IP Library Granted Patent US 12,674,138
Granted Patent B2
US 12,674,138 · App. 15/948,619 · Granted Jul 7, 2026

Method for the induction and expansion of natural killer cells derived from peripheral blood mononuclear cells

Inventors: Kyung Mi Lee (Seoul, KR); Seon Ah Lim (Seoul, KR); Cassian Yee (Seoul, KR)
Assignee: NKMAX Co., Ltd.
C12N5/0646A61K40/15A61K40/46C12N2501/2302C12N2502/1114C12N2502/30
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Quick Facts
Patent No.
US 12,674,138
App. No.
15/948,619
Filed
Apr 9, 2018
Granted
Jul 7, 2026
Kind
B2
Art Unit
1631
USPC
424/93.71
Abstract

The present invention relates to a method for inducing and expanding natural killer cells derived from peripheral blood mononuclear cells, which comprises co-culturing, as feeder cells, irradiated Jurkat cells and irradiated Epstein-Barr virus transformed lymphocyte continuous line (EBV-LCL) cells in the presence of cytokines, along with peripheral blood mononuclear cells. According to the present invention, a large quantity of natural killer cells can be induced and proliferated from a small quantity of peripheral blood mononuclear cells even without the use of high-cost equipment or various kinds of expensive cytokines, thereby making it possible to significantly improve the efficiency and efficacy of the prevention and treatment of cancer using the natural killer cells.

Claims (22)

1 . A method for treating a cancer in a subject in need thereof, wherein the method comprises:

expanding natural killer cells in a co-culture comprising peripheral blood mononuclear cells and feeder cells, wherein the feeder cells comprise irradiated Jurkat cells and irradiated Epstein-Barr virus transformed lymphocyte continuous cell line (EBV-LCL) cells and the co-culture is in the presence of one or more cytokines; and

administering an effective amount of a composition comprising the expanded natural killer cells to the subject, thereby treating the cancer.

2 . The method of claim 1 , wherein the one or more cytokines is selected from IL-2, IL-15, IL-21, Flt3-L, SCF, or IL-7.

3 . The method of claim 2 , wherein the one or more cytokines is IL-2.

4 . The method of claim 3 , wherein the IL-2 is present at a concentration of 500 U/ml.

5 . The method of claim 1 , wherein the peripheral blood mononuclear cells are obtained from a normal person or a person suffering from the cancer.

6 . The method of claim 1 , wherein the peripheral blood mononuclear cells are obtained from the subject.

7 . The method of claim 1 , wherein the peripheral blood mononuclear cells are obtained from a healthy subject.

8 . The method of claim 1 , wherein each of the irradiated Jurkat cells or the irradiated EBV-LCL cells is obtained by treatment with radiation of 100 to 500 Gy.

9 . The method of claim 1 , wherein the peripheral blood mononuclear cells are co-cultured for 5 days to 14 days.

10 . The method of claim 1 , wherein the peripheral blood mononuclear cells and feeder cells are mixed at a ratio of 1:0.5:0.5 during the co-culturing.

11 . The method of claim 1 , wherein the co-culturing comprises adding the irradiated Jurkat cells, the irradiated EBV-LCL cells and the one or more cytokines on the 1st to 15th day.

12 . The method of claim 1 , wherein the cancer comprises lung cancer, liver cancer, breast cancer, or blood cancer.

13 . A method for treating a cancer in a subject in need thereof, the method comprising:

providing a composition comprising natural killer cells, wherein providing the composition comprises expanding natural killer cells in a co-culture comprising peripheral blood mononuclear cells and feeder cells for 5 days to 14 days,

wherein the feeder cells comprise irradiated Jurkat cells and irradiated Epstein-Barr virus transformed lymphocyte continuous cell line (EBV-LCL) cells,

wherein the co-culture is in the presence of one or more cytokines, wherein the one or more cytokines comprise IL-2, and

wherein the peripheral blood mononuclear cells and feeder cells are mixed at a ratio of 1:0.5:0.5 during the co-culturing; and

administering an effective amount of the composition to the subject, thereby treating the cancer.

14 . The method of claim 13 , wherein the one or more cytokines are IL-2.

