Granted Patent
B2
US 12,285,480 · App. 17/405,393 · Granted Apr 29, 2025
Method of inducing immunity against SARS-CoV-2 using spike and nucleocapsid-ETSD immunogens delivered by RNA and replication-defective adenoviruses
Assignee:
NantCell, Inc.
A61K39/215C07K14/005C07K14/165C12N15/86A61K38/00A61K39/235C07K2317/52C07K2319/01C12N1/16C12N2710/10341C12N2770/20034C12Y304/17023
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Disclosed herein are methods for inducing immunity against a severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2) in a patient in need thereof. The method comprises administering a vaccine composition comprising a self-adjuvanted SARS-CoV2 Spike (S) RNA-based vaccine (AAHI-SC2), followed by administering a replication defective adenovirus (hAd5) vaccine composition, wherein the adenovirus comprises an E1 gene region deletion and an E2b gene region deletion.
Claims (18)
1. A method of inducing immunity against an antigen in a patient, the method comprising:
administering a vaccine composition comprising a self-adjuvanted RNA-based vaccine, wherein the RNA encodes a SARS-CoV-2 spike (S) protein; and
administering a replication defective adenovirus (hAd5) vaccine composition, wherein the adenovirus comprises an E1 gene region deletion and an E2b gene region deletion, and wherein the hAd5 comprises a nucleotide encoding 1) a SARS-CoV-2 S protein having the amino acid sequence of SEQ ID NO:6; and 2) a chimeric protein comprising a SARS-CoV-2 nucleocapsid (N) protein and an endosomal targeting sequence (ETSD), wherein the chimeric protein has the amino acid sequence of SEQ ID NO: 2.
2. The method of claim 1 , wherein the RNA-based vaccine composition further 025comprises nonstructural proteins 1-4 derived from the Venezuelan equine encephalitis virus (VEEV) vaccine.
3. The method of claim 1 , wherein the RNA-based vaccine composition is delivered to the patient by intramuscular (IM) injection, intravenous (IV) injection, and/or subcutaneous injection.
4. The method of claim 3 , wherein the RNA-based vaccine composition comprises a lipid nanoparticle encasing coronaviral mRNA.
5. The method of claim 1 , wherein the hAd5 vaccine composition is delivered to the nasal mucosa, oral mucosa, and/or alimentary mucosa of the patient.
6. The method of claim 1 , wherein the hAd5 vaccine composition is delivered by subcutaneous injection.
7. The method of claim 1 , wherein the hAd5 vaccine composition is administered orally after the RNA-based vaccine injection.
8. The method of claim 7 , wherein the hAd5 vaccine composition comprises aragonite particle beads.
9. The method of claim 1 , wherein the hAd5 vaccine composition is administered as a booster immunization at least one week after the RNA-based vaccine injection.
10. The method of claim 9 , wherein the hAd5 vaccine composition is administered at least two weeks after the RNA-based vaccine injection.
11. The method of claim 1 , wherein the hAd5 further comprises an E3 gene region deletion and/or an E4 gene region deletion.
12. The method of claim 1 , further comprising analyzing a sample of saliva from the treated patient for antibodies targeting the SARS-CoV-2 and/or for a protein specific to the SARS-CoV-2, wherein in the absence of said antibodies in the sample saliva, the method further comprises administering a booster of the vaccine to the patient.
13. The method of claim 12 , further comprising administering a second dose of the hAd5 vaccine to the patient.
14. The method of claim 1 , wherein the hAd5 vaccine composition further comprises a nucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 10.
15. The method of claim 1 , wherein the hAd5 vaccine composition further comprises a nucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 12.
16. The method of claim 1 , wherein the hAd5 vaccine composition comprises the nucleic acid sequence of SEQ ID NO: 11, SEQ ID NO: 13 or SEQ ID NO: 14.
Assignments (3)
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 →
CHANGE OF NAME
Recorded Sep 8, 2021
From: IMMUNITYBIO, INC.
To: NANTCELL, INC.
Reel/Frame 057528/0064 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 18, 2021
From: RICE, ADRIAN; VERMA, MOHIT
To: IMMUNITYBIO, INC.
