# US 2021/0330738 A1 · Antimicrobial, bacteriophage-derived polypeptides and their use against gram-negative bacteria

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- Number: US 2021/0330738 A1
- Document ID: US20210330738A1
- Status: Published application
- Kind: A1
- Application number: 17/041,638
- Filed: 2019-03-29
- Published: 2021-10-28
- Earliest claimed: 2018-03-29
- Applicants: Contrafect Corporation
- Inventors: Raymond SCHUCH
- Web page: https://patentgrep.com/patent/US20210330738A1

## CPC

- A61K 38/162: {from virus}
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 31/427: not condensed and containing further heterocyclic rings
- 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 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5383: ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 31/665: having oxygen as a ring hetero atom, e.g. fosfomycin
- A61K 31/7036: having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
- A61K 31/7052: having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C07K 14/005: from viruses
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C12N 2795/14222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2795/14231: Uses of virus other than therapeutic or vaccine, e.g. disinfectant
- C12N 2795/14233: Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- 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. 1-4, 6-26 and 54-66, 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 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 bacteria and methods of treating a bacterial infection in a subject.

## 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. 1-4, 6-26 and 54-66 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. 1-4, 6-26 and 54-66, wherein the modified Chp peptide inhibits the growth, reduces the population, or kills at least one species of Gram-negative bacteria; and
a pharmaceutically acceptable carrier
wherein the Chp peptide contains at least one non-natural modification relative to the amino acid sequence of any one of SEQ ID NOs. 1-4, 6-26 and 54-66 or active fragments thereof.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the non-natural modification is selected from the group consisting of substitution modifications, N-terminal acetylation modifications, and C-terminal amidation modifications.

### 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.

### Claim 8

A vector comprising a nucleic acid molecule that encodes (i) a Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 1-4, 6-26 and 54-66 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. 1-4, 6-26 and 54-66, wherein the modified Chp peptide inhibits the growth, or reduces the population, or kills at least one species of Gram-negative bacteria.

### Claim 9 (depends on 8)

The vector according to claim 8, wherein the vector is a recombinant expression vector and wherein the nucleic acid is operatively linked to a heterologous promoter.

### Claim 10

(canceled)

### Claim 11

(canceled)

### Claim 12 (depends on 8)

The vector of claim 8, wherein the nucleic acid molecule is a cDNA sequence.

### Claim 13 (depends on 8)

An isolated host cell comprising the vector of claim 8.

### Claim 14

An isolated, purified nucleic acid encoding a Chp peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 1-4, 6-26 and 54-66 or active fragments thereof or a nucleic acid comprising a sequence complementary thereto, wherein the Chp peptide contains at least one non-natural modification relative to the amino acid sequence of any one of SEQ ID NOs. 1-4, 6-26 and 54-66 or active fragments thereof.

### Claim 15

(canceled)

### Claim 16 (depends on 14)

The isolated, purified nucleic acid of claim 14 wherein the non-natural modification is selected from the group consisting of substitution modifications, N-terminal acetylation modifications, and C-terminal amidation modifications.

### Claim 17

An isolated, purified DNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs. 27-30, SEQ ID NOs. 32-53, and SEQ ID NOs. 68-79 wherein the nucleotide sequence contains at least one non-natural modification.

### Claim 18

(canceled)

### Claim 19 (depends on 17)

The isolated, purified DNA of claim 17, wherein the non-natural modification is a mutation or a nucleic acid sequence encoding an N-terminal acetylation modification or a C-terminal amidation modification.

### 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. 1-4, 6-26 and 54-66 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. 1-4, 6-26 and 54-66, 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

(canceled)

### Claim 22

(canceled)

### Claim 23 (depends on 1)

A method of preventing or treating a bacterial infection caused by at least one species of Gram-negative 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 24 (depends on 20)

The method of claim 20, wherein the 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 25 (depends on 20)

The method of claim 20, wherein the at least one species of Gram-negative bacteria is Pseudomonas aeruginosa.

### Claim 26 (depends on 20)

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

### Claim 27 (depends on 23)

The method of claim 23, further comprising administering to the subject an antibiotic suitable for the treatment of Gram-negative bacterial infection.

### Claim 28 (depends on 27)

The method of claim 27, wherein the antibiotic 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 29

(canceled)

### Claim 30 (depends on 27)

The method of claim 27, wherein administering the pharmaceutical composition is more effective in inhibiting the growth, reducing the population, or killing the Gram-negative bacteria than administering the antibiotic alone.

### Claim 31 (depends on 1)

A method for preventing or treating a bacterial infection caused by at least one species of Gram-negative bacteria, comprising co-administering to a subject diagnosed with, at risk for, or exhibiting symptoms of a bacterial infection, a combination of a first amount of a pharmaceutical composition according to claim 1 and a second amount of an antibiotic suitable for the treatment of Gram-negative bacterial infection, wherein the first and the second amounts together are effective for preventing or treating the bacterial infection.

### Claim 32 (depends on 31)

The method of claim 31, wherein the antibiotic 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 1)

A method for augmenting the efficacy of an antibiotic suitable for the treatment of a bacterial infection caused by at least one species of Gram-negative bacteria, comprising co-administering the antibiotic in combination with a pharmaceutical composition according to claim 1,
wherein administration of the combination is more effective in inhibiting growth, reducing the population, or killing the Gram-negative bacteria than administration of either the antibiotic or the pharmaceutical composition individually.