VORONINA, VERA,MOMONT, COREY,MCWHIRTER, JOHN,TU, NAXIN,MACDONALD, LYNN,MURPHY, ANDREW J.
申请号:
CA3093850
公开号:
CA3093850A1
申请日:
2019.03.25
申请国别(地区):
CA
年份:
2019
代理人:
摘要:
Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (? or ?) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a ß-2-microglobulin polypeptide (ß2?), a Fc e receptor 1 a (FceR1a), a Fc ? receptor 1 alpha (Fc?R1a), a Fc gamma receptor 2a (Fc?R2a), a Fc gamma receptor 2b (Fc?R2b), a Fc gamma receptor 3a (Fc?R3a), a Fc gamma receptor 3b (Fc?R3b), a Fc gamma receptor 2c (Fc?R2c)). The transmembrane and cytoplasmic domain of such receptors can be human or non-human (e.g., rodent).