Claims for Patent: 11,529,362

Summary for Patent: 11,529,362

Title:	Physiologically balanced injectable formulations of fosnetupitant
Abstract:	Injectable dosages and formulations of fosnetupitant and pharmaceutically acceptable salts thereof are provided that are efficacious, chemically stable and physiologically balanced for safety and efficacy.
Inventor(s):	Alessio Venturini, Roberta Cannella
Assignee:	Helsinn Healthcare SA
Application Number:	US16/817,683
Patent Claims:	1. A pharmaceutically stable intravenous liquid formulation of fosnetupitant comprising: a) from 2.3 to 30 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) an alkalizing agent; and c) an alkaline pH. 2. The pharmaceutically stable intravenous liquid formulation of claim 1 comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) sodium hydroxide as the alkalizing agent; at a pH of from 7.5 to 10. 3. The pharmaceutically stable intravenous liquid formulation of claim 1 comprising sodium hydroxide as the alkalizing agent at a pH of from 7.5 to 10. 4. A pharmaceutically stable intravenous lyophilized formulation of fosnetupitant comprising: a) from 2.3 to 30 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) an alkalizing agent; at an alkaline pH, based on a suitable reconstitution volume. 5. The pharmaceutically stable intravenous lyophilized formulation of claim 4 comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) sodium hydroxide as the alkalizing agent; at a pH of from 7.5 to 10. 6. The pharmaceutically stable intravenous lyophilized formulation of claim 4 comprising sodium hydroxide as the alkalizing agent at a pH of from 7.5 to 10. 7. The pharmaceutically stable intravenous liquid formulation of claim 1 in the absence of a phosphate. 8. The pharmaceutically stable intravenous lyophilized formulation of claim 4 in the absence of a phosphate. 9. The pharmaceutically stable intravenous liquid formulation of claim 1 further comprising netupitant, wherein the netupitant and fosnetupitant are present at a weight ratio of from 0.01:99.99 to 2:98. 10. The pharmaceutically stable intravenous lyophilized formulation of claim 4 further comprising netupitant, wherein the netupitant and fosnetupitant are present at a weight ratio of from 0.01:99.99 to 2:98. 11. The pharmaceutically stable intravenous liquid formulation of claim 1, wherein the 2.3 to 30 mg/mL is based on the weight of the fosnetupitant free base. 12. The pharmaceutically stable intravenous liquid formulation of claim 1, wherein the 2.3 to 30 mg/mL is based on the weight of the fosnetupitant chloride hydrochloride. 13. The intravenous liquid formulation of claim 1 further comprising: a) sodium hydroxide; b) disodium edetate; and c) mannitol. 14. The intravenous lyophilized formulation of claim 4 further comprising: a) sodium hydroxide; b) disodium edetate; and c) mannitol. 15. The liquid intravenous formulation of claim 13 comprising from 0.05 to 2.0 mg/mL disodium edetate and from 10 to 100 mg/mL mannitol; at a pH of 7.5-10.0; and water q.s. 16. The lyophilized powder intravenous formulation of claim 14 comprising from 0.05 to 2.0 mg/mL disodium edetate and from 10 to 100 mg/mL mannitol; at a pH of 7.5-10.0. 17. The lyophilized powder intravenous formulation of claim 16, comprising from 0.1 to 0.9 mg/mL disodium edetate and from 10 to 100 mg/mL mannitol; further comprising HCl q.s. to pH 7.5-10.0. 18. The lyophilized powder intravenous formulation of claim 16, comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; b) about 0.32 mg/mL disodium edetate; and c) about 38 mg/mL mannitol; at a pH 8.5-9.5; based on a reconstitution in water volume of 20 mL. 19. A method of manufacturing a liquid intravenous or lyophilized intravenous formulation of fosnetupitant comprising: a) admixing fosnetupitant or a pharmaceutically acceptable salt thereof with sodium hydroxide in water at a basic pH to form a solution; b) after step (a), reducing the pH of the solution to a basic pH by the addition of one or more acidic pH adjusting agents; and c) after step (a), admixing the solution with one or more pharmaceutically acceptable excipients. 20. The liquid intravenous formulation of claim 15, comprising from 0.1 to 0.9 mg/mL disodium edetate; further comprising HCl. 21. The liquid intravenous formulation of claim 15 at a pH of 8.5-9.5, comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; b) about 0.32 mg/mL disodium edetate; and c) about 38 mg/mL mannitol; further comprising HCl. 22. The lyophilized powder intravenous formulation of claim 14 comprising from 0.1 to 0.9 mg/mL disodium edetate; and from 10 to 100 mg/mL mannitol. 23. The lyophilized powder intravenous formulation of claim 14 comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; b) about 0.32 mg/mL disodium edetate; and c) about 38 mg/mL mannitol; further comprising HCl. 24. The liquid intravenous formulation of claim 13 at a pH of from 7.5 to 10.0. 25. The lyophilized powder intravenous formulation of claim 14 at a pH of from 7.5 to 10.0 upon reconstitution in water. 26. The lyophilized powder intravenous formulation of claim 22 at a pH of from 7.5 to 10.0 upon reconstitution in water. 27. The lyophilized powder intravenous formulation of claim 23 at a pH of from 7.5 to 10.0 upon reconstitution in water. 28. The method of claim 19, wherein the acidic pH adjusting agent comprises hydrochloric acid.