Dermaseptin-type and piscidin-type antimicrobial peptides

Patent metadata

Field	Value
Publication number	US-10428126-B2
Application number	US-201916241583-A
Country	US
Kind code	B2
Filing date	Jan 7, 2019
Priority date	Jan 24, 2014
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

Antimicrobial agents, including antimicrobial peptides (AMPs) and uses thereof. Compositions and methods of using dermaseptin-type and piscidin-type antimicrobial peptides that demonstrate activity and improved therapeutic indices against microbial pathogens. The peptide compositions demonstrate the ability to not only maintain or improve antimicrobial activity against bacterial pathogens including Gram-negative microorganisms Acinetobacter baumannii and Pseudomonas aeruginosa, but also significantly decrease hemolytic activity against human red blood cells. Specificity determinants within the AMPS change selectivity from broad spectrum antimicrobial activity to AMPS with gram-negative selectivity.

First claim

What is claimed is:

1. An antimicrobial peptide (AMP) comprising the amino acid sequence selected from the group consisting of: ALWMTLKKKVLKAKAKALNAVLKGANA (SEQ ID NO: 16); ALWMTLKKKVLKAKAKALNAVLAGVNA (SEQ ID NO: 17); and ALWMTLKKKVLKAKAKALNAVLVGLNA (SEQ ID NO: 19)
or a pharmaceutically-acceptable salt thereof.

2. The AMP of claim 1 , wherein the amino acid sequence of the AMP comprises the sequence of SEQ ID NO: 16.

3. The AMP of claim 1 , wherein the amino acid sequence of the AMP comprises the sequence of SEQ ID NO: 17.

4. The AMP of claim 1 , wherein the amino acid sequence of the AMP consists of the sequence of SEQ ID NO: 19.

5. The AMP of claim 1 , wherein the AMP inhibits propagation of a Gram-negative bacterium.

6. The AMP of claim 5 , wherein the Gram-negative bacterium is at least one of A. baumannii and P. aeruginosa.

7. A pharmaceutical composition comprising at least one peptide of claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 , comprising a mono-phasic pharmaceutical composition suitable for parenteral or oral administration consisting essentially of a therapeutically-effective amount of at least one peptide of claim 1 , and a pharmaceutically acceptable carrier.

9. A method of treating a Gram-negative bacterial infection comprising administering to a subject in need thereof a therapeutically effective amount of at least one peptide of claim 1 or a pharmaceutical composition of claim 7 .

10. The method of claim 9 , wherein the Gram-negative bacterial infection is an antibiotic resistant bacterial infection.

11. The method of claim 9 , wherein an infecting microorganism is at least one of Acinetobacter baumannii and Pseudomonas aeruginosa.

12. The method of claim 9 , wherein an infecting microorganism is multi-drug resistant Pseudomonas aeruginosa or Acinetobacter baumannii.

13. The method of claim 9 , wherein the administration of the peptide or pharmaceutical composition is by an administration route selected from oral, topical, intravenous, intraperitoneal, intramuscular, intradermal, intrasternal, intraarticular injection, or infusion.

Assignees

• Univ Colorado Regents

Inventors

• Jiang Ziqing
• Hodges Robert S
• Gera Lajos
• Mant Colin T

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/461

  from fish · CPC title

• C07K14/463 Primary

  from amphibians · CPC title

• Y02A50/471

  Cross-Sectional Technologies · mapped topic

• Y02A50/473

  Cross-Sectional Technologies · mapped topic