WO2005107364A9 - Nouvelles sequences de nucleotides et d'acides amines, et leurs dosages et procedes d'utilisation pour le diagnostic - Google Patents

Nouvelles sequences de nucleotides et d'acides amines, et leurs dosages et procedes d'utilisation pour le diagnostic

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Publication number
WO2005107364A9
WO2005107364A9 PCT/IB2005/002407 IB2005002407W WO2005107364A9 WO 2005107364 A9 WO2005107364 A9 WO 2005107364A9 IB 2005002407 W IB2005002407 W IB 2005002407W WO 2005107364 A9 WO2005107364 A9 WO 2005107364A9
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Prior art keywords
pea
node
hscreact
amino acids
amino acid
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2005/002407
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English (en)
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WO2005107364A2 (fr
WO2005107364A3 (fr
Inventor
Amir Toporik
Sarah Pollock
Zurit Levine
Michal Ayalon-Soffer
Gad S Cojocaru
Alexander Diber
Amit Novik
Dvir Dahary
Pinchas Akiva
Rotem Sorek
Ronen Shemesh
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Compugen USA Inc
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Compugen USA Inc
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Application filed by Compugen USA Inc filed Critical Compugen USA Inc
Priority to EP05767217A priority Critical patent/EP1735342A2/fr
Priority claimed from US11/043,806 external-priority patent/US7368548B2/en
Publication of WO2005107364A2 publication Critical patent/WO2005107364A2/fr
Publication of WO2005107364A9 publication Critical patent/WO2005107364A9/fr
Anticipated expiration legal-status Critical
Publication of WO2005107364A3 publication Critical patent/WO2005107364A3/fr
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Definitions

  • the present invention is related to novel nucleotide and protein sequences, and assays and methods of use thereof.
  • Diagnostic markers are important for early diagnosis of many diseases, as well as monitoring treatment and determining prognosis of such diseases.
  • Serum markers are examples of such diagnostic markers and are used for diagnosis of many different diseases. Such serum markers typically encompass secreted proteins and/or peptides; however, some serum markers may be released to the blood upon trauma, such as trauma to the heart (for example through cardiac failure).
  • Immunohistochemistry is the study of distribution of an antigen of choice in a sample based on specific antibody-antigen binding, typically on tissue slices. The antibody features a label which can be detected, for example as a stain which is detectable under a microscope. The tissue slices are prepared by being fixed. IHC is therefore particularly suitable for antibody- antigen reactions that are not disturbed or destroyed by the process of fixing the tissue slices. IHC permits determining the localization of binding, and hence mapping of the presence of the antigen within the tissue and even within different compartments in the cell. Such mapping can provide useful diagnostic information, including:
  • IHC information is valuable for more than diagnosis. It can also be used to determine prognosis and therapy treatment (as in the case of HER-2 in breast cancer) and monitor disease.
  • IHC protein markers could be from any cellular location. Most often these markers are membrane proteins but secreted proteins or intracellular proteins (including intranuclear) can be used as an IHC marker too.
  • IHC has at least two major disadvantages. It is performed on tissue samples and therefore a tissue sample has to be collected from the patient, which most often requires invasive procedures like biopsy associated with pain, discomfort, hospitalization and risk of infection. In addition, the interpretation of the result is observer dependant and therefore subjective. There is no measured value but rather an estimation (on a scale of 1-4) of how prevalent the antigen on target is.
  • the present invention provides, in different embodiments, many novel amino acid and nucleic acid sequences, which may optionally be used as diagnostic markers.
  • the present invention provides a number of different variants of known serum proteins, which may optionally be used as diagnostic markers, preferably as serum markers, or optionally as IHC markers.
  • the present invention therefore overcomes the many deficiencies of the background art with regard to the need to obtain tissue samples and subjective interpretations of results.
  • serum markers require only a simple blood test and their result is typically a scientifically measured number.
  • IHC markers the variants of the present invention may also provide different and/or better measurement parameters for various diseases and/or pathological conditions.
  • the present invention also provides a number of different variants of known IHC proteins, which may optionally be used as diagnostic markers, preferably as serum markers, or optionally as IHC markers.
  • the present invention therefore overcomes the many deficiencies of the background art with regard to the need to obtain tissue samples and subjective interpretations of results.
  • serum markers require only a simple blood test and their result is typically a scientifically measured number.
  • the variants of the present invention may also provide different and/or better measurement parameters for various diseases and/or pathological conditions.
  • Other variants are also provided by the present invention as described in greater detail below.
  • a "marker- detectable disease” refers to a disease that may be detected by a particular marker, with regard to the description of such diseases below.
  • the markers of the present invention alone or in combination, show a high degree of differential detection between disease and non-disease states.
  • the present invention therefore also relates to diagnostic assays for disease detection optionally and preferably in a biological sample taken from a subject (patient), which is more preferably some type of body fluid or secretion including but not limited to seminal plasma, blood, serum, urine, prostatic fluid, seminal fluid, semen, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, cerebrospinal fluid, sputum, saliva, milk, peritoneal fluid, pleural fluid, cyst fluid, broncho alveolar lavage, lavage of the reproductive system and/or lavage of any other part of the body or system in the body, and stool or a tissue sample.
  • the term may also optionally encompass samples of in vivo cell culture constituents.
  • the sample can optionally be diluted with a suitable eluant before contacting the sample to an antibody and/or performing any other diagnostic assay.
  • signalp_hmm and “signalp_nn” refer to two modes of operation for the program SignalP: hmni 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.
  • T - > C means that the SNP results in a change at the position given in the table from T to C.
  • 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 (*).
  • 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 header of the first column is "SNP position(s) 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 and/or 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 and/or nucleic acid sequence described herein.
  • P- value including the le ⁇ el of expression in cell- lines (P2)
  • 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.