Reel/Frame 057214/0427 →
Continuity (27)
Continuation In Part
17198164
Provisional Application
63135380
· Jan 8, 2021
Provisional Application
63121102
· Dec 3, 2020
Provisional Application
63118697
· Nov 26, 2020
Provisional Application
63117460
· Nov 24, 2020
Provisional Application
63117922
· Nov 24, 2020
Provisional Application
63117847
· Nov 24, 2020
Provisional Application
63115127
· Nov 18, 2020
Provisional Application
63082145
· Sep 23, 2020
Provisional Application
63080887
· Sep 21, 2020
Provisional Application
63069598
· Aug 24, 2020
Provisional Application
63067033
· Aug 18, 2020
Provisional Application
63064157
· Aug 11, 2020
Provisional Application
63059975
· Aug 1, 2020
Provisional Application
63053691
· Jul 19, 2020
Provisional Application
63036445
· Jun 9, 2020
Provisional Application
63022146
· May 8, 2020
Provisional Application
63016048
· Apr 27, 2020
Provisional Application
63016241
· Apr 27, 2020
Provisional Application
63009960
· Apr 14, 2020
Provisional Application
63010010
· Apr 14, 2020
Provisional Application
62991504
· Mar 18, 2020
Provisional Application
62988328
· Mar 11, 2020
References Cited (225)
US 6133036A
· Putcha et al.
· 2000
[cited by applicant]
US 6716392B1
· Putcha et al.
· 2004
[cited by applicant]
US 7618817B2
· Campbell
· 2009
[cited by applicant]
US 7750123B2
· Marasco et al.
· 2010
[cited by applicant]
US 8034332B2
· Klingemann
· 2011
[cited by applicant]
US 8313943B2
· Campbell
· 2012
[cited by applicant]
US 9150636B2
· Campbell
· 2015
[cited by applicant]
US 9181322B2
· Campbell
· 2015
[cited by applicant]
US 20040161388A1
· Liu et al.
· 2004
[cited by applicant]
US 20050003548A1
· Korokhov et al.
· 2005
[cited by applicant]
US 20060171962A1
· Enjuanes Sanchez et al.
· 2006
[cited by applicant]
US 20070105193A1
· Vilalta et al.
· 2007
[cited by applicant]
US 20100150923A1
· Jiang et al.
· 2010
[cited by applicant]
US 20100196411A1
· Duke et al.
· 2010
[cited by applicant]
US 20120076820A1
· Amara et al.
· 2012
[cited by applicant]
US 20120107347A1
· Hodge et al.
· 2012
[cited by applicant]
US 20120288502A1
· Diskin et al.
· 2012
[cited by applicant]
US 20130123136A1
· Abassi et al.
· 2013
[cited by applicant]
US 20160076053A1
· Jones et al.
· 2016
[cited by applicant]
US 20160168591A1
· Brennan et al.
· 2016
[cited by applicant]
US 20160223564A1
· Lee et al.
· 2016
[cited by applicant]
US 20170224794A1
· Franzusoff et al.
· 2017
[cited by applicant]
US 20170246276A1
· Palena et al.
· 2017
[cited by applicant]
US 20180244756A1
· Graham et al.
· 2018
[cited by applicant]
US 20180296663A1
· Hipp et al.
· 2018
[cited by applicant]
US 20190307819A1
· Drew et al.
· 2019
[cited by applicant]
US 20200164058A1
· Hashem
· 2020
[cited by applicant]
US 20210284713A1
· Niazi et al.
· 2021
[cited by applicant]
US 20210284716A1
· Niazi et al.
· 2021
[cited by applicant]
CN 1488646A
· 2004
[cited by applicant]
CN 1572875A
· 2005
[cited by applicant]
CN 102844329A
· 2012
[cited by applicant]
CN 111249454A
· 2020
[cited by applicant]
CN 111254155A
· 2020
[cited by applicant]
CN 111330003A
· 2020
[cited by applicant]
CN 111375055A
· 2020
[cited by applicant]
EP 1508615A1
· 2005
[cited by applicant]
JP 2008505114A
· 2008
[cited by applicant]
JP 2019521148A
· 2019
[cited by applicant]
JP 2021167805A
· 2021
[cited by applicant]
KR 101453923B1
· 2014
[cited by applicant]
KR 20220006125A
· 2022
[cited by applicant]
WO 2003066820A2
· 2003
[cited by applicant]
WO WO03066820A2
· 2003
[cited by examiner]
WO 2005120565A2
· 2005
[cited by applicant]
WO 2006068663A2
· 2006
[cited by applicant]
WO 2006113214A2
· 2006
[cited by applicant]
WO 2009006479A3
· 2009
[cited by applicant]
WO 2011129468A1
· 2011
[cited by applicant]
WO 2012109404A1
· 2012
[cited by applicant]
WO 2014031178A1
· 2014
[cited by applicant]
WO 2016112188A1
· 2016
[cited by applicant]
WO 2016116398A1
· 2016
[cited by applicant]
WO 2018014008A1
· 2018
[cited by applicant]
WO 2018140456A1
· 2018
[cited by applicant]
WO 2018200389A1
· 2018
[cited by applicant]
WO 2019143606A1
· 2019
[cited by applicant]
WO 2020086745A1
· 2020
[cited by applicant]
WO 2020219974A1
· 2020
[cited by applicant]
WO 2021165448A1
· 2021
[cited by applicant]
WO 2021183665A1
· 2021
[cited by applicant]
WO 2021183717A1
· 2021
[cited by applicant]
WO 2021188599A1
· 2021
[cited by applicant]
WO 2021212021A2
· 2021
[cited by applicant]
WO 2021250467A2
· 2021
[cited by applicant]
WO 2021248853A1
· 2021
[cited by applicant]
WO 2021254287A1
· 2021
[cited by applicant]
WO 2022132625A1
· 2022
[cited by applicant]
Zhou, W., et al., 2023, Vaccines' New Era—RNA Vaccine, Viruses 15, 1760, pp. 1-19.
