Granted Patent
B2
US 12,559,723 · App. 18/066,612 · Granted Feb 24, 2026
Platform for generating safe cell therapeutics
C12N5/0662A61K9/0019A61K35/12A61K35/17A61K35/28A61K38/2066A61K38/208A61K39/001102A61K39/215A61P35/00C12N5/0646C12N5/0667C12N5/10C12N15/85C12N15/88A61K39/00A61K2039/515A61K2039/545C12N2501/999C12N2510/00C12N2513/00
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided herein are cytoplasts, compositions comprising cytoplasts, methods of using cytoplasts, and methods of treating a subject, such as providing benefits to a healthy or unhealthy subject, or treating or diagnosing a disease or condition in a subject. In some embodiments, methods of treating a subject include: administering to the subject a therapeutically effective amount of a composition comprising a cytoplast. Also, provided herein are compositions (e.g., pharmaceutical compositions) that include a cytoplast. Also, provided herein are kits comprising instructions for using the compositions or methods.
Claims (13)
1 . An enucleated cell, comprising:
an immune cell lacking a nucleus; and
one or more intracellular organelles sufficient for performing an immune cell function.
2 . The enucleated cell of claim 1 , wherein the immune cell comprises a natural killer (NK) cell, a neutrophil, a macrophage, a lymphocyte, a mast cell, a basophil, a dendritic cell, a monocyte, a myeloid-derived suppressor cell, or an eosinophil.
3 . The enucleated cell of claim 1 , wherein the immune cell comprises a NK cell.
4 . The enucleated cell of claim 1 , wherein the performing the immune cell function comprises inducing an immune response to the presence of a pathogen.
5 . The enucleated cell of claim 1 , wherein the performing the immune cell function comprises inducing an immune response to the presence of a tumor.
6 . The enucleated cell of claim 1 , further comprising an exogenous therapeutic agent.
7 . The enucleated cell of claim 6 , wherein the exogenous therapeutic agent comprises a cytokine or a portion thereof.
8 . The enucleated cell of claim 1 , wherein the enucleated cell has a diameter that is less than or equal to about 100 micrometers (μm).
9 . The enucleated cell of claim 1 , wherein the enucleated cell is isolated and purified.
10 . The enucleated cell of claim 1 , formulated as a pharmaceutical composition, wherein the pharmaceutical formulation further comprises a pharmaceutically acceptable carrier, excipient, or diluent.
11 . A method, comprising delivering the enucleated cell of claim 1 to a subject.
Assignments (3)
CONFIRMATORY LICENSE
Recorded Aug 3, 2023
From: UNIVERSITY OF CALIFORNIA SAN DIEGO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064479/0871 →
CONFIRMATORY LICENSE
Recorded Aug 3, 2023
From: UNIVERSITY OF CALIFORNIA SAN DIEGO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064479/0880 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 23, 2023
From: KLEMKE, RICHARD; WANG, HUAWEI
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 063071/0546 →
Continuity (7)
References Cited (212)
US 6054281A
· Russel et al.
· 2000
[cited by applicant]
US 6511967B1
· Weissleder et al.
· 2003
[cited by applicant]
US 6538121B1
· He et al.
· 2003
[cited by applicant]
US 6583121B1
· Johnston et al.
· 2003
[cited by applicant]
US 6951756B2
· Lubitz et al.
· 2005
[cited by applicant]
US 9364504B2
· Godfrin et al.
· 2016
[cited by applicant]
US 9546371B2
· Mamoun et al.
· 2017
[cited by applicant]
US 9950049B2
· Godfrin et al.
· 2018
[cited by applicant]
US 20020142397A1
· Collas et al.
· 2002
[cited by applicant]
US 20030113910A1
· Levanduski
· 2003
[cited by examiner]
US 20040214783A1
· Terman
· 2004
[cited by applicant]
US 20040259249A1
· Strelchenko et al.
· 2004
[cited by applicant]
US 20080182292A1
· Gerdes et al.
· 2008
[cited by applicant]
US 20090004744A1
· Surber et al.
· 2009
[cited by applicant]
US 20100158871A1
· Terman
· 2010
[cited by applicant]
US 20110070153A1
· Hyde et al.
· 2011
[cited by applicant]
US 20110286978A1
· Klimanskaya et al.
· 2011
[cited by applicant]
US 20150104428A1
· Shi et al.
· 2015
[cited by applicant]
US 20160166613A1
· Spencer et al.
· 2016
[cited by applicant]
US 20160199413A1
· Simonson et al.
· 2016
[cited by applicant]
US 20160257932A1
· Kahvejian et al.
· 2016
[cited by applicant]
US 20160272707A1
· Levine et al.
· 2016
[cited by applicant]
US 20160289645A1
· Tufaro et al.
