 40 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster AA583399, demonstrating overexpression in brain malignant tumors,
epithelial
malignant tumors, a mixture of malignant tumors from different tissues and
gastric carcinoma.

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Figure 41 is the histogram showing expression of the AA583399 transcripts,
which are
detectable by amplicon as depicted in sequence name AA583399seg30-32, in
normal and
cancerous colon tissues.
Figure 42 is the histogram showing expression of the AA583399 transcripts
which are
detectable by amplicon as depicted in sequence name AA583399seg17 in normal
and cancerous
colon tissues.
Figure 43 is the histogram showing expression of the AA583399 transcripts
which are
detectable by amplicon as depicted in sequence name AA583399segl in normal and
cancerous
colon tissues.
Figure 44 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster AI684092, demonstrating overexpression in brain malignant tumors,
epithelial
malignant tumors and a mixture of malignant tumors from different tissues.
Figure 45 is the histogram showing expression of the AA5315457 transcripts
which are
detectable by amplicon as depicted in sequence name AA5315457seg8 in normal
and cancerous
colon tissues.
Figure 46 is the histogram showing Cancer and cell-Iine vs. normal tissue
expression for
the cluster HUMCACH1A, demonstrating overexpression in a mixture of malignant
tumors
from different tissues.
Figure 47 is the histogram showing expression of the Voltage-dependent L-type
calcium
channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform
2 Transcripts,
which are detectable by seg 1 I3, 35, 109, 125,_in normal and cancerous colon
tissues.
Figure 48 is the histogram showing expression of the HUMCACHIA Transcripts,
which
are detectable by amplicon as depicted in sequence name HUMCACHIAseg101~in
normal and
cancerous colon tissues.
Figure 49 is the histogram showing Cancer and cel2-line vs. normal tissue
expression for
the cluster HUMCEA, demonstrating overexpression in epithelial malignant
tumors, a mixture
of malignant tumors from different tissues and pancreas carcinoma.
Figure 50 is the histogram showing expression of the HUMCEA transcripts which
are
detectable by segl2 and seg9~in normal and cancerous colon tissues.

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Figure 51 is the histogram showing expression of the Carcinoembryonic antigen-
related
cell adhesion molecule 5 CEACAMS HUMCEA transcripts which are detectable by
amplicon as
depicted in sequence name HUMCEA seg31 in normal and cancerous colon tissues;
Figure 52 is the histogram showing expression of the Carcinoembryonic antigen-
related
cell adhesion molecule 5 CEACAMS HUMCEA transcripts which are detectable by
amplicon as
depicted in sequence name HUMCEA seg33 in normal and cancerous colon tissues.
Figure 53 is the histogram showing expression of the Carcinoembryonic antigen-
related
cell adhesion molecule 5 CEACAMS HUMCEA transcripts which are detectable by
amplicon as
depicted in sequence name HUMCEA seg35 in normal and cancerous colon tissues.
Figure 54 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster M78035, demonstrating overexpression in brain malignant tumors,
colorectal cancer,
epithelial malignant tumors, a mixture of malignant tumors from different
tissues, malignant
tumors involving the lymph nodes and pancreas carcinoma.
Figure 55 is the histogram showing expression of the S-adenosylhomocysteine
hydrolase
(AHCY) M78035 transcripts, which are detectable by amplicon as depicted in
sequence name
M78035seg42, in normal and cancerous colon tissues
Figure 56 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster 830650, demonstrating overexpression in epithelial malignant
tumors and a mixture
of malignant tumors from different tissues.
Figure 57 is the histogram showing expression of the 830650 transcripts which
are
detectable by amplicon as depicted in sequence name 830650 seg76 in normal and
cancerous
colon tissues.
Figure 58 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster T23657, demonstrating overexpression in epithelial malignant
tumors.
Figure 59 is the histogram showing expression of solute carrier organic anion
transporter
family, member 4A1 (SLC04A1) T23657 transcripts, which are detectable by
amplicon as
depicted in sequence name T23657 segl7-18, in normal and cancerous colon
tissues.
Figure 60 is the histogram showing expression of solute carrier organic anion
transporter
family, member 4A1 (SLC04A1) T23657 transcripts, which are detectable by
amplicon as
depicted in sequence name T23657 seg22, in normal and cancerous colon tissues.

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Figure 61 is the histogram showing expression of solute carrier organic anion
transporter
family, member 4A1 (SLC04A1) T23657 transcripts, which are detectable by
amplicon as
depicted in sequence name T23657 seg29-32, in normal and cancerous colon
tissues.
Figure 62 is the histogram showing expression of solute carrier organic anion
transporter
family, member 4A1 (SLC04A1) T23657 transcripts, which are detectable by
amplicon as
depicted in sequence name T23657 seg4l, in normal and cancerous colon tissues.
Figure 63 is the histogram showing Cancer and cell-line vs, normal tissue
expression for
the cluster T51958, demonstrating overexpression in epithelial malignant
tumors and a mixture
of malignant tumors from different tissues.
IO
Figure 64 is the histogram showing expression of PTK7 protein tyrosine kinase
7
(PTK7) TSI9S8 transcripts which are detectable by amplicon as depicted in
sequence name T
51958seg38 in normal and cancerous colon tissues.
15 Figure 65 is the histogram showing expression of PTK7 protein tyrosine
kinase 7
(PTK7) T51958 transcripts which are detectable by amplicon as depicted in
sequence name T
51958seg7 in normal and cancerous colon tissues.
Figure 66 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster 217877, demonstrating overexpression in brain malignant tumors and
malignant
20 tumors involving the bone marrow.
Figure 67 is the histogram showing expression of c-myc-P64 mRNA, initiating
from
promoter PO Z 17877 transcripts, which are detectable by amplicon as depicted
in sequence
name Z17877seg8, in normal and cancerous colon tissues.
Figure 68 is the histogram showing combined expression of 19 sequences
(T23657seg
25 29, T23657seg 22, T23657seg 41, T23657seg17-18, AA315457seg8, R30650seg76,
HLTM-
CEASeg 33, CEA-Seg35, CEA-Seg3l, AA583399segl, AA583399seg17, AA58339-seg30-
32,
HUMCACHIAseg101, HSHCGI seg20, HSHCGI seg35, M78035seg 42, T51958seg7, T51958
seg3 and, Z 17877 seg8 ) in normal and cancerous colon tissues.
Figure 69 is the histogram showing expression of TRIM31 tripartite motif
30 HSHCGI transcripts which are detectable by amplicon as depicted in sequence
name HSHCGI
seg20in normal and cancerous colon tissues.

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Figure 70 is the histogram showing expression ofTRIM31 tripartite motif
HSHCGI transcripts which are detectable by amplicon as depicted in sequence
name HSHCGI
seg35 in normal and cancerous colon tissues.
Figure 71 is a histogram showing the expression of fibroblast growth factor
receptor-like
1 (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon(s)
and H53626
seg25F and H53626 seg25R in different normal tissues.
Figure 72 is a histogram showing the expression of fibroblast growth factor
receptor-like
1 (FGFRLl) transcripts detectable by or according to H53626 seg25 amplicon(s)
and H53626
seg25F and H53626 junc24-27F1R3 in different normal tissues.
Figure 73 is a histogram showing over expression of the Matrix
metalloproteinase 11
(stromelysin 3) (MMP11) transcripts, which are detectable by amplicon as
depicted in sequence
name HSSTROL3 junc2l-27, in cancerous colon samples relative to the normal
samples.
Figure 74 is a histogram showing over expression of the Matrix
metalloproteinase 11
(stromelysin 3) (MMP11) transcripts, which are detectable by amplicon as
depicted in sequence
name HSSTROL3 seg25, in cancerous colon samples relative to the normal
samples.
Figure 75 is the histogram showing Cancer and cell-line vs. normal tissue
expression for
the cluster HSSTROL3, demonstrating overexpression in transitional cell
carcinoma, epithelial
malignant tumors, a mixture of malignant tumors from different tissues and
pancreas carcinoma.
Figure 76 is a histogram showing the expression of of Stromelysin-3 HSSTROL3
transcripts, which are detectable by amplicon as depicted in sequence name
HSSTROL3 seg24,
in different normal tissues.
DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention is of novel markers for colon cancer that are both
sensitive and
accurate. Biomolecular sequences (amino acid and/or nucleic acid sequences)
uncovered using
the methodology of the present invention and described herein can be
efficiently utilized as
tissue or pathological markers and/or as drugs or drug targets for treating or
preventing a
disease.

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These markers are specifically released to the bloodstream under conditions of
colon
cancer and/or other colon pathology, and/or are otherwise expressed at a much
higher level
and/or specifically expressed in colon cancer tissue or cells. The measurement
of these markers,
alone or in combination, in patient samples provides information that the
diagnostician can
correlate with a probable diagnosis of colon cancer and/or pathology.
The present invention therefore also relates to diagnostic assays for colon
cancer and/or
colon pathology, and methods of use of such markers for detection of colon
cancer and/or colon
pathology, optionally and preferably in a sample taken from a subject
(patient), which is more
preferably some type of blood sample.
In another embodiment, the present invention relates to bridges, tails, heads
and/or
insertions, and/or analogs, homologs and derivatives of such peptides. Such
bridges, tails, heads
and/or insertions are described in greater detail below with regard to the
Examples.
As used herein a "tail" refers to a peptide sequence at the end of an amino
acid sequence
that is unique to a splice variant according to the present invention.
Therefore, a splice variant
having such a tail may optionally be considered as a chimera, in that at least
a first portion of the
splice variant is typically highly homologous (often 100% identical) to a
portion of the
corresponding known protein, while at least a second portion of the variant
comprises the tail.
As used herein a "head" refers to a peptide sequence at the beginning of an
amino acid
sequence that is unique to a splice variant according to the present
invention. Therefore, a splice
variant having such a head may optionally be considered as a chimera, in that
at least a first
portion of the splice variant comprises the head, while at least a second
portion is typically
highly homologous (often 100% identical) to a portion of the corresponding
known protein.
As used herein "an edge portion" refers to a connection between two portions
of a splice
variant according to the present invention that were not joined in the wild
type or known
protein. An edge may optionally arise due to a join between the above "known
protein" portion
of a variant and the tail, for example, and/or may occur if an internal
portion of the wild type
sequence is no longer present, such that two portions of the sequence are now
contiguous in the
splice variant that were not contiguous in the known protein. A "bridge" may
optionally be an
edge portion as described above, but may also include a join between a head
and a "known
protein" portion of a variant, or a join between a tail and a "known protein"
portion of a variant,
or a join between an insertion and a "known protein" portion of a variant.

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Optionally and preferably, a bridge between a tail or a head or a unique
insertion, and a
"known protein" portion of a variant, comprises at least about 10 amino acids,
more preferably
at Least about 20 amino acids, most preferably at least about 30 amino acids,
and even more
preferably at least about 40 amino acids, in which at least one amino acid is
from the
tail/head/insertion and at least one amino acid is from the "known protein"
portion of a variant.
Also optionally, the bridge may comprise any number of amino acids from about
10 to about 40
amino acids (for example, 10, 1 l, 12, 13...37, 38, 39, 40 amino acids in
length, or any number
in between).
It should be noted that a bridge cannot be extended beyond the length of the
sequence in
either direction, and it should be assumed that every bridge description is to
be read in such
manner that the bridge length does not extend beyond the sequence itself.
Furthermore, bridges are described with regard to a sliding window in certain
contexts
below. For example, certain descriptions of the bridges feature the following
format: a bridge
between two edges (in which a portion of the known protein is not present in
the variant) may
optionally be described as follows: a bridge portion of CONTIG-NAME P1
(representing the
name of the protein), comprising a polypeptide having a length "n", wherein n
is at least about
10 amino acids in length, optionally at least about 20 amino acids in length,
preferably at least
about 30 amino acids in length, more preferably at least about 40 amino acids
in length and most
preferably at least about 50 amino acids in length, wherein at least two amino
acids comprise
XX (2 amino acids in the center of the bridge, one from each end of the edge),
having a
structure as follows (numbering according to the sequence of CONTIG-NAME Pl):
a sequence
starting from any of amino acid numbers 49-x to 49 (for example); and ending
at any of amino
acid numbers 50 + ((n-2) - x) (for example), in which x varies from 0 to n-2.
In this example, it
should also be read as including bxidges in which n is any number of amino
acids between 10-50
amino acids in length. Furthermore, the bridge polypeptide cannot extend
beyond the sequence,
so it should be read such that 49-x (for example) is not less than 1, nor 50 +
((n-2) - x) (for
example) greater than the total sequence length.
In another embodiment, this invention provides antibodies specifically
recognizing the
splice variants and polypeptide fragments thereof of this invention.
Preferably such antibodies
differentially recognize splice variants of the present invention but do not
recognize a

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l92
corresponding known protein (such known proteins are discussed with regard to
their splice
variants in the Examples below).
In another embodiment, this invention provides an isolated nucleic acid
molecule
encoding for a splice variant according to the present invention, having a
nucleotide sequence as
set forth in any one of the sequences listed herein, or a sequence
complementary thereto. In
another embodiment, this invention provides an isolated nucleic acid molecule,
having a
nucleotide sequence as set forth in any one of the sequences listed herein, or
a sequence
complementary thereto. In another embodiment, this invention provides an
oligonucleotide of at
least about 12 nucleotides, specifically hybridizable with the nucleic acid
molecules of this
invention. In another embodiment, this invention provides vectors, cells,
liposomes and
compositions comprising the isolated nucleic acids of this invention.
In another embodiment, this invention provides a method for detecting a splice
variant
according to the present invention in a biological sample, comprising:
contacting a biological
sample with an antibody specifically recognizing a splice variant according to
the present
invention under conditions whereby the antibody specifically interacts with
the splice variant in
the biological sample but do not recognize known corresponding proteins
(wherein the known
protein is discussed with regard to its splice variants) in the Examples
below), and detecting
said interaction; wherein the presence of an interaction correlates with the
presence of a splice
variant in the biological sample.
In another embodiment, this invention provides a method for detecting a splice
variant
nucleic acid sequences in a biological sample, comprising: hybridizing the
isolated nucleic acid
molecules or oligonucleotide fragments of at least about a minimum length to a
nucleic acid
material of a biological sample and detecting a hybridization complex; wherein
the presence of a
hybridization complex con-elates with the presence of a splice variant nucleic
acid sequence in
the biological sample.
According to the present invention, the splice variants described herein are
non-limiting
examples of markers for diagnosing colon cancer and/or colon pathology. Each
splice variant
marker of the present invention can be used alone or in combination, for
various uses, including
but not limited to, prognosis, prediction, screening, early diagnosis,
determination of
progression, therapy selection and treatment monitoring of colon cancer and/or
colon pathology.

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According to optional but preferred embodiments of the present invention, any
marker
according to the present invention may optionally be used alone or
combination. Such a
combination may optionally comprise a plurality of markers described herein,
optionally
including any subcombination of markers, and/or a combination featuring at
least one other
marker, for example a known marker. Furthermore, such a combination may
optionally and
preferably be used as described above with regard to determining a ratio
between a quantitative
or semi-quantitative measurement of any marker described herein to any other
marker described
herein, and/or any other known marker, and/or any other marker. With regard to
such a ratio
between any marker described herein (or a combination thereof) and a known
marker, more
preferably the known marker comprises the "known protein" as described in
greater detail
below with regard to each cluster or gene.
According to other preferred embodiments of the present invention, a splice
variant
protein or a fragment thereof, or a splice variant nucleic acid sequence or a
fragment thereof,
may be featured as a biomarker for detecting colon cancer and/or colon
pathology, such that a
biomarlter may optionally comprise any of the above.
According to still other preferred embodiments, the present invention
optionally and
preferably encompasses any amino acid sequence or fragment thereof encoded by
a nucleic acid
sequence corresponding to a splice variant protein as described herein. Any
oligopeptide or
peptide relating to such an amino acid sequence or fragment thereof may
optionally also
(additionally or alternatively) be used as a biomarker, including but not
limited to the unique
amino acid sequences of these proteins that are depicted as tails, heads,
insertions, edges or
bridges. The present invention also optionally encompasses antibodies capable
of recognizing,
and/or being elicited by, such oligopeptides or peptides.
The pxesent invention also optionally and preferably encompasses any nucleic
acid
sequence or fragment thereof, or amino acid sequence or fragment thereof,
corresponding to a
splice variant of the present invention as described above, optionally for any
application.
Non-limiting examples of methods or assays are described below.
The present invention also relates to kits based upon such diagnostic methods
or assays.
Nucleic acid sequences and Ol~onucleotides

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Various embodiments of the present invention encompass nucleic acid sequences
described hereinabove; fragments thereof, sequences hybridizable therewith,
sequences
homologous thereto, sequences encoding similar polypeptides with different
codon usage,
altered sequences characterized by mutations, such as deletion, insertion or
substitution of one or
more nucleotides, either naturally occurring or artificially induced, either
randomly or in a
targeted fashion.
The present invention encompasses nucleic acid sequences described herein;
fragments
thereof, sequences hybridizable therewith, sequences homologous thereto [e.g.,
at least 50 %, at
least 55 %, at least 60%, at least 65 %, at least 70 %, at least 75 %, at
least 80 %, at least 85 %, at
least 95 % or more say 100 % identical to the nucleic acid sequences set forth
below], sequences
encoding similar polypeptides with different codon usage, altered sequences
characterized by
mutations, such as deletion, insertion or substitution of one or more
nucleotides, either naturally
occurring or man induced, either randomly or in a targeted fashion. The
present invention also
encompasses homologous nucleic acid sequences (i.e., which form a part of a
polynucleotide
sequence of the present invention) which include sequence regions unique to
the polynucleotides
of the present invention.
In cases where the polynucleotide sequences of the present invention encode
previously
unidentified polypeptides, the present invention also encompasses novel
polypeptides or portions
thereof, which are encoded by the isolated polynucleotide and respective
nucleic acid fragments
thereof described hereinabove.
A "nucleic acid fragment" or an "oligonucleotide" or a "polynucleotide" are
used herein
interchangeably to refer to a polymer of nucleic acids. A polynucleotide
sequence of the present
invention refers to a single or double stranded nucleic acid sequences which
is isolated and
provided in the form of an RNA sequence, a complementary polynucleotide
sequence (cDNA), a
genomic polynucleotide sequence and/or a composite polynucleotide sequences
(e.g., a
combination of the above).
As used herein the phrase "complementary polynucleotide sequence" refers to a
sequence, which results from reverse transcription of messenger RNA using a
reverse
transcriptase or any other RNA dependent DNA polymerase. Such a sequence can
be
subsequently amplified ifz vivo or in vitYO using a DNA dependent DNA
polymerase.

