Humanized Anti-CCR2 Antibodies and Methods of Use Therefor

Abstract

The present invention relates to a humanized antibody or functional fragment thereof which binds to a mammalian (e.g., human) CC-chemokine receptor 2 (CCR2) or a portion of the receptor and blocks binding of a ligand to the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR2 with a ligand thereof, and to use of the antibodies and fragments in therapeutic, prophylactic and diagnostic methods.

1 .- 38 . (canceled) 
     
     
         39 . An antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a chemokine to said receptor and inhibits one or more functions associated with binding of the chemokine to said receptor. 
     
     
         40 . The antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is humanized. 
     
     
         41 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the light chain of the 1D9 antibody and a framework region sequence of the variable light chain of the HF21/28 antibody. 
     
     
         42 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the variable heavy chain of monoclonal antibody 1D9 and a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         43 . The method of  claim 41 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the variable heavy chain of monoclonal antibody 1D9. 
     
     
         44 . The method of  claim 43 , wherein the humanized antibody or antigen-binding fragment thereof further comprises a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         45 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the variable light chain of monoclonal antibody 1D9, a framework region sequence of the variable light chain of the HF 21/28 antibody, three complementarity determining region sequence of the variable heavy chain of monoclonal antibody 1D9 and a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         46 . The method of  claim 45 , wherein the humanized antibody or antigen-binding fragment thereof comprises a heavy chain constant region or portion thereof. 
     
     
         47 . The method of  claim 46 , wherein the human constant region or portion thereof is of the gamma type. 
     
     
         48 . The method of  claim 47 , wherein the human constant region or portion thereof is mutated to minimize binding to Fc receptors, the ability to fix complement or both. 
     
     
         49 . The method of  claim 45 , wherein the humanized antibody or antigen-binding fragment thereof, comprises a light chain constant region. 
     
     
         50 . The method of  claim 49 , wherein the human light chain constant region is of the kappa type. 
     
     
         51 . A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of  claim 39 . 
     
     
         52 . The pharmaceutical composition of  claim 51 , wherein the composition is lyophilized. 
     
     
         53 . The pharmaceutical composition of  claim 51 , further comprising a pharmaceutically acceptable carrier. 
     
     
         54 . A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of  claim 45 . 
     
     
         55 . The pharmaceutical composition of  claim 54 , wherein the composition is lyophilized. 
     
     
         56 . The pharmaceutical composition of  claim 54 , further comprising a pharmaceutically acceptable carrier.