TWEAK receptor

• US 6,727,225 B2
• Filed: 06/18/2001
• Issued: 04/27/2004
• Est. Priority Date: 12/20/1999
• Status: Expired due to Fees

• Current Assignee: Immunex Corporation (Amgen Inc.)
• Original Assignee: Immunex Corporation (Amgen Inc.)
• Inventors: Wiley, Steven R.
• Primary Examiner(s): Caputa, Anthony C.
• Assistant Examiner(s): YAEN, CHRISTOPHER H
• Application Number:
  US09/883,777
• Publication Number:
  US 20020110853A1
• Time in Patent Office: 1,044 Days
• Field of Search: 530/300, 530/350, 514/2, 514/12
• US Class Current: 424/134.1
• 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 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• 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 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 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• 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
• CPC Class Codes: C07K 2319/73 containing coiled-coiled motif (leucine zippers)

Abstract

The present invention provides the TWEAK receptor and methods for identifying and using agonists and antagonists of the TWEAK receptor. In particular, the invention provides methods of screening for agonists and antagonists and for treating diseases or conditions mediated by angiogenesis, such as solid tumors and vascular deficiencies of cardiac or peripheral tissue.

Claims

1. An isolated polypeptide consisting of a sequence of amino acids that is at least 80% identical to a reference sequence of amino acids, wherein said reference sequence of amino acids consists of residue 28 to residue x₁ of SEQ ID NO:

4, x₁ is selected from the group of residues 68 to 80 of SEQ ID NO;

4, and said isolated polypeptide binds to TWEAK.

2. The isolated polypeptide of claim 1 wherein said isolated polypeptide consists of a sequence of amino acids that is at least 90% identical to said reference sequence of amino acids.

3. The isolated polypeptide of claim 2, wherein said isolated polypeptide consists of a sequence of amino acids that is at least 95% identical to said reference sequence of amino acids.

9. A fusion polypeptide comprising the polypeptide of claim 1 operably linked to a polypeptide of interest.

10. The fusion polypeptide of claim 9, wherein the polypeptide of interest is an Fc polypeptide, leucine zipper polypeptide, or an peptide linker.

4. An isolated polypeptide comprising a sequence Z₁-X-Z₂, wherein Z₁ and Z₂ each individually is a polypeptide consisting of a sequence of amino acids that is at least 80% identical to a reference sequence of amino acids, wherein said reference sequence of amino acids consists of residue 28 to residue x₁ of SEQ ID NO:

4, x₁ is selected from the group of residues 68 to 80 of SEQ ID NO;

4, X is a peptide linker, and said isolated polypeptide binds to TWEAK.

5. The isolated polypeptide of claim 4, wherein said Z₁ and Z₂ each individually is a polypeptide consisting of a sequence of amino acids that is at least 90% identical to said reference sequence of amino acids.

6. The isolated polypeptide of claim 4, wherein said Z₁ and Z₂ each individually is a polypeptide consisting of a sequence of amino acids that is at least 95% identical to said reference sequence of amino acids.

7. The isolated polypeptide of claim 4, wherein Z₁ and Z₂ have the same amino acid sequence.

8. The isolated polypeptide of claim 4 wherein X is selected from the group consisting of:

—

Gly—

Gly—

, GGGGS (SEQ ID NO;

     10), (GGGGS)_n (SEQ ID NO;

     11), GKSSGSGSESKS (SEQ ID NO;

     12), GSTSGSGKSSEGKG (SEQ ID NO;

13), GSTSGSGKSSEGSGSTKG (SEQ ID NO;

14), GSTSGSGKPGSGEGSTKG (SEQ ID NO;

15), and EGKSSGSGSESKEF (SEQ ID NO;

16).