15 . The method of claim 13 , wherein the cancer comprises lung cancer, liver cancer, breast cancer, or blood cancer.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2020
From: KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION
To: NKMAX CO., LTD.
Reel/Frame 052713/0453 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2020
From: LEE, KYUNG MI; YEE, CASSIAN; LIM, SEON AH
To: KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION
Reel/Frame 052712/0909 →
Priority Claims (2)
KR 10-2012-0048165 · May 7, 2012 · national
KR 10-2013-0051442 · May 7, 2013 · national
Continuity (2)
Division 14399371
Related Publication 20180223257A1 · Aug 9, 2018
References Cited (400)
US 4645830A · Yasushi et al. · 1987 [cited by applicant]
US 5415874A · Bender et al. · 1995 [cited by applicant]
US 6194204B1 · Crawford et al. · 2001 [cited by applicant]
US 6261839B1 · Multhoff et al. · 2001 [cited by applicant]
US 7544355B2 · Velardi · 2009 [cited by applicant]
US 7829075B2 · Novak et al. · 2010 [cited by applicant]
US 8257970B2 · Lowdell · 2012 [cited by applicant]
US 8318491B2 · Choi et al. · 2012 [cited by applicant]
US 8637308B2 · Lowdell · 2014 [cited by applicant]
US 8877182B2 · Alici · 2014 [cited by applicant]
US 8926964B2 · Hariri et al. · 2015 [cited by applicant]
US 9121008B2 · Tsai · 2015 [cited by applicant]
US 9175266B2 · Peled et al. · 2015 [cited by applicant]
US 9222072B2 · Chang · 2015 [cited by applicant]
US 9260696B2 · Kaufman et al. · 2016 [cited by applicant]
US 9404083B2 · Yonemitsu et al. · 2016 [cited by applicant]
US 9464274B2 · Hariri et al. · 2016 [cited by applicant]
US 9623082B2 · Copik et al. · 2017 [cited by applicant]
US 9655925B2 · Lowdell · 2017 [cited by applicant]
US 9834753B2 · Min et al. · 2017 [cited by applicant]
US 9938498B2 · Lee et al. · 2018 [cited by applicant]
US 10151745B2 · Hermine et al. · 2018 [cited by applicant]
US 10195231B2 · Liao et al. · 2019 [cited by applicant]
US 10300089B2 · Copik et al. · 2019 [cited by applicant]
US 10450547B1 · Sun et al. · 2019 [cited by applicant]
US 10463715B2 · Copik et al. · 2019 [cited by applicant]
US 10590385B2 · Park · 2020 [cited by examiner]
US 10774311B2 · Campana et al. · 2020 [cited by applicant]
US 10864245B2 · Romagnani et al. · 2020 [cited by applicant]
US 11066644B2 · Park et al. · 2021 [cited by applicant]
US 11110126B2 · Lee et al. · 2021 [cited by applicant]
US 11504396B2 · Kim et al. · 2022 [cited by applicant]
US 12098388B2 · Park et al. · 2024 [cited by applicant]
US 20030068306A1 · Dilber · 2003 [cited by applicant]
US 20040173778A1 · Roncarolo · 2004 [cited by examiner]
US 20040224402A1 · Bonyhadi · 2004 [cited by examiner]
US 20050191743A1 · Wu et al. · 2005 [cited by applicant]
US 20060067914A1 · Iizuka et al. · 2006 [cited by applicant]
US 20080166326A1 · Lowdell · 2008 [cited by applicant]
US 20090068141A1 · Parkhurst et al. · 2009 [cited by applicant]
US 20090104170A1 · Childs et al. · 2009 [cited by applicant]
US 20100322898A1 · Nelson et al. · 2010 [cited by applicant]
US 20110135687A1 · Koelle et al. · 2011 [cited by applicant]
US 20120121544A1 · Choi et al. · 2012 [cited by applicant]
US 20130059379A1 · Schmidt-Wolf · 2013 [cited by applicant]
US 20130287688A1 · Jain et al. · 2013 [cited by applicant]
US 20140017713A1 · Lee et al. · 2014 [cited by applicant]
US 20140023626A1 · Pelled et al. · 2014 [cited by applicant]
US 20140080148A1 · Spanholtz · 2014 [cited by applicant]
US 20140120072A1 · Yonemitsu et al. · 2014 [cited by applicant]
US 20140286898A1 · Gavin et al. · 2014 [cited by applicant]
US 20140369955A1 · Markovic et al. · 2014 [cited by applicant]
US 20140369977A1 · Zhang et al. · 2014 [cited by applicant]
US 20150118207A1 · Min et al. · 2015 [cited by applicant]
US 20150139943A1 · Campana et al. · 2015 [cited by applicant]
US 20150152387A1 · Lee et al. · 2015 [cited by applicant]
US 20160068584A1 · Bechard et al. · 2016 [cited by applicant]
US 20160229901A1 · Merchant · 2016 [cited by applicant]
US 20160297821A1 · Stefinovic et al. · 2016 [cited by applicant]
US 20160324964A1 · Markovic et al. · 2016 [cited by applicant]
US 20170002322A1 · Hariri et al. · 2017 [cited by applicant]
US 20170107490A1 · Maeurer · 2017 [cited by applicant]
US 20170121673A1 · Wolpe · 2017 [cited by applicant]
US 20170240859A1 · Yamano et al. · 2017 [cited by applicant]
US 20170349880A1 · Doucey et al. · 2017 [cited by applicant]
US 20180010087A1 · Miltenyi et al. · 2018 [cited by applicant]
US 20180015123A1 · Choi et al. · 2018 [cited by applicant]
US 20180021378A1 · Kang et al. · 2018 [cited by applicant]
US 20180057795A1 · Childs et al. · 2018 [cited by applicant]
US 20180155690A1 · Park et al. · 2018 [cited by applicant]
US 20180161371A1 · O'Dwyer · 2018 [cited by applicant]
US 20180223257A1 · Lee et al. · 2018 [cited by applicant]
US 20180245044A1 · Granzin et al. · 2018 [cited by applicant]
US 20180291341A1 · Molleryd et al. · 2018 [cited by applicant]
US 20180371093A1 · Bilic et al. · 2018 [cited by applicant]
US 20190112577A1 · Wu et al. · 2019 [cited by applicant]
US 20190153389A1 · Ffischkoff et al. · 2019 [cited by applicant]
US 20190169276A1 · Novak et al. · 2019 [cited by applicant]
US 20190309070A1 · Copik et al. · 2019 [cited by applicant]
US 20190314412A1 · Copik et al. · 2019 [cited by applicant]
US 20190330592A1 · Hariri et al. · 2019 [cited by applicant]
US 20190345449A1 · Park et al. · 2019 [cited by applicant]
US 20200095543A1 · BhattacharyA et al. · 2020 [cited by applicant]
US 20200108096A1 · Min et al. · 2020 [cited by applicant]
US 20200172869A1 · Park et al. · 2020 [cited by applicant]
US 20200181220A1 · Ptacin et al. · 2020 [cited by applicant]
US 20200188484A1 · Ptacin et al. · 2020 [cited by applicant]
US 20200246179A1 · Peyman · 2020 [cited by applicant]
US 20200392177A1 · Martinez Botella et al. · 2020 [cited by applicant]
US 20210032597A1 · Park et al. · 2021 [cited by applicant]
US 20210228640A1 · Lu et al. · 2021 [cited by applicant]
