Antisense inhibition of TNFR1 expression

• US 6,007,995 A
• Filed: 06/26/1998
• Issued: 12/28/1999
• Est. Priority Date: 06/26/1998
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Baker, Brenda F., Cowsert, Lex M.
• Primary Examiner(s): Degen, Nancy
• Assistant Examiner(s): WANG, ANDREW J
• Application Number:
  US09/106,038
• Time in Patent Office: 550 Days
• Field of Search: 435/6, 435/91.1, 435/325, 435/366, 435/377, 536/23.1, 536/24.31, 536/24.5, 514/44
• US Class Current: 435/6.14
• 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: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/335 Modified T or U
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• 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 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of TNFR1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TNFR1. Methods of using these compounds for modulation of TNFR1 expression and for treatment of diseases associated with expression of TNFR1 are provided.

Claims

1. An antisense compound up to 30 nucleobases in length comprising SEQ ID NO:

11, 15, 16, 17, 21, 22, 23, 25, 28, 29, 30, 31, 33, 35, 36, 37, 38, 39, 41, 42, 43, 45, 46, 47, 48, 50, 59, 62, 67, 70, 71, 74, 76, 77, 78, 81, 82, 84, 90 or 91.

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

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

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

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

6. The antisense compound of claim 5 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

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

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

9. The antisense compound of claim of claim 2 which is a chimeric oligonucleotide.

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

11. A method of inhibiting the expression of the TNFR1 in human cells or tissues comprising contacting said human cells or tissues with the antisense compound of claim 1 in vitro so that expression of human TNFR1 is inhibited.