Human antibodies to tn antigen

Abstract

The present invention provides compositions for the production of an antibody or functional fragment thereof directed against Tn antigen or sTn antigen. The compositions disclosed herein include isolated antibody or functional fragments thereof that binds to Tn antigen or sTn antigen and polynucleotides encoding the heavy chain and/or a light chain variable domains of such antibody or functional fragment. The invention also provides methods of treating or preventing a disease, such as cancer or tumor formation, wherein the antibody or functional fragment includes a variable heavy chain domain and a variable light chain domain that has an amino acid sequence provided herein. The invention further provides a conjugate of an antibody or functional fragment thereof conjugated or recombinantly fused to a localizing agent, detectable agent or therapeutic agent, and methods of treating, preventing or diagnosing a disease in a subject in need thereof.

1 . A monoclonal antibody that binds to a tumor glycoprotein containing a Thomsen-nouvelle (Tn) carbohydrate antigen, wherein said antibody comprises:
 a variable heavy chain polypeptide comprising the following complementarity determining regions (CDRs): a heavy chain variable CDR1 that is in SEQ ID NO: 117; a heavy chain variable CDR2 that is in SEQ ID NO: 117; a heavy chain variable CDR3 that is in SEQ ID NO: 117; and   a variable light chain polypeptide comprising the following complementarity determining regions (CDRs): a light chain variable CDR1 that is in SEQ ID NO: 112; a light chain variable CDR2 that is in SEQ ID NO: 112; and a light chain variable CDR3 that is in SEQ ID NO: 112.   
     
     
         2 . The monoclonal antibody of  claim 1 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 117. 
     
     
         3 . The monoclonal antibody of  claim 1 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 123. 
     
     
         4 . The monoclonal antibody of  claim 1 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:112. 
     
     
         5 . The monoclonal antibody of  claim 1 , wherein the VH domain comprises an amino acid sequence consisting of SEQ ID NO: 117 and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. 
     
     
         6 . The monoclonal antibody of  claim 1 , wherein the VH domain comprises an amino acid sequence consisting of SEQ ID NO: 123 and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. 
     
     
         7 . The monoclonal antibody of  claim 5 , wherein the monoclonal antibody binds Tn antigen expressed by a cancer cell, wherein said cancer cell is selected from the group consisting of: breast cancer, ovarian cancer, colon cancer, lung cancer, prostate cancer, gastric cancer, endometrial cancer, and pancreatic cancer. 
     
     
         8 . The monoclonal antibody of  claim 5 , wherein the antibody is a human antibody. 
     
     
         9 . The monoclonal antibody of  claim 5 , wherein the antibody is an IgG. 
     
     
         10 . The monoclonal antibody of  claim 9 , wherein the IgG antibody is an IgG1 subclass. 
     
     
         11 . A conjugate comprising the monoclonal antibody of  claim 5  conjugated or recombinantly fused to a therapeutic agent wherein the therapeutic agent is an agent that modifies a given biological response or a cytotoxin. 
     
     
         12 . The conjugate of  claim 11 , wherein the cytotoxin is a chemotherapeutic. 
     
     
         13 . The conjugate of  claim 12 , wherein the chemotherapeutic is an Auristatin molecule. 
     
     
         14 . A pharmaceutical composition comprising the monoclonal antibody of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         15 . A pharmaceutical composition comprising the conjugate of  claim 11  and a pharmaceutically acceptable carrier. 
     
     
         16 . The monoclonal antibody of  claim 6 , wherein the monoclonal antibody binds Tn antigen expressed by a cancer cell, wherein said cancer cell is selected from the group consisting of: breast cancer, ovarian cancer, colon cancer, lung cancer, prostate cancer, gastric cancer, endometrial cancer, and pancreatic cancer. 
     
     
         17 . The monoclonal antibody of  claim 6 , wherein the antibody is a human antibody. 
     
     
         18 . The monoclonal antibody of  claim 6 , wherein the antibody is an IgG. 
     
     
         19 . The monoclonal antibody of  claim 14 , wherein the IgG antibody is an IgG1 subclass. 
     
     
         20 . A conjugate comprising the monoclonal antibody of  claim 6  conjugated or recombinantly fused to a therapeutic agent wherein the therapeutic agent is an agent that modifies a given biological response or a cytotoxin. 
     
     
         21 . The conjugate of  claim 20 , wherein the cytotoxin is a chemotherapeutic. 
     
     
         22 . The conjugate of  claim 21 , wherein the chemotherapeutic is an Auristatin molecule. 
     
     
         23 . A pharmaceutical composition comprising the monoclonal antibody of  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         24 . A pharmaceutical composition comprising the conjugate of  claim 20  and a pharmaceutically acceptable carrier.