SUPER-HUMANIZED ANTIBODIES AGAINST RESPIRATORY SYNCYTIAL VIRUS

摘要

Disclosed herein are humanized antibodies that bind to an epitope on the F protein of respiratory syncytial virus. The humanized antibodies were designed by comparing the canonical CDR structure types of the CDRs from a non-human antibody (HNK20) to the canonical CDR structure types found in the human antibody germline sequences as the basis for selecting human variable region frameworks in a method denoted "super-humanization." Human antibody variable regions having the same or similar canonical CDR structure types as the non-human CDR provided a subset of candidate sequences from which to select the human frameworks. Chimeric variable regions were made comprising the non-human CDRs grafted in corresponding locations into the human frameworks from the candidate human variable regions. Several humanized antibodies that bind the same antigen as HNK20 and that have low immunogenicity were thereby designed, including examples where the framework sequences have less than 65% amino acid identity to the non-human frameworks.