US2015366175A1PendingUtilityA1

Humanized il-15 animals

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Assignee: REGENERON PHARMAPriority: Oct 15, 2013Filed: Sep 1, 2015Published: Dec 24, 2015
Est. expiryOct 15, 2033(~7.2 yrs left)· nominal 20-yr term from priority
Inventors:Jose F. RojasKa-Man Venus LaiAndrew J. Murphy
C07K 14/5443A01K 67/0278A01K 2227/10A01K 2217/07A01K 2227/105A01K 2217/072C12N 15/8509A01K 2207/15C12N 2015/8527A01K 2267/03A01K 2267/0387
60
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Claims

Abstract

Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A genetically modified rodent, whose genome comprises a replacement at an endogenous rodent IL-15 locus of a rodent genomic segment comprising rodent exon sequences encoding a mature rodent IL-15 polypeptide with a human genomic segment comprising human IL-15 exons-3-6 encoding a mature human IL-15 polypeptide to form a humanized IL-15 gene, wherein the humanized IL-15 gene is under control of endogenous rodent IL-15 upstream regulatory elements at the endogenous rodent IL-15 locus, and wherein the genetically modified rodent expresses a human IL-15 polypeptide in serum following treatment of the rodent with Poly I:C. 
     
     
         2 . The rodent of  claim 1 , wherein the rodent is a mouse. 
     
     
         3 . The rodent of  claim 1 , wherein the rodent is a rat. 
     
     
         4 . The rodent of  claim 1 , wherein human IL-15 exons 3-6 are the only human IL-15 exons in the human genomic segment. 
     
     
         5 . The rodent of  claim 1 , wherein the humanized IL-15 gene comprises endogenous rodent IL-15 exons 1-2 and human IL-15 exons 3-6. 
     
     
         6 . A genetically modified rodent, comprising in its germline a humanized IL-15 gene, wherein the humanized IL-15 gene comprises human IL-15 exons 3-6 and is operably linked to an endogenous rodent IL-15 5′ regulatory region, wherein the genetically modified rodent expresses a human IL-15 polypeptide in serum following treatment of the rodent with Poly I:C. 
     
     
         7 . The rodent of  claim 6 , wherein the rodent is a mouse. 
     
     
         8 . The rodent of  claim 6 , wherein the rodent is a rat. 
     
     
         9 . The rodent of  claim 6 , wherein human IL-15 exons 3-6 are the only human IL-15 exons in the humanized IL-15 gene. 
     
     
         10 . The rodent of  claim 6 , wherein the humanized IL-15 gene further comprises endogenous rodent IL-15 exons 1-2, operably linked to the human IL-15 exons 3-6. 
     
     
         11 . The rodent of  claim 6 , wherein the humanized IL-15 gene is at a position in the genome of the rodent that is other than an endogenous IL-15 locus. 
     
     
         12 . A method of making a genetically modified rodent, comprising modifying the genome of a rodent by replacing at an endogenous rodent IL-15 locus a rodent genomic segment comprising rodent exon sequences coding for a mature rodent IL-15 polypeptide with a human genomic segment comprising human IL-15 exons 3-6 coding for a mature human IL-15 polypeptide to form a humanized IL-15 gene, wherein the humanized IL-15 gene is under control of endogenous rodent IL-15 upstream regulatory elements at the endogenous rodent IL-15 locus, and wherein the genetically modified rodent expresses a human IL-15 polypeptide in serum following treatment of said genetically modified rodent with Poly I:C. 
     
     
         13 . The method of  claim 12 , wherein the rodent is a mouse. 
     
     
         14 . The method of  claim 12 , wherein the rodent is a rat. 
     
     
         15 . The method of  claim 12 , wherein human IL-15 exons 3-6 are the only human IL-15 exons in the human genomic segment. 
     
     
         16 . The method of  claim 12 , wherein the humanized IL-15 gene comprises endogenous rodent IL-15 exons 1-2 and human IL-15 exons 3-6. 
     
     
         17 . A method of making a genetically modified rodent, comprising introducing into the genome of a rodent a humanized IL-15 gene, wherein the humanized IL-15 gene comprises human IL-15 exons 3-6 and is operably linked to an endogenous rodent IL-15 5′ regulatory region, wherein the genetically modified rodent expresses a human IL-15 polypeptide in serum following treatment of the rodent with Poly I:C. 
     
     
         18 . The rmethod of  claim 17 , wherein the rodent is a mouse. 
     
     
         19 . The method of  claim 17 , wherein the rodent is a rat. 
     
     
         20 . The method of  claim 17 , wherein human IL-15 exons 3-6 are the only human IL-15 exons in the humanized IL-15 gene. 
     
     
         21 . The method of  claim 17 , wherein the humanized IL-15 gene further comprises endogenous rodent IL-15 exons 1-2, operably linked to the human IL-15 exons 3-6. 
     
     
         22 . The method of  claim 17 , wherein the humanized IL-15 gene is at a position in the genome of the rodent that is other than an endogenous IL-15 locus.

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