# US 2022/0401514 A1 · Antimicrobial, bacteriophage-derived polypeptides and their use against gram-negative and acid-fast bacteria

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- Number: US 2022/0401514 A1
- Document ID: US20220401514A1
- Status: Published application
- Kind: A1
- Application number: 17/621,357
- Filed: 2020-07-02
- Published: 2022-12-22
- Earliest claimed: 2019-07-05
- Applicants: Contrafect Corporation
- Inventors: Raymond SCHUCH
- Web page: https://patentgrep.com/patent/US20220401514A1

## CPC

- A61K 38/162: {from virus}
- C07K 14/005: from viruses
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C12N 2795/14222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed herein are pharmaceutical compositions comprising an effective amount of an isolated Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 81-91 and 94-102, or a modified Chp peptide having about 80% sequence identity therewith, wherein the modified Chp peptide inhibits growth, reduces the population, or kills at least one species of Gram-negative or acid-fast bacteria; and a pharmaceutically acceptable carrier. Further disclosed herein are isolated Chp peptides, as well as vectors comprising a nucleic acid molecule that encode the Chp peptides and host cells comprising a vector. Also disclosed herein are methods of inhibiting the growth, reducing the population, or killing of at least one species of Gram-negative or acid-fast bacteria, methods of treating a bacterial infection in a subject, and methods for prevention, disruption, or treatment of a biofilm comprising a Gram-negative bacteria.

## Claims

### Claim 1

A pharmaceutical composition comprising:
an effective amount of (i) an isolated Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 81-91 and 94-102 or active fragment thereof, or (ii) a modified Chp peptide having 80% sequence identity with the amino acid sequence of at least one of SEQ ID NOs. 81-91 and 94-102, wherein the modified Chp peptide inhibits the growth, reduces the population, or kills at least one species of Gram-negative bacteria or acid-fast bacteria; and
a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the Chp peptide has an amino acid sequence selected from SEQ ID NO: 81, SEQ ID NO: 89, or active fragments thereof.

### Claim 3

(canceled)

### Claim 4

(canceled)

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The pharmaceutical composition according to claim 1, which is a solution, a suspension, an emulsion, an inhalable powder, an aerosol, or a spray.

### Claim 7 (depends on 1)

The pharmaceutical composition according to claim 1, further comprising one or more antibiotics suitable for the treatment of Gram-negative bacteria or acid-fast bacteria.

### Claim at position 8

-19. (canceled)

### Claim 20

A method of inhibiting the growth, reducing the population, or killing of at least one species of Gram-negative bacteria, the method comprising contacting the bacteria with a composition comprising an effective amount of (i) a Chp peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 81-91 and 94-102 or active fragments thereof, or (ii) a modified Chp peptide having 80% sequence identity with the amino acid sequence of at least one of SEQ ID NOs. 81-91 and 94-102, said Chp peptide or modified Chp peptide having lytic activity for a period of time sufficient to inhibit said growth, reduce said population, or kill said at least one species of Gram-negative bacteria.

### Claim 21 (depends on 20)

The method of inhibiting the growth, reducing the population, or killing of at least one species of Gram-negative bacteria according to claim 20, wherein the amino acid sequence is selected from SEQ ID NO: 81, SEQ ID NO: 89, or active fragments thereof.

### Claim 22

A method of inhibiting the growth, reducing the population, or killing of at least one species of acid-fast bacteria, the method comprising contacting the bacteria with a composition comprising an effective amount of (i) a Chp peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 4, 6, 8-21, 23-26, 59-61, 63-65, 67, 81, 87-89, 91, 97, and 99-101 or active fragments thereof, or (ii) a modified Chp peptide having 80% sequence identity with the amino acid sequence of at least one of SEQ ID NOs. 1, 2, 4, 6, 8-21, 23-26, 59-61, 63-65, 67, 81, 87-89, 91, 97, and 99-101, said Chp peptide or modified Chp peptide having lytic activity for a period of time sufficient to inhibit said growth, reduce said population, or kill said at least one species of acid-fast bacteria.

