IP Library › Granted Patent US 12,691,234
Granted Patent B2
US 12,691,234 · App. 17/779,709 · Granted Jul 28, 2026

Methods employing gaseous nitric oxide for inhibiting tumor growth

Inventors: Hila Confino (Rehovot, IL); Steven A. Lisi (Garden City, NY); Rinat Kalaora (Rehovot, IL); Amir Avniel (Rehovot, IL)
Assignee: Beyond Air, Inc.
A61M13/003A61K9/0019A61K33/00A61K39/0011A61K40/24A61M39/223A61P35/00A61M2202/0275A61M2205/3334A61M2205/3344A61M2205/7536
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Quick Facts
Patent No.
US 12,691,234
App. No.
17/779,709
Filed
May 25, 2022
Granted
Jul 28, 2026
Kind
B2
Art Unit
1699
USPC
424/93.71
Abstract

Methods of inhibiting growth of cells or tissue of a primary and/or secondary tumor, and/or of stimulating an immunological response to the tumor, in a subject in need thereof, and systems for performing same, are provided. The methods employ local administration of a gas, such as gaseous nitric oxide, typically at a high dose. Immune cells obtained upon treating a tumor with gaseous nitric oxide, either in vivo or ex vivo, and methods employing same are also provided.

Claims (17)

1 . A method of inhibiting growth of cells or tissue of a primary and/or secondary tumor in a subject in need thereof, the method comprising locally administering to the tumor gaseous nitric oxide (gNO) at a dose of from about 1,000 ppm to about 1,000,000 ppm for a time period of from about 1 second to about 60 minutes at a volumetric flow of from about 0.00001 LPM to about 1 LPM, wherein locally administering said gNO is by intratumoral injection.

2 . The method according to claim 1 , wherein the gNO is administered at a dose of from about 20,000 ppm to about 200,000 ppm or from about 20,000 ppm to about 50,000 ppm.

3 . The method according to claim 1 , wherein the gNO is administered for a time period that ranges from about 30 seconds to about 10 minutes.

4 . The method according to claim 1 , wherein the gNO is administered at a volumetric flow of from about 0.001 LPM to about 0.5 LPM.

5 . The method according to claim 1 , wherein the gNO is administered at two or more administration sites in the tumor.

6 . The method according to claim 5 , wherein the distance between the two or more administration sites is, independently, from about 2.5 mm to about 1 cm, or from about 0.25 cm to about 0.5 cm.

7 . The method according to claim 1 , wherein the gNO is administered at a dose of from about 0.1 mg to about 300 mg, per cm 3 tumor.

8 . The method according to claim 1 , wherein gNO is administered at a dose of from about 0.01 mg to about 100 mg, or from 0.1 mg to about 10 mg, per a tumor of 20 mm 3 or less.

9 . The method according claim 1 , further comprising scavenging excess gNO from the administration site.

10 . The method according to claim 1 , wherein locally administering said gNO is pulsed from about 2 to about 20 times.

11 . The method according to claim 1 , wherein locally administering said gNO to the subject is performed at least once.

12 . The method according to claim 1 , wherein locally administering said gNO to the subject is performed at least twice, and wherein a time interval between said two administrations is at least one week.

13 . The method according to claim 1 , further comprising co-administering to the subject an anti-cancer therapy.

14 . The method according to claim 1 , being for inhibiting growth and/or killing cells of a primary tumor.

15 . The method according to claim 1 , being for preventing occurrence, inhibiting growth and/or killing cells of a secondary tumor.

16 . The method according to claim 1 , wherein said secondary tumor comprises metastasizing tumor and/or a recurrent tumor.

17 . The method according to claim 1 , being for stimulating in the subject an immunological response to the tumor, thereby inhibiting growth of a primary tumor and/or a secondary tumor.