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As used herein the phrase "genomic polynucleotide sequence" refers to a
sequence
derived (isolated) from a chromosome and thus it represents a contiguous
portion of a
chromosome.
As used herein the phrase "composite polynucleotide sequence" refers to a
sequence,
which is composed of genomic and cDNA sequences. A composite sequence can
include some
exonal sequences required to encode the polypeptide of the present invention,
as well as some
intronic sequences interposing therebetween. The intronic sequences can be of
any source,
including of other genes, and typically will include conserved splicing signal
sequences. Such
intronic sequences may further include cis acting expression regulatory
elements.
Preferred embodiments of the present invention encompass oligonucleotide
probes.
An example of an oligonucleotide probe which can be utilized by the present
invention is
a single stranded polynucleotide which includes a sequence complementary to
the unique
sequence region of any variant according to the present invention, including
but not limited to a
nucleotide sequence coding for an amino sequence of a bridge, tail, head
and/or insertion
according to the present invention, andlor the equivalent portions of any
nucleotide sequence
given herein (including but not limited to a nucleotide sequence of a node,
segment or amplicon
described herein).
Alternatively, an oligonucleotide probe of the present invention can be
designed to
hybridize with a nucleic acid sequence encompassed by any of the above nucleic
acid sequences,
particularly the portions specified above, including but not limited to a
nucleotide sequence
coding for an amino sequence of a bridge, tail, head and/or insertion
according to the present
invention, and/or the equivalent portions of any nucleotide sequence given
herein (including but
not limited to a nucleotide sequence of a node, segment or amplicon described
herein).
Oligonucleotides designed according to the teachings of the present invention
can be
generated according to any oligonucleotide synthesis method known in the art
such as enzymatic
synthesis or solid phase synthesis. Equipment and reagents for executing solid-
phase synthesis
are commercially available from, for example, Applied Biosystems. Any other
means for such
synthesis may also be employed; the actual synthesis of the oligonucleotides
is well within the
capabilities of one skilled in the art and can be accomplished via established
methodologies as
detailed in, for example, "Molecular Cloning: A laboratory Manual" Sambrook et
al., (1989);
"Current Protocols in Molecular Biology" Volumes I-III Ausubel, R. M., ed.
(1994); Ausubel et

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196
al., "Current Protocols in Molecular Biology", John Wiley and Sons, Baltimore,
Maryland
(1989); Perbal, "A Practical Guide to Molecular Cloning", John Wiley & Sons,
New York
(1988) and "Oligonucleotide Synthesis" Gait, M. J., ed. (1984) utilizing solid
phase chemistry,
e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and
purification by for
example, an automated trityl-on method or HPLC.
Oligonucleotides used according to this aspect of the present invention are
those having a
length selected from a range of about 10 to about 200 bases preferably about
15 to about 150
bases, more preferably about 20 to about 100 bases, most preferably about 20
to about 50 bases.
Preferably, the oligonucleotide of the present invention features at least 17,
at least 18, at least
19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases
specifically hybridizable
with the biomarkers of the present invention.
The oligonucleotides of the present invention may comprise heterocylic
nucleosides
consisting of purines and the pyrimidines bases, bonded in a 3' to 5'
phosphodiester linkage.
Preferably used oligonucleotides are those modified at one or more of the
backbone,
internucleoside linkages or bases, as is broadly described hereinunder.
Specific examples of preferred oligonucleotides useful according to this
aspect of the
present invention include oligonucleotides containing modified backbones or
non-natural
internucleoside linkages. Oligonucleotides having modified backbones include
those that retain
a phosphorus atom in the backbone, as disclosed in U.S. Pat. NOs: 4,469,863;
4,476,301;
5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717;
5,321,131;
5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466, 677; 5,476,925; 5,519,126;
5,536,821;
5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050.
Preferred modified oligonucleotide backbones include, for example,
phosphorothioates,
chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl
phosphotriesters,
methyl and other alkyl phosphonates including 3'-allcylene phosphonates and
chiral
phosphonates, phosphinates, phosphoramidates including 3'-amino
phosphoramidate and
aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates,
thionoalkylphosphotriesters, and boranophosphates having normal 3'-5'
linkages, 2'-5' linked
analogs of these, and those having inverted polarity wherein the adjacent
pairs of nucleoside
units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts
and free acid forms can
also be used.

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Alternatively, modified oligonucleotide backbones that do not include a
phosphorus atom
therein have backbones that are formed by short chain alkyl or cycloallcyl
internucleoside
linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages,
or one or more
short chain heteroatomic or heterocyclic internucleoside linkages. These
include those having
S morpholino linkages (formed in part from the sugar portion of a nucleoside);
siloxane
backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and
thioformacetyl baclcbones;
methylene formacetyl and thioformacetyl backbones; allcene containing
backbones; sulfamate
backbones; methyleneimino and methylenehydrazino backbones; sulfonate and
sulfonamide
backbones; amide backbones; and others having mixed N, O, S and CHZ component
parts, as
disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134;
5,216,141; 5,235,033;
5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677;
5,541,307;
5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289;
5,618,704; 5,623,
070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439.
Other oligonucleotides which can be used according to the present invention,
are those
modified in both sugar and the intenzucleoside linkage, i.e., the backbone, of
the nucleotide units
are replaced with novel groups. The base units are maintained for
complementation with the
appropriate polynucleotide target. An example for such an oligonucleotide
mimetic, includes
peptide nucleic acid (PNA). United States patents that teach the preparation
of PNA compounds
include, but are riot limited to, U.S. Pat. Nos. S,S39,082; S,7I4,331; and
5,719,262, each of
which is herein incorporated by reference. Other backbone modifications, which
can be used in
the present invention are disclosed in U.S. Pat. No: 6,303,374.
Oligonucleotides of the present invention may also include base modifications
or
substitutions. As used herein, "unmodified" or "natural" bases include the
purine bases adenine
(A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and
uracil (U).
Modified bases include but are not limited to other synthetic and natural
bases such as S-
methylcytosine (5-me-C), S-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-
aminoadenine,
6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and
other alkyl derivatives
of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, S-
halouracil and
cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine,
S-uracil
(pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioallcyl, 8-
hydroxyl and other 8-
substituted adenines and guanines, S-halo particularly S-bromo, S-
trifluoromethyl and other S-

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substituted uraciIs and cytosines, 7-methylguanine and 7-methyladenine, 8-
azaguanine and 8-
azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-
deazaadenine.
Further bases particularly useful for increasing the binding affinity of the
oligomeric compounds
of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2,
N-6 and O-6
substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-
propynylcytosine.
5-methylcytosine substitutions have been shown to increase nucleic acid duplex
stability by 0.6-
1.2 °C and are presently preferred base substitutions, even more
particularly when combined
with 2'-O-methoxyethyl sugar modifications.
Another modification of the oligonucleotides of the invention involves
chemically
linking to the oligonucleotide one or more moieties or conjugates, which
enhance the activity,
cellular distribution or cellular uptake of the oligonucleotide. Such moieties
include but are not
lirilited to lipid moieties such as a cholesterol moiety, cholic acid, a
thioether, e.g., hexyl-S
tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or
undecyl residues, a
phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-
hexadecyl-rac
glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or
adamantane acetic
acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-
oxycholesterol moiety,
as disclosed in U.S. Pat. No: 6,303,374.
It is not necessary for all positions in a given oligonucleotide molecule to
be uniformly
modified, and in fact more than one of the aforementioned modifications may be
incorporated in
a single compound or even at a single nucleoside within an oligonucleotide.
It will be appreciated that oligonucleotides of the present invention may
include further
modifications for more efficient use as diagnostic agents and/or to increase
bioavailability,
therapeutic efficacy and reduce cytotoxicity.
To enable cellular expression of the polynucleotides of the present invention,
a nucleic
acid construct according to the present invention may be used, which includes
at least a coding
region of one of the above nucleic acid sequences, and further includes at
least one cis acting
regulatory element. As used herein, the phrase "cis acting regulatory element"
refers to a
polynucleotide sequence, preferably a promoter, which binds a trans acting
regulator and
regulates the transcription of a coding sequence located downstream thereto.
Any suitable promoter sequence can be used by the nucleic acid construct of
the present
invention.

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is9
Preferably, the promoter utilized by the nucleic acid construct of the present
invention is
active in the specific cell population transformed. Examples of cell type-
specific and/or tissue-
specific promoters include promoters such as albumin that is liver specific,
lymphoid specific
promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular
promoters of T-cell
receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins;
[Banerji et al.
(1983) Cell 33729-740), neuron-specific promoters such as the neurofilament
promoter [Byrne
et al. (1989) Proc. Natl. Aced. Sci. USA 86:5473-5477], pancreas-specific
promoters [Edlunch
et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as
the milk
whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication
No. 264,166).
The nucleic acid construct of the present invention can further include an
enhancer, which can
be adjacent or distant to the promoter sequence and can function in up
regulating the
transcription therefrom.
The nucleic acid construct of the present invention preferably further
includes an
appropriate selectable marker and/or an origin of replication. Preferably, the
nucleic acid
construct utilized is a shuttle vector, which can propagate both in E. coli
(wherein the construct
comprises an appropriate selectable marker and origin of replication) and be
compatible for
propagation in cells, or integration in a gene and a tissue of choice. The
construct according to
the present invention can be, for example, a plasmid, a bacmid, a phagemid, a
cosmid, a phage,
a virus or an artificial chromosome.
Examples of suitable constructs include, but are not limited to, pcDNA3,
pcDNA3.1
(+/-), pGL3, PzeoSV2 (+/-), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of
which is
commercially available from Invitrogen Co. (www.invitrogen.com). Examples of
retroviral
vector and packaging systems are those sold by Clontech, San Diego, Calif.,
includingRetro-X
vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and
the trasgene
is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also
included such as
pBabe, where the transgene will be transcribed from the 5'LTR promoter.
Currently preferred in vivo nucleic acid transfer techniques include
transfection with
viral or non-viral constructs, such as adenovirus, Ientivirus, Herpes simplex
I virus, or adeno-
associated virus (AAV) and lipid-based systems. Useful lipids for lipid-
mediated transfer of the
gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer
Investigation,
14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy
are viruses, most

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preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct
such as a
retroviral construct includes at least one transcriptional promoter/enhancer
or locus-defining
element(s), or other elements that control gene expression by other means such
as alternate
splicing, nuclear RNA export, or post-translational modification of messenger.
Such vector
constructs also include a packaging signal, long terminal repeats (LTRs) or
portions thereof, and
positive and negative strand primer binding sites appropriate to the virus
used, unless it is
already present in the viral construct. Tn addition, such a construct
typically includes a signal
sequence for secretion of the peptide from a host cell in which it is placed.
Preferably the signal
sequence for this purpose is a mammalian signal sequence or the signal
sequence of the
polypeptide variants of the present invention. Optionally, the construct may
also include a
signal that directs polyadenylation, as well as one or more restriction sites
and a translation
termination sequence. By way of example, such constructs will typically
include a 5' LTR, a
tRNA binding site, a packaging signal, an origin of second-strand DNA
synthesis, and a 3' LTR
or a portion thereof Other vectors can be used that are non-viral, such as
cationic lipids,
polylysine, and dendrimers.
Hybridization assays
Detection of a nucleic acid of interest in a biological sample may optionally
be effected
by hybridization-based assays using an oligonucleotide probe (non-limiting
examples of probes
according to the present invention were previously described).
Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase
protection, in-situ hybridization, primer extension, Southern blots (DNA
detection), dot or slot
blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are
described in
greater detail below). More recently, PNAs have been described (Nielsen et al.
1999, Current
Opin. Biotechnol. 10:71-75). Other detection methods include kits containing
probes on a
dipstick setup and the like.
Hybridization based assays which allow the detection of a variant of interest
(i.e., DNA
or RNA) in a biological sample rely on the use of oligonucleotides which can
be 10, I5, 20, or
to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to
50 nucleotides
30 long.

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Thus, the isolated polynucleotides (oligonucleotides) of the present invention
are
preferably hybridizable with any of the herein described nucleic acid
sequences under moderate
to stringent hybridization conditions.
Moderate to stringent hybridization conditions are characterized by a
hybridization
solution such as containing 10 % dextrane sulfate, 1 M NaCI, 1 % SDS and 5 x
106 cpm 32P
labeled probe, at 65 °C, with a final wash solution of 0.2 x SSC and
0.1 % SDS and anal wash
at 65°C and whereas moderate hybridization is effected using a
hybridization solution
containing 10 % dextrane sulfate, 1 M NaCI, 1 % SDS and 5 x 106 cpm 32P
labeled probe, at 65
°C, with a final wash solution of 1 x SSC and 0.1 % SDS and final wash
at 50 °C.
More generally, hybridization of short nucleic acids (below 200 by in length,
e.g. 17-40
by in length) can be effected using the following exemplary hybridization
protocols which can
be modified according to the desired stringency; (i) hybridization solution of
6 x SSC and 1
SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 %
SDS,
100 ~g/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk,
hybridization temperature
of 1 - 1.5 °C below the Tm, final wash solution of 3 M TMACI, 0.01 M
sodium phosphate (pH
6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS at 1 - 1.5 °C below the Tm; (ii)
hybridization solution
of 6 x SSC and 0.1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM
EDTA
(pH 7.6), 0.5 % SDS, 100 pglml denatured salmon sperm DNA and 0.1 % nonfat
dried milk,
hybridization temperature of 2 - 2.5 °C below the Tm, final wash
solution of 3 M TMACI, 0.01
M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS at 1 - 1.5
°C below the Tm,
final wash solution of 6 x SSC, and final wash at 22 °C; (iii)
hybridization solution of 6 x SSC
and 1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH
7.6), 0.5
SDS, 100 ~g/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk,
hybridization
temperature.
The detection of hybrid duplexes can be carried out by a number of methods.
Typically,
hybridization duplexes are separated from unhybridized nucleic acids and the
labels bound to the
duplexes are then detected. Such labels refer to radioactive, fluorescent,
biological or enzymatic
tags or labels of standard use in the art. A label can be conjugated to either
the oligonucleotide
probes or the nucleic acids derived from the biological sample.

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Probes can be labeled according to numerous well known methods. Non-limiting
examples of radioactive labels include 3H, 14C, 32P, and 355. Non-limiting
examples of
detectable markers include ligands, fluorophores, chemiluminescent agents,
enzymes, and
antibodies. Other detectable markers for use with probes, which can enable an
increase in
sensitivity of the method of the invention, include biotin and radio-
nucleotides. It will become
evident to the person of ordinary skill that the choice of a particular label
dictates the manner in
which it is bound to the probe.
For example, oligonucleotides of the present invention can be labeled
subsequent to
synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means
(e.g., photo-
cross-linking a psoralen derivative of biotin to RNAs), followed by addition
of labeled
streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent.
Alternatively, when
fluorescently-labeled oligonucleotide probes are used, fluorescein, lissamine,
phycoerythrin,
rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, CyS, Cy5.5, Cy7, FluorX
(Amersham) and
others [e.g., Kricka et al. (1992), Academic Press San Diego, CalifJ can be
attached to the
oligonucleotides.
Those skilled in the art will appreciate that wash steps may be employed to
wash away
excess target DNA or probe as well as unbound conjugate. Further, standard
heterogeneous assay
formats are suitable for detecting the hybrids using the labels present on the
oligonucleotide
primers and probes.
It will be appreciated that a variety of controls may be usefully employed to
improve
accuracy of hybridization assays. For instance, samples may be hybridized to
an irrelevant probe
and treated with RNAse A prior to hybridization, to assess false
hybridization.
Although the present invention is not specifically dependent on the use of a
label for the
detection of a particular nucleic acid sequence, such a label might be
beneficial, by increasing
the sensitivity of the detection. Furthermore, it enables automation. Probes
can be labeled
according to numerous well known methods.
As commonly known, radioactive nucleotides can be incorporated into probes of
the
invention by several methods. Non-limiting examples of radioactive labels
include 3H, 14C, 3aP,
and 355.
Those skilled in the art will appreciate that wash steps may be employed to
wash away
excess target DNA or probe as well as unbound conjugate. Further, standard
heterogeneous assay

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formats are suitable for detecting the hybrids using the labels present on the
oligonucleotide
primers and probes.
It will be appreciated that a variety of controls may be usefully employed to
improve
accuracy of hybridization assays.
Probes of the invention can be utilized with naturally occurring sugar-
phosphate
backbones as well as modified backbones including phosphorothioates,
dithionates, alkyl
phosphonates and a-nucleotides and the like. Probes of the invention can be
constructed of either
ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA.
NAT Assays
Detection of a nucleic acid of interest in a biological sample may also
optionally be
effected by NAT-based assays, which involve nucleic acid amplification
technology, such as
PCR for example (or variations thereof such as real-time PCR for example).
As used herein, a "primer" defines an oligonucleotide which is capable of
annealing to
1S (hybridizing with) a target sequence, thereby creating a double stranded
region which can serve
as an initiation point for DNA synthesis under suitable conditions.
Amplification of a selected, or target, nucleic acid sequence may be carried
out by a
number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol.
Lab. 8:14
Numerous amplification techniques have been described and can be readily
adapted to suit
particular needs of a person of ordinary skill. Non-limiting examples of
amplii~ication techniques
include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand
displacement
amplification (SDA), transcription-based amplification, the q3 replicase
system and NASBA
(Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al.,
1988,
BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260;
and
2S Sambrook et al., 1989, supra).
The terminology "amplification pair" (or "primer pair") refers herein to a
pair of
oligonucleotides (oligos) of the present invention, which are selected to be
used together in
amplifying a selected nucleic acid sequence by one of a number of types of
amplification
processes, preferably a polymerase chain reaction. Other types of
amplification processes
include ligase chain reaction, strand displacement amplification, or nucleic
acid sequence-based

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amplification, as explained in greater detail below. As commonly known in the
art, the oligos
are designed to bind to a complementary sequence under selected conditions.
In one particular embodiment, amplification of a nucleic acid sample from a
patient is
amplified under conditions which favor the amplification of the most abundant
differentially
expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on
an mRNA
sample from a patient under conditions which favor the amplification of the
most abundant
mRNA. In another preferred embodiment, the amplification of the differentially
expressed
nucleic acids is carried out simultaneously. It will be realized by a person
skilled in the art that
such methods could be adapted for the detection of differentially expressed
proteins instead of
IO differentially expressed nucleic acid sequences.
The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be
obtained according to well known methods.
Oligonucleotide primers of the present invention may be of any suitable
length,
depending on the particular assay format and the particular needs and targeted
genomes
employed. Optionally, the oligonucleotide primers are at least 12 nucleotides
in length,
preferably between 15 and 24 molecules, and they may be adapted to be
especially suited to a
chosen nucleic acid amplification system. As commonly known in the art, the
oligonucleotide
primers can be designed by taking into consideration the melting point of
hybridization thereof
with its targeted sequence (Sambrook et al., 1989, Molecular Cloning -A
Laboratory Manual,
2nd Edition, CSE Laboratories; Ausubel et al., 1989, in Current Protocols in
Molecular Biology,
John Wiley & Sons Inc., N.Y.).
It will be appreciated that antisense oligonucleotides may be employed to
quantify
expression of a splice isoform of interest. Such detection is effected at the
pre-mRNA level.
Essentially the ability to quantitate transcription from a splice site of
interest can be effected
based on splice site accessibility. Oligonucleotides may compete with splicing
factors for the
splice site sequences. Thus, low activity of the antisense oligonucleotide is
indicative of
splicing activity.
The polymerase chain reaction and other nucleic acid amplification reactions
are well
known in the art (various non-limiting examples of these reactions are
described in greater detail
below). The pair of oligonucleotides according to this aspect of the present
invention are
preferably selected to have compatible melting temperatures (Tm), e.g.,
melting temperatures

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which differ by less than that 7 °C, preferably Less than 5 °C,
more preferably less than 4 °C,
most preferably less than 3 °C, ideally between 3 °C and 0
°C.
Polyrnef-ase Chain Reaction (PCR): The polymerise chain reaction (PCR), as
described
in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a
method of increasing
the concentration of a segment of target sequence in a mixture of genomic DNA
without cloning
or purification. This technology provides one approach to the problems of low
target sequence
concentration. PCR can be used to directly increase the concentration of the
target to an easily
detectable Level. This process for amplifying the target sequence involves the
introduction of a
molar excess of two oligonucleotide primers which are complementary to their
respective strands
of the double-stranded target sequence to the DNA mixture containing the
desired target
sequence. The mixture is denatured and then allowed to hybridize. Following
hybridization, the
primers are extended with polymerise so as to form complementary strands. The
steps of
denaturation, hybridization (annealing), and polymerise extension (elongation)
can be repeated
as often as needed, in order to obtain relatively high concentrations of a
segment of the desired
I S target sequence.
The length of the segment of the desired target sequence is determined by the
relative
positions of the primers with respect to each other, and, therefore, this
length is a controllable
parameter. Because the desired segments of the target sequence become the
dominant sequences
(in ternls of concentration) in the mixture, they are said to be "PCR-
amplified."
Ligase CJ~ain Reaction (LCR of- LAR): The ligase chain reaction [LCR;
sometimes
referred to as "Ligase Amplification Reaction" (LAR)] has developed into a
well-recognized
alternative method of amplifying nucleic acids. In LCR, four oligonucleotides,
two adjacent
oligonucleotides which uniquely hybridize to one strand of target DNA, and a
complementary set
of adjacent oligonucleotides, which hybridize to the opposite strand are mixed
and DNA ligase is
added to the mixture. Provided that there is complete complementarity at the
junction, ligase
will covalently link each set of hybridized molecules. Importantly, in LCR,
two probes are
ligated together only when they base-pair with sequences in the target sample,
without gaps or
mismatches. Repeated cycles of denaturation, and ligation amplify a short
segment of DNA.
LCR has also been used in combination with PCR to achieve enhanced detection
of single-base
changes: see for example Segev, PCT Publication No. W09001069 A1 (1990).
However,
because the four oligonucleotides used in this assay can pair to form two
short ligatable

