Mice that produce antigen-binding proteins with pH-dependent binding characteristics

摘要

Genetically modified non-human animals are provided that comprise an immunoglobulin heavy chain locus comprising an unrearranged human heavy chain variable region nucleotide sequence comprising an addition of at least one histidine codon or a substitution of at least one endogenous non-histidine codon with a histidine codon. Compositions and methods for making the genetically modified non-human animals as described herein are provided. Non-human animals capable of expressing an antigen-binding protein characterized by pH-dependent antigen binding, enhanced recyclability and/or enhanced serum half-life are also provided.

主权项

1. A non-human animal comprising
(i) in its germline genome a genetically modified immunoglobulin heavy chain locus comprising an unrearranged human immunoglobulin heavy chain variable region nucleotide sequence, wherein the unrearranged heavy chain variable region nucleotide sequence comprises an addition of at least one histidine codon or a substitution of at least one non-histidine codon with a histidine codon, wherein the histidine codon is not encoded by a corresponding human germline heavy chain variable region gene segment; and wherein the added or substituted histidine codon is present in a complementary determining region 3 (CDR3) encoding sequence.