Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis

Abstract

Novel splice variants, amino acid sequences and nucleotide sequences thereof, and methods of using same.

1 - 134 . (canceled) 
     
     
         135 . An isolated polynucleotide comprising the polynucleotide sequence set forth in a member selected from the group consisting of SEQ ID NOs: 1-15, 61-64, 96-98, 114-126, 189-193, 211-214, 235, 244, 252-253, 305-306, 340-344, 458, 32-60, 71-95, 103-113, 139-188, 196-210, 220-234, 237-243, 246-251, 256-304, 309-339, 350-358, 502-530, 363, 414, 417, 420, 424, 427, 431, 434, 437, 444, 447, 452 and 455, or a sequence at least about 95% identical thereto. 
     
     
         136 . An isolated polypeptide comprising the polypeptide sequence set forth in a member selected from the group consisting of SEQ ID NOs: 16-31, 65-70, 99-102, 127-138, 194-195, 215-219, 236, 245, 254-255, 307-308, 345-349, 459-501, 576-591 and 592, or a sequence at least about 95% identical thereto. 
     
     
         137 . An expression vector comprising the polynucleotide sequence according to  claim 135 . 
     
     
         138 . A host cell comprising the vector of  claim 137 . 
     
     
         139 . A process for producing a polypeptide comprising:
 culturing the host cell according to  claim 138  under conditions suitable to produce the polypeptide encoded by said polynucleotide; and recovering said polypeptide.   
     
     
         140 . An isolated primer pair for amplifying the polynucleotide sequence of  claim 135 , comprising the pair of nucleic acid sequences selected from the group consisting of: SEQ NOs: 361-362, 415-416, 418-419, 421-422, 425-426, 428-429, 432-433, 435-436, 438-439, 445-446, 448-449, 453-454 and 456-457. 
     
     
         141 . An antibody to specifically bind to the polypeptide of  claim 136 . 
     
     
         142 . A kit for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammatory disease and cancer, the kit comprising at least one primer pair of  claim 140  for detecting the polynucleotide sequence set forth in a member selected from the group consisting of SEQ ID NOs:, 1-15, 61-64, 96-98, 114-126, 189-193, 211-214, 235, 244, 252-253, 305-306, 340-344, 458, 32-60, 71-95, 103-113, 139-188, 196-210, 220-234, 237-243, 246-251, 256-304, 309-339, 350-358, 502-530, 363, 414, 417, 420, 424, 427, 431, 434, 437, 444, 447, 452 and 455. 
     
     
         143 . A kit for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammatory disease and cancer, the kit comprising the antibody of  claim 141  for detecting the polypeptide sequence set forth in a member selected from the group consisting of SEQ ID NOs:, 16-31, 65-70, 99-102, 127-138, 194-195, 215-219, 236, 245, 254-255, 307-308, 345-349, 459-501, 576-591 and 592. 
     
     
         144 . The kit of  claim 143 , wherein said kit further comprises at least one immunoassay reagent. 
     
     
         145 . The kit of  claim 144 , wherein said immunoassay is selected from the group consisting of an enzyme linked immunosorbent assay (ELISA), an immunoprecipitation assay, an immunofluorescence analysis, an enzyme immunoassay (EIA), a radioimmunoassay (RIA), or a Western blot analysis. 
     
     
         146 . A method for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammatory disease and cancer, the method comprising detecting overexpression of the polynucleotide sequence set forth in a member selected from the group consisting of SEQ ID NOs: 1-15, 61-64, 96-98, 114-126, 189-193, 211-214, 235, 244, 252-253, 305-306, 340-344, 458, 32-60, 71-95, 103-113, 139-188, 196-210, 220-234, 237-243, 246-251, 256-304, 309-339, 350-358, 502-530, 363, 414, 417, 420, 424, 427, 431, 434, 437, 444, 447, 452, 455, or a sequence at least about 95% identical thereto in a sample from a patient. 
     
     
         147 . The method of  claim 146 , wherein said detecting overexpression comprises performing nucleic acid amplification. 
     
     
         148 . The method of  claim 146 , wherein the disease is cardiovascular disease, and is selected from the group consisting of myocardial infarct, acute coronary syndrome, coronary artery disease, angina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure or any type of heart failure, reinfarction, assessment of thrombolytic therapy, assessment of myocardial infarct size, differential diagnosis between heart-related versus lung-related conditions (such as pulmonary embolism), the differential diagnosis of Dyspnea, cardiac valves related conditions, vascular disease, cardiac death, from arrhythmia or any other heart related reason; rejection of a transplanted heart; conditions that lead to heart failure including myocardial infarction, angina, arrhythmias, valvular diseases, atrial and/or ventricular septal defects; conditions that cause atrial and or ventricular wall volume overload, including systemic arterial hypertension, pulmonary hypertension and pulmonary embolism; conditions which have similar clinical symptoms as heart failure and as states that cause atrial and or ventricular pressure-overload, where the differential diagnosis between these conditions to the latter is of clinical importance including breathing difficulty and/or hypoxia due to pulmonary disease, anemia or anxiety. 
     
