OX40/TRAIL fusion proteins

• US 9,221,895 B2
• Filed: 03/11/2010
• Issued: 12/29/2015
• Est. Priority Date: 03/13/2009
• 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: Tykocinski, Mark L.
• Primary Examiner(s): DESAI, ANAND U
• Application Number:
  US13/256,401
• Publication Number:
  US 20120121640A1
• Time in Patent Office: 2,119 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Fusion proteins which act on the OX40/TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, and alloimmune diseases, as well as cancer.

Claims

1. A fusion protein comprising a first domain and a second domain, wherein the first domain consists of a portion of the extracellular domain of an OX40 protein that binds OX40 ligand and interferes with its ability to bind and trigger a membrane-bound OX40 receptor and the second domain consists of a TRAIL protein that binds to a TRAIL receptor and directs inhibitory signals through the receptor.

2. The fusion protein of claim 1, wherein the fusion protein is SEQ ID NO:

1 or SEQ ID NO;

2.

4. The fusion protein of claim 1, wherein the first domain is human OX40 and the second domain is human TRAIL.

5. The fusion protein of claim 1, in a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising the fusion protein of claim 1.

7. A method of treating or ameliorating an autoimmune disease in a patient comprising administering the fusion protein of claim 5 or claim 6 to a patient in need of such treatment.

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

9. The method of claim 7, wherein administration is parenteral.

10. A method of treating or ameliorating an alloimmune disease in a patient comprising administering the fusion protein of claim 5 or claim 6 to a patient in need of such treatment.

11. A method of treating or ameliorating cancer in a patient comprising administering the fusion protein of claim 5 or claim 6 to a patient in need of such treatment.

3. A fusion protein comprising a sequence selected from the group consisting of SEQ ID NO:

1 and SEQ ID NO;

2.