Granted Patent
B2
US 12,685,787 · App. 19/431,261 · Granted Jul 21, 2026
Lipid nanoparticles with RNA for cosmetic treatment
Assignee:
Lipovectra Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
A method for directing a change in cell state of white adipose tissue (WAT) which involve treating WAT cells with mRNA encapsulated inside lipid nanoparticles (LNPs). The mRNA encodes UCP1 or other proteins that may transition WAT to brown adipose tissue (BAT). The LNP may contain (C14-4:NCL:Cholesterol:PEG/Lipid Conjugate) at the molar ratio of (35:16:46.5:2.5), (50:10:38.5:1.5) or (56.5:10:31.8:1.7).
Claims (21)
1 . A pharmaceutical composition comprising:
a synthetic mRNA comprising the nucleotide sequence set forth in SEQ ID NO: 6;
wherein the synthetic mRNA is packaged in a lipid nanoparticle (LNP).
2 . The pharmaceutical composition of claim 1 , wherein the LNP comprises (C14-4: non-cationic lipids (NCL): Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (35:16:46.5:2.5), (50:10:38.5:1.5) or (56.5:10:31.8:1.7).
3 . The pharmaceutical composition of claim 1 , wherein the LNP comprises (SM-102:NCL:Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (50:10:38.5:1.5), (48.3:9.1:40.5:2.1) or (46.6:10.4:41.2:1.8).
4 . The pharmaceutical composition of claim 1 , wherein all uridine nucleotides of the synthetic mRNA are substituted with pseudouridines.
5 . The pharmaceutical composition of claim 1 , wherein all uridine nucleotides of the synthetic mRNA are substituted with N1-Methylpseudouridines.
6 . A pharmaceutical composition comprising:
a synthetic mRNA comprising the nucleotide sequence set forth in SEQ ID NO: 3;
wherein the synthetic mRNA is packaged in a lipid nanoparticle (LNP).
7 . The pharmaceutical composition of claim 6 , wherein the LNP comprises (C14-4: non-cationic lipids (NCL): Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (35:16:46.5:2.5), (50:10:38.5:1.5) or (56.5:10:31.8:1.7).
8 . The pharmaceutical composition of claim 6 , wherein the LNP comprises (SM-102:NCL:Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (50:10:38.5:1.5), (48.3:9.1:40.5:2.1) or (46.6:10.4:41.2:1.8).
9 . The pharmaceutical composition of claim 6 , wherein all uridine nucleotides of the synthetic mRNA are substituted with pseudouridines.
10 . The pharmaceutical composition of claim 6 , wherein all uridine nucleotides of the synthetic mRNA are substituted with N1-Methylpseudouridines.
11 . A pharmaceutical composition comprising:
a synthetic mRNA comprising the nucleotide sequence set forth in SEQ ID NO: 4;
wherein the synthetic mRNA is packaged in a lipid nanoparticle (LNP).
12 . The pharmaceutical composition of claim 11 , wherein the LNP comprises (C14-4: non-cationic lipids (NCL): Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (35:16:46.5:2.5), (50:10:38.5:1.5) or (56.5:10:31.8:1.7).
13 . The pharmaceutical composition of claim 11 , wherein the LNP comprises (SM-102:NCL:Cholesterol:PEG/Lipid Conjugate) at a molar ratio of (50:10:38.5:1.5), (48.3:9.1:40.5:2.1) or (46.6:10.4:41.2:1.8).
14 . The pharmaceutical composition of claim 11 , wherein all uridine nucleotides of the synthetic mRNA are substituted with pseudouridines.
15 . The pharmaceutical composition of claim 11 , wherein all uridine nucleotides of the synthetic mRNA are substituted with N1-Methylpseudouridines.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 2, 2026
From: HO PAK LAU, FRANK
To: BOURGEOIS, JASON
Reel/Frame 074823/0566 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 2, 2026
From: BOURGEOIS, JASON
To: LIPOVECTRA INC.
Reel/Frame 074823/0717 →
Continuity (5)
Continuation In Part
PCTUS2025031590
· May 30, 2025
Provisional Application
63868661
· Aug 22, 2025
Provisional Application
63771940
· Mar 14, 2025
Provisional Application
63653319
· May 30, 2024
Related Publication
20260115326A1
· Apr 30, 2026
References Cited (123)
US 8058069B2
· Yaworski et al.
· 2011
[cited by applicant]
US 8158601B2
· Chen et al.
