US 12,004,495 B2
Genetically modified non-human animals with humanized immunoglobulin locus
Yuelei Shen, Beijing (CN); Jiawei Yao, Beijing (CN); Huizhen Zhao, Beijing (CN); Yabo Zhang, Beijing (CN); Lili Liu, Beijing (CN); Hui Lu, Beijing (CN); and Shuwen Huang, Beijing (CN)
Assigned to Biocytogen Pharmaceuticals (Beijing) Co., Ltd., Beijing (CN)
Filed by Biocytogen Pharmaceuticals (Beijing) Co., Ltd., Beijing (CN)
Filed on Sep. 2, 2020, as Appl. No. 17/010,587.
Application 17/010,587 is a continuation of application No. PCT/CN2020/075698, filed on Feb. 18, 2020.
Claims priority of application No. PCT/CN2019/075406 (WO), filed on Feb. 18, 2019; and application No. PCT/CN2019/106320 (WO), filed on Sep. 18, 2019.
Prior Publication US 2020/0390073 A1, Dec. 17, 2020
Int. Cl. A01K 67/0278 (2024.01); C07K 16/00 (2006.01)
CPC A01K 67/0278 (2013.01) [C07K 16/00 (2013.01); A01K 2207/15 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); C07K 2317/24 (2013.01)] 22 Claims
 
1. A genetically-modified rodent comprising at an endogenous heavy chain immunoglobulin gene locus human Immunoglobulin Heavy Variable (IGHV) genes, human Immunoglobulin Heavy Diversity (IGHD) genes, and human Immunoglobulin Heavy Joining (IGHJ) genes at the heavy chain immunoglobulin gene locus of human chromosome 14 from a human cell, wherein the human IGHV genes, the human IGHD genes, and the human IGHJ genes are operably linked and can undergo VDJ rearrangement, wherein a contiguous human sequence is integrated into the endogenous chromosome by recombination, and the human sequence is at least 500 kb, wherein the modification can be detected by PCR using one or more primer pairs selected from the group consisting of:
(a) SEQ ID NO: 13 and SEQ ID NO: 14;
(b) SEQ ID NO: 15 and SEQ ID NO: 16;
(c) SEQ ID NO: 17 and SEQ ID NO: 18;
(d) SEQ ID NO: 19 and SEQ ID NO: 20;
(e) SEQ ID NO: 21 and SEQ ID NO: 22;
(f) SEQ ID NO: 23 and SEQ ID NO: 24; and
(g) SEQ ID NO: 25 and SEQ ID NO: 26.