MICE THAT PRODUCE ANTIGEN-BINDING PROTEINS WITH PH-DEPENDENT BINDING CHARACTERISTICS

摘要

Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a hisidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, andor in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidne clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non- human animals that make immunoglobulin domains that bind antigens in a pH- sensitive manner are provided.