Claims for Patent: 8,895,557

Summary for Patent: 8,895,557

Title:	Pharmaceutical formulations of ecteinascidin compounds
Abstract:	Ecteinascidin formulations, methods of preparing the same, articles of manufacture and kits with such formulations, and methods of treating proliferative diseases with the same formulations are provided.
Inventor(s):	Beijnen; Jacob Hendrik (Amsterdam, NL), Nuijen; Bastiaan (Amsterdam, NL), Salve; Pilar Calvo (Madrid, ES), Barreira; Maria Tobio (Madrid, ES)
Assignee:	Pharma Mar, S.A., Sociedad Unipersonal (Madrid, ES)
Application Number:	11/261,876
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,895,557
Patent Claims:	1. A lyophilised anti-tumor composition comprising a single active anti-tumor compound and a disaccharide selected from sucrose, lactose and a combination thereof, wherein the anti-tumor compound is ET-743 and wherein the disaccharide is present in a sufficient amount to inhibit conversion of the ET-743 into ET-701, such that the ET-743 composition comprises less than 2% ET-701 after storage of the ET-743 composition at 5.degree. C. for 3 months. 2. The lyophilised anti-tumor composition according to claim 1, wherein said disaccharide is lactose. 3. The lyophilised anti-tumor composition according to claim 1, wherein said disaccharide is sucrose. 4. The lyophilised anti-tumor composition according to claim 1, wherein the ratio (w/w) of ET-743 to disaccharide is from about 1:100 to about 1:1500. 5. The lyophilised anti-tumor composition according to claim 4, wherein the ratio (w/w) of ET-743 to disaccharide is from about 1:250 to about 1:600. 6. The lyophilised anti-tumor composition according to claim 5, wherein the ratio (w/w) of ET-743 to disaccharide is about 1:400. 7. The lyophilised anti-tumor composition according to claim 1, which further comprises a buffering agent. 8. The lyophilised anti-tumor composition according to claim 7, wherein said buffering agent is selected from phosphate buffer, citrate buffer, glycine/hydrochloric acid buffer, and mixtures thereof. 9. The lyophilised anti-tumor composition according to claim 1, which further comprises a surface-active agent. 10. The lyophilised anti-tumor composition according to claim 9, wherein the surface-active agent is selected from polyoxyethylene 20 sorbitan monooleate, polyoxyl 40 stearate, and mixtures thereof. 11. The lyophilised anti-tumor composition according to claim 1, wherein the lyophilised formulation is in a vial. 12. The lyophilised anti-tumor composition according to claim 11, wherein ET-743 is present in an amount of about 250 micrograms. 13. The lyophilised anti-tumor composition according to claim 12, wherein said vial contains a composition comprising: about 0.25 mg ET-743, about 100 mg sucrose, and about 6.8 mg potassium dihydrogen phosphate. 14. The lyophilised anti-tumor composition according to claim 11, wherein ET-743 is present in an amount of about 1 mg. 15. The lyophilised anti-tumor composition according to claim 14, wherein said vial contains a formulation comprising: about 1.0 mg ET-743, about 400 mg sucrose, and about 27.2 mg potassium dihydrogen phosphate. 16. A method of making a lyophilised composition of ET-743 according to claim 1, comprising freeze-drying a bulk solution that comprises ET-743 and a disaccharide wherein said disaccharide is selected from sucrose, lactose and a combination thereof. 17. A method of reducing the formation of ET-701 in a composition of ET-743, comprising freeze-drying a bulk solution that comprises ET-743 and a disaccharide to yield a composition according to claim 1 wherein said disaccharide is selected from sucrose, lactose and a combination thereof. 18. A method of preparing a bulk solution for lyophilising to yield a composition according to claim 1, comprising dissolving ET-743 in an acidic medium, mixing the pre-dissolved ET-743 with other components of the bulk solution and, optionally, adjusting the pH of the final solution. 19. A method of preparing a solution for intravenous infusion, comprising: providing a vial that comprises a lyophilised ET-743 composition according to claim 1, adding water to form a reconstituted solution, and diluting said reconstituted solution with an aqueous system. 20. The lyophilised anti-tumor composition according to claim 3, further comprising a buffering agent. 21. The lyophilised anti-tumor composition according to claim 20, further comprising a surface-active agent. 22. A lyophilized anti-tumor composition comprising a single active anti-tumor compound and a disaccharide selected from sucrose, lactose and a combination thereof, wherein the anti-tumor compound is ET-743 and wherein the disaccharide is present in a sufficient amount to inhibit conversion of the ET-743 into ET-701, such that the ET-743 composition comprises less than 2% ET-701 after storage of the ET-743 composition at 25.degree. C. for 3 months. 23. The lyophilised anti-tumor composition according claim 22, wherein the lyophilised composition is in a vial. 24. The lyophilised anti-tumor composition according to claim 22, wherein the disaccharide is sucrose. 25. The lyophilised anti-tumor composition according to claim 22, wherein the disaccharide is lactose. 26. The lyophilised anti-tumor composition according to claim 22, further comprising a buffer.