Compositions and methods for the diagnosis and treatment of tumor

Abstract

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

1 - 54 . (canceled) 
     
     
         55 . An isolated monoclonal antibody that binds to an antigenic epitope located between amino acids 320-361 of the polypeptide sequence of SEQ ID NO:2. 
     
     
         56 . An isolated monoclonal antibody, wherein the antibody is a first antibody and wherein the first antibody binds to the same antigenic epitope as a second antibody, wherein the second antibody comprises:
 (a) a complementarity determining region (CDR)-L1 sequence of any one of SEQ ID NOS:21-34;   (b) a CDR-L2 sequence of any one of SEQ ID NOS:35-38;   (c) a CDR-L3 sequence of any one of SEQ ID NOS:39-41;   (d) a CDR-H1 sequence of any one of SEQ ID NOS:42-45;   (e) a CDR-H2 sequence of any one of SEQ ID NOS:46-60; and   (f) a CDR-H3 sequence of any one of SEQ ID NOS:61-65.   
     
     
         57 . The antibody of  claim 56 , wherein the second antibody comprises:
 (a) a CDR-L1 sequence of SEQ ID NO:23;   (b) a CDR-L2 sequence of SEQ ID NO:36;   (c) a CDR-L3 sequence of SEQ ID NO:41;   (d) a CDR-H1 sequence of SEQ ID NO:43;   (e) a CDR-H2 sequence of SEQ ID NO:49; and   (f) a CDR-H3 sequence of SEQ ID NO:65.   
     
     
         58 . The antibody of  claim 57 , wherein the second antibody comprises the VL sequence of SEQ ID NO:9 and the VH sequence of SEQ ID NO:18. 
     
     
         59 . The antibody of any one of  claims 55 - 58  which is an antibody fragment. 
     
     
         60 . The antibody of any one of  claims 55 - 58  which is a chimeric or a humanized antibody. 
     
     
         61 . The antibody of any one of  claims 55 - 58  which is conjugated to a growth inhibitory agent. 
     
     
         62 . The antibody of any one of  claims 55 - 58  which is conjugated to a cytotoxic agent. 
     
     
         63 . The antibody of  claim 62 , wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 
     
     
         64 . The antibody of  claim 63 , wherein the cytotoxic agent is a toxin. 
     
     
         65 . The antibody of  claim 64 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 
     
     
         66 . The antibody of  claim 64 , wherein the toxin is an auristatin. 
     
     
         67 . The antibody of  claim 66 , wherein the toxin is monomethyl auristatin E (MMAE). 
     
     
         68 . The antibody of  claim 66 , wherein the toxin is monomethyl auristatin F (MMAF). 
     
     
         69 . The antibody of any one of  claims 55 - 58  which is conjugated to maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-val-cit-PAB-MMAE). 
     
     
         70 . The antibody of any one of  claims 55 - 58  which is produced in bacteria. 
     
     
         71 . The antibody of any one of  claims 55 - 58  which is produced in CHO cells. 
     
     
         72 . The antibody of any one of  claims 55 - 58  which induces death of a cell to which it binds. 
     
     
         73 . The antibody of  claim 72 , wherein said cell is an ovarian cancer cell. 
     
     
         74 . The antibody of  claim 72 , wherein said cell is a lung cancer cell. 
     
     
         75 . The antibody of any one of  claims 55 - 58  which is detectably labeled. 
     
     
         76 . The antibody of any one of  claims 55 - 58  further comprising a VH acceptor human consensus framework sequence of any one of SEQ ID NOS:66-75 and a VL acceptor human consensus framework sequence of any one of SEQ ID NOS:76-79. 
     
     
         77 . A cell which produces an antibody of any one of  claims 55 - 58 . 
     
     
         78 . A therapeutic formulation comprising the antibody of any one of  claims 55 - 58 .