US 12,672,643 B2Granted

Genetically modified non-human animals and methods of use thereof

AssigneesRegeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)

InventorsDietmar Herndler-Brandstetter, Richard A. Flavell, Davor Frleta, Cagan Gurer, Markus Gabriel Manz, Andrew J. Murphy, Noah W. Palm, Liang Shan, Sean Stevens, Till Strowig, George D. Yancopoulos, Marcel de Zoete

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Abstract

Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

Claims19

Dependent claims

A genetically modified mouse comprising in its genome:

a humanized SIRPα gene comprising exon 1 of a mouse SIRPα gene, exons 2, 3 and 4 of a human SIRPα gene, and exons 5, 6, 7 and 8 of the mouse SIRPα gene, wherein the humanized SIRPα gene is operably linked to a mouse SIRPα promoter at the endogenous mouse SIRPα locus, and expresses in the mouse a humanized SIRPα protein comprising an extracellular portion of the human SIRPα protein encoded by the human SIRPα gene and an intracellular portion of the mouse SIRPα protein encoded by the mouse SIRPα gene;
and
a humanized IL-15 gene comprising exons 3 and 4 of a mouse IL-15 gene and exons 5, 6, 7 and 8 of a human IL-15 gene, wherein the humanized IL-15 gene is operably linked to a mouse IL-15 promoter at the endogenous mouse IL-15 locus, and expresses in the mouse a humanized IL-15 protein.

Dependencies are inferred from the claim text.

Facts

Application: 18/152,086Filed 9 Jan 2023 · continuation
Priority: 13 Apr 2015
Published: US 2023/0292721 A121 Sep 2023
Granted: 7 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

A01K 67/0278
Genetically modified vertebrates, e.g. transgenic: knock-in vertebrates, e.g. humanised vertebrates
A01K 67/0271
New or modified breeds of vertebrates: chimeric vertebrates, e.g. comprising exogenous cells
A61K 49/0008
Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for…:…
A61P 35/00
Antineoplastic agents

Family

Application62/146,938Us provisional application · filed 13 Apr 2015
Application62/148,667Us provisional application · filed 16 Apr 2015
Application62/287,842Us provisional application · filed 27 Jan 2016
Application15/097,239Parent of this continuation · filed 12 Apr 2016
Application15/954,450Parent of this continuation · filed 16 Apr 2018
US 10,123,518 B2Parent of this continuation · filed 13 Nov 2018
Application16/782,708Parent of this continuation · filed 5 Feb 2020
US 10,561,126 B2Parent of this continuation · filed 18 Feb 2020
US 2023/0292721 A1Pre-grant publication · published 21 Sep 2023
US 11,576,356 B2Parent of this continuation
US 2016/0295844 A1Published application
US 2018/0295820 A1Published application
US 2020/0229410 A1Published application
US 12,672,643 B2This patent

From the US filing history. Foreign family members aren’t listed.