US 11,903,966 B2
Intracellular genomic transplant and methods of therapy
Branden Moriarity, Shoreview, MN (US); Beau Webber, Coon Rapids, MN (US); Modassir Choudhry, New York, NY (US); Steven A. Rosenberg, Potomac, MD (US); Douglas C. Palmer, North Bethesda, MD (US); and Nicholas P. Restifo, Chevy Chase, MD (US)
Assigned to REGENTS OF THE UNIVERSITY OF MINNESOTA, Minneapolis, MN (US); INTIMA BIOSCIENCE, INC., New York, NY (US); and The U.S.A., as represented by the Secretary, Department f Health and Human Services, Bethesda, MD (US)
Filed by REGENTS OF THE UNIVERSITY OF MINNESOTA, Minneapolis, MN (US); INTIMA BIOSCIENCE, INC., New York, NY (US); and The U.S.A. as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Nov. 5, 2018, as Appl. No. 16/180,867.
Application 16/180,867 is a continuation of application No. 15/224,151, filed on Jul. 29, 2016, granted, now 10,166,255.
Claims priority of provisional application 62/199,905, filed on Jul. 31, 2015.
Claims priority of provisional application 62/232,983, filed on Sep. 25, 2015.
Claims priority of provisional application 62/286,206, filed on Jan. 22, 2016.
Claims priority of provisional application 62/295,670, filed on Feb. 16, 2016.
Claims priority of provisional application 62/330,464, filed on May 2, 2016.
Claims priority of provisional application 62/360,245, filed on Jul. 8, 2016.
Prior Publication US 2019/0054122 A1, Feb. 21, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/00 (2006.01); A61K 35/17 (2015.01); A61P 35/00 (2006.01); C07K 14/715 (2006.01); C12N 15/113 (2010.01); C07K 14/47 (2006.01); C07K 14/725 (2006.01); C12N 5/0783 (2010.01); C07K 14/705 (2006.01); C12N 15/90 (2006.01); C12N 9/22 (2006.01); C12N 9/96 (2006.01); C12N 15/87 (2006.01)
CPC A61K 35/17 (2013.01) [C07K 14/4718 (2013.01); C07K 14/7051 (2013.01); C07K 14/70503 (2013.01); C07K 14/7158 (2013.01); C12N 5/0636 (2013.01); C12N 9/22 (2013.01); C12N 9/96 (2013.01); C12N 15/113 (2013.01); C12N 15/907 (2013.01); C12N 15/87 (2013.01); C12N 2310/20 (2017.05); C12N 2510/00 (2013.01)] 46 Claims
 
1. A method of treating a neoantigen expressing cancer in a human subject, the method comprising:
administering to said human subject an immunosuppressive agent; and
administering to said human subject a population of ex vivo engineered neoantigen targeting human primary cells, wherein said population of ex vivo engineered neoantigen targeting human primary cells comprises CD4+ T cells that comprise:
a) an endonuclease mediated genomic disruption within exon 2 or exon 3 of a cytokine inducible SH2-containing protein gene (CIS-1) sequence, wherein said endonuclease mediated genomic disruption comprises an indel, and wherein said genomic disruption suppresses expression of a protein encoded by the cytokine inducible SH2-containing protein gene (CIS-1); and
b) an exogenous functional neoantigen targeting T cell receptor polypeptide or functional neoantigen targeting fragment thereof, or an exogenous functional neoantigen targeting chimeric antigen receptor polypeptide or functional neoantigen targeting fragment thereof, wherein said neoantigen is expressed by said neoantigen expressing cancer, and
wherein said cancer is selected from the group consisting of: bladder cancer, bone cancer, brain cancer, breast cancer, esophageal cancer, gastrointestinal cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, anal cancer, rectal cancer, ocular cancer, cancer of the neck, gallbladder cancer, pleural cancer, oral cancer, cancer of the vulva, colon cancer, cervical cancer, fibrosarcoma, kidney cancer, mesothelioma, mastocytoma, nasopharynx cancer, pancreatic cancer, peritoneal cancer, small intestine cancer, stomach cancer, testicular cancer, and thyroid cancer.