Claims for Patent: 11,197,909

Summary for Patent: 11,197,909

Title:	Compositions and methods for the treatment of fungal infections
Abstract:	The disclosure features non-irritating pharmaceutical compositions containing CD101 in pharmaceutical acceptable salt (e.g., CD101 acetate) or neutral form. The pharmaceutical compositions can be intravenously administered to a subject to treat fungal infections (e.g., candidiasis) in the subject.
Inventor(s):	Kenneth BARTIZAL, Paul Daruwala, David Hughes, Martin Patrick HUGHES, Navdeep B. Malkar, Balasingam Radhakrishnan, Anuradha Vaidya
Assignee:	NAPP PHARMACEUTICAL GROUP Ltd
Application Number:	US16/629,711
Patent Claims:	1. A pharmaceutical composition for intravenous injection comprising an aqueous solution comprising at least 85% (w/w) water, between 0.4 mg/mL and 10 mg/mL CD101 acetate, between 0.12% to 0.6% (w/w) of a saccharide, and an intravenous solubility promoter, wherein the weight to weight (w/w) ratio of the intravenous solubility promoter to the CD101 acetate in the pharmaceutical composition is at least 2, and the pharmaceutical composition has a pH of between 5 and 7. 2. The pharmaceutical composition of claim 1, wherein the w/w ratio of the intravenous solubility promoter to the CD101 acetate in the pharmaceutical composition is between 2 and 8. 3. The pharmaceutical composition of claim 1, wherein the intravenous solubility promoter is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, β-cyclodextrin, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, D-α-tocopheryl polyethylene glycol 1000 succinate, sorbitan monooleate, sorbitan monolaurate, polyoxyl 8 stearate, PEG 400 monostearate, polyoxyl 40 stearate, PEG 1750 monostearate, PEG 400 caprylic/capric glycerides, PEG 300 oleic glycerides, phosphatidylcholine, lecithin, alkylglucoside, sucrose monolaurate, sucrose monooleate, and polyoxyethylene-polyoxypropylene block copolymer. 4. The pharmaceutical composition of claim 3, wherein the intravenous solubility promoter is polysorbate 80. 5. The pharmaceutical composition of claim 1, wherein the concentration of CD101 acetate in the pharmaceutical composition is between 0.4 mg/mL and 4 mg/mL. 6. The pharmaceutical composition of claim 5, wherein the concentration of CD101 acetate in the pharmaceutical composition is about 0.8 mg/mL or is about 1.6 mg/mL. 7. The pharmaceutical composition of claim 1, further comprising a buffer. 8. The pharmaceutical composition of claim 7, wherein the buffer is histidine, citrate, succinate, lactate, propanoate, arginine, tris(hydroxymethyl)aminomethane (tris), glycine, acetate, or formate. 9. The pharmaceutical composition of claim 1, wherein the saccharide is mannitol, sucrose, trehalose, maltose, dextrose, or lactose. 10. A pharmaceutical composition comprising an effective amount of CD101 acetate, between 2% to 10% (w/w) of a saccharide, and an intravenous solubility promoter in a lyophilized composition, wherein the weight to weight (w/w) ratio of the intravenous solubility promoter to the CD101 acetate in the lyophilized composition is between 2 and 8, and the lyophilized composition, once reconstituted, provides an aqueous solution having a pH of between 5 and 7. 11. The pharmaceutical composition of claim 10, wherein the intravenous solubility promoter is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, β-cyclodextrin, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, D-α-tocopheryl polyethylene glycol 1000 succinate, sorbitan monooleate, sorbitan monolaurate, polyoxyl 8 stearate, PEG 400 monostearate, polyoxyl 40 stearate, PEG 1750 monostearate, PEG 400 caprylic/capric glycerides, PEG 300 oleic glycerides, phosphatidylcholine, alkylglucoside, sucrose monolaurate, sucrose monooleate, and polyoxyethylene-polyoxypropylene block copolymer. 12. The pharmaceutical composition of claim 11, wherein the intravenous solubility promoter is polysorbate 80. 13. The pharmaceutical composition of claim 10, further comprising a buffer. 14. The pharmaceutical composition of claim 13, wherein the buffer is histidine, citrate, succinate, lactate, propanoate, arginine, tris(hydroxymethyl)aminomethane (tris), glycine, acetate, or formate. 15. The pharmaceutical composition of claim 10, wherein the saccharide is mannitol, sucrose, trehalose, maltose, dextrose, or lactose. 16. A method of treating or preventing a fungal infection in a subject, comprising intravenously administering the pharmaceutical composition of claim 1 to the subject. 