     
         149 . The method of  claim 146 , wherein the disease is cerebrovascular disease, and is selected from the group consisting of any type of stroke or neural tissue injury, or any type of cerebrovascular accident, ischemic stroke, hemorrhagic stroke or transient ischemic attacks, thrombotic, embolic, lacunar or hypoperfusion types of strokes, brain trauma. 
     
     
         150 . The method of  claim 146 , wherein the disease is chronic inflammatory disease, and is selected from the group consisting of diseases where an inflammatory process plays a substantial role, such as hypercholesterolemia, diabetes, atherosclerosis, inflammation that involves blood vessels—whether acute or chronic including the coronary arteries and blood vessels of the brain, myocardial infarction, cerebral stroke, peripheral vascular disease, vasculitis, polyarteritis nodosa, ANCA associated small vessel vasculitis, Churg-Strauss syndrome, Henoch-Schonlein purpura, scleroderma, thromboangiitis obliterans, temporal arteritis, Takayasu's arteritis, hypersensitivity vasculitis, Kawasaki disease, Behçet syndrome, and their complications including coronary disease, angina pectoris, deep vein thrombosis, renal disease, diabetic nephropathy, lupus nephritis, renal artery thrombosis, renal artery stenosis, atheroembolic disease of the renal arteries, renal vein thrombosis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, arteriolar nephrosclerosis, preeclampsia, eclampsia, albuminuria, microalbuminuria, glomerulonephritis, renal failure, hypertension, uremia, cerebrovascular disease, peripheral vascular disease, intermittent claudication, abdominal angina; rheumatic/autoimmune diseases that involve systemic immune reaction including rheumatoid arthritis, scleroderma, mixed connective tissue disease, Sjogren syndrome, ankylosing spondylitis, spondyloarthropathy, psoriasis, psoriatic arthritis, myositis and systemic lupus erythematosus; acute and/or chronic infective processes that involve systemic immune reaction including pneumonia, bacteremia, sepsis, pyelonephritis, cellulitis, osteomyelitis, meningitis and viral hepatitis; malignant and idiopathic processes that involve systemic immune reaction and/or proliferation of immune cells including granulomatous disorders, Wegener's granulomatosis, lymphomatoid granulomatosis/polymorphic reticulosis, idiopathic midline granuloma, multiple myeloma, Waldenstrom's macroglobulinemia, Castleman's disease, amyloidosis, lymphoma, histiocytosis, renal cell carcinoma and paraneoplastic syndromes; conditions where CRP was shown to have a positive correlation with the presence of the condition including weight loss, anorexia-cachexia syndrome, extent of disease, recurrence in advanced cancer, diabetes (types 1 & 2), obesity, hypertension, preterm delivery; conditions which have similar symptoms, signs and complications as the conditions above and where the differential diagnosis between them and the conditions above is of clinical importance including other (non vascular) causes of heart disease, renal disease and cerebral disease; other (non rheumatic) causes of arthropathy and musculoskeletal pain; other causes of non-specific symptoms and signs such as fever of unknown origin, loss of appetite, weight loss, nonspecific pains, breathing difficulties, anxiety, or any combination thereof, or any disease disorder or condition associated with inflammation. 
     
     
         151 . The method of  claim 146 , wherein the disease is cancer, and is selected from the group consisting of colon cancer, breast cancer, ovarian cancer, prostate cancer, lung cancer, and wherein the cancer is invasive or metastatic. 
     
     
         152 . A method for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the polypeptide sequence set forth in a member selected from the group consisting of SEQ ID NOs:, 16-31, 65-70, 99-102, 127-138, 194-195, 215-219, 236, 245, 254-255, 307-308, 345-349, 459-501, 576-592 in a sample from a patient. 
     
     
         153 . The method of  claim 152 , wherein said detecting comprises detecting binding of the antibody of claim  7  to the polypeptide in said sample from said patient. 
     
     
         154 . The method of  claim 153 , wherein the disease is cardiovascular disease, and is selected from the group consisting of myocardial infarct, acute coronary syndrome, coronary artery disease, angina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure or any type of heart failure, reinfarction, assessment of thrombolytic therapy, assessment of myocardial infarct size, differential diagnosis between heart-related versus lung-related conditions (such as pulmonary embolism), the differential diagnosis of Dyspnea, cardiac valves related conditions, vascular disease, cardiac death, from arrhythmia or any other heart related reason; rejection of a transplanted heart; conditions that lead to heart failure including myocardial infarction, angina, arrhythmias, valvular diseases, atrial and/or ventricular septal defects; conditions that cause atrial and or ventricular wall volume overload, including systemic arterial hypertension, pulmonary hypertension and pulmonary embolism; conditions which have similar clinical symptoms as heart failure and as states that cause atrial and or ventricular pressure-overload, where the differential diagnosis between these conditions to the latter is of clinical importance including breathing difficulty and/or hypoxia due to pulmonary disease, anemia or anxiety. 
     
