US 12,329,826 B2
Therapeutic agents comprising nucleic acids and CAR-modified immune cells, and uses thereof
Fang Hu, Zhejiang (CN); Can Chen, Zhejiang (CN); Lin Xiao, Zhejiang (CN); Jin Fu, Zhejiang (CN); Rong Zhang, Zhejiang (CN); and Jinlu Cai, Zhejiang (CN)
Assigned to HANGZHOU CONVERD CO., LTD., Zhejiang (CN)
Appl. No. 17/270,924
Filed by HANGZHOU CONVERD CO., LTD., Zhejiang (CN)
PCT Filed Aug. 26, 2019, PCT No. PCT/CN2019/102480
§ 371(c)(1), (2) Date Feb. 24, 2021,
PCT Pub. No. WO2020/038490, PCT Pub. Date Feb. 27, 2020.
Claims priority of application No. 201810972140.3 (CN), filed on Aug. 24, 2018.
Prior Publication US 2023/0321238 A1, Oct. 12, 2023
Int. Cl. A61K 40/31 (2025.01); A61K 35/17 (2015.01); A61K 38/17 (2006.01); A61K 39/00 (2006.01); A61K 40/11 (2025.01); A61K 40/15 (2025.01); A61K 40/42 (2025.01); A61K 47/68 (2017.01); A61K 48/00 (2006.01); A61P 35/00 (2006.01); C12N 5/0783 (2010.01)
CPC A61K 47/6891 (2017.08) [A61K 35/17 (2013.01); A61K 38/1774 (2013.01); A61K 39/0011 (2013.01); A61K 40/11 (2025.01); A61K 40/15 (2025.01); A61K 40/31 (2025.01); A61K 40/42 (2025.01); A61K 48/0058 (2013.01); A61P 35/00 (2018.01); C12N 5/0636 (2013.01); C12N 5/0638 (2013.01); C12N 5/0646 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/50 (2023.05); A61K 2239/59 (2023.05)] 17 Claims
 
1. A therapeutic agent for treatment of tumors and/or cancers, comprising:
(a) a first composition, wherein the first composition comprises a first active ingredient in a first pharmaceutically acceptable carrier, and the first active ingredient includes or contains a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell; the labeling polypeptide has a extracellular antigen determining region, a spacer portion and a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and/or cancer cell; an amino acid sequence of the extracellular antigen determining region comprises one or more amino acid sequences of epitope polypeptide; and wherein, in the natural state, an amino acid sequence of a protein on cell membrane or a secreted protein of mammal does not comprise the amino acid sequence of the epitope polypeptide; and
(b) a second composition, wherein the second composition comprises a second active ingredient in a second pharmaceutically acceptable carrier, and the second active ingredient comprises a chimeric antigen receptor-modified immune cell; the chimeric antigen receptor-modified immune cell can specifically recognize and bind to the extracellular antigen determining region of the labeling polypeptide;
wherein the spacer portion is derived from the hinge region of CD8α, the hinge region of IgG or the hinge region of IgD;
wherein the amino acid sequence of the epitope polypeptide includes an amino acid sequence of the following tags: Myc tag, HA tag, Strep tag II, Flag tag, HAT tag, S tag, S1 tag, protein C tag, tag-100 tag, E2 tag, TAP tag, HSV tag, KT3 tag, V5 tag, VSV-G tag, His tag or RFP tag; and
wherein the amino acid sequence of the extracellular antigen determining region is as shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5.