[cited by examiner]
Liniger, M., et al., 2008, Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles virus, Vaccine 26:2164-2174.
[cited by examiner]
Enjuanes, L., et al., 2008, Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease, Vir. Res. 133:45-62.
[cited by examiner]
See, R. H., et al., 2006, Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus, J. Gen. Virol. 87:641-650.
[cited by examiner]
Final Office Action received for U.S. Appl. No. 16/880,804 dated Oct. 25, 2021, 16 pages.
[cited by applicant]
Lei et al., “Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig”, bioRxiv, 2020, 11 pages.
[cited by applicant]
Amalfitano et al., “Production and Characterization of Improved Adenovirus Vectors with the E1, E2b, and E3 Genes Deleted”, Journal of Virology, 1998, vol. 72, No. 2, pp. 926-933.
[cited by applicant]
Yan et al., “Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2”, Science, 2020, pp. 1-9.
[cited by applicant]
Zhang et al., “Angiotensin-converting enzyme 2(ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target”, Intensive Care Med, 2020, 5 pages.
[cited by applicant]
Zhonghua Yi Xue Za Zhi, “Dynamic Changes of T-lymphocytes and Immunoglobulins in Patients With Severe Acute Respiratory Syndrome”, Natl Med J China, Jun. 25, 2003, vol. 83, No. 12, pp. 1014-1017 (English Abstract only).
[cited by applicant]
“The Involvement of Natural Killer Cells in the Pathogenesis of Severe Acute Respiratory Syndrome”, National Research Project for SARS, Beijing Group, American Journal of Clinical Pathology, 2004, vol. 121, pp. 507-511.
[cited by applicant]
Bergamaschi et al., “Intracellular Interaction of Interleukin-15 with Its Receptor alpha during Production Leads to Mutual Stabilization andIncreased Bioactivity”, The Journal of Biological Chemistry, 2008, vol. 283, No…
[cited by applicant]
Bessard et al., “High Antitumor Activity of RLI, an interleukin-15 (IL-15)-IL-15 Receptor Alpha Fusion Protein, in Metastatic Melanoma and Colorectal Cancer”, Mol Cancer Ther, 2009, vol. 8, No. 9, pp. 2736-2745.
[cited by applicant]
Clay et al., “Severe Acute Respiratory Syndrome-Coronavirus Infection in Aged Nonhuman Primates Is Associated With Modulated Pulmonary and Systemic Immune Responses”, Immunity & Ageing, 2014, vol. 11, No. 4, pp. 1-16.
[cited by applicant]
Dubois et al., “Preassociation of IL-15 With IL-15R alpha-IgG1-Fc Enhances Its Activity on Proliferation of NK and CD8 +/CD44high T Cells and Its Antitumor Action”, The Journal of Immunology, 2008, vol. 180, pp. 2099-21…
[cited by applicant]
Duitman et al., “How a Cytokine Is Chaperoned Through the Secretory Pathway by Complexing With Its Own Receptor: Lessons From interleukin-15 (IL-15)/IL-15 Receptor Alpha”, molecular and Cellular Biology, Aug. 2008, vol.…
[cited by applicant]
Ellis-Connell et al., “ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment”, Journal of Virology, 2018, vol. 92, No. 3, pp. 1-21.
[cited by applicant]
Epardaud et al., “Interleukin-15/interleukin-15R Alpha Complexes Promote Destruction of Established Tumors by Reviving Tumor-Resident CD8+ T Cells”, Cancer Research, 2008, vol. 68, No. 8, pp. 2972-2983.
[cited by applicant]
Fehniger et al., “Interleukin-2 and interleukin-15: Immunotherapy for Cancer”, Cytokine Growth Factor Rev, 2002, vol. 13, No. 2, pp. 169-183.