  • 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.
  • 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
  • the probe names follow the
  • ADP adipocyte
  • BM bone marrow
  • BRS mammary gland
  • CAR cartilage
  • CNS central nervous system
  • E-ADR endocrine_adrenal_gland
  • E-PAN endocrine_pancreas
  • E-PT endocrine_parathyroid_thyroid
  • EPID epididymis
  • GI gastrointestinal tract
  • lymph node MUS muscle
  • PNS peripheral nervous system
  • TCELL immune T cells
  • THYM thymus
  • TST testes
  • UTER cervix- uterus
  • VAS vascular endothelial artery
  • testisseminiferoustubule "S6"
  • nucleic acid sequences of the present invention 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 bebw.
  • 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.
  • the phrase "disease” includes any type of pathology and/or damage, including both chronic and acute damage, as well as a progress from acute to chronic damage.
  • 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 patients (subjects) having one of the herein- described diseases or conditions, as compared to a comparable sample taken from subjects who do not have one the above-described diseases or conditions.
  • 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.
  • the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present.
  • a relatively low amount of up- regulation may serve as the marker, as described herein.
  • One of ordinary skill in the art could easily determine such relative levels of the markers; further guidance is provided in the description of each individual marker below.
  • diagnostic means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity.
  • 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 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 suffices if the method provides a positive indication that aids in diagnosis.
  • diagnosis 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.
  • detecting may also optionally encompass any of the above.
  • Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide ⁇ 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.
  • a biological sample obtained from the subject may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below.
  • 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).
  • 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.
  • test amount of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of a particular disease or condition.
  • a test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).
  • control amount of a marker can be any amount or a range of amounts to be compared against a test amount of a marker.
  • a control amount of a marker can be the amount of a marker in a patient with a particular disease or condition or a person without such a disease or condition.
  • 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.
  • useful labels include 32 P, 35 S, 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.
  • 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. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry.
  • Exemplary detectable labels 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.
  • 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.
  • 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 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.
  • 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 immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein.
  • 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 immunoreactivity).
  • a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HSAPHOL T9 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • HSAPHOL P8 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSAPHOL_P2, 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 PHSGPAAAFIRRRGWWPGPRCA corresponding to. amino acids 1 - 22 of HSAPHOLJP2, second amino acid sequence being at least 90 % homologous to
  • PATPRPLSWLRAPTRLCLDGPSPVLCA corresponding to amino acids 1 - 27 of AAH21289, which also corresponds to amino acids 23 - 49 of HSAPHOLJP2, and a third amino acid sequence being at least 90 % homologous to EKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAAT ERSRCNTTQGNEVTSILRWAKDAGKSVG ⁇ VTTTRVNHATPSAAYAHSADRDWYSDNE MPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLD GLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVD YLLGLFEPGDMQYELNRNNVT DPSLSEMWVAIQILRKNPKGFFLLVEGGRTDHGHHE
  • YVPHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF corresponding to amino acids 83 - 586 of AAH21289, which also corresponds to amino acids 50 - 553 of HSAPHOL_P2, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a head of HSAPHOL_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 PHSGPAAAFIRRRGWWPGPRCA of HSAPHOL_P2.
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOLJP2 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 AE, having a structure as follows: a sequence starting from any of amino acid numbers 49-x to 50; and ending at any of amino acid numbers 50+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP2 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 PHSGPAAAFIRRRGWWPGPRCAPATPRPLSWLRAPTRLCLDGPSPVLCA corresponding to amino acids 1 - 49 of HSAPHOL_P2, second amino acid sequence being at least 90 % homologous to
  • YVPHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF corresponding to amino acids 21 - 524 of PPBT_HUMAN, which also corresponds to amino acids 50 - 553 of
  • HSAPHOLJP2 wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a head of HSAPHOLJP2 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
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOL_P2 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 AE, having a structure as follows: a sequence starting from any of amino acid numbers 49-x to 50; and ending at any of amino acid numbers 50+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP3, comprising a first amino acid sequence being at least 90 % homologous to MISPFLVLAIGTCLTNSLVP corresponding to amino acids 63 - 82 of AAH21289, which also corresponds to amino acids 1 - 20 of HSAPHOL_P3, and a second amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOL_P3, 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 PG, having a structure as follows: a sequence starting from any of amino acid numbers 20-x to 20; and ending at any of amino acid numbers 21+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP3, comprising a first amino acid sequence being at least 90 % homologous to MISPFLVL AIGTCLTN SLVP corresponding to amino acids 1 - 20 of PPBT_HUMAN, which also corresponds to amino acids 1 - 20 of HSAPHOL_P3, and a second amino acid sequence being at least 90 % homologous to GMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYL CGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSA AYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTD VEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFE PGDMQYELNRNN
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOLJP3, 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 PG, having a structure as follows: a sequence starting from any of amino acid numbers 20-x to 20; and ending at any of amino acid numbers 21+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P4 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for HSAPHOLJP5 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOLJP5 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 MD, having a structure as follows: a sequence starting from any of amino acid numbers 355-x to 355; and ending at any of amino acid numbers 356+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P5 comprising a first amino acid sequence being at least 90 % homologous to MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFL GDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTAT AYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVG ⁇ VTTTRVNHA
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOLJP5 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 MD, having a structure as follows: a sequence starting from any of amino acid numbers 355-x to 355; and ending at any of amino acid numbers 356+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P6 comprising a first amino acid sequence being at least 90 % homologous to MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFL GDGMGVSTVTAARILKGQLHHNPGEETPvLEMDKFPFVALSKTYNTNAQVPDSAGTAT AYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHA TPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPK NKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLL corresponding to amino acids 63 - 349 of AAH21289, which also corresponds to amino acids 1 - 287 of HSAPHOLJP6, and
  • SLAAGPLLLALALYPLSVLF corresponding to amino acids 395 - 586 of AAH21289, which also corresponds to amino acids 288 - 479 of HSAPHOLJP6, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOL_P6, 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 LG, having a structure as follows: a sequence starting from any of amino acid numbers 287-x to 287; and ending at any of amino acid numbers 288+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P6, comprising a first amino acid sequence being at least 90 % homologous to
  • SLAAGPLLLALALYPLSVLF corresponding to amino acids 333 - 524 of PPBTJHUMAN, which also corresponds to amino acids 288 - 479 of HSAPHOL_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of HSAPHOL_P6, 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 LG, having a structure as follows: a sequence starting from any of amino acid numbers 287-x to 287; and ending at any of amino acid numbers 288+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P7 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSAPHOLJP7 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
  • an isolated chimeric polypeptide encoding for HSAPHOLJP7 comprising a first amino acid sequence being at least 90 % homologous to MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFL GDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTAT AYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHA TPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPK NKTDVEYESDEKARGTRLDGLDLVDTWKSFKPR corresponding to amino acids 1 - 262 of PPBT_HUMAN, which also corresponds to amino acids 1 - 262 of HSAPHOLJP7, and a second amino acid sequence being at least 70%, optional
  • an isolated polypeptide encoding for a tail of HSAPHOL_P7 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 YKLPPRCPLANRVDFSWAGREYRLQTFSKPLIFLANVFLQTQRP in HSAPHOL_P7.
