Isoform specific anti-her4 antibodies

Abstract

Compositions and methods useful for detecting and treating cancers which express the HER4 JM-a isoform are disclosed.

1 . An isolated anti-HER4 antibody that specifically binds to the HER4 JM-a isoform. 
     
     
         2 . The antibody of  claim 1 , wherein the antibody competes for binding to the JM-a isoform with the anti-HER4 antibody mAb 1479 produced by the hybridoma cell line deposited with ATCC having accession No. PTA-9655. 
     
     
         3 . The antibody of  claim 1 , wherein the antibody binds to the same epitope as the epitope to which the monoclonal antibody mAb 1479 produced by the hybridoma cell line deposited with the ATCC having accession No. PTA-9655 binds. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody is a chimeric, human, or humanized antibody. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody comprises a fragment from the monoclonal antibody mAb 1479 produced by the hybridoma cell line deposited with the ATCC having accession No. PTA-9655 that specifically binds to the HER4 JM-a isoform. 
     
     
         6 . The antibody of  claim 5 , wherein the fragment comprise the variable region of the monoclonal antibody mAb 1479. 
     
     
         7 . The antibody of  claim 5 , wherein the antibody is a humanized antibody. 
     
     
         8 . The antibody of  claim 5 , wherein the antibody is affinity matured. 
     
     
         9 . An isolated anti-HER4 antibody comprising monoclonal antibody mAb 1479 produced by the hybridoma cell line deposited with the ATCC having accession No. PTA-9655 or humanized form thereof. 
     
     
         10 . The antibody of  claim 1 , wherein the antibody is linked to a cytotoxic agent. 
     
     
         11 . The antibody of  claim 1 , wherein the antibody has less cardiotoxicity than an anti-HER4 antibody that is not specific for the HER4 JM-a isoform. 
     
     
         12 . A method of inhibiting the proliferation of a cancer cell that expresses the HER4 JM-a isoform, comprising contacting the cancer cell with an therapeutically effective amount of an anti-HER4 antibody that specifically binds to the HER4 JM-a isoform. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein the anti-HER4 antibody reduces HER4 ectodomain shedding. 
     
     
         15 - 22 . (canceled) 
     
     
         23 . A method of treating cancer in a patient comprising the steps of:
 a. selecting a patient whose cancerous cells comprise increased levels of shed Her4 ectodomain as compared with non-cancerous cells of the same tissue type; and   b. administering to the patient a therapeutically effective amount of an anti-HER4 antibody that specifically binds to the HER4 JM-a isoform.   
     
     
         24 - 31 . (canceled) 
     
     
         32 . A method of diagnosing a tumor in a patient comprising detecting the presence of shed HER4 ectodomain in the tumor. 
     
     
         33 - 35 . (canceled)