# US 11,026,894 B2 · Lipid nanoparticles and use thereof to deliver RNA polynucleotides > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,894 B2 - Document ID: US11026894B2 - Status: Granted - Kind: B2 - Application number: 16/739,197 - Filed: 2020-01-10 - Published: 2020-07-16 - Granted: 2021-06-08 - Earliest claimed: 2019-01-10 - Assignees: Massachusetts Institute of Technology - Applicants: Massachusetts Institute of Technology - Inventors: Darrell J. Irvine; Ron Weiss; Tasuku Kitada; Mariane Melo; Yuan Zhang - Web page: https://patentgrep.com/patent/US11026894B2 ## CPC - A61K 9/5123: {Organic compounds, e.g. fats, sugars} - C12N 15/86: Viral vectors - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) - A61K 38/2086: {IL-13 to IL-16} - A61P 35/00: Antineoplastic agents - A61K 48/0033: {the non-active part being non-polymeric} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed herein are lipid nanoparticles comprising 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000](DSPE-PEG2000), compositions including such lipid nanoparticles, and methods of treatment using such lipid nanoparticles and compositions. ## Claims ### Claim 1 A lipid nanoparticle comprising 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000), wherein the molar ratio of DOTAP: DSPC: cholesterol: DSPE-PEG2000 is 40:10:48:2. ### Claim 2 (depends on 1) The lipid nanoparticle of claim 1, consisting of DOTAP: DSPC: cholesterol:DSPE-PEG2000 at a molar ratio of 40:10:48:2. ### Claim 3 (depends on 1) The lipid nanoparticle of claim 1, wherein the lipid nanoparticle is about 100 nM in diameter. ### Claim 4 (depends on 1) The lipid nanoparticle of claim 1, wherein the surface charge of the lipid nanoparticle is about neutral to about 25 mV. ### Claim 5 (depends on 1) A composition comprising the lipid nanoparticle of claim 1 and one or more RNA polynucleotide. ### Claim 6 (depends on 5) The composition of claim 5, wherein the one or more RNA polynucleotide comprises one or more self-replicating RNA derived from an alphavirus. ### Claim 7 (depends on 6) The composition of claim 6, wherein the alphavirus is a Venezuelan equine encephalitis virus, optionally wherein the Venezuelan equine encephalitis virus is TC-83 or a variant thereof. ### Claim 8 (depends on 6) The composition of claim 6, wherein at least one of the self-replicating RNA comprises a 5′ cap. ### Claim 9 (depends on 6) The composition of claim 6, wherein the ratio of cationic amines in the lipid nanoparticle to anionic phosphates in the self-replicating RNA (N:P ratio) is about 0.5:1 to about 20:1. ### Claim 10 (depends on 6) The composition of claim 6, wherein at least one of the self-replicating RNA comprises a sequence encoding a therapeutic agent. ### Claim 11 (depends on 10) The composition of claim 10, wherein the therapeutic agent is (i) a cytokine, a chemokine, or a growth factor, or (ii) an anti-tumor agent, optionally wherein the anti-tumor agent is interleukin-15 (IL-15) or an IL-15 superagonist. ### Claim 12 (depends on 6) The composition of claim 6, wherein the composition comprises two or more self-replicating RNAs. ### Claim 13 (depends on 6) The composition of claim 6, wherein the self-replicating RNA is present within the lipid nanoparticle. ### Claim 14 (depends on 10) A method of treating a disease or disorder in a subject in need thereof, comprising providing to the subject the composition of claim 10, wherein the self-replicating RNA comprises the sequence encoding the therapeutic agent. ### Claim 15 (depends on 14) The method of claim 14, wherein the disease or disorder is a cancer, and the therapeutic agent is an anti-tumor agent, optionally wherein the anti-tumor agent is interleukin-15 (IL-15) or an IL-15 superagonist. ### Claim 16 (depends on 15) The method of claim 15, wherein the cancer is a a breast cancer, a head and neck cancer, a lymphoma or a skin cancer, optionally wherein the skin cancer is a melanoma. ### Claim 17 (depends on 14) The method of claim 14, wherein the composition is provided to the subject systemically locally, or parenterally. ### Claim 18 (depends on 14) The method of claim 14, wherein the composition is provided in one or more doses, optionally wherein the one or more doses are two or more doses provided within two weeks of each other. ### Claim 19 (depends on 14) The method of claim 14, wherein the composition is provided at about 1 μg/dose to about 1000 μg/dose. ### Claim 20 (depends on 15) The method of claim 15, wherein the treatment inhibits tumor growth by at least 10% as compared to growth of an untreated tumor. ### Claim 21 (depends on 17) The method of claim 17, wherein the composition is provided to the subject intratumorally or intravenously.