US2004033509A1PendingUtilityA1

Novel 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 and 32252 molecules and uses therefor

Assignee: MILLENNIUM PHARM INCPriority: Jul 18, 2000Filed: Feb 28, 2003Published: Feb 19, 2004
Est. expiryJul 18, 2020(expired)· nominal 20-yr term from priority
A61K 48/00A01K 2217/05C12N 9/1205C07K 2319/00
57
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Claims

Abstract

The invention provides isolated nucleic acids molecules, designated 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 and 32252 nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 and 32252 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 gene has been introduced or disrupted. The invention still further provides isolated 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 proteins, fusion proteins, antigenic peptides and anti-13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . An isolated 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    b) a nucleic acid molecule comprising a fragment of at least 15 nucleotides of the nucleotide sequence of SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or a complement thereof, under stringent conditions;    f) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425; and    g) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425.    
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , which is the nucleotide sequence SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151.  
     
     
         3 . A host cell which contains the nucleic acid molecule of  claim 1 .  
     
     
         4 . An isolated 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 polypeptide selected from the group consisting of: 
 a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, or a complement thereof;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153, or a complement thereof under stringent conditions;    c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152; and    d) the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152.    
     
     
         5 . An antibody which selectively binds to a polypeptide of  claim 4 .  
     
     
         6 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425;    c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number PTA-3436, PTA-2339, PTA-1774, PTA-1681 or PTA-3425, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO: 1, 3, 4, 6, 7, 9, 10, 12, 39, 41, 54, 56, 58, 59, 61, 63, 65, 66, 68, 75, 77, 79, 81, 82, 84, 89, 91, 92, 94, 95, 97, 107, 109, 112, 114, 117, 119, 120, 122, 127, 129, 139, 141, 151 or 153; and    d) the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152;    comprising culturing the host cell of  claim 3  under conditions in which the nucleic acid molecule is expressed.    
     
     
         7 . A method for detecting the presence of a nucleic acid molecule of  claim 1  or a polypeptide encoded by the nucleic acid molecule in a sample, comprising: 
 a) contacting the sample with a compound which selectively hybridizes to the nucleic acid molecule of  claim 1  or binds to the polypeptide encoded by the nucleic acid molecule; and  
 b) determining whether the compound hybridizes to the nucleic acid or binds to the polypeptide in the sample.  
 
     
     
         8 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  or binds to a polypeptide encoded by the nucleic acid molecule and instructions for use.  
     
     
         9 . A method for identifying a compound which binds to a polypeptide or modulates the activity of the polypeptide of  claim 4  comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 4  with a test compound; and  
 b) determining whether the polypeptide binds to the test compound or determining the effect of the test compound on the activity of the polypeptide.  
 
     
     
         10 . A method for modulating the activity of a polypeptide of  claim 4  comprising contacting the polypeptide or a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         11 . A method for identifying a compound capable of treating cancer or a cellular proliferation and/or differentiation disorder, comprising assaying the ability of the compound to modulate 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 nucleic acid expression or 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 polypeptide activity, thereby identifying a compound capable of treating cancer or a cellular proliferation and/or differentiation disorder.  
     
     
         12 . A method of identifying a nucleic acid molecule associated with cancer or a cellular proliferation and/or differentiation disorder comprising: 
 a) contacting a sample from a subject with or at risk of developing cancer or a cellular proliferation and/or differentiation disorder, comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151 defined in  claim 2;  and    b) detecting the presence of a nucleic acid molecule in the sample that hybridizes to the probe, thereby identifying a nucleic acid molecule associated with cancer or a cellular proliferation and/or differentiation disorder.    
     
     
         13 . A method of identifying a polypeptide associated with cancer or a cellular proliferation and/or differentiation disorder, comprising: 
 a) contacting a sample comprising polypeptides with a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 polypeptide defined in  claim 4;  and    b) detecting the presence of a polypeptide in the sample that binds to the 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 binding partner, thereby identifying the polypeptide associated with cancer or a cellular proliferation and/or differentiation disorder.    
     
     
         14 . A method of identifying a subject having cancer or a cellular proliferation and/or differentiation disorder, or at risk for developing cancer or a cellular proliferation and/or differentiation disorder, comprising: 
 a) contacting a sample obtained from the subject comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151 defined in  claim 2;  and    b) detecting the presence of a nucleic acid molecule in the sample that hybridizes to the probe, thereby identifying a subject having cancer or a cellular proliferation and/or differentiation disorder, or at risk for developing a cancer or a cellular proliferation and/or differentiation disorder.    
     
     
         15 . A method for treating a subject having cancer or a cellular proliferation and/or differentiation disorder, or at risk of developing cancer or a cellular proliferation and/or differentiation disorder, comprising administering to the subject a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 modulator of the nucleic acid molecule defined in  claim 1  or the polypeptide encoded by the nucleic acid molecule or contacting a cell with a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 modulator.  
     
     
         16 . The method defined in  claim 18  wherein said cancer or cellular proliferation and/or differentiation disorder is breast, lung, colon, ovarian or liver cancer or cellular proliferation and/or differentiation disorder.  
     
     
         17 . The method of  claim 18 , wherein the 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 modulator is 
 a) a small molecule;    b) peptide;    c) phosphopeptide;    d) anti-13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 antibody;    e) a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, or a fragment thereof;    f) a 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 polypeptide comprising an amino acid sequence which is at least 90 percent identical to the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, wherein the percent identity is calculated using the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4; or    g) an isolated naturally occurring allelic variant of a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151 at 6×SSC at 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 65° C.    
     
     
         18 . The method of  claim 18 , wherein the 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 modulator is 
 a) an antisense 13237, 18480, 2245, 16228, 7677, 26320, 46619, 33166, 16836, 46867, 21617, 55562, 39228, 62088, 46745, 23155, 21657, 42755, 32229, 22325, 46863 or 32252 nucleic acid molecule;    b) is a ribozyme;    c) the nucleotide sequence of SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151 or a fragment thereof;    d) a nucleic acid molecule encoding a polypeptide comprising an amino acid sequence which is at least 90 percent identical to the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, wherein the percent identity is calculated using the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4;    e) a nucleic acid molecule encoding a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 8, 11, 40, 55, 57, 60, 64, 67, 76, 80, 83, 90, 93, 96, 108, 113, 118, 121, 128, 140 or 152, wherein the nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO: 1, 4, 7, 10, 39, 54, 59, 63, 66, 75, 79, 82, 89, 92, 95, 107, 112, 117, 120, 127, 139 or 151 at 6×SSC at 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 65° C.; or    f) a gene therapy vector.

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