Assignments (2)
SECURITY INTEREST Recorded Nov 6, 2025
From: BEYOND AIR, INC.
To: STREETERVILLE CAPITAL, LLC
Reel/Frame 072815/0119 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 19, 2022
From: CONFINO, HILA; LISI, STEVEN A.; KALAORA, RINAT; AVNIEL, AMIR
To: BEYOND AIR, INC.
Reel/Frame 060541/0802 →
Continuity (8)
Provisional Application 63090345 · Oct 12, 2020
Provisional Application 63027120 · May 19, 2020
Provisional Application 62985611 · Mar 5, 2020
Provisional Application 62984926 · Mar 4, 2020
Provisional Application 62982817 · Feb 28, 2020
Provisional Application 62963849 · Jan 21, 2020
Provisional Application 62939975 · Nov 25, 2019
Related Publication 20230338416A1 · Oct 26, 2023
References Cited (65)
US 5345928A · Lindkvist · 1994 [cited by applicant]
US 5873359A · Zapol et al. · 1999 [cited by applicant]
US 6962154B2 · Krebs · 2005 [cited by applicant]
US 7955294B2 · Stenzler et al. · 2011 [cited by applicant]
US 8017582B2 · Shirwan et al. · 2011 [cited by applicant]
US 8168232B2 · Graham et al. · 2012 [cited by applicant]
US 12569628B2 · Scholz · 2026 [cited by examiner]
US 20020078958A1 · Stenzler · 2002 [cited by applicant]
US 20020155164A1 · Figley et al. · 2002 [cited by applicant]
US 20040258772A1 · Otterbein · 2004 [cited by applicant]
US 20050004511A1 · Figley et al. · 2005 [cited by applicant]
US 20050217679A1 · Miller et al. · 2005 [cited by applicant]
US 20060290525A1 · Andersen et al. · 2006 [cited by applicant]
US 20070275100A1 · Miller · 2007 [cited by applicant]
US 20080193566A1 · Miller et al. · 2008 [cited by applicant]
US 20090205655A1 · Montgomery et al. · 2009 [cited by applicant]
US 20130239962A1 · Goldstein · 2013 [cited by applicant]
US 20150320951A1 · Acker et al. · 2015 [cited by applicant]
US 20170043115A1 · Murphy et al. · 2017 [cited by applicant]
US 20180280654A1 · Borrello · 2018 [cited by applicant]
US 20220111173A1 · Lautner et al. · 2022 [cited by applicant]
DE 10306766A1 · 2004 [cited by applicant]
WO 2005110441A2 · 2005 [cited by applicant]
WO WO2008095311 · 2008 [cited by applicant]
WO WO2008095312 · 2008 [cited by applicant]
WO 2009023750A1 · 2009 [cited by applicant]
WO WO2013132500 · 2013 [cited by applicant]
WO WO2013132503 · 2013 [cited by applicant]
WO WO2014008490 · 2014 [cited by applicant]
WO WO20171055995 · 2014 [cited by applicant]
WO 2016077635A1 · 2016 [cited by applicant]
WO WO2016168680 · 2016 [cited by applicant]
WO 2019130117A1 · 2019 [cited by applicant]
WO WO2021105900 · 2021 [cited by applicant]
WO WO2021105901 · 2021 [cited by applicant]
WO WO2021105900A1 · 2021 [cited by examiner]
WO 2022043931A2 · 2022 [cited by applicant]
WO 2022249104A1 · 2022 [cited by applicant]
Wang et al. “Nitric Oxide Delivery System for Cell Culture Studies” Annals of Biomedical Engineering, vol. 31, pp. 65-79, 2003 (Year: 2003). [cited by examiner]
Olson, S. Y, et al., “Abstract 5631: Nitric oxide-based immune response modifications: A novel paradigm in tumor vaccine development against melanoma”, Can. Res., 51(8), Suppl., Apr. 1, 2010, 1 pg. [cited by applicant]
International Preliminary Report on Patentability Dated Jun. 9, 2022 From the International Bureau of WIPO Re. Application No. PCT/IB2020/061149. (8 Pages). [cited by applicant]
International Preliminary Report on Patentability Dated Jun. 9, 2022 From the International Bureau of WIPO Re. Application No. PCT/IB2020/061150. (15 Pages). [cited by applicant]
International Search Report and the Written Opinion Dated Jul. 9, 2021 From the International Searching Authority Re. Application No. PCT/IB2020/061150. (27 Pages). [cited by applicant]
International Search Report and the Written Opinion Dated May 12, 2021 From the International Searching Authority Re. Application No. PCT/IB2020/061149. (13 Pages). [cited by applicant]
Invitation to Pay Additional Fees Dated May 3, 2021 From the International Searching Authority Re. Application No. PCT/IB2020/061150. (2 Pages). [cited by applicant]