· 2016
[cited by applicant]
US 20170166877A1
· Bayle et al.
· 2017
[cited by applicant]
US 20180092951A1
· Szalay et al.
· 2018
[cited by applicant]
US 20180153989A1
· Kahvejian et al.
· 2018
[cited by applicant]
US 20190153409A1
· Arber et al.
· 2019
[cited by applicant]
US 20190160102A1
· Hoffman et al.
· 2019
[cited by applicant]
US 20200054675A1
· DiPersio et al.
· 2020
[cited by applicant]
US 20200108066A1
· Goel et al.
· 2020
[cited by applicant]
US 20200181251A1
· Buckler et al.
· 2020
[cited by applicant]
US 20200215114A1
· Rodriguez-Araujo et al.
· 2020
[cited by applicant]
US 20200216918A1
· Langlois et al.
· 2020
[cited by applicant]
US 20200276318A1
· Patrick et al.
· 2020
[cited by applicant]
US 20200318073A9
· Draganov et al.
· 2020
[cited by applicant]
US 20200345845A1
· Kahvejian et al.
· 2020
[cited by applicant]
US 20200362052A1
· Tachado
· 2020
[cited by applicant]
US 20200407421A1
· Hermiston et al.
· 2020
[cited by applicant]
US 20210000750A1
· Gu et al.
· 2021
[cited by applicant]
US 20210040205A1
· Jang et al.
· 2021
[cited by applicant]
US 20210060052A1
· Quay
· 2021
[cited by applicant]
US 20210060126A1
· Youssef et al.
· 2021
[cited by applicant]
US 20210139846A1
· Bazan
· 2021
[cited by applicant]
US 20210180059A1
· Maresca et al.
· 2021
[cited by applicant]
US 20230015661A1
· Klemke et al.
· 2023
[cited by applicant]
US 20230103075A1
· Klemke et al.
· 2023
[cited by applicant]
US 20230218733A1
· Moomiaie et al.
· 2023
[cited by applicant]
CN 102803473A
· 2012
[cited by applicant]
CN 104877965
· 2015
[cited by applicant]
EP 3583946A1
· 2019
[cited by applicant]
JP 2013144707
· 2013
[cited by applicant]
JP 2016519933
· 2016
[cited by applicant]
JP 2017504568
· 2017
[cited by applicant]
JP 2017517485
· 2017
[cited by applicant]
JP 2020530454A
· 2020
[cited by applicant]
WO WO0128583A2
· 2001
[cited by examiner]
WO WO200224897
· 2002
[cited by applicant]
WO WO0239951A2
· 2002
[cited by examiner]
WO WO2007095747
· 2007
[cited by applicant]
WO WO2013038066
· 2013
[cited by applicant]
WO WO2015128492
· 2015
[cited by applicant]
WO WO2015153102
· 2015
[cited by applicant]
WO WO2016141357
· 2016
[cited by applicant]
WO WO2016183482
· 2016
[cited by applicant]
WO WO2017123644
· 2017
[cited by applicant]
WO WO2017165245
· 2017
[cited by applicant]
WO WO2017173034
· 2017
[cited by applicant]
WO WO2018006880
· 2018
[cited by applicant]
WO WO2018064513
· 2018
[cited by applicant]
WO WO2018081738
· 2018
[cited by applicant]
WO WO2018112032
· 2018
[cited by applicant]
WO WO2018148378
· 2018
[cited by applicant]
WO WO2018208728
· 2018
[cited by applicant]
WO WO2019017940
· 2019
[cited by applicant]
WO WO2019032628
· 2019
[cited by applicant]
WO WO2019055851
· 2019
[cited by applicant]
WO WO2019090355
· 2019
[cited by applicant]
WO WO2019113512
· 2019
[cited by applicant]
WO WO2019113711
· 2019
[cited by applicant]
WO WO2019126818
· 2019
[cited by applicant]
WO WO2019169141
· 2019
[cited by applicant]
WO WO2019195819
· 2019
[cited by applicant]
WO WO2019213706
· 2019
[cited by applicant]
WO WO2019217646
· 2019
[cited by applicant]
WO WO2019236633
· 2019
[cited by applicant]
WO WO2019246111
· 2019
[cited by applicant]
WO WO2019246528
· 2019
[cited by applicant]
WO WO2020016900
· 2020
[cited by applicant]
WO WO2020023350
· 2020
[cited by applicant]
WO WO2020028533
· 2020
[cited by applicant]
WO WO2020037434
· 2020
[cited by applicant]
WO WO2020049158
· 2020
[cited by applicant]
WO WO2020069452
· 2020
[cited by applicant]
WO WO2020069454
· 2020
[cited by applicant]
WO WO2020072126
· 2020
[cited by applicant]
WO WO2020205579
· 2020
[cited by applicant]
WO WO2021041473
· 2021
[cited by applicant]
Cheng-Jun, et al., 2008, Journal of Clinical and Rehabilitative Tissue Engineering Research, 12(43): 8449-53 (Year: 2008).
