# US 10,307,370 B2 · Rapamycin for the treatment of lymphangioleiomyomatosis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,370 B2 - Document ID: US10307370B2 - Status: Granted - Kind: B2 - Application number: 15/028,365 - Filed: 2014-10-07 - Published: 2016-08-18 - Granted: 2019-06-04 - Earliest claimed: 2013-10-08 - Assignees: AI Therapeutics, Inc. - Applicants: LAM Therapeutics, Inc. - Inventors: Henri Lichenstein; Jonathan M. Rothberg; Thomas Armer; Lawrence S. Melvin, Jr. - Web page: https://patentgrep.com/patent/US10307370B2 ## CPC - A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles} - A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions} - A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} - A61K 9/145: {with organic compounds} - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 11/00: Drugs for disorders of the respiratory system - A61P 35/00: Antineoplastic agents - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to methods and compositions for treating lymphangioleiomyomatosis in a human subject in need of such treatment. The methods comprise administering to the subject via inhalation an aerosol composition comprising rapamycin or a prodrug or derivative (including analog) thereof. ## Claims ### Claim 1 A pharmaceutical dry powder composition for pulmonary delivery comprising microparticles of sirolimus, particles of a carrier, and one or more optional excipients, wherein the microparticles of sirolimus have a mean diameter of from 1 to 5 microns and the sirolimus is the only therapeutic agent in the composition. ### Claim 2 (depends on 1) The composition of claim 1, wherein the carrier is selected from the group consisting of arabinose, glucose, fructose, ribose, mannose, sucrose, trehalose, lactose, maltose, starches, dextran, mannitol, lysine, leucine, isoleucine, dipalmitylphosphatidylcholine, lecithin, polylactic acid, poly(lactic-co-glutamic) acid, and xylitol, or mixtures of any of the foregoing. ### Claim 3 (depends on 2) The composition of claim 2, wherein the carrier comprises or consists of a blend of two different carriers, a first carrier and a second carrier. ### Claim 4 (depends on 3) The composition of claim 3, wherein the carrier consists of a blend of two different lactose carriers. ### Claim 5 (depends on 3) The composition of claim 3, wherein the first carrier consists of particles having diameters ranging from about 30-100 microns and the second carrier consists of particles having diameters of less than 10 microns. ### Claim 6 (depends on 5) The composition of claim 5, wherein the ratio of the two different carriers is in the range of from 3:97 to 97:3. ### Claim 7 (depends on 1) The composition of claim 1, wherein the one or more optional excipients is present and is selected from a phospholipid and a metal salt of a fatty acid. ### Claim 8 (depends on 7) The composition of claim 7, wherein the phospholipid is selected from dipalmitylphosphatidylcholine and lecithin. ### Claim 9 (depends on 7) The composition of claim 7, wherein the metal salt of a fatty acid is magnesium stearate. ### Claim 10 (depends on 9) The composition of claim 9, wherein the optional excipient or excipients is present and the magnesium stearate is coated on the carrier particles. ### Claim 11 (depends on 1) The composition of claim 1, wherein the amount of sirolimus is an amount effective to inhibit the biological activity of mTORC1. ### Claim 12 (depends on 11) The composition of claim 11, wherein the amount of sirolimus is an amount effective to inhibit the phosphorylation of the S6 protein. ### Claim 13 (depends on 1) The composition of claim 1, wherein the amount of sirolimus is an amount effective to achieve a respirable dose of from 5 to 400 micrograms delivered to the lung. ### Claim 14 (depends on 1) The composition of claim 1, wherein the composition has a fine particle fraction (FPF) greater than 20% with a corresponding fine particle dose (FPD) ranging from 10 micrograms to 500 micrograms following 1 to 12 months of storage. ### Claim 15 (depends on 1) The composition of claim 1, where the composition is adapted for once daily administration. ### Claim 16 (depends on 1) The composition of claim 1, wherein the carrier consists of a blend of two different lactose carriers, the first carrier consists of particles having average diameters ranging from about 30-100 microns and the second carrier consists of particles having average diameters of less than 10 microns and the ratio of the two different carriers is about 97:3 to 3:97. ### Claim 17 (depends on 1) A unit dosage form comprising the composition of claim 1, wherein the amount of sirolimus is from 50 to 250 micrograms. ### Claim 18 (depends on 17) The unit dosage form of claim 17, wherein the dosage form is a capsule suitable for use in a dry powder inhaler device. ### Claim 19 (depends on 1) A method for treating lymphangioleiomyomatosis in a human subject in need of such treatment, the method comprising administering to the subject via inhalation the composition of claim 1.