Official Action Dated Jun. 17, 2022 from US Patent and Trademark Office Re. U.S. Appl. No. 17/620,696. (13 pages). [cited by applicant]
Bonavida et al. “Nitric Oxide-Mediated Sensitization of Resistant Tumor Cells to Apoptosis by Chemo-Immunotherapeutics”, Redox Biology, 6: 486-494, Available Online Aug. 18, 2015. [cited by applicant]
Confino et al. “Beyond Air® to Present New Nitric Oxide Data in an e-Poster Presentation at the North America Conference on Lung Cancer 2020 (NACLC 2020)”, Globe News Wire, 7 P., Aug. 27, 2020. [cited by applicant]
Confino et al. “Gaseous Nitric Oxide at High Concentrations Is A Powerful Anti-Tumor Agent Both In-Vitro and In-Vivo”, AACR, Poster, Jun. 2020. [cited by applicant]
Confino et al. “Nitric Oxide Lung Cancer Active Vaccination”, 2020 North America Conference on Lung Cancer, #NACLC20, Worldwide Virtual Event, Oct. 16-17, 2020, Slide Show, 14 P., Oct. 16, 2020. [cited by applicant]
Confino et al. “Nitric Oxide Tumor Ablation Stimulates An Anti-Tumor Immune Response in Mice”, AACR, American Association for Cancer Research, AACR Virtual Special Conference on Tumor Immunology and Immunotherapy, Israe… [cited by applicant]
El-Naa ct al. “Sildenafil Potentiates the Antitumor Activity of Cisplatin by Induction of Apoptosis and Inhibition of Proliferation and Angiogenesis”, Drug Design, Development and Therapy, 10: 3661-3672, Published Onlin… [cited by applicant]
Huerta “Nitric Oxide for Cancer Therapy”, Future Science, 1(1): FSO44-1-FSO44-9, Aug. 1, 2015. [cited by applicant]
Keisari et al. “Activation of Local and Systemic Anti-Tumor Immune Responses by Ablation of Solid Tumors With Intratumoral Electrochemical or Alpha Radiation Treatments”, Cancer Immunology, Immunotherapy, 63(1): 1-9, Pu… [cited by applicant]
Knavel et al. “Tumor Ablation: Common Modalities and General Practices”, Techniques in Vascular and Interventional Radiology, 16(4): 192-200, Dec. 2013. [cited by applicant]
Lin et al. “Non-Thermal Plasma as a Unique Delivery System of Short-Lived Reactive Oxygen and Nitrogen Species for Immunogenic Cell Death in Melanoma Cells”, Advanced Science, 6(6): 1802062-1-802062-15, Jan. 28, 2019. [cited by applicant]
Nath et al. “Nitric Oxide-Releasing Aspirin Suppresses NF-KB Signaling in Estrogen Receptor Negative Breast Cancer Cells In Vitro and In Vivo”, Molecules, 20(7): 12481-12499, Jul. 9, 2015.2015. [cited by applicant]
Ning et al. “Novel Nitric Oxide Generating Compound Glycidyl Nitrate Enhances the Therapeutic Efficacy of Chemotherapy and Radiotherapy”, Biochemical and Biophysical Research Communications, 447(3): 537-542, Available O… [cited by applicant]
Rizi et al. “Nitric Oxide: The Forgotten Child of Tumor Metabolism”, Trends in Cancer, 3(9): 659-672, Published Online Aug. 18, 2017. [cited by applicant]
Schairer et al. “The Potential of Nitric Oxide Releasing Therapies as Antimicrobial Agents”, Virulence, 3(3): 271-279, Published Online May 1, 2012. [cited by applicant]
Seabra et al. “Nitric Oxide Donors for Prostate and Bladder Cancers: Current State and Challenges”, European Journal of Pharmacology, 826: 158-168, Published Online Mar. 1, 2018. [cited by applicant]
Slovak et al. “Immuno-Thermal Ablations—Boosting the Anticancer Immune Response”, Journal for Immuno Therapy of Cancer, 5(1): 78-1-78-15, Oct. 17, 2017. [cited by applicant]
Srivatsan et al. “Allogeneic Tumor Cell Vaccines. The Promise and Limitations in Clinical Trials”, Human Vaccines & Immunotherapeutics, 10(1): 52-63, Published Online Sep. 24, 2013. [cited by applicant]
Vannini et al. “The Dual Role of iNOS in Cancer”, Redox Biology, 6: 334-343, Available Online Aug. 24, 2015. [cited by applicant]
Weyerbrock et al. “Growth Inhibition and Chemosensitization of Exogenous Nitric Oxide Released From NONOates in Glioma Cells In Vitro: Laboratory Investigation”, Journal of Neurosurgery, 110(1): 128-136, Jan. 2009. [cited by applicant]