Claims for Patent: 9,000,021

Summary for Patent: 9,000,021

Title:	Method of treating bendamustine-responsive conditions in patients requiring reduced volumes for administration
Abstract:	Methods of treating bendamustine responsive conditions in patients having fluid and/or sodium intake restrictions are disclosed. The methods include identifying patients having such restrictions and in need of bendamustine, and then administering thereto a bendamustine-containing composition in a volume of about 120 ml or less intravenously over a period of about 15 minutes or less. The smaller volumes and reduced sodium load as compared to currently known methods of treatment minimize cardiac and/or renal stress in patients having diseases such as congestive heart failure or renal disease.
Inventor(s):	Sundaram; Srikanth (Somerset, NJ), Tarriff; Scott L. (Mahwah, NJ)
Assignee:	Eagle Pharmaceuticals, Inc. (Woodcliff Lake, NJ)
Application Number:	13/838,267
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,000,021
Patent Claims:	1. A method of treating a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake; b) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing: i) from about 0.05 to about 12.5 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof; ii) a solubilizer comprising polyethylene glycol and propylene glycol, the polyethylene glycol being present in an amount of from about 0.3 to about to 45% volume and the propylene glycol being present in an amount of from about 0.03 to about 5% volume; and, optionally iii) a parenterally acceptable diluent over a substantially continuous period of less than or equal to about 30 minutes. 2. The method of claim 1, wherein the diluent comprises 0.9% NaCl or 0.45% NaCl. 3. The method of claim 1, wherein the subject has congestive heart disease. 4. The method of claim 1, wherein the subject has renal insufficiency. 5. The method of claim 4, wherein the renal insufficiency is renal failure or renal suppression. 6. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt is from about 0.1 to about 3.2 mg/ml. 7. The method of claim 1, wherein the concentration of the bendamustine or pharmaceutically acceptable salt is from about 0.5 to about 5.6 mg/ml. 8. The method of claim 1, wherein the amount of solubilizer is from about 0.5 to about 26.5% vol. 9. The method of claim 1, wherein the amount of solubilizer is from about 2.0 to about 22.4% vol. 10. The method of claim 1, where the polyethylene glycol is PEG 400. 11. The method of claim 1, wherein the weight ratio of polyethylene glycol to propylene glycol is about 90:10. 12. The method of claim 1, wherein the weight ratio of polyethylene glycol to propylene glycol is about 85:15. 13. The method of claim 1, wherein the volume administered is about 50, 30 or 15 ml. 14. The method of claim 1, wherein the composition further comprises monothioglycerol and NaOH. 15. The method of claim 7, wherein the volume administered is about 50 ml+/-15% or less and the composition is administered over a time period of about 10 minutes or less. 16. The method of claim 6, wherein the volume administered is about 100 ml+/-15% or less and the composition is administered over a time period of about 15 minutes or less. 17. The method of claim 1, wherein the parenterally acceptable diluent is 0.9% NaCl (normal saline). 18. The method of claim 1, wherein the bendamustine-responsive condition is chronic lymphocytic leukemia. 19. The method of claim 18, wherein the composition is administered intravenously in a volume of about 50 ml over a time period of about 10 minutes or less on days 1 and 2 of a 28 day cycle. 20. The method of claim 18, wherein the composition is administered intravenously in a volume of about 100 ml over a time period of about 15 minutes or less on days 1 and 2 of a 28 day cycle. 21. The method of claim 18, wherein the composition is administered for up to 6 cycles. 22. The method of claim 18, wherein the volume of the composition administered to the subject provides a dosage amount ranging from about 25 mg/m.sup.2 to about 100 mg/m.sup.2 to the subject. 23. The method of claim 1, wherein the bendamustine-responsive condition is indolent B-cell non-Hodgkin's lymphoma. 24. The method of claim 23, wherein the composition is administered intravenously in a volume of about 50 ml over a time period of about 10 minutes or less on days 1 and 2 of a 21 day cycle. 25. The method of claim 23, wherein the composition is administered intravenously in a volume of about 100 ml over a time period of about 15 minutes or less on days 1 and 2 of a 21 day cycle. 26. The method of claim 23, wherein the composition is administered for up to 8 cycles. 27. The method of claim 23, wherein the volume of the composition administered to the subject provides a dosage amount ranging from about 60 mg/m.sup.2 to about 120 mg/m.sup.2 to the subject. 28. A method of treating a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake; b) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing: TABLE-US-00009 Ingredient Concentration Range (mg/ml) Bendamustine HCl 0.05 to 1.6 Solubilizer 1 propylene glycol 0.3 to 6.5 Solubilizer 2 PEG 400 3.3 to 65 Monothioglycerol 0.02 to 0.35 NaOH 0.0 to 0.01 and, optionally a parenterally acceptable diluent, over a substantially continuous period of less than or equal to about 30 minutes. 29. A method of treating a bendamustine-responsive condition in a subject requiring restricted fluid and/or sodium intake, comprising a) identifying a subject in need of bendamustine therapy and having a physiological condition requiring restricted fluid and/or sodium intake; b) parenterally administering to said subject a volume of about 100 ml or less of a liquid composition containing: TABLE-US-00010 Ingredient Concentration Range (mg/ml) Bendamustine HCl 1.1 to 12.5 Solubilizer 1 propylene glycol 4.5 to 51 Solubilizer 2 PEG 400 45 to 500 Monothioglycerol 0.2 to 2.5 NaOH 0.0 to 0.04 and, optionally a parenterally acceptable diluent, over a substantially continuous period of less than or equal to about 30 minutes. 30. A method according to claim 1, wherein the bendamustine is present as the hydrochloride salt.