Claims for Patent: 9,827,317

Summary for Patent: 9,827,317

Title:	Sustained release of antiinfectives
Abstract:	Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
Inventor(s):	Lawrence T. Boni, Brian S. Miller, Vladimir Malinin, Xingong Li
Assignee:	Insmed Inc
Application Number:	US14/319,018
Patent Claims:	1. A liposomal aminoglycoside formulation comprising a liposome having a lipid bilayer and an aminoglycoside or a pharmaceutically acceptable salt thereof encapsulated therein, wherein the lipid bilayer comprises a neutral phospholipid and a sterol, the weight ratio of lipid to the aminoglycoside, or the pharmaceutically acceptable salt thereof in the formulation is 0.75:1 or less and the liposome has a mean diameter of about 0.1 μm to about 1.0 μm. 2. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin, gentamicin, tobramycin, streptomycin, netilmicin, kanamycin, or a pharmaceutically acceptable salt thereof. 3. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin, or a pharmaceutically acceptable salt thereof. 4. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is streptomycin, or a pharmaceutically acceptable salt thereof. 5. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is tobramycin, or a pharmaceutically acceptable salt thereof. 6. The liposomal aminoglycoside formulation of claim 1, wherein the neutral phospholipid is a phosphatidylcholine. 7. The liposomal aminoglycoside formulation of claim 1, wherein the neutral phospholipid is dipalmitoylphosphatidylcholine (DPPC). 8. The liposomal aminoglycoside formulation of claim 1, wherein the sterol is cholesterol. 9. The liposomal aminoglycoside formulation of claim 1, wherein the neutral phospholipid is DPPC, and the sterol is cholesterol. 10. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin or a pharmaceutically acceptable salt thereof, the neutral phospholipid is DPPC and the sterol is cholesterol. 11. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is an aminoglycoside sulfate. 12. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin sulfate. 13. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is tobramycin sulfate. 14. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is streptomycin sulfate. 15. The liposomal aminoglycoside formulation of claim 1, wherein the liposome has a mean diameter of about 0.2 μm to about 1.0 μm. 16. The liposomal aminoglycoside formulation of claim 1, wherein the liposome has a mean diameter of about 0.2 μm to about 0.5 μm. 17. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 1. 18. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 3. 19. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 6. 20. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 7. 21. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 8. 22. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 9. 23. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 10. 24. A method of treating a patient for a pulmonary infection comprising administering to the patient a therapeutically effective amount of the liposomal aminoglycoside formulation of claim 1. 25. The method of claim 24, wherein the pulmonary infection is a Pseudomonas, staphylococcal, streptococcal, Escherichia, Kiebsiella, Enterobacter, Serratia, Haemophilus, Yersinia, Burkholderia, or mycobacterial infection. 26. The method of claim 24, wherein the pulmonary infection is a mycobacterial infection. 27. The method of claim 24, wherein the pulmonary infection is a Pseudomonas infection. 28. The method of claim 24, wherein the liposome has a mean diameter of about 0.2 μm to about 1.0 μm. 29. The method of claim 24, wherein the liposome has a mean diameter of about 0.2 μm to about 0.5 μm. 30. The method of claim 24, wherein the patient is a cystic fibrosis patient. 31. The method of claim 24, wherein the aminoglycoside is amikacin or a pharmaceutically acceptable salt thereof. 32. The method of claim 25, wherein the mycobacterial infection is Mycobacterium tuberculosis, Mycobacterium avium complex (MAC) (Mycobacterium avium and Mycobacterium intracellulare), Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans, or Mycobacterium fortuitum complex (M. fortuitum and M. chelonae). 33. The method of claim 27, wherein the Pseudomonas infection is a Pseudomonas aeruginosa infection. 34. The method of claim 27, wherein the Pseudomonas infection is a chronic Pseudomonas infection. 35. The method of claim 32, wherein the mycobacterial infection is a Mycobacterium avium complex (MAC) (Mycobacterium avium and Mycobacterium intracellulare) infection. 36. The method of claim 34, wherein the chronic Pseudomonas infection is a chronic Pseudomonas aeruginosa infection. 37. The method of claim 26, wherein the aminoglycoside is amikacin sulfate. 38. The method of claim 27, wherein the aminoglycoside is amikacin sulfate. 39. The method of claim 28, wherein the aminoglycoside is amikacin sulfate. 40. The method of claim 29, wherein the aminoglycoside is amikacin sulfate. 41. The method of claim 30, wherein the aminoglycoside is amikacin sulfate. 42. The method of claim 31, wherein the aminoglycoside is amikacin sulfate. 43. The method of claim 32, wherein the aminoglycoside is amikacin sulfate. 44. The method of claim 33, wherein the aminoglycoside is amikacin sulfate. 45. The method of claim 34, wherein the aminoglycoside is amikacin sulfate. 46. The method of claim 35, wherein the aminoglycoside is amikacin sulfate. 47. The method of claim 36, wherein the aminoglycoside is amikacin sulfate. 48. The method of claim 26, wherein the aminoglycoside is amikacin sulfate. 49. The method of claim 37, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 50. The method of claim 38, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 51. The method of claim 39, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 52. The method of claim 40, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 53. The method of claim 41, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 54. The method of claim 42, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 55. The method of claim 43, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 56. The method of claim 44, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 57. The method of claim 45, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 58. The method of claim 46, wherein the neutral phospholipid is DPPC and the sterol is cholesterol. 59. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 11. 60. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 12.