Intracellular genomic transplant and methods of therapy

Patent metadata

Field	Value
Publication number	US-11266692-B2
Application number	US-202016900372-A
Country	US
Kind code	B2
Filing date	Jun 12, 2020
Priority date	Jul 31, 2015
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

First claim

What is claimed is:

1. A pharmaceutical composition that comprises a population of engineered human primary lymphocytes that comprise a genomic disruption within a cytokine-inducible SH2-containing protein gene target sequence that comprises any one of SEQ ID NO: 75-SEQ ID NO: 86, wherein said genomic disruption comprises an endonuclease-mediated indel.

2. The pharmaceutical composition of claim 1 , wherein the target sequence comprises SEQ ID NO: 82.

3. The pharmaceutical composition of claim 1 , wherein the population of engineered human primary lymphocytes are tumor infiltrating lymphocytes.

4. The pharmaceutical composition of claim 1 , wherein the genomic disruption results in reduced expression of a protein encoded by cytokine-inducible SH2-containing protein gene as compared to comparable human primary lymphocytes lacking the genomic disruption.

5. The pharmaceutical composition of claim 1 , wherein the population of engineered human primary lymphocytes comprises at least about 1×10 9 or at least about 1×10 10 lymphocytes.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is cryopreserved.

7. The pharmaceutical composition of claim 1 , wherein the population of engineered human primary lymphocytes further comprise at least one of an exogenous T cell receptor or an exogenous chimeric antigen receptor.

8. The pharmaceutical composition of claim 7 , wherein the population of engineered human primary lymphocytes target an antigen comprising BCMA, HER-2, CD19, MUC1, or any combination thereof.

9. The pharmaceutical composition of claim 1 , wherein the population of engineered human primary lymphocytes comprise a T cell.

10. The pharmaceutical composition of clam 1 , wherein the population of engineered human primary lymphocytes comprise an NK cell.

11. A genetically modified human cell is replaced with “comprising a genomic disruption within a target sequence that comprises any one of SEQ ID NO: 75-SEQ ID NO: 86, wherein the genomic disruption suppresses or eliminates expression of a protein encoded by a cytokine inducible SH2-containing protein gene, and wherein the genomic disruption comprises an endonuclease-mediated indel.

12. The genetically modified human cell of claim 11 , wherein the genomic disruption is within exon 2 of the cytokine inducible SH2-containing protein gene.

13. The genetically modified human cell of claim 11 , wherein the genomic disruption is within exon 3 of the cytokine inducible SH2-containing protein gene.

14. The genetically modified human cell of claim 11 , wherein the genetically modified human cell is a tumor infiltrating lymphocyte.

15. The genetically modified human cell of claim 11 , wherein the genetically modified human cell is a peripheral blood lymphocyte.

16. The genetically modified human cell of claim 11 , wherein the genetically modified human cell is a T cell.

17. The genetically modified human cell of claim 11 , wherein the genetically modified human cell is an NK cell.

18. The genetically modified human cell of claim 11 , further comprising at least one of an exogenous T cell receptor or an exogenous chimeric antigen receptor.

19. The genetically modified human cell of claim 18 , wherein the genetically modified human cell targets an antigen comprising BCMA, HER-2, CD19, MUC1, or any combination thereof.

Assignees

• Univ Minnesota
• Intima Bioscience Inc
• Us Health

Inventors

• Moriarity Branden
• Webber Beau
• Choudhry Modassir
• Rosenberg Steven A
• Palmer Douglas C
• Restifo Nicholas P

Classifications

• C12N15/907

  in mammalian cells · CPC title

• C12N15/87

  Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation · CPC title

• C12N9/96

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title

• C12N9/22

  Ribonucleases {[RNase]; Deoxyribonucleases [DNase]} · CPC title

• C12N2310/20

  involving clustered regularly interspaced short palindromic repeats [CRISPR] · CPC title