IP Library › Granted Patent US 12,544,447
Granted Patent B2
US 12,544,447 · App. 18/604,387 · Granted Feb 10, 2026

Nuclease-dendrimer formulations for Covid-19 and broad-spectrum antiviral therapy and prophylaxis

Inventors: Xiaohua Su (Houston, TX); Leonid I. Rudin (San Marino, CA)
Assignee: Fulu Labs Corporation
A61K47/54A61P31/14
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Quick Facts
Patent No.
US 12,544,447
App. No.
18/604,387
Granted
Feb 10, 2026
Kind
B2
Abstract

Compositions of nucleases in formulations with dendrimers are used in pharmaceutically effective dosages as therapeutics for covid-19 and a broad spectrum of viruses in various embodiments. When cationized nucleases are mixed and/or complexed with a dendrimer, an unexpected positive dendrimer effect is manifest. This positive dendrimer effect is shown to be highly effective for catalyzing anti-viral RNase properties. In various embodiments compositions of cationized nucleases in combination with a dendrimer demonstrated this synergistic amplification of anti-viral effectiveness and are used in pharmaceutically effective dosages as therapeutics against covid-19 and a broad spectrum of viruses. An exemplar formulation which exhibits a positive dendrimer effect is cationized RNase A mixed and/or complexed with gen 2 PAMAM dendrimer.

Claims (16)

1 . A method for treating a mammal infected by an RNA virus, comprising:

administering a therapeutically effective amount of a pharmaceutical composition to the mammal, wherein the pharmaceutical composition comprises an ethylenediamine modified RNAse A mixed with a generation 2 poly PAMAM dendrimer;

wherein the ethylenediamine modified RNase A is in a range of 10 μg/ml to 20 μg/ml and is mildly-cationized to an aggregate net charge of about +11 to +13; and

wherein the PAMAM dendrimer is in a range of 50 μM to 100 μM.

2 . The method of claim 1 , wherein the ethylenediamine modified RNase A is ethylenediamine modified bovine pancreatic RNase A.

3 . The method of claim 1 , wherein the virus is a coronavirus.

4 . The method of claim 1 , wherein the coronavirus is SARS-COV-2 or HCoV-OC43.

5 . The method of claim 1 , wherein the concentration of ethylenediamine modified RNase A is about 10 μg/ml.

6 . The method of claim 1 , wherein the concentration of ethylenediamine modified RNase A is about 20 μg/ml.

7 . The method of claim 1 , wherein the concentration of PAMAM dendrimer is about 50 μM.

8 . The method of claim 1 , wherein the concentration of PAMAM dendrimer is about 100 μM.

9 . The method of claim 1 , wherein the concentration of ethylenediamine modified RNase A is about 10 μg/ml and the concentration of PAMAM dendrimer is about 50 μM.

10 . A composition for treating a viral infection comprising a therapeutically effective formulation of an ethylenediamine modified RNAse A mixed with a generation 2 poly PAMAM dendrimer; wherein the ethylenediamine modified RNase A is in a range of 10 μg/ml to 20 μg/ml and is mildly-cationized; and wherein the PAMAM dendrimer is in a range of 50 μM to 100 μM.

11 . The composition of claim 10 , wherein the cationized RNase A is chosen from the group of: RNase A-SO3−, RNaseA-OH, and RNaseA-NH3+.

12 . The composition of claim 10 , wherein the virus is a coronavirus.

