Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders
First Claim
1. A method for identifying a polypeptide antigen on the surface of a cell which may be used as a target for cancer therapy comprising identifying a polypeptide antigen which is more highly expressed on the surface of a proliferating cancer cell than on the surface of a proliferating non-cancer cell, thereby identifying said polypeptide antigen.
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Accused Products
Abstract
Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and/or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.
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Citations
36 Claims
- 1. A method for identifying a polypeptide antigen on the surface of a cell which may be used as a target for cancer therapy comprising identifying a polypeptide antigen which is more highly expressed on the surface of a proliferating cancer cell than on the surface of a proliferating non-cancer cell, thereby identifying said polypeptide antigen.
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10. A method for producing a cytotoxic compound useful in the treatment of cancer, said method comprising:
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(a) identifying a polypeptide antigen which is more highly expressed on the surface of a proliferating cancer cell than on the surface of a proliferating non-cancer cell;
(b) producing an antibody that binds to said polypeptide antigen; and
(c) linking at least one anti-mitotic compound to said antibody, thereby producing said cytotoxic compound. - View Dependent Claims (11, 12, 13, 14, 15)
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16. A method for inhibiting the proliferation of cancer cells comprising:
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(a) identifying a polypeptide antigen which is more highly expressed on the surface of said cancer cells than on the surface of a proliferating non-cancer cell;
(b) producing an antibody that binds to said polypeptide antigen;
(c) linking at least one anti-mitotic compound to said antibody to provide a cytotoxic compound, and (d) contacting said cancer cells with said cytotoxic compound, thereby inhibiting the proliferation thereof. - View Dependent Claims (17, 18, 19, 20, 21)
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22. A method for treating cancer in a mammal comprising:
administering to said mammal a therapeutically effective amount a cytotoxic compound which comprises (i) an antibody that binds to a polypeptide antigen that is more highly expressed on the surface of a cancer cell than on the surface of a proliferating non-cancer cell and (ii) at least one anti-mitotic compound linked to said antibody, wherein said cancer in said mammal is effectively treated. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30)
- 31. A composition comprising an anti-mitotic compound linked to an antibody wherein said antibody binds to a polypeptide antigen which is more highly expressed on the surface of a proliferating cancer cell than on the surface of a proliferating non-cancer cell.
Specification