Fn14/TRAIL fusion proteins

• US 8,039,437 B2
• Filed: 06/30/2009
• Issued: 10/18/2011
• Est. Priority Date: 06/30/2008
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Razmara, Marjaneh, Tykocinski, Mark L.
• Primary Examiner(s): Spector; Lorraine
• Assistant Examiner(s): KAUFMAN, CLAIRE M
• Application Number:
  US12/494,680
• Publication Number:
  US 20100048478A1
• Time in Patent Office: 840 Days
• Field of Search: None
• US Class Current: 514/12.2
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Fusion proteins which act on the TWEAK and TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, as well as other diseases such as alloimmune diseases and cancer.

Claims

1. A fusion protein comprising a first domain and a second domain, wherein the first domain is a polypeptide that binds to TWEAK and the second domain is a polypeptide that binds to a TRAIL receptor, wherein the first domain is at least a portion of the extracellular domain of Fn14 protein and the second domain is at least a portion of the extracellular domain of a TRAIL protein.

5. A pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier.

6. A method of inhibiting inflammation in a patient having autoimmune disease comprising administering an effective amount of the pharmaceutical composition of claim 5.

7. The method of claim 6, wherein the autoimmune disease is multiple sclerosis.

8. The method of claim 6, wherein administration is parenteral.

9. The method of claim 6 wherein the patient has an alloimmune disease.

2. A fusion protein comprising a first domain and a second domain, wherein the first domain is a polypeptide that binds to TWEAK and the second domain is a polypeptide that binds to a TRAIL receptor, wherein the fusion protein is SEQ. ID. NO:

1 or SEQ. ID. NO;

2.

3. A fusion protein consisting of a first domain and a second domain, wherein the first domain is at least a TWEAK-binding portion of the extracellular domain of Fn14 protein and the second domain is at least a TRAIL receptor-binding portion of the extracellular domain of TRAIL protein.

4. A fusion protein comprising a first domain and a second domain, wherein the first domain is human Fn14 and the second domain is human TRAIL.