Antibodies to human gdf8

Abstract

The present invention provides isolated human or humanized antibodies or antigen-binding fragments thereof which specifically bind to Growth and Differentiation Factor-8 (GDF8) and block GDF8 activity. The antibodies and antibody fragments of the present invention may be used in therapeutic methods for treating conditions or disorders which are ameliorated or improved by inhibition of GDF8.

1 - 18 . (canceled) 
     
     
         19 . An antibody or antigen-binding fragment thereof, which specifically binds to, or blocks the biological activity of wild-type mature human growth and differentiation factor-8 (GDF8), comprising: an amino acid sequence comprising three heavy chain complementarity determining region (CDR) sequences which differ by only a single conservative amino acid substitution within only one of the sequences SEQ ID NO: 362, SEQ ID NO:364, and SEQ ID NO: 366; and an amino acid sequence comprising three light chain complementarity determining region (CDR) sequences which differ by only a single conservative amino acid amino acid substitution within only one of the sequences SEQ ID NO: 370, SEQ ID NO: 372, and SEQ ID NO: 374. 
     
     
         20 . The antibody or antigen-binding fragment of  claim 19 , wherein the wild-type mature human growth and differentiation factor-8 (GDF8) comprises an amino acid sequence comprising SEQ ID NO: 340. 
     
     
         21 . The antibody or antigen-binding fragment of  claim 19 , wherein the antibody or antigen-binding fragment does not bind to or block the biological activity of a chimeric GDF8/TGFβ1 construct having amino acids 48-72 of mature human GDF8 replaced with the corresponding amino acid sequence of TGFβ1. 
     
     
         22 . The antibody or antigen-binding fragment of  claim 21 , wherein the chimeric GDF8/TGFβ1 construct comprises the amino acid sequence of SEQ ID NO:352. 
     
     
         23 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 19 ; and a pharmaceutically acceptable carrier. 
     
     
         24 . The antibody or antigen-binding fragment of  claim 19 , comprising: an amino acid sequence heavy chain variable region (HCVR) of SEQ ID NO: 360 with a single conservative amino acid substitution. 
     
     
         25 . The antibody or antigen-binding fragment of  claim 19 , comprising: an amino acid sequence light chain variable region (LCVR) of SEQ ID NO: 368 with a single conservative amino acid substitution. 
     
     
         26 . An antibody or antigen-binding fragment thereof, which specifically binds to, or blocks the biological activity of wild-type mature human growth and differentiation factor-8 (GDF8), comprising: a first amino acid sequence which differs from a heavy chain variable region (HCVR) comprising SEQ ID NO: 360 by only a single conservative amino acid substitution; a second amino acid sequence which differs from a light chain variable region (LCVR) comprising SEQ ID NO: 368 by only a single conservative amino acid substitution. 
     
     
         27 . The antibody or antigen-binding fragment of  claim 26 , wherein the wild-type mature human growth and differentiation factor-8 (GDF8) comprises an amino acid sequence comprising SEQ ID NO: 340. 
     
     
         28 . The antibody or antigen-binding fragment of  claim 26 , wherein the antibody or antigen-binding fragment does not bind to or block the biological activity of a chimeric GDF8/TGFβ1 construct having amino acids 48-72 of mature human GDF8 replaced with the corresponding amino acid sequence of TGFβ1. 
     
     
         29 . The antibody or antigen-binding fragment of  claim 28 , wherein the chimeric GDF8/TGFβ1 construct comprises the amino acid sequence of SEQ ID NO:352. 
     
     
         30 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 26 ; and a pharmaceutically acceptable carrier. 
     
     
         31 . An antibody or antigen-binding fragment thereof, which specifically binds to wild-type mature human growth and differentiation factor-8 (GDF8), wherein the antibody or antigen-binding fragment comprises a heavy chain and a light chain, each comprising CDR1, CDR2 and CDR3 domains, and wherein the heavy chain comprises: an amino acid sequence which differs from SEQ ID NO: 360 by only a single amino acid substitution; and the light chain comprises: an amino acid sequence which differs from SEQ ID NO: 368 by only a single amino acid substitution, wherein the antibody or antigen-binding fragment has at least the same binding affinity and specificity for (GDF8) as an antibody or antigen-binding fragment thereof which comprises SEQ ID NO: 360 and SEQ ID NO: 368. 
     
     
         32 . The antibody or antigen-binding fragment of  claim 31 , wherein the wild-type mature human growth and differentiation factor-8 (GDF8) comprises an amino acid sequence comprising SEQ ID NO: 340. 
     
     
         33 . The antibody or antigen-binding fragment of  claim 31 , wherein the antibody or antigen-binding fragment does not bind to or block the biological activity of a chimeric GDF8/TGFβ1 construct having amino acids 48-72 of mature human GDF8 replaced with the corresponding amino acid sequence of TGFβ1. 
     
     
         34 . The isolated antibody or antigen-binding fragment of  claim 33 , wherein the chimeric GDF8/TGFβ1 construct comprises the amino acid sequence of SEQ ID NO:352. 
     
     
         35 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 31 ; and a pharmaceutically acceptable carrier.