US 20220249564A1 · Yu et al. · 2022 [cited by applicant]
US 20230002731A1 · Park et al. · 2023 [cited by applicant]
US 20250059510A1 · Park et al. · 2025 [cited by applicant]
US 20250195574A1 · Song et al. · 2025 [cited by applicant]
US 20250255903A1 · Song et al. · 2025 [cited by applicant]
US 20260048083A1 · Song et al. · 2026 [cited by applicant]
CN 102533648A · 2012 [cited by applicant]
CN 104705291 · 2015 [cited by applicant]
CN 105524880 · 2016 [cited by applicant]
CN 105524880A · 2016 [cited by applicant]
CN 107922925A · 2018 [cited by applicant]
CN 107970258 · 2018 [cited by applicant]
CN 104321425 · 2018 [cited by applicant]
CN 114929249 · 2022 [cited by applicant]
EP 409655 · 1991 [cited by applicant]
EP 248642 · 1992 [cited by applicant]
EP 1941027 · 2014 [cited by applicant]
EP 2401364 · 2015 [cited by applicant]
EP 2923208 · 2015 [cited by applicant]
EP 1899459 · 2016 [cited by applicant]
EP 2878666 · 2017 [cited by applicant]
EP 2142642 · 2017 [cited by applicant]
EP 2794859 · 2017 [cited by applicant]
EP 3057986 · 2017 [cited by applicant]
EP 2593542 · 2018 [cited by applicant]
EP 2841563 · 2019 [cited by applicant]
EP 2411507 · 2019 [cited by applicant]
EP 2725100 · 2019 [cited by applicant]
EP 2812011 · 2020 [cited by applicant]
EP 2881462 · 2020 [cited by applicant]
EP 3656851 · 2020 [cited by applicant]
EP 2947144 · 2020 [cited by applicant]
EP 3344759 · 2020 [cited by applicant]
JP 2015502756 · 2015 [cited by applicant]
JP 2016008198A · 2016 [cited by applicant]
JP 2017508479 · 2017 [cited by applicant]
JP 2017515506 · 2017 [cited by applicant]
KR 1020120016427 · 2012 [cited by examiner]
KR 102010007877 · 2012 [cited by applicant]
KR 1020180012938A · 2018 [cited by applicant]
KR 1020180012942A · 2018 [cited by applicant]
KR 1020190093499 · 2019 [cited by applicant]
KR 1020190093500 · 2019 [cited by applicant]
RU 2394561 · 2008 [cited by applicant]
TW I439275B · 2014 [cited by applicant]
WO WO1990009798 · 1990 [cited by applicant]
WO 0000587A1 · 2000 [cited by applicant]
WO 2004011673A1 · 2004 [cited by applicant]
WO WO2006050270A2 · 2006 [cited by examiner]
WO 2006058248A2 · 2006 [cited by applicant]
WO WO2008118369A2 · 2008 [cited by applicant]
WO WO2010013947 · 2010 [cited by applicant]
WO 2012009422A1 · 2012 [cited by applicant]
WO 2013168978A1 · 2013 [cited by applicant]
WO WO2014005072 · 2014 [cited by applicant]
WO WO2014123879 · 2014 [cited by applicant]
WO WO2015125113 · 2015 [cited by applicant]
WO WO2015132415 · 2015 [cited by applicant]
WO WO2015154012A1 · 2015 [cited by applicant]
WO 2016096903A1 · 2016 [cited by applicant]
WO WO2016122147 · 2016 [cited by applicant]
WO WO2016209021 · 2016 [cited by applicant]
WO WO2017037083A1 · 2017 [cited by applicant]
WO WO2017188790 · 2017 [cited by applicant]
WO WO2017196657 · 2017 [cited by applicant]
WO 2018118907A1 · 2018 [cited by applicant]
WO WO2018161026A1 · 2018 [cited by applicant]
WO WO2018194215 · 2018 [cited by applicant]
WO WO2019014684 · 2019 [cited by applicant]
WO WO2019046444 · 2019 [cited by applicant]
WO WO2019152663 · 2019 [cited by applicant]
WO WO2019165097 · 2019 [cited by applicant]
WO WO2019168222 · 2019 [cited by applicant]
WO WO2019175802 · 2019 [cited by applicant]
WO WO2019182392 · 2019 [cited by applicant]
WO WO2019213610 · 2019 [cited by applicant]
WO WO2019229109 · 2019 [cited by applicant]
WO WO2020006139 · 2020 [cited by applicant]
WO WO2020095058 · 2020 [cited by applicant]
WO WO2020101361 · 2020 [cited by applicant]
WO WO2020103777 · 2020 [cited by applicant]
WO WO2020104676 · 2020 [cited by applicant]
WO WO2020112493 · 2020 [cited by applicant]
WO WO2020112563 · 2020 [cited by applicant]
WO WO2020146221 · 2020 [cited by applicant]
WO WO2020172328 · 2020 [cited by applicant]
WO WO2020187340 · 2020 [cited by applicant]
WO WO2020205359 · 2020 [cited by applicant]
WO WO2021108389 · 2021 [cited by applicant]
WO WO2023235806 · 2023 [cited by applicant]
WO WO2024015822 · 2024 [cited by applicant]
WO WO2024036005 · 2024 [cited by applicant]
WO WO2024036226 · 2024 [cited by applicant]
WO WO2024238387 · 2024 [cited by applicant]
Lee et al., machine translation for KR-10-2012-0016427, published Feb. 24, 2012, pp. 1-32. (Year: 2012). [cited by examiner]
Edited by Mary L. Disis, Immunotherapy of Cancer, Humana Press, 2006, Chapter 3/ NK Cells and Cancer Immunotherapy, pp. 47-51. (Year: 2006). [cited by examiner]
Lim et al., “GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo”, LPOS, Jan. 2013, vol. 8, No. 1, e53611, pp. 1-9. (Year: 2013). [cited by examiner]
Marquedant, Katie, “Study reveals how to activate natural killer cells to protect against cancer and other diseases”, https://www.massgeneral.org/news/press-release/study-reveals-how-to-activate-natural-killer-cells-to-… [cited by examiner]
Weiler, Nicholas, “Invisible' Stem Cells Evade Natural Killer Cells Using Immune Off-Switch”, https://www.ucsf.edu/news/2021/01/419496/invisible-stem-cells-evade-natural-killer-cells-using-immune-switch, 2021, pp. 1-9. … [cited by examiner]
Chan et al., “The changing role of natural killer cells in cancer metastasis”, The Journal of Clinical Investigation, 2022, vol. 132, No. 6, pp. 1-9. (Year: 2022). [cited by examiner]
Van De Griend et al., “Rapid Expansion of Human Cytotoxic T Cell Clones: Growth Promotion by a Heat-Labile Serum Component and by Various Types of Feeder Cells”, Journal of Immunological Methods, 1984, vol. 66, pp. 285-… [cited by examiner]
U.S. Appl. No. 17/009,558, filed Sep. 1, 2020, Park et al. [cited by applicant]
Allan et al., “The role of 2 FOXP3 isoforms in the generation of human CD4 [cited by applicant]
International Search Report mailed on Jul. 29, 2013 for International Patent Application No. PCT/KR2013/003981 in 5 pages. [cited by applicant]
Written Opinion mailed on Jul. 29, 2013 for International Patent Application No. PCT/KR2013/003981 in 6 pages. [cited by applicant]