[cited by applicant]
Furuya et al., “Effectiveness of two different dose administration regimens of an IL-15 superagonist complex (ALT-803) in an orthotopic bladder cancer mouse model”, Journal of translational Medicine, 2019, vol. 17, No. …
[cited by applicant]
Gomes-Giacoia et al., “Intravesical ALT-803 and BCG Treatment Reduces Tumor Burden in a Carcinogen Induced Bladder Cancer Rat Model; A Role for Cytokine Production and NK Cell Expansion”, Plos One, 2014, vol. 9, No. 6, …
[cited by applicant]
Guan et al., “Clinical Characteristics of Coronavirus Disease 2019 in China”, The New England Journal of Medicine, 2020, 13, pages.
[cited by applicant]
Guilliams et al., “The function of Fc gamma receptors in dendritic cells and macrophages”, Nature Reviews Immunology, 2014, vol. 14, pp. 94-108.
[cited by applicant]
Huang et al., “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China”, Lancet, 2020, vol. 395, No. 10223, pp. 1-10.
[cited by applicant]
Huntington et al., “IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo”, Proceedings of the National Academy of Sciences, 2011, vol. 108, No. 15, pp. 6217-6…
[cited by applicant]
Jones et al., “A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes”, Plos Pathogens, 2016, pp. 1-25.
[cited by applicant]
Kim et al., “IL-15 superagonist/IL-15RaSushi-Fc Fusion Complex (IL-15SA/IL-15RαSu-Fc; ALT-803) Markedly Enhances Specific Subpopulations of NK and Memory CD8+ T Cells, and Mediates Potent Anti-Tumor Activity Against Mur…
[cited by applicant]
Law et al., “Chemokine Up-Regulation in SARS-coronavirus-infected, Monocyte-Derived Human Dendritic Cells”, Blood, 2005, vol. 106, No. 7, pp. 2366-2374.
[cited by applicant]
Mah et al., “Glycolytic Requirement for NK Cell Cytotoxicity and Cytomegalovirus Control”, JCI Insight, 2017, vol. 2, No. 23, 18 pages.
[cited by applicant]
Margolin et al., “Phase I Trial of ALT-803, A Novel Recombinant IL 15 Complex, in Patients With Advanced Solid Tumors”, Clinical Cancer Research, 2018, vol. 24, No. 22, pp. 555-5561.
[cited by applicant]
Mathios et al., “Therapeutic Administration of IL-15 Superagonist Complex ALT-803 Leads to Long-Term Survival and Durable Antitumor Immune Response in a Murine Glioblastoma Model”, International Journal of Cancer, 2016,…
[cited by applicant]
McBrien et al., “Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells”, Nature, Feb. 6, 2020, vol. 578, pp. 154-159.
[cited by applicant]
Mortier et al., “Soluble Interleukin-15 Receptor α (IL-15Rα)-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rβ/γ Hyperagonist IL-15-IL-15Rα Fusion Proteins”, Journal of Biological Chemistry, 2006, …
[cited by applicant]
Rhode et al., “Comparison of the Superagonist Complex, ALT-803, to IL 15 as Cancer Immunotherapeutics in Animal Models”, Cancer Immunol Res, 2016, vol. 4, pp. 1-12.
[cited by applicant]
Romee et al., “First-in-human Phase 1 Clinical Study of the IL-15 Superagonist Complex ALT-803 to Treat Relapse After Transplantation”, Blood, 2018, vol. 131, No. 23, pp. 2515-2527.
[cited by applicant]
Rosario et al., “The IL-15-Based ALT-803 Complex Enhances FcγRIIIa-Triggered NK Cell Responses and In Vivo Clearance of B Cell Lymphomas”, Clinical Cancer Research, 2016, vol. 22, No. 3, pp. 596-608.
[cited by applicant]
Seay et al., “In Vivo Activation of Human NK Cells by Treatment With an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice”, Journal of Virology, 2015, 46 pages.
[cited by applicant]
Spiegel et al., “Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3”, Journal of Virology, 2005, vol. 79, …
[cited by applicant]
Waldmann Thomas A., “The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design”, Nature Reviews Immunology vol. 2006, vol. 6, pp. 595-601.
[cited by applicant]
Wang et al., “IgG Fc engineering to modulate antibody effector functions”, 2017, 11 pages.
[cited by applicant]
Webb et al., “The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles”, Blood Advances, 2018, vol. 2, No. 2, pp. 76-84.
[cited by applicant]
Weiss et al., “Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus”, Microbiology and molecular Biology Reviews, 2005, vol. 69, No. 4, 31 pages.
[cited by applicant]
Wrangle et al., “ALT-803, an IL-15 Superagonist, in Combination With Nivolumab in Patients With Metastatic Non-Small Cell Lung Cancer: A Non-Randomised, Open-Label, Phase 1b Trial”, Lancet Oncol, 2018, vol. 19, No. 5, p…
[cited by applicant]
Xu et al., “Efficacy and Mechanism-Of-Action of a Novel Superagonist interleukin-15: Interleukin-15 Receptor αSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma”, Cancer Research, 2013, vol. 73, No. 10,…
[cited by applicant]
Zhu et al., “Novel Human Interleukin-15 Agonists”, The Journal of Immunology, 2009, vol. 183, pp. 3598-3607.
