IP Library › Granted Patent US 12,384,852
Granted Patent B2
US 12,384,852 · App. 17/530,211 · Granted Aug 12, 2025

Genetically modified NK-92 cells having a safety switch

Inventors: Tien Lee (San Diego, CA); Hans G. Klingemann (San Diego, CA); Barry J. Simon (San Diego, CA); Laurent Boissel (San Diego, CA); Kerry Campbell (Wyncote, PA)
Assignees: Institute for Cancer Research; ImmunityBio, Inc.
C07K16/2887A61K39/39558A61K40/15A61K40/42C07K16/2803C07K16/2827C07K16/32C12N5/0646A61K2039/572A61K2239/31A61K2239/38A61K2239/48A61K2300/00C07K2317/24C07K2317/732C12N2501/2302C12N2501/48C12N2501/599C12N2501/727C12N2510/00
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Quick Facts
Patent No.
US 12,384,852
App. No.
17/530,211
Granted
Aug 12, 2025
Kind
B2
Abstract

This invention is directed to treatment of a subject having or suspected of having a cancer comprising administering to the subject a monoclonal antibody and NK-92 expressing Fc receptor.

Claims (22)

1. A cell line comprising engineered NK-92 cells genetically modified to express:

(i) a bicistronic nucleic acid construct encoded by a non-retroviral vector, wherein the bicistronic construct comprises a polynucleotide that encodes a CD16 polypeptide having a valine at position 158 of the mature form of the CD16 polypeptide, and a polynucleotide that encodes an interleukin-2 (IL-2) polypeptide targeted to the endoplasmic reticulum (ER); and

(ii) a safety system gene that allows the NK-92 cells to be killed by introduction of a selective agent.

2. The cell line of claim 1 , wherein the safety system gene is selected from the group consisting of an inducible caspase 9 gene, a thymidine kinase gene, a cytosine deaminase gene, a cytochrome p450 gene, a nitroreductase gene, an Escherichia coli gpt gene, and an Escherichia coli deo gene.

3. The cell line of claim 2 , wherein the safety system gene is a mutant thymidine kinase gene selected from the group consisting of tk30, tk75, and sr39tk.

4. The cell line of claim 1 , wherein the bicistronic nucleic acid construct is encoded by a plasmid vector.

5. The cell lines of claim 1 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO:2.

6. The cell lines of claim 1 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO:2.

7. The cell line of claim 1 , wherein the CD16 polypeptide comprises the amino acid sequence of SEQ ID NO:2.

8. The cell line of claim 1 , wherein the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 90% identity to SEQ ID NO:7.

9. The cell lines of claim 1 , wherein the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 95% identity to SEQ ID NO:7.

10. The cell line of claim 1 , wherein the IL-2 polypeptide targeted to the ER comprises the amino acid sequence of SEQ ID NO:7.

11. The cell line of claim 1 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 90% identity to SEQ ID NO:7.

12. The cell line of claim 1 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 95% identity to SEQ ID NO:7.

13. The cell line of claim 1 , wherein the CD16 polypeptide comprises the amino acid sequence of SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises the amino acid sequence of SEQ ID NO:7.

14. The cell line of claim 2 , wherein the safety system gene is a wildtype thymidine kinase gene.

15. The cell line of claim 14 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO:2.

16. The cell line of claim 14 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO:2.

17. The cell line of claim 14 , wherein the CD16 polypeptide comprises the amino acid sequence of SEQ ID NO:2.

18. The cell line of claim 14 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 90% identity to SEQ ID NO:7.

19. The cell line of claim 14 , wherein the CD16 polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises an amino acid sequence having at least 95% identity to SEQ ID NO:7.

20. The cell line of claim 14 , wherein the CD16 polypeptide comprises the amino acid sequence of SEQ ID NO:2; and the IL-2 polypeptide targeted to the ER comprises the amino acid sequence of SEQ ID NO:7.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2024
From: LEE, TIEN; KLINGEMANN, HANS G.; SIMON, BARRY J.; BOISSEL, LAURENT
To: NANTKWEST, INC.
Reel/Frame 066738/0859 →
CHANGE OF NAME Recorded Mar 12, 2024
From: NANTKWEST, INC.
To: IMMUNITYBIO, INC.
Reel/Frame 066801/0776 →
SECURITY INTEREST Recorded Jan 2, 2024
From: IMMUNITYBIO, INC.; NANTCELL, INC.; RECEPTOME, INC.; VBC HOLDINGS LLC; ALTOR BIOSCIENCE, LLC; ETUBICS CORPORATION; IGDRASOL, INC.
To: INFINITY SA LLC, AS PURCHASER AGENT
Reel/Frame 066179/0074 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 23, 2023
From: CAMPBELL, KERRY
To: INSTITUTE FOR CANCER RESEARCH D/B/A THE RESEARCH INSTITUTE OF FOX CHASE CANCER CENTER
Reel/Frame 065304/0975 →
Continuity (6)
Continuation 17217839 · Mar 30, 2021
Continuation 16903882 · Jun 17, 2020
Continuation 16541847 · Aug 15, 2019
Continuation 15529848
Provisional Application 62139258 · Mar 27, 2015
Related Publication 20220062343A1 · Mar 3, 2022
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