# US 9,751,919 B2 · Antimicrobial compositions comprising a hyaluronic acid binding peptide and a β-lactam antibiotic

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- Number: US 9,751,919 B2
- Document ID: US9751919B2
- Status: Granted
- Kind: B2
- Application number: 14/398,402
- Filed: 2013-05-03
- Published: 2015-08-06
- Granted: 2017-09-05
- Earliest claimed: 2012-05-04
- Assignees: Emergent Biosolutions Canada Inc.
- Applicants: Emergent BioSolutions Canada Inc.
- Inventors: Laura Saward; Xiaobing Han; George G. Zhanel
- Web page: https://patentgrep.com/patent/US9751919B2

## CPC

- C07K 14/47: from mammals
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- 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 31/545: Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-A61K-0953.gif] , e.g. cephalosporins, {cefaclor, or cephalexine}
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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

Compositions and methods for the treatment of antibiotic resistant Staphylococcus aureus infections are provided comprising β-lactam antibiotics, as well as a hyaluronic acid binding peptide. The antibiotics include cephalosporins as well as the ηoη-β lactam antibiotic vancomycin. The methods provide administering the composition to the subject in an amount effective to reduce or eliminate the infection.

## Claims

### Claim 1

A method for the prevention or treatment of antibiotic resistant S. aureus infection or reinfection, comprising administering a therapeutically effective amount of a beta-lactam antibiotic and a hyaluronic acid binding peptide comprising the amino acid sequence SEQ ID NO: 2.

### Claim 2 (depends on 1)

The method of claim 1 wherein the S. aureus is a methicillin resistant variant (MRSA), a vancomycin resistant variant (VRSA), or a vancomycin intermediate resistant variant (VISA).

### Claim 3 (depends on 1)

The method of claim 1 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are administered within 15 minutes of each other.

### Claim 4 (depends on 1)

The method of claim 1 wherein the beta-lactam antibiotic is a cephalosporin.

### Claim 5 (depends on 1)

The method of claim 1 wherein the cephalosporin is a first generation cephalosporin.

### Claim 6 (depends on 1)

The method of claim 1 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.

### Claim 7 (depends on 4)

The method of claim 4 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.

### Claim 8 (depends on 1)

The method of claim 1 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.

### Claim 9 (depends on 1)

The method of claim 1 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.

### Claim 10

A method of potentiating a beta-lactam antibiotic against antibiotic resistant S. aureus comprising administering a hyaluronic acid binding peptide, comprising the amino acid sequence SEQ ID NO: 2, with the beta-lactam antibiotic.

### Claim 11 (depends on 10)

The method of claim 10 wherein the antibiotic resistant S. aureus is a methicillin resistant variant (MRSA), a vancomycin resistant variant (VRSA) or a vancomycin intermediate resistant variant (VISA).

### Claim 12 (depends on 10)

The method of claim 10 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are administered simultaneously or concurrently.

### Claim 13 (depends on 12)

The method of claim 12 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are for administration within 15 minutes of each other.

### Claim 14 (depends on 12)

The method of claim 12 wherein the beta-lactam antibiotic is a cephalosporin.

### Claim 15 (depends on 14)

The method of claim 14 wherein the cephalosporin is a first generation cephalosporin.

### Claim 16 (depends on 14)

The method of claim 14 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.

### Claim 17 (depends on 14)

The method of claim 14 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime, Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime, Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.

### Claim 18 (depends on 12)

The method of claim 12 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.

### Claim 19 (depends on 12)

The method of claim 12 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.

### Claim 20

A composition comprising a beta-lactam antibiotic and a hyaluronic acid binding peptide comprising the amino acid sequence SEQ ID NO: 2.

### Claim 21 (depends on 20)

The composition of claim 20 wherein the beta-lactam antibiotic is a cephalosporin.

### Claim 22 (depends on 21)

The composition of claim 21 wherein the cephalosporin is a first generation cephalosporin.

### Claim 23 (depends on 21)

The composition of claim 21 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.

### Claim 24 (depends on 21)

The composition of claim 21 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cofactor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime, Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime, Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.

### Claim 25 (depends on 20)

The composition of claim 20 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.

### Claim 26 (depends on 20)

The composition of claim 20 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.

### Claim 27 (depends on 2)

The method of claim 2, wherein the combination of the hyaluronic acid binding protein with the antibiotic reduces the minimum inhibitory concentration of the MRSA strain.

### Claim 28 (depends on 2)

The method of claim 2, wherein the combination of the hyaluronic acid binding protein with the antibiotic reduces the minimum inhibitory concentration of the MRSA strain 2-256 fold.

### Claim 29 (depends on 2)

The method of claim 2, wherein the combination of the hyaluronic acid binding protein with the antibiotic reverts the minimum inhibitory concentration of the MRSA strain to susceptible (≦8 ug/mL).