METHOD OF PRODUCING HUMAN IGG ANTIBODIES WITH ENHANCED EFFECTOR FUNCTIONS

摘要

A method for generating human IgG1 antibodies with enhanced Fc effectorfunction is disclosed. In practicing the method, an IgG1 Fc look-throughmutagenesis (LTM) coding library directed at four receptor-contact regions ofthe Fc CH2 portion of in human IgG1 Fc is expressed in a system in which themutated Fc fragments are displayed on the surfaces of the expression cells.The fragments are then screened for altered binding affinity to a selected Fcreceptor or other Fc-binding protein. The selected mutations may be used, inturn, to guide the selection of multiple substitutions in the construction ofa walk-through mutation (WTM) library, for generating additional Fc fragmentmutations with desired binding properties. The antibodies so produced have avariety of therapeutic and diagnostic applications.