# US 11,298,401 B2 · Compositions and uses of antimicrobial materials with tissue-compatible properties

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- Number: US 11,298,401 B2
- Document ID: US11298401B2
- Status: Granted
- Kind: B2
- Application number: 15/240,197
- Filed: 2016-08-18
- Published: 2017-02-16
- Granted: 2022-04-12
- Earliest claimed: 2012-03-23
- Assignees: Amicrobe, Inc.
- Applicants: Amicrobe, Inc.
- Inventors: Michael P. Bevilacqua; Diego Benitez; Jarrod A. Hanson
- Web page: https://patentgrep.com/patent/US11298401B2

## CPC

- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A01N 37/44: containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
- A01N 37/46: N-acyl derivatives
- A01N 47/44: Guanidine; Derivatives thereof
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K 31/765: Polymers containing oxygen
- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61L 15/42: Use of materials characterised by their function or physical properties (liquid bandages A61L26/00)
- A61L 15/46: Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
- A61L 24/001: {Use of materials characterised by their function or physical properties}
- A61L 24/0015: {Medicaments; Biocides}
- A61L 24/0036: {Porous materials, e.g. foams or sponges}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/46: for decreasing, blocking or antagonising the activity of glucocorticosteroids
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/02: Local antiseptics
- A61P 31/04: Antibacterial agents
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- A61L 2400/04: Materials for stopping bleeding
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compositions comprising a mixture of an antimicrobial cationic polypeptide and a second pharmaceutically-acceptable polymer are disclosed, as well as methods and uses thereof for the treatment and prevention of infections that occur when our natural barriers of defense are broken.

## Claims

### Claim 1

A method of treating a biofilm, comprising:
selecting a site capable of supporting biofilm formation;
applying to the site a composition comprising one or more synthetic polypeptide(s) having a length of at least 40 amino acid residues;
wherein the one or more synthetic polypeptide(s) has a net cationic charge at neutral pH;
wherein the one or more synthetic polypeptide(s) has at least one cationic segment with a plurality of positively charged amino acid residues and at least one hydrophobic segment with a plurality of hydrophobic amino acid residues; and
wherein the synthetic cationic polypeptide(s) are configured to self-assemble into multimeric structures in an aqueous composition,
wherein the one or more synthetic polypeptide(s) inhibits or kills microbes in biofilms.

### Claim 2 (depends on 1)

The method of claim 1, wherein the site is selected from the group consisting of an acute wound, a chronic wound, a devitalized tissue, and a foreign body.

### Claim 3 (depends on 2)

The method of claim 2, wherein the foreign body is selected from the group consisting of a prosthetic device, mesh, ventilator equipment, and a catheter.

### Claim 4 (depends on 3)

The method of claim 3, wherein the mesh is an implantable mesh.

### Claim 5 (depends on 3)

The method of claim 3, wherein the mesh is a synthetic mesh.

### Claim 6 (depends on 1)

The method of claim 1, wherein the synthetic polypeptide(s) contains one cationic segment and one hydrophobic segment.

### Claim 7 (depends on 1)

The method of claim 1, wherein the composition further comprises a pharmaceutically-acceptable polymer that is not a synthetic cationic polypeptide.

### Claim 8 (depends on 1)

The method of claim 1, wherein the site comprises a biofilm.

### Claim 9 (depends on 1)

The method of claim 1, wherein an antimicrobial activity of the one or more synthetic polypeptide(s) when in an aqueous composition at a concentration of 100 μg/mL or less is greater than 3 logs killing of Staphylococcus epidermidis and Escherichia coli in standard 60 minute time-kill assays.

### Claim 10 (depends on 1)

The method of claim 1, wherein the at least one cationic segment comprises one or more of lysine or arginine.

### Claim 11 (depends on 10)

The method of claim 10, wherein the at least one hydrophobic segment comprises one or more of leucine, isoleucine, valine, and alanine.

### Claim 12 (depends on 1)

The method of claim 1, wherein the composition further comprises a second pharmaceutically-acceptable polymer that is not a synthetic, cationic polypeptide(s); and
wherein the one or more synthetic polypeptide(s) and the second pharmaceutically-acceptable polymer are mutually miscible in water.

### Claim 13 (depends on 12)

The method of claim 12, wherein the amounts of the one or more synthetic polypeptide(s) and the second pharmaceutically-acceptable polymer are each at least about 100 μg/mL based on the total volume of the aqueous composition.

### Claim 14 (depends on 13)

The method of claim 13, wherein the amount of the second pharmaceutically-acceptable polymer is at least about 10% by weight, based on the weight of the one or more synthetic polypeptide(s).

### Claim 15 (depends on 1)

The method of claim 1, wherein the one or more synthetic polypeptide(s) comprises a block containing 50 to 200 or more lysine amino acid residues.

### Claim 16 (depends on 1)

The method of claim 1, wherein the one or more synthetic polypeptide(s) comprises K50(rac-L)10 (SEQ ID NO: 1), K50(rac-L)20 (SEQ ID NO: 2), K50(rac-L)30 (SEQ ID NO: 3), K50(rac-L)40 (SEQ ID NO: 4), K50(rac-L)50 (SEQ ID NO: 5), K50L10 (SEQ ID NO: 6), K50L20 (SEQ ID NO: 7), K50L30 (SEQ ID NO: 8), K50L40 (SEQ ID NO: 9), K50L50 (SEQ ID NO: 10), K100(rac-L)10 (SEQ ID NO: 11), K100(rac-L)20 (SEQ ID NO: 12), K100(rac-L)30 (SEQ ID NO: 13), K100(rac-L)40 (SEQ ID NO: 14), K100(rac-L)50 (SEQ ID NO: 15), K100L10 (SEQ ID NO: 16, K100L20 (SEQ ID NO: 17), K100L30 (SEQ ID NO: 18), K100L40 (SEQ ID NO: 19), K100L50 (SEQ ID NO: 20), K200(rac-L)10 (SEQ ID NO: 21), K200(rac-L)20 (SEQ ID NO: 22), K200(rac-L)30 (SEQ ID NO: 23), K200(rac-L)40 (SEQ ID NO: 24), K200(rac-L)50 (SEQ ID NO: 25), K200L10 (SEQ ID NO: 26), K200L20 (SEQ ID NO: 27), K200L30 (SEQ ID NO: 28), K20L40 (SEQ ID NO: 29), K200L50 (SEQ ID NO: 30), or combinations of more than one of the foregoing.

### Claim 17 (depends on 1)

The method of claim 1, wherein the composition is characterized by a barrier activity, as measured by a decrease in the diffusion rate of an anionic dye.