Antibodies that specifically block the biological activity of a tumor antigen

Abstract

Novel monoclonal antibodies that specifically bind to KAAG1 are described. In some embodiments, the antibodies block the biological activity of KAAG1 and are useful in composition in certain cancers, more particularly in cancers that have increased cell surface expression of KAAG1, such as ovarian, renal, lung, colorectal, breast, brain, and prostate cancer, as well as melanoma. The invention also relates to cells expressing the monoclonal antibodies and antigen binding fragments such as humanized and chimeric antibodies. Additionally, methods of detecting and treating cancer using the antibodies and fragments are also disclosed.

1 .- 21 . (canceled) 
     
     
         22 . An isolated antibody or antigen binding fragment thereof capable of specific binding to KAAG1 (SEQ ID NO.:2) or to a KAAG1 variant having at least 80% sequence identity with SEQ ID NO.:2 comprising a light chain variable domain comprising a CDRL1 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:39, a CDRL2 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:40 and a CDRL3 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:41 and a heavy chain variable domain comprising a CDRH1 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:42, a CDRH2 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:43 and a CDRH3 having an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO.:44. 
     
     
         23 .- 108 . (canceled) 
     
     
         109 . An isolated antibody or antigen binding fragment thereof capable of specific binding to KAAG1 (SEQ ID NO.:2) or to a variant thereof at least 80% sequence identity with SEQ ID NO.:2, the antibody or antigen binding fragment thereof comprising:
 a. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:105 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:132,   b. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:106 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:133,   c. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:107 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:134,   d. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:109 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:153,   e. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:126 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:145,   f. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:127 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:157,   g. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:128 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:155,   h. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:129 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:156, or;   i. the 3CDRs of a light chain variable domain defined in SEQ ID NO.:130 and the 3CDRs of a heavy chain variable domain defined in SEQ ID NO.:151.   
     
     
         110 .- 199 . (canceled) 
     
     
         200 . The isolated antibody or antigen binding fragment thereof of  claim 22 , conjugated with a cytotoxic moiety. 
     
     
         201 . The isolated antibody or antigen binding fragment thereof of  claim 22 , conjugated with a detectable moiety. 
     
     
         202 . The isolated antibody or antigen binding fragment thereof of  claim 109 , conjugated with a cytotoxic moiety. 
     
     
         203 . The isolated antibody or antigen binding fragment thereof of  claim 109 , conjugated with a detectable moiety. 
     
     
         204 . A pharmaceutical composition comprising the isolated antibody or antigen binding fragment thereof of  claim 22  and a pharmaceutically acceptable carrier. 
     
     
         205 . A pharmaceutical composition comprising the isolated antibody or antigen binding fragment thereof of  claim 109  and a pharmaceutically acceptable carrier. 
     
     
         206 . A pharmaceutical composition comprising the isolated antibody or antigen binding fragment thereof of  claim 200  and a pharmaceutically acceptable carrier. 
     
     
         207 . A pharmaceutical composition comprising the isolated antibody or antigen binding fragment thereof of  claim 202  and a pharmaceutically acceptable carrier. 
     
     
         208 . A composition comprising the isolated antibody and antigen binding fragment thereof of  claim 201 . 
     
     
         209 . A composition comprising the isolated antibody and antigen binding fragment thereof of  claim 203 . 
     
     
         210 . A method of treating cancer comprising administering the pharmaceutical composition of  claim 204  to an individual in need. 
     
     
         211 . A method of treating cancer comprising administering the pharmaceutical composition of  claim 205  to an individual in need. 
     
     
         212 . A method of treating cancer comprising administering the pharmaceutical composition of  claim 206  to an individual in need. 
     
     
         213 . A method of treating cancer comprising administering the pharmaceutical composition of  claim 207  to an individual in need. 
     
     
         214 . A method for detecting KAAG1 or a KAAG1 variant, the method comprising contacting a cell expressing KAAG1 or the KAAG1 variant or a sample comprising or suspected of comprising KAAG1 or the KAAG1 variant with the composition of  claim 208 . 
     
     
         215 . A method for detecting KAAG1 or a KAAG1 variant, the method comprising contacting a cell expressing KAAG1 or the KAAG1 variant or a sample comprising or suspected of comprising KAAG1 or the KAAG1 variant with the composition of  claim 209 .