Peptides as active agents to stabilize biological barriers

• US 9,012,403 B2
• Filed: 06/17/2011
• Issued: 04/21/2015
• Est. Priority Date: 06/18/2010
• Status: Expired due to Fees

• Current Assignee: XiberScience GmbH
• Original Assignee: XiberScience GmbH
• Inventors: Petzelbauer, Peter, Reingruber, Sonja
• Primary Examiner(s): Ha, Julie
• Application Number:
  US13/702,490
• Publication Number:
  US 20130143791A1
• Time in Patent Office: 1,404 Days
• Field of Search: 514/15.4, 514/1.5, 514/21.6, 530/327, 530/328
• US Class Current: 514/15.4
• CPC Class Codes: A61K 38/00 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 Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The present invention relates to compounds, in particular peptides which are capable of stabilizing barrier functions of epithelium and endothelium. The peptides and other compounds of the present invention are useful in the treatment and prevention of diseases or disorders associated with a localized or systemic breakdown of epithelial and endothelial barrier functions. Particular diseases and disorders to be treated and/or prevented with the peptides or other compounds, methods and uses provided herein are burns, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ventilator induced lung injury (VILI), systemic inflammatory response syndrome (SIRS), acute kidney injury (AKI), sepsis, multiorgan dysfunction syndrome (MODS), or edema.

Claims

1. A peptide with an amino acid sequence consisting of:

2. Peptide of claim 1, further comprising X₇ at the C-terminus of the sequence, wherein X₇ is a moiety selected from the group consisting of NH₂, albumin, polyethyleneglycol, dextrane, ferritine, hydroxyethyl-starch and Fc-moiety of an antibody.

3. The peptide of claim 1, wherein X₂ is L or V.

4. The peptide of claim 3, wherein X₂ is L.

5. The peptide of claim 1, wherein X₃ is PPP.

6. The peptide of claim 1, wherein X₄ is GG.

7. The peptide of claim 1, wherein X₆ is omitted.

8. The peptide of claim 1, wherein X₂ is L, X₃ is omitted and X6 is omitted, or wherein X₂ is V, X₃ is omitted and X₆ is omitted.

9. The peptide of claim 1, wherein the amino acid sequence consist of:

10. A pharmaceutical composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier and/or diluent.

11. The peptide of claim 1, wherein the peptide is synthetic.

12. The peptide of claim 9, wherein the peptide is synthetic.

13. A method of treating a disease or disorder selected from the group consisting of acute lung injury (ALI), acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), ventilator induced lung injury (VILI), systemic inflammatory response syndrome (SIRS), sepsis, burns and multiorgan dysfunction syndrome (MODS) by administering an effective dose of the pharmaceutical composition of claim 10 to a subject.

14. The method of claim 13, wherein the route of administration is parenterally or orally.