PD-L1 and PD-L2-based fusion proteins and uses thereof

• US 9,657,082 B2
• Filed: 01/31/2014
• Issued: 05/23/2017
• Est. Priority Date: 01/31/2013
• Status: Active Grant

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Tykocinski, Mark L.
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US14/763,649
• Publication Number:
  US 20150361155A1
• Time in Patent Office: 1,208 Days
• Field of Search: None
• 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: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/70521 CD28, CD152
• 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 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

Provided are fusion proteins comprising a first domain and a second domain, wherein the first domain comprises a polypeptide that binds to and triggers PD-1 and the second domain comprises a polypeptide that binds to and triggers a TRAIL receptor or Fas. In some embodiments, the polypeptide that binds to and triggers PD-1 comprises at least a portion of the extracellular domain of PD-L1 or PD-L2 and the second domain comprises at least a portion of the extracellular domain of TRAIL or Fas ligand. Also provided are methods for treating autoimmune, alloimmune or inflammatory diseases, and methods for treating cancer, using the fusion proteins.

Claims

1. A PD-L1/TRAIL fusion protein comprising the amino acid sequence of SEQ ID NO:

1.

2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a fusion protein according to claim 1.

3. A PD-L1/TRAIL fusion protein comprising the amino acid sequence of SEQ ID NO:

2.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a fusion protein according to claim 3.

5. A PD-L1/TRAIL fusion protein comprising the amino acid sequence of SEQ ID NO:

3.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a fusion protein according to claim 5.

7. A PD-L1/TRAIL fusion protein comprising the amino acid sequence of SEQ ID NO:

4.

8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a fusion protein according to claim 7.