Ovr110 antibody compositions and methods of use

Abstract

Isolated antibodies and antigen binding fragments thereof directed against Ovr110 which is expressed by head and neck, ovarian, endometrial, kidney, pancreatic, lung or breast cancer are provided. Also provided are cells and methods for their production as well as methods for their use in killing an Ovr110-expressing cancer cells and alleviating or treating an Ovr110-expressing cancer in a mammal. The anti-Ovr110 antibodies modulate Ovr110 function or internalize upon binding to Ovr110 expressed by mammalian cells in vitro and in vivo. Compositions comprising an anti-Ovr110 antibody and a carrier as well as articles of manufacture or kits thereof are also provided. In addition, isolated nucleic acids encoding an anti-Ovr110 antibody, expression vectors containing the isolated nucleic acids, and host cells containing the vectors are provided.

1 . An isolated monoclonal antibody or antigen binding fragment thereof which binds to Ovr110, said antibody or antigen binding fragment thereof comprising:
 (a) a light chain variable region comprising CDR1, CDR2 and CDR3 sequences, wherein the light chain variable region CDR1 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 3, 13, 23, 33 and 43, and conservative modifications thereof; and   (b) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences, wherein the heavy chain variable region CDR1 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8, 18, 28, 38 and 48, and conservative modifications thereof.   
     
     
         2 . The antibody or antigen binding fragment thereof of  claim 1 , wherein the light chain variable region CDR2 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4, 14, 24, 34 and 44, and conservative modifications thereof; and the heavy chain variable region CDR2 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 19, 29, 39 and 49, and conservative modifications thereof. 
     
     
         3 . The antibody or antigen binding fragment thereof of  claim 1 , wherein the light chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 15, 25, 35 and 45, and conservative modifications thereof; and the heavy chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 10, 20, 30, 40 and 50, and conservative modifications thereof. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody is a human, humanized or chimeric antibody. 
     
     
         5 . An isolated monoclonal antibody or antigen binding fragment thereof which binds to Ovr110, said monoclonal antibody or antigen binding fragment thereof comprising:
 (a) a light chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3, 13, 23, 33 and 43;   (b) a light chain variable region CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 4, 14, 24, 34 and 44;   (c) a light chain variable region CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 15, 25, 35 and 45;   (d) a heavy chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, 18, 28, 38 and 48;   (e) a heavy chain variable region CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 19, 29, 39 and 49; and   (f) a heavy chain variable region CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 10, 20, 30, 40 and 50.   
     
     
         6 . An isolated monoclonal antibody or antigen binding fragment thereof which binds Ovr110, said monoclonal antibody or antigen binding fragment thereof comprising:
 (a) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 12, 22, 32 and 42; and   (b) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 17, 27, 37 and 47.   
     
     
         7 . The antibody of  claim 6 , wherein the antibody is a human, humanized or chimeric antibody. 
     
     
         8 . The antibody or antigen binding fragment thereof of  claim 1  which inhibits Ovr110 function. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . A composition comprising the antibody or antigen binding fragment thereof of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         13 . An immunoconjugate comprising the antibody or antigen binding fragment thereof of  claim 1  conjugated to a cytotoxic agent. 
     
     
         14 . (canceled) 
     
     
         15 . A composition comprising the immunoconjugate of  claim 13 , and a pharmaceutically acceptable carrier. 
     
     
         16 . A bispecific molecule comprising the antibody or antigen binding fragment thereof of  claim 1 , linked to a second functional moiety having a different binding specificity than said antibody or antigen binding fragment thereof. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . A cell that produces the antibody or antigen binding fragment thereof of  claim 1 . 
     
     
         23 . (canceled) 
     
     
         24 . A method for inhibiting growth of tumor cells expressing Ovr110, said method comprising contacting the cells with the antibody or antigen binding fragment thereof of  claim 1  in an amount effective to inhibit growth of the tumor cells. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 24 , wherein the antibody or antigen binding fragment thereof is administered in combination with at least one chemotherapeutic agent. 
     
     
         27 . (canceled) 
     
     
         28 . A method of inhibiting suppression of an immune response against an Ovr110-expressing tumor cell comprising contacting the tumor cell with the antibody or antigen binding fragment thereof of  claim 1 . 
     
     
         29 . (canceled) 
     
     
         30 . A method for detecting Ovr110 over-expression in a subject, said method comprising:
 (a) contacting a sample from the subject with an antibody or antigen binding fragment thereof of  claim 1  under conditions suitable for binding;   (b) determining the level of Ovr110 in the sample; and   (c) comparing the level of Ovr110 in the sample to the level of Ovr110 in a control or normal range;   wherein an increase in the level of Ovr110 in the sample from the subject as compared to the control or normal range is indicative of Ovr110 over-expression.   
     
     
         31 - 32 . (canceled) 
     
     
         33 . A composition comprising the antibody or antigen binding fragment thereof of  claim 6 , and a pharmaceutically acceptable carrier. 
     
     
         34 . An immunoconjugate comprising the antibody or antigen binding fragment thereof of  claim 6  conjugated to a cytotoxic agent. 
     
     
         35 . A cell that produces the antibody or antigen binding fragment thereof of  claim 6 .