Soluble TNF receptors and their use in treatment of disease

• US 7,785,834 B2
• Filed: 05/01/2007
• Issued: 08/31/2010
• Est. Priority Date: 11/10/2005
• Status: Active Grant

• Current Assignee: Roche Innovation Center Copenhagen A/S (Roche Holding AG), Ercole Biotech, Inc. (Sarepta Therapeutics, Inc.), University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: Santaris Pharma A/S (Roche Holding AG), Ercole Biotech, Inc. (Sarepta Therapeutics, Inc.), University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Graziewicz, Maria, Kole, Ryszard, Orum, Henrik, Sazani, Peter L.
• Primary Examiner(s): Spector; Lorraine
• Application Number:
  US11/799,117
• Publication Number:
  US 20070249538A1
• Time in Patent Office: 1,218 Days
• Field of Search: None
• US Class Current: 435/69.1
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• 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 14/7151 for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3231 having an additional ring, e.g. LNA, ENA
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2320/33 Alteration of splicing
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to tumor necrosis factor (TNF) antagonists and corresponding nucleic acids derived from tumor necrosis factor receptors (TNFRs) and their use in the treatment of inflammatory diseases. These proteins are soluble secreted decoy receptors that bind to TNF and prevent TNF from signaling to cells. In particular, the proteins are mammalian TNFRs that lack exon 7 and which can bind TNF and can act as a TNF antagonist.

Claims

1. An isolated nucleic acid molecule that encodes a polypeptide that consists of an amino acid sequence selected from the group consisting of:

the amino acid sequence of SEQ ID NO;

10 and the amino acid sequence of amino acids 23-245 of SEQ ID NO;

10.

3. An expression vector comprising the nucleic acid molecule of claim 1, operably linked to a regulatory sequence.

4. A cell transformed with the expression vector of claim 3.

5. The cell of claim 4, wherein said cell is a mammalian cell, an insect cell, or a microbial cell.

6. A process for producing a polypeptide consisting of SEQ ID NO:

10 or the amino acid sequence of amino acids 23-245 of SEQ ID NO;

10, which process comprises culturing the cell of claim 5 under conditions suitable to express said polypeptide, and recovering said polyptide.

2. An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of:

SEQ ID NO;

10 and the amino acid sequence of amino acids 23-435 of SEQ ID NO;

10.