Identification of tumour-associated cell surface antigens for diagnosis and therapy

Abstract

The present invention provides agents with tumor-inhibiting activity, and which are selective for cells expressing or abnormally expressing a tumor-associated antigen. Said tumor-associated antigen has a nucleotide sequence selected from the group consisting of: (a) a nucleotide sequence selected from the specific sequences set forth herein, or a 6-50 contiguous nucleotide residue portion thereof; (b) a nucleotide sequence of a nucleic acid which hybridizes with a nucleic acid having the nucleotide sequence of (a) under stringent conditions; (c) a nucleotide sequence which is degenerate with respect to the nucleotide sequence of (a) or (b); and (d) a nucleotide sequence which is complementary to the nucleotide sequence of (a), (b) or (c). Pharmaceutical compositions and kits comprising the agents are also provided, as well as methods treating, diagnosing or monitoring a disease characterized by expression or abnormal expression of the tumor-associated antigen.

1 . (canceled) 
     
     
         2 . A pharmaceutical composition, comprising an agent with tumor-inhibiting activity, which is selective for cells expressing or abnormally expressing a tumor-associated antigen, said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of:
 (a) a nucleic acid which comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOS.: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 269, 271, 273, 275, 277, 279, 309 of the sequence listing, a part or derivative thereof,   (b) a nucleic acid which hybridizes with the nucleic acid of (a) under stringent conditions,   (c) a nucleic acid which is degenerate with respect to the nucleic acid of (a) or (b), and   (d) a nucleic acid which is complementary to the nucleic acid of (a), (b) or (c).   
     
     
         3 . The pharmaceutical composition as claimed in  claim 2 , in which the agent causes induction of cell death, reduction in cell growth, damage to the cell membrane or secretion of cytokines 
     
     
         4 . The pharmaceutical composition as claimed in  claim 2 , in which the agent is an antisense nucleic acid which hybridizes selectively with the nucleic acid coding for the tumor-associated antigen. 
     
     
         5 . The pharmaceutical composition as claimed in  claim 2 , in which the agent is an antibody which binds selectively to the tumor-associated antigen. 
     
     
         6 . The pharmaceutical composition as claimed in  claim 2 , in which the agent is a complement-activating antibody which binds selectively to the tumor-associated antigen. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . A pharmaceutical composition, comprising one or more components selected from the group consisting of:
 (i) a tumor-associated antigen or a part thereof,   (ii) a nucleic acid which codes for a tumor-associated antigen or a part thereof,   (iii) an antibody which binds to a tumor-associated antigen or a part thereof,   (iv) an antisense nucleic acid which hybridizes specifically with a nucleic acid coding for a tumor-associated antigen,   (v) a host cell which expresses a tumor-associated antigen or a part thereof, and   (vi) isolated complexes between a tumor-associated antigen or a part thereof and an HLA molecule,   said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of:   (a) a nucleic acid which comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 269, 271, 273, 275, 277, 279, 309 of the sequence listing, a part or derivative thereof,   (b) a nucleic acid which hybridizes with the nucleic acid of (a) under stringent conditions,   (c) a nucleic acid which is degenerate with respect to the nucleic acid of (a) or (b), and   (d) a nucleic acid which is complementary to the nucleic acid of (a), (b) or (c).   
     
     
         11 - 19 . (canceled) 
     
     
         20 . The pharmaceutical composition as claimed in  claim 10 , in which the antibody is a monoclonal antibody. 
     
     
         21 . The pharmaceutical composition as claimed in  claim 10 , in which the antibody is a chimeric or humanized antibody. 
     
     
         22 . The pharmaceutical composition as claimed in  claim 10 , in which the antibody is a fragment of a natural antibody. 
     
     
         23 . The pharmaceutical composition as claimed in  claim 10 , in which the antibody is coupled to a therapeutic or diagnostic agent. 
     
     
         24 . The pharmaceutical composition as claimed in  claim 10 , in which the antisense nucleic acid comprises a sequence of 6-50 contiguous nucleotides of the nucleic acid coding for the tumor-associated antigen. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The pharmaceutical composition as claimed in  claim 10 , further comprising a pharmaceutically acceptable carrier and/or an adjuvant. 
     
     
         28 - 56 . (canceled) 
     
     
         57 . A method of treating, diagnosing or monitoring a disease characterized by expression or abnormal expression of a tumor-associated antigen, which method comprises administering an antibody binding to said tumor-associated antigen or to a part thereof and coupled to a therapeutic or diagnostic agent, said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of:
 (a) a nucleic acid which comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 269, 271, 273, 275, 277, 279, 309 of the sequence listing, a part or derivative thereof,   (b) a nucleic acid which hybridizes with the nucleic acid of (a) under stringent conditions,   (c) a nucleic acid which is degenerate with respect to the nucleic acid of (a) or (b), and   (d) a nucleic acid which is complementary to the nucleic acid of (a), (b) or (c).   
     
     
         58 . The method as claimed in  claim 57 , in which the antibody is a monoclonal antibody. 
     
     
         59 . The method as claimed in  claim 57 , in which the antibody is a chimeric or humanized antibody. 
     
     
         60 . The method as claimed in  claim 57 , in which the antibody is a fragment of a natural antibody. 
     
     
         61 - 73 . (canceled) 
     
     
         74 . A nucleic acid, which codes for a protein or polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS.: 2,6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 270, 272, 274, 276, 278, 280 to 308, 310 of the sequence listing, a part or derivative thereof. 
     
     
         75 - 82 . (canceled) 
     
     
         83 . A protein or polypeptide, which comprises an amino acid sequence selected from the group consisting of SEQ ID NOS.: 2,6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 270, 272, 274, 276, 278, 280 to 308, 310 of the sequence listing, a part or derivative thereof. 
     
     
         84 - 94 . (canceled) 
     
     
         95 . A kit for detecting expression or abnormal expression of a tumor-associated antigen, which kit comprises agents for detection
 (I) of the nucleic acid which codes for the tumor-associated antigen or of a part thereof,   (ii) of the tumor-associated antigen or of a part thereof,   (iii) of antibodies which bind to the tumor-associated antigen or to a part thereof, and/or   (iv) of T cells which are specific for a complex between the tumor-associated antigen or a part thereof and an MHC molecule, said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of:   (a) a nucleic acid which comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOS.: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 269, 271, 273, 275, 277, 279, 309 of the sequence listing, a part or derivative thereof,   (b) a nucleic acid which hybridizes with the nucleic acid of (a) under stringent conditions,   (c) a nucleic acid which is degenerate with respect to the nucleic acid of (a) or (b), and   (d) a nucleic acid which is complementary to the nucleic acid of (a), (b) or (c).   
     
     
         96 . The kit as claimed in  claim 95 , in which the agents for detection of the nucleic acid which codes for the tumor-associated antigen or of a part thereof are nucleic acid molecules for selective amplification of said nucleic acid. 
     
     
         97 - 114 . (canceled)