· 2012
[cited by applicant]
US 8492359B2
· Yaworski et al.
· 2013
[cited by applicant]
US 8822668B2
· Yaworski et al.
· 2014
[cited by applicant]
US 8969353B2
· Mahon et al.
· 2015
[cited by applicant]
US 9364435B2
· Yaworski et al.
· 2016
[cited by applicant]
US 9738593B2
· Ansell et al.
· 2017
[cited by applicant]
US 20230277457A1
· Shepard et al.
· 2023
[cited by applicant]
US 20240050908A1
· Mitchell et al.
· 2024
[cited by applicant]
US 20240261381A1
· Bevers et al.
· 2024
[cited by applicant]
US 20250049954A1
· Karve et al.
· 2025
[cited by applicant]
US 20250115872A1
· Pourquie et al.
· 2025
[cited by applicant]
US 20250152518A1
· Hennessy et al.
· 2025
[cited by applicant]
CN 102423493B
· 2013
[cited by applicant]
CN 116875603A
· 2023
[cited by applicant]
CN 117551183A
· 2024
[cited by applicant]
CN 118453868A
· 2024
[cited by applicant]
CN 118496341A
· 2024
[cited by applicant]
CN 118549656A
· 2024
[cited by applicant]
CN 118557595A
· 2024
[cited by applicant]
CN 118638750A
· 2024
[cited by applicant]
CN 118662636A
· 2024
[cited by applicant]
CN 118879889A
· 2024
[cited by applicant]
CN 118909932A
· 2024
[cited by applicant]
CN 119302966A
· 2025
[cited by applicant]
CN 119679688A
· 2025
[cited by applicant]
CN 119732889A
· 2025
[cited by applicant]
EP 4509118A2
· 2025
[cited by applicant]
EP 3638678B1
· 2025
[cited by applicant]
JP 2024138266A
· 2024
[cited by applicant]
JP 2025005946A
· 2025
[cited by applicant]
KR 102512998B1
· 2023
[cited by applicant]
WO 2006095837A1
· 2008
[cited by applicant]
WO 2019046809A1
· 2019
[cited by applicant]
WO 2020061284A1
· 2020
[cited by applicant]
WO 2023118450A1
· 2023
[cited by applicant]
WO 2024005157A1
· 2024
[cited by applicant]
WO 2024130374A1
· 2024
[cited by applicant]
WO 2024159175A2
· 2024
[cited by applicant]
WO 2025085373A1
· 2025
[cited by applicant]
Kim et al., “Tongue Fat and its Relationship to Obstrucitve Sleep Apnea”, Sleep, vol. 37, No. 10, 2014, pp. 1639-1648D.
[cited by applicant]
“Beige is all the Rage: Drug Treatment Stimulates Beige Fat Formation Resulting in Metabolic Health Benefits in People with Obesity”, National Institute of Diabetes and Digestive and Kidney Diseases, News, May 1, 2020, …
[cited by applicant]
Wang et al., “Effect of Weight Loss on Upper Airway Anatomy and the Apnea-Hypopnea Index”, American Journal of Respiratory and Critical Care Medicine, 2020, vol. 201, No. 6, pp. 718-727.
[cited by applicant]
Xue et al., “LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing”, Nature Communications, 2024, vol. 15:739. 13 pages.
[cited by applicant]
Gavin, Kathleen M., “Origins of Adult Adipose Progenitors”, Encyclopedia of Tissue Engineering and Regenerative Medicine, vol. 2, 2019, pp. 299-312.
[cited by applicant]
Carrière et al., “Browning of White Adipose Cells by Intermediate Metabolites: An Adaptive Mechanism to Alleviate Redox Pressure”, Diabetes, 2014, vol. 63, pp. 3253-3265.
[cited by applicant]
An et al., “Adipose Tissue and Metabolic Health”, Diabetes and Metabolism Journal, 2023, 47, pp. 595-611.
[cited by applicant]
Arch, Jonathan R. S., “Challenges in b3-adrenoceptor agonist drug development”, Therapeutic Advances in Endocrinology and Metabolism, 2011, 2(2), pp. 59-64.
[cited by applicant]
Bartesaghi et al., “Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice”, Molecular Therapy: Nucleic Acids, 2022, vol. 28, pp. 500-513.
[cited by applicant]
Baskaran et al., “TRPV1 Activation Antagonizes High-Fat Diet-Induced Obesity at Thermoneutrality and Enhances UCP-1 Transcription via PRDM-16”, Pharmaceutials, 2024, vol. 17, No. 1098, 16 pages.
