	US 12,280,111 B2
	Gene-regulating compositions and methods for improved immunotherapy
Micah Benson, Lexington, MA (US); Jason J. Merkin, Lexington, MA (US); Gregory V. Kryukov, Lexington, MA (US); Solomon Martin Shenker, Lexington, MA (US); Michael R. Schlabach, Lexington, MA (US); Noah Jacob Tubo, Lexington, MA (US); and James Martin Kaberna, II, Lexington, MA (US)
Assigned to KSQ Therapeutics, Inc., Lexington, MA (US)
Filed by KSQ Therapeutics, Inc., Lexington, MA (US)
Filed on Aug. 7, 2024, as Appl. No. 18/796,740.
Application 18/796,740 is a continuation of application No. 18/065,580, filed on Dec. 13, 2022, granted, now 12,084,682.
Application 18/065,580 is a continuation of application No. 17/707,725, filed on Mar. 29, 2022, granted, now 12,123,021.
Application 17/707,725 is a continuation of application No. 16/951,310, filed on Nov. 18, 2020, granted, now 11,332,713.
Application 16/951,310 is a continuation of application No. 16/354,100, filed on Mar. 14, 2019, granted, now 11,261,428.
Claims priority of provisional application 62/804,261, filed on Feb. 12, 2019.
Claims priority of provisional application 62/790,192, filed on Jan. 9, 2019.
Claims priority of provisional application 62/790,179, filed on Jan. 9, 2019.
Claims priority of provisional application 62/768,441, filed on Nov. 16, 2018.
Claims priority of provisional application 62/768,428, filed on Nov. 16, 2018.
Claims priority of provisional application 62/736,185, filed on Sep. 25, 2018.
Claims priority of provisional application 62/692,010, filed on Jun. 29, 2018.
Claims priority of provisional application 62/692,016, filed on Jun. 29, 2018.
Claims priority of provisional application 62/643,584, filed on Mar. 15, 2018.
Claims priority of provisional application 62/643,578, filed on Mar. 15, 2018.
Prior Publication US 2024/0390494 A1, Nov. 28, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/64 (2006.01); A61K 39/00 (2006.01); A61P 27/16 (2006.01); A61P 35/00 (2006.01); A61P 35/04 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/28 (2006.01); C07K 16/32 (2006.01); C12N 5/0783 (2010.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01); A61K 38/00 (2006.01)

CPC A61K 39/4611 (2023.05) [A61K 39/4631 (2023.05); A61K 39/4632 (2023.05); A61K 39/4644 (2023.05); A61K 39/464412 (2023.05); A61K 39/464491 (2023.05); A61K 39/464492 (2023.05); A61P 35/00 (2018.01); A61P 35/04 (2018.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 16/2803 (2013.01); C07K 16/2863 (2013.01); C07K 16/32 (2013.01); C12N 5/0636 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12N 15/113 (2013.01); C12N 15/1135 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/50 (2023.05); C07K 2317/24 (2013.01); C07K 2317/622 (2013.01); C07K 2319/30 (2013.01); C12N 2310/122 (2013.01); C12N 2310/14 (2013.01); C12N 2310/20 (2017.05); C12N 2310/531 (2013.01); C12N 2800/80 (2013.01)]

20 Claims

1. A method of treating cancer in a subject in need thereof, the method comprising: administering to the subject a composition comprising a therapeutically effective amount of modified human tumor infiltrating lymphocytes (TILs) that comprise an insertion, deletion, or mutation in an endogenous SOCS1 gene, wherein endogenous SOCS1 gene expression is reduced in the modified human TILs, relative to unmodified human TILs obtained from the subject.

19. A method of treating a solid tumor in a subject in need thereof, the method comprising:

selecting a subject who has a solid tumor that is insensitive to, or resistant to, is resistant to treatment with an immune checkpoint inhibitor; and

administering to the subject a composition comprising about 1×10⁷and about 1×10¹²modified human tumor infiltrating lymphocytes (TILs) that comprise an insertion, deletion, or mutation in an endogenous SOCS1 gene, wherein endogenous SOCS1 gene expression is reduced in the modified human TILs, relative to unmodified human TILs obtained from the subject.