[cited by applicant]
Zhu et al., “MHC Class I-Related Neonatal Fc Receptor for IgG Is Functionally Expressed in Monocytes, Intestinal Macrophages, and Dendritic Cells”, The Journal of immunology, 2001, vol. 166, pp. 3266-3276.
[cited by applicant]
Saiki et al., “Induction of Humoral Responses Specific for Paraneoplastic Cerebellar Degeneration-Associated Antigen by Whole Recombinant Yeast Immunization”, Journal of Autoimmunity, 2005, vol. 24, pp. 203-208.
[cited by applicant]
Lei et al., “Yeast Surface-Displayed H5N1 Avian Influenza Vaccines”, Hindawi publishing Corporation, 2016, pp. 1-12.
[cited by applicant]
Kim et al., “Oral Immunization With Whole Yeast Producing Viral Capsid Antigen Provokes a Stronger Humoral Immune Response Than Purified Viral Capsid Antigen”, Letters in Applied Microbiology, 2013, vol. 58, pp. 285-291.
[cited by applicant]
Safdari et al., “Use of Single-Chain Antibody Derivatives for Targeted Drug Delivery”, Molecular Medicine, 2016, vol. 22, pp. 258-270.
[cited by applicant]
“Sorrento Develops STI-4398 (COVIDTRAP™ Protein) for Potential Prevention and Treatment of SARS-COV-2 Coronavirus Disease (COVID-19)”, Sorrento Therapeutics, 2020, 4 pages.
[cited by applicant]
Batlle et al., “Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?”, Clinical Science, 2020, vol. 134, pp. 543-545.
[cited by applicant]
Kruse Robert L., “Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China [version 2; peerreview: 2 approved]”, F1000 Research, 2020, vol. 9, No. 7, 14 pages.
[cited by applicant]
Lu et al., “Arg15-Lys17-Arg18 Turkey Ovomucoid Third Domain Inhibits Human Furin”, The Journal of Biological Chemistry, 1993, vol. 268, No. 20, pp. 14583-14585.
[cited by applicant]
Coutard et al., “The spike glycoprotein of the new coronavirus 2019-nCOV contains a furin-like cleavage site absent in CoV of the same clade”, Antiviral Research, 2020, No. 176, 6 pages.
[cited by applicant]
Yao et al., “Polyethyleneimine-coating enhances adenoviral transduction of mesenchymal stem cells”, Biochemical and Biophysical Research Communications, 2014, vol. 447, No. 3, pp. 383-387.
[cited by applicant]
Yin et al., “[Measurement of subsets of blood T lymphocyte in 93 patients with severe acute respiratory syndrome and its clinical significance]”, Chinese Journal of Tuberculosis and Respiratory Diseases, 2003, vol. 26, …
[cited by applicant]
Non-Final Office Action received for U.S. Appl. No. 16/880,804 dated Jan. 1, 2021, 40 pages.
[cited by applicant]
Levin et al., “Fc fusion as a platform technology: potential for modulating immunogenicity”, Trends Biotechnol., 2015, vol. 33, No. 1, pp. 27-34.
[cited by applicant]
Renegar et al., “Role of IgA versus IgG in the Control of Influenza Viral Infection in the Murine Respiratory Tract”, J Immunol. 2004, vol. 173, pp. 1978-1986.
[cited by applicant]
Raftery et al., “Chitosan for Gene Delivery and Orthopedic TissueEngineering Applications”, Molecules, 2013, vol. 18, pp. 5611-5647.
[cited by applicant]
Cunningham et al., “Effective Long-term Preservation of Biological Evidence”, Bode Technology, 2014, 153 pages.
[cited by applicant]
Roth et al., “Functionalized Calcium Carbonate Microparticles for theDelivery of Proteins”, European Journal of Pharmaceutics and Biopharmaceutics, 2017, 38 pages.
[cited by applicant]
Rogers et al., “Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model”, Science, 2020, 12 pages.
[cited by applicant]
Wec et al., “Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARSCoV-2 spike protein”, Version 2. bioRxiv., 2020, 18 pages.
[cited by applicant]
Yuan et al., “A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV”, Science, 2020,, vol. 368, pp. 1-4.
[cited by applicant]
Glasgow et al., “Engineered ACE2 receptor traps potently neutralize SARS-CoV-2”, PNAS, 2020, 25 pages.
[cited by applicant]
Rice et al., “A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T-cell and Neutralizing Antibody Responses”, BioRxiv, 2020, 36 pages.
[cited by applicant]
Final Office Action received for U.S. Appl. No. 16/880,804 dated Mar. 22, 2021, 40 pages.
