# US 10,500,191 B2 · Compositions and methods of use of antibacterial drug combinations

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- Number: US 10,500,191 B2
- Document ID: US10500191B2
- Status: Granted
- Kind: B2
- Application number: 15/743,203
- Filed: 2016-07-08
- Published: 2018-07-19
- Granted: 2019-12-10
- Earliest claimed: 2015-07-09
- Assignees: Washington University
- Applicants: Washington University
- Inventors: Gautam Dantas; Patrick Gonzales; Kevin Forsberg; Mitchell Pesesky; Mayland Chang; Shahriar Mobashery
- Web page: https://patentgrep.com/patent/US10500191B2

## CPC

- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 31/424: condensed with heterocyclic ring systems, e.g. clavulanic acid
- A61K 31/43: Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems
- A61K 31/431: containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure encompasses antibacterial compositions and methods of treating bacterial infections caused by resistant bacteria.

## Claims

### Claim 1

A composition useful for the treatment of an infection caused by a methicillin-resistant Staphylococcus aureus (MRSA), wherein the resistance is due to a penicillin-binding protein 2a (PBP2a)-driven mechanism, the composition comprising:
i) at least one carbapenem or another β-lactam capable of binding the allosteric site of PBP2a;
ii) at least one β-lactamase inhibitor; and
iii) at least one β-lactam that binds the open configuration of the active site of PBP2a;
wherein the composition is selected from the group consisting of
a) meropenem/piperacillin/tazobactam (ME/PI/TZ);
b) cefepime/piperacillin/tazobactam (CP/PI/TZ);
c) aztreonam/piperacillin/tazobactam (AZ/PI/TZ);
d) meropenem/amoxicillin/tazobactam (ME/AX/TZ);
e) meropenem/amoxicillin/clavulanate (ME/AX/CV); and
f) imipenem/piperacillin/clavulanate (IM/PI/CV).

### Claim 2 (depends on 1)

The composition of claim 1, wherein the ratio of the carbapenem or another β-lactam to the β-lactamase inhibitor is in the range of 64:1 to 1:64.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the ratio of the carbapenem or another β-lactam to the PBP2a binding β-lactam is in the range of 64:1 to 1:64.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the ratio of the β-lactamase inhibitor to the PBP2a binding β-lactam is in the range of 64:1 to 1:64.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the ratio of the antibiotics in the combination may range from 64:1:1, 1:64:1, and 1:1:64 to 1:1:1.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising a composition of claim 1 and at least one pharmaceutically acceptable excipient.

### Claim 7 (depends on 1)

A method for treating an infection caused by a methicillin-resistant Staphylococcus aureus (MRSA) in a subject, wherein the resistance is due to a penicillin-binding protein 2a (PBP2a)-driven mechanism, the method comprising administering to the subject an effective amount of a composition of claim 1.

### Claim 8 (depends on 1)

A method for treating an infection caused by methicillin-resistant Staphylococcus aureus (MRSA), the method comprising administering to the subject an effective amount of a composition of claim 1.