Combination therapy and kit for the prevention and treatment of cystic fibrosis

Patent metadata

Field	Value
Publication number	US-9333235-B2
Application number	US-201314105646-A
Country	US
Kind code	B2
Filing date	Dec 13, 2013
Priority date	Oct 22, 2008
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.

First claim

What is claimed is:

1. A method for treating cystic fibrosis comprising administering to a subject in need of treatment an effective amount of an agent that selectively inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR-Associated Ligand in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof, thereby treating the subject's cystic fibrosis, wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof.

2. The method of claim 1 , wherein the degradation-prone CFTR is ΔF508 CFTR or R1066C CFTR.

3. The method of claim 1 , wherein the agent is a peptide of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 or SEQ ID NO:23.

4. The method of claim 1 , wherein the agent is derivatized with a label, one or more post-translational modifications, a cell-penetrating sequence, or a combination thereof.

5. The method of claim 4 , wherein the cell-penetrating sequence comprises an amino acid sequence of SEQ ID NO:42.

6. The method of claim 1 , wherein the peptidomimetic is a peptide of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32 or SEQ ID NO:33.

7. A kit comprising
(a) an agent that inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR-Associated Ligand (CAL), wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof; and
(b) a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof.

8. The kit of claim 7 , wherein the agent is a peptide of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 or SEQ ID NO:23.

9. The kit of claim 8 , wherein the agent is derivatized with a label, one or more post-translational modifications, a cell-penetrating sequence, or a combination thereof.

10. The kit of claim 9 , wherein the cell-penetrating sequence comprises the amino acid sequence of SEQ ID NO:42.

11. The kit of claim 7 , wherein the peptidomimetic is a peptide of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32 or SEQ ID NO:33.

Assignees

• Dartmouth College

Inventors

• Madden Dean R
• Cushing Patrick R
• Boisguérin Prisca
• Volkmer Rudolf
• Vouilleme Lars

Classifications

• A61K31/47

  Quinolines; Isoquinolines · CPC title

• C07K14/4703

  Inhibitors; Suppressors · CPC title

• A61K38/04

  Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof ({enzyme inhibitors A61K38/005;} gastrins {A61K38/2207}, somatostatins A61K38/31, melanotropins A61K38/34 {; protease inhibitors A61K38/55}) · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title