HUMANIZED ANTIBODIES

摘要

Disclosed herein are humanized antibodies in which human germline residues are introduces to the complementarity determining regions (CDRs) of a non-human donor antibody. Also described herein are libraries of antibody variable domains (e.g., phage-display libraries) and methods for screening for humanized antibodies.

主权项

1. A humanized antibody or antigen-binding fragment thereof that binds to a target antigen, wherein:
(a) said antibody or antigen-binding fragment thereof comprises (i) a VH domain comprising: a human germline VH framework sequence, and CDR-H1, CDR-H2, and CDR-H3; and (ii) a VL domain comprising: a human germline VL framework sequence, and CDR-L1, CDR-L2, and CDR-L3; (b) said CDR-L1, CDR-L2, CDR-L3, CDR-H1, and CDR-H2 are derived from corresponding CDRs from a non-human donor antibody that binds to said target antigen; (c) for each position within said CDR-L1, CDR-L2, CDR-L3, CDR-H1, and CDR-H2, the residue is either human germline residue from said human germline VL or VH, or corresponding residue from said non-human donor antibody; (d) said CDR-L1, CDR-L2, CDR-L3, CDR-H1, and CDR-H2 each comprises at least one more human germline residue as compared to the corresponding non-human donor CDR, (e) said CDR-L1, CDR-L2, CDR-L3, CDR-H1, and CDR-H2 each comprises at least one more non-human donor residue as compared to the corresponding human germline VH or VL CDR; and (f) for each position within CDR-H3, the residue is any one of the 20 natural amino acid residues.