Antisense modulation of expression of tumor necrosis factor receptor-associated factors (TRAFs)

• US 6,399,297 B1
• Filed: 10/06/1998
• Issued: 06/04/2002
• Est. Priority Date: 10/06/1998
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Xu, Xaoxing S., Monia, Brett P., Baker, Brenda F., Cowsert, Lex M.
• Primary Examiner(s): Wang, Andrew
• Application Number:
  US09/167,109
• Time in Patent Office: 1,337 Days
• Field of Search: 514/44, 536/23.1, 536/24.3, 536/24.5, 435/6, 435/91.1, 435/325, 435/366, 435/375
• US Class Current: 435/6.12
• 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 35/04 specific for metastasis
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Compositions and methods are provided for modulating the expression of tumor necrosis factor receptor-associated factor (TRAF). Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TRAF are preferred. Methods of using these compounds for modulation of TRAF expression and for treatment of diseases associated with expression of TRAF are provided.

Claims

1. An antisense compound 8 to 30 nucleotides in length comprising at least an 8 nucleobase portion of SEQ ID NO:

151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 276, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189 or 190.

2. The antisense compound of claim 1 which is an antisense oligonucleotide.

3. The antisense oligonucleotide of claim 2 which comprises at least one modified internucleoside linkage.

4. The antisense oligonucleotide of claim 3 wherein the modified internucleoside linkage is a phosphorothioate linkage.

5. The antisense oligonucleotide of claim 2 which comprises at least one modified sugar moiety.

6. The antisense oligonucleotide of claim 5 wherein the modified sugar moiety is a 2′

-o-methoxyethyl sugar.

7. The antisense oligonucleotide of claim 2 which comprises at least one modified nucleobase.

8. The antisense oligonucleotide of claim 7 wherein the modified nucleobase is a 5-methylcytosine.

9. The antisense compound of claim 1 which is a chimeric oligonucleotide.

10. A composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

11. The composition of claim 10 comprising a colloidal dispersion system.

12. The composition of claim 10 wherein the antisense compound is an antisense oligonucleotide.

13. A method for inhibiting the expression of tumor necrosis factor receptor-associated factor 5 in human cell or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 1 so that expression of tumor necrosis factor receptor-associated factor 5 is inhibited.