[cited by examiner]
Mo, et al., Nature Communications, 2014; 5:3364, pp. 1-10 (Year: 2014).
[cited by examiner]
Alarcon, “Therapeutic Functions of Bioengineered, Enucleated Cells,” Thesis for the degree of Doctor of Philosophy, University of California San Diego, School of Biomedical Sciences, 2020, 122 pages.
[cited by applicant]
Chernega et al., “Mitochondria-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases,” Molecular Therapy Nucleic Acids, Oct. 27, 2022, 30:359-377.
[cited by applicant]
Galluzzi et al., “Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors,” Nature Reviews Clinical oncology, Dec. 2020, 17(12):725-741.
[cited by applicant]
Klemke et al., “Abstract LB-067: Cargocytes: A novel cell therapy platform to drive anti-tumor immunity,” Cancer Research, Jul. 1, 2019, 79(13_Supplement):LB-067 (Abstract only).
[cited by applicant]
Wang et al., “Enucleated human mesenchymal stromal cells for the homing and the delivery of therapeutic cargos in vivo,” Nature Biomedical Engineering, Jul. 2022, 6(7):882-897.
[cited by applicant]
Alarcón et al., “Enucleated Cells as Delivery Vehicles to Treat Cancer,” In Molecular Biology of the Cell, Dec. 15, 2018, 29(26): 1 page.
[cited by applicant]
Ardolino et al., “Cytokine treatment in cancer immunotherapy,” Oncotarget, Aug. 14, 2015, 6(23):19346-19347.
[cited by applicant]
Bahadoran et al., “Immune responses to influenza virus and its correlation to age and inherited factors,” Frontiers in microbiology, Nov. 22, 2016, 7: 11 Pages.
[cited by applicant]
Bhat et al., “Rab35 and its effectors promote formation of tunneling nanotubes in neuronal cells,” Scientific reports, Oct. 8, 2020, 10(1):1-14.
[cited by applicant]
Buszczak et al., “Signaling by cellular protrusions: keeping the conversation private,” Trends in cell biology, Jul. 1, 2016, 26(7):526-534.
[cited by applicant]
Carpi et al., “Cytokines in the management of high risk or advanced breast cancer: an update and expectation,” Current Cancer Drug Targets, Dec. 1, 2009, 9(8):888-903.
[cited by applicant]
Chen et al., “Alteration of T cell immunity by lentiviral transduction of human monocyte-derived dendritic cells,” Retrovirology, Dec. 1, 2004, 1(1): 12 Pages.
[cited by applicant]
Cheng-Jun et al., “Preparation and activity of cytoplasts from bone marrow mesenchymal stem cells,” Journal of Clinical and Rehabilitative Tissue Engieering Research, 2008, 12(43): 1 page.
[cited by applicant]
Cook, “Evidence based route of administration of vaccines,” Human vaccines, Jan. 1, 2008, 4(1): 8 Pages.
[cited by applicant]
Dias et al., “IL-12 regulates VEGF and MMPs in a murine breast cancer model,” International journal of cancer, Oct. 29, 1998, 78(3):361-365.
[cited by applicant]
Du et al., “Cytoplast containing reprogramming-related factors from human embryonic stem cells arrested at metaphase,” Development, Growth, & Differentiation, 2010, 53(1):18-25.
[cited by applicant]
Eliopoulos et al., “Neo-organoid of marrow mesenchymal stromal cells secreting interleukin-12 for breast cancer therapy,” Cancer research, Jun. 15, 2008, 68(12):4810-4818.
[cited by applicant]
Extended European Search Report in EP Appln. No. 18845202, dated May 19, 2020, 9 pages.
[cited by applicant]
Hekmatshoar et al., “The role of metabolism and tunneling nanotube-mediated intercellular mitochondria exchange in cancer drug resistance,” Biochemical Journal, Jul. 31, 2018, 475(14):2305-2328.
[cited by applicant]
Huang, “Vaccinia Virus-mediated Therapy of Solid Tumor Xenografts: Intra-tumoral Delivery of Therapeutic Antibodies,” 2013, 172 pages.
[cited by applicant]
International Preliminary Report on Patentability in Appln. No. PCT/US2018/045686, dated Feb. 11, 2020, 7 pages.
[cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/016919, dated Jul. 28, 2022, 7 pages.
[cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2018/045686, dated Oct. 19, 2018, 10 pages.
[cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/016919, dated Apr. 28, 2021, 9 pages.
[cited by applicant]
Ishikawa et al., “The protective effects of intranasal administration of IL-12 given before influenza virus infection and the negative effects of IL-12 treatment given after viral infection,” Journal of Medical Virology…
[cited by applicant]
Iyer et al., “Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease,” Crit Rev Immunol, 2012, 32(1): 23-63.
