# US 7,745,401 B2 · Antifungal peptides and methods of use thereof

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- Number: US 7,745,401 B2
- Document ID: US7745401B2
- Status: Granted
- Kind: B2
- Application number: 11/497,178
- Filed: 2006-07-31
- Published: 2007-06-14
- Granted: 2010-06-29
- Earliest claimed: 2005-08-01
- Assignees: The Board of Regents of the University of Oklahoma
- Inventors: H. Anne Pereira; Paul Fidel
- Web page: https://patentgrep.com/patent/US7745401B2

## CPC

- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61P 31/10: Antimycotics
- C07K 14/4723: {Cationic antimicrobial peptides, e.g. defensins}
- 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)

## Abstract

A method of treating fungal infections by treatment with CAP37 peptides and derivatives thereof, including peptide analogs having serine or threonine substitutions at least one of the two cysteine residues therein. Other substitutions of the amino acid residues of the peptide are also contemplated.

## Claims

### Claim 1

A method of treating a fungal infection in a subject in need of such treatment, comprising:
administering to the subject in need of treatment of the fungal infection a therapeutically effective amount of a peptide having 20-25 amino acids, the peptide comprising SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14, and wherein the peptide comprises an arginine residue immediately adjacent to a histidine residue.

### Claim 2 (depends on 1)

The method of claim 1 wherein the peptide comprises SEQ ID NO: 6 or SEQ ID NO: 12.

### Claim 3 (depends on 1)

The method of claim 1 wherein the peptide comprises SEQ ID NO: 7 or SEQ ID NO: 13.

### Claim 4 (depends on 1)

The method of claim 1 wherein the peptide comprises SEQ ID NO: 8 or SEQ ID NO: 14.

### Claim 5 (depends on 1)

The method of claim 1 wherein the fungal infection treated in the subject is caused by at least one of a Candida spp., Saccharomyces cerevisiae, Histoplasma spp., Aspergillus spp., and Cryptococcus spp.

### Claim 6 (depends on 1)

The method of claim 1 wherein the subject is a mammal.

### Claim 7 (depends on 1)

The method of claim 1 wherein the subject is a human.

### Claim 8 (depends on 1)

The method of claim 1 wherein the peptide has from one to three additional amino acids on an N-terminal end of the peptide and one to two additional amino acids on a C-terminal end of the peptide.

### Claim 9 (depends on 1)

The method of claim 1 wherein the peptide is pegylated.

### Claim 10 (depends on 1)

The method of claim 1 wherein the peptide is covalently pegylated to a polyethylene glycol molecule via a linker molecule comprising 1 to 15 amino acids.

### Claim 11

A method of treating a fungal infection in a subject in need of such treatment, comprising:
administering to the subject in need of treatment of the fungal infection a therapeutically effective amount of a peptide comprising 20 to 25 amino acids, the peptide comprising the sequence (SEQ ID NO: 15):
R-H-X3-X4-X5-X6-X7-X8-X9-H-X11-R-X13-X14-M-X16-X17-X18-X19-X20
wherein:
X3 is phe, tyr, arg, lys or his;
X4 is cys, ser, thr, arg, lys or his;
X5 is gly, ala, arg, lys or his;
X6 is gly, ala, arg, lys or his;
X8, X9, X17, and X18 are selected from the group consisting of ala, leu, ile and val;
X7, X11 and X14 are selected from the group consisting of ala, leu, ile, val, arg, lys, and his;
X13 is phe or tyr;
X16 is ser or thr;
X19 is ser, thr, his, arg or lys;
X20 is ser, cys or thr;
R is arg;
H is his; and
M is met.

### Claim 12 (depends on 1)

The method of claim 1 wherein the X4 is cys and the X20 is serine or threonine.

### Claim 13 (depends on 1)

The method of claim 1 wherein the X20 is cys and the X4 is serine or threonine.

### Claim 14 (depends on 1)

The method of claim 1 wherein in the peptide:
X3 and X13 are selected from the group consisting of phe and tyr;
X4 and X20 are selected from the group consisting of cys, ser, and thr;
X5 and X6 are selected from the group consisting of gly and ala;
X7, X8, X9, X11, X14, X17 and X18 are selected from the group consisting of ala, leu, ile, and val;
X16 is ser or thr; and
X19 is ser, thr, his, arg, or lys.

### Claim 15 (depends on 1)

The method of claim 1 wherein the fungal infection treated in the subject is caused by at least one of a Candida spp., Saccharomyces cerevisiae, Histoplasma spp., Aspergillus spp., and Cryptococcus spp.

### Claim 16 (depends on 1)

The method of claim 1 wherein the subject is a mammal.

### Claim 17 (depends on 1)

The method of claim 1 wherein the subject is human.

### Claim 18 (depends on 1)

The method of claim 1 wherein the peptide has from one to three additional amino acids on an N-terminal end of the peptide and one to two additional amino acids on a C-terminal end of the peptide.

### Claim 19 (depends on 1)

The method of claim 1 wherein the peptide is pegylated.

### Claim 20 (depends on 1)

The method of claim 1 wherein the peptide is covalently pegylated to a polyethylene glycol molecule via a linker molecule comprising 1 to 15 amino acids.