  • an isolated chimeric polypeptide encoding for HSAPHOL_P7 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSAPHOL_P7 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 LPPRCPLANRVDFSWAGREYRLQTFSKPLIFLANVFLQTQRP in HSAPHOLJP7.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP8 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSAPHOL_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 KWRGWRGGCMARSLVAGAACGQHLGTRP in HSAPHOL_P8.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP8 comprising a first amino acid sequence being at least 90 % homologous to
  • G corresponding to amino acids 1 - 288 of PPBTJEIUMAN, which also corresponds to amino acids 1 - 288 of HSAPHOL_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
  • KWRGWRGGCMARSLVAGAACGQHLGTRP corresponding to amino acids 289 - 316 of HSAPHOLJP8, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSAPHOLJP8 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 KWRGWRGGCMARSLVAGAACGQHLGTRP in HSAPHOLJP8.
  • an isolated chimeric polypeptide encoding for HSAPHOLJP8 comprising a first amino acid sequence being at least 90 % homologous to MISPFLVLMGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFL GDGMGVSTVTAAR ⁇ LKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTAT AYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHA TPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPK NKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLL
  • HSAPHOL_P8 HSAPHOL_P8
  • a second amino acid sequence being at least 70%, optionally at least
  • HSAPHOL_P8 wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSAPHOL_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
  • the Alkaline phosphatase variant-detectable disease comprises one or more of the following: liver diseases including but not limited to infectious, malignant, degenerating, cholestatic and autoimmune diseases, bone conditions including but not limited to
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HSKITCR_T6 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • HSKITCR_P5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSKITCR_P2, comprising a first amino acid sequence being at least 90 % homologous to
  • CSPNRQKPW corresponding to amino acids 1 - 951 of KIT_HUMAN, which also corresponds to amino acids 1 - 951 of HSKITCR_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
  • an isolated polypeptide encoding for a tail of HSKITCR_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 LQGHFIESFVLDILESLYFYNFFLHQMFLCSGLMFEIILWLFL in HSKITCRJP3.
  • an isolated chimeric polypeptide encoding for HSK ⁇ TCR_P4 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSKITCR_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 VSTHSLLDSPAKDF in HSKITCR_P4.
  • an isolated chimeric polypeptide encoding for HSKITCR_P5 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSKITCR_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 GKCLAFCSAVLSRI in HSKITCR_P5.
  • CDl 17-detectable cancers comprise gastrointestinal stromal tumors, mast cell tumors, and/or seminomatous germ cell tumors.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HSCREACT_PEA_1_T39 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated chimeric polypeptide encoding for HSCREACT_PEA_1_P9 comprising a first amino acid sequence being at least 90 % homologous to
  • MEKLLCFLVLTSLSHAFGQTDMSRKAFVFPKESDTSYVSLKAPLTKPLKAFTVCLHFYT ELSST corresponding to amino acids 1 - 64 of CRP_HUMAN, which also corresponds to amino acids 1 - 64 of HSCREACT_PEA_1_P9, second (bridging) amino acid sequence comprising H, and a third amino acid sequence being at least 90 % homologous to EINTIYLGGPFSPNVLNWRALKYEVQGEVFTKPQLWP corresponding to amino acids 188 - 224 of CRP_HUMAN, which also corresponds to amino acids 66 - 102 of HSCREACT_PEA_1_P9, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for an edge portion of HSCREACT_PEA_1_P9 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 THE having a structure as follows
  • an isolated chimeric polypeptide encoding for HSCREACTJPEA_l_P10 comprising a first amino acid sequence being at least 90 % homologous to MEKLLCFLVLTSLSHAFGQTDMSRKAFVFPKESDTSYVSLKAPLTKPLKAFTVCLHFYT
  • ELSSTRG corresponding to amino acids 1 - 66 of CRP_HUMAN, which also corresponds to amino acids 1 - 66 of HSCREACT_PEA_l_P10.
  • an isolated chimeric polypeptide encoding for HSCREACT_PEA_1_P12 comprising a first amino acid sequence being at least 90 % homologous to
  • ELSSTRG corresponding to amino acids 1 - 66 of CRP_HUMAN, which also corresponds to amino acids 1 - 66 of HSCREACT_PEA_1JP12, and a second amino acid sequence being at least 90 % homologous to PNVLNWRALKYEVQGEVFTKPQLWP corresponding to amino acids 200 - 224 of CRP_HUMAN, which also corresponds to amino acids 67 - 91 of
  • HSCREACT_PEA_1_P12 wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of HSCREACT_PEA_1_P12 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 GP, having a structure as follows: a sequence starting from any of amino acid numbers 66-x to 66; and ending at any of amino acid numbers 61 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSCREACT_PEA_1_P16 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSCREACT_PEA_1_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 VSESGHWPGVWFGSRVLIIMS in HSCREACT_PEA_1_P16.