[cited by applicant]
UniProtKB—Q9BYF1 (ACE2_HUMAN), Aug. 2, 2005.
[cited by applicant]
See et al., “Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus”, Journal of General Virology, 2006, vol. 87, pp. 641-650.
[cited by applicant]
Sieling et al., “Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T CellRecall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells fromPatients Previously Infected with SAR…
[cited by applicant]
Gabitzsch et al., “Complete Protection of Nasal and Lung Airways Against SARS-CoV-2 Challengeby Antibody Plus Th1 Dominant N- and S-Specific T-Cell Responses to SubcutaneousPrime and Thermally-Stable Oral Boost Bivalent…
[cited by applicant]
Seif et al., “Yeast (
[cited by applicant]
Biondo et al., “Recognition of yeast nucleic acids triggers a host-protective type I interferon response”, Eur. J. Immunol., 2011, vol. 41, pp. 1969-1979.
[cited by applicant]
Non Final Office Action received for U.S. Appl. No. 17/379,849 dated Dec. 10, 2021, 30 pages.
[cited by applicant]
Final Office Action received for U.S. Appl. No. 17/379,849 dated Mar. 24, 2022, 83 pages.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 16/883,263 dated Oct. 5, 2021, 40 pages.
[cited by applicant]
Liniger et al., “Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles virus”, Vaccine, 2008, vol. 26, pp. 2164-2174.
[cited by applicant]
Wu et al., “A new coronavirus associated with human respiratory disease in China”, Nature, 2020, vol. 579, pp. 265-271.
[cited by applicant]
Gen Bank MN908947.3, Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome, Mar. 2020, 12 pages.
[cited by applicant]
Non Final Office Action received for U.S. Appl. No. 16/883,263 dated Sep. 2, 2022, 62 pages.
[cited by applicant]
Tan et al., “Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells”, Nucleic Acids Research, vo…
[cited by applicant]
Lin et al., “Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction”, Journal of General Virology, vol. 89,…
[cited by applicant]
Lu et al., “Importance of SARS-CoV spike protein Trp-rich region in viral infectivity”, Science Direct, Biochemical Biophysical Research Communications, vol. 371, 2008, pp. 356-360.
[cited by applicant]
Guo et al., “Identification of a new region of SARS-CoV S protein critical for viral entry”, Science Direct, J. Mol. Biol., vol. 394, 2009, pp. 600-605.
[cited by applicant]
Non Final Office Action received for U.S. Appl. No. 17/082,994 dated Mar. 3, 2022, 73 pages.
[cited by applicant]
Pietravalle et al., “Cleavage of membrane-bound CD40 ligand is not required for inducing B cell proliferation and differentiation”, Eur. J. Immunol, vol. 26, 1996, pp. 725-728.
[cited by applicant]
Final Office Action received for U.S. Appl. No. 16/883,263 dated Apr. 14, 2022, 40 pages.
[cited by applicant]
International Search Report and Written Opinion received for PCT Application Serial No. PCT/IB2021/054887 dated Sep. 6, 2021, 13 pages.
[cited by applicant]
Khodaei et al., “Covalent Immobilization of Protein A on Chitosan and Aldehyde Double-Branched Chitosan as Biocompatible Carriers for Immunoglobulin G (Igg) Purification”, Journal of Chromatographic Science, 2018, pp. 1…
[cited by applicant]
Byrnes et al., “A SARS-CoV-2 serological assay to determine the presence of blocking antibodies that compete for human ACE2 binding”, medRxiv, 2020, 23 pages.
[cited by applicant]
Wang et al., “A human monoclonal antibody blocking SARS-CoV-2 infection”, NatureCommunications, 2020, vol. 11, No. 2251, pp. 1-6.
[cited by applicant]
International Search Report and Written Opinion received for PCT Application Serial No. PCT/US2021/021737 dated Jun. 25, 2021, 11 pages.
[cited by applicant]
Zhao et al., “Identification and characterization of dominant helper T-cell epitopes in the nucleocapsid protein of severe acute respiratory syndrome coronavirus”, Journal of Virology, 2007, vol. 81, No. 11, pp. 6079-60…
[cited by applicant]
Gabitzsch et al., “Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA”, Cancer Immunology Immunotherapy, 2010, vol. 59, pp. 1131-1135.
[cited by applicant]
Fan et al., “The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties”, Structure, 2005, vol. 13, pp. 1859-1868.
[cited by applicant]
International Search Report and Written Opinion received for PCT Application Serial No. PCT/US2021/021819 dated Jun. 21, 2021, 20 pages.
