Claims for Patent: 10,543,274

Summary for Patent: 10,543,274

Title:	Lyophilized preparation of cytotoxic dipeptides
Abstract:	The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; .beta.-cyclodextrin; ocyclodextrin; hydroxypropyl-.beta.-cyclodextrin; sulfobutylether-.beta.-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy.
Inventor(s):	Spira; Jack (Tyreso, SE), Lehmann; Fredrik (Knivsta, SE)
Assignee:	ONCOPEPTIDES AB (Stockholm, SE)
Application Number:	16/382,276
Patent Claims:	1. A method for treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition prepared by directly dissolving a lyophilized pharmaceutical preparation comprising melphalan flufenamide or a pharmaceutically acceptable salt thereof and sucrose in a physiologically acceptable aqueous solution, wherein the cancer is ovarian cancer, lung cancer, bladder cancer, mesothelioma, multiple myeloma, breast cancer or hematological cancer. 2. The method of claim 1, wherein the amount of sucrose in the lyophilized pharmaceutical preparation is 10-100% by weight of said melphalan flufenamide. 3. The method of claim 1, wherein the lyophilized pharmaceutical preparation consists essentially of melphalan flufenamide or a pharmaceutically acceptable salt thereof and sucrose. 4. The method of claim 1, wherein sucrose is the sole excipient in the lyophilized pharmaceutical preparation. 5. The method of claim 1, wherein the lyophilized pharmaceutical preparation is free from organic solvents. 6. The method of claim 1, wherein the lyophilized pharmaceutical preparation contains less than 0.1% by weight organic solvents. 7. The method of claim 1, wherein the lyophilized pharmaceutical preparation is obtained by lyophilizing a solution comprising melphalan flufenamide or a pharmaceutically acceptable salt thereof, sucrose, an organic solvent and water. 8. The method of claim 1, wherein the physiologically acceptable solution comprises glucose. 9. The method of claim 1, wherein the pharmaceutical composition is free from organic solvents. 10. The method of claim 1, wherein the pharmaceutical composition consists essentially of melphalan flufenamide or a pharmaceutically acceptable salt thereof, sucrose, glucose, and water. 11. The method of claim 1, further comprising preparing the pharmaceutical composition by dissolving the lyophilized pharmaceutical preparation in the physiologically acceptable solution. 12. The method of claim 1, wherein the lyophilized pharmaceutical preparation contains less than 0.5% by weight organic solvents. 13. The method of claim 1, wherein the pharmaceutical composition contains less than 0.1% by weight organic solvents. 14. The method of claim 1, wherein the pharmaceutical composition contains less than 0.5% by weight organic solvents. 15. A method for treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition prepared by directly dissolving a lyophilized pharmaceutical preparation comprising melphalan flufenamide hydrochloride (J1) and sucrose in a physiologically acceptable aqueous solution, wherein the cancer is ovarian cancer, lung cancer, bladder cancer, mesothelioma, multiple myeloma, breast cancer or hematological cancer. 16. The method of claim 15, wherein the amount of sucrose in the lyophilized pharmaceutical preparation is 10-100% by weight of said J1. 17. The method of claim 15, wherein the lyophilized pharmaceutical preparation consists essentially of J1 and sucrose. 18. The method of claim 15, wherein sucrose is the sole excipient in the lyophilized pharmaceutical preparation. 19. The method of claim 15, wherein the lyophilized pharmaceutical preparation is free from organic solvents. 20. The method of claim 15, wherein the lyophilized pharmaceutical preparation contains less than 0.1% by weight organic solvents. 21. The method of claim 15, wherein the physiologically acceptable solution comprises glucose.