Joao F. Lacerda et al., “Humans Epstein-Barr Virus (EBV)-specific Cytotoxic T Lymphocytes Home Preferentially to and Induce Selective Regressions of Autologous EBV-indeed B Cell Lymphoproliferations in Xenografted C.B-1… [cited by applicant]
Liu et al., “Growth and Activation of Natural Killer Cells Ex Vivo from Children with Neuroblastoma for Adoptive Cell Therapy”, Clinical Cancer Research, vol. 19, No. 8, pp. 2132-2143, (2013). [cited by applicant]
Motohashi, S. et al., “A Phase I Study of In vitro Expanded Natural Killer T Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer,” [cited by applicant]
Numbenjapon et al., “Antigen-independent and antigen-dependent methods to numerically expand CD19-specific CD8 [cited by applicant]
Rubnitz et al., “NKAML: A Pilot Study to Determine the Safety and Feasibility of Haploidentical Natural Killer Cell Transplantation in Childhood Acute Myeloid Leukemia”, Journal of Clinical Onocology, vol. 28, No. 6, pp… [cited by applicant]
Tai et al., “CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2” Nature Immunology, vol. 6, No. 2, pp. 152-162 (2005). [cited by applicant]
Turtle et al., “Artificial antigen presenting cells for use in adoptive immunotherapy”, NIH Public Access, Author Manuscript, Cancer J. Author manuscript; available in PMC Jul. 1, 2011, Published in final edited form as… [cited by applicant]
File history of U.S. Appl. No. 14/399,371, filed Nov. 6, 2014. [cited by applicant]
File history of U.S. Appl. No. 16/523,964, filed Jul. 26, 2019. [cited by applicant]
File history of U.S. Appl. No. 16/773,888, filed Jan. 27, 2020. [cited by applicant]
International Search Report and Written Opinion mailed on Apr. 25, 2019 for International Patent Application No. PCT/US2019/016076 in 15 pages. [cited by applicant]
Notice of Allowance dated Apr. 23, 2021 in U.S. Appl. No. 16/773,888 in 11 pages. [cited by applicant]
Notice of Allowance dated Feb. 4, 2021 in U.S. Appl. No. 16/773,888 in 14 pages. [cited by applicant]
Loza et al., The IL-12 Signature: NK Cell Terminal CD56 [cited by applicant]
#3037: A phase I/IIa randomized trial evaluating safety and efficacy of SNK01 (non-genetically modified autologous natural killer cells with enhanced cytotoxicity) plus Pembrolizumab in patients with Stage IV Non-Small … [cited by applicant]
#3037: A phase I/IIa randomized trial evaluating safety and efficacy of SNK01 (non-genetically modified autologous natural killer cells with enhanced cytotoxicity) plus Pembrolizumab in patients with Stage IV Non-Small … [cited by applicant]
A. Jiang et al., Expansion of NK cells by engineered K562 cells co-expressing 4-1BBL and mMICA, combined with soluble IL-21. Cell Immunol. Jul. 2014;290(1):10-20. [cited by applicant]
Akagi et al., Caspase-8 cleavage of the interleukin-21 (IL-21) receptor is a negative feedback regulator of IL-21 signaling, FEBS Letters, vol. 585, pp. 1835-1840, 2011. [cited by applicant]
Apel et al., Chem. Ingen. Tech., 85:103-110 (2013). [cited by applicant]
Asao, H., et al., Cutting Edge: The Common γ-Chain Is an Indispensable Subunit of the IL-21 Receptor Complex, Journal of Immunology, vol. 167, No. 1, pp. 1-5, 2001. [cited by applicant]
Bauernhofer, T. et al., Preferential apoptosis of CD56dim Natural Killer Cell Subset in Patients With Cancer, European Journal of Immunology, vol. 33, pp. 119-124, 2003. [cited by applicant]
Berg et al., “Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells”, Cytotherapy 2009; 11:341-55. [cited by applicant]
Brady J., et al., IL-21 Induces the Functional Maturation of Murine NK Cells, Journal of Immunology, vol. 172, No. 4, pp. 2048-2058, 2004. [cited by applicant]
Burns et al., “IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial”, Bone Marrow Transplantation (2003) 32, 177-186. [cited by applicant]
Carlens S. A New Method For In Vitro Expansion of Cytotoxic Human CD3-CD56+ Natural Killer Cells, Human Immunology, vol. 62, No. 10, pp. 1092-1098, 2001. [cited by applicant]
Carrega, P.et al., Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56brightCD16-cells and display an impaired capability to kill tumor cells, Cancer, vol. 112, pp. 863-875, 2008. [cited by applicant]
Childs et al., “Bringing natural killer cells to the clinic: ex vivo manipulation”, Hematology Am Soc Hematol Educ Program 2013; 2013:234-46. [cited by applicant]
Chu et al., CS1-Specific Chimeric Antigen Receptor (CAR)-Engineered Natural Killer Cells Enhance In Vitro and In Vivo Anti-tumor Activity Against Human Multiple Myeloma. Leukemia, vol. 28, pp. 917-927, 2014. [cited by applicant]
Claims in U.S. Appl. No. 17/009,558, in a preliminary amendment filed Sep. 30, 2020. [cited by applicant]
Corrected Notice of Allowability dated Jun. 18, 2021 in U.S. Appl. No. 16/773,888 in 3 pages. [cited by applicant]
Declaration Under 37 C.F.R $1.132 by Kyung Mi Lee in U.S. Appl. No. 14/399,371, dated Sep. 19, 2016, in 33 pages. [cited by applicant]
Denman et al., “Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells”, PLoS ONE 7(1), Jan. 18, 2019 in 13 pages. [cited by applicant]
Disanto at al., Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain, Proc. Natl. Acad. Sci USA, vol. 92, pp. 377-381, 1995. [cited by applicant]
DiSanto J. P., et al., Absence of interleukin 2 production in a severe combined immunodeficiency disease syndrome with T cells, Journal of Experimental Medicine, vol. 171, No. 5, pp. 1697-1704, 1990. [cited by applicant]
Final Office Action in International Japanese Application No. 2020-541915 dated Jan. 12, 2021 in 5 pages. [cited by applicant]
Final Office Action in U.S. Appl. No. 15/756,955 dated Nov. 6, 2020 in 12 pages. [cited by applicant]
First Action Interview Pilot Program Pre-Interview Communication mailed Oct. 1, 2019, in U.S. Appl. No. 16/523,964 7 pages. [cited by applicant]
Fujisaki et al., “Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy,” Expansion of Highly Cytotoxic NK Cells, American Association for Cancer Research, 69: (9), May 1, 2009, in 8 pages. [cited by applicant]