[cited by applicant]
Carpentier et al., “Brown Adipose Tissue—A Translational Perspective”, Endocrine Reviews, 2023, 44, pp. 143-192.
[cited by applicant]
Chen et al., “CPEB2-dependent translation of long 3′-UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue”, The EMBO Journal, 2018, 37: e99071. 15 pages.
[cited by applicant]
Choe et al., “Adipose Tissue Remodeling: its Role in energy Metabolism and Metabolic Disorders”, Frontiers in Endocrinology, 2016, vol. 7, article 30, 16 pages.
[cited by applicant]
Cohen et al., “Cell biology of fat storage”, MBoC Perspective on Cell Biology and Human Health, 2016, vol. 27, p. 2523-2527.
[cited by applicant]
Cohen et al., “The cellular and functional complexity of thermogenic fat”, Nat Rev Mol Cell Biol., 2021, vol. 22, No. 6, pp. 393-409. 47 pages.
[cited by applicant]
Cojocaru et al., “Mitochondrial Dysfunction, Oxidative Stress, and Therapeutic Strategies in Diabetes, Obesity, and Cardiovascular Disease”, Antioxidants, 2023, 12, 658, 19 pages.
[cited by applicant]
Fedorenko et al., “Mechanism of Fatty-Acid Dependent UCP1 Uncoupling in Brown Fat Mitochondria”, Cell, 2012, vol. 151, No. 2, pp. 400-413. 26 pages.
[cited by applicant]
El-Araby et al., “Adiponectin mRNA Conjugated with Lipid Nanoparticles Specifically Targets the Pathogenesis of Type 2 Diabetes”, Aging and Disease, 2025, vol. 16, No. 2, pp. 1059-1079.
[cited by applicant]
Emont et al., “A single-cell atlas of human and mouse white adipose tissue”, Nature, 2022, vol. 603:926-933. 37 pages.
[cited by applicant]
Hu et al., “Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation”, Frontiers in Immunology, 2019, vol. 10, Article 1998, 14 pages.
[cited by applicant]
Galmozzi et al., “ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue”, Cell Rep., 2014, vol. 9, No. 5: 1584-1593. 19 pages.
[cited by applicant]
Gaspar et al., “An update on brown adipose tissue biology: a discussion of recent findings”, American Journal of Physiology, Endocrinology and Metabolism, 2021, 320, pp. E488-E495.
[cited by applicant]
Gong et al., “Keys to the switch of fat burning: stimuli that trigger the uncoupling protein 1 (UCP1) activation in adipose tissue”, Lipids in Health and Disease, 2024, 23:322, 27 pages.
[cited by applicant]
Ikeda et al., “UCP1 Dependent and Independent Thermogenesis in Brown and Beige Adipocytes”, Frontiers in Endocrinology, 2020, vol. 11, article 498, 6 pages.
[cited by applicant]
Kim et al., “Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders”, Diabetes and Metabolism Journal, 2016; 40(1), pp. 12-21.
[cited by applicant]
Kissig et al., “Brown and Beige Adipose Thermogenesis” Cell, 2016, 116(1), 3 pages.: 258-258.e1. 3 pages.
[cited by applicant]
Kurylowicz et al., “Induction of Adipose Tissue Browning as a Strategy to Combat Obesity”, International Journal of Molecular Sciences, 2020, vol. 21: 6241. 28 pages.
[cited by applicant]
Laursen et al., “Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation”, PNAS, vol. 112, No. 5, pp. 1607-1612.
[cited by applicant]
Lee et al., “Strategies for targeted gene delivery using lipid nanoparticles and cell-derived nanovesicles”, Nanoscale Adv., 2023, vol. 5, pp. 3834-3856.
[cited by applicant]
Liu et al., “An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications”, Frontiers in Endocrinology, 2023, 13:1065263. 14 pages.
[cited by applicant]
Liu et al., “The secretory function of adipose tissues in metabolic regulation”, Life Metabolism, 2024, 3(2), loae003. 15 pages.
[cited by applicant]
Lu et al., “Alternative Polyadenylation and Differential Regulation of Ucp1: Implications for Brown Adipose Tissue Thermogenesis Across Species”, Frontiers in Pediatrics, 2021, vol. 8, Article 612279, 8 pages.
