US 12,256,720 B2
Humanized dipeptidyl-peptidase IV (DPP4) animals
Christos Kyratsous, Irvington, NY (US); and Alexander Mujica, Elmsford, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Apr. 21, 2021, as Appl. No. 17/236,083.
Application 17/236,083 is a continuation of application No. 16/239,028, filed on Jan. 3, 2019, granted, now 11,013,220.
Application 16/239,028 is a continuation of application No. 15/295,955, filed on Oct. 17, 2016, granted, now 10,212,923, issued on Feb. 26, 2019.
Application 15/295,955 is a continuation of application No. 14/723,855, filed on May 28, 2015, granted, now 9,497,945, issued on Nov. 22, 2016.
Claims priority of provisional application 62/072,692, filed on Oct. 30, 2014.
Claims priority of provisional application 62/051,626, filed on Sep. 17, 2014.
Claims priority of provisional application 62/005,476, filed on May 30, 2014.
Prior Publication US 2021/0235674 A1, Aug. 5, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/63 (2006.01); A01K 67/0276 (2024.01); A01K 67/0278 (2024.01); C12N 5/0735 (2010.01); C12N 15/09 (2006.01); C12N 15/85 (2006.01); C12Q 1/68 (2018.01); C12Q 1/6883 (2018.01); C12Q 1/70 (2006.01); G01N 33/569 (2006.01)
CPC A01K 67/0278 (2013.01) [A01K 67/0276 (2013.01); C12N 5/0606 (2013.01); C12N 15/63 (2013.01); C12N 15/85 (2013.01); C12Q 1/68 (2013.01); C12Q 1/6883 (2013.01); C12Q 1/70 (2013.01); C12Y 304/14005 (2013.01); G01N 33/56983 (2013.01); A01K 2207/15 (2013.01); A01K 2217/072 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); A01K 2267/03 (2013.01); A01K 2267/0337 (2013.01)] 5 Claims
 
1. A targeting nucleic acid vector, comprising:
(i) a 5′ homology arm comprising a mouse genomic DNA sequence which comprises mouse Dpp4 exon 1 including the initiation ATG codon,
(ii) a human genomic fragment of about 81.7 Kb comprising intron 1, and exon 2 through the Stop codon of exon 26 and a portion of the 3′ untranslated region of a human Dipeptidyl peptidase IV (DPP4) gene, and
(iii) a 3′ homology arm comprising a mouse genomic DNA sequence which comprises the 3′ untranslated region of the mouse DPP4 gene,
wherein the 5′ and 3′ homology arms mediate replacement of a mouse genomic fragment comprising exon 2 through the Stop codon in exon 26 of a mouse Dpp4 gene at a mouse Dpp4 locus, with the human genomic fragment, to form a humanized Dpp4 gene, and
wherein the humanized Dpp4 gene is under control of mouse regulatory elements at the endogenous mouse Dpp4 locus.