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fragments, there is the potential for the generation of target-independent
background signal. The
use of LCR for mutant screening is limited to the examination of specific
nucleic acid positions.
Se~Sustaifzed Syfztlzetic Reaction (3SRlNASBA): The self sustained sequence
replication
reaction (3SR) is a transcription-based in vitro amplification system that can
exponentially
amplify RNA sequences at a uniform temperature. The amplii-ied RNA can then be
utilized for
mutation detection. In this method, an oligonucleotide primer is used to add a
phage RNA
polymerase promoter to the 5' end of the sequence of interest. In a cocktail
of enzymes and
substrates that includes a second primer, reverse transcriptase, RNase H, RNA
polymerase and
ribo-and deoxyribonucleoside triphosphates, the target sequence undergoes
repeated rounds of
transcription, cDNA synthesis and second-strand synthesis to amplify the area
of interest. The
use of 3SR to detect mutations is kinetically limited to screening small
segments of DNA (e.g.,
200-300 base pairs).
O-Beta (Q(3) Replicase: In this method, a probe which recognizes the sequence
of
interest is attached to the replicatable RNA template for Q(3 replicase. A
previously identified
major problem with false positives resulting from the replication of
unhybridized probes has
been addressed through use of a sequence-specific ligation step. However,
available
thermostable DNA ligases are not effective on this RNA substrate, so the
ligation must be
performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents
the use of high
temperature as a means of achieving specificity as in the LCR, the ligation
event can be used to
detect a mutation at the junction site, but not elsewhere.
A successful diagnostic method must be very specific. A straight-forward
method of
controlling the specificity of nucleic acid hybridization is by controlling
the temperature of the
reaction. While the 3SRlNASBA, and Q(3 systems axe all able to generate a
large quantity of
signal, one or more of the enzymes involved in each cannot be used at high
temperature (i.e., >
55 degrees C). Therefore the reaction temperatures cannot be raised to prevent
non-specific
hybridization of the probes. If probes are shortened in order to make them
melt more easily at
low temperatures, the likelihood of having more than one perfect match in a
complex genome
increases. For these reasons, PCR and LCR currently dominate the research
field in detection
technologies.
The basis of the amplification procedure in the PCR and LCR is the fact that
the products
of one cycle become usable templates in all subsequent cycles, consequently
doubling the

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population with each cycle. The final yield of any such doubling system can be
expressed as:
(1+X)n =y, where "X" is the mean efficiency (percent copied in each cycle),
"n" is the number of
cycles, and "y" is the overall efficiency, or yield of the reaction. If every
copy of a target DNA is
utilized as a template in every cycle of a polymerase chain reaction, then the
mean efficiency is
100 %. If 20 cycles of PCR are performed, then the yield will be 220, or
1,048,576 copies of the
starting material. If the reaction conditions reduce the mean efficiency to 85
%, then the yield in
those 20 cycles will be only 1.8520, or 220,513 copies of the starting
material. In other words, a
PCR running at 85 % efficiency will yield only 21 % as much final product,
compared to a
reaction running at 100 % efficiency. A reaction that is reduced to 50 % mean
efficiency will
yield less than 1 % of the possible product.
In practice, routine polymerase chain reactions rarely achieve the theoretical
maximum
yield, and PCRs are usually run for more thal~ 20 cycles to compensate for the
lower yield. At
50 % mean efficiency, it would take 34 cycles to achieve the million-fold
amplification
theoretically possible in 20, and at lower efficiencies, the number of cycles
required becomes
prohibitive. In addition, any background products that amplify with a better
mean efficiency
than the intended target will become the dominant products.
Also, many variables can influence the mean efficiency of PCR, including
target DNA
length and secondary structure, primer length and design, primer and dNTP
concentrations, and
buffer composition, to name but a few. Contamination of the reaction with
exogenous DNA
(e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major
consideration.
Reaction conditions must be carefully optimized for each different primer pair
and target
sequence, and the process can take days, even for an experienced investigator.
The
laboriousness of this process, including numerous technical considerations and
other factors,
presents a significant drawback to using PCR in the clinical setting. Indeed,
PCR has yet to
penetrate the clinical market in a significant way. The same concerns arise
with LCR, as LCR
must also be optimized to use different oligonucleotide sequences for each
target sequence. In
addition, both methods require expensive equipment, capable of precise
temperature cycling.
Many applications of nucleic acid detection technologies, such as in studies
of allelic
variation, involve not only detection of a specific sequence in a complex
baclcground, but also
the discrimination between sequences with few, or single, nucleotide
differences. One method of
the detection of allele-specific variants by PCR is based upon the fact that
it is difficult for Taq

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polymerise to synthesize a DNA strand when there is a mismatch between the
template strand
and the 3' end of the primer. An allele-specific variant may be detected by
the use of a primer
that is perfectly matched with only one of the possible alleles; the mismatch
to the other allele
acts to prevent the extension of the primer, thereby preventing the
amplification of that sequence.
This method has a substantial limitation in that the base composition of the
mismatch influences
the ability to prevent extension across the mismatch, and certain mismatches
do not prevent
extension or have only a minimal effect.
A similar 3'-mismatch strategy is used with greater effect to prevent ligation
in the LCR.
Any mismatch effectively blocks the action of the thermostable ligase, but LCR
still has the
' 10 drawback of target-independent background ligation products initiating
the amplification.
Moreover, the combination of PCR with subsequent LCR to identify the
nucleotides at individual
positions is also a clearly cumbersome proposition for the clinical
laboratory.
The direct detection method according to various preferred embodiments of the
present
invention may be, for example a cycling probe reaction (CPR) or a branched DNA
analysis.
When a sufficient amount of a nucleic acid to be detected is available, there
are
advantages to detecting that sequence directly, instead of making more copies
of that target,
(e.g., as in PCR and LCR). Most notably, a method that does not amplify the
signal
exponentially is more amenable to quantitative analysis. Even if the signal is
enhanced by
attaching multiple dyes to a single oligonucleotide, the correlation between
the final signal
intensity and amount of target is direct. Such a system has an additional
advantage that the
products of the reaction will not themselves promote further reaction, so
contamination of lab
surfaces by the products is not as much of a concern. Recently devised
techniques have sought to
eliminate the use of radioactivity and/or improve the sensitivity in
automatable formats. Two
examples are the "Cycling Probe Reaction" (CPR), and "Branched DNA" (bDNA).
Cycling ps-obe reaction (CPR): The cycling probe reaction (CPR), uses a long
chimeric
oligonucleotide in which a central portion is made of RNA while the two
termini are made of
DNA. Hybridization of the probe to a target DNA and exposure to a thermostable
RNase H
causes the RNA portion to be digested. This destabilizes the remaining DNA
portions of the
duplex, releasing the remainder of the probe from the target DNA and allowing
another probe
molecule to repeat the process. The signal, in the form of cleaved probe
molecules, accumulates

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at a linear rate. While the repeating process increases the signal, the RNA
portion of the
oligonucleotide is vulnerable to RNases that may carried through sample
preparation.
Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched
structures that allow each individual oligonucleotide to carry 35 to 40 labels
(e.g., alkaline
phosphatase enzymes). While this enhances the signal from a hybridization
event, signal from
non-specific binding is similarly increased.
The detection of at least one sequence change according to various preferred
embodiments of the present invention may be accomplished by, for example
restriction fragment
length polymorphism (RFLP analysis), allele specific oIigonucleotide (ASO)
analysis,
Denaturing/Ternperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-
Strand
Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF).
The demand for tests which allow the detection of specific nucleic acid
sequences and
sequence changes is growing rapidly in clinical diagnostics. As nucleic acid
sequence data for
genes from humans and pathogenic organisms accumulates, the demand for fast,
cost-effective,
and easy-to-use tests for as yet mutations within specific sequences is
rapidly increasing.
A handful of methods have been devised to scan nucleic acid segments for
mutations.
One option is to determine the entire gene sequence of each test sample (e.g.,
a bacterial isolate).
For sequences under approximately 600 nucleotides, this may be accomplished
using amplified
material (e.g., PCR reaction products). This avoids the time and expense
associated with cloning
the segment of interest. However, specialized equipment and highly trained
personnel are
required, and the method is too labor-intense and expensive to be practical
and effective in the
clinical setting.
In view of the difficulties associated with sequencing, a given segment of
nucleic acid
may be characterized on several other levels. At the lowest resolution, the
size of the molecule
can be determined by electrophoresis by comparison to a known standard run on
the same gel. A
more detailed picture of the molecule may be achieved by cleavage with
combinations of
restriction enzymes prior to electrophoresis, to allow construction of an
ordered map. The
presence of specific sequences within the fragment can be detected by
hybridization of a labeled
probe, or the precise nucleotide sequence can be determined by partial
chemical degradation or
by primer extension in the presence of chain-terminating nucleotide analogs.

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Restriction f-agrner~t length polyrrrorphisnZ (RFLP): For detection of single-
base
differences between like sequences, the requirements of the analysis are often
at the highest level
of resolution. For cases in which the position of the nucleotide in question
is known in advance,
several methods have been developed for examining single base changes without
direct
sequencing. For example, if a mutation of interest happens to fall within a
restriction recognition
sequence, a change in the pattern of digestion can be used as a diagnostic
tool (e.g., restriction
fragment length polymorphism [RFLP~ analysis).
Single point mutations have been also detected by the creation or destruction
of RFLPs.
Mutations are detected and localized by the presence and size of the RNA
fragments generated
by cleavage at the mismatches. Single nucleotide mismatches in DNA
heteroduplexes are also
recognized and cleaved by some chemicals, providing an alternative strategy to
detect single
base substitutions, generically named the "Mismatch Chemical Cleavage" (MCC).
However, this
method requires the use of osmium tetroxide and piperidine, two highly noxious
chemicals
which are not suited for use in a clinical laboratory.
RFLP analysis suffers from low sensitivity and requires a large amount of
sample. When
RFLP analysis is used for the detection of point mutations, it is, by its
nature, limited to the
detection of only those single base changes which fall within a restriction
sequence of a known
restriction endonuclease. Moreover, the majority of the available enzymes have
4 to 6 base-pair
recognition sequences, and cleave too frequently for many large-scale DNA
manipulations.
Thus, it is applicable only in a small fraction of cases, as most mutations do
not fall within such
sites.
A handful of rare-cutting restriction enzymes with 8 base-pair specificities
have been
isolated and these are widely used in genetic mapping, but these enzymes are
few in number, are
limited to the recognition of G+C-rich sequences, and cleave at sites that
tend to be highly
clustered. Recently, endonucleases encoded by group I introns have been
discovered that might
have greater than 12 base-pair specificity, but again, these axe few in
number.
Allele specific oligonucleotide (ASO): If the change is not in a recognition
sequence,
then allele-specific oligonucleotides (ASOs), can be designed to hybridize in
proximity to the
mutated nucleotide, such that a primer extension or ligation event can bused
as the indicator of a
match or a mis-match. Hybridization with radioactively labeled allelic
specific oligonucleotides
(ASO) also has been applied to the detection of specific point mutations. The
method is based

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21l
on the differences in the melting temperature of short DNA fragments differing
by a single
nucleotide. Stringent hybridization and washing conditions can differentiate
between mutant and
wild-type alleles. The ASO approach applied to PCR products also has been
extensively utilized
by various researchers to detect and characterize point mutations in ras genes
and gsp/gip
oncogenes. Because of the presence of various nucleotide changes in multiple
positions, the
ASO method requires the use of many oligonucleotides to cover all possible
oncogenic
mutations.
With either of the techniques described above (i.e., IRFLP and ASO), the
precise location
of the suspected mutation must be known in advance of the test. That is to
say, they are
inapplicable when one needs to detect the presence of a mutation within a gene
or sequence of
interest.
DehaturinglTenaperature Gradieiat Gel ElectYOplaof-esis (DGGElTGGE): Two other
methods rely on detecting changes in electrophoretic mobility in response to
minor sequence
changes. One of these methods, termed "Denaturing Gradient Gel
Electrophoresis" (DGGE) is
based on the observation that slightly different sequences will display
different patterns of local
melting when electrophoretically resolved on a gradient gel. In this manner,
variants can be
distinguished, as differences in melting properties of homoduplexes versus
heteroduplexes
differing in a single nucleotide can detect the presence of mutations in the
target sequences
because of the corresponding changes in their electrophoretic mobilities. The
fragments to be
analyzed, usually PCR products, are "clamped" at one end by a long stretch of
G-C base pairs
(30-i~0) to allow complete denaturation of the sequence of interest without
complete dissociation
of the strands. The attachment of a GC "clamp" to the DNA fragments increases
the fraction of
mutations that can be recognized by DGGE. Attaching a GC clamp to one primer
is critical to
ensure that the amplified sequence has a low dissociation temperature.
Modifications of the
technique have been developed, using temperature gradients, and the method can
be also applied
to RNA:RNA duplexes.
Limitations on the utility of DGGE include the requirement that the denaturing
conditions
must be optimized for each type of DNA to be tested. Furthermore, the method
requires
specialized equipment to prepare the gels and maintain the needed high
temperatures during
electrophoresis. The expense associated with the synthesis of the clamping
tail on one
oligonucleotide for each sequence to be tested is also a major consideration.
Tn addition, long

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running times are required for DGGE. The long running time of DGGE was
shortened in a
modification of DGGE called constant denaturant gel electrophoresis (CDGE).
CDGE requires
that gels be performed under different denaturant conditions in order to reach
high efficiency for
the detection of mutations.
A technique analogous to DGGE, termed temperature gradient gel electrophoresis
(TGGE), uses a thermal gradient rather than a chemical denaturant gradient.
TGGE requires the
use of specialized equipment which can generate a temperature gradient
perpendicularly oriented
relative to the electrical field. TGGE can detect mutations in relatively
small fragments of DNA
therefore scanning of large gene segments requires the use of multiple PCR
products prior to
running the gel.
Single-Sty°arad ConforrnatiorZ Polym~rplZism (SSCP): Another common
method, called
"Single-Strand Conformation Polymorphism" (SSCP) was developed by Hayashi,
Sekya and
colleagues and is based on the observation that single strands of nucleic acid
can take on
characteristic conformations in non-denaturing conditions, and these
conformations influence
electrophoretic mobility. The complementary strands assume sufficiently
different structures
that one strand xnay be resolved from the other. Changes in sequences within
the fragment will
also change the conformation, consequently altering the mobility and allowing
this to be used as
an assay for sequence variations.
The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that
is
labeled on both strands, followed by slow electrophoretic separation on a non-
denaturing
polyacrylamide gel, so that intra-molecular interactions can form and not be
disturbed during the
run. This technique is extremely sensitive to variations in gel composition
and temperature. A
serious limitation of this method is the relative difficulty encountered in
comparing data
generated in different laboratories, under apparently similar conditions.
Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another
technique
developed to scan genes for the presence of mutations. The ddF technique
combines
components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing
reaction is
performed using one dideoxy terminator and then the reaction products are
electrophoresed on
nondenaturing polyacrylamide gels to detect alterations in mobility of the
termination segments
as in SSCP analysis. While ddF is an improvement over SSCP in terms of
increased sensitivity,
ddF requires the use of expensive dideoxynucleotides and this technique is
still limited to the

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analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-
300 bases for optimal
detection of mutations).
In addition to the above limitations, all of these methods are limited as to
the size of the
nucleic acid fragment that can be analyzed. For the direct sequencing
approach, sequences of
greater than 600 base pairs require cloning, with the consequent delays and
expense of either
deletion sub-cloning or primer walking, in order to cover the entire fragment.
SSCP and DGGE
have even more severe size limitations. Because of reduced sensitivity to
sequence changes,
these methods are not considered suitable for larger fragments. Although SSCP
is reportedly able
to detect 90 % of single-base substitutions within a 200 base-pair fragment,
the detection drops
to less than 50 % for 400 base pair fragments. Similarly, the sensitivity of
DGGE decreases as
the length of the fragment reaches 500 base-pairs. The ddF technique, as a
combination of direct
sequencing and SSCP, is also limited by the relatively small size of the DNA
that can be
screened.
According to a presently preferred embodiment of the present invention the
step of
~ 5 searching for any of the nucleic acid sequences described here, in tumor
cells or in cells derived
from a cancer patient is effected by any suitable technique, including, but
not limited to, nucleic
acid sequencing, polymerase chain reaction, ligase chain reaction, self
sustained synthetic
reaction, Q(3-Replicase, cycling probe reaction, branched DNA, restriction
fragment length
polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis,
allele-specific
oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant
gel
electrophoresis, temperature gradient gel electrophoresis and dideoxy
fingerprinting.
Detection may also optionally be performed with a chip or other such device.
The nucleic
acid sample which includes the candidate region to be analyzed is preferably
isolated, amplified
and labeled with a reporter group. This reporter group can be a fluorescent
group such as
phycoerythrin. The labeled nucleic acid is then incubated with the probes
immobilized on the
chip using a fluidics station. describe the fabrication of fluidics devices
and particularly
microcapillary devices, in silicon and glass substrates.
Once the reaction is completed, the chip is inserted into a scanner and
patterns of
hybridization are detected. The hybridization data is collected, as a signal
emitted from the
reporter groups already incorporated into the nucleic acid, which is now bound
to the probes

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attached to the chip. Since the sequence and position of each probe
immobilized on the chip is
known, the identity of the nucleic acid hybridized to a given probe can be
determined.
It will be appreciated that when utilized along with automated equipment, the
above
described detection methods can be used to screen multiple samples for a
disease and/or
pathological condition both rapidly and easily.
Amino acid sequences and peptides
The terms "polypeptide," "peptide" and "protein" are used interchangeably
herein to
refer to a polymer of amino acid residues. The terms apply to amino acid
polymers in which one
or more amino acid residue is an analog or mimetic of a corresponding
naturally occurring
amino acid, as well as to naturally occurring amino acid polymers.
Polypeptides can be
modified, e.g., by the addition of carbohydrate residues to form
glycoproteins. The terms
"polypeptide," "peptide" and "protein" include glycoproteins, as well as non-
glycoproteins.
Polypeptide products can be biochemically synthesized such as by employing
standard
solid phase techniques. Such methods include but are not limited to exclusive
solid phase
synthesis, partial solid phase synthesis methods, fragment condensation,
classical solution
synthesis. These methods are preferably used when the peptide is relatively
short (i.e., 10 kDa)
and/or when it cannot be produced by recombinant techniques (i.e., not encoded
by a nucleic
acid sequence) and therefore involves different chemistry.
Solid phase polypeptide synthesis procedures are well known in the art and
further
described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide
Syntheses (2nd
Ed-., Pierce Chemical Company, 1984).
Synthetic polypeptides can optionally be purified by preparative high
performance liquid
chromatography [Creighton T. (1983) Proteins, structures and molecular
principles. WH
Freeman and Co. N.Y.], after which their composition can be confirmed via
amino acid
sequencing.
In cases where large amounts of a polypeptide are desired, it can be generated
using
recombinant techniques such as described by Bitter et al., (1987) Methods in
Enzymol. 153:516-
544, Studies et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al.
(1984) Nature 310:511-
514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J.
3:1671-1680
and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell.
Biol. 6:559-565

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and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic
Press, NY,
Section VIII, pp 421-463.
The present invention also encompasses polypeptides encoded by the
polynucleotide
sequences of the present invention, as well as polypeptides according to the
amino acid
sequences described herein. The present invention also encompasses homologues
of these
polypeptides, such homologues can be at least 50 %, at least 55 %, at least
60%, at least 65 %, at
least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 95 % or more
say 100
homologous to the amino acid sequences set forth below, as can be determined
using BlastP
software of the National Center of Biotechnology Information (NCBI) using
default parameters,
optionally and preferably including the following: filtering on (this option
filters repetitive or
low-complexity sequences from the query using the Seg (protein) program),
scoring matrix is
BLOSUM62 for proteins, word size is 3, E value is 10, gap costs are 11, 1
(initialization and
extension), and number of alignments shown is 50. Optionally and preferably,
nucleic acid
sequence homology/identity may be determined by using BlastN software of the
National Center
of Biotechnology Information (NCBI) using default parameters, which preferably
include using
the DUST filter program, and also preferably include having an E value of 10,
filtering low
complexity sequences and a word size of 11. Finally, the present invention
also encompasses
fragments of the above described polypeptides and polypeptides having
mutations, such as
deletions, insertions or substitutions of one or more amino acids, either
naturally occurnng or
artificially induced, either randomly or in a targeted fashion.
It will be appreciated that peptides identified according the present
invention may be
degradation products, synthetic peptides or recombinant peptides as well as
peptidomimetics,
typically, synthetic peptides and peptoids and semipeptoids which are peptide
analogs, which
may have, for example, modifications rendering the peptides more stable while
in a body or
more capable of penetrating into cells. Such modifications include, but are
not limited to N
terminus modification, C terminus modification, peptide bond modification,
including, but not
limited to, CH2-NH, CH2-S, CH2-S=O, O=C-NH, CH2-O, CH2-CH2, S=C-NH, CH=CH or
CF=CH, backbone modifications, and residue modification. Methods for preparing
peptidomirnetic compounds are well known in the art and are specified. Further
details in this
respect are provided hereinunder.