[cited by applicant]
Luo et al., “Adipose tissue in control of metabolism”, J Endocrinol., 2016, vol. 231, No. 3, pp. R77-R99. 39 pages.
[cited by applicant]
McNeill et al., “Human brown adipose tissue as a therapeutic target: warming up or cooling down?” Eur J Endocrinol. 2021; 184(6), R243-R259.
[cited by applicant]
Norota et al., “Lipid nanoparticle delivery of the CRISPR/Cas9 system directly into the mitochondria of cells carrying m.7778G>T mutation in MtDNA (mt-Atp8)”, Scientific Reports, 2025, vol. 15, Article No. 18717, 13 pag…
[cited by applicant]
O'mara et al., “Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity”, The Journal of Clinical Investigation, 2020, vol. 130, No. 5, pp. 2209-2219.
[cited by applicant]
Poher et al., “Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance”, Frontiers in Physiology, 2015, vol. 6, article 4, 9 pages.
[cited by applicant]
Porter et al., “The therapeutic potential of brown adipocytes in humans”, Frontiers in Endocrinology, 2015, vol. 6, article 156, 8 pages.
[cited by applicant]
Richard et al., “Adipose Tissue: Physiology to Metabolic Dysfunction”, Endotext, Apr. 2020, 67 pages.
[cited by applicant]
Ricquier, Daniel, “Uncoupling Protein 1 of Brown Adipocytes, the Only Uncoupler: A Historical Perspective”, Frontiers in Endocrinology, 2011, vol. 2, Article 85. 7 pages.
[cited by applicant]
Rosen et al., “What We Talk About When We Talk About Fat”, Cell 2014, 156(0):20-44. 46 pages.
[cited by applicant]
Sakaguchi, Masaji, “Adipose Tissue Dynamics, Thermogenesis, and Interorgan Connections for Preventing Obesity and Metabolic Disorders”, JMA Journal, 2024, vol. 7, Iss. 2, pp. 172-177.
[cited by applicant]
Schachner-Nedherer et al., “Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes” Pharmaceutics. 2023, vol. 15, 1983. 20 pages.
[cited by applicant]
Schirinzi et al., “Browning of Adipocytes: A Potential Therapeutic Approach to Obesity”, Nutrients, 2023, vol. 15, 2229, 20 pages.
[cited by applicant]
Sidossis et al., “Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis”, The Journal of Clinical Investigation, 2015, vol. 125, No. 2, pp. 478-486.
[cited by applicant]
Solmonson et al.,“Uncoupling Proteins and the Molecular Mechanisms of Thyroid Thermogenesis”, Endocrinology. 2016;157(2):455-462.
[cited by applicant]
Wang et al., “Specific muscle targeted delivery of miR-130a loaded lipid nanoparticles: a novel approach to inhibit lipid accumulation in skeletal muscle and obesity”, Journal of Nanobiotechnology, 2025, 23:159, 18 page…
[cited by applicant]
Vegiopoulos et al., “Adipose tissue: between the extremes”, The EMBO Journal, 2017, vol. 36, No. 14, pp. 1999-2017.
[cited by applicant]
Yamada et al., “Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases”, Adv. Drug Deliv. Rev. 2008; 60, pp. 1439-1462.
[cited by applicant]
Yamada et al., “MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion”, Biochim. Biophys. Acta. 2008; 1778: pp. 423-432.
[cited by applicant]
Yamada et al., “Dual Function MITO-Porter, a Nano Carrier Integrating Both Efficient Cytoplasmic Delivery and Mitochondrial Macromolecule Delivery”, Molecular Therapy, 2011, vol. 19, No. 8, pp. 1449-1456.
[cited by applicant]
Yasuzaki et al., Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes, Biochem. Biophys. Res. Commun. 2010; 397(2):181-186. 38 pages.
[cited by applicant]
Zhou et al., “Functional Attenuation of UCP1 as the Potential Mechanism for a Thickened Blubber Layer in Cetaceans”, Mol Biol Evol., 2022, vol. 39, No. 11: msac230. 12 pages.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2025/031590 mailed Dec. 4, 2025. (9 pages).
[cited by applicant]
Christian, Mark, “The browning of white fat”, Endocrinologist, Issue 126, 2017, 6 pages.
[cited by applicant]
Kahn et al., “Keeping It Local in Metabolic Disease: Adipose Tissue Paracrine Signaling and Insulin Resistance”, Diabetes, vol. 71, 2022, pp. 599-609.
[cited by applicant]