Antibodies that bind cell-associated ca 125/o772p

Abstract

The present invention provides antibodies, and antigen-binding fragments of antibodies, fusion polypeptides and analogs that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides. The present invention further provides methods of preventing, managing, treating or ameliorating one or more symptoms associated with a CA 125/O772P-related disorder. In particular, the present invention provides methods of preventing, managing, treating, or ameliorating one or more symptoms associated with a cell proliferative disorder, such as cancer, e.g., ovarian cancer. The present invention still further provides methods for diagnosing a CA 125/O772P-related disorder or predisposition to developing such a disorder, as well as methods for identifying antibodies, and antigen-binding fragments of antibodies, that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides.

What is claimed is: 
     
         1 . A method of diagnosing or monitoring a CA 125/O772P-positive cancer in a subject, comprising:
 a) administering to said subject a monoclonal antibody or antibody fragment thereof that preferentially binds cell-associated CA 125/O772P polypeptide relative to shed CA 125/O772P polypeptide, wherein the antibody or antibody fragment thereof binds an epitope in residues 14-452 of SEQ ID NO: 1, and wherein said antibody or antibody fragment thereof is labeled with a detectable imaging moiety;   b) imaging said subject with an imaging system that can detect the imaging moiety in step a); and   c) detecting the presence of the labeled antibody in said subject, thereby diagnosing or monitoring a CA 125/O772P-positive cancer.   
     
     
         2 . The method of  claim 1 , wherein the CA 125/O772P-positive cancer is ovarian cancer. 
     
     
         3 . The method of  claim 1 , wherein the detectable imaging moiety is an enzyme label, radioisotope, or luminescent label. 
     
     
         4 . The method of  claim 1 , wherein the imaging system is computerized tomography, PET scan, MRI, or sonography. 
     
     
         5 . The method of  claim 1 , wherein detecting the presence of the labeled antibody in said subject, diagnoses a CA 125/O772P-positive cancer. 
     
     
         6 . A method of diagnosing or monitoring a CA 125/O772P-positive cancer in a subject, comprising:
 a) administering to said subject a monoclonal antibody or antibody fragment thereof that binds cell-associated CA 125/O772P polypeptide and comprises (i) a VH CDR1 sequence of SEQ ID NO:21, (ii) a VH CDR2 sequence of SEQ ID NO:22, (iii) a VH CDR3 sequence of SEQ ID NO:23, (iv) a VL CDR1 sequence of SEQ ID NO:24, (v) a VL CDR2 sequence of SEQ ID NO:25, and (vi) a VL CDR3 sequence of SEQ ID NO:26, wherein said antibody or antibody fragment thereof is labeled with a detectable imaging moiety;   b) imaging said subject with an imaging system that can detect the imaging moiety in step a); and   c) detecting the presence of the labeled antibody in said subject, thereby diagnosing or monitoring a CA 125/O772P-positive cancer.   
     
     
         7 . The method of  claim 6 , wherein the CA 125/O772P-positive cancer is ovarian cancer. 
     
     
         8 . The method of  claim 6 , wherein the detectable imaging moiety is an enzyme label, radioisotope, or luminescent label. 
     
     
         9 . The method of  claim 6 , wherein the imaging system is computerized tomography, PET scan, MRI, or sonography. 
     
     
         10 . The method of  claim 6 , wherein detecting the presence of the labeled antibody in said subject, diagnoses a CA 125/O772P-positive cancer.