HUMANIZED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ANTIBODIES, A METHOD FOR PREPARING SUCH HUMANIZED ANTIBODIES AND USE THEREOF IN THE PREPARATION OF MEDICAMENTS FOR INHIBITING TUMOR GROWTH

摘要

Described herein is a humanized antibody to vascular endothelial growth factor (VEGF). Also described herein is a method for rapidly producing and identifying framework mutations which improve the binding of humanized antibodies to their cognate antigens. In a preferred embodiment, non-human CDRs are grafted onto a human V1λI-V HIII framework. Random mutagenesis of a small set of critical framework residues is also performed followed by monovalent display of the resultant library of antibody molecules on the surface of filamentous phage. The optimal framework sequences are then identified by affinity-based selection. Optionally, the selected antibodies can be further mutated so as to replace vernier residues which sit at the VL-VH interface by residues which match the non-human parent antibody. The methods described herein can be applied to any non-human antibody. Accordingly, humanized antibodies are provided.