Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody.

ABSTRACT: Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the c

SUBMITTER: Apgar JR 

PROVIDER: S-EPMC5058614 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature