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 or antigen-binding fragment thereof that specifically binds to loop 9 in domain 2 of human platelet glycoprotein VI (GPVI) protein, wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) with 3 complementarity determining regions (CDR) and a variable light chain (VL) with 3 complementarity determining regions (CDR), comprising the following VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, respectively of:
(i) SEQ ID NOs: 18, 19, 20, 54, 55 and 56;
(ii) SEQ ID NOs: 24, 25, 26, 60, 61 and 62;
(iii) SEQ ID NOs: 48, 49, 50, 84, 85 and 86;
(iv) SEQ ID NOs: 362, 363, 364, 404, 405, and 406; and
(v) SEQ ID NOs: 365, 366, 367, 407, 408, and 409.
2. The antibody or antigen-binding fragment thereof of claim 1 , which is a chimeric antibody.
3. The antibody or antigen-binding fragment thereof of claim 1 , which is a humanized antibody.
4. The antibody or antigen-binding fragment thereof of claim 1 , wherein its antigen-binding valency is monovalent.
5. The antibody or antigen-binding fragment thereof of claim 1 , which is polyethyleneglycolated (PEGylated).
6. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 , and a pharmaceutically acceptable excipient.
7. 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.
8. 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.