     
         155 . The method of  claim 153 , wherein the disease is cerebrovascular disease, and is selected from the group consisting of any type of stroke or neural tissue injury, or any type of cerebrovascular accident, ischemic stroke, hemorrhagic stroke or transient ischemic attacks, thrombotic, embolic, lacunar or hypoperfusion types of strokes, brain trauma. 
     
     
         156 . The method of  claim 153 , wherein the disease is chronic inflammation disease, and is selected from the group consisting of diseases where an inflammatory process plays a substantial role, such as hypercholesterolemia, diabetes, atherosclerosis, inflammation that involves blood vessels—whether acute or chronic including the coronary arteries and blood vessels of the brain, myocardial infarction, cerebral stroke, peripheral vascular disease, vasculitis, polyarteritis nodosa, ANCA associated small vessel vasculitis, Churg-Strauss syndrome, Henoch-Schonlein purpura, scleroderma, thromboangiitis obliterans, temporal arteritis, Takayasu's arteritis, hypersensitivity vasculitis, Kawasaki disease, Behçet syndrome, and their complications including coronary disease, angina pectoris, deep vein thrombosis, renal disease, diabetic nephropathy, lupus nephritis, renal artery thrombosis, renal artery stenosis, atheroembolic disease of the renal arteries, renal vein thrombosis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, arteriolar nephrosclerosis, preeclampsia, eclampsia, albuminuria, microalbuminuria, glomerulonephritis, renal failure, hypertension, uremia, cerebrovascular disease, peripheral vascular disease, intermittent claudication, abdominal angina; rheumatic/autoimmune diseases that involve systemic immune reaction including rheumatoid arthritis, scleroderma, mixed connective tissue disease, Sjogren syndrome, ankylosing spondylitis, spondyloarthropathy, psoriasis, psoriatic arthritis, myositis and systemic lupus erythematosus; acute and/or chronic infective processes that involve systemic immune reaction including pneumonia, bacteremia, sepsis, pyelonephritis, cellulitis, osteomyelitis, meningitis and viral hepatitis; malignant and idiopathic processes that involve systemic immune reaction and/or proliferation of immune cells including granulomatous disorders, Wegener's granulomatosis, lymphomatoid granulomatosis/polymorphic reticulosis, idiopathic midline granuloma, multiple myeloma, Waldenstrom's macroglobulinemia, Castleman's disease, amyloidosis, lymphoma, histiocytosis, renal cell carcinoma and paraneoplastic syndromes; conditions where CRP was shown to have a positive correlation with the presence of the condition including weight loss, anorexia-cachexia syndrome, extent of disease, recurrence in advanced cancer, diabetes (types 1 & 2), obesity, hypertension, preterm delivery; conditions which have similar symptoms, signs and complications as the conditions above and where the differential diagnosis between them and the conditions above is of clinical importance including other (non vascular) causes of heart disease, renal disease and cerebral disease; other (non rheumatic) causes of arthropathy and musculoskeletal pain; other causes of non-specific symptoms and signs such as fever of unknown origin, loss of appetite, weight loss, nonspecific pains, breathing difficulties, anxiety, or any combination thereof, or any disease disorder or condition associated with inflammation. 
     
     
         157 . The method of  claim 153 , wherein the disease is cancer, and is selected from the group consisting of colon cancer, breast cancer, ovarian cancer, prostate cancer, lung cancer, and wherein the cancer is invasive or metastatic. 
     
     
         158 . A biomarker for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the biomarker, comprising said polypeptide of  claim 136 , marked with a label. 
     
     
         159 . A method to screen for or to diagnose a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the disease with the biomarker of  claim 158 . 
     
     
         160 . A method for monitoring disease progression, treatment efficacy or relapse of a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the disease with the biomarker of  claim 158 . 
     
     
         161 . A method of selecting a therapy for a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method, comprising detecting the disease with the biomarker of  claim 158  and selecting a therapy according to said detection. 
     
     
         162 . A biomarker for detecting a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the biomarker, comprising the nucleotide acid sequence set forth in the member selected from the group consisting of SEQ ID NOs: 1-15, 61-64, 96-98, 114-126, 189-193, 211-214, 235, 244, 252-253, 305-306, 340-344, 458, 32-60, 71-95, 103-113, 139-188, 196-210, 220-234, 237-243, 246-251, 256-304, 309-339, 350-358, 502-530, 363, 414, 417, 420, 424, 427, 431, 434, 437, 444, 447, 452, 455, or a sequence at least about 95% identical thereto, marked with a label. 
     
     
         163 . A method to screen for or to diagnose a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the disease with the biomarker of  claim 162 . 
     
     
         164 . A method for monitoring disease progression, treatment efficacy or relapse of a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the disease with the biomarker of  claim 162 . 
     
     
         165 . A method of selecting a therapy for a disease selected from the group consisting of cardiovascular disease, cerebrovascular disease, chronic inflammation disease and cancer, the method comprising detecting the disease with the biomarker of  claim 162  and selecting a therapy according to said detection.