Therapy and kit for the prevention and treatment of cystic fibrosis

Patent metadata

Field	Value
Publication number	US-9421239-B2
Application number	US-201514719910-A
Country	US
Kind code	B2
Filing date	May 22, 2015
Priority date	Oct 22, 2008
Publication date	Aug 23, 2016
Grant date	Aug 23, 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, thereby treating the subject's cystic fibrosis.

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 small organic compound having the structure of Formula I:

wherein, R 1 , R 2 and R 3 are each independently hydrogen, —OR 4 , lower alkyl, amino, halo, or a carboxyl group; and R 4 is hydrogen or a lower alkyl group.

4. The method of claim 1 , wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof.

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

6. The method of claim 1 , further comprising administering a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof.

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); 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 small organic molecule having the structure of Formula I:

wherein, R 1 , R 2 and R 3 are each independently hydrogen, —OR 4 , lower alkyl, amino, halo, or a carboxyl group; and R 4 is hydrogen or a lower alkyl group.

9. The kit of claim 7 , wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof.

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

Assignees

• Dartmouth College

Inventors

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

Classifications

• A61K38/16

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• C07K5/1013

  the side chain containing O or S as heteroatoms, e.g. Cys, Ser · CPC title

• A61K31/655

  Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds · 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

• C07K7/06

  having 5 to 11 amino acids · CPC title