Anti-platelet membrane glycoprotein vi monoclonal antibody

Abstract

The present invention provides an antibody which has the following features, its active fragment, or a derivative thereof: a) It specifically binds to human platelet membrane glycoprotein VI (GPVI); b) The function to activate a platelet and/or the function to induce a thrombocytopenia in vivo are low; and c) It at least partially depletes GPVI on the platelet membrane by contacting with a platelet.

1 - 16 . (canceled) 
     
     
         17 . An isolated antibody that specifically binds to a human platelet glycoprotein VI (GPVI) protein comprising the amino acid sequence of SEQ ID NO:419 or antigen binding fragment thereof,
 wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) and a variable light chain (VL), comprising the following VH and VL amino acid sequences, respectively of: (i) SEQ ID NOs: 281 and 285; (ii) SEQ ID NOs: 281 and 287; (iii) SEQ ID NOs: 283 and 285; or (iv) SEQ ID NOs: 283, and 287,   wherein the VH and/or VL of said antibody or antigen-binding fragment thereof may comprise one to several residues of additions, deletions, substitutions, and/or insertions as compared to the reference sequence.   
     
     
         18 . The isolated antibody or antigen binding fragment thereof of  claim 17 ,
 wherein said antibody or antigen-binding fragment thereof comprises the following VH and VL amino acid sequences, respectively of: (i) SEQ ID NOs: 281 and 285; (ii) SEQ ID NOs: 281 and 287; (iii) SEQ ID NOs: 283 and 285; or (iv) SEQ NOs: 283, and 287.   
     
     
         19 . The isolated antibody or antigen binding fragment according to  claim 18 , wherein said antibody or antigen-binding fragment thereof comprises the amino acid sequence of the constant region of human IgG4. 
     
     
         20 . The isolated antibody or antigen binding fragment thereof of  claim 18 , wherein its antigen-binding valency is monovalent. 
     
     
         21 . An isolated cell which produces the isolated antibody or antigen binding fragment thereof according to  claim 18 . 
     
     
         22 . The isolated antibody or antigen binding fragment thereof of  claim 18 , which is polyethylene glycolated (PEGylated). 
     
     
         23 . A composition comprising the isolated antibody or antigen binding fragment thereof of  claim 18  and a pharmaceutically acceptable excipient. 
     
     
         24 . The antigen binding fragment according to  claim 18 , which is an Fab, Fab′, F(ab′)2, single-chain antibody (scFv), sc(Fv)2, disulfide-stabilized Fv (dsFv), or a diabody. 
     
     
         25 . The antibody or antigen-binding fragment according to  claim 18 , which is labeled with a labeling substance; conjugated to a radioisotope, protein, peptide or low molecular weight compound, or fused to another protein or peptide.