  • an isolated chimeric polypeptide encoding for HSCREACT_PEA_1_P22 comprising a first amino acid sequence being at least 90 % homologous to MEKLLCFLVLTSLSHAFGQTDMSRKAFVFPKESDTSYVSLKAPLTKPLKAFTVCLHFYT ELSSTRG corresponding to amino acids 1 - 66 of CRP_HUMAN, which also corresponds to amino acids 1 - 66 of HSCREACT_PEA_1_P22, 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 AFLILWLFWETPPLFHTNLVGL corresponding to amino acids 67 - 88 of HSCREACT_PEA_1_P22, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSCREACT_PEA_1_P22 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 AFLILWLFWETPPLFHTNLVGL in HSCREACT_PEA_1_P22.
  • an isolated chimeric polypeptide encoding for HSCREACT_PEA_1_P28 comprising a first amino acid sequence being at least 90 % homologous to
  • MEKLLCFLVLTSLSHAFGQTDMSRKAFVFPKESDTSYVSLBLAPLTKPLKAFTVCLHFYT ELSST corresponding to amino acids 1 - 64 of CRP_HUMAN, which also corresponds to amino acids 1 - 64 of HSCREACTJPEA_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 LLS corresponding to amino acids 65 - 67 of HSCREACT_PEA_1_P28, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • the CRP variant- detectable disease may comprise one or more of the following: Assessment of disease activity in inflammatory conditions (Juvenile rheumatoid arthritis, Rheumatoid arthritis, Ankylosing spondylitis, Reiter disease, Psoriatic arthropathy, Vasculitides Behcet syndrome, Wegener granulomatosis, Polyarteritis nodosa, Polymyalgia rheumatica, Crohn's disease, Rheumatic fever, Familial fevers including familial Mediterranean fever, Acute pancreatitis); Diagnosis and management of infection (Bacterial endocarditis, Neonatal septicemia and meningitis, Intercurrent infection in systemic lupus erythematosus, Intercurrent infection in leukemia and its treatment, Postoperative complications including infection, and thromboembolism); Differential diagnosis/classification of inflammatory disease (Systemic lupus erythematosus vs.
  • rheumatoid arthritis Crohn disease vs. ulcerative colitis
  • Tissue necrosis after myocardial infarction and/or outcome of such an infarction 1. Coronary artery disease, non- fatal and fatal 2. Stroke 3. Progression of peripheral vascular disease 4. Development of Congestive Heart Failure 5. Sudden Cardiac Death. 6. Poor prognosis in severe unstable angina 7. Poor prognosis after angioplasty.
  • low-grade upregulation of CRP variant production may be detected for predicting coronary Events, stroke and cerebrovascular events, and other cardiovascular diseases such as unstable angina.
  • a diagnostic method or assay according to measurement of upregulated, slightly upregulated and/or baseline levels of a CRP variant according to the present invention.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • Z25227 T19 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HSCAMPATl PEA 1 T2 a nucleic acid sequence comprising a sequence in the table below: Segment Name
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • HSTIR PEA l_node_19 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HSCDIA PEA 1 TlO HSCDIA PEA 1 TIl a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • S69686 T48 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HUMTCXAAA_PEA_1_T11 HUMTCXAAA_PEA_1_T12 a nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • T87096_PEA_l_P39 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:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • HSPRO204 PEA 1 P21 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:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated chimeric polypeptide encoding for HSMUC1A_PEA_1_P63 comprising a first amino acid sequence being at least 90 % homologous to MTPGTQSPFFLLLLLTVLTWTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1 - 45 of MUC1_HUMAN, which also corresponds to amino acids 1 - 45 of HSMUC 1A_PEA_1_P63, 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 EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK corresponding to amino acids 46 - 85 of HSMUCl A_PEA_1_P63, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSMUC1AJPEA_1_P63 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 EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK in HSMUC1A_PEA_1_P63.
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P2 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 SRRNYGKWKLDGMFLLRRYVCIFTEKLKNQAELYVFLS corresponding to amino acids 1 - 38 of S42303_PEA_l_P2, and a second amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a head of S42303_PEA_l_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 SRRNYGKWKLDGMFLLRRYVCIFTEKLKNQAELYVFLS of S42303_PEA_l_P2.
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P3, 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 MCNTQRM corresponding to amino acids 1 - 7 of S42303_PEA_l_P3, and a second amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P4 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P5 comprising a first amino acid sequence being at least 90 % homologous to MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEGQPLLNVK
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P6 comprising a first amino acid sequence being at least 90 % homologous to MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEGQPLLNVK FSNCNGKRKVQYESSEPADFKVDEDGMVYAVRSFPLSSEHAKFLIYAQDKETQEKWQ VAVKLSLKPTLTEESVKESAEVEE ⁇ WPRQFSKHSGHLQRQKRDWVPP ⁇ NLPENSRGPFP QELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDREQIARFHLRAH AVDMGNQVENPIDIVINVROMNDNI ⁇ EFLHQV ⁇ GTVPEGSKPGTYVMTVTAIDADDP NALNGMLRYRIVSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQYTL
  • an isolated chimeric polypeptide encoding for S42303_PEA_l_P7 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of S42303_PEA_l_P7 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 VRFQPADN in S42303_PEA_l_P7.