[cited by applicant]
Oi-Wing et al., “Substitution at Aspartic Acid 1128 in the SARSCoronavirus Spike Glycoprotein Mediates Escape from aS2 Domain-Targeting Neutralizing Monoclonal Antibody”, Plos one, 2014, vol. 9, No. 7, pp. 1-11.
[cited by applicant]
Pak et al., “Structural Insights into Immune Recognition of theSevere Acute Respiratory Syndrome Coronavirus SProtein Receptor Binding Domain”, Journal of Molecular Biology, 2009, vol. 388, pp. 815-823.
[cited by applicant]
Park et al., “Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2”, bioRxiv , 2020, 22 pages.
[cited by applicant]
Tripp et al., “Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): Identification of neutralizing and antibodies reactive to S, N, M and E viral proteins”, Journal of Virological Methods, 2005, vol. 128, pp…
[cited by applicant]
Zheng et al., “Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2”, Eurosurveillance, 2020, vol. 25, No. 28, pp. 19-28.
[cited by applicant]
Non Final Office Action received for U.S. Appl. No. 17/726,427 dated Aug. 2, 2022, 10 pages.
[cited by applicant]
Partial Supplementary European Search Report received in European Patent Application Serial No. 21846127.5 dated Aug. 2, 2024, 14 pages.
[cited by applicant]
Bosnjak Berislav et al: “Low serum neutralizing anti-SARS-COV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods”, Cellular & Molecular Immunology, vol. 18,…
[cited by applicant]
Abe Kento T et al: “A simple protein-based surrogate neutralization assay for SARS-COV-2”, JCI Insight, vol. 5, No. 19, Oct. 2, 2020 (Oct. 2, 2020), XP055780531, ISSN: 2379-3708, DOI: 10.1172/jci.insight. 142362 Retriev…
[cited by applicant]
Edward P. Gniffke et al: “Plasma from recovered COVID19 subjects inhibits spike protein binding to ACE2 in a microsphere-based inhibition assay.”, MEDRXIV, Jun. 11, 2020 (Jun. 11, 2020), XP055769440, DOI: 10.1101/2020.0…
[cited by applicant]
Chan et al., “A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster”, lancet, vol. 395, pp. 514-523.
[cited by applicant]
Extended European Search Report received in European Patent Application Serial No. 21846127.5 dated Nov. 5, 2024, 16 pages.
[cited by applicant]
Rosales-Mendoza Sergio et al: “What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19?”, Vaccines, vol. 8, No. 2, Apr. 14, 2020 (Apr. 14, 2020), p. 183, XP093151469, CH ISSN: 2076-393X, DOI: 10.339…
[cited by applicant]
Wang Ning et al: “Aluminum Nanoparticles Acting as a Pulmonary Vaccine Adjuvant-Delivery System (VADS) Able to Safely Elicit Robust Systemic and Mucosal Immunity”, Journal of Inorganic and Organometallic Polymers and Ma…
[cited by applicant]
First Examination Report received in Australia Patent Application Serial No. 2021236141 dated Apr. 9, 2024, 05 pages.
[cited by applicant]
Notice of Acceptance for Patent Application received in Australia Patent Application Serial No. 2021236141 dated May 17, 2024, 03 pages.
[cited by applicant]
First Examination Report received in Australia Patent Application Serial No. 2021312381 dated May 22, 2024, 04 pages.
[cited by applicant]
Second Examination Report received in Australia Patent Application Serial No. 2021312381 dated Jun. 24, 2024, 05 pages.
[cited by applicant]
Third Examination Report received in Australia Patent Application Serial No. 2021312381 dated Sep. 4, 2024, 03 pages.
[cited by applicant]
Fourth Examination Report received in Australia Patent Application Serial No. 2021312381 dated Oct. 8, 2024, 08 pages.
[cited by applicant]
Ali, Amanat, et al., Dynamics of the ACE2-SARS-COV-2/SARS-COV spike protein interface reveal unique mechanisms', 2020, Scientific reports, vol. 10(1), pages (2020), Article 14214.
[cited by applicant]
Fukushi, Shuetsu., ‘Competitive ELISA for the detection of serum antibodies specific for middle east respiratory syndrome coronavirus (MERS-COV)’, 2020, Coronaviruses: Methods and Protocols, pp. 55-65.
[cited by applicant]
Neumann MM , Volodkin D . Porous antibody-containing protein microparticles as novel carriers for ELISA. Analyst. Feb. 1, 20207;145(4): 1202-1206. doi: 10.1039/c9an01888c. PMID: 31859691.
[cited by applicant]
Zhuang, Wei, et al. “Sensitive and portable electrochemical immunoassay for lipoprotein-associated phospholipase A 2 using BSA-doped CaCO 3 nanospheres to regulate pH readout.” Analytical Methods 11.12 (2019): 1631-1638.
