Designed peptides for tight junction barrier modulation

Patent metadata

Field	Value
Publication number	US-9757428-B2
Application number	US-201414912098-A
Country	US
Kind code	B2
Filing date	Aug 18, 2014
Priority date	Aug 16, 2013
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

According to aspects illustrated herein, there is provided an agent that transiently disrupts claudin-1 within tight junctions. The agent includes a peptide having at least 40% polar, uncharged amino acid residues and a self-assembled β-sheet secondary structure. According to aspects illustrated herein, there is also provided a transepithelial drug and vaccine formulations, as well as isolated peptides, pharmaceutical compositions, and transdermal delivery devices. Also described herein are methods of disrupting epithelial barrier and methods of administering the transepithelial formulations described herein.

First claim

What is claimed:

1. A transepithelial drug formulation comprising:
a pharmaceutically suitable carrier;
an effective amount of a therapeutic agent; and
an agent that transiently disrupts claudin-1 within tight junctions, wherein the agent comprises one or more peptides including at least 40% polar, uncharged amino acid residues and a self-assembled β-sheet secondary structure, wherein the one or more peptides comprise the amino acid sequence of SEQ ID NO:6.

2. The transepithelial drug formulation according to claim 1 , wherein the drug formulation is a transdermal or transmucosal drug formulation.

3. The transepithelial drug formulation according to claim 1 , wherein the peptides form one or more fibrils.

4. The transepithelial drug formulation according to claim 1 , wherein the amino acid sequence of the one or more peptides comprise at least 50% polar, uncharged amino acid residues.

5. The transepithelial drug formulation according to claim 4 , wherein the amino acid sequence of the one or more peptides comprise at least 60% polar, uncharged amino acid residues.

6. The transepithelial drug formulation according to claim 1 , wherein the one or more peptides comprise an amino acid sequence of less than 53 amino acid residues.

7. The transepithelial drug formulation according to claim 1 , wherein the agent consists of the one or more peptides.

8. The transepithelial drug formulation according to claim 1 , wherein the carrier includes a surfactant.

9. A transepithelial vaccine formulation comprising:
a pharmaceutically suitable carrier;
an effective amount of an antigen or antigen-encoding nucleic acid molecule present in the carrier, and optionally one or more adjuvants; and
an agent that transiently disrupts claudin-1 within tight junctions, wherein the agent comprises one or more peptides including at least 40% polar, uncharged amino acid residues and a self-assembled β-sheet secondary structure, wherein the one or more peptides comprise the amino acid sequence of SEQ ID NO:6.

10. A pharmaceutical composition comprising:
an isolated peptide comprising the amino acid sequence SILTGVSTLDQSLKQLSNFSQAVSTQSSR (SEQ ID NO:6) and
a pharmaceutically suitable carrier.

11. The pharmaceutical composition according to claim 10 further comprising:
a therapeutic agent.

12. The transepithelial vaccine formulation according to claim 9 , wherein the vaccine formulation is a transdermal or transmucosal vaccine formulation.

13. The transepithelial vaccine formulation according to claim 9 , wherein the one or more peptides form one or more fibrils.

14. The transepithelial vaccine formulation according to claim 9 , wherein the amino acid sequence of the one or more peptides comprise at least 50% polar, uncharged amino acid residues.

15. The transepithelial vaccine formulation according to claim 14 , wherein the amino acid sequence of the one or more peptides comprise at least 60% polar, uncharged amino acid residues.

16. The transepithelial vaccine formulation according to claim 9 , wherein the one or more peptides comprise an amino acid sequence of less than 53 amino acid residues.

17. The transepithelial vaccine formulation according to claim 9 , wherein the agent consists of the one or more peptides.

18. The transepithelial vaccine formulation according to claim 9 , wherein the carrier includes a surfactant.

19. A method of disrupting an epithelial barrier comprising:
applying to an epithelial site an amount of an agent that transiently disrupts claudin-1 within tight junctions that is effective to disrupt claudin-1 in epithelial cells present at the site, wherein the agent comprises a peptide including at least 40% polar, uncharged amino acid residues and a self-assembled β-sheet secondary structure, thereby disrupting barrier formation at the epithelial site, wherein the peptide comprises the amino acid sequence of SEQ ID NO: 6.

Assignees

• Miller Benjamin L
• De Benedetto Anna
• Beck Lisa A
• Anderson Elizabeth A
• Univ Rochester

Inventors

• Miller Benjamin L
• De Benedetto Anna
• Beck Lisa A
• Anderson Elizabeth A

Classifications

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/55516

  Proteins; Peptides · CPC title

• A61K38/44

  Oxidoreductases (1) · CPC title

• A61K38/17 Primary

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• C12Y113/12007

  Photinus-luciferin 4-monooxygenase (ATP-hydrolysing) (1.13.12.7), i.e. firefly-luciferase · CPC title