  • an isolated chimeric polypeptide encoding for T87O96_PEA_1_P11 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T87096_PEA_l_Pll 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 VSAGGWGWGWGWQGEPQGHHYHPDTAVTPLST in T87O96_PEA_1_P11.
  • an isolated chimeric polypeptide encoding for T87096_PEA_l_P27 comprising a first amino acid sequence being at least 90 % homologous to MQPSSLLPLALCLLAAPASALVRIPLHKPTSIRRTMSEVGGSVEDLIAKGPVSKYSQAVP AVTEGPIPEVLKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIH HKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLSQDTVSVPCQSASSASALGGVKVERQVF GEATKQPGITFIAAKFDGILGMAYPRISVNNVLPVFDNLMQQKLVDQNIFSFYLSRDPD AQPGGELMLGGTDSKYYKGSLSYLNVTRKAYWQVHLDQV corresponding to amino acids 1 - 277 of CATD_HUMAN, which also corresponds to amino acids 1 - 277 of T8
  • an isolated polypeptide encoding for a tail of T87096_PEA_l_P27 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 WAAVG in T87096_PEA_l_P27.
  • an isolated chimeric polypeptide encoding for T87096_PEA_l_P39 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of T87096_PEA_l_P39 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 CESRTLAPSPRSCPSGMSLQGCLRNHLGNAILLPLGPVSQASPPPCSSH in T87096_PEA_l_P39.
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_P3, comprising a first amino acid sequence being at least 90 % homologous to MNIKGSPWKGSLLLLLVSNLLLCQSVAPLPICPGGAARCQVTLRDLFDRAWLSHYIHN LSSEMFSEFDKRYTHGRGFITKAINSCHTSSLATPEDKEQAQQMN corresponding to amino acids 1 - 104 of PRL_HUMAN, which also corresponds to amino acids 1 - 104 of HSPRO204_PEA_l_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 KTF corresponding to amino acids 105 - 107 of HSPRO204_PEA_l_P3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_P4 comprising a first amino acid sequence being at least 90 % homologous to MNIKGSPWKGSLLLLLVSNLLLCQSVAPLPICPGGAARCQVTLRDLFDRAVVLSHYIHN LSSEMFSEFDKRYTHGRGFITKAINSCHTSSLATPEDKEQAQQMNQKDFLSLIVSILRSW NEPLYHLVTEVRGMQEAPEAILSKAVEIEEQTKRLLEGMELIVSQ corresponding to amino acids 1 - 164 of PRL_HUMAN, which also corresponds to amino acids 1 - 164 of HSPRO204JPEA_l_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 LERTRTYKY corresponding to amino acids 165
  • an isolated polypeptide encoding for a tail of HSPRO204_PEA_l_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 LERTRTYKY in HSPRO204_PEA_l_P4.
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_P5 comprising a first amino acid sequence being at least 90 % homologous to Sl
  • an isolated polypeptide encoding for a tail of HSPRO204_PEA_lJP5 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 SLFFCVMRFILKPKKMRSTLSGRDFHPCRWLMKSLAFLLIITCSTAYAGIHIKST ⁇ SSS in HSPRO204_PEA_l_P5.
  • an isolated polypeptide encoding for a tail of HSPRO204_PEA_l_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 SSLLVLLCFSH in HSPRO204JPEA_l_P6.
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_Pll comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_P12 comprising a first amino acid sequence being at least 90 % homologous to MNKGSPWKGSLLLLLVSNLLLCQSVAPLPICPGGAARCQVTLRDLFDRAWLSHYIHN LSSEMFSEFDKRYTHGRGFITKAINSCHTSSLATPEDKEQAQQMN corresponding to amino acids 1 - 104 of PRL_HUMAN, which also corresponds to amino acids 1 - 104 of HSPRO204_PEA_l_P12 5 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 AKRTDCSASSMGQAW corresponding to amino acids 105 - 120 of HSPRO204_PEA_l_P12, wherein said first amino acid sequence and second amino acid sequence are
  • an isolated polypeptide encoding for a tail of HSPRO204_PEA_l_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 AKRTDCSASSMGQAW in HSPRO204JPEA_l_P12.
  • an isolated chimeric polypeptide encoding for HSPRO204_PEA_l_P21 comprising a first amino acid sequence being at least 90 % homologous to
  • LPHFFPCHPRRQGASPTDESKRLSEPDSQHIAILE corresponding to amino acids 41 - 75 of HSPRO204_PEA_l_P21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSPRO204_PEA_l_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 LPHFFPCHPRRQGASPTDESKRLSEPDSQHIAILE in HSPRO204_PEA_l_P21.
  • an isolated chimeric polypeptide encoding for S69686_P2 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 MLRLPYPLTWRQRPKQLEALCVGAATGPRA corresponding to amino acids 1 - 30 of S69686JP2, and a second amino acid sequence being at least 90 % homologous to MWLCPLALNLILMAASGAVCEVKDVCVGSPGIPGTPGSHGLPGRDGRDGLKGDPGPPG PMGPPGEMPCPPGNDGLPGAPGIPGECGEKGEPGERGPPGLPAHLDEELQATLHDFRHQ ILQTRGALSLQGSMTVGEKWSSNGQSITFDAIQEACARAGGRIAVPRNPEENEAIASFV KKYNTYAYVGLTEGPSPGDFRYSDGTPVNYTNWYRGEPA
  • an isolated polypeptide encoding for a head of S69686_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 MLRLPYPLTWRQRPKQLEALCVGAATGPRA of S69686_P2.
