Anti-platelet membrane glycoprotein VI monoclonal antibody
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. 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 heavy chain variable region (VH) comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:42, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:43 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:44 and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:78, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:79 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:80.
2. The isolated antibody according to claim 1 , which is a chimeric antibody.
3. The isolated antibody according to claim 1 , which is a humanized antibody.
4. The isolated antibody according to claim 1 , wherein its antigen-binding valency is monovalent.
5. An isolated cell which produces the isolated antibody or antigen binding fragment thereof according to claim 1 .
6. The isolated antibody or antigen binding fragment thereof according to claim 1 , which is polyethylene glycolated (PEGylated).
7. A composition comprising the isolated antibody or antigen binding fragment according to claim 1 and a pharmaceutically acceptable excipient.
8. The antigen binding fragment according to claim 1 , which is an Fab, Fab′, F(ab′) 2 , single-chain antibody (scFv), sc(Fv) 2 , disulfide-stabilized Fv (dsFv), or a diabody.
9. The antibody or antigen-binding fragment according to claim 1 , 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.