Claims for Patent: 9,566,234

Summary for Patent: 9,566,234

Title:	Systems for treating pulmonary infections
Abstract:	Provided herein are systems for treating a subject with a pulmonary infection, for example, a nontuberculous mycobacterial pulmonary infection, a Burkholderia pulmonary infection, a pulmonary infection associated with bronchiectasis, or a Pseudomonas pulmonary infection. The system includes a pharmaceutical formulation comprising a liposomal aminoglycoside dispersion, and the lipid component of the liposomes consist essentially of electrically neutral lipids. The system also includes a nebulizer which generates an aerosol of the pharmaceutical formulation at a rate greater than about 0.53 gram per minute. The aerosol is delivered to the subject via inhalation for the treatment of the pulmonary infection.
Inventor(s):	Walter Perkins, Vladimir Malinin, Xingong Li, Brian Miller, Dominique Seidel, Philipp Holzmann, Harald Schulz, Michael Hahn
Assignee:	PARI Pharma GmbH , Insmed Inc
Application Number:	US13/899,457
Patent Claims:	1. A system for treating or providing prophylaxis against a pulmonary infection in a patient, comprising: (a) a pharmaceutical formulation comprising an aqueous dispersion of liposomal complexed aminoglycoside, wherein the lipid component of the liposomal complexed aminoglycoside is present at 45-60 mg/mL and consists of dipalmitoylphosphatidylcholine (DPPC) and cholesterol, and (b) a nebulizer comprising a vibrating mesh membrane, which generates an aerosol of the pharmaceutical formulation at a rate of 0.60 g per minute to 0.80 g per minute, wherein the fine particle fraction (FPF) of the aerosol is greater than or equal to about 64%, as measured by the Andersen Cascade Impactor (ACI), or greater than or equal to about 51%, as measured by the Next Generation Impactor (NGI) and the percent associated aminoglycoside of the aerosol is from 60% to 70%. 2. The system of claim 1, wherein the aminoglycoside is selected from amikacin, apramycin, arbekacin, astromicin, capreomycin, dibekacin, framycetin, gentamicin, hygromycin B, isepamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodestreptomycin, ribostamycin, sisomicin, spectinomycin, streptomycin, tobramycin, verdamicin, or a combination thereof. 3. The system of claim 1, wherein the aminoglycoside is amikacin. 4. The system of claim 3, wherein the amikacin is amikacin sulfate. 5. The system of claim 1, wherein the liposomes of the liposomal aminoglycoside formulation are unilamellar vesicles, multilamellar vesicles, or a mixture thereof. 6. The system of claim 1, wherein the aminoglycoside is amikacin, and the liposomes of the liposomal aminoglycoside formulation are unilamellar vesicles, multilamellar vesicles, or a mixture thereof. 7. The system of claim 1, wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 8. A method for treating or providing prophylaxis against a pulmonary infection in a patient, the method comprising: aerosolizing with a nebulizer comprising a vibrating mesh membrane at a rate of 0.60 g per minute to 0.80 g per minute, a pharmaceutical formulation comprising an aqueous dispersion of liposomal complexed aminoglycoside, wherein the lipid component of the liposomal complexed aminoglycoside is present at 45-60 mg/mL and consists of dipalmitoylphosphatidylcholine (DPPC) and cholesterol, to form an aerosolized pharmaceutical formulation, and administering the aerosolized pharmaceutical formulation to the lungs of the patient; wherein the aerosolized pharmaceutical formulation comprises a mixture of free aminoglycoside and liposomal complexed aminoglycoside, the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is greater than or equal to about 64%, as measured by the Andersen Cascade Impactor (ACI), or greater than or equal to about 51%, as measured by the Next Generation Impactor (NGI) and the percent liposomal complexed aminoglycoside of the aerosolized pharmaceutical formulation is from 60% to 70%. 9. The method of claim 8, wherein the aminoglycoside is selected from amikacin, apramycin, arbekacin, astromicin, capreomycin, dibekacin, framycetin, gentamicin, hygromycin B, isepamicin, kanamycin, neomycin, netilmicin, paromomycin, ribostamycin, sisomicin, rhodestreptomycin, spectinomycin, streptomycin, tobramycin, verdamicin, or a combination thereof. 10. The method of claim 8, wherein the aerosolized pharmaceutical formulation is administered once per day in a single dosing session. 11. The method of claim 8, wherein the aminoglycoside is amikacin. 12. The method of claim 11, wherein the amikacin is amikacin sulfate. 13. The method of claim 8, wherein the patient has cystic fibrosis. 14. The method of claim 8, wherein the pulmonary infection is a nontuberculous mycobacterial infection. 15. The method of claim 8, wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 16. The method of claim 14, wherein the nontuberculous mycobacterial infection is M. avium, M. avium subsp. hominissuis (MAH), M. abscessus, M. chelonae, M. bolletii, M. kansasii, M. ulcerans, M. avium, M. avium complex (MAC), M. conspicuum, M. kansasii, M. peregrinum, M. immunogenum, M. xenopi, M. marinum, M. malmoense, M. marinum, M. mucogenicum, M. nonchromogenicum, M. scrofulaceum, M. simiae, M. smegmatis, M. szulgai, M. terrae, M. terrae complex, M. haemophilum, M. genavense, M. asiaticum, M. shimoidei, M. gordonae, M. nonchromogenicum, M. triplex, M. lentiflavum, M. celatum, M. fortuitum or M. fortuitum complex. 17. The method of claim 16, wherein the nontuberculous mycobacterial infection is M. avium complex (MAC). 18. The method of claim 17, wherein the aminoglycoside is amikacin. 19. The method of claim 18, wherein the amikacin is amikacin sulfate. 20. The method of claim 8, wherein the pulmonary infection is a nontuberculous mycobacterial infection and the aminoglycoside is amikacin sulfate. 21. The method of claim 8, wherein the pulmonary infection is a M. avium complex (MAC) infection, and the aminoglycoside is amikacin sulfate. 22. The system of claim 1, wherein the mass median aerodynamic diameter (MMAD) of the aerosol is < about 4.2 as measured by the ACI, or < about 4.9 as measured by the NGI. 23. The system of claim 22, wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 as measured by the ACI; or about 4.4 μm to about 4.9 as measured by the NGI. 24. The method of claim 8, wherein the mass median aerodynamic diameter (MMAD) of the aerosol is < about 4.2 as measured by the ACI, or < about 4.9 as measured by the NGI. 25. The method of claim 24, wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 as measured by the ACI; or about 4.4 μm to about 4.9 as measured by the NGI.