Pharmaceutical compositions for treating arthritis and inflammatory disease

• US 7,399,465 B2
• Filed: 10/15/2004
• Issued: 07/15/2008
• Est. Priority Date: 05/14/1998
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Gatanaga, Tetsuya, Granger, Gale A.
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Assistant Examiner(s): Emch; Gregory S
• Application Number:
  US10/967,092
• Publication Number:
  US 20050090647A1
• Time in Patent Office: 1,369 Days
• Field of Search: None
• US Class Current: 424/94.1
• 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: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C12N 9/6421 from mammals
• CPC Class Codes: C12N 9/6489 Metalloendopeptidases (3.4.24)
• CPC Class Codes: G01N 2333/525 Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

The biological effects of the cytokine TNF are mediated by binding to receptors on the surface of cells. This disclosure describes new proteins and polynucleotides that promote enzymatic cleavage and release of TNF receptors. Also provided are methods for identifying additional compounds that influence TNF receptor shedding. As the active ingredient in a pharmaceutical composition, the products of this invention increase or decrease TNF signal transduction, thereby alleviating the pathology of disease.

Claims

1. A method for preparing a pharmaceutical composition, comprising compounding a protein in an excipient suitable for human administration,

wherein the protein comprises a consecutive amino acid sequence that is at least 90% identical to the sequence encoded in SEQ. ID NO:

9, or fragment of said sequence, and

wherein the protein causes cleavage of TNF receptor from human cells on which TNF receptor is expressed.

5. The method of claim 1, wherein the protein cleaves TNF receptor from the surface of cells.

6. The method of claim 1, wherein the protein causes release of the human p55 TNF receptor from cells expressing the receptor.

7. The method of claim 1, wherein the protein causes release of the human p75 TNF receptor from cells expressing the receptor.

2. A method for preparing a pharmaceutical composition, comprising compounding a protein in an excipient suitable for human administration,

wherein the protein comprises a consecutive amino acid sequence that is identical to the sequence encoded in SEQ. ID NO:

9, or fragment of said sequence, and

wherein the protein causes cleavage of TNF receptor from human cells in which TNF receptor is expressed.

3. A method for preparing a pharmaceutical composition, comprising compounding a protein in an excipient suitable for human administration,

wherein the protein comprises a consecutive amino acid sequence that is at least 80% identical to the sequence encoded in SEQ. ID NO:

9, or fragment of said sequence, and

wherein the protein protects mice against septic shock caused by administration of an otherwise lethal dose of lipopolysaccharide (LPS).

4. A method for preparing a pharmaceutical composition, comprising compounding a protein in an excipient suitable for human administration,

wherein the protein comprises a consecutive amino acid sequence that is at least 90% identical to the sequence encoded in SEQ. ID NO:

9, or fragment of said sequence, and

wherein the protein protects mice against septic shock caused by administration of an otherwise lethal dose of LPS.