Non-human animals having humanized Fc-gamma receptors
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAndrew J. Murphy, Lynn Macdonald, Cagan Gurer, Karolina A. Meagher, Naxin Tu
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Abstract
Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an FcγRI protein.
Claims18
A mouse cell whose genome comprises a FcγRI gene comprising a replacement of a nucleic acid sequence encoding an endogenous FcγRI α chain extracellular portion with a nucleic acid sequence encoding a human FcγRI α chain extracellular portion, wherein the FcγRI gene encodes a functional FcγRI α chain comprising the human FcγRI α chain extracellular portion and a mouse FcγRI α chain intracellular portion, wherein the functional FcγRI α chain comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 5.
A method of assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with a human antibody, the method comprising:
- (a) administering the human antibody to a mouse whose genome comprises a replacement of a nucleic acid sequence encoding an endogenous FcγRI α chain extracellular portion with a nucleic acid sequence encoding a human FcγRI α chain extracellular portion, wherein the mouse expresses a functional FcγRI α chain comprising the human FcγRI α chain extracellular portion and a mouse FcγRI α chain intracellular portion, wherein the functional FcγRI α chain comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 5, and wherein the mouse has been implanted with tumor cells;
- and
- (b) measuring tumor cell depletion in the mouse, thereby assessing ADCC.
A method of measuring a pharmacokinetic property of a human antibody in vivo, the method comprising:
- (a) administering the human antibody to a mouse whose genome comprises a replacement of a nucleic acid sequence encoding an endogenous FcγRI α chain extracellular portion with a nucleic acid sequence encoding a human FcγRI α chain extracellular portion, wherein the mouse expresses a functional FcγRI α chain comprising the human FcγRI α chain extracellular portion and a mouse FcγRI α chain intracellular portion, wherein the functional FcγRI α chain comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 5;
- and
- (b) measuring one or more pharmacokinetic properties of the administered human antibody in the mouse.
Dependencies are inferred from the claim text.