Non-human animals having a humanized programmed cell death 1 gene
AssigneeRegeneran Pharmaceuticals, Inc.
InventorsElena Burova, Alexander O. Mujica, Ka-Man Venus Lai, Andrew J. Murphy
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Abstract
Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
Claims14
A method of assessing pharmacokinetic properties of an antibody targeting human PD-1, the method comprising the steps of
- administering the antibody to a mouse whose genome comprises a humanized Programmed cell death 1 (Pdcd1) gene at an endogenous Pdcd1 locus,
- wherein the humanized Pdcd1 gene is operably linked to a Pdcd1 promoter and expresses a humanized Programmed cell death 1 (PD-1) polypeptide on the surface of activated T cells in the mouse,
- wherein the humanized Pdcd1 gene comprises exon 2 and at least a part of exon 3 of a human Pdcd1 gene, wherein the humanized PD-1 polypeptide comprises the N-terminal immunoglobulin V domain of a human PD-1 polypeptide and the intracellular domain of an endogenous mouse PD-1 polypeptide;
- and
- performing an assay to determine pharmacokinetic properties of the antibody.
A method of assessing anti-tumor effect of an antibody targeting human PD-1, the method comprising the steps of
- administering the antibody to a mouse whose genome comprises a humanized Programmed cell death 1 (Pdcd1) gene at an endogenous Pdcd1 locus,
- wherein the humanized Pdcd1 gene is operably linked to a Pdcd1 promoter and expresses a humanized Programmed cell death 1 (PD-1) polypeptide on the surface of activated T cells in the mouse,
- wherein the humanized Pdcd1 gene comprises exon 2 and at least a part of exon 3 of a human Pdcd1 gene, wherein the humanized PD-1 polypeptide comprises the N-terminal immunoglobulin V domain of a human PD-1 polypeptide and the intracellular domain of an endogenous mouse PD-1 polypeptide, and
- wherein the mouse comprises a tumor;
- and
- monitoring the mouse by measuring the size of the tumor to determine whether the antibody has an antitumor effect.
Dependencies are inferred from the claim text.