Combination therapy for treatment of resistant bacterial infections
Inventors
DeJonge, Boudewijn Lodewijk Maria • Durand-Reville, Thomas Francois • Verheijen, Jeroen Cunera • Tommasi, Ruben • Mueller, John
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10376499-B2
Publication Date
2019-08-13
Expiration Date
Abstract
The present invention is directed to combinations of a β-lactamase inhibitor with sulbactam and, optionally, imipenem/cilastatin. The combinations are useful for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant pathogens. More particularly, the invention relates to a combination of β-lactamase inhibitor compound 1: or a pharmaceutically acceptable salt thereof, with sulbactam, or a pharmaceutically acceptable salt thereof, and, optionally, imipenem/cilastatin, or a pharmaceutically acceptable salt thereof.
Core Innovation
The patent describes therapeutic combinations for resistant bacterial infections that center on a novel β-lactamase inhibitor identified as compound 1, together with sulbactam. The combination is defined with a “consisting essentially of” scope for the active ingredients, focusing on pairing a β-lactamase inhibitor or a pharmaceutically acceptable salt thereof with sulbactam or a pharmaceutically acceptable salt thereof.
The problem addressed is the treatment of resistant and MDR bacterial infections, including infections involving β-lactamases and clinically relevant β-lactamase activity classes. The background context emphasizes that β-lactamase mediated resistance complicates the use of β-lactam antibiotics, motivating a combination approach using a β-lactamase inhibitor to restore or improve antibacterial activity.
The patent supports the use of compound 1 in combination with sulbactam and optionally with additional antibiotics such as imipenem/cilastatin, and it identifies target pathogens including MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, and Burkholderia spp. It reports β-lactamase inhibitor-driven potency outcomes using MIC comparisons and reports synergy and potentiation with other β-lactam regimens, and it also describes in vivo efficacy in neutropenic thigh and lung A. baumannii models and a murine melioidosis model involving Burkholderia pseudomallei.
Claims Coverage
The independent claims cover a “consisting essentially of” pharmaceutical combination containing a β-lactamase inhibitor and sulbactam, an analogous combination that optionally includes pharmaceutically acceptable carriers, diluents and/or excipients and optionally includes additional antibiotics, and a method of treating a bacterial infection by administering an effective amount of the β-lactamase inhibitor and sulbactam. Across the independent claims, there are two main inventive elements: selecting a β-lactamase inhibitor component paired with sulbactam, with “consisting essentially of” limitation; and administering effective amounts to treat bacterial infection.
Essentially defined β-lactamase inhibitor–sulbactam combination
A combination consisting essentially of the β-lactamase inhibitor or a pharmaceutically acceptable salt thereof and sulbactam or a pharmaceutically acceptable salt thereof.
Essentially defined β-lactamase inhibitor–sulbactam combination optionally with formulation components and an additional antibiotic
A combination consisting essentially of the β-lactamase inhibitor or a pharmaceutically acceptable salt thereof and sulbactam or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable carriers, diluents and/or excipients, and optionally ampicillin or cefoperazone.
Treating bacterial infection by administering β-lactamase inhibitor with sulbactam
A method of treating bacterial infection in a subject in need thereof, consisting essentially of administering to the subject in need thereof an effective amount of the β-lactamase inhibitor or a pharmaceutically acceptable salt thereof, and an effective amount of sulbactam or a pharmaceutically acceptable salt thereof.
Overall, the independent claim set focuses on an essentially defined pharmaceutical combination of a β-lactamase inhibitor together with sulbactam, including optional formulation components and optional additional antibiotics in one independent claim, and on a corresponding method of treating bacterial infection by administering effective amounts of the same two active components.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?