PRODUCTION OF CHIMERIC ANTIBODIES - A COMBINATORIAL APPROACH

摘要

Methods are disclosed which may be used for the production of antibodies, or antibody fragments, which have the same binding specificity as a parent antibody but which have increased human characteristics. Humanised an- tibodies may be obtained by chain shuffling, perhaps using phage display technology. In one embodiment, a polypep- tide comprising a heavy or light chain variable domain of a non-human antibody specific for an antigen of interest is combined with a repertoire of human complementary (light or heavy) chain variable domains. Hybrid pairings which are specific for the antigen of interest are selected. Human chains from the selected pairings may then be combined with a repertoire of human complementary variable do- trains (heavy or light) and humanised antibody polypeptide dimers can then be selected for binding specificity for anti- gen. The methods may be combined with CDR-imprinting. In another embodiment, component part of an antigen- binding site of a non-human antibody known to bind a par- ticular antigen is combined with a repertoire of component parts of an antigen-binding site of human antibody, forming a library of antibody polypeptide dimers with antigen-bind- ing sites. Hybrids selected from this library may be used in a second humanising shuffling step, or may already beof suf- ficient human character to be of value, perhaps after some modification to increase human character still further.