IP Library Granted Patent US 12,516,093
Granted Patent B2
US 12,516,093 · App. 17/732,190 · Granted Jan 6, 2026

Recombinant erIL-15 NK cells

Inventors: Patrick Soon-Shiong (Culver City, CA); Shahrooz Rabizadeh (Agoura Hills, CA); Kayvan Niazi (Culver City, CA); Hans G. Klingemann (Culver City, CA)
Assignees: ImmunityBio, Inc.; NantBio, Inc.; NantCell, Inc.
C07K14/5443A61K40/15A61K40/30A61K40/31A61K40/35A61K40/421A61K40/4211A61K40/4221A61P35/00C12N5/0646
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,516,093
App. No.
17/732,190
Granted
Jan 6, 2026
Kind
B2
Abstract

Systems and methods are presented that provide for improved NK cell function. In preferred aspects, NK-92 cells express recombinant er/LSP-IL-15 to so render the NK-92 cells independent of exogenous cytokines and to provide extracellular immune stimulation.

Claims (15)

1 . A method of treatment for cancer, the method comprising administering to a patient in need thereof a genetically modified NK cell comprising a recombinant nucleic acid that encodes erLSP-IL-15 according to SEQ ID NO:5.

2 . The method of claim 1 , wherein the NK cell is an NK-92 cell.

3 . The method of claim 1 , wherein the recombinant nucleic acid is a DNA.

4 . The method of claim 3 , wherein the recombinant nucleic acid is a linearized plasmid.

5 . The method of claim 3 , wherein the recombinant nucleic acid further comprises a second segment encoding CD16 or a high affinity CD16.

6 . The method of claim 5 , wherein the recombinant nucleic acid further comprises a third segment encoding a chimeric antigen receptor.

7 . The method of claim 6 , wherein the recombinant nucleic acid further comprises a fourth segment encoding a protein that interferes with checkpoint inhibition, that provides immune stimulation, a protein that binds/inhibits a cytokine involved with immune suppression, and/or a IL-15 receptor alpha chain.

8 . The method of claim 1 , wherein the recombinant nucleic acid comprises a promotor having a sufficient strength to drive expression of the erLSP-IL-15 in an amount sufficient to (a) render the modified NK cell independent from exogenous cytokines, and to (b) allow for stimulation/activation of other immune competent cells that are in proximity to the modified NK cell.

9 . The method of claim 1 , further comprising administering an antibody coupled to the NK cell via CD16, wherein the coupling occurs prior to administration.

10 . The method of claim 1 , wherein between 5×10 7 and 5×10 10 cells are administered.

11 . The method of claim 1 , wherein between 7×10 8 and 7×10 9 cells are administered.

12 . The method of claim 1 , wherein 2×10 9 cells are administered.

13 . The method claim 1 , wherein the cells are administered intravenously.

14 . The method of claim 1 , wherein the cells are co-administered with one or more therapeutic agents comprising a chemotherapy, an immune stimulant, a cancer vaccine, and/or tumor-targeted IL-12.

