US 12,016,315 B2
Genetically modified non-human animal with human or chimeric CD3e
Yuelei Shen, Beijing (CN); Yanan Guo, Beijing (CN); Rui Huang, Beijing (CN); Xiaofei Zhou, Beijing (CN); Yang Bai, Beijing (CN); Jiawei Yao, Beijing (CN); and Chaoshe Guo, Beijing (CN)
Assigned to Biocytogen Pharmaceuticals (Beijing) Co., Ltd., Beijing (CN); and Biocytogen JiangSu Co., Ltd., Jiangsu (CN)
Filed by Biocytogen Pharmaceuticals (Beijing) Co., Ltd., Beijing (CN); and Biocytogen JiangSu Co., Ltd., Haimen (CN)
Filed on Feb. 5, 2021, as Appl. No. 17/168,603.
Application 17/168,603 is a division of application No. 16/436,805, filed on Jun. 10, 2019, granted, now 10,945,420.
Application 16/436,805 is a continuation of application No. PCT/CN2018/120713, filed on Dec. 12, 2018.
Prior Publication US 2021/0259220 A1, Aug. 26, 2021
Int. Cl. A01K 67/027 (2006.01); A01K 67/0278 (2024.01); A61K 35/51 (2015.01); A61K 49/00 (2006.01)
CPC A01K 67/0278 (2013.01) [A61K 35/51 (2013.01); A61K 49/0008 (2013.01); A01K 2207/15 (2013.01); A01K 2227/105 (2013.01); A01K 2267/0331 (2013.01)] 19 Claims
 
1. A method of determining effectiveness of a therapeutic agent targeting CD3 for treating cancer, comprising:
administering the therapeutic agent targeting CD3 to a genetically-modified, non-human mammal whose genome comprises a replacement of a nucleic acid sequence encoding all or a portion of the extracellular region of an endogenous CD3e with a nucleic acid sequence encoding the corresponding region of a human CD3e, wherein the replacement results in a sequence encoding a chimeric CD3e comprising an amino acid sequence that is at least 95% identical to amino acids 1-126 of SEQ ID NO: 7, wherein the chimeric CD3e associates with endogenous CD3γ and endogenous CD3δ, forming a functional CD3 complex on T cells in the mammal, wherein the non-human mammal detectably expresses the chimeric CD3e on the surface of one or more T cells, wherein the mammal has a cancer; and
determining the inhibitory effects of the therapeutic agent to the cancer.