17. A method of treating or preventing a fungal infection in a subject, comprising: (i) reconstituting the pharmaceutical composition of claim 10 to form an aqueous solution; and (ii) intravenously administering the aqueous solution to the subject, wherein the concentration of the CD101 acetate in the aqueous solution is between 0.4 mg/mL and 10 mg/mL. 18. The method of claim 16, wherein: (i) the method comprises intravenously administering to the subject by infusion; (ii) the method comprises intravenously administering to the subject by infusion at a constant infusion rate of between 2 mL/minute and 9 mL/minute; (iii) the method comprises intravenously administering to the subject by infusion over 30 to 120 minutes; (iv) the method comprises intravenously administering one dose every 5 to 15 days; (v) the fungal infection is selected from candidemia, invasive candidiasis, tinea capitis, tinea corporis, tinea pedis, onychomycosis, perionychomycosis, pityriasis versicolor, oral thrush, vaginal candidiasis, respiratory tract candidiasis, biliary candidiasis, eosophageal candidiasis, urinary tract candidiasis, systemic candidiasis, mucocutaneous candidiasis, aspergillosis, mucormycosis, paracoccidioidomycosis, North American blastomycosis, histoplasmosis, coccidioidomycosis, sporotrichosis, fungal sinusitis, or chronic sinusitis; (vi) the fungal infection is candidemia or invasive candidiasis; and/or (vii) the fungal infection is an infection of Candida albicans, C. glabrata, C. dubliniensis, C. krusei, C. parapsilosis, C. tropicalis, C. orthopsilosis, C. guilliermondii, C. rugosa, C. auris, C. lusitaniae, Aspergillus fumigatus, A. flavus, A. terreus, A. niger, A. candidus, A. clavatus, or A. ochraceus. 19. The method of claim 17, wherein: (i) the method comprises intravenously administering to the subject by infusion; (ii) the method comprises intravenously administering to the subject by infusion at a constant infusion rate of between 2 mL/minute and 9 mL/minute; (iii) the method comprises intravenously administering to the subject by infusion over 30 to 120 minutes; (iv) the method comprises intravenously administering one dose every 5 to 15 days; (v) the fungal infection is selected from candidemia, invasive candidiasis, tinea capitis, tinea corporis, tinea pedis, onychomycosis, perionychomycosis, pityriasis versicolor, oral thrush, vaginal candidiasis, respiratory tract candidiasis, biliary candidiasis, eosophageal candidiasis, urinary tract candidiasis, systemic candidiasis, mucocutaneous candidiasis, aspergillosis, mucormycosis, paracoccidioidomycosis, North American blastomycosis, histoplasmosis, coccidioidomycosis, sporotrichosis, fungal sinusitis, or chronic sinusitis; (vi) the fungal infection is candidemia or invasive candidiasis; and/or (vii) the fungal infection is an infection of Candida albicans, C. glabrata, C. dubliniensis, C. krusei, C. parapsilosis, C. tropicalis, C. orthopsilosis, C. guilliermondii, C. rugosa, C. auris, C. lusitaniae, Aspergillus fumigatus, A. flavus, A. terreus, A. niger, A. candidus, A. clavatus, or A. ochraceus. 20. A method of treating or preventing a fungal infection in a subject, comprising intravenously administering a pharmaceutical composition comprising an aqueous solution comprising at least 85% (w/w) water, between 0.4 mg/mL and 10 mg/mL CD101 acetate, and an intravenous solubility promoter, wherein the weight to weight (w/w) ratio of the intravenous solubility promoter to the CD101 acetate in the pharmaceutical composition is between 2 and 8, and the pharmaceutical composition has a pH of between 5 and 7. 21. The method of claim 20, wherein the intravenous solubility promoter is selected from the group consisting of polysorbate 20, polysorbate, 40, polysorbate 60, polysorbate 80, β-cyclodextrin, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, D-α-tocopheryl polyethylene glycol 1000 succinate, sorbitan monooleate, sorbitan monolaurate, polyoxyl 8 stearate, PEG 400 monostearate, polyoxyl 40 stearate, PEG 1750 monostearate, PEG 400 caprylic/capric glycerides, PEG 300 oleic glycerides, phosphatidylcholine, lecithin, alkylglucoside, sucrose monolaurate, sucrose monooleate, and polyoxyethylene-polyoxypropylene block copolymer. 22. The method of claim 21, wherein the intravenous solubility promoter is polysorbate 80. 23. The method of claim 21, wherein the pharmaceutical composition further comprises between 2% to 10% (w/w) of a saccharide.