Granzin et al., “Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy”, Cytotherapy 2015; 17:621-32. [cited by applicant]
Granzin et al., “Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma”, Oncoimmunology 2016, vol. 5, No. 9 in 11 pages. [cited by applicant]
Granzin, M. et al., Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation, Front. Immunol. 2017, vol. 8:458, pp. 1-18. [cited by applicant]
Habib et al., IL-21: A novel IL-2-family lymphokine that modulates B, T, and natural killer cell responses, Molecular mechanisms in allergy and clinical immunology, pp. 1033-1044, 2003. [cited by applicant]
Iyengar et al., “Purification of Human Natural Killer Cells Using a Clinical-Scale Immunomagnetic Method”, International Society for Cellular Therapy, Cytotherapy, vol. 5, No. 6, 2003, 479-484. [cited by applicant]
Jinushi, M., et al., Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas, Journal of Hepatology, vol. 43, No. 6, … [cited by applicant]
Kim et al., A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer, Cancer Research and Treatment, 2021. [cited by applicant]
Klingemann et al., “Ex vivo expansion of natural killer cells for clinical applications”, Cytotherapy 2004; 6:15-22. [cited by applicant]
Kloess et al., “Optimization of human NK cell manufacturing: Fully-automated separation, improved ex vivo expansion using IL-21 with autologous feeder cells and generation of anti-CD123-CAR-expressing effector cells”, H… [cited by applicant]
Koehl et al., “IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation”, Blood Cells Mol Dis 2004; 33:261-6. [cited by applicant]
Koehl, U. et al., Clinical grade purification and expansion of NK cell products for an optimized manufacturing protocol, Front. Oncol. 2013, vol. 3: Oncol. 2013, vol. 3: 118, pp. 1-12. [cited by applicant]
Lang et al., “Clinical Scale Isolation of T Cell-depleted CD56+ Donor Lymphocytes in Children”, Bone Marrow Transplantation (2002) 29, 497-502, in 6 pages. [cited by applicant]
Lim et al., Effect of exposure to interleukin-21 at various time points on human natural killer cell culture. Cytotherapy, 16:1419-1431 (2014). [cited by applicant]
Lim, A. L., et al., Ex Vivo Expansion of Highly Cytotoxic Human NK Cells by Cocultivation with Irradiated Tumor Cells for Adoptive Immunotherapy, Therapeutics, Targets, and Chemical Biology, Cancer Research, vol. 73, No… [cited by applicant]
Loza et al., The IL-12 signature: NK cell terminal CD56+high stage and effector functions. Journal of Immunology, vol. 172, No. 88-96. 2004. [cited by applicant]
Miller et al., “Successful Adoptive Transfer and in Vivo Expansion of Human Haploidentical NK Calls in Cancer Patients”, American Society of Hematology, 2005 in 33 pages. [cited by applicant]
Miller., Low Dose Subcutaneous Interleukin-2 After Autologous Transplantation Generates Sustained In Vivo Natural Killer Cell Activity, Biology of Blood and Marrow Transplantation, vol. 3, No. 1, pp. 34-44, 1997. [cited by applicant]
Mocchegiani, E., et al. Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma. Br Journal of Cancer, No. 79, … [cited by applicant]
MojoSort(TM) Human NK Cell Isolation Kit, Biolegend, Apr. 18, 2016, [retrieved on Dec. 22, 2020]. [cited by applicant]
Mrozek, E., et al., Role of Interleukin-15 in the Development of Human CD56' Natural Killer Cells From CD34+ Hematopoietic Progenitor Cells, Rapid Communication, Blood, vol. 87, No. 7, pp. 2632-2640, 1996. [cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 16/773,888 dated Mar. 30, 2020 in 9 pages. [cited by applicant]
Notice of Allowance mailed Dec. 20, 2019, in U.S. Appl. No. 16/523,964 in 8 pages. [cited by applicant]
Notice of Allowance mailed Jul. 28, 2020, in U.S. Appl. No. 16/773,888 in 9 pages. [cited by applicant]
Office Action Dated Apr. 8, 2021 in EP Application No. 19746979.4 in 1 page. [cited by applicant]
Office Action Dated Dec. 23, 2020 in Japanese Application No. 2020-541915 in 10 pages. [cited by applicant]
Office Action in Australian Application No. 2019215034, dated Aug. 12, 2020. [cited by applicant]
Office Action received in Russian Application No. 2020128764 dated Jan. 20, 2021. [cited by applicant]
Office Action with English Translation dated Dec. 22, 2021 in Iranian Application No. 139950140003004045 in 14 pages. [cited by applicant]
Office Action with English Translation Dated Dec. 23, 2021 in Saudi Arabian Patent Application No. 520412566 in 6 pages. [cited by applicant]
Office Action with English Translation Dated Feb. 10, 2022 in European Patent Application No. 19746979.4 in 18 pages. [cited by applicant]
Office Action with English Translation Dated Jan. 7, 2022 in Chinese Patent Application No. 201980011279.4 in 10 pages. [cited by applicant]
Office Action with English Translation in Iranian Application No. 139950140003004045 in 12 pages, dated May 24, 2021. [cited by applicant]
Office Action with English Translation in Japanese Patent Application No. 2020-541915 in 13 pages dated Jun. 8, 2021. [cited by applicant]
Office Action with English Translation in Russian Application No. 2020128764/10(051457) in 12 paged, dated Apr. 14, 2021. [cited by applicant]
Office Action with English Translation in Russian Application No. 2020128764/10(051457), dated Oct. 12, 2021. [cited by applicant]
Ogasawara, K. et al. Requirement for I RF-1 in the microenvironment supporting development of natural killer cells, Nature, vol. 391, pp. 700-703, 1998. [cited by applicant]
Park et al., “Gene expression analysis of ex vivo expanded and freshly isolated NK cells from cancer patients”, J Immunother 33(9): 945-955 (2010). [cited by applicant]
Parrish-Novak, J., et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function, Nature, vol. 408, 57-63, 2000. [cited by applicant]
Passweg et al., “Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation” Nature Publishing Group, Leukemia 18, 2004, 1835-1838. [cited by applicant]
