FUNCTIONAL HUMANIZATION OF COMPLEMENTARITY DETERMINING REGIONS (CDRS)

摘要

Current humanization approaches for immunoglobulins focus mostly on modifying the framework regions into human sequences. Herein is provided a method for humanizing antibody complementarity-determining regions (CDRs) through functional humanization to reduce the potential immunogenicity of non-human CDR-containing antibodies. CDRs with high sequence homology to the parent CDR are identified from a database of human CDR sequences. One or more human CDRs that are highly homologous to the parent CDR sequence can be used to replace the corresponding CDRs of murine immunoglobulins (or their humanized, or re-engineered versions). Human CDRs that improve or have minimal effects on the antigen binding affinity and specificity are adopted.