[cited by applicant]
Jones et al., “Viral persistence: IL-10 is the key,” Nature Reviews Microbiology, Dec. 2006, 4(12):879.
[cited by applicant]
Kagawa et al., “Gene therapy of mitochondrial diseases using human cytoplasts,” Gene Therapy, 1997, 4:6-10.
[cited by applicant]
Mo et al., “ATP-triggered anticancer drug therapy,” Nature Communications, 2014, 5:3364, 10 pages.
[cited by applicant]
Neve et al., “A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes,” Cancer cell, Dec. 1, 2006, 10(6):515-527.
[cited by applicant]
Office Action in United Kingdom Appln. No. 2000541.9, dated Jan. 30, 2020, 3 pages.
[cited by applicant]
Page et al., “Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer,” NPJ breast cancer, Oct. 8, 2019, 5(34): 1-9.
[cited by applicant]
Patil et al., “Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody,” PLoS One, 2021, 7(10): e47472, 13 pages.
[cited by applicant]
Philips et al., “Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies,” International immunology, Jan. 1, 2015, 27(1):39-46.
[cited by applicant]
Rakhmilevich et al., “Treatment of experimental breast cancer using interleukin-12 gene therapy combined with anti-vascular endothelial growth factor receptor-2 antibody,” Molecular cancer therapeutics, Aug. 1, 2004, 3(…
[cited by applicant]
Ruella et al., “Next-generation chimeric antigen receptor T-cell therapy: going off the shelf,” BioDrugs, Dec. 2017, 31(6): 15 pages.
[cited by applicant]
Sabel et al., “Intratumoral delivery of encapsulated IL-12, IL-18 and TNF-α in a model of metastatic breast cancer,” Breast cancer research and treatment, Jul. 2010, 122(2): 12 pages.
[cited by applicant]
Schlake et al., “mRNA: a novel avenue to antibody therapy?,” Molecular Therapy, Apr. 10, 2019, 27(4):773-784.
[cited by applicant]
Serwer et al., [online], “Systemic and Local Drug Delivery for Treating Diseases of the Central Nervous System in Rodent Models,” J Vis Exp., 2010 retrieved on Nov. 10, 2022, 6 pages.
[cited by applicant]
Shi et al., “Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes,” Proceedings of the National Academy of Science, 2014, 111(28):10131-10136.
[cited by applicant]
St. Clair, “Interleukin 10 treatment for rheumatoid arthritis,” Annals of the Rheumatic Diseases, 1999, 58(1):199-1102.
[cited by applicant]
Tena et al., “Transgenic expression of human CD47 markedly increases engraftment in a murine model of pig-to-human hematopoietic cell transplantation,” American Journal of Transplantation, 2014, 14(12):2713-2722.
[cited by applicant]
Wang et al., “Potential of CXCR4/CXCL12 chemokine axis in cancer drug delivery,” Current pharmacology reports, Feb. 2016, 2(1):1-10.
[cited by applicant]
Yadav et al., “Golgi proteins in circulating human platelets are distributed across non-stacked, scattered structures,” Platelets May 19, 2017, 28(4):400-408.
[cited by applicant]
Yang et al., “Interleukin-12 activated CD8+ T cells induces apoptosis in breast cancer cells and reduces tumor growth,” Biomedicine & Pharmacotherapy, Dec. 1, 2016, 84:1466-1471.
[cited by applicant]
Yeo et al., “Cellular dynamics of mammalian red blood cell production in the erythroblastic island niche,” Biophysical reviews, Dec. 2019, 11(6):873-894.
[cited by applicant]
Yoo et al., “Bio-inspired, bioengineered and biomimetic drug delivery carriers,” Nature reviews Drug discovery, Jul. 2011, 10(7): 16 pages.
[cited by applicant]
Zakhartsev et al. “Cell size and morphological properties of yeast
[cited by applicant]
Baliaka et al., “Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector-p53,” Gene Therapy, Feb. 2014, 21…
[cited by applicant]
Kim et al., “Intratumoral versus intravenous gene therapy using a transcriptionally targeted viral vector in an orthotopic hepatocellular carcinoma rat model,” Journal of Vascular and Interventional Radiology, May 1, 20…
[cited by applicant]
Krueger et al., “Concise review: mesenchymal stem cell-based drug delivery: the good, the bad, the ugly, and the promise,” Stem Cells Translational Medicine, Sep. 1, 2018, 7(9):651-663.
[cited by applicant]
Watson et al., “Enhancing Chemotaxis of Enucleated Cells by Genetic Engineering,” Molecular Biology of the Cell, Dec. 15, 2018, 29(26):31-32.
[cited by applicant]