### Claim 23 (depends on 22)

The method of inhibiting the growth, reducing the population, or killing of at least one species of acid-fast bacteria according to claim 22, wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 81, 87, 88, 89, 91, 97, 100, and 101 or active fragments thereof.

### Claim 24 (depends on 1)

A method of preventing or treating a bacterial infection caused by at least one species of Gram-negative or acid-fast bacteria, comprising administering to a subject diagnosed with, at risk for, or exhibiting symptoms of a bacterial infection, a pharmaceutical composition according to claim 1.

### Claim 25 (depends on 20)

The method of claim 20, wherein the at least one species of Gram-negative bacteria is selected from the group consisting of Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Salmonella, Neisseria gonorrhoeae, and Shigella.

### Claim 26

(canceled)

### Claim 27 (depends on 20)

The method of claim 20, wherein the at least one species of Gram-negative bacteria comprises persister cells.

### Claim 28 (depends on 22)

The method of claim 22, wherein the at least one species of acid-fast bacteria is selected from the group consisting of Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium scrofulaceum, Mycobacterium peregrinum, Mycobacterium marinum, Mycobacterium intracellulare, and Mycobacterium fortuitum.

### Claim 29

(canceled)

### Claim 30 (depends on 20)

The method of claim 20, wherein the bacterial infection is a topical or systemic bacterial infection.

### Claim 31 (depends on 24)

The method of claim 24, further comprising administering to the subject an antibiotic suitable for the treatment of Gram-negative or acid-fast bacterial infection.

### Claim 32 (depends on 31)

The method of claim 31, wherein the antibiotic suitable for the treatment of a Gram-negative bacterial infection is selected from one or more of azithromycin, aztreonam, fosfomycin, ceftazidime, cefepime, cefoperazone, ceftobiprole, ciprofloxacin, levofloxacin, aminoglycosides, imipenem, meropenem, doripenem, gentamicin, tobramycin, amikacin, piperacillin, ticarcillin, penicillin, rifampicin, polymyxin B, and colistin.

### Claim 33

(canceled)

### Claim 34 (depends on 30)

The method of claim 30 wherein the antibiotic suitable for the treatment of an acid-fast bacterial infection is selected from one or more of isoniazid, rifampin, ethambutol, and pyrazinamide.

### Claim 35 (depends on 30)

The method of claim 30, wherein administering the pharmaceutical composition is more effective in inhibiting the growth, reducing the population, or killing the Gram-negative or acid-fast bacteria than administering the antibiotic alone.

### Claim 36 (depends on 30)

The method of claim 30, wherein the Gram-negative or acid-fast bacteria is present in human serum and/or pulmonary surfactant.

### Claim 37

A method for prevention, disruption, or eradication of a biofilm comprising at least one species of Gram-negative bacteria, the method comprising contacting a biofilm with a pharmaceutical composition comprising (i) an isolated Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 81-91 and 94-102 or active fragment thereof, or (ii) a modified Chp peptide having 80% sequence identity with the amino acid sequence of at least one of SEQ ID NOs. 81-91 and 94-102, wherein the modified Chp peptide inhibits the growth, reduces the population, or kills at least one species of Gram-negative bacteria, and wherein the biofilm is effectively prevented, dispersed, or eradicated.

### Claim 38 (depends on 37)

The method of claim 37, wherein the at least one species of Gram-negative bacteria is Stenotrophomonas maltophilia.

### Claim 39 (depends on 37)

The method of claim 37, wherein the isolated Chp peptide has an amino acid sequence of SEQ ID NO: 81 or active fragment thereof or a modified Chp peptide having 80% identity with SEQ ID NO: 81 wherein the modified Chp peptide inhibits the growth, reduces the population, or kills at least one species of Gram-negative bacteria.

### Claim 40 (depends on 20)

The method of claim 20, wherein the at least one species of Gram-negative bacteria is resistant to at least one antibiotic suitable for the treatment of a Gram-negative bacterial infection.

### Claim 41 (depends on 22)

The method of claim 22, wherein the Chp peptide comprises SEQ ID NO: 2.