IP Library › Granted Patent US 12,343,405
Granted Patent B2
US 12,343,405 · App. 18/599,893 · Granted Jul 1, 2025

High sterol-containing lipid nanoparticles

Inventors: Kevin An (Vancouver, CA); Daniel Kurek (Vancouver, CA); Jayesh Kulkarni (Vancouver, CA); Dominik Witzigmann (Vancouver, CA)
Assignee: Nano Vation Therapeutics Inc.
A61K47/6909A61K31/575A61K31/661C12N15/113
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Quick Facts
Patent No.
US 12,343,405
App. No.
18/599,893
Granted
Jul 1, 2025
Kind
B2
Abstract

The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 3 mol %, wherein each mol % content is relative to total lipid present in the lipid nanoparticle.

Claims (10)

1. A method for delivery of mRNA or vector DNA for in vivo production of protein or peptide in the liver, the method comprising administering to a mammal a lipid nanoparticle having 49 to 85 mol % of a sterol or a derivative thereof, a phospholipid or a phospholipid-sterol conjugate at 0 to 7 mol % that is in a neutral zwitterionic form at physiological pH, an ionizable lipid and a hydrophilic polymer-lipid conjugate present at 0.5 to 1.8 mol %, wherein the mRNA or vector DNA is encapsulated within the lipid nanoparticle and wherein the administering of the lipid nanoparticle results in liver-specific expression of the protein or peptide encoded by the mRNA or vector DNA, wherein the lipid nanoparticle has increased expression of the protein or peptide encoded by the mRNA or vector DNA in the liver over the spleen by at least 20-fold.

2. The method of claim 1 , wherein the phospholipid or the phospholipid-sterol conjugate content is between 1 and 5 mol %.

3. The method of claim 2 , wherein the phospholipid or the phospholipid-sterol conjugate content is between 1 and 3.5 mol %.