[cited by applicant]
Peng J, Feng LN, Zhang K, Li XH, Jiang LP, Zhu JJ. Calcium carbonate-gold nanocluster hybrid spheres: synthesis and versatile application in immunoassays. Chemistry. Apr. 2, 20123;18(17):5261-8. doi: 10.1002/chem.201102…
[cited by applicant]
Mou, Huihui et al. “Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-COV-2.” bioRxiv : the preprint server for biology 2020.06.29.178459. Jun. 30, 2020, doi: 10.1101/2020.06.29.178459. P…
[cited by applicant]
Request for the Submission of an Opinion received in Korea Patent Application Serial No. 10-2023-7006003 dated Oct. 25, 2024, 11 pages (including English Translation).
[cited by applicant]
Seth J. zost et al., nature, (Jul. 15, 2020), vol. 584, and the pp. 443-449.
[cited by applicant]
First Office Action received in China Patent Application Serial No. 202180020795.0 dated Jun. 19, 2024, 18 pages.
[cited by applicant]
Notice of Reasons for Refusal received in Japan Patent Application Serial No. 2022-554944 dated Dec. 26, 2023, 11 pages.
[cited by applicant]
Decision of Refusal received in Japan Patent Application Serial No. 2022-554944 dated Aug. 2, 2024, 06 pages.
[cited by applicant]
Notice of Reasons for Refusal received in Japan Patent Application Serial No. 2023-503132 dated Aug. 13, 2024, 13 pages.
[cited by applicant]
Lee, Y., et al., Oct. 2023, Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics, Exp. Mol. Med. 55:2085-2096.
[cited by applicant]
Hou, X., et al., Dec. 2021, Lipid nanoparticles for mRNA delivery, Nat. Rev. Mat. 6:1078-1094.
[cited by applicant]
Sharon D., and A. Kamen, 2018, Advancements in the design and scalable production of viral gene transfer vectors, Biotechnology and Bioengineering, 115:25-40.
[cited by applicant]
Tan, Y. W., et al., Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells, Nucleic Acids Res. 3…
[cited by applicant]
Bhatti, J. S., et al., Nov. 2020, Therapeutic Strategies in the Development of Anti-viral Drugs and Vaccines Against SARS-COV-2 Infection, Mol. Neurobiol., DOI: 10.1007/s12035-020-02074-2, published online Aug. 18, 2020…
[cited by applicant]
Rice et al, “Intranasal plus subcutaneous prime vaccination with a dual antigen COVID 19 vaccine elicits T cell and antibody responses in mice” Scientific Reports, (2021) 11:14917 p. 1-15.
[cited by applicant]
International Preliminary Report on Patentability received for PCT Application Serial No. PCT/IB2021/054887 dated Feb. 2, 2023, 06 pages.
[cited by applicant]
International Preliminary Report on Patentability received for PCT Application Serial No. PCT/US2021/021737 dated Sep. 6, 2022, 06 pages.
[cited by applicant]
Office Action received in Canada Patent Application Serial No. 3170513 dated Aug. 21, 2023, 05 pages.
[cited by applicant]
Office Action received in Canada Patent Application Serial No. 3170513 dated Oct. 22, 2024, 03 pages.
[cited by applicant]
Extended European Search Report received in European Patent Application Serial No. 21768699.7 dated Mar. 18, 2024, 15 pages.
[cited by applicant]
Enjuanes, L. et al. (2008) Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Research, vol. 133, No. 1, 45 - 62, ISSN: 0168-1702, DOI: 10.1016/J.VIRUSRES.2007.01.021.
[cited by applicant]
Shi, J. et al. (2015) Epitope-based vaccine target screening against highly pathogenic MERS—CoV: an in silico approach applied to emerging infectious diseases. PLOS One, vol. 10, No. 12, e0144475, US ISSN: 1932-6203, DO…
[cited by applicant]
Abdelzaher, H. M., et al., 2021, RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement, Vaccines 9: 1-23.
[cited by applicant]
Nilvebrant, J., and J. Rockberg, 2018, An introduction to epitope mapping, Meth. Mol. Biol. 1785:1-10.
[cited by applicant]
Sanchez-Trincado, J. L., et al., 2017, Fundamentals and methods for T- and B-cell epitope prediction, J. Immunol. Res. Article ID 2680160, pp. 1-14.
[cited by applicant]
Lavarone, C., et al., 2017, Mechanism of action of mRNA-based vectors, Exp. Rev. Vaccines 16(9):871-881.
[cited by applicant]
Robert-Guroff, M., 2007, Replicating and non-replicating viral vectors for vaccine development, Curr. Opin. Biotechnol. 18:546-556.
[cited by applicant]
Second Office Action received in China Patent Application Serial No. 202180020795.0 dated Jan. 22, 2025, 09 pages.
[cited by applicant]