  • an isolated chimeric polypeptide encoding for S69686_P6, 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 MLRLPYPLTWRQRPKQLEALCVATGPRA corresponding to amino acids 1 - 28 of S69686_P6, and a second amino acid sequence being at least 90 % homologous to MWLCPLALNLILMAASGA VCEVKDVCVGSPGIPGTPGSHGLPGRDGRDGLKGDPGPPG PMGPPGEMPCPPGNDGLPGAPGPGECGEKGEPGERGPPGLPAHLDEELQATLHDFRHQ ILQTRGALSLQGSIMTVGEKVFSSNGQSITFDAIQEACARAGGRIAVPRNPEENEAIASFV KKYNTYAYVGLTEGPSPGDFRYSDGTPVNYTNWYRGEPA
  • an isolated polypeptide encoding for a head of S69686JP6, 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 MLRLPYPLTWRQRPKQLEALCVATGPRA of S69686_P6.
  • an isolated chimeric polypeptide encoding for S69686JP7 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 MLRLPYPLTWRQRPKQLEALCVGAATGPRA corresponding to amino acids 1 - 30 of S69686_P7, a second amino acid sequence being at least 90 % homologous to MWLCPLALNLILMAASGAVCEVKDVCVGSPGIPGTPGSHGLPGRDGRDGLKGDPGPPG PMGPPGEMPCPPGNDGLPGAPGIPGECGEKGEPGERGPP corresponding to amino acids 1 - 97 of PSPA_HUMAN_V1, which also corresponds to amino acids 31 - 127 of S69686_P7, and a third amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a head of S69686_P7 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 MLRLPYPLTWRQRPKQLEALCVGAATGPRA of S69686_P7.
  • an isolated chimeric polypeptide encoding for an edge portion of S69686_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 PA, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for S69686JP13 comprising a first amino acid sequence being at least 90 % homologous to MWLCPLALNLILMAASGAVCEVKDVCVGSP corresponding to amino acids 1 - 30 ofPSPA_HUMAN_Vl, which also corresponds to amino acids 1 - 30 of S69686_P13, and a second amino acid sequence being at least 90 % homologous to GRGKEQCVEMYTDGQWNDRNCLYSRLTICEF corresponding to amino acids 218 - 248 of PSPAJEUMANJVl, which also corresponds to amino acids 31 - 61 of S69686_P13, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of S69686_P13 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 PG, having a structure as follows: a sequence starting from any of amino acid numbers 30-x to 30; and ending at any of amino acid numbers 31+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HUMTCXAAA_PEA_1_P6 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 MRNQAPGRPKGATFPPRRPTGSRAPPLAPELRAKQRPGERV corresponding to amino acids 1 - 41 of HUMTCXAAAJPEA_1JP6, a second amino acid sequence being at least 90 % homologous to MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQ PRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSAL SNSIMYFSHFVPVFLP corresponding to amino acids 1 - 134 of CD8A_HUMAN, which also corresponds to amino acids 42 -
  • an isolated polypeptide encoding for a head of HUMTCXAAA_PEA_1_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 MRNQAPGRPKGATFPPRRPTGSRAPPLAPELRAKQRPGERV of HUMTCXAAA_PEA_1_P6.
  • an isolated chimeric polypeptide encoding for HUMTCXAAA_PEA_1_P12 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for an edge portion of HUMTCXAAA_PEA_1_P12 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 AGN having a structure as follows (numbering according to HUMTCXAAA_PEA_1_P12): a sequence starting from any of amino acid numbers 171-x to l71; and ending at any of amino acid numbers 173 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HUMTCXAAA_PEA_1_P13 comprising a first amino acid sequence
  • HUMTCXAAA_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 SKSRGIAAGRSRPRSCPWLC corresponding to amino acids 209 - 228 of HUMTCXAAA_PEA_1_P13, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HUMTCXAAA_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 SKSRGIAAGRSRPRSCPWLC in HUMTCXAAA_PEA_1_P13.
  • an isolated chimeric polypeptide encoding for HUMTCXAAA_PEA_1_P14 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for an edge portion of HUMTCXAAA_PEA_1_P14 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 HF, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HUMTCXAAAJPEA_1_P15 comprising a first amino acid sequence being at least 90 % homologous to MALPVTALLLPLALLLHAAI ⁇ SQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQ PRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSAL SNSIMYFSHFVPVFLP corresponding to amino acids 1 - 134 of CD8A_HUMAN, which also corresponds to amino acids 1 - 134 of HUMTCXAAA_PEA_1_P15, a second amino acid sequence bridging amino acid sequence comprising of G, and a third amino acid sequence being at least 90 % homologous to NRRRVCKCPRPWKSGDKPSLSARYV corresponding to amino acids 210 - 235 of CD8A_HUMAN, which also corresponds to amino acids
  • an isolated polypeptide encoding for an edge portion of HUMTCXAAA_PEA_1_P15 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 PGN having a structure as follows (numbering according to HUMTCXAAA_PEA_1_P15): a sequence starting from any of amino acid numbers 134-x to 134; and ending at any of amino acid numbers 136 + ((n-2) - x), in which x varies from 0 to n-2.
  • HSPPI_PEA_1_P6 wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for HSPPI_PEA_1_P9 comprising a first amino acid sequence being at least 90 % homologous to MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRRE AEDLQ corresponding to amino acids 1 - 62 of INS_HUMAN, which also corresponds to amino acids 1 - 62 of HSPPI_PEA_1_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 GEPTAHCCPWPPPAITCSWRSHPAWAEGGRRLPPSRGSGALF corresponding to amino acids 63 - 104 of HSPPI_PEA_1_P9, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of HSPPIJPEA_1_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 GEPTAHCCPWPPPATPCSWRSHPAWAEGGRRLPPSRGSGALF in HSPPI_PEA_1_P9.