4. The method of claim 1 , wherein the phospholipid or the phospholipid-sterol conjugate content is less than 7 mol %.

5. The method of claim 4 , wherein the phospholipid or the phospholipid-sterol conjugate content is less than 6 mol %.

6. The method of claim 5 , wherein the phospholipid or the phospholipid-sterol conjugate content is less than 5 mol %.

7. The method of claim 6 , wherein the phospholipid or the phospholipid-sterol conjugate content is less than 4 mol %.

8. The method of claim 1 , wherein the sterol or derivative thereof is present at 49 to 80 mol %.

9. The method of claim 8 , wherein the sterol or derivative thereof is present at 49 to 65 mol %.

10. The method of claim 1 , wherein the hydrophilic polymer-lipid conjugate is present in the lipid nanoparticle at a content between 0.5 and 1.6 mol %.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2024
From: AN, KEVIN; KUREK, DANIEL; KULKARNI, JAYESH; WITZIGMANN, DOMINIK
To: NANOVATION THERAPEUTICS INC.
Reel/Frame 066706/0004 →
Continuity (3)
Division 18187904 · Mar 22, 2023
Provisional Application 63269815 · Mar 23, 2022
Related Publication 20240207439A1 · Jun 27, 2024
References Cited (68)
US 5041278A · Janoff et al. · 1991 [cited by applicant]
US 5830499A · Bouwstra · 1998 [cited by applicant]
US 7220833B2 · Nelson et al. · 2007 [cited by applicant]
US 7514099B2 · Chen et al. · 2009 [cited by applicant]
US 8058069B2 · Yaworski et al. · 2011 [cited by applicant]
US 8492359B2 · Yaworski et al. · 2013 [cited by applicant]
US 8822668B2 · Yaworski et al. · 2014 [cited by applicant]
US 9301923B2 · Baryza et al. · 2016 [cited by applicant]
US 9364435B2 · Yaworski et al. · 2016 [cited by applicant]
US 9878042B2 · Yaworski et al. · 2018 [cited by applicant]
US 10228371B2 · Baumeister et al. · 2019 [cited by applicant]
US 11052052B2 · Schentag et al. · 2021 [cited by applicant]
US 11141378B2 · Yaworski et al. · 2021 [cited by applicant]
US 11191849B2 · Abrams · 2021 [cited by examiner]
US 11219634B2 · Prieve et al. · 2022 [cited by applicant]
US 11229609B2 · Cheng et al. · 2022 [cited by applicant]
US 11291734B2 · Guild et al. · 2022 [cited by applicant]
US 11338044B2 · Guild et al. · 2022 [cited by applicant]
US 11547754B2 · Guild et al. · 2023 [cited by applicant]
US 12011507B2 · Kurek · 2024 [cited by examiner]
US 20050037200A1 · Wallach · 2005 [cited by applicant]
US 20100297242A1 · Park et al. · 2010 [cited by applicant]
US 20110111044A1 · Zhao et al. · 2011 [cited by applicant]
US 20110177156A1 · Szoka, Jr. et al. · 2011 [cited by applicant]
US 20120308663A1 · Roger · 2012 [cited by applicant]
US 20150140069A1 · Hong et al. · 2015 [cited by applicant]
US 20190314291A1 · Besin et al. · 2019 [cited by applicant]
US 20200078313A1 · Roy et al. · 2020 [cited by applicant]
US 20200129445A1 · Patel et al. · 2020 [cited by applicant]
US 20210267895A1 · Yaworski et al. · 2021 [cited by applicant]
US 20210346306A1 · Dimitrov et al. · 2021 [cited by applicant]
US 20230302153A1 · An et al. · 2023 [cited by applicant]
CA 1337332C · 1995 [cited by applicant]
CA 3088321A1 · 2019 [cited by applicant]
CA 3158293A1 · 2021 [cited by applicant]
WO WO2019067992A1 · 2019 [cited by applicant]
WO WO2019141814A1 · 2019 [cited by applicant]
WO WO2021055892A1 · 2021 [cited by applicant]
WO WO2021163002A1 · 2021 [cited by applicant]
Bach, D., and Wachtel, E., “Phospholipid/cholesterol model membranes: formation of cholesterol crystallites”, Biochimica et Biophysica Acta 1610 (2003) 187-197. [cited by applicant]
Brockerhoff and Ramsammy, “Preparation and Structural Studies of Cholesterol Bilayers”, Biochimica et Biophysica Acta, 1982, 691 :227-232. [cited by applicant]
Cheng and Lee, “The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery”, Advanced Drug Delivery Reviews, 2016, 99:129-137. [cited by applicant]
Cheng et al., “Selective Organ Targeting (SORT) nanoparticles for tissue specific mRNA delivery and CRISPR/Cas Jene editing”, Nat. Nanotechnol., Apr. 2020, 15(4): 313-320. [cited by applicant]
Dabkowska et al., “The effect of neutral helper lipids on the structure of cationic lipid monolayers”, J_ R. Soc. interface, 2012, 9:548-561. [cited by applicant]
Drummond et al., “Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors”, Pharmacological Reviews, 1999, 51(4):691-743. [cited by applicant]
Foglia et al., “Structural Studies of the Monolayers and Bilayers Formed by a Novel Cholesterol- Phospholipid; chimera”, Langmuir, 2011, 27:8275-8281. [cited by applicant]
Hayes et al., “Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery”, 3ene Therapy, 2006, 13:646-651. [cited by applicant]
Huang and Szoka, “Sterol-Modified Phospholipids: Cholesterol and Phospholipid Chimeras with Improved Biomembrane Properties”, J. Am. Chem. Soc., 2008, 130:15702-15712. [cited by applicant]
Huang et al., “Disterolphospholipids: Nonexchangeable Lipids and Their Application to Liposomal Drug Delivery”, unchristen Agnew Chem., 2009, 121:4210-4213. [cited by applicant]
Man et al., “Characterization of the colloidal properties, in vitro antifungal activity, antileishmanial activity and toxicity n mice of a distagmasterylhemisuccinoyl-glycero-phosphocholine liposome-intercalated amphote… [cited by applicant]
Kieler-Ferguson et al., “Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids”, European Journal of Pharmaceutical Sciences, 2017, 103:8… [cited by applicant]
Kubota et al., “Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation”, International Journal of Nanomedicine, 2017, 12:5121-5133. [cited by applicant]
Kulkarni et al., “Lipid nanoparticles enabling gene therapies: from concepts to clinical utility”, Nucleic Acid Therapeutics, 2018, 28(3):146-157. [cited by applicant]
Kulkarni et al., “On the Formation and Morphology of Lipid Nanoparticles Containing ionizable Cationic Lipids and iRNA”, ACS Nano, 2018, 12:4787-4795. [cited by applicant]
Kulkarni et al., “On the role of helper lipids in lipid nanoparticle formulations of siRNA”, Nanoscale, 2019, 11 :21733-21739. [cited by applicant]
Patel et al., “Naturally—Occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA”, Nature Communications, 2020, 11(1):3435. [cited by applicant]
Pozzi et al., “Transfection efficiency boost of cholesterol-containing lipoplexes”, Biochimica et Biophysica Acta, 2012, 1818:2335-2343. [cited by applicant]
Ramsammy et al., “Association of Cholesterol with Lysophosphatidylcholine”, Chemistry and Physics of Lipids, 1983, 32:83-89. [cited by applicant]
Roces et al., “Manufacturing considerations for the development of lipid nanoparticles using microfluidics”, Pharmaceutics, 2020, 12:1095. [cited by applicant]
Sakurai et al., “Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol Jr DOPE as a helper lipid in the single-pass rat lung perfusion system”, European Journal of Pharmace… [cited by applicant]
Sato et al., “Hydrophobic scaffolds of pH-sensitive cationic lipids contribute to miscibility with phospholipids and improve the efficiency of delivering short interfering RNA by small-sized lipid nanoparticles”, Acta B… [cited by applicant]
Tenchov et al., “Cubic Phases in Phosphatidylcholine-cholesterol mixtures: Cholesterol as Membrane ‘Fusogen’”, Biophysical Journal, 2006, 91:2508-2516. [cited by applicant]
Written Opinion and International Search Report of the PCT, for PCT international application No. PCT/CA2023/050370, dated May 30, 2023, Issued by the Canadian Intellectual Property Office acting as the International Se… [cited by applicant]
Yoshioka et al., “Cationic liposomes-mediated plasmid DNA delivery in murine hepatitis induced by carbon tetrachloride”, Journal of Liposome Research, 2009, 19(2):141-147. [cited by applicant]
Yuan et al., “Ternary nanoparticles of anionic lipid nanoparticles/protamine/DNA for gene delivery”, Int J Pharm, 2010, 392 (1-2):224-31. [cited by applicant]
Zhang et al., “Helper lipid structure influences protein adsorption and delivery of lipid nanoparticles to spleen and liver”, Biomater. Sci., 2021, 9:1449-1463. [cited by applicant]
Zhang et al., “Helper lipid structure influences protein adsorption and delivery of lipid nanoparticles to spleen and liver”, Biomater. Sci, 2021, 9:1449-1463, Supplementary Information. [cited by applicant]
Office Action issued in U.S. Appl. No. 18/187,904 dated Sep. 21, 2023. [cited by applicant]