15 . The method of claim 14 , wherein the cells are co-administered with Alt-803.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: NIAZI, KAYVAN
To: NANTBIO, INC.
Reel/Frame 070898/0765 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: RABIZADEH, SHAHROOZ; SOON-SHIONG, PATRICK
To: NANTCELL, INC.
Reel/Frame 070898/0919 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: KLINGEMANN, HANS G.
To: IMMUNITYBIO, INC.
Reel/Frame 070899/0036 →
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 →
Continuity (3)
Division 17438386
Provisional Application 62819256 · Mar 15, 2019
Related Publication 20220257660A1 · Aug 18, 2022
References Cited (55)
US 9487800B2 · Schonfeld et al. · 2016 [cited by applicant]
US 20170312351A1 · Niazi et al. · 2017 [cited by applicant]
US 20180044424A1 · June et al. · 2018 [cited by applicant]
US 20180344768A1 · O'dwyer et al. · 2018 [cited by applicant]
AU 2013203171B2 · 2016 [cited by applicant]
CN 106459914A · 2017 [cited by applicant]
CN 107567461A · 2018 [cited by applicant]
JP 2013501817A · 2013 [cited by applicant]
JP 7411674B2 · 2024 [cited by applicant]
TW 202102666A · 2021 [cited by applicant]
WO 2011020047A1 · 2011 [cited by applicant]
WO 2012136231A1 · 2012 [cited by applicant]
WO 2013040371A2 · 2013 [cited by applicant]
WO 2015174928A1 · 2015 [cited by applicant]
WO 2016109410A2 · 2016 [cited by applicant]
WO 2016160602A2 · 2016 [cited by applicant]
WO 2016201304A1 · 2016 [cited by applicant]
WO 2017132202A1 · 2017 [cited by applicant]
WO 2017192440A1 · 2017 [cited by applicant]
WO 2018005973A1 · 2018 [cited by applicant]
WO 2018165291A1 · 2018 [cited by applicant]
WO 2018183169A1 · 2018 [cited by applicant]
WO 2020205100A1 · 2020 [cited by applicant]
Rataj et al. High-affinity CD 16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptormodified T cells for cancer therapy. British Journal of Cancer (online Nov. 15, 2018). 120:79-8… [cited by examiner]
Wong et al. The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8+T cells into innate-like effector cells with antitumor activity. Haematologica (2004), 89:338-347. (Year: 2004). [cited by examiner]
Zhang et al. Characterization of interleukin-15 gene-modified human natural killer cells: implications for adoptive cellular immunotherapy. Oncoimmunology (2013),211, e26442. (Year 2013). [cited by examiner]
Tonn et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy (2013), 15, 1563-1570. (Year: 2013). [cited by examiner]
Williams et al. A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy. Oncotarget (2017), 8(51), 892… [cited by examiner]
Konstantinidis etal., “Targeting IL-2 to the Endoplasmic Reticulum Confines Autocrine Growth Stimulation to NK-92 Cells”, Experimental Hematology, 2005, vol. 33, No. 2, pp. 159-164 (Cited from Specification). [cited by applicant]
Brhuns et al., “Specificity and Affinity of Human Fcy Receptors and their Polymorphic Variants for Human lgG Subclasses”, Blood, 2009, vol. 113, No. 16, pp. 3716-3725 (Cited from Specification). [cited by applicant]
Kalaitsidou et al., “CAR T-Cell Therapy: Toxicity and the Relevance of Preclinical Models”, Immunotherapy, 2015, vol. 7, No. 5, pp. 487-497 (Cited from Specification). [cited by applicant]
Niazi et al., “Activation of Human CD4+ T Cells by Targeting MHC Class II Epitopes to Endosomal Compartments Using Human CD1 Tail Sequences”, Cancer Immunology Immunotherapy, 2012, vol. 122, pp. 522-531 (Cited from Spec… [cited by applicant]
Office Action received for Taiwanese Patent Application Serial No. 109106960 dated Mar. 22, 2021, 19 pages (Including English Translation). [cited by applicant]
Sadelain et al., “The basic principles of chimeric antigen receptor (CAR) design”, Cancer Discovery, 2013, vol. 3, No. 4, 21 pages. [cited by applicant]
Lakna Panawala., “Difference Between NK Cells and NKT Cells”, EPEDIAA, 2017, 6 pages. [cited by applicant]
International Search Report and Written Opinion received for PCT Application Serial No. PCT/US2020/019991 dated Jun. 30, 2020, 11 pages. [cited by applicant]
Kurys et al., ‘The Long Signal Peptide Isoform and Its Alternative Processing Direct the Intracellular Trafficking of Interleukin-15’, The Journal of Biological Chemistry, 2000, vol. 275, No. 39, pp. 30653-30659. [cited by applicant]
Fujii et al., “A potential therapy for chordoma via antibody-dependent cell-mediated cytotoxicity employing NK or high-affinity NK cells in combination with cetuximab”, Journal of Neurosurgery, 2018, vol. 128, pp. 1419-… [cited by applicant]
Bergamaschi et al., “Secretion and Biological Activity of Short Signal Peptide IL-15 Is Chaperoned by IL-15 Receptor Alpha in Vivo”, The Journal of Immunology, 2009, vol. 183, pp. 3064-3072. [cited by applicant]
Zhang et al., “Characterization of Interleukin-15 Gene-Modified Human Natural Killer Cells: Implications for Adoptive Cellular Immunotherapy”, Haematologica, 2004, vol. 89, No. 3, pp. 338-347. [cited by applicant]
Sahm et al., “Expression of IL-15 in NK Cells Results in Rapid Enrichment and Selective Cytotoxicity of Gene-Modified Effectors That Carry a Tumor-Specific Antigen Receptor”, Cancer Immunology Immunotherapy, 2012, vol. … [cited by applicant]
Office Action received for Taiwanese Patent Application Serial No. 109106960 dated Sep. 6, 2021, 2 pages. [cited by applicant]
International Preliminary Report on Patentability Chapter I received for PCT Application Serial No. PCT/US20/19991 dated Sep. 30, 2021, 8 pages. [cited by applicant]
Notice of Allowance received for U.S. Appl. No. 17/438,386 dated Apr. 13, 2022, 24 pages. [cited by applicant]
Notice of reasons for refusal received for Japanese Patent Application Serial No. 2021-555571 dated Aug. 19, 2022, 11 pages. [cited by applicant]
Extended European Search Report received for the EP Patent Application Serial No. 20784677.5 dated Mar. 28, 2023, 5 pages. [cited by applicant]
Jalah et al., “Efficient Systemic Expression of Bioactive IL-15 in Mice upon Delivery of Optimized DNA Expression Plasmids”, Original Papers, DNA & Cell Biology, vol. 26, No. 12, Dec. 2007, pp. 827-840. [cited by applicant]
Office Action received for CN Application No. 202080010863.0 dated Jul. 5, 2023, 19 Pages (Including English Translation). [cited by applicant]
Notice of Reasons for Refusal received for JP Application No. 2023-217265 dated Jan. 7, 2025, 08 Pages (Including English Translation). [cited by applicant]
Notice of Reasons for Rejection received for JP Application No. 2021-555571 dated Jul. 28, 2023, 07 Pages (Including English Translation). [cited by applicant]
Notice of Reasons for Refusal received for JP Application No. 2021-555571 dated Feb. 17, 2023, 08 Pages (Including English Translation). [cited by applicant]
Notice of Reasons for Rejection received for JP Application No. 2021-555571 dated Aug. 19, 2022, 13 pages (including English Translation). [cited by applicant]
Sahm C. et al. , “Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of genemodified effectors that carry a tumor-specific antigen receptor” , Cancer Immunol Immunother , 2012 , vol. … [cited by applicant]
Bergamaschi C et al. , “Secretion and biological activity of short signal peptide IL-15 is chaperoned by IL-15 receptor alpha in vivo” , J Immunol , 2009 , vol. 183(5) , pp. 3064-3072. [cited by applicant]
Fujii R. et al. , “A potential therapy for chordoma via antibody-dependent cell-mediated cytotoxicity employing NK or high-affinity NK cells in combination with cetuximab” , J Neurosurg , 2018 , vol. 128(5) , pp. 1419-1… [cited by applicant]