  • an isolated chimeric polypeptide encoding for HSPPI_PEA_l_P10 comprising a first amino acid sequence being at least 90 % homologous to MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRRE AEDLQ corresponding to amino acids 1 - 62 of INS_HUMAN, which also corresponds to amino acids 1 - 62 of HSPPI_PEA_lJP10, 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 GGAGRGPWCRQPAALGPGGVPAEAWHCGTMLYQHLLPLPAGELLQLDAARRQPHTR RLLHRERWNKALEPA corresponding to amino acids 63 - 133 of HSPPI_PEA_lJP10, wherein said first amino acid sequence being at least 90 % homologous to MAL
  • an isolated polypeptide encoding for a tail of HSPPI_PEA_l_P10 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 GGAGRGPWCRQPAALGPGGWAEAWHCGTMLYQHLLPLPAGELLQLDAARRQPHTR RLLHRERWNKALEPA in HSPPI_PEA_l_P10.
  • an isolated chimeric polypeptide encoding for HSPPI_PEA_1_P12 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSPPI_PEA_1_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 AGELLQLDAARRQPHTRRLLHRERWNKALEPA in HSPPI_PEA_1JP12.
  • an isolated chimeric polypeptide encoding for HSPPIJPEA_1_P14 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSPPI_PEA_1_P14 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 AGELLQLDAAIUtQPHTRRLLHRERWNKALEPALLCRLCVLGALGQAPLPGTVVSPSQL SPRSLGAHRCQRRPGPACSGSPQSGHACRLPAAPTLWLRVQYGSCGGL in HSPPI_PEA_1_P14.
  • an isolated chimeric polypeptide encoding for HSPPI_PEA_1_P15 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated polypeptide encoding for a tail of HSPPI_PEA_1_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 GGAGRGPWCRQPAALGPGGVPAEAWHCGTMLYQHLLPLPAGELLQLDAARRQPHTR RLLHRERWNKALEP ALLCRLCVLGALGQ APLPGTVVSPSQLSPRSLGAHRCQRRPGPA CSGSPQSGHACRLPAAPTLWLRVQYGSCGGL in HSPPI_PEA_1_P15.
  • an isolated chimeric polypeptide encoding for D11581_PEA_l_P10 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for D11581_PEA_1_P12 comprising a first amino acid sequence being at least 90 % homologous to MKWVESIFLIFLLNFTESRTLHRNEYGIASILDSYQCTAEISLADLATIFFAQFVQEATYK
  • D11581_PEA_1_P12 wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of D11581JPEA_1JP12 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 AS, having a structure as follows: a sequence starting from any of amino acid numbers 352-x to 352; and ending at any of amino acid numbers 353+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for D11581_PEA_1_P16 comprising a first amino acid sequence being at least 90 % homologous to MKWVESIFLIFLLNFTESRTLHRNEYGIASILDSYQCTAEISLADLATIFFAQFVQEATYK EVSKMVKDALTAIEKPTGDEQSSGCLENQ corresponding to amino acids 1 - 90 of
  • FETA_HUMAN which also corresponds to amino acids 1 - 90 of Dl 1581_PEA_1_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 NFAMRKKFWRSTDIQTAAAKVKREDITVFLHTKSPLQFlRSHFSKFQNLSQAVKHMKKT GRHS corresponding to amino acids 91 - 152 of D11581_PEA_1_P16, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of Dl 1581JPEA_1_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 NFAMMOKFWRSTDIQTAAAKVKREDITVFLHTKSPLQHRSHFSKFQNLSQAVKHMKKT GRHS in D11581_PEA_1_P16.
  • an isolated chimeric polypeptide encoding for Z25227_P10 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for T87719_P2 comprising a first amino acid sequence being at least 90 % homologous to MRCALALSALLLLLSTPPLLPS corresponding to amino acids 1 - 22 of PODX_HUMAN_V1, which also corresponds to amino acids 1 - 22 of T87719_P2, a second amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for an edge portion of T87719_P2 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 SS, having a structure as follows: a sequence starting from any of amino acid numbers 22-x to 23; and ending at any of amino acid numbers 23+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated polypeptide encoding for a tail of T87719_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 VTPAGVGQVGEPRLG in T87719_P2.
  • an isolated chimeric polypeptide encoding for T87719_P8 comprising a first amino acid sequence being at least 90 % homologous to MRCALALSALLLLLSTPPLLPS corresponding to amino acids 1 - 22 of PODX_HUMAN, which also corresponds to amino acids 1 - 22 of T87719_P8, a second amino acid sequence being at least 90 % homologous to SPSPSPSPSQNATQTTTDSSNKTAPTPASSVTIMATDTAQQSTVPTSKANEILASVKATTL GVSSDSPGTTTLAQQVSGPVNTTVARGGGSGNPTTTIESPKSTKSADTTTVATSTATAKP NTTSSQNGAEDTTNSGGKSSHSVTTDLTSTKAE corresponding to amino acids 25 - 178 of PODX_HUMAN, which also corresponds to amino acids 23 - 176 of T87719JP8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%
  • an isolated chimeric polypeptide encoding for an edge portion of T87719_P8, 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 SS, having a structure as follows: a sequence starting from any of amino acid numbers 22-x to 23; and ending at any of amino acid numbers 23+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated polypeptide encoding for a tail of T87719_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 RARVKL in T87719_P8.
  • an isolated chimeric polypeptide encoding for HSTIR_PEA_1_P6 comprising a first amino acid sequence being at least 90 % homologous to
  • an isolated chimeric polypeptide encoding for HSCDIA_PEA_1_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 LQWGRKNLGAMFAF corresponding to amino acids 1 - 14 of HSCDIA_PEA_1_P5, a bridging amino acid T corresponding to amino acid 18 of HSCDIA_PEA_1_P5, and a second amino acid sequence being at least 90 % homologous to GLKEPLSFHVTWIASFYNHSWKQNLVSGWLSDLQTHTWDSNSSTTVFLWPWSRGNFSN EEWKELETLFRIRTIRSFEGIKRYAHELQFEYPFEIQVTGGCELHSGKVSGSFLQLAYQGS DFVSFQNNSWLPYPVAGNMAKHFCKVLNQNQ
  • an isolated polypeptide encoding for a head of HSCDIA_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 LQWGRKNLGAMFAF of HSCDIA_PEA_1_P5.