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Peptide bonds (-CO-NH-) within the peptide may be substituted, for example, by
N-
methylated bonds (-N(CH3)-CO-), ester bonds (-C(R)H-C-O-O-C(R)-N-),
ketomethylen bonds
(-CO-CH2-), a-aza bonds (-NH-N(R)-CO-), wherein R is any alkyl, e.g., methyl,
carba bonds (-
CH2-NH-), hydroxyethylene bonds (-CH(OH)-CH2-), thioamide bonds (-CS-NH-),
olefinic
double bonds (-CH=CH-), retro amide bonds (-NH-CO-), peptide derivatives (-
N(R)-CH2-CO-),
wherein R is the "normal" side chain, naturally presented on the carbon atom.
These modifications can occur at any of the bonds along the peptide chain and
even at
several (2-3) at the same time.
Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for
synthetic non-
natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-
methylated derivatives of
Phe, halogenated derivatives of Phe or o-methyl-Tyr.
In addition to the above, the peptides of the present invention may also
include one or
more modified amino acids or one or more non-amino acid monomers (e.g. fatty
acids, complex
carbohydrates etc).
As used herein in the specification and in the claims section below the term
"amino acid"
or "amino acids" is understood to include the 20 naturally occurring amino
acids; those amino
acids often modified post-translationally in vivo, including, for example,
hydroxyproline,
phosphoserine and phosphothreonine; and other unusual amino acids including,
but not limited
to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine
and ornithine.
Furthermore, the term "amino acid" includes both D- and L-amino acids.
Table 1 non-conventional or modified amizzo acids which can be used with the
present
invezztiozz.
Table 1
Non-conventional Code Non-conventional Code
amino amino acid
acid
a-aminobutyric Abu L-N-methylalanine Nmala
acid
a-amino-a-methylbutyrateMgabu L-N-methylarginine Nmarg
aminocyclopropane-Cpro L-N-methylasparagineNmasn

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Carboxylate L-N-methylaspartic Nmasp
acid
aminoisobutyric Aib L-N-methylcysteine Nmcys
acid
aminonorbornyl- Norb L-N-methylglutamine Nmgin
Carboxylate L-N-methylglutamic Nmglu
acid
Cyclohexylalanine Chexa L-N-methylhistidine Nmhis
CyclopentylalanineCpen L-N-methylisolleucineNmile
D-alanine Dal L-N-methylleucine Nmleu
D-arginine Darg L-N-rnethyllysine Nmlys
D-aspartic acid Dasp L-N-methylmethionineNmmet
D-cysteine Dcys L-N-methylnorleucineNmnle
D-glutamine Dgln L-N-methylnorvaline Nmnva
D-glutamic acid Dglu L-N-methylornithine Nmorn
D-histidine Dhis L-N-methylphenylalanineNmphe
D-isoleucine Dile L-N-methylproline Nmpro
D-leucine Dleu L-N-methylserine Nmser
D-lysine Dlys L-N-methylthreonine Nmthr
D-methionine Dmet L-N-methyltryptophanNmtrp
D-ornithine Dorn L-N-methyltyrosine Nmtyr
D-phenylalanine Dphe L-N-methylvaline Nmval
D-proline Dpro L-N-methylethylglycineNmetg
D-serine Dser L-N-methyl-t-butylglycineNmtbug
D-threonine Dthr L-norleucine NIe
D-tryptophan Dtrp L-norvaline Nva
D-tyrosine Dtyr a-methyl-aminoisobutyrateMaib
D-valine Dval a-methyl-y-aminobutyrateMgabu
D-a-methylalanine Dmala a-methylcyclohexylalanineMchexa
D-a-methylarginineDmarg a-methylcyclopentylalanineMcpen
D-a-methylasparagineDmasn a-methyl-a-napthylalanineManap
I D-a-methylaspartateDmasp a- methylpenicillamineMpen

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2l8
D-a-methylcysteineDmcys N-(4-aminobutyl)glycineNglu
D-a-methylglutamineDmgln N-(2-aminoethyl)glycineNaeg
D-a-methylhistidineDmhis N-(3-aminopropyl)glycineNorn
D-a-methylisoleucineDmile N- amino-a-methylbutyrateNmaabu
D-a-methylleucineDmleu a-napthylalanine Anap
D-a-methyllysine Dmlys N-benzylglycine Nphe
D-a-methylmethionineDmmet N-(2-carbamylethyl)glycineNgln
D-a-methylornithineDmorn N-(carbamylmethyl)glycineNasn
D-a-methylphenylalanineDmphe N-(2-carboxyethyl)glycineNglu
D-a-methylprolineDmpro N-(carboxymethyl)glycineNasp
D-a-methylserine Denser N-cyclobutylglycineNcbut
D-a-methylthreonineDmthr N-cycloheptylglycineNchep
D-a-methyltryptophanDmtrp N-cyclohexylglycineNchex
D-a-methyltyrosineDmty N-cyclodecylglycineNcdec
D-a-methylvaline Dmval N-cyclododeclglycineNcdod
D-a-methylalnine Dnmala N-cyclooctylglycineNcoct
D-a-methylarginineDnmarg N-cyclopropylglycineNcpro
D-a-methylasparagineDnmasn N-cycloundecylglycineNcund
D-a-methylasparatateDnmasp N-(2,2-diphenylethyl)glycineNbhm
D-a-methylcysteineDnmcys N-(3,3- Nbhe
diphenylpropyl)glycine
D-N-methylleucineDnmleu N-(3-indolylyethyl)Nhtrp
glycine
D-N-methyllysine Drunlys N-methyl-y-aminobutyrateNmgabu
N- Nmchexa D-N-methylmethionineDnmmet
methylcyclohexylalanine
D-N-methylornithineDnmorn N-methylcyclopentylalanineNmcpen
N-methylglycine Nala D-N-methylphenylalanineDnmphe
N-methylaminoisobutyrateNmaib D-N-methylproline Dnmpro
N-(I-methylpropyl)glycineNile D-N-methylserine Dnmser

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N-(2-methylpropyl)glycineNile D-N-methylserine Dmnser
N-(2-methylpropyl)glycineNleu D-N-methylthreonine Dnmthr
D-N-methyltryptophanDnmtrp N-(1-methylethyl)glycineNva
D-N-methyltyrosineDnmtyr N-methyla-napthylalanineNmanap
D-N-methylvaline Dnmval N-methylpenicillamineNmpen
y-aminobutyric Gabu N-(p-hydroxyphenyl)glycineNhtyr
acid
L-t-butylglycine Tbug N-(thiomethyl)glycineNcys
L-ethylglycine Etg penicillamine Pen
L-homophenylalanineHphe L-a-methylalanine Mala
L-a-methylarginineMarg L-a-methylasparagineMasn
L-a-methylaspartateMasp L-a-methyl-t-butylglycineMtbug
L-a-methylcysteineMcys L-methylethylglycineMetg
L-a-methylglutamineMgln L-a-methylglutamate Mglu
L-a-methylhistidineMhis L-a-methylhomo Mhphe
phenylalanine
L-a-methylisoleucineMile N-(2-methylthioethyl)glycineNmet
D-N-methylglutamineDnmgln N-(3- Narg
guanidinopropyl)glycine
D-N-methylglutamateDnmglu N-(1-hydroxyethyl)glycineNthr
D-N-methylhistidineDnmhis N-(hydroxyethyl)glycineNser
D-N-methylisoleucineDnmile N-(imidazolylethyl)glycineNhis
D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycineNhtrp
D-N-methyllysine Dnmlys N-methyl-y-aminobutyrateNmgabu
N- Nmchexa D-N-methylmethionineDnmmet
methylcyclohexylalanine
D-N-methylornithineDnmorn N-methylcyclopentylalanineNmcpen
N-methylglycine Nala D-N-methylphenylalanineDnmphe
N-methylaminoisobutyrateNmaib D-N-methylproline Dnmpro
!N-(1-methylpropyl)glycineNile D-N-methylserine Dnmser

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N-(2-methylpropyl)glycineNleu D-N-methylthreonine Dnmthr
D-N-methyltryptophanDnmtrp N-(1-methylethyl)glycineNval
D-N-methyltyrosineDnmtyr N-methyla-napthylalanineNmanap
D-N-methylvaline Dnmval N-methylpenicillamineNmpen
y-aminobutyric Gabu N-(p-hydroxyphenyl)glycineNhtyr
acid
L-t-butylglycine Tbug N-(thiomethyl)glycineNcys
L-ethylglycine Etg penicillamine Pen
L-homophenylalanineHphe L-a-methylalanine Mala
L-a-methylarginineMarg L-a-methylasparagineMasn
L-a-methylaspartateMasp L-a-methyl-t-butylglycineMtbug
L-a-methylcysteineMcys L-methylethylglycineMetg
L-a-methylglutamineMgln L-a-methylglutamate Mglu
L-a-methylhistidineMhis L-a- Mhphe
methylhomophenylalanine
L-a-methylisoleucineMile N-(2-methylthioethyl)glycineNmet
L-a-rnethylleucineMleu L-a-methyllysine Mlys
L-a-methyhnethionineMmet L-a-methylnorleucineMnle
L-a-methylnorvalineMnva L-a-methylomithine Morn
L-a-methylphenylalanineMphe L-a-methylproline Mpro
L-a-methylserine mser L-a-methylthreonine Mthr
L-a-methylvaline Mtrp L-a-methyltyrosine Mtyr
L-a-methylleucine Mval L-N- Nmhphe
Nnbhm methylhomophenylalanine
N-(N-(2,2-diphenylethyl) N-(N-(3,3-diphenylpropyl)
carbamylmethyl-glycineNnbhm carbamylmethyl(1)glycineNnbhe
1-carboxy-1-(2,2-diphenylNmbc
~ethylanuno)cyclopropane
1 able 1 C,'ozzt.

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Since the peptides of the present invention are preferably utilized in
diagnostics which
require the peptides to be in soluble form, the peptides of the present
invention preferably
include one or more non-natural ox natural polar amino acids, including but
not limited to serine
and threonine which are capable of increasing peptide solubility due to their
hydroxyl-containing
side chain.
The peptides of the present invention are preferably utilized in a linear
form, although it
will be appreciated that in cases where cyclicization does not severely
interfere with peptide
characteristics, cyclic forms of the peptide can also be utilized.
The peptides of present invention can be biochemically synthesized such as by
using
standard solid phase techniques. These methods include exclusive solid phase
synthesis well
known in the art, partial solid phase synthesis methods, fragment
condensation, classical solution
synthesis. These methods are preferably used when the peptide is relatively
short (i.e., IO kDa)
and/or when it cannot be produced by recombinant techniques (i.e., not encoded
by a nucleic
acid sequence) and therefore involves different chemistry.
1S Synthetic peptides can be purified by preparative high performance liquid
chromatography and the composition of which can be confirmed via amino acid
sequencing.
In cases where large amounts of the peptides of the present invention are
desired, the
peptides of the present invention can be generated using recombinant
techniques such as
described by Bitter et al., (I987) Methods in Enzymol. 153:516-544, Studier et
aI. (1990)
Methods in Enzyrnol. 185:60-89, Brisson et al. (1984) Nature 310:SII-514,
Takamatsu et al.
(1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli
et al.,
(1984) Science 224:838-843, Gurley et al. (1986) Mol. CeII. Biol. 6:SS9-S6S
and Weissbach &
Weissbach, 1988, Methods fox Plant Molecular Biology, Academic Press, NY,
Section VIII, pp
421-463 and also as described above.
2S
Antibodies
"Antibody" refers to a polypeptide ligand that is preferably substantially
encoded by an
immunoglobulin gene or immunoglobulin genes, or fragments thereof, which
specifically binds
and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin
genes include the
kappa and lambda light chain constant region genes, the alpha, gamma, delta,
epsilon and mu

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heavy chain constant region genes, and the myriad-immunoglobulin variable
region genes.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well
characterized fragments
produced by digestion with various peptidases. This includes, e.g., Fab' and
F(ab)'~ fragments.
The teen "antibody," as used herein, also includes antibody fragments either
produced by the
modification of whole antibodies or those synthesized de novo using
recombinant DNA
methodologies. It also includes polyclonal antibodies, monoclonal antibodies,
chimeric
antibodies, humanized antibodies, or single chain antibodies. "Fc" portion of
an antibody refers
to that portion of an immunoglobulin heavy chain that comprises one or more
heavy chain
constant region domains, CH1, CH2 and CH3, but does not include the heavy
chain variable
region.
The functional fragments of antibodies, such as Fab, F(ab')2, and Fv that are
capable of
binding to macrophages, are described as follows: (1) Fab, the fragment which
contains a
monovalent antigen-binding fragment of an antibody molecule, can be produced
by digestion of
whole antibody with the enzyme papain to yield an intact light chain and a
portion of one heavy
chain; (2) Fab', the fragment of an antibody molecule that can be obtained by
treating whole
antibody with pepsin, followed by reduction, to yield an intact light chain
and a portion of the
heavy chain; two Fab' fragments are obtained per antibody molecule; (3)
(Fab')2, the fragment
of the antibody that can be obtained by treating whole antibody with the
enzyme pepsin without
subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together
by two disulfide
bonds; (4) Fv, defined as a genetically engineered fragment containing the
variable region of the
light chain and the variable region of the heavy chain expressed as two
chains; and (5) Single
chain antibody ("SCA"), a genetically engineered molecule containing the
variable region of the
light chain and the variable region of the heavy chain, linked by a suitable
polypeptide linker as
a genetically fused single chain molecule.
Methods of producing polyclonal and monoclonal antibodies as well as fragments
thereof are well known in the art (See for example, Harlow and Lane,
Antibodies: A Laboratory
Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by
reference).
Antibody fragments according to the present invention can be prepared by
proteolytic
hydrolysis of the antibody or by expression in E. coli or mammalian cells
(e.g. Chinese hamster
ovary cell culture or other protein expression systems) of DNA encoding the
fragment.
Antibody fragments can be obtained by pepsin or papain digestion of whole
antibodies by

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conventional methods. For example, antibody fragments can be produced by
enzymatic
cleavage of antibodies with pepsin to provide a SS fragment denoted F(ab')2.
This fragment can
be further cleaved using a thiol reducing agent, and optionally a blocking
group for the
sulfhydryl groups resulting from cleavage of disulfide linkages, to produce
3.SS Fab'
monovalent fragments. Alternatively, an enzymatic cleavage using pepsin
produces two
monovalent Fab' fragments and an Fc fragment directly. These methods are
described, for
example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references
contained
therein, which patents are hereby incorporated by reference in their entirety.
See also Porter, R.
R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies,
such as separation
I O of heavy chains to form monovalent light-heavy chain fragments, further
cleavage of fragments,
or other enzymatic, chemical, or genetic techniques may also be used, so long
as the fragments
bind to the antigen that is recognized by the intact antibody.
Fv fragments comprise an association of VH and VL chains. This association may
be
noncovalent, as described in mbar et al. [Proc. Nat'1 Acad. Sci. USA 69:2659-
62 (19720].
IS Alternatively, the variable chains can be linked by an intermolecular
disulfide bond or cross
linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments
comprise VH and VL
chains connected by a peptide linker. These single-chain antigen binding
proteins (sFv) are
prepared by constructing a structural gene comprising DNA sequences encoding
the VH and VL
domains connected by an oligonucleotide. The structural gene is inserted into
an expression
20 vector, which is subsequently introduced into a host cell such as E. coli.
The recombinant host
cells synthesize a single polypeptide chain with a linker peptide bridging the
two V domains.
Methods for producing sFvs are described, for example, by [Whitlow and
Filpula, Methods 2:
97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al.,
Bio/Technology 11:1271-77
(1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference
in its entirety.
25 Another form of an antibody fragment is a peptide coding for a single
complementarity-
deterlnining region (CDR). CDR peptides ("minimal recognition units") can be
obtained by
constructing genes encoding the CDR of an antibody of interest. Such genes are
prepared, for
example, by using the polymerase chain reaction to synthesize the variable
region from RNA of
antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: I06-
10 (1991)].
30 Humanized forms of non-human (e.g., marine) antibodies are chimeric
molecules of
immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab,
Fab', F(ab') or

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224
other antigen-binding subsequences of antibodies) which contain minimal
sequence derived
from non-human irnmunoglobulin. Humanized antibodies include human
immunoglobulins
(recipient antibody) in which residues from a complementary determining region
(CDR) of the
recipient are replaced by residues from a CDR of a non-human species (donor
antibody) such as
mouse, rat or rabbit having the desired specificity, affinity and capacity. In
some instances, Fv
framework residues of the human inmnunoglobulin are replaced by corresponding
non-human
residues. Humanized antibodies may also comprise residues which are found
neither in the
recipient antibody nor in the imported CDR or framework sequences. In general,
the humanized
antibody will comprise substantially all of at least one, and typically two,
variable domains, in
which all or substantially all of the CDR regions correspond to those of a non-
human
immunoglobulin and all or substantially all of the FR regions are those of a
human
immunoglobulin consensus sequence. The humanized antibody optimally also will
comprise at
least a portion of an immunoglobulin constant region (Fc), typically that of a
human
imrnunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al.,
Nature, 332:323-
329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)].
Methods for humanizil~g non-human antibodies are well known in the art.
Generally, a
humanized antibody has one or more amino acid residues introduced into it from
a source which
is non-human. These non-human amino acid residues are often referred to as
import residues,
which are typically taken from an import variable domain. Humanization can be
essentially
performed following the method of Winter and co-workers [Jones et al., Nature,
321:522-525
(1986); Riechmann et aL, Nature 332:323-327 (1988); Verhoeyen et al., Science,
239:1534-
1536 (1988)], by substituting rodent CDRs or CDR sequences for the
corresponding sequences
of a human antibody. Accordingly, such humanized antibodies are chimeric
antibodies (U.S.
Pat. No. 4,816,567), wherein substantially less than an intact human variable
domain has been
substituted by the corresponding sequence from a non-human species. In
practice, humanized
antibodies are typically human antibodies in which some CDR residues and
possibly some FR
residues are substituted by residues from analogous sites in rodent
antibodies.
Human antibodies can also be produced using various techniques known in the
art,
including phage display libraries [Hoogenboom and Winter, J. Mol. BioL,
227:381 (199I);
Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al.
and Boerner et al. are
also available for the preparation of human monoclonal antibodies (Cole et
al., Monoclonal

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225
Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et aL,
J. Immunol.,
147(1):86-95 (1991)]. Similarly, human antibodies can be made by introduction
of human
immunoglobulin Ioci into transgenic animals, e.g., mice in which the
endogenous
immunoglobulin genes have been partially or completely inactivated. Upon
challenge, human
antibody production is observed, which closely resembles that seen in humans
in alI respects,
including gene rearrangement, assembly, and antibody repertoire. This approach
is described,
for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126;
5,633,425;
5,661,016, and in the following scientific publications: Marks et al.,
Bio/Technology IO,: 779-
783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368
812-13 (1994);
IO Fishwild et aL, Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature
Biotechnology 14:
826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. I3, 65-93 (1995).
Preferably, the antibody of this aspect of the present invention specifically
binds at least
one epitope of the polypeptide variants of the present invention. As used
herein, the term
"epitope" refers to any antigenic determinant on an antigen to which the
paratope of an antibody
binds.
Epitopic determinants usually consist of chemically active surface groupings
of
molecules such as amino acids or carbohydrate side chains and usually have
specific three
dimensional structural characteristics, as well as specific charge
characteristics.
Optionally, a unique epitope may be created in a variant due to a change in
one or more
post-translational modifications, including but not limited to glycosylation
and/or
phosphorylation, as described below. Such a change may also cause a new
epitope to be
created, for example through removal of glycosylation at a particular site.
An epitope according to the present invention may also optionally comprise
part or all of
a unique sequence portion of a variant according to the present invention in
combination with at
least one other portion of the variant which is not contiguous to the unique
sequence portion in
the linear polypeptide itself, yet which are able to form an epitope in
combination. One or more
unique sequence portions may optionally combine with one or more other non-
contiguous
portions of the variant (including a portion which may have high homology to a
portion of the
known protein) to form an epitope.
Immunoassays

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In another embodiment of the present invention, an immunoassay can be used to
qualitatively or quantitatively detect and analyze markers in a sample. This
method comprises:
providing an antibody that specifically binds to a marker; contacting a sample
with the antibody;
and detecting the presence of a complex of the antibody bound to the marker in
the sample.
To prepare an antibody that specifically binds to a marker, purified protein
markers can
be used. Antibodies that specifically bind to a protein marker can be prepared
using any suitable
methods known in the art.
After the antibody is provided, a marker can be detected and/or quantified
using any of a
number of well recognized immunological binding assays. Useful assays include,
for example,
IO an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay
(ELISA), a
radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g.,
U.S. Pat. Nos.
4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained
from a subject
can be contacted with the antibody that specifically binds the marker.
Optionally, the antibody can be fixed to a solid support to facilitate washing
and
subsequent isolation of the complex, prior to contacting the antibody with a
sample. Examples
of solid supports include but are not limited to glass or plastic in the form
of, e.g., a microtiter
plate, a stick, a bead, or a microbead. Antibodies can also be attached to a
solid support.
After incubating the sample with antibodies, the mixture is washed and the
antibody
marker complex formed can be detected. This can be accomplished by incubating
the washed
mixture with a detection reagent. Alternatively, the marker in the sample can
be detected using
an indirect assay, wherein, for example, a second, labeled antibody is used to
detect bound
marker-specific antibody, and/or in a competition or inhibition assay wherein,
for example, a
monoclonal antibody which binds to a distinct epitope 'of the marker are
incubated
simultaneously with the mixture.
Throughout the assays, incubation and/or washing steps may be required after
each
combination of reagents. Incubation steps can vary from about 5 seconds to
several hours,
preferably from about 5 minutes to about 24 hours. However, the incubation
time will depend
upon the assay format, marker, volume of solution, concentrations and the
lilee. Usually the
assays will be carried out at ambient temperature, although they can be
conducted over a range
of temperatures, such as 10 °C to 40 °C.

