Variants of TACE pro-domain as TNF-A inhibitor and their medical use

Patent metadata

Field	Value
Publication number	US-9764008-B2
Application number	US-201314398754-A
Country	US
Kind code	B2
Filing date	May 9, 2013
Priority date	May 9, 2012
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R 58 , R 56 and K 57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

First claim

What is claimed is:

1. A method of treating an inflammatory disease, the method comprising administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-α converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a substitution at each of the sites R 58 , R 211 and C 184 thereby rendering said polypeptide resistant to furin degradation, said polypeptide being capable of downregulating an activity of TACE, wherein the numbering of the substitution corresponds to the full length human TACE enzyme.

2. The method of claim 1 , wherein said inflammatory disease is selected from the group consisting of an autoimmune disease, cancer and hepatitis.

3. The method of claim 2 , wherein said autoimmune disease is Crohn's disease or rheumatoid arthritis.

4. The method of claim 1 , wherein said substitution at position 211 is a replacement of arginine to alanine, wherein said substitution at position 214 is a replacement of arginine to glycine, and wherein said substitution at position 184 is a replacement of cysteine to alanine.

5. The method of claim 1 , wherein said substitution at position 58 is a replacement of arginine to alanine.

6. The method of claim 1 , wherein said polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs. 6-8.

Assignees

• Yeda Res & Dev

Inventors

• Sagi Irit
• Wong Eitan
• Afik Ran

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title