Patent examination report dated Sep. 29, 2020 in New Zealand Application No. 766453. [cited by applicant]
Response to First Action Interview Office Action filed Oct. 23, 2019, in U.S. Appl. No. 16/523,964 in 12 pages. [cited by applicant]
Roseneberg al., “Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer” ClinicalTrials.gov: NCT00328861, May 22, 2006 in 10 pages. [cited by applicant]
Shibuya A. et al., Lymphokine Requirement for the Generation of Natural Killer Cells From CD34+ Hematopoietic Progenitor Cells, Blood, vol. 85, pp. 3538-3546, 1995. [cited by applicant]
Smyth. New Aspects of Natural-Killer-Cell Surveillance and Therapy of Cancer, Nature Reviews Cancer, vol. 2, No. 11, pp. 850-861, 2002. [cited by applicant]
Strengell et al., IL-21 in Synergy with IL-15 or IL-18 Enhances IFN-y Production in Human NK and T Cells, Journal of Immunology, vol. 170, pp. 5464-5469, 2003. [cited by applicant]
Supplementary European Search Report completed Mar. 10, 2021 received in European Application No. 19746979 in 287 pages. [cited by applicant]
Tajima, F., et al., Natural Killer Cell Activity and Cytokine Production a Prognostic Factors in Adult Acute Leukemia, Leukemia, vol. 10m pp. 478-482, 1996. [cited by applicant]
Takaki, R., et al., IL-21 Enhances Tumor Rejection through a NKG2D-Dependent Mechanism, Journal of Immunology, vol. 175, No. 4, pp. 2167-2173, 2005. [cited by applicant]
Wendt et al., “Interleukin-21 Differentially Affects Human Natural Killer Cell Subsets”, The Authors Journal compilation, 2007 Blackwell Publishing Ltd, Immunology, 122, 486-495. [cited by applicant]
Xiaomei, L. et al., Expansion of NK cells from PBMCs using immobilized 4-1 BBL and interleukin-21, International Journal of Oncology, vol. 47, No. 1, pp. 335-342, 2015. [cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 14/399,371 dated Aug. 11, 2017 in 9 pages. [cited by applicant]
International Search Report and Written Opinion mailed on Feb. 12, 2021 for International Patent Application No. PCT/US2020/061984 in 22 pages. [cited by applicant]
Office Action dated Mar. 10, 2022 received in European Application No. 19746979 in 18 pages. [cited by applicant]
Office Action with English Summary dated Aug. 23, 2022 in Malaysian Application No. PI2020003935 in 4 pages. [cited by applicant]
Korean Application with English Translation filed May 7, 2013, in Korean Application No. 10-2013-051442 in 66 pages. [cited by applicant]
Korean Application with English Translation filed May 7, 2012, in Korean Application No. 10-2012-0048165 in 50 pages. [cited by applicant]
Lehmann, C. et al., Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells, British Journal of Haematology, vol. 114, 660-665, 2001. [cited by applicant]
Office Action with English Translation in Indonesia Patent Application No. P-00202006013, dated May 12, 2022. [cited by applicant]
Notice of Acceptance with English Translation in Indonesia Patent Application No. P-00202006013, dated Jun. 19, 2023. [cited by applicant]
Office Action with English Translation in Japanese Patent Application No. 2020-541915, dated Oct. 26, 2022. [cited by applicant]
Office Action with English Translation in Iran Patent application No. 139950140003010289, dated Dec. 12, 2022. [cited by applicant]
Office Action in Malaysian Application No. PI2020003935, dated Dec. 7, 2022. [cited by applicant]
Office Action with English Translation in Egyptian Patent Application No. 1112/2020 D1, dated Jan. 18, 2023. [cited by applicant]
Office Action with English Translation in Japanese Patent Application No. 2021-165698, dated Jan. 31, 2023. [cited by applicant]
Office Action in U.S. Appl. No. 17/009,558 Dated Mar. 27, 2023. [cited by applicant]
Office Action with English Translation in Egyptian Patent Application No. 1112/2020, dated Apr. 10, 2023. [cited by applicant]
Office Action and Search Report in Malaysia Application No. PI2020003935 dated Aug. 23, 2022. [cited by applicant]
Office Action in Indian Application No. 202017036642 dated May 18, 2023. [cited by applicant]
Modified Substantive Examination Adverse Report (Section 30(20)) and Search Report in Malaysian Application No. PI2021005196 dated May 24, 2023. [cited by applicant]
Office Action in Phillipine Application No. 1-2020-551151 dated Jul. 17, 2023. [cited by applicant]
Office Action with English Translation in Vienamese Application No. 1-2020-04880 dated Jun. 22, 2023. [cited by applicant]
Office Action with English Translation in Ukrainian Application No. a 2020 05595 dated Apr. 11, 2023. [cited by applicant]
Chan et.al, The Changing Role of Natural Killer Cells in Cancer Metastasis, The Journal of Clinical Investigation, 2022, vol. 132, No. 6, pp. 1-9. [cited by applicant]
Notice of Allowance mailed Jul. 16, 2020, in Mexican Application No. MX/a/2020/008039 in 2 pages. [cited by applicant]
Notice of Allowance with English Translation in Japanese Application No. 2021-165698, dated Jul. 14, 2023. [cited by applicant]
Notice of Allowance in U.S. Appl. No. 17/009,558, dated Oct. 17, 2023 in 13 pages. [cited by applicant]
Office Action received in Philippine Patent Application No. 1-2020-551151, dated Nov. 16, 2023. [cited by applicant]
Office Action with English Summary dated Aug. 22, 2023 in Bangkok—Patent application No. 2001004285. [cited by applicant]
Office Action with English Summary dated Sep. 12, 2023 in Saudi Arabia—Patent application No. 520420878. [cited by applicant]
Office Action with English Summary received Iran Patent Application No. 140150140003000836, dated Dec. 12, 2023. [cited by applicant]
Office Action with English Translation in Iran Patent application No. 139950140003010289, dated Jan. 13, 2023. [cited by applicant]
Chantal Reina-Ortiz, Expanded NK Cells From Umbilical Cord Blood and Adult Peripheral Blood Combined With Daratumumab Are Effective Against Tumor Cells From Multiple Myeloma Patients, OncoImmunology, Jan. 2021, vol. 10,… [cited by applicant]