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The immunoassay can be used to determine a test amount of a marker in a sample
from a
subject. First, a test amount of a marker in a sample can be detected using
the imununoassay
methods described above. If a marker is present in the sample, it will form an
antibody-marker
complex with an antibody that specifically binds the marker under suitable
incubation
conditions described above. The amount of an antibody-marker complex can
optionally be
determined by comparing to a standard. As noted above, the test amount of
marker need not be
measured in absolute units, as long as the unit of measurement can be compared
to a control
amount and/or signal.
Preferably used are antibodies which specifically interact with the
polypeptides of the
IO present invention and not with wild type proteins or other isofonns
thereof, for example. Such
antibodies are directed, for example, to the unique sequence portions of the
polypeptide variants
of the present invention, including but not limited to bridges, heads, tails
arid insertions described
in greater detail below. Preferred embodiments of antibodies according to the
present invention
are described in greater detail with regard to the section entitled
"Antibodies".
Radio-immunoassay (RIA): In one version, this method involves precipitation of
the
desired substrate and in the methods detailed hereinbelow, with a specific
antibody and
radiolabelled antibody binding protein (e.g., protein A labeled with II25)
immobilized on a
precipitable carrier such as agarose beads. The number of counts in the
precipitated pellet is
proportional to the amount of substrate.
In an alternate version of the RIA, a labeled substrate and an unlabelled
antibody binding
protein are employed. A sample containing an unknown amount of substrate is
added in varying
amounts. The decrease in precipitated counts from the labeled substrate is
proportional to the
amount of substrate in the added sample.
Enzyme lin7~ed iznznuraosorbent assay (ELISA): This method involves Exation of
a sample
(e.g., fixed cells or a proteinaceous solution) containing a protein substrate
to a surface such as a
well of a microtiter plate. A substrate specific antibody coupled to an enzyme
is applied and
allowed to bind to the substrate. Presence of the antibody is then detected
and quantitated by a
colorimetric reaction employing the enzyme coupled to the antibody. Enzymes
commonly
employed in this method include horseradish peroxidase and alkaline
phosphatase. If well
calibrated and within the linear range of response, the amount of substrate
present in the sample

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is proportional to the amount of color produced. A substrate standard is
generally employed to
improve quantitative accuracy.
Westef°n blot: This method involves separation of a substrate from
other protein by means
of an acrylamide gel followed by transfer of the substrate to a membrane
(e.g., nylon or PVDF).
Presence of the substrate is then detected by antibodies specific to the
substrate, which are in turn
detected by antibody binding reagents. Antibody binding reagents may be, for
example, protein
A, or other antibodies. Antibody binding reagents may be radiolabelled or
enzyme linked as
described hereinabove. Detection may be by autoradiography, colorimetric
reaction or
chemiluminescence. This method allows both quantitation of an amount of
substrate and
IO determination of its identity by a relative position on the membrane which
is indicative of a
migration distance in the acrylamide gel during electrophoresis.
Ir~a~Tauyaohistochenzical analysis: This method involves detection of a
substrate in situ in
fixed cells by substrate specific antibodies. The substrate specific
antibodies may be enzyme
linked or linleed to fluorophores. Detection is by microscopy and subjective
evaluation. If
enzyme linked antibodies are employed, a colorimetric reaction may be
required.
Fluorescerace activated cell sorting (FAGS): This method involves detection of
a
substrate in situ in cells by substrate specific antibodies. The substrate
specific antibodies are
linked to fluorophores. Detection is by means of a cell sorting machine which
reads the
wavelength of light emitted from each cell as it passes through a light beam.
This method may
employ two or more antibodies simultaneously.
Radio-ima~in~ Methods
These methods include but are not limited to, positron emission tomography
(PET)
single photon emission computed tomography (SPELT). Both of these techniques
are non-
invasive, and can be used to detect and/or measure a wide variety of tissue
events and/or
functions, such as detecting cancerous cells for example. Unlike PET, SPELT
can optionally be
used with two labels simultaneously. SPELT has some other advantages as well,
for example
with regard to cost and the types of labels that can be used. For example, US
Patent No.

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6,696,686 describes the use of SPELT for detection of breast cancer, and is
hereby incorporated
by reference as if fully set forth herein.
Display Libraries
According to still another aspect of the present invention there is provided a
display
library comprising a plurality of display vehicles (such as phages, viruses or
bacteria) each
displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15,
12-17, 15-20, 15-30 or 20-
50 consecutive amino acids derived from the polypeptide sequences of the
present invention.
Methods of constructing such display libraries are well known in the art. Such
methods
are described in, for example, Young AC, et al., "The three-dimensional
structures of a
polysaccharide binding antibody to Cryptococcus neoformans and its complex
with a peptide
from a phage display library: implications for the identification of peptide
mimotopes" J Mol
Biol 1997 Dec 12;274(4):622-34; Giebel LB et al. "Screening of cyclic peptide
phage libraries
identifies Iigands that bind streptavidin with high affinities" Biochemistry
1995 Nov
28;34(47):15430-5; Davies EL et al., "Selection of specific phage-display
antibodies using
libraries derived from chicken immunoglobulin genes" J Immunol Methods 1995
Oct
12;186(1):125-35; Jones C RT al. "Current trends in molecular recognition and
bioseparation" J
Chromatogr A 1995 Jul 14;707(1):3-22; Deng SJ et al. "Basis for selection of
improved
carbohydrate-binding single-chain antibodies from synthetic gene libraries"
Proc Natl Acad Sci
U S A 1995 May 23;92(11):4992-6; and Deng SJ et al. "Selection of antibody
single-chain
variable fragments with improved carbohydrate binding by phage display" J Biol
Chem 1994
Apr 1;269(13):9533-8, which are incorporated herein by reference.
The following sections relate to Candidate Marker Examples (first section) and
to
Experimental Data for these Marker Examples (second section).
It should be noted that Table numbering is restarted within each section.
CANDIDATE MARKER EXAMPLES SECTION
This Section relates to Examples of sequences according to the present
invention,
including illustrative methods of selection thereof.

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Description of the methodology undertaken to uncover the biomolecular
sequences of
the present invention
Human ESTs and cDNAs were obtained from GenBank versions 136 (June 15, 2003
ftp.ncbi.nih.gov/genbank/release.notes/gb136.release.notes); NCBI genome
assembly ofApril
2003; Re~eq sequences from June 2003; Genbank version 139 (December 2003);
Human
Genome from NCBI (Build 34) (from Oct 2003); and Ref~eq sequences from
December 2003;
and from the LifeSeq library of Incyte Corporation (Wilmington, DE, USA; ESTs
only). With
regard to GenBank sequences, the human EST sequences from the EST (GBEST)
section and
the human mRNA sequences from the primate (GBPRI) section were used; also the
human
nucleotide RefSeq mRNA sequences were used (see for example
www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html and for a reference to the
EST section,
see www.ncbi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST
database in
GenBank, may be found in Boguski et al, Nat Genet. 1993 Aug;4(4):332-3; all of
which are
hereby incorporated by reference as if fully set forth herein).
Novel splice variants were predicted using the LEADS clustering and assembly
system
as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are
alternatively spliced.
Genome Res 12, 1060-7 (2002); US patent No: 6,625,545; and U.S. Pat. Appl. No.
10/426,002,
published as US20040101876 on May 27 2004; all of which are hereby
incorporated by
reference as if fully set forth herein. Briefly, the software cleans the
expressed sequences from
repeats, vectors and immunoglobulins. It then aligns the expressed sequences
to the genome
taking alternatively splicing into account and clusters overlapping expressed
sequences into
"clusters" that represent genes or partial genes.
These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel)
platform. The
GeneCarta platform includes a rich pool of annotations, sequence information
(particularly of
spliced sequences), chromosomal information, alignments, and additional
information such as
SNPs, gene ontology terms, expression profiles, functional analyses, detailed
domain structures,
known and predicted proteins and detailed homology reports.
A brief explanation is provided with regard to the method of selecting the
candidates.
However, it should noted that this explanation is provided for descriptive
purposes only, and is
not intended to be limiting in any way. The potential markers were identified
by a computational
process that was designed to find genes and/or their splice variants that are
over-expressed in

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tumor tissues, by using databases of expressed sequences. Various parameters
related to the
information in the EST libraries, determined according to a manual
classification process, were
used to assist in locating genes and/or splice variants thereof that are over-
expressed in
cancerous tissues. The detailed description of the selection method is
presented in Example 1
below. The cancer biomarkers selection engine and the following wet validation
stages are
schematically summarized in Figure 1.
EXAMPLE 1
Ide~ttifzcation of differ°eratially expr°essed gefze py-
oducts -Algorith~z
In order to distinguish between differentially expressed gene products and
constitutively
expressed genes (i.e., house keeping genes ) an algorithm based on an analysis
of frequencies was
configured. A specific algorithm for identification of transcripts over
expressed in cancer is
described hereinbelow.
Dry analysis
Library annotation - EST Libraries are manually classified according to:
(i) Tissue origin
(ii) Biological source - Examples of frequently used biological sources for
construction of EST libraries include cancer cell-lines; normal tissues;
cancer
tissues; fetal tissues; and others such as normal cell lines and pools of
normal
cell-Lines, cancer cell-lines and combinations thereof. A specific description
of
abbreviations used below with regard to these tissues/cell lines etc is given
above.
(iii) Protocol of library construction - various methods are known in the art
for
library construction including normalized library construction; non-normalized
library construction; subtracted libraries; ORESTES and others. It will be
appreciated that at times the protocol of library construction is not
indicated.
The following rules are followed:
EST libraries originating from identical biological samples are considered as
a single
library.
EST libraries which included above-average levels of contamination, such as
DNA
contamination for example, were eliminated. The presence of such contamination
was determined
as follows. For each library, the number of unspliced ESTs that are not fully
contained within

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other spliced sequences was counted. If the percentage of such sequences (as
compared to all
other sequences) was at least 4 standard deviations above the average for all
libraries being
analyzed, this library was tagged as being contaminated and was eliminated
from further
consideration in the below analysis (see also Sorek, R. & Safer, H.M. A novel
algorithm for
computational identification of contaminated EST libraries. Nucleic Acids Res
31, 1067-74
(2003)for further details).
Clusters (genes) having at least five sequences including at least two
sequences from the
tissue of interest were analyzed. Splice variants were identified by using the
LEADS software
package as described above.
EXAMPLE 2
Identification of genes over expressed in cancer.
Two different scoring algorithms were developed.
Libraries score -candidate sequences which are supported by a number of cancer
libraries,
are more likely to serve as specific and effective diagnostic markers.
The basic algorithm - for each cluster the number of cancer and normal
libraries
contributing sequences to the cluster was counted. Fisher exact test was used
to check if cancer
libraries are significantly over-represented in the cluster as compared to the
total number of
cancer and normal libraries.
Library counting: Small libraries (e.g., less than 1000 sequences) were
excluded from
consideration unless they participate in the cluster. For this reason, the
total number of libraries is
actually adjusted for each cluster.
Clones no. score - Generally, when the number of ESTs is much higher in the
cancer
libraries relative to the normal libraries it might indicate actual over-
expression.
The algorithm -
Clone counting: For counting EST clones each library protocol class was given
a weight
based on our belief of how much the protocol reflects actual expression
levels:
(i) non-normalized : 1
(ii) normalized : 0.2
(iii) all other classes : 0.1

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Clones number score - The total weighted number of EST clones from cancer
libraries
was compared to the EST clones from normal libraries. To avoid cases where one
library
contributes to the majority of the score, the contribution of the library that
gives most clones for a
given cluster was limited to 2 clones.
The score was computed as
c+1
C
n ~-1
N
where:
c - weighted number of "cancer" clones in the cluster.
C- weighted number of clones in all "cancer" libraries.
n - weighted number of "normal" clones in the cluster.
N- weighted number of clones in all "normal" libraries.
Clones number score si ni~cance - Fisher exact test was used to check if EST
clones from
cancer libraries are significantly over-represented in the cluster as compared
to the total number
of EST clones from cancer and normal libraries.
Two search approaches were used to End either general cancer-specific
candidates or
tumor specific candidates.
~ Libxaries/sequences originating from tumor tissues are counted as well as
libraries originating from cancer cell-lines ("normal" cell-lines were
ignored).
~ Only libraries/sequences originating from tumor tissues are counted
EXAMPLE 3
Tdentification of tissue specific genes
For detection of tissue specific clusters, tissue libraries/sequences were
compared to the
total number of libraries/sequences in cluster. Similar statistical tools to
those described in above
were employed to identify tissue specific genes. Tissue abbreviations are the
same as for
cancerous tissues, but are indicated with the header "normal tissue".

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The algorithm - for each tested tissue T and for each tested cluster the
following were
examined:
1. Each cluster includes at least 2 libraries from the tissue T. At least 3
clones
(weighed - as described above) from tissue T in the cluster; and
2. Clones from the tissue T are at least 40 % from all the clones
participating in the
tested cluster
Fisher exact test P-values were computed both for library and weighted clone
counts to
check that the counts are statistically significant.
EXAMPLE 4
Identification of splice variants over expressed in cancer of clusters which
are not over
expressed in cancer
Cancer-specific splice variants containing a uniaue region were identified.
Identification of unique sequence regions in splice variants
A Region is defined as a group of adjacent exons that always appear or do not
appear
together in each splice variant.
A "segment" (sometimes referred also as "seg" or "node") is defined as the
shortest
contiguous transcribed region without known splicing inside.
Only reliable ESTs were considered for region and segment analysis. An EST was
defined as unreliable if:
(i) Unspliced;
(ii) Not covered by RNA;
(iii) Not covered by spliced ESTs; and
(iv) Alignment to the genome ends in proximity of ,long poly-A stretch or
starts in
proxiunity of long poly-T stretch.
Only reliable regions were selected for further scoring. Unique sequence
regions were
considered reliable if
(i) Aligned to the genome; and
(ii) Regions supported by more than 2 ESTs.
The algorithm
Each unique sequence region divides the set of transcripts into 2 groups:

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(i) Transcripts containing this region (group TA).
(ii) Transcripts not containing this region (group TB).
The set of EST clones of every cluster is divided into 3 groups:
(i) Supporting (originating from) transcripts of group TA (Sl).
(ii) Supporting transcripts of group TB (S2).
(iii) Supporting transcripts from both groups (S3).
Library and clones number scores described above were given to Sl group.
Fisher Exact Test P-values were used to check if:
Sl is significantly enriched by cancer EST clones compared to S2; and
S1 is significantly enriched by cancer EST clones compared to cluster
background
(S1+S2+S3).
Identification of unique sequence regions and division of the group of
transcripts
accordingly is illustrated in Figure 2. Each of these unique sequence regions
corresponds to a
segment, also termed herein a "node".
Region 1: common to all transcripts, thus it is not considered; Region 2:
specific to Transcript l:
T I unique regions (2+6) against T 2+3 unique regions (3+4); Region 3:
specific to Transcripts
2+3: T 2+3 unique regions (3+4) against TI unique regions (2+6); Region 4:
specific to
Transcript 3: T 3 unique regions (4) against T1+2 unique regions (2+S+6);
Region 5: specific to
Transcript I+2: T 1+2 unique regions (2+5+6) against T3 unique regions (4);
Region 6: specific
to Transcript l: same as region 2.
EXAMPLE 5
Identification of cancer specific splice variants of genes over expressed in
cancer
A search for EST supported (no mRNA) regions for genes of:
(i) known cancer markers
(ii) Genes shown to be over-expressed in cancer in published micro-array
experiments.

