# US 12,178,921 B2 · Method of lyophilizing lipid nanoparticles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,921 B2 - Document ID: US12178921B2 - Status: Granted - Kind: B2 - Application number: 17/402,077 - Filed: 2021-08-13 - Published: 2022-02-17 - Granted: 2024-12-31 - Earliest claimed: 2020-08-14 - Assignees: Arcturus Therapeutics, Inc. - Applicants: Arcturus Therapeutics, Inc. - Inventors: Amit Sagi; Yanjie Bao; Priya Prakash Karmali - Web page: https://patentgrep.com/patent/US12178921B2 ## CPC - A61K 9/5123: {Organic compounds, e.g. fats, sugars} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 9/5115: {Inorganic compounds} - A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 48/0033: {the non-active part being non-polymeric} - C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle - 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 9/0073: {Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M)} - 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) ## Abstract Methods of preparing lyophilized lipid nanoparticle-nucleic acid compositions are provided. The methods comprise preparing a suspension of lipid nanoparticles with a monosaccharide and one or more excipients selected from thiosulfate, potassium sorbate, sodium benzoate, and iodixanol. Lyophilized lipid nanoparticle-nucleic acid compositions and methods of reconstituting and administering the same are further provided. ## Claims ### Claim 1 A pharmaceutical composition comprising a solid lyophilized composition, wherein the solid lyophilized composition comprises: i. lipid nanoparticles encapsulating from about 0.001 to about 1.0% w/w of a ribonucleic acid (RNA) by the weight of the lyophilized composition, ii. a lyoprotectant composition comprising from about 0.01% w/w to about 1.0% w/w of a poloxamer by the weight of the lyophilized composition and from about 0.5% w/w to about 5.0% w/w of potassium sorbate by the weight of the lyophilized composition, and iii. from about 85% w/w to about 96% w/w of a sugar by the weight of the lyophilized composition. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the poloxamer is poloxamer 188. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the solid lyophilized composition comprises from about 0.5 to about 5.0% w/w of lipids by the weight of the solid lyophilized composition. ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the solid lyophilized composition further comprises from about 0.5 to about 2.5% w/w of tris(hydroxymethyl)aminomethane by the weight of the solid lyophilized composition. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the solid lyophilized composition further comprises from about 0.75 to about 2.75% w/w of NaCl by the weight of the solid lyophilized composition. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the sugar is sucrose. ### Claim 7 (depends on 1) A method of preserving the solid lyophilized composition of claim 1 comprising storing the lyophilized product at a temperature of about 2° C. to about 8° C. ### Claim 8 (depends on 1) A method of preserving the solid lyophilized composition of claim 1 comprising storing the lyophilized product at a temperature of about −20° C. ### Claim 9 (depends on 1) A method of reconstituting the solid lyophilized composition of claim 1 comprising adding a liquid medium to the lyophilized composition. ### Claim 10 (depends on 9) The method of claim 9, wherein the liquid medium is an aqueous medium. ### Claim 11 (depends on 9) The method of claim 9, wherein the liquid medium further comprises a buffer having a pH of about 7.0 to about 8.5. ### Claim 12 (depends on 1) A method of treating a disease or disorder in a subject comprising administering to the subject the solid lyophilized composition of claim 1 reconstituted in a liquid medium. ### Claim 13 (depends on 12) The method of claim 12, wherein the reconstituted lyophilized composition is administered intravenously, mucosally, or subcutaneously. ### Claim 14 (depends on 12) The method of claim 12, wherein the reconstituted lyophilized composition is administered intramuscularly. ### Claim 15 (depends on 12) The method of claim 12, wherein the reconstituted lyophilized composition is administered via inhalation. ### Claim 16 A pharmaceutical composition comprising a solid lyophilized composition, wherein the solid lyophilized composition comprises: i. lipid nanoparticles encapsulating from about 0.001 to about 1.0% w/w of an RNA by the weight of the lyophilized composition, ii. from about 0.01% w/w to about 1.0% w/w of a poloxamer by the weight of the lyophilized composition and from about 0.5% w/w to about 5.0% w/w of potassium sorbate by the weight of the lyophilized composition, iiii. from about 0.75% w/w to about 2.75% w/w of a salt by the weight of the lyophilized composition, and iv. from about 85% w/w to about 96% w/w of a sugar by the weight of the lyophilized composition, wherein upon reconstitution of the solid lyophilized composition with a liquid medium the lipid nanoparticles have a change in mean diameter less than about 15 nm as compared to a mean diameter prior to lyophilization.