  • an isolated chimeric polypeptide encoding for HSCDIA_PEA_1_P6 comprising a first amino acid sequence being at least 90 % homologous to MLFLLLPLLAVLPGDGNADGLKEPLSFHVTWIASFYNHSWKQNLVSGWLSDLQTHTW DSNSST ⁇ VFLWPWSRGNFSNEEWKELETLFRIRTIRSFEGIRRYAHELQFEYPFEIQVTGG CELHSGKVSGSFLQLAYQGSDFVSFQNNSWLPYPVAGNMAKHFCKVLNQNQHENDIT HNLLSDTCPRFILGLLDAGKAHLQRQVKPEAWLSHGPSPGPGHLQLVCHVSGFYPKPV WVMWMRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEGQD ⁇ VLYWEHHSSVGF ⁇ LAV ⁇ VPLLLLIGLALWFRKR corresponding to amino acids 1
  • an isolated chimeric polypeptide encoding for HSCDIA_PEA_1_P7 comprising a first amino acid sequence being at least 90 % homologous to MLFLLLPLLAVLPGDGNADGLKEPLSFHVTWIASFYNHSWKQNLVS GWLSDLQTHTW
  • an isolated polypeptide encoding for a tail of HSCDIA_PEA_1_P7 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 GEKKLRPRLEMPGSGPQA in HSCDIA_PEA_1JP7.
  • an isolated chimeric polypeptide encoding for HSCDIA_PEA_1_P8 comprising a first amino acid sequence being at least 90 % homologous to MLFLLLPLLAVLPGDGNADGLKEPLSFHVTWIASFYNHSWKQNLVSGWLSDLQTHTW DSNSSTIWLWPWSRGNFSNEEWKELETLFRIRTIRSFEGIRRYAHELQFEYPFEIQVTGG CELHSGKVSGSFLQLAYQGSDFVSFQNNSWLPYPVAGNMAKHFCKVLNQNQHENDIT HNLLSDTCPRFILGLLDAGKAHLQRQVKPEAWLSHGPSPGPGHLQLVCHVSGFYPKPV WVMWMRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEGQD IVLYW corresponding to amino acids 1 - 294 of CDl A_HUM AN_V1, which also corresponds to amino acids
  • an isolated chimeric polypeptide encoding for HSCDIAJPEA_1_P9 comprising a first amino acid sequence being at least 90 % homologous to MLFLLLPLLA VLPGDGNAD corresponding to amino acids 1 - 19 of CD1A_HUMAN, which also corresponds to amino acids 1 - 19 of
  • HSCDIA_PEA_1_P9 and a second amino acid sequence being at least 90 % homologous to GWLSDLQTHTWDSNSSTIVFLWPWSRGNFSNEEWKELETLFRIRTIRSFEGIRRYAHELQ FEYPFEIQVTGGCELHSGKVSGSFLQLAYQGSDFVSFQNNSWLPYPVAGNMAKHFCKV LNQNQHENDITHNLLSDTCPRFILGLLDAGKAHLQRQVKPEAWLSHGPSPGPGHLQLV CHVSGFYPKPVWVMWMRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSC RVKHSSLEGQDIVLYWEHHSSVGFIILAVIVPLLLLIGLALWFRKRCFC corresponding to amino acids 47 - 327 of CD1A_HUMAN, which also corresponds to amino acids 20 - 300 of HSCDIA_PEA_1_P9, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a
  • an isolated chimeric polypeptide encoding for an edge portion of HSCDIA_PEA_1_P9 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 DG, having a structure as follows: a sequence starting from any of amino acid numbers 19-x to 19; and ending at any of amino acid numbers 20+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for HSCDIA_PEA_1_P11 comprising a first amino acid sequence being at least 90 % homologous to
  • WVMWMR corresponding to amino acids 1 - 239 of CD1A_HUMAN_V1, which also corresponds to amino acids 1 - 239 of HSCDIA_PEA_1_P11
  • a second amino acid sequence being at least 90 % homologous to EHHSSVGFIILAVIVPLLLLIGLALWFRKRCFC corresponding to amino acids 295 - 327 of CD1A_HUMAN_V1, which also corresponds to amino acids 240 - 272 of HSCDIA_PEA_1_P11, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of HSCDIA_PEA_1JP11 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 RE, having a structure as follows: a sequence starting from any of amino acid numbers 239-x to 239; and ending at any of amino acid numbers 240+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • HUMEDF . .PEA. .2. .TI l a nucleic acid sequence comprising a sequence in the table below:
  • HUMEDF_PEA_2_node_20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:
  • nucleic acid sequence comprising a sequence in the table below:
  • an isolated polypeptide comprising an amino acid sequence in the table below:
  • an isolated chimeric polypeptide encoding for HUMINHA_PEA_1_P5 comprising a first amino acid sequence being at least 90 % homologous to MVLHLLLFLLLTPQGGHSCQGLELARELVLAKVRALFLDALGPPAVTREGGDPGVRRL PRRHALGGFTHRGSEPEEEEDVSQAILFPAT corresponding to amino acids 1 - 89 of IHA_HUMAN, which also corresponds to amino acids 1 - 89 of HXJMINHA_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

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Abstract

La présente invention a trait à de nouveaux variants d'épissage, des séquences d'acides aminés de ceux-ci, et leurs procédés d'utilisation.
PCT/IB2005/002407 2004-01-27 2005-01-27 Nouvelles sequences de nucleotides et d'acides amines, et leurs dosages et procedes d'utilisation pour le diagnostic Ceased WO2005107364A2 (fr)

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