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Reliable EST supported-regions were defined as supported by minimum of one of
the
following:
(i) 3 spliced ESTs; or
(ii) 2 spliced ESTs from 2 libraries;
(iii) IO unspliced ESTs from 2 libraries, or
(iv) 3libraries.
Actual Marker Examples
The following examples relate to specific actual marker examples.
EXPERIMENTAL EXAMPLES SECTION
This Section relates to Examples describing experiments involving these
sequences, and
illustrative, non-limiting examples of methods, assays and uses thereof. The
materials and
experimental procedures are explained first, as all experiments used them as a
basis for the work
that was performed.
The markers of the present invention were tested with regard to thezr
expression in
various cancerous and non-cancerous tissue samples. A description of the
samples used in the
panel is provided in Table 1 below. A description of the samples used in the
normal tissue panel
is provided in Table 2 below. Tests were then performed as described in the
"Materials and
Experimental Procedures" section below.
Table I: Tissue samples in testing panel

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COLON PANEL
sam le name Lot tissuesourceatholo y Gradegenderlag~
No.
58-B-Adeno A609152ColonbiochainAdenocarcinoma 1 M/73
G1
59-B-Adeno A609059ColonbiochainAdenocarcinoma, 1 MI5B
G1 Ulcer
14-CG-Pol CG-222RectumIchilovWell o! aid adeocarcinoma F/49
aid Adeno 2 Duke's C
G1 D-C
17-CG-Adeno CG-163RectumIchilovAdenocarcinoma 2 M/73
G1-2
10-CG-Adeno CG-311Si IchilovAdenocarcinoma Astler-Caller1-2 M/88
G1-2 D-B2 mod B2.
co
i 1-CG-Adeno CG-337ColonIchilovAdenocarcinoma Astler-Caller1-2 NA
G1-2 D-C2 C2.
6-CG-Adeno CG-303ColonlchilovAdenocarcinoma Astler-Caller1-2 FI77
G1-2 D-C2 3 C2.
5-CG-Adeno CG-308ColonIchilovAdenocarcinoma. 2 F/80
G2 Si
16-CG-Adeno CG-278CcolonIchilovAdenocarcinoma 2 F/60
G2
56-B-Adeno A609148ColonbiochainAdenocarcinoma 2 F48
G2
61-B-Adeno A606258ColonbiochainAdenocarcinoma, 2 M/41
G2 Ulcer
60-B-Adeno A609058ColonbiochainAdenocarcinoma, 2 M/67
G2 Ulcer
22-CG-Adeno CG-229CColonIchilovAdenocarcinoma Duke's2 FI55
G2 D-B B
1-CG-Adeno CG-335GecumIchilovAdenocarcinoma Dukes2 F/66
G2 D-B2 B2.
12-CG-Adeno CG-340ColonIchilovAdenocarcinoma Astler-Caller2 M/66
G2 D-B2 Si B2.
28-CG-Adeno CG-284si IchilovAdenocarcinoma Duke's2 F/72
G2 D-B2 ma B2
2-CG-Adeno CG-307CecumIchilovAdenocarcinoma Astler-Caller2 F/89
G2 D-C2 X2 C2.
9-CG-Adeno CG-297RectumIchilovAdenocarcinoma Dukes2 MI62
G2 D-D X2 D.
13-CG-Adeno CG-290RectosiIchilovAdenocarcinoma Dukes2 MI47
G2 D -D X2 m D.
26-CG-Adeno CG-283si fchilovColonic adenocarcinoma2 F/63
G2 D-D ma Duke's D
4-CG-Adeno CG-276ColonJchilovCarcinoma. 3 M/64
G3
53-B-Adeno A609161ColonbiochainAdenocarcinoma 3 F/53
G3
54-B-Adeno A609142ColonbiochainAdenocarcinoma 3 M/53
G3
55-B-Adeno A609144ColonbiochainAdenocarcinoma 3 M/68
G3
57-B-Adeno A609150ColonbiochainAdenocarcinoma 3 F/45
G3
72-CG-Adeno CG-309colonIchilovAdenocarcinoma 3 F/88
G3
20-CG-Adeno CG-249CotonIchilovUlcerated adenocarcinoma3 M/36
G3 D-B2 Duke's B2
7-CG-Adeno CG-235RectumIchilovAdenocarcinoma intramucosal F/66
D-A Duke's A.
23-CG-Adeno CG-282si IchilovMucinus adenocarcinoma M/51
D-C ma Astler Caller C
3-CG-Muo adenoCG-224ColonichilovMucinois adenocarcinoma M/48
D-D Duke's D
18-CG-Adeno CG-22CColonIchilovAdenocarcinoma NA
19-CG-Adeno CG-19CColonIchilovAdenocarcinoma NA
1
21-CG-Adeno CG-18CColonIchilovAdenocarcinoma NA
24-CG-Adeno CG-12 ColonIchilovAdenocarcinoma NA
2
25-CG-Adeno CG-2 ColonIchilovAdenocarcinoma NA
27-CG-Adeno CG-4 ColonIchilovAdenocarcinoma NA
8-CG-diverticolosis,CG-291WallIchilovDiverticolosis and F/65
diverticulitis of diverticulitis
si of the Colon
46-CG-Crohn'sCG-338CCecumIchllovCrohn's disease M/22
disease
47-CG-Crohn'sCG-338ACColonIchilovCrohri s disease. M/22
disease
42-CG-N M20 CG-249NColonIchilovNormal M/36
43-CG-N M8 CG-291NWallIchilovNormal FI65
of
si
44-CG-N M21 CG-18NColonIchilovNormal NA
45-CG-N M11 CG-337NColonIchilovNormal M/75
49-CG-N M14 CG-222NRectumIchilovNormal F/49
50-CG-N M5 CG-308NSi IchilovWithin normal limits F/80
ma
51-CG-N M26 CG-283NSi IchilovNormal F/63
ma
41-B-N A501156ColonbiochainNormal PM M/78
52-CG-N CG-309TRColonIchitovWithin normal limits F/88
62-B-N A608273ColonbiochainNormal PM M/66
63-B-N A609260ColonbiochainNormal PM M/61
64-B-N A609261ColonbiochainNormal PM F/68
65-8-N A607115ColonbiochainNormal PM M/24
66-B-N A609262ColonbiochainNormal PM M/58
67-B-N A406029ColonbiochainNormal PM Pool of
10
69-B-N A41i078CotonbiochainNormal PM Pool of F&M
10
70-CI-N 1110101ColonclontechNormal PM Pool of
3
71-Am-N 071P10BColonAmbionNormal IC BLEED F/34
45-CG Adsno l7-A CG-235 Reotum lcliilov Adaraocarcinoma intramucosal Duke's A,
FI68 ,
Table 2: Tissue samples in normal panel:
Lot no. Source Tissue Pathology Sex/Age

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1-Am-Colon (C71)071P10BAmbion Colon PM F/43
2-B-Colon (C69)A411078BiochainColon PM-Pool M&F
of lO
3-Cl-Colon (C70)1110101ClontechColon PM-Pool M&F
of 3
4-Am-Small Intestine091P0201AAmbion Small IntestinePM M/75
5-B-Small IntestineA501158BiochainSmall IntestinePM M/63
6-B-Rectum A605138BiochainRectum PM M/25
7-B-Rectum A610297BiochainRectum PM M124
8-B-Rectum 610298 BiochainRectum PM M/27
9-Am-Stomach 110P04AAmbion Stomach PM M/16
IO-B-Stomach ASOI159BiochainStomach PM M/24
11-B-Esophagus A603814BiochainEsophagus PM M/26
12-B-Esophagus A603813BiochainEsophagus PM M/41
I3-Am-Pancreas 071P25CAmbion Pancreas PM M/25
I4-CG-Pancreas CG-255-2IchilovPancreas PM M/75
15-B-Lung A409363BiochainLung PM F/26
16-Am-Lung (L93)111P0103AAmbion Lung PM F161
17-B-Lung (L92)A503204BiochainLung PM M/28
18-Am-Ovaiy 061P43AAmbion Ovary PM F/16
(047)
19-B-Ovary (048)A504087BiochainOvary PM F/51
20-B-Ovary (046)A504086BiochainOvary PM F/41
21-Arn-Cervix lOIPOlOlAAmbion Cervix PM F/40
22-B-Cervix A408211BiochainCervix PM F/36
23-B-Cervix A504089BiochainCervix PM-Pool M&F
of 5
24-B-Uterus A411074BiochainUterus PM-Pool M&F
of 10
25-B-Uterus A409248BiochainUterus PM F/43
26-B-Uterus A504090BiochainUterus PM-Pool M8zF
of 5
27-B-Bladder ASOI157BiochainBladder PM M/29
28-Am-Bladder 071P02CAmbion Bladder PM M/20
29-B-Bladder A504088BiochainBladder PM-Pool M&F
of 5
30-Am-Placenta 021P33AAmbion Placenta PB F/33

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31-B-Placenta A4I0165BiochainPlacenta PB F/26
32-B-Placenta A411073BiochainPlacenta PB-Pool M&F
of 5
33-B-Breast A607155BiochainBreast PM F/36
(B59)
34-Am-Breast 26486 Ambion Breast PM F/43
(B63)
35-Am-Breast 23036 ArnbionBreast PM F/57
(B64)
36-C1-Prostate 1070317ClontechProstate PB-Pool M&F
(P53) of 47
37-Am-Prostate 061P04AAmbion Prostate PM M/47
(P42)
38-Am-Prostate 25955 Ambion Prostate PM M/62
(P59)
39-Am-Testis 111P0104AAmbion Testis PM M/25
40-B-Testis A411147BiochainTestis PM M/74
41-Cl-Testis 1110320ClontechTestis PB-Pool M&F
of 45
42-CG-Adrenal CG-184-lOIchilovAdrenal PM F/81
43-B-Adrenal A610374BiochainAdrenal PM F/83
44-B-Heart A4I BiochainHeart PB-Pool M&F
1077 of 5
45-CG-Heart CG-255-9IchilovHeart PM M/75
46-CG-Heart CG-227-1IchilovHeart PM F/36
47-Am-Liver 081POlOlAAmbion Liver PM M/64
48-CG-Liver CG-93-3IchilovLiver PM F/19
49-CG-Liver CG-124-4IchilovLiver PM F/34
50-CI-BM 1110932ClontechBone MarrowPM-Pool M&F
of 8
51-CGEN-Blood WBC#5 CGEN Blood M
52-CGEN-Blood WBC#4 CGEN Blood M
53-CGEN-Blood WBC#3 CGEN Blood M
54-CG-Spleen CG-267 IchilovSpleen PM F/25
SS-CG-Spleen 111P0106BAmbion Spleen PM M/25
56-CG-Spleen A409246BiochainSpleen PM F/12
S6-CG-Thymus CG-98-7IchilovThymus PM F/28
58-Am-Thymus lOIPOlOlAAmbion Thymus PM M/14
59-B-Thymus A409278BiochainThymus PM M/28
60-B-Thyroid A610287BiochainThyroid PM M/27

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6I-B-Thyroid A610286 BiochainThyroid PM M/24
62-CG-Thyroid CG-lI9-2IchilovThyroid PM F/66
63-Cl-Salivary 1070319 ClontechSalivary PM-Pool M&F
Gland Gland of 24
64-Am-Kidney I llPOlOIBAmbionKidney PM-Pool M&F
of 14
65-CI-Kidney 1110970 ClontechKidney PM-Pool M&F
of 14
66-B-Kidney A4I 1080BiochainKidney PM-Pool M&F
of 5
67-CG-CerebellumCG-183-5IchilovCerebellum PM M/74
68-CG-CerebellumCG-212-5IchilovCerebellum PM M/54
69-B-Brain A411322 BiochainBrain PM M/28
70-CI-Brain I 120022ClontechBrain PM-Pool M&F
of 2
71-B-Brain A411079 BiochainBrain PM-Pool M&F
of 2
72-CG-Brain CG-1 IchilovBrain PM F/86
S 1-1
73-Arn-SkeletallO1P013AAmbionSkeletal PM F/28
Muscle Muscle
74-Cl-Skeletal 1061038 ClontechSkeletal PM-Pool M&F
Muscle Muscle of 2
Materials and Experirnef2tal Procedures
.RNA prepaf-atiora - RNA was obtained from Clontech (Franklin Lakes, NJ USA
07417,
www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA
www.biochain.com), ABS
(Wilmington, DE I980I, USA, http://www.absbioreagents.com) or Ambion (Austin,
TX 78744
USA, http://www.ambion.com). Alternatively, RNA was generated from tissue
samples using
TRI-Reagent (Molecular Research Center), according to Manufacturer's
instructions. Tissue and
RNA samples were obtained from patients or from postmortem. Total RNA samples
were
treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen).
RT PCR - Purified RNA (1 fig) was mixed with 150 ng Random Hexamer primers
(Invitrogen) and S00 ~.M dNTP in a total volume of 15.6 ~,1. The mixture was
incubated for 5
min at 65 °C and then quickly chilled on ice. Thereafter, 5 pl of SX
SuperscriptII first strand
buffer (Invitrogen), 2.4,1 0.1M DTT and 40 units RNasin (Prornega) were added,
and the
mixture was incubated for 10 min at 25 °C, followed by further
incubation at 42 °C for 2 min.

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Then, I yI (200units) of SuperscriptII (Invitrogen) was added and the reaction
(final volume of
251) was incubated for 50 min at 42 °C and then inactivated at 70
°C for l5min. The resulting
cDNA was diluted 1:20 in TE buffer ( 10 mM Tris pH=8, 1 mM EDTA pH=8).
Real-Time RT PCR afzalysis- cDNA (Spl), prepared as described above, was used
as a
template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied
Biosystem)
with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The
amplification was
effected as follows: 50 °C for 2 min, 95 °C for 10 min, and then
40 cycles of 95 °C for l5sec,
followed by 60 °C for 1 min. Detection was performed by using the PE
Applied Biosystem SDS
7000. The cycle in which the reactions achieved a threshold level (Ct) of
fluorescence was
registered and was used to calculate the relative transcript quantity in the
RT reactions. The
relative quantity was calculated using the equation Q=efficiency~-~'. The
efficiency of the PCR
reaction was calculated from a standard curve, created by using serial
dilutions of several
reverse transcription (RT) reactions. To minimize inherent differences in the
RT reaction, the
resulting relative quantities were normalized to the geometric mean of the
relative quantities of
several housekeeping (HSKP) genes. Schematic surmnary of quantitative real-
time PCR
analysis is presented in Figure 3. As shown, the x-axis shows the cycle
number.The CT =
Threshold Cycle point, which is the cycle that the amplification curve crosses
the fluorescence
threshold that was set in the experiment. This point is a calculated cycle
number in which PCR
products signal is above the background level (passive dye ROX) and still in
the
Geometric/Exponential phase (as shown, once the level of fluorescence crosses
the
measurement threshold, it has a geometrically increasing phase, during which
measurements are
most accurate, followed by a linear phase and a plateau pliase; for
quantitative measurements,
the latter two phases do not provide accurate measurements). The y-axis shows
the normalized
reporter fluorescence. It should be noted that this type of analysis provides
relative
quantification.
The sequences of the housekeeping genes measured in all the examples on tissue
testing
panel were as follows:
PBGD (GenBank Accession No. BC019323),

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PBGD Forward primer (SEQ ID N0:529): TGAGAGTGATTCGCGTGGG
PBGD Reverse primer (SEQ ID NO:530): CCAGGGTACGAGGCTTTCAAT
PBGD-amplicon (SEQ ID N0:531):
TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGAC
AGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG
HPRT1 (GenBanle Accession No. NM 000194),
HPRT1 Forward primer (SEQ ID N0:532): TGACACTGGCAAAACAATGCA
HPRT1 Reverse primer (SEQ ID N0:533): GGTCCTTTTCACCAGCAAGCT
HPRT1-amplicon (SEQ ID N0:612):
TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCCAA
AGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC
G6PD (GenBank Accession No. NM 000402)
G6PD Forward primer (SEQ ID N0:613): gaggccgtcaccaagaacat
G6PD Reverse primer (SEQ ID NO:614): ggacagccggtcagagctc
G6PD-amplicon (SEQ ID NO:615):
gaggecgtcaccaagaacattcacgagtcctgcatgagccagataggctggaaccgcatcatcgtggagaagcccttcg
ggagggacct
gcagagctctgaccggctgtcc
RPS27A (GenBank Accession No. NM 002954)
RPS27A Forward primer (SEQ ID N0:642): CTGGCAAGCAGCTGGAAGAT
RPS27A Reverse primer (SEQ ID N0:1260): TTTCTTAGCACCACCACGAAGTC
RPS27A-amplicon (SEQ ID NO:1261):
CTGGCAAGCAGCTGGAAGATGGACGTACTTTGTCTGACTACAATATTCAAAAGGAG
TCTACTCTTCATCTTGTGTTGAGACTTCGTGGTGGTGCTAAGAAA
The sequences of the housekeeping genes measured in all the examples on normal
tissue
panel were as follows:
RPL19 (GenBank Accession No. NM 000981),

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RPL19 Foxward primer (SEQ ID N0:1262): TGGCAAGAAGAAGGTCTGGTTAG
RPL19 Reverse primer (SEQ ID NO:1263): TGATCAGCCCATCTTTGATGAG
RPLI9 -amplicon (SEQ ID NO:I264):
TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA
ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA
TATA box (GenBank Accession No. NM 003194),
TATA box Forward primer (SEQ ID N0:1265): CGGTTTGCTGCGGTAATCAT
TATA box Reverse primer(SEQ ID N0:1266): TTTCTTGCTGCCAGTCTGGAC
TATA box -amplicon (SEQ ID NO:1267):
CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT
CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG
GCAGCAAGAAA
Ubiquitin(GenBank Accession No. BC000449)
Ubiquitin Forward primer (SEQ ID NO:I268): ATTTGGGTCGCGGTTCTTG
Ubiquitin Reverse primer (SEQ ID N0:1269): TGCCTTGACATTCTCGATGGT
Ubiquitin -amplicon (SEQ ID N0:1270):
ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT
CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG
TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA
SDHA (GenBank Accession No. NM 004168)
SDHA Forward primer (SEQ ID N0:1271): TGGGAACAAGAGGGCATCTG
SDHA Reverse primer (SEQ ID N0:1272): CCACCACTGCATCAAATTCATG
SDHA-amplicon (SEQ ID N0:1273):
TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT
AGTGGATCATGAATTTGATGCAGTGGTGG
Oligonucleotide-based micro-of°ray experiment protocol-
Microarray fabrication
Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII
600
robot from BioRobtics Limited (Cambridge, UK). 50-mer oligonucleotides target
sequences

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were designed by Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et al,
"Optical
technologies and informatics", Proceedings of SPIE. Vol 4266, pp. 86-95
(2001). The designed
oligonucleotides were synthesized and purified by desalting with the Sigma-
Genosys system
(The Woodlands, TX, US) and all of the oligonucleotides were joined to a C6
amino-modified
linker at the 5' end, or being attached directly to CodeLink slides (Cat #25-
6700-O1. Amersham
Bioscience, Piscataway, NJ, US). The 50-mer oligonucleotides, forming the
target sequences,
were first suspended in Ultra-pure DDW (Cat # O1-866-lA Kibbutz Beit-Haemelc,
Israel) to a
concentration of 50~M. Before printing the slides, the oligonucleotides were
resuspended in
300mM sodium phosphate (pH 8.5) to final concentration of 150mM and printed at
35-40%
relative humidity at 21°C.
Each slide contained a total of 9792 features in 32 subarrays. Of these
features, 4224
features were sequences of interest according to the present invention and
negative controls that
were printed in duplicate. An additional 288 features (96 target sequences
printed in triplicate)
contained housekeeping genes from Human Evaluation Library2, Compugen Ltd,
Israel.
I5 Another 384 features axe E.coli spikes I-6, which are oligos to E-Coli
genes which are
commercially available in the Array Control product (Array control- sense
oligo spots, Ambion
Inc. Austin, TX. Cat #1781, Lot #112K06).
Post-couplin processing ofprinted slides
After the spotting of the oligonucleotides to the glass (CodeLink) slides, the
slides were
incubated for 24 hours in a sealed saturated NaCI humidification chamber
(relative humidity 70-
75%).
Slides were treated for blocking of the residual reactive groups by incubating
them in
blocking solution at 50°C for 15 minutes (lOml/slide of buffer
containing O.IM Tris, 50mM
ethanolamine, O.I% SDS). The slides were then rinsed twice with Ultra-pure DDW
(double
distilled water). The slides were then washed with wash solution (lOml/slide.
4X SSC, 0.1%
SDS)) at 50°C for 30 minutes on the shaker. The slides were then rinsed
twice with Ultra-pure
DDW, followed by drying by centrifugation for 3 minutes at 800 rpm.
Next, in order to assist in automatic operation of the hybridization protocol,
the slides
were treated with Ventana Discovery hybridization station barcode adhesives.
The printed
slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device
and were

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incubated for 10 minutes in SOml of 3-Aminopropyl Triethoxysilane (Sigma A3648
lot
#122K589). Excess fluid was dried and slides were then incubated for three
hours in 20 mm/Hg
in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding CA).
The following protocol was then followed with the Genisphere 900-RP (random
primer),
with mini elute columns on the Ventana Discovery HybStationTM, to perform the
microarray
experiments. Briefly, the protocol was performed as described with regard to
the instructions
and information provided with the device itself. The protocol included cDNA
synthesis and
labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems.
Sunnyvale, CA.) PicoFlour, which is used with the OliGreen ssDNA Quantitation
reagent and
kit.
Hybridization was performed with the Ventana Hybridization device, according
to the
provided protocols (Discovery Hybridization Station Tuscon AZ).
The slides were then scanned with GenePix 4000B dual Iaser scanner from Axon
Instruments Inc, and analyzed by GenePix Pro 5.0 software.
Schematic summary of the oligonucleotide based microan-ay fabrication and the
experimental flow is presented in Figures 4 and 5.
Briefly, as shown in Figure 4, DNA oligonucleotides at 25uM were deposited
(printed)
onto Amersham 'CodeLinlc' glass slides generating a well defined 'spot'. These
slides are
covered with a long-chain, hydrophilic polymer chemistry that creates an
active 3-D surface that
covalently binds the DNA oligonucleotides 5'-end via the
C6-amine modification. This binding ensures that the full length of the DNA
oligonucleotides is
available for hybridization to the cDNA and also allows lower background, high
sensitivity and
reproducibility.
Figure 5 shows a schematic method for performing the microarray experiments.
It
should be noted that stages on the left-hand or right-hand side may optionally
be performed in
any order, including in parallel, until stage 4 (hybridization). Briefly, on
the left-hand side, the
target oligonucleotides are being spotted on a glass microscope slide
(although optionally other
materials could be used) to form a spotted slide (stage 1). On the right hand
side, control sample
RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to
form labeled

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probes. It should be noted that the control and cancer samples come from
corresponding tissues
(for example, normal prostate tissue and cancerous prostate tissue).
Furthermore, the tissue
from which the RNA was taken is indicated below in the specific examples of
data for particular
clusters, with regard to overexpression of an oligonucleotide from a "chip"
(microarray), as for
example "prostate" for chips in which prostate cancerous tissue and normal
tissue were tested as
described above. In stage 3, the probes are mixed. In stage 4, hybridization
is
performed to form a processed slide. In stage 5, the slide is washed and
scanned to form an
image file, followed by data analysis in stage 6.