13 . The composition of claim 12 , wherein the coronavirus is SARS-COV-2 or HCoV-OC43.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2024
From: SU, XIAOHUA, DR.
To: FULU LABS CORPORATION
Reel/Frame 066898/0878 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2024
From: RUDIN, LEONID I., DR.
To: FULU LABS CORPORATION
Reel/Frame 066908/0798 →
Continuity (5)
Continuation 17367357 · Jul 3, 2021
Provisional Application 63166407 · Mar 26, 2021
Provisional Application 63083493 · Sep 25, 2020
Provisional Application 63063419 · Aug 9, 2020
Related Publication 20250009887A1 · Jan 9, 2025
References Cited (37)
US 5484589A · Salganik · 1996 [cited by applicant]
US 5795582A · Wright · 1998 [cited by applicant]
US 6190650B1 · Matthews et al. · 2001 [cited by applicant]
US 7235583B1 · Webb et al. · 2007 [cited by applicant]
US 9592277B2 · Appelbaum et al. · 2017 [cited by applicant]
US 10335372B2 · Applebaum · 2019 [cited by applicant]
US 20140294851A1 · Nguyen · 2014 [cited by applicant]
US 20220040315A1 · Su et al. · 2022 [cited by applicant]
WO WO2019198068A1 · 2019 [cited by applicant]
WO WO2022035789A1 · 2022 [cited by applicant]
Ellis, Gregory A., Megan L. Hornung, and Ronald T. Raines. “Potentiation of ribonuclease cytotoxicity by a poly (amidoamine) dendrimer.” Bioorganic & medicinal chemistry letters 21.9 (2011): 2756-2758. (Year: 2011). [cited by examiner]
Ilinskaya, O. N., and R. Shah Mahmud. “Ribonucleases as antiviral agents.” Molecular Biology 48.5 (2014): 615-623. (Year: 2014). [cited by examiner]
Abbott et al., “Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza”. Cell. May 14, 2020; 181(4): 865-76. [cited by applicant]
Dijkman et al., “The dominance of human coronavirus OC43 and NL63 infections in infants”. Journal of Clinical Virology. Feb. 1, 2012; 53(2): 135-9. [cited by applicant]
Drayman et al. “Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2”. Science. Aug. 20, 2021; 373(6557): 931-6. [cited by applicant]
Dubois et al., “Cationic poly (amidoamine) promotes cytosolic delivery of bovine RNase A in melanoma cells, while maintaining its cellular toxicity”. Journal of Materials Chemistry B. 2015; 3(31): 6501-8. [cited by applicant]
Ellis et al., “Potentiation of ribonuclease cytotoxicity by a poly (amidoamine) dendrimer”. Bioorganic & Medicinal Chemistry Letters. May 1, 2011; 21(9): 2756-8. [cited by applicant]
Ferruti et al., “Poly (amidoamine) s: Past, present, and perspectives. Journal of Polymer Science Part A: Polymer Chemistry”. Jun. 2013; 51(11): 2319-53. [cited by applicant]
Futami et al., “Optimum modification for the highest cytotoxicity of cationized ribonuclease”. The Journal of Biochemistry. 2002; 132(2): 223-8. [cited by applicant]
Futami et al., “Preparation of potent cytotoxic ribonucleases by cationization: enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups”. Biochemistry. … [cited by applicant]
Gupta et al., “Dendrimers: A review on synthetic approaches”. Journal of Applied Pharmaceutical Science. Mar. 28, 2015; 5(3): 117-22. [cited by applicant]
Illinskaya et al., “Cytotoxicity of RNases is increased by cationization and counteracted by KCa channels”. Biochemical and biophysical research communications. Feb. 6, 2004; 314(2): 550-4. [cited by applicant]
Illinskaya et al., “Ribonucleases as antiviral agents”. Molecular Biology. Sep. 2014; 48: 615-23. [cited by applicant]
International Preliminary Report issued in International Application No. PCT/US2021/045282 mailed Feb. 7, 2023, 9 pages. [cited by applicant]
International Search Report and Written issued in International Application No. PCT/US2021/045282 mailed Dec. 28, 2021, 10 pages. [cited by applicant]
Keiser et al., “Automation of infectious focus assay for determination of filovirus titers and direct comparison to plaque and TCID50 assays”. Microorganisms. Jan. 12, 2021; 9(1): pp. 1-13. [cited by applicant]
Leland et al., “Ribonuclease A variants with potent cytotoxic activity”. Proceedings of the National Academy of Sciences. Sep. 1, 1998; 95(18): 10407-12. [cited by applicant]
Liu et al., “Human coronavirus-229E,-OC43,-NL63, and-HKU1 (Coronaviridae)”. Encyclopedia of virology. 2021: 13 pages. [cited by applicant]
Michen et al., “Isoelectric points of viruses. Journal of applied microbiology”. Aug. 1, 2010; 109(2): 388-97. [cited by applicant]
Mitkevich et al., Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge. Oncoscience. 2014; 1(11): 7 pages. [cited by applicant]
Mohanraju, et al., “Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems”; Science; vol. 353, No. 6299, 14 pages (Aug. 5, 2016). [cited by applicant]
Mousavizadeh et al., “Genotype and phenotype of COVID-19: Their roles in pathogenesis”. Journal of Microbiology, Immunology and Infection. Apr. 1, 2021; 54(2): 159-63. [cited by applicant]
Ranucci et al., “Polyamidoamines: Versatile bioactive polymers with potential for biotechnological applications”. Chemistry Africa. Jun. 1, 2019; 2(2): 167-93. [cited by applicant]
Salganik et al., “Effect of Deoxyribonuclease on the Course of Lymphatic Leukaemia in AKR Mice”. Nature 214, 100-102 (1967). https://doi.org/10.1038/214100a0. [cited by applicant]
Salganik et al., Inhibition of RNA synthesis and reproduction of tick-encephalitis virus under the influence of ribonuclease. Doklady Akademii nauk SSSR. Jun. 21, 1968; 180(6): 1473-5. [cited by applicant]
Ulyanova et al., “Anti-influenza activity of the ribonuclease binase: Cellular targets detected by quantitative proteomics”. International Journal of Molecular Sciences. Nov. 5, 2020; 21(21): 23 pages. [cited by applicant]
Wang et al., “Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. Jama”. Mar. 17, 2020; 323(11): 1061-9. [cited by applicant]