# US 11,304,898 B2 · Method of treating carcinoma > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,304,898 B2 - Document ID: US11304898B2 - Status: Granted - Kind: B2 - Application number: 15/580,732 - Filed: 2016-06-08 - Published: 2018-05-24 - Granted: 2022-04-19 - Earliest claimed: 2015-06-09 - Assignees: Sun Pharma Advanced Research Company Ltd. - Applicants: Sun Pharma Advanced Research Company Ltd - Inventors: Wen Wee Ma; Alex Adjei; Lynne Bui; Ronald Harning; Ajay Khopade; Subhas Bhowmick; Natarajan Arulsudar; Narendra Lakkad - Web page: https://patentgrep.com/patent/US11304898B2 ## CPC - A61K 9/10: Dispersions; Emulsions - 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 9/5123: {Organic compounds, e.g. fats, sugars} - A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides} - A61K 31/337: having four-membered rings, e.g. taxol - 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 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - 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 A method of treating patients suffering from carcinoma of intrahepatic or extra hepatic bile duct or gall bladder which is locally advanced or metastatic, by intravenously administering to the patient, paclitaxel in the form of a nanodispersion. The nanodispersion comprises particles with a mean particle size less than 300 nm and is free of polyoxyethylated castor oil and free of a protein. ## Claims ### Claim 1 A method of treating a patient suffering from carcinoma of intrahepatic or extra hepatic bile duct or gall bladder which is metastatic, said method comprising intravenously administering to the patient, paclitaxel in the form of a nanodispersion, wherein said nanodispersion comprises (a) particles comprising (i) paclitaxel, (ii) a water soluble polymer, and (iii) a surfactant comprising a mixture of a fatty acid or a salt thereof and a sterol or a salt thereof, the particles having a mean particle size less than 300 nm, and (b) a water miscible solvent, wherein the nanodispersion is free of polyoxyethylated castor oil and is free of any protein, and wherein the paclitaxel is administered once in a 21 day cycle at a dose of 295 mg/m2. ### Claim 2 (depends on 1) The method as claimed in claim 1, wherein the method does not involve premedication with any corticosteroids. ### Claim 3 (depends on 1) The method as claimed in claim 1, wherein the patient suffering from carcinoma of intrahepatic or extra hepatic bile duct or gall bladder which is metastatic has failed to respond to one or more lines of treatment with one or more anti-cancer agents selected from mitomycin, 5-fluorouracil, cisplatin, oxaliplatin, leucovorin, capecitabine, bevacizumab, etoposide, gemcitabine, divotinib, cetuximab, regorafenib, carboplatin, lupron, casodex, bleomycin, pemetrexed, everolimus, sunitinib, crizotinib or doxorubicin. ### Claim 4 (depends on 1) The method as claimed in claim 1, wherein the patient suffering from carcinoma of intrahepatic or extra hepatic bile duct or gall bladder which is metastatic has failed more than two lines of treatment with anti-cancer agents. ### Claim 5 (depends on 4) The method as claimed in claim 4, wherein the lines of treatment that have failed include two or more of treatments with one or more anti-cancer agents selected from mitomycin, 5-fluorouracil, cisplatin, oxaliplatin, leucovorin, capecitabine, bevacizumab, etoposide, gemcitabine, divotinib, cetuximab, regorafenib, carboplatin, lupron, casodex, bleomycin, pemetrexed, everolimus, sunitinib, crizotinib or doxorubicin. ### Claim 6 (depends on 1) The method as claimed in claim 1, wherein the method comprises: a) preparing a solution comprising paclitaxel, a water soluble polymer, a surfactant and a water miscible solvent, b) preparing a nanodispersion that remains stable for at least 4 hours with no aggregation or crystallization of the said drug by adding the solution to a sterile aqueous perfusion vehicle with mild agitation or shaking, and c) intravenously administering the nanodispersion to the patient. ### Claim 7 (depends on 6) The method as claimed in claim 6, wherein the water soluble polymer is selected from the group consisting of polyvinylpyrrolidone, polyglutamic acid or its salt and hyaluronic acid or its salt, the surfactant consists of a mixture of sterol or its salts and fatty acid or its salts and the water miscible solvent is selected from the group consisting of alcohol, polyethylene glycol, polypropylene glycol and mixtures thereof. ### Claim 8 (depends on 1) The method as claimed in claim 1, wherein the nanodispersion comprises (a) a polymer selected from the group consisting of polyvinylpyrrolidone, polyglutamic acid or its salts and hyaluronic acid or its salts, (b) a surfactant consisting of a mixture of caprylic acid or its salts and cholesteryl sulphate or cholesterol acid salts, and (c) a water miscible solvent selected from the group consisting of alcohol, polyethylene glycol, polypropylene glycol and mixtures thereof. ### Claim 9 (depends on 1) The method as claimed in claim 1, wherein the water soluble polymer is selected from the group consisting of polyvinylpyrrolidone, polyglutamic acid or its salts and hyaluronic acid or its salts; the fatty acid is selected from the group consisting of caprylic acid, oleic acid and stearic acid; the sterol is selected from the group consisting of cholesteryl sulfate, cholesterol, sodium cholesteryl sulfate, sodium glychocholate and ursodeoxycholic acid; and the water miscible solvent is selected from the group consisting of alcohol, polyethylene glycol, polypropylene glycol and mixtures thereof. ### Claim 10 A method of treating a patient suffering from metastatic carcinoma of the intrahepatic or extra hepatic bile duct or gall bladder who has failed to respond to one or more lines of treatment with one or more anti-cancer agents selected from mitomycin, 5-fluorouracil, cisplatin, oxaliplatin, leucovorin, capecitabine, bevacizumab, etoposide, gemcitabine, divotinib, cetuximab, regorafenib, carboplatin, lupron, casodex, bleomycin, pemetrexed, everolimus, sunitinib, crizotinib and doxorubicin, the method comprising intravenously administering to the patient paclitaxel at a dose of 295 mg/m2 in the form of a nanodispersion once in a 21 day cycle, wherein the nanodispersion comprises (a) particles comprising (i) paclitaxel, (ii) a water soluble polymer, and (iii) a surfactant comprising a mixture of a fatty acid or a salt thereof and a sterol or a salt thereof, the particles having a mean particle size less than 300 nm, and (b) a water miscible solvent. ### Claim 11 (depends on 10) The method of claim 10, wherein the carcinoma is unresectable. ### Claim 12 (depends on 1) The method of claim 1, wherein the carcinoma is unresectable. ### Claim 13 A method of treating a patient suffering from adenocarcinoma of intrahepatic or extra hepatic bile duct or gall bladder which is (a) unresectable and (b) locally advanced or metastatic, said method comprising intravenously administering to the patient, paclitaxel in the form of a nanodispersion, wherein the paclitaxel is administered once in a 21 day cycle at a dose of 295 mg/m2, wherein said nanodispersion comprises (a) particles comprising (i) paclitaxel, (ii) a water soluble polymer, and (iii) a surfactant comprising a mixture of a fatty acid or a salt thereof and a sterol or a salt thereof, the particles having a mean particle size less than 300 nm, and (b) a water miscible solvent, wherein the nanodispersion is free of polyoxyethylated castor oil and is free of any protein.