PRODUCTION OF BISPECIFIC ANTIBODIES

摘要

Bispecific antibodies comprising (a) a first light-heavy chain pair having specificity for a first target and a sufficient number of substitutions in its heavy chain constant domain with respect to a corresponding wild-type antibody of the same isotype to significantly reduce the formation of first heavy chain-first heavy chain dimers and (b) a second light-heavy chain pair comprising a heavy chain having a sequence that is complementary to the sequence of the first pair heavy chain sequence with respect to the formation of intramolecular ionic interactions, wherein the first pair or second pair comprises a substitution in the light chain and complementary substitution in the heavy chain that reduces the ability of the light chain to interact with the heavy chain of the other light chain-heavy chain pair are provided. Methods of producing such antibodies in one or more cells also are provided.