Structure-Based Selection and Affinity Maturation of Antibody Library

摘要

The present invention provides a structure-based methodology for efficiently generating and screening a library of recombinant antibodies for optimized antibodies with desirable functions, such as higher binding affinity or low immunogenicity. In one embodiment, a method is provided for constructing a library of antibody sequences based on a three dimensional structure of a lead antibody. The method comprises: providing a lead structural template comprising the amino acid sequence of the variable region of the heavy chain (VH) or light chain (VL) of a lead antibody, comparing the lead template sequence with a plurality of tester protein sequences; selecting a hit library from the tester protein sequences; determining if a member of the hit library is structurally compatible with the lead structural template using a scoring function; selecting members for the hit library that score equal to or better than the lead sequence and screening members for improved function(s).