	US 12,369,570 B2
	Humanized IL-15 animals
Jose F. Rojas, Newburgh, NY (US); Ka-Man Venus Lai, San Francisco, CA (US); Andrew J. Murphy, Croton-on-Hudson, NY (US); and Cagan Gurer, Chappaqua, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Oct. 17, 2022, as Appl. No. 18/047,014.
Application 18/047,014 is a continuation of application No. 16/732,400, filed on Jan. 2, 2020, granted, now 11,503,813.
Application 16/732,400 is a continuation of application No. 15/832,976, filed on Dec. 6, 2017, granted, now 10,561,125, issued on Feb. 18, 2020.
Application 15/832,976 is a continuation of application No. 14/842,342, filed on Sep. 1, 2015, abandoned.
Application 14/842,342 is a continuation of application No. 14/514,454, filed on Oct. 15, 2014, granted, now 9,155,290, issued on Oct. 13, 2015.
Claims priority of provisional application 61/891,013, filed on Oct. 15, 2013.
Prior Publication US 2023/0189772 A1, Jun. 22, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/85 (2006.01); A01K 67/0278 (2024.01); C07K 14/54 (2006.01); C12N 15/63 (2006.01)

CPC A01K 67/0278 (2013.01) [C07K 14/5443 (2013.01); C12N 15/8509 (2013.01); A01K 2207/15 (2013.01); A01K 2217/07 (2013.01); A01K 2217/072 (2013.01); A01K 2227/10 (2013.01); A01K 2227/105 (2013.01); A01K 2267/03 (2013.01); A01K 2267/0387 (2013.01); C12N 2015/8527 (2013.01)]

6 Claims

1. A targeting nucleic acid vector comprising

(i) a 5′ homology arm comprising a mouse genomic DNA sequence upstream of exon 3 of a mouse IL-15 gene,

(ii) a human genomic DNA fragment comprising exon 3 through the stop codon in exon 6 and the 3′ UTR of a human IL-15 gene and coding for a mature human IL-15 polypeptide,

(iii) a 3′ homology arm comprising a mouse genomic DNA sequence downstream of the 3′ UTR of the mouse IL-15 gene, and

(iv) a drug selection cassette,

wherein the 5′ and 3′ homology arms mediate homologous recombination and integration of the human genomic fragment into a mouse IL-15 gene locus, such that a genomic fragment of a mouse IL-15 gene at the mouse IL-15 gene locus is replaced with the human genomic fragment to form a humanized IL-15 gene,

wherein the genomic fragment of the mouse IL-15 gene being replaced comprises sequences of exons 3, 4, 5 and 6 of the mouse IL-15 gene coding for a mature mouse IL-15 polypeptide, and

wherein the humanized IL-15 gene is under control of endogenous mouse IL-15 upstream regulatory elements at the endogenous mouse IL-15 locus.