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DESCRIPTION FOR CLUSTER M85491
Cluster M85491 features 2 transcripts) and 11 segments) of interest, the names
for
which are given in Tables 1 and 2, respectively, the sequences themselves are
given at the end
of the application. The selected protein variants are given in table 3.
Table 1 - Ti~anscr-ipts of irTtef~est
TranseztpYl~ame :,,. . ~' ~EQID~NO : ;~1 " : y
: .
, .
M85491 PEA 1 T16 I
M85491 PEA 1 T20 2
Table 2 - Segments of interest
Seg~ienY ~ SEQ Z3J N0: ' .
Name
M8549I PEA 1 0 89
node
M8549I PEA 1 13 90
node
M85491 PEA I 21 91
node
M85491 PEA 1 23 92
node
M85491 PEA 1 24 93
node
M8549I PEA 1 8 94
node
M8549I PEA 1 9 95
node
M85491 PEA 1 10 96
node
M85491 PEA 1 18 97
node
M85491 PEA 1 19 98
node
M8549I PEA 1 6 99
node
Table 3 - Proteifas of interest
Protein Name SEQ ID N4:
M85491 PEA I P I3 534

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M85491 PEA_1 P 14 535
These sequences are variants of the known protein Ephrin type-B receptor 2
[precursor]
(SwissProt accession identifier EPB2 HUMAN; known also according to the
synonyms EC
2.7.1.112; Tyrosine-protein kinase receptor EPH-3; DRT; Receptor protein-
tyrosine kinase
HEKS; ERK), SEQ ID NO: 616, referred to herein as the previously known
protein.
Protein Ephrin type-B receptor 2 [precursor] is known or believed to have the
following
function(s): Receptor for members of the ephrin-B family. The sequence for
protein Ephrin
type-B receptor 2 [precursor] is given at the end of the application, as
"Ephrin type-B receptor 2
[precursor] amino acid sequence" (SEQ ID N0:616). Known polymorphisms for this
sequence
are as shown in Table 4.
Table 4 - Amino acid nzutatiorzs for Known Protein
SNPpositiob(s) ~amment ,
- . tfn f
aminci ;acid ~
~~quenc~:
671 A
-> R. /FTId=VAR 004162.
1 - 20 MALRRLGAALLLLPLLAAVE ->
MWVPVLALPVCTYA
923 E -> K
956 L -> V
958 V->L
154 G->D
476 K -> KQ
495 - 496 Missing
532 E -> D
568 R -> RR
589 M->I
788 I->F
853 S -> A

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Protein Ephrin type-B receptor 2 [precursor] localization is believed to be
Type I
membrane protein.
The following GO Annotations) apply to the previously known protein. The
following
annotations) were found: protein amino acid phosphorylation; transmembrane
receptor protein
tyrosine kinase signaling pathway; neurogenesis, which are annotations)
related to Biological
Process; protein tyrosine lcinase; receptor; transrnembrane-ephrin receptor;
ATP binding;
transferase, which are annotations) related to Molecular Function; and
integral membrane
protein, which are annotations) related to Cellular Component.
The GO assignment relies on information from one or more of the
SwissProt/TremBl
Protein knowledgebase, available from <http://www.expasy.chlsprot/>; or
Locuslink, available
from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.
Cluster M85491 can be used as a diagnostic marker according to overexpression
of
transcripts of this cluster in cancer. Expression of such transcripts in
normal tissues is also given
according to the previously described methods. The term "number" in the left
hand column of
the table and the numbers on the y-axis of the figure below refer to weighted
expression of ESTs
in each category, as "parts per million" (ratio of the expression of ESTs for
a particular cluster to
the expression of all ESTs in that category, according to parts per million).
Overall, the following xesults were obtained as shown with regard to the
histograms in
Figure 6 and Table 5. This cluster is overexpressed (at least at a minimum
level) in the
following pathological conditions: epithelial malignant tumors and a mixture
of malignant
tumors from different tissues.
Table 5 - Normal tissue distribution
Name of Tissue Number
bladder 0
Bone 0
Brain 10
Colon 31
epithelial 10

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general 12
Kidney 0
Liver 0
Lung 5
Breast 8
Muscle 5
Ovary 36
pancreas 10
Skin 0
stomach 0
Table 6 - P values arid ratios for expYession izz cazzcerous tissue
Fame of'1'zasue,;.pl ,~2 SPA R3 ~ S',p~ R4.
:.
bladder 5.4e-01 6.0e-Ol3.2e-OI2.5 4.6e-OI1.9
Bone 1 2.8e-O11 1.0 7.Oe-Ol1.8
Brain 3.4e-O1 3.6e-O11.2e-O12.9 1.8e-022.7
Colon 3.4e-02 5.7e-028.2e-022.8 2.Oe-Ol2.1
epithelial I.7e-03 3.Se-032.Oe-032.8 l.le-022.2
general 4.8e-04 5.2e-046.7e-042.3 1.3e-03I.9
Kidney 4.3e-Ol 3.7e-O11 1.1 7.Oe-O 1.5
1
Liver 1 4.Se-Ol1 1.0 6.9e-O11.5
Lung 2.2e-O1 2.7e-O16.9e-023.6 3.4e-023.6
Breast 8.2e-O1 7.3e-Ol6.9e-O11.2 6.8e-Ol1.2
Muscle 9.2e-Ol 4.8e-Ol1 0.8 l .5e-Ol3.2
Ovary 8.Se-O1 7.3e-Ol9.Oe-O10.7 6.7e-O11.0
pancreas S.Se-O1 2.Oe-O16.7e-Ol1.2 3.Se-OI1.8
Skin 2.9e-OI 4.7e-O11.4e-O17.0 6.4e-Ol1.6
stomach l.Se-O1 3.2e-O11 1.0 8.Oe-O11.3

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As noted above, cluster M85491 features 2 transcript(s), which were listed in
Table 1
above. These transcripts) encode for proteins) which are variants) of protein
Ephrin type-B
receptor 2 [precursor]. A description of each variant protein according to the
present invention is
now provided.
Variant protein M85491 PEA 1 P 13 according to the present invention has an
amino
acid sequence as given at the end of the application; it is encoded by
transcripts)
M85491 PEA 1 T16. An alignment is given to the known protein (Ephrin type-B
receptor 2
[precursor]) at the end of the application. One or more alignments to one or
more previously
published protein sequences are given at the end of the application. A brief
description of the
relationship of the variant protein according to the present invention to each
such aligned protein
is as follows:
Comparison report between M85491 PEA 1 P 13 and EPB2 HUMAN:
l.An isolated chimeric polypeptide encoding for M85491 PEA_I P13, comprising a
first
amino acid sequence being at least 90 % homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR
TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY
EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMK1NTEVRSFGPVSRSGF
YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD
VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN
SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG
GREDLVYNITCKSCGSGRGACTRCGDNVQYAPRQLGLTEPRTYISDLLAHTQYTFEIQAV
NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL
QYYEK corresponding to amino acids 1 - 476 of EPB2 HUMAN, which also
corresponds to
amino acids 1 - 476 of M85491 PEA 1 P13, and a second amino acid sequence
being at least
70%, optionally at least 80%, preferably at least 85%, more preferably at
least 90% and most
preferably at least 95% homologous to a polypeptide having the sequence
VPIGWVLSPSPTSLRAPLPG corresponding to amino acids 477 - 496 of

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M85491 PEA 1 P13, wherein said first and second amino acid sequences are
contiguous and
in a sequential order.
2.An isolated polypeptide encoding for a tail of M85491 PEA 1 P13, comprising
a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% arid most preferably at least about 95%
homologous to the
sequence VPIGWVLSPSPTSLRAPLPG in M85491 PEA 1 P13.
The location of the variant protein was determined according to results from a
number of
different software programs and analyses, including analyses from SignalP and
other specialized
programs. The variant protein is believed to be located as follows with regard
to the cell:
secreted. The protein localization is believed to be secreted because both
signal-peptide
prediction programs predict that this protein has a signal peptide, and
neither trans-membrane
region prediction program predicts that this protein has a trans-membrane
region.
Variant protein M8549I PEA 1 P13 is encoded by the following transcript(s):
M85491 PEA_l T16, for which the sequences) is/are given at the end of the
application. The
coding portion of transcript M85491 PEA 1'T16 is shown in bold; this coding
portion starts at
position I43 and ends at position 1630. The transcript also has the following
SNPs as listed in
Table 7 (given according to their position on the nucleotide sequence, with
the alternative
nucleic acid listed; the last column indicates whether the SNP is known or
not; the presence of
known SNPs in variant protein M85491 PEA 1 P13 sequence provides support for
the
deduced sequence of this variant protein according to the present invention).
Table 7 - Nucleic acid SNPs
SI~tP .:~oszti~~ a~ Alternative nucleic Prevxausly:I:nown
nrxcleo~ide acid ~ SNP'?
sequence
799 G -> A Yes
1066 C -> T Yes
I S I 9 A -> G Yes
1872 C -> T Yes
2044 T -> C Yes

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2156 G -> A Yes
2606 C -> A Yes
2637 G -> C Yes
Variant protein M85491 PEA_l P14 according to the present invention has an
amino
acid sequence as given at the end of the application; it is encoded by
transcripts)
M85491 PEA 1 T20. An alignment is given to the known protein (Ephrin type-B
receptor 2
[precursor]) at the end of the application. One or more alignments to one or
more previously
published protein sequences are given at the end of the application. A brief
description of the
relationship of the variant protein according to the present invention to each
such aligned protein
is as follows:
Comparison report between M8549I PEA_l P14 and EPB2 HUMAN:
l.An isolated chimeric polypeptide encoding for M85491_PEA 1 P14, comprising a
first
amino acid sequence being at least 90 % homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEV SGYDENMNTIR
TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY
EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMK1NTEVRSFGPVSRSGF
YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD
VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1 -
270 of EPB2 HUMAN, which also corresponds to amino acids 1 - 270 of
M85491 PEA 1 P14, and a second amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence
ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL corresponding to amino acids 271 - 301 of
M85491 PEA 1 P14, wherein said first and second amino acid sequences are
contiguous and
in a sequential order.
2.An isolated polypeptide encoding for a tail of M85491 PEA 1 P14, comprising
a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,

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more preferably at least about 90% and most preferably at Ieast about 95%
homologous to the
sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL in M85491 PEA_1 P14.
The location of the variant protein was determined according to results from a
number of
different software programs and analyses, including analyses from SignalP and
other specialized
programs. The variant protein is believed to be located as follows with regard
to the cell:
secreted. The protein localization is believed to be secreted because both
signal-peptide
prediction programs predict that this protein has a signal peptide, and
neither trans-membrane
region prediction program predicts that this protein has a trans-membrane
region..
Variant protein M85491 PEA_l P14 is encoded by the following transcript(s):
M85491 PEA 1 T20, for which the sequences) is/are given at the end of the
application. The
coding portion of transcript M85491 PEA-1 T20 is shown in bold; this coding
portion starts at
position 143 and ends at position 1045. The transcript also has the following
SNPs as listed in
Table 8 (given according to their position on the nucleotide sequence, with
the alternative
nucleic acid listed; the last column indicates whether the SNP is known or
not; the presence of
known SNPs in variant protein M85491 PEA 1 P14 sequence provides support for
the
deduced sequence of this variant protein according to the present invention).
Table ~ - Nucleic acid SNPs
SNP ,,.position on Alternative nucleic Previcius~y known
:nucleotide acid SNP? ..
sequence, ; .,
799 G -> A Yes
1135 T -> C Yes
1160 T -> C Yes
1172 A -> C Yes
1176 T -> A Yes

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As noted above, cluster M8549I features I1 segment(s), which were listed in
Table 2
above and for which the sequences) axe given at the end of the application.
These segments)
are portions of nucleic acid sequences) which are described herein separately
because they are
of particular interest. A description of each segment according to the present
invention is now
provided.
Segment cluster M85491 PEA 1 node 0 according to the present invention is
supported
by 5 Libraries. The number of libraries was determined as previously
described. This segment
can be found in the following transcript(s): M85491 PEA 1 T16 and M85491 PEA-1
T20.
Table 9 below describes the starting and ending position of this segment on
each transcript.
Table 9 - Segfzzefzt location orz tra~rscf°ipts
'.Transcxipt .x~~ane Segxxierit starting : Segment e~zdi~g
~ positlow position .
M85491. PEA I T16 1 203
M85491 PEA_1 T20 1 203
Segment cluster M85491 PEA 1 node 13 according to the present invention is
supported by 6 libraries. The number of libraries was determined as previously
described. This
segment can be found in the following transcript(s): M85491 PEA 1 T20. Table
10 below
describes the starting and ending position of this segment on each transcript.
Table 10 - Seg~neyat location on tr~anscYipts
Transcript name Segment starting Segment endizlg position
pasitio~a
M85491 PEA 1 T20 954 ~~ I182
Microarray (chip) data is also available for this segment as follows. As
described above
with regard to the cluster itself, various oligonucleotides were tested fox
being differentially
expressed in various disease conditions, particularly cancer. The following
oligonuclaotides
were found to hit this segment, shown in Table 11.
Table Il - Oligofzucleotides related to tlzis segnzefzt

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Oligonucleotide Uvere~pressed in Chip reference
i~a~ne cancers
M85491 0 0 25999 colorectal cancer Colon
Segment cluster M85491 PEA 1 node 21 according to the present invention is
supported by 18 libraries. The nmnber of libraries was determined as
previously described. This
segment can be found in the following transcript(s): M8549I PEA_I T16. Table
12 below
describes the starting and ending position of this segment on each transcript.
Table 12 - Segnae~ct locatioyr oyz t~ahsc~°ipts
firanscrxpt name, Segtrient starting ~egrnent ending position
position ~.
M85491 PEA I T16 1110 1445
Segment cluster M85491 PEA 1 node 23 according to the present invention is
supported by 18 libraries. The number of libraries was determined as
previously described. This
segment can be found in the following transcript(s): M85491 PEA 1 T16. Table
13 below
describes the starting and ending position of this segment on each transcript.
Table 13 - Segrnerat location o~ transcripts
Transcript name - Segr~.e~t startiu~ S~g~ne~it ending.positzon
~ , position
M85491 PEA 1 T16 1446~~~ 1570
I5
Segment cluster M8549I PEA 1 node 24 according to the present invention is
supported by 3 libraries. The number of libraries was determined as previously
described. This
segment can be found in the following transcript(s): M8549I PEA 1 T16. Table
I4 below
describes the starting and ending position of this segment on each transcript.
Table 14 - Segment location on transcripts
Trarisaript name Segment starting position Segment ending position

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~M85491 PEA_1~TI6 1571 2875
Segment cluster M85491 PEA'1'node 8 according to the present invention is
supported
by 25 libraries. The number of libraries was determined as previously
described. This segment
can be found in the following transcript(s): M85491 PEA 1 T16 and M85491 PEA 1
T20.
Table 15 below describes the starting and ending position of this segment on
each transcript.
Table I S - Segment locatioro oJa trartscJ°ipts
Transcript name Segment starting Segment ending pcisition
~ po~itic~w . , .
M85491 PEA 1 T16 269 672
M85491 PEA_l T20 269 672
Microarray (chip) data is also available for this segment as follows. As
described above
with regard to the cluster itself, various oligonucleotides were tested for
being differentially
expressed in various disease conditions, particularly cancer. The following
oligonucleotides
were found to hit this segment with regard to colon cancer, shown in Table 16.
Table 16 - Oligonucleotides related to dais segment
Clligci~uchoticle name .: CJverexpressed iii eaiicers Chip.reference . ,
M85491 0 14 0 ~ colorectal cancer ~ Colon
Segment cluster M85491 PEA 1 node 9 according to the present invention is
supported
by 20 libraries. The number of libraries was determined as previously
described. This segment
can be found in the following transcript(s): M85491 PEA 1 T16 and M85491 PEA 1
T20.
Table 17 below describes the starting and ending position of this segment on
each transcript.
Table 17 - Segment location on transcripts
Transcxxpt nape Sent starting pasztion Segment en~ng position
M85491 PEA 1 T16 673 ~ 856
M85491 PEA 1 T20 673 856

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According to an optional embodiment of the present invention, short segments
related to
the above cluster are also provided. These segments are up to about 120 by in
length, and so are
included in a separate description.
Segment cluster M85491 PEA_l node~10 according to the present invention is
supported by 17 libraries. The number of libraries was determined as
previously described. This
segment can be found in the following transcript(s): M85491~PEA 1 T16 and
M8549I PEA_I T20. Table I8 below describes the starting and ending position of
this
segment on each transcript.
Table 18 - Segment locatiof-z on t~anscj°ipts
Transcrrpt ~a~ne Se anent staftin osit~ori Se erlt ~ndiin osition
.. .: K Y ,.
e. , ~ : . 4 g y ,.: .. , yw g ~ ,
g p, 4 ~
M85491 PEA 1 T16 857 ~ ,
953
M85491 PEA 1 T20 857 953
Segment cluster M85491 PEA 1 node_l8 according to the present invention is
supported by 15 libraries. The number of libraries was determined as
previously described. This
segment can be found in the following transcript(s): M85491 PEA 1 T16. Table
19 below
describes the starting and ending position of this segment on each transcript.
Table 19 - Segment location on transcripts
Transcript name Segment starting position Segxnezzt ending position
M85491 PEA 1 T16 954 1044
Segment cluster M85491 PEA 1 node 19 according to the present invention is
supported by 15 libraries. The number of libraries was determined as
previously described. This

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segment can be found in the following transcript(s): M8S49I PEA 1 T16. Table
20 below
describes the starting and ending position of this segment on each transcript.
Table 20 - Segment locatiorz on transcripts
Transcriptwarrxe.. ~eg~ent starting Segmebt ending position
position . .
M8S491 PEA I T16 ~I04S ~~ ~~ 1109
Segment cluster M85491 PEA-1'node 6 according to the present invention is
supported
by 11 libraries. The number of libraries was determined as previously
described. This segment
can be found in the following transcript(s): M8S491 PEA I T16 and M8S491 PEA 1
T20.
Table 21 below describes the starting and ending position of this segment on
each transcript.
Table 21 - Segment location ova tf°anscripts
Transcript mine ~e~ent starting Segmeri't endhi~ posiYiari
. position
M8S491 PEA 1 T16 204 '~ ~ 268
M8S491 PEA 1 T20 204 268
1S
Variant protein alignment to the previously known protein:
Sequence name: /tmp/qfmsU9VtxS/DylcZC9j8v:EPB2 HUMAN
Sequence documentation:
Alignment of: M85491 PEA 1 P13 x EPB2 HUMAN ..
Alignment segment 1/1:

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Quality: 4726.00
Escore: 0
Matching length: 476 Total
length: 476
Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00
Total Percent Similarity: 100.00 Total Percent
Identity: 100.00
Gaps: 0
Alignment:
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
ililllllllllllil(1111111(IIIIIIIIIIIIII(IIIIIIIIII
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSST 100
111111lllllllllllllllllllllllllllllllllllllllllill
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
, , _ . .
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
Illllllllllllllllllllllllll11111111111111111111111
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
IIIIllllllllllllllllllllllllllllllilllllllllllllll
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
IlllllllllllllliflllllilllllllllllllIIIIIIIIIIIffI
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250

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251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS350
IIIIIIIIIIII
IIIII
I
302 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII 350
TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS
IO 351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA400
IIIIliilllllll
l
l
l
351 l 400
lllllillllillllll11111IIIIIIIIII
GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYTSDLLA
401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD450
15 IIIIIIIIIIIIIIIiIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD450
451 SITLSWSQPDQPNGVILDYELQYYEK 476
Iill
l
l
20 451 llllllllllllllllllll 476
SITLSWSQPDQPNGVILDYELQYYEK
Sequence name: /tmp/rmnzuDbot6/GiHbjeUBiR:EPB2 HUMAN
Sequence documentation:
Alignment of: M85491 PEA l P14 x EPB2 HUMAN ..

