Claims for Patent: 12,478,606

Summary for Patent: 12,478,606

Title:	Methods of treating bacterial infections
Abstract:	Methods of treating or ameliorating urinary tract infection (UTI), including complicated urinary tract infection (cUTI) and acute pyelonephritis (AP), comprising administering a composition comprising a cyclic boronic acid ester vaborbactam in combination with meropenem are disclosed herewith.
Inventor(s):	Jeffrey S. Loutit, Michael N. Dudley, Elizabeth E. Morgan, Karen FUSARO, David C. Griffith, Olga Lomovskaya
Assignee:	Melinta Subsidiary Corp
Application Number:	US16/474,487
Patent Claims:	1. A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject, wherein the subject has a Charlson comorbidity score equal to or greater than 3. 2. The method of claim 1, wherein the subject is suffering from cUTI. 3. The method of claim 1, wherein the subject is suffering from AP. 4. The method of claim 1, wherein the subject is also suffering from concomitant bacteremia. 5. The method of claim 1, wherein the administration continues for at least five days. 6. The method of claim 1, wherein the subject is a female. 7. The method of claim 1, wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min. 8. The method of claim 1, wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min. 9. The method of claim 1, wherein the subject has a systemic inflammatory response syndrome (SIRS). 10. A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising: selecting for treatment a subject having a systemic inflammatory response syndrome (SIRS) who is also suffering from cUTI or AP; and administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject, wherein the subject has a Charlson comorbidity score equal to or greater than 3. 11. The method of claim 10, wherein the subject has one or more of the following characteristics at the time of treatment: body temperature less than 36° C. or more than 38° C., heart rate more than 90 bpm, respiratory rate greater than 20 breaths/min, an arterial partial pressure of carbon dioxide less than 4.3 kPa (32 mmHg), white blood cell count more than 12,000 cells/mm3 or less than 4,000 cells/mm3, or the presence of greater than 10% immature neutrophils. 12. A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising: selecting for treatment a subject having a Charlson comorbidity score of equal to or greater than 3, who is also suffering from cUTI or AP; and administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject. 13. The method of claim 12, wherein the subject is also suffering from concomitant bacteremia. 14. The method of claim 12, wherein the administration continues for at least five days. 15. The method of claim 12, wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min. 16. The method of claim 12, wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min. 17. The method of claim 1, wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa, or combinations thereof. 18. A method of treating or ameliorating a serious infection due to carbapenem-resistant enterobacteriaceae (CRE) in a subject in need thereof, comprising: selecting for treatment a subject having a CRE infection that requires at least 7 days of treatment with intravenous antibiotics; and administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject. 19. The method of claim 18, wherein the CRE infection is selected from the group consisting of cUTI, AP, cIAI, HABP, VABP, and bacteremia, and combinations thereof. 20. The method of claim 18, wherein the method provides less adverse events in the treatment of the CRE infection as compared to a subject treated with best available therapy. 21. The method of claim 18, wherein the method provides a higher success rate in the treatment of the CRE infection as compared to a subject treated with best available therapy. 22. The method of claim 21, wherein the best available therapy is selected from the group consisting of ciprofloxacin, polymyxin B, colistin, amikacin, meropenem, gentamicin, ertapenem, tigecycline, and ceftazidime-avibactam, and combinations thereof. 23. The method of claim 18, wherein the subject has a Charlson comorbidity score of equal to or greater than 3. 24. The method of claim 23, wherein the subject has a Charlson comorbidity score of equal to or greater than 5. 25. The method of claim 18, wherein the subject has a systemic inflammatory response syndrome (SIRS). 26. The method of claim 18, wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g. 27. The method of claim 18, wherein the amount of meropenem is about 2 g. 28. The method of claim 18, wherein the combination is administered at least once per day. 29. The method of claim 28, wherein the combination is administered every 8 hours. 30. The method of claim 18, wherein the administration is by intravenous infusion. 31. The method of claim 30, wherein the intravenous infusion is completed is about 3 hours. 32. The method of claim 18, wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem. 33. The method of claim 18, wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form. 34. The method of claim 18, further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof. 35. The method of claim 10, wherein the subject is also suffering from concomitant bacteremia. 36. The method of claim 10, wherein the administration continues for at least five days. 37. The method of claim 10, wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min. 38. The method of claim 10, wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min. 39. The method of claim 10, wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa, or combinations thereof. 40. The method of claim 12, wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa, or combinations thereof. 41. The method of claim 21, wherein the best available therapy is selected from the group consisting of ciprofloxacin, polymyxin B, colistin, amikacin, meropenem, gentamicin, ertapenem, tigecycline, and ceftazidime-avibactam, and combinations thereof. 42. The method of claim 1, wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g. 43. The method of claim 1, wherein the amount of meropenem is about 2 g. 44. The method of claim 1, wherein the combination is administered at least once per day. 45. The method of claim 44, wherein the combination is administered every 8 hours. 46. The method of claim 1, wherein the administration is by intravenous infusion. 47. The method of claim 46, wherein the intravenous infusion is completed in about 3 hours. 48. The method of claim 1, wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem. 49. The method of claim 1, wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form. 50. The method of claim 1, further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof. 51. The method of claim 10, wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g. 52. The method of claim 10, wherein the amount of meropenem is about 2 g. 53. The method of claim 10, wherein the combination is administered at least once per day. 54. The method of claim 53, wherein the combination is administered every 8 hours. 55. The method of claim 10, wherein the administration is by intravenous infusion. 56. The method of claim 55, wherein the intravenous infusion is completed in about 3 hours. 57. The method of claim 10, wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem. 58. The method of claim 10, wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form. 59. The method of claim 10, further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof. 60. The method of claim 12, wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g. 61. The method of claim 12, wherein the amount of meropenem is about 2 g. 62. The method of claim 12, wherein the combination is administered at least once per day. 63. The method of claim 62, wherein the combination is administered every 8 hours. 64. The method of claim 12, wherein the administration is by intravenous infusion. 65. The method of claim 64, wherein the intravenous infusion is completed in about 3 hours. 66. The method of claim 12, wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem. 67. The method of claim 12, wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form. 68. The method of claim 12, further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof. 69. The method of claim 1, wherein the subject is a human suffering from moderate or severe liver disease.