Death domain containing receptors

• US 6,713,061 B1
• Filed: 04/21/2000
• Issued: 03/30/2004
• Est. Priority Date: 03/12/1996
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC), Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Gentz, Reiner L., Yu, Guo-Liang, Ni, Jian, Dillon, Patrick J., Dixit, Vishva M.
• Primary Examiner(s): Eyler, Yvonne
• Assistant Examiner(s): O HARA, EILEEN B
• Application Number:
  US09/557,908
• Time in Patent Office: 1,439 Days
• Field of Search: 530/350, 536/23.5, 435/69.1, 424/185.1, 424/192.1
• US Class Current: 424/185.1
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• 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 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus

Abstract

The present invention relates to novel Death Domain Containing Receptor (DR3 and DR3-V1) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR3 and DR3-V1 proteins. DR3 and DR3-V1 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR3 and DR3-V1 activity.

Claims

1. An isolated polypeptide comprising an amino acid sequence at least 90% identical to amino acids 30 to 215 of SEQ ID NO:

2, wherein said polypeptide inhibits apoptosis.

2. The isolated polypeptide of claim 1, wherein said amino acid sequence is at least 95% identical to amino acids 30 to 215 of SEQ ID NO:

2.

3. The isolated polypeptide of claim 1, which is produced by a recombinant host cell.

4. The isolated polypeptide of claim 1, which comprises a heterologous polypeptide.

5. A composition comprising the isolated polypeptide of claim 1, and a pharmaceutically acceptable carrier.

6. An isolated polypeptide comprising an amino acid sequence at least 90% identical to the mature amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97456, wherein said polypeptide induces apoptosis.

7. The isolated polypeptide of claim 6, which comprises an amino acid sequence at least 95% identical to the mature amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97456.

8. The isolated polypeptide of claim 6, which comprises an amino acid sequence at least 90% identical to the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97456.

9. The isolated polypeptide of claim 8, which comprises an amino acid sequence at least 95% identical to the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97456.

10. The isolated protein of claim 6, which is produced by a recombinant host cell.

11. The isolated protein of claim 6, which comprises a heterologous polypeptide.

12. A composition comprising the isolated protein of claim 6, and a pharmaceutically acceptable carrier.