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Alignment segment 1/1:
Quality: 2673.00
Escore: 0
Matching length: 270 Total
length: 270
Matching Percent Similarity: 200.00 Matching Percent
Identity; 100.00
IO Total Percent Similarity: 100.00 Total Percent
Identity: 100.00
Gaps: 0
Alignment:
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
Ilillllllllllllllllllfllflllllllllllllllllllllllll
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSST 100
Illilllllllllllllllllllllllllllllllllllilfllllllll
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
lllllllilIIIlIIIIl11111IIIIIIIIIIIiIIlIIIIIIIIIIii
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
IilllllllllllIIIIIIIIIIillllllllllllllllllllllllll
151 DLGGRVMKTNTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200

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201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
251 IGRCMCKAGFEAVENGTVCR 270
251 IGRCMCKAGFEAVENGTVCR 270
15 Expression of Ephs°in type-B receptor 2 precursor (EC 2.7.1.112)
(Tyj°osine protein kiraase
~°eceptof° EP.F~ 3) M85491 transcripts which are detectable by
afraplicora as depicted in sequerace
name M~5491seg24 in normal arid cancerous colon tissues
Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-
protein
kinase xeceptor EPH-3) transcripts detectable by or according to seg24 ,
M85491seg24 amplicon
and M85491 seg24F and M85491 seg24R primers was measured by zeal time PCR. In
parallel the
expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323;
amplicon
- PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM 000194;
amplicon
- HPRTl-amplicon, SEQ ID N0:612), G6PD (GenBank Accession No. NM 000402; G6PD
amplicon, SEQ ID N0:615), and RPS27A (GenBank Accession No. NM 002954; RPS27A
amplicon, SEQ ID N0:1261) was measured similarly. For each RT (RT-PCR) sample,
the
expression of the above amplicon was normalized to the geometric mean of the
quantities of the
housekeeping genes. The normalized quantity of each RT sample was then divided
by the
median of the quantities of the normal post-mortem (PM) samples (Sample Nos.
41, 52, 62-67,
69-71, Table 1, "Tissue samples in testing panel", above), to obtain a value
of fold up-regulation
for each sample relative to median of the normal PM samples.

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Figure 7 is a histogram showing over expression of the above-indicated Ephrin
type-B
receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein Icinase receptor EPH-3)
transcripts in
cancerous colon samples relative to the normal samples. Values represent the
average of
duplicate experiments. Error bars indicate the minimal and maximal values
obtained..
S As is evident from Figure 7, the expression of Ephrin type-B receptor 2
precursor (EC
2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by
the above
amplicon in cancer samples was significantly higher than in the non-cancerous
samples (Sample
Nos. 41,52, 62-67, 69-7I Table 1, "Tissue samples in testing panel"). Notably
over-expression
of at least 3 fold was found in 13 out of 37 adenocarcinoma samples.
Statistical analysis was applied to verify the significance of these results,
as described
below.
The P value for the difference in the expression levels of Ephrin type-B
receptor 2
precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts
detectable by the
above amplicon(s) in colon cancer samples versus the normal tissue samples was
determined by
T test as 6.83E-04 Threshold of 3 fold over expression was found to
differentiate between
cancer and normal samples with P value of 2.66E-02 in as checked by exact
fisher test. The
above values demonstrate statistical significance of the results.
Primer pairs are also optionally and preferably encompassed within the present
invention; for example, for the above experiment, the following primer pair
was used as a non-
limiting illustrative example only of a suitable primer pair: M85491seg24F
forward primer; and
M85491 seg24R reverse primer.
The present invention also preferably encompasses any amplicon obtained
through the
use of any suitable primer pair; for example, for the above experiment, the
following amplicon
was obtained as a non-limiting illustrative example only of a suitable
amplicon: M85491seg24.
M85491 seg24F (SEQ ID NO: 1274)- GGCGTCTTTCTCCCTCTGAAC
M85491 seg24R (SEQ ID NO: 1275)- GTCCCATTCTGGGTGCTGTG

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M85491 seg24 ~SEQ ID NO: 1276) -
GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGTGAGACCC
CTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGCACGCAGAATGGG
AC
S
Expression of Eplzrin type-B receptor 2 pf°ecm sor (EC 2. 7.1.112)
(Tyrosine protein Ieinase
receptor- EPH 3) M85491 transcripts which are detectable by arnplacou as
depicted ifa sequence
name M85491seg24 in different nor~rnal tissues.
Expression of Ephrin type-B receptor 2 precursor transcripts detectable by or
according to
M85491 seg24 amplicon(s) and M85491 seg24F and M85491 seg24R was measured by
real
1 S time PCR. In parallel the expression of four housekeeping genes -RPL19
(GenBank Accession
No. NM 000981; RPL19 amplicon), TATA box (GenBank Accession No. NM 003194;
TATA
amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-
amplicon) and
SDHA (GenBank Accession No. NM 004168; amplicon ~ SDHA-amplicon) was measured
similarly. For each RT sample, the expression of the above amplicon was
normalized to the
geometric mean of the quantities of the housekeeping genes. The normalized
quantity of each
RT sample was then divided by the median of the quantities of the lung samples
(Sample Nos.
1S-17 Table 2 Tissue samples in normal panel), to obtain a value of relative
expression of each
sample relative to median of the lung samples.
The results axe described in Figure 8, presenting the histogram showing the
expression of
2S M85491 transcripts which are detectable by amplicon as depicted in sequence
name
M85491 seg24 in different normal tissues.
Forward primer (SEQ ID NO: I274): GGCGTCTTTCTCCCTCTGAAC
Reverse primer (SEQ ID NO: 1275): GTCCCATTCTGGGTGCTGTG

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Amplicon (SEQ ID NO: 1276):
GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGTGAGACCC
CTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGCACCCAGAATGGG
AC
DESCRIPTION FOR CLUSTER T10888
Cluster T10888 features 4 transcripts) and 8 segments) of interest, the names
for which
are given in Tables 1 and 2, respectively, the sequences themselves are given
at the end of the
application. The selected protein variants are given in table 3.
Table 1 - Transcripts of interest
Transcript i~~mev. SEQ xI>:NO: a
T10888 PEA 1 T1 3~
T10888 PEA 1 T4 4
T10888 PEA 1 TS 5
T10888 PEA 1 T6 6
Table 2 - Segments of intef°est
Segmen ._....~..~ _._...._...~~Q ~ 1VU:
Name . -~
t
T10888PEA 1 l1 100
node
T10888PEA 1 12 101
node
T10888PEA 1 17 102
node
T10888PEA 1 4 103
node
T10888PEA 1 6 104
node
T10888PEA 1 7 105
node
T10888PEA 1 9 106
node
T10888PEA 1 15 107
node
Table 3 - Proteins of interest

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protein SEQ ID NO :
Naii~e
T10888 PEA P2 536
1
T10888 PEA P4 537
1
T10888 PEA PS 538
1
T10888 PEA P6 539
1
These sequences are variants of the known protein Carcinoembryonic antigen-
related cell
adhesion molecule 6 precursor (SwissProt accession identifier CEA6 HUMAN;
known also
according to the synonyms Normal cross-reacting antigen; Nonspecific
crossreacting antigen;
CD66c antigen), SEQ ID NO: 617, referred to herein as the previously lenown
protein.
The sequence for protein Carcinoembryonic antigen-related cell adhesion
molecule 6
precursor is given at the end of the application, as "Carcinoembryonic antigen-
related cell
adhesion molecule 6 precursor amino acid sequence". Known polymorphisms for
this sequence
are as shown in Table 4.
239 I V->G
Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor
localization
is believed to be Attached to the membrane by a GPI-anchor.
The previously known protein also has the following indications) and/or
potential
therapeutic use(s): Cancer. It has been investigated for clinicalltherapeutic
use in humans, for
example as a target for an antibody or small molecule, and/or as a direct
therapeutic; available
information related to these investigations is as follows. Potential
pharmaceutically related or
therapeutically related activity or activities of the previously lenown
protein are as follows:
hrununostiinulant. A therapeutic role for a protein represented by the cluster
has been predicted.
The cluster was assigned this held because there was information in the drug
database or the
public databases (e.g., described herein above) that this protein, or part
thereof, is used or can be

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268
used for a potential therapeutic indication: Imaging agent; Anticancer;
Immunostimulant;
Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody.
The following GO Annotations) apply to the previously known protein. The
following
annotations) were found: signal transduction; cell-cell signaling, which are
annotations)
related to Biological Process; and integral plasma membrane protein, which are
annotations)
related to Cellular Component.
The GO assignment relies on information from one or more of the
SwissProt/TremBl
Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or
Locuslink, available
from <http:/lwww.ncbi.nlm.nih.gov/projects/LocusLink/>.
Cluster T10888 can be used as a diagnostic marker according to overexpression
of
transcripts of this cluster in cancer. Expression of such transcripts in
normal tissues is also given
according to the previously described methods. The term "number" in the right
hand column of
the table and the numbers on the y-axis of the figure below refer to weighted
expression of ESTs
I S in each category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to
the expression of all ESTs in that category, according to parts per million).
Overall, the following results were obtained as shown with regard to the
histograms in
Figure 9 and Table 5. This cluster is overexpressed (at least at a minimum
level) in the
following pathological conditions: colorectal cancer, a mixture of malignant
tumors from
different tissues, pancreas carcinoma and gastric carcinoma.
Table 5 - NoYmal tissue distf°ibutiorz
Name of 'issue Number
bladder 0
Colon 107
epithelial 52
general 22
head and neck 40
lung 237

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breast 0
pancreas ~ 32
prostate 12
stomach 0
Table 6 - P values azzd ratios for expression izz cancerous tissue
~~e of TissuepI p2 SP1 R3 8P2' R.4
'
bladder 5.4e-O1 3.4e-O15.6e-O11.8 4.6e-O11.9
colon I.2e-O1 1.7e-Ol2.8e-OS3.7 7.9e-042.8
epithelial 3.3e-02 2.1e-Ol2.8e-202.8 4.8e-10I.9
general 3.3e-OS 2.2e-031.9e-444.9 4.6e-273.3
head and neck4.6e-01 4.3e-Ol1 0.8 7.Se-O11.0
Lung 7.6e-O 8.2e-O 8.9e-O 0.6 1 0.3
I 1 I
breast 3.7e-02 4.1e-02l.Se-O13.3 3.Ie-O12.4
pancreas 2.6e-O1 2.4e-Ol8,6e-232.8 l.Se-194.5
prostate 9.1 e-O19.3e-O14.1 1.2 1.Oe-O11.0
e-02
stomach 4.Se-02 5.6e-02S.Ie-044.1 4.7e-046.3
As noted above, cluster ~t'1U888 features 4 transcript(s), which were listed
in Table 1
above. These transcripts) encode for proteins) which are variants) of protein
Carcinoembryonic antigen-related cell adhesion molecule 6 precursor. A
description of each
variant protein according to the present invention is now provided.
Variant protein T10888 PEA 1 P2 according to the present invention has an
amino acid
sequence as given at the end of the application; it is encoded by transcripts)
TI0888 PEA I T1. An alignment is given to the known protein (Carcinoembryonic
antigen-
related cell adhesion molecule 6 precursor) at the end of the application. One
or more
alignments to one or more previously published protein sequences axe given at
the end of the
application. A brief description of the relationship of the variant protein
according to the present
invention to each such aligned protein is as follows:

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Comparison report between T10888 PEA I PZ and CEA6 HUMAN:
I.An isolated chimeric polypeptide encoding for T10888 PEA_1 P2, comprising a
first
amino acid sequence being at least 90 % homologous to
MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP
QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG
FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL
WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY
GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS
YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1 - 319 of
CEA6 HUMAN, which also corresponds to amino acids 1 - 319 of T10888 PEA 1 P2,
and a
second amino acid sequence being at Ieast 70%, optionally at least 80%,
preferably at least 85%,
more preferably at least 90% and most preferably at least 95% homologous to a
polypeptide
having the sequence DWTRP corresponding to amino acids 320 - 324 of T10888 PEA
1 P2,
wherein said first and second amino acid sequences are contiguous and in a
sequential order.
2.An isolated polypeptide encoding for a tail of T10888 PEA 1 P2, comprising a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence DWTRP in T10888 PEA 1 P2.
The location of the variant protein was determined according to results from a
number of
different software programs and analyses, including analyses from SignalP and
other specialized
programs. The variant protein is believed to be located as follows with regard
to the cell:
secreted. The protein localization is believed to be secreted because both
signal-peptide
prediction programs predict that this protein has a signal peptide, and
neither trans-membrane
region prediction program predicts that this protein has a trans-membrane
region..
Variant protein TI0888 PEA_I P2 also has the following non-silent SNPs (Single
Nucleotide Polymorphisms) as listed in Table 7, (given according to their
positions) on the
amino acid sequence, with the alternative amino acids) listed; the last column
indicates whether
the SNP is known or not; the presence of known SNPs in variant protein TI0888
PEA 1 P2
sequence provides support for the deduced sequence of this variant protein
according to the
present invention).

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Table 7 - Anzino acid nZZatatiohs
SNP-position(s)' Alternative amino Previously known SNP?
on anii~o acid acids)
sequence
13 V -> No
232 N -> D No
324 P -> No
63 I -> No
92 G -> No
Variant protein T10888 PEA 1 P2 is encoded by the following transcript(s):
T10888 PEA 1 T1, for which the sequences) is/are given at the end of the
application. The
coding portion of transcript T10888 PEA 1 T1 is shown in bold; this coding
portion starts at
position 151 and ends at position 1122. The transcript also has the following
SNPs as listed in
Table 8 (given according to their position on the nucleotide sequence, with
the alternative
nucleic acid listed; the last column indicates whether the SNP is known or
not; the presence of
known SNPs in variant protein T10888 PEA 1 P2 sequence provides support for
the deduced
sequence of this variant protein according to the present invention).
Table 8 - Nucleic acid SNPs
SNP ~os~tio~a '~ Alternative Previously known SNP?
on . nucleotide tacleic acid
n
seclpeixce
119 C -> T No
120 A -> T No
1062 A -> G Yes
1120 C -> No
1297 G -> T Yes
1501 A -> G Yes
1824 G -> A No
2036 A -> C No
2036 A -> G No

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2095 A -> C No
2242 A -> C No
2245 A -> C No
189 C -> No
2250 A -> T Yes
2339 C -> A Yes
276 G -> A Yes
338 T _> No
424 G -> No
546 A -> G No
702 C -> T No
844 A -> G No
930 C -> T Yes
Variant protein T10888 PEA 1 P4 according to the present invention has an
amino acid
sequence as given at the end of the application; it is encoded by transcripts)
T10888 PEA 1 T4. An alignment is given to the known protein (Carcinoembryonic
antigen-
related cell adhesion molecule 6 precursor) at the end of the application. One
or more
alignments to one or more previously published protein sequences are given at
the end of the
application. A brief description of the relationship of the variant protein
according to the present
invention to each such aligned protein is as follows:
Comparison report between T10888 PEA 1 P4 and CEA6 HUMAN:
l.An isolated chimeric polypeptide encoding for T10888 PEA 1 P4, comprising a
first
amino acid sequence being at least 90 % homologous to
MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP
1S QNRIGYSWYI~GERVDGNSLIVGYVTGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG
FYTLQVIKSDLVNEEATGQFHVYPELPI~PSISSNNSNPVEDKDAVAFTCEPEVQNTTYL
VVWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL

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corresponding to amino acids 1 - 234 of CEA6 HUMAN, which also corresponds to
amino
acids 1 - 234 of T10888 PEA 1 P4, and a second amino acid sequence being at
least 70%,
optionally at least 80%, preferably at least 85%, more preferably at least 90%
and most
preferably at least 95% homologous to a polypeptide having the sequence
LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of
T10888 PEA 1'P4, wherein said first and second amino acid sequences are
contiguous and in a
sequential order.
2.An isolated polypeptide encoding for a tail of TI0888 PEA 1 P4, comprising a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence LLLSSQLWPPSASRLECWPGWL in T10888 PEA 1 P4.
Comparison report between TI0888 PEA_l~P4 and Q13774 (SEQ ID N0:1382):
l.An isolated chimeric polypeptide encoding for T10888 PEA-1 P4, comprising a
first
amino acid sequence being at least 90 % homologous to
MGPPSAPPCRLHVPWI~EVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP
QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG
FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL
WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL
corresponding to amino acids 1 - 234 of Q 13774, which also corresponds to
amino acids 1 - 234
of T10888 PEA 1 P4, and a second amino acid sequence being at least 70%,
optionally at least
80%, preferably at least 85%, more preferably at least 90% and most preferably
at least 95%
homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL
corresponding to amino acids 235 - 256 of T10888 PEA 1 P4, Wherein said first
and second
amino acid sequences are contiguous and in a sequential order.
2.An isolated polypeptide encoding for a tail of T10888 PEA 1 P4, comprising a
polypeptide being at least 70%, optionally at least about 80%, preferably at
least about 85%,
more preferably at least about 90% and most preferably at least about 95%
homologous to the
sequence LLLSSQLWPPSASRLECWPGWL in T10888 PEA 1 P4.

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The location of the variant protein was determined according to results from a
number of
different software programs and analyses, including analyses from SignalP and
other specialized
programs. The variant protein is believed to be located as follows with regard
to the cell:
secreted. The protein localization is believed to be secreted because both
signal-peptide
prediction programs predict that this protein has a signal peptide, and
neither trans-membrane
region prediction program predicts that this protein has a trans-membrane
region..
Variant protein T10888 PEA 1 P4 also has the following non-silent SNPs (Single
Nucleotide Polymorphisms) as listed in Table 9, (given according to their
positions) on the
amino acid sequence, with the alternative amino acids) listed; the last column
indicates whether
the SNP is known or not; the presence of known SNPs in variant protein T10888
PEA 1 P4
sequence provides support for the deduced sequence of this variant protein
according to the
present invention).
Table 9 - Amiho acid mutations
SNP ~osi~ion(s) on Alternative amino Previously known SNP
ammo acid. acids)
seqiisnce .:.: , - .: . ,. No
. ; V ->
13
232 N -> D No
63 I -> No
92 G -> No
Variant protein T10888_PEA-1 P4 is encoded by the following transcript(s):
T10888 PEA 1 T4, for which the sequences) is/are given at the end of the
application. The
coding portion of transcript T10888 PEA 1 T4 is shown in bold; this coding
portion starts at
position 151 and ends at position 918. The transcript also has the following
SNPs as listed in
Table 10 (given according to their position on the nucleotide sequence, with
the alternative
nucleic acid listed; the last column indicates whether the SNP is known or
not; the presence of
known SNPs in variant protein T10888 PEA 1 P4 sequence provides support for
the deduced
sequence of this variant protein according to the present invention).
Table 10 - Nucleic acid SNPs

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SNP position on nucleotideAlternative nucleic Previously lrnown
sequence acid, SNP?
,
119 C->T No
120 A -> T No
978 C -> No
1155 G -> T Yes
1359 A -> G Yes
1682 G -> A No
I 894 A -> C No
1894 A -> G No
1953 A -> C No
2100 A -> C No
2103 A -> C No
2108 A -> T Yes
189 C -> No
2197 C -> A Yes
276 G -> A Yes
338 T -> No
424 G -> No
546 A -> G No
702 C -> T No
844 A -> G No
958 G -> No
Variant protein TI0888 PEA 1 PS according to the present invention has an
amino acid
sequence as given at the end of the application; it is encoded by transcripts)
T10888 PEA 1 T5. An alignment is given to the known protein (Carcinoembryonic
antigen-
related cell adhesion molecule 6 precursor) at the end of the application. One
or more
alignments to one or more previously published protein sequences are given at
the end of the

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