Corrected Notice of Allowability received in U.S. Appl. No. 17/009,558, dated Aug. 26, 2024, in 3 pages. [cited by applicant]
Corrected Notice of Allowability received in U.S. Appl. No. 17/009,558, dated Aug. 7, 2024, in 3 pages. [cited by applicant]
De Rham, Casimir, et al., The Proinflammatory Cytokines IL-2, IL-15 and IL-21 Modulate the Repertoire of Mature Human Natural Killer Cell Receptors, Arthritis Research & Therapy 2007, 9:R125. [cited by applicant]
Extended European Search Report, received in European Patent Application No. 20892302.9, dated Jan. 3, 2024. [cited by applicant]
File History of U.S. Appl. No. 16/773,888, filed Sep. 1, 2020. [cited by applicant]
Final Office Action received in U.S. Appl. No. 14/399,371 dated Jan. 25, 2017 in 15 pages. [cited by applicant]
First Examination Report, received in Australian Patent Application No. 2021266198, dated Feb. 27, 2024. [cited by applicant]
First Substantive Examination Report, received in United Arab Emirates Patent Application No. P6001104/2020, dated Dec. 20, 2023. [cited by applicant]
Hui Xu, et al. Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer's Disease, Frontiers in Immunology, Aug. 2021, vol. 12, pp. 1-12. [cited by applicant]
International Preliminary Report on Patentability, received in PCT Application No. PCT/US2020/061984, dated May 17, 2022, in 11 pages. [cited by applicant]
Krause, S., et al., Treatment of Colon and Lung Cancer Patients with ex Vivo Heat Shock Protein 70-Peptide-Activated, Autologous Natural Killer Cells: A Clinical Phase I Trial, Clinical Cancer Research, vol. 10, 3699-37… [cited by applicant]
Mao Lin, et al. Pembrolizumab Plus Allogeneic NK Cells in Advanced Non-Small Cell Lung Cancer Patients, The Journal of Clinical Investigation, 2020; vol. 130, No. 5, pp. 2560-2569. [cited by applicant]
Non-Final Office Action received in Application No. 201380028253.3 dated Mar. 28, 2017. [cited by applicant]
Notice of Allowance Dated Jul. 28, 2020 in U.S. Appl. No. 16/773,888 in 9 pages. [cited by applicant]
Notice of Allowance received in U.S. Appl. No. 17/009,558, dated May 24, 2024, in 11 pages. [cited by applicant]
Notice of Allowance received in U.S. Appl. No. 17/009,558, dated Feb. 5, 2024, in 8 pages. [cited by applicant]
Notice of Preliminary Rejection, received in Korean Patent Application No. 10-2019-0001981, dated Jan. 11, 2024. [cited by applicant]
Notice of Preliminary Rejection, received in Korean Patent Application No. 10-2019-0001983, dated Jan. 19, 2024. [cited by applicant]
Office Action Dated Apr. 1, 2021 in New Zealand Application No. 766453 in 3 pages. [cited by applicant]
Office Action Dated Aug. 13, 2021 in New Zealand Application No. 766453 in 4 pages. [cited by applicant]
Office Action Dated Dec. 23, 2020 in Japanese Application No. 2020-541915 in 1 O pages. [cited by applicant]
Office Action Dated Feb. 22, 2022 in New Zealand Application No. 766453 in 3 pages. [cited by applicant]
Office Action Dated Mar. 30, 2020 in U.S. Appl. No. 16/773,888 in 9 pages. [cited by applicant]
Office Action in Korean Patent Application No. 10-2019-7021322 Dated Mar. 17, 2023. [cited by applicant]
Office Action received in European Patent Application No. 19746979.4, dated Jun. 20, 2024, in 20 pages. [cited by applicant]
Office Action received in Australian application No. 2019/215034 dated Aug. 12, 2020, in 3 pages. [cited by applicant]
Office Action received in Ukrainian Patent Application No. PI2020003935, dated Sep. 12, 2024, in 15 pages. [cited by applicant]
Sainiteesh Maddineni, et al. Emerging NK Cell Therapies for Cancer and the Promise of Next Generation Engineering of IPSC-Derived NK Cells, Journal for Immuno Therapy of Cancer, May 17, 2022, vol. 10, No. 5. [cited by applicant]
Second Examination Report, received in Egypt Patent Application No. 1112/2020 D1, dated Mar. 27, 2024. [cited by applicant]
Second Substantive Examination Report, received in Egypt Patent Application No. 1112/2020, dated Jan. 30, 2024. [cited by applicant]
Tran, et al., TGFI3R1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells, Clin Cancer Res. Oct. 10, 2016. pii: clincanres.174… [cited by applicant]
Walewski, J. et al., Evaluation of natural killer and lymphokine-activated killer (LAK) cell activity in vivo in patients treated with high-dose interleukin-2 and adoptive transfer of autologous LAK cells, Journal of Ca… [cited by applicant]
Written Opinion, received in Singapore Patent Application No. 11202205535X, dated Feb. 29, 2024. [cited by applicant]
Ye Li, et al. Human IPSC-Derived Natural Killer Cells Engineered With Chimeric Antigen Receptors Enhance Antitumor Activity, Cell Stem Cell, Aug. 2, 2018, pp. 181-182. [cited by applicant]
Chen et al., Development and dynamics of robust T-cell responses to CML under imatinib treatment, Blood. Jun. 1, 2008;111(11):5342-9. [cited by applicant]
Chinese Office Action dated Mar. 28, 2017 in Application No. 201380028253.3, 6 pages. [cited by applicant]
Egyptian Office Action in Patent Application No. 1112/2020 dated Oct. 28, 2024 in 12 pages. [cited by applicant]
Hassold et al., Enhancement of natural killer cell effector functions against selected lymphoma and leukemia cell lines by dasatinib, Int J Cancer. Sep. 15, 2012;131(6): E916-27. [cited by applicant]
International Preliminary Report on Patentability received for PCT Patent Application No. PCT/KR2013/003981, mailed on Nov. 20, 2014, 15 pages (9 pages of English Translation and 6 pages of Original Document). [cited by applicant]
International Preliminary Report on Patentability received for PCT Patent Application No. PCT/US2017/067289, mailed on Jul. 4, 2019, 7 pages. [cited by applicant]
International Preliminary Report on Patentability received for PCT Patent Application No. PCT/US2019/016076, mailed on Aug. 13, 2020, 7 pages. [cited by applicant]
International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2017/067289, mailed on Mar. 1, 2018, 8 pages. [cited by applicant]
