Mica binding agents

Abstract

The present invention relates to methods for the treatment of disorders mediated by MICA-expressing cells using antibodies, antibody fragments, and derivatives thereof that specifically bind MICA. The invention also relates to antibodies; cells producing such antibodies; methods of making such antibodies; fragments, variants, and derivatives of the antibodies; and pharmaceutical compositions comprising the same.

1 - 47 . (canceled) 
     
     
         48 . A monoclonal antibody comprising (i) a heavy chain comprising the CDR 1 (SEQ ID NO: 92), 2 (SEQ ID NO: 95) and 3 (SEQ ID NO: 97) of the heavy chain variable region of SEQ ID NO: 90 and (ii) a light chain comprising the CDR 1 (SEQ ID NO: 98), 2 (SEQ ID NO: 99) and 3 (SEQ ID NO: 100) of the light chain variable region of SEQ ID NO: 91. 
     
     
         49 . The antibody of  claim 48 , wherein said antibody binds to a cell surface bound MICA polypeptide comprising an amino acid sequence of SEQ ID NO: 1, a cell surface bound MICA polypeptide comprising an amino acid sequence of SEQ ID NO: 2, and a cell surface bound MICA polypeptide comprising an amino acid sequence of SEQ ID NO: 4. 
     
     
         50 . The antibody of  claim 48 , wherein said antibody has reduced binding to a mutant MICA polypeptide comprising a mutation at 1, 2, 3, 4 or more residues selected from the group consisting of E100, D101, N102, S103, T104, R105, N121, E123, T124 and E126, relative to binding between the antibody and a wild-type MICA polypeptide of SEQ ID NO: 1. 
     
     
         51 . A pharmaceutical composition comprising an antibody of  claim 48 , and a pharmaceutically acceptable carrier. 
     
     
         52 . The antibody of  claim 48 , wherein said antibody is coupled to a cytotoxic agent. 
     
     
         53 . The antibody of  claim 48 , wherein said antibody is conjugated or coupled to a detectable agent. 
     
     
         54 . A recombinant nucleic acid encoding a heavy and/or light chain of the antibody of  claim 48 . 
     
     
         55 . A hybridoma or recombinant host cell producing the antibody of  claim 48 . 
     
     
         56 . A method for the treatment of a cancer in a patient in need thereof, the method comprising administering to said patient an effective amount a composition of  claim 51 . 
     
     
         57 . A method for identifying a MICA-expressing cell in a subject, the method comprising obtaining a biological sample from a subject comprising cells, bringing said cells into contact with an antibody of  claim 48  and assessing whether the antibody binds to the cells. 
     
     
         58 . The method of  claim 57 , wherein said method is free of an additional prior step of determining whether said subject or cells comprise a MICA allele selected from the group consisting of MICA*001, MICA*004, MICA*007 and MICA*008. 
     
     
         59 . A method for delivering a toxic molecule to a tumor cell, the method comprising exposing a tumor cell which expresses a MICA polypeptide to a monoclonal antibody of  claim 48  linked to a toxic agent.