	US 12,275,787 B2
	Chimeric antigen receptors (CARs), compositions and methods 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 LLC, Stony Brook, NY (US)
Appl. No. 16/626,233
Filed by iCell Gene Therapeutics LLC, Stony Brook, NY (US)
PCT Filed Jun. 20, 2018, PCT No. PCT/US2018/038529 § 371(c)(1), (2) Date Dec. 23, 2019, PCT Pub. No. WO2018/237022, PCT Pub. Date Dec. 27, 2018.
Application 16/626,233 is a continuation of application No. 15/538,620, filed on Jun. 21, 2017, granted, now 11,820,819.
Claims priority of provisional application 62/523,147, filed on Jun. 21, 2017.
Prior Publication US 2020/0223918 A1, Jul. 16, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); A61P 37/06 (2006.01); C07K 14/54 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/30 (2006.01); C12N 5/0783 (2010.01); A61K 38/00 (2006.01)

CPC C07K 16/2803 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4613 (2023.05); A61K 39/4631 (2023.05); A61K 39/464402 (2023.05); A61K 39/464411 (2023.05); A61K 39/464412 (2023.05); A61K 39/464413 (2023.05); A61K 39/464417 (2023.05); A61K 39/464424 (2023.05); A61K 39/46444 (2023.05); A61K 39/464463 (2023.05); A61K 39/464471 (2023.05); A61P 35/00 (2018.01); A61P 35/02 (2018.01); A61P 37/06 (2018.01); C07K 14/5443 (2013.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 16/2812 (2013.01); C07K 16/2866 (2013.01); C07K 16/3061 (2013.01); C12N 5/0636 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2239/28 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C07K 16/28 (2013.01); C07K 16/2887 (2013.01); C07K 16/289 (2013.01); C07K 16/2896 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/74 (2013.01)]

2 Claims

1. A method for treating an autoimmune disease, said method comprising administering to a patient in need thereof 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 nucleotide encoding a promoter selected from human elongation factor-1 alpha (EF-1α) or spleen focus forming virus (SFFV), a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a first cleavage peptide, and a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR), wherein the engineered cell further comprises a nucleotide encoding secreted IL-15/IL-15sushi or a functional fragment thereof, wherein the nucleotide encoding said enhancer is attached to the nucleotide encoding the first CAR or the nucleotide encoding the second CAR by a nucleotide encoding a second cleavage peptide that flanks either end of the two distinct encoded CAR units, wherein:

the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and

the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; and

wherein the first antibody binding domain and the second antibody binding domain are different and each bind to a different target, wherein the targets of the first and second antibody binding domains irrespective of order are CD19 and BMCA (CD269), wherein the first and second co-stimulatory domains are intracellular, and wherein the first and second cleavage peptides are selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A), and wherein said autoimmune disease is systemic lupus erythematosus (SLE).