Iranian Office Action dated Dec. 12, 2023 in Application No. 140150140003000836, 13 pages. [cited by applicant]
Iranian Office Action in Iranian Application No. 139950140003004045, dated Dec. 22, 2021 in 14 pages. [cited by applicant]
Kaneko et al., A report of three patients treated with immunocell therapy with imatinib mesylate, Anticancer Res. Sep.-Oct. 2004;24(5C):3303-3309. [cited by applicant]
Koelle, D. M., et al., “Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes,” J. Clin. Invest., vol. 91, 1993, pp. 961-968. [cited by applicant]
Lee et al, “Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in COCA-induced nypertensive rats”, Korean J Physiol Pharmacol, vol. 20 No. 5, p. 477-485, (2016). [cited by applicant]
Lee et al, “A randomized, multicenter, phase III trial to evaluate the efficacy and safety of Polmacoxib compared with Celecoxib and placebo for patients with Osteoarthritis”; Clin Ortho Surg. Dec. 1, 2017; 9(4): 439-45… [cited by applicant]
Min et al., Optimization of large-scale expansion and cryopreservation of human natural killer cells for anti-tumor therapy. Immune network. Aug. 21, 2018;18(4):e31; pp. 1-13. [cited by applicant]
Raj et al., Autologous Immune Enhancement Therapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, Indian J Hematol Blood Transfus. Sep. 2014;30(Suppl 1):202-4. [cited by applicant]
Russian Notice of Allowance dated Aug. 1, 2022 in Application No. 2020128764, 15 pages. [cited by applicant]
U.S. Office Action dated Jul. 10, 2020 in U.S. Appl. No. 15/948,619, 11 pages. [cited by applicant]
U.S. Office Action Dated Oct. 22, 2021 in U.S. Appl. No. 16/471,548 in 10 pages. [cited by applicant]
U.S. Office Action in U.S. Appl. No. 16/471,548 dated Mar. 11, 2022 in 10 pages. [cited by applicant]
File History of U.S. Appl. No. 17/009,558, filed Sep. 1, 2020. [cited by applicant]
International Search Report and Written Opinion, received in PCT Application No. PCT/US2023/067766, dated Oct. 17, 2023, in 14 pages. [cited by applicant]
International Search Report and Written Opinion, received in PCT Application No. PCT/US2023/070004, dated Nov. 29, 2023, in 17 pages. [cited by applicant]
International Search Report and Written Opinion, received in PCT Application No. PCT/US2023/070005, dated Dec. 8, 2023, in 19 pages. [cited by applicant]
International Search Report and Written Opinion, received in PCT Application No. PCT/US2023/071954, dated Jan. 2, 2024, in 18 pages. [cited by applicant]
International Search Report and Written Opinion, received in PCT Application No. PCT/US2023/080167, dated Apr. 19, 2024, in 18 pages. [cited by applicant]
Lim Dong-Pyo, et al. Effect of Exposure to Interleukin-21 at Various Time Points on Human Natural Killer Cell Culture, Cytotherapy, vol. 16, No. 10, Oct. 1, 2024, pp. 1419-1430. [cited by applicant]
Lim et al., GMP-Compliant, large scale expanded allogenic natural killer cells have potent cytolytic activity against cancer cells in vitro and in in vivo, PLoS One, Jan. 2013, vol. 8, No. 1, E53611, pp. 1-9. [cited by applicant]
Office Action in Philippines Application No. 1-2020-551151 dated Jul. 17, 2023. [cited by applicant]
Office Action received in Australian Patent Application No. 2021266198, dated Oct. 29, 2024, in 4 pages. [cited by applicant]
Office Action received in Australian Patent Application No. 2021266198, dated Aug. 9, 2024, in 4 pages. [cited by applicant]
Office Action received in Taiwan Patent Application No. 109141339, dated Jul. 31, 2024, in 41 pages. [cited by applicant]
Office Action received in Taiwan Patent Application No. 109141339, dated Jan. 21, 2025, in 7 pages. [cited by applicant]
Office Action English Summary dated Aug. 23, 2022 in Malaysian Application No. PI2020003935 in 4 pages. [cited by applicant]
Office Action with English Summary dated Aug. 29, 2022 in Saudi Arabia—Patent application No. 520420878. [cited by applicant]
Office Action with English Summary dated Oct. 10, 2024 in Japanese Application No. 2023-136268 in 11 pages. [cited by applicant]
Office Action with English Translation dated Oct. 11, 2024 in Chilean Patent Application No. 202002011, in 5 pages. [cited by applicant]
Office Action with English Translation Dated Oct. 28, 2024 in Egypt Patent Application No. 1112/2020 in 12 pages. [cited by applicant]
Office Action with English translation dated Sep. 15, 2024 in Saudi Arabia—Patent application No. 520420878 in 9 pages. [cited by applicant]
Office Action with English Translation in Chilean Patent Application No. 202002011, dated Feb. 8, 2022. [cited by applicant]
Office Action with English Translation in Chilean Patent Application No. 202002011, dated Jul. 25, 2022. [cited by applicant]
Office Action with English Translation received in Korean Application No. 10-2019-0001983 dated Sep. 25, 2024 in 7 pages. [cited by applicant]
Office Action with English Translation in Japanese Patent Application No. 2022-531631 dated Nov. 22, 2024. [cited by applicant]
Supplementary European Search Report Dated Mar. 10, 2021 in European Application No. 19746979 in 287 pages. [cited by applicant]
Apel et al., Integrated clinical scale manufacturing system for cellular products derived by magnetic cell separation, centrifugation and cell culture. Chem Ing Tech. Feb. 2013; 85(1-2):103-110. [cited by applicant]
Baust et al. Cryopreservation: An emerging paradigm change. Organogenesis. Jul. 2009; 5(3):90-6 (Year: 2009). [cited by applicant]
India Office Action in Application No 202017036642 dated Aug. 18, 2025 in 3 pages. [cited by applicant]
Iranian Office Action in Patent Application No. 139950140003010289, dated Apr. 27, 2025; 14 pages. [cited by applicant]
Japanese Office Action dated May 20, 2025 for Patent Application No. 2022-531631; 14 pages. [cited by applicant]
Karnieli, Bioreactors and Downstream Processing for Stem Cell Manufacturing; Cryopreservation section; Stem Cell Manufacturing 2016, pp. 141-160 (Year: 2016). [cited by applicant]