ALTERED ANTIBODIES HAVING IMPROVED ANTIGEN-BINDING AFFINITY

摘要

The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation o f a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and t he antigen in a solvent. Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen bindi ng by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent.