	US 11,905,528 B2
	Compound chimeric antigen receptor (cCAR) targeting multiple antigens, compositions and methods of use thereof
Yupo Ma, Stony Brook, NY (US); Kevin Pinz, Stony Brook, NY (US); Xun Jiang, Stony Brook, NY (US); Masayuki Wada, Stony Brook, NY (US); and Kevin Chen, Stony Brook, NY (US)
Assigned to ICell Gene Therapeutics Inc., Stony Brook, NY (US)
Appl. No. 16/753,951
Filed by ICELL GENE THERAPEUTICS, LLC, Stony Brook, NY (US)
PCT Filed Oct. 12, 2018, PCT No. PCT/US2018/055705 § 371(c)(1), (2) Date Apr. 6, 2020, PCT Pub. No. WO2019/075395, PCT Pub. Date Apr. 18, 2019.
Claims priority of provisional application 62/628,973, filed on Feb. 10, 2018.
Claims priority of provisional application 62/571,608, filed on Oct. 12, 2017.
Prior Publication US 2020/0308541 A1, Oct. 1, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61P 35/00 (2006.01); A61K 35/17 (2015.01); C07K 14/435 (2006.01); C07K 14/54 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 14/73 (2006.01); C07K 14/715 (2006.01); C12N 9/10 (2006.01)

CPC C12N 5/0636 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 14/435 (2013.01); C07K 14/54 (2013.01); C07K 14/5443 (2013.01); C07K 14/705 (2013.01); C07K 14/7051 (2013.01); C07K 14/70503 (2013.01); C07K 14/70514 (2013.01); C07K 14/70575 (2013.01); C07K 14/70589 (2013.01); C07K 14/7155 (2013.01); C12N 5/0646 (2013.01); C12N 9/1081 (2013.01); C07K 2319/03 (2013.01); C12N 2510/00 (2013.01)]

7 Claims

1. An ex vivo engineered T cell or NK cell co-expressing two distinct chimeric antigen receptor (CAR) units at the cell surface, wherein the engineered T cell or NK cell comprises a nucleotide sequence comprising from 5′ to 3′ a first polynucleotide encoding a first chimeric antigen receptor polypeptide (first CAR), a second polynucleotide encoding a second chimeric antigen receptor polypeptide (second CAR), a nucleotide encoding porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), FMDV 2A (F2A) or equine rhinitis A virus (ERAV) 2A (E2A1 disposed between the first CAR and second CAR, under the transcriptional control of a single promoter, wherein:

(i.) the first CAR polypeptide comprises a first antigen recognition domain; a first signal peptide; a first hinge region; a first transmembrane domain; a first co-stimulatory domain; and a first signaling domain; and

(ii.) the second CAR comprises a second antigen recognition domain; a second signal peptide; a second hinge region; a second transmembrane domain; a second co-stimulatory domain; and a second signaling domain;

wherein the first antigen recognition domain and the second antigen recognition domain are different;

wherein the engineered T cell or NK cell comprises an enhancer selected from the group consisting of IL-15/IL-15sushi, IL-15/IL-15 sushi anchor, 4-1BBL, and IL-15: and

wherein the engineered T cell or NK cell comprises SEQ ID NO: 1, SEQ ID NO: 28, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 52, or SEQ ID NO: 60.