Antisense modulation of NF-kappa-B p65 subunit expression

• US 6,069,008 A
• Filed: 11/25/1998
• Issued: 05/30/2000
• Est. Priority Date: 11/25/1998
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Monia, Brett P., Bennett, C. Frank, Cowsert, Lex M.
• Primary Examiner(s): Elliott, George C.
• Assistant Examiner(s): SCHMIDT, MARY M
• Application Number:
  US09/199,859
• Time in Patent Office: 552 Days
• Field of Search: 435/6, 435/91.1, 435/375, 435/325, 435/366, 536/23.1, 536/24.3, 536/24.5, 514/44
• US Class Current: 435/375
• 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 15/113 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 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/334 Modified C
• 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 2310/3525 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 NF-kappa-B p65 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding NF-kappa-B p65 subunit. Methods of using these compounds for modulation of NF-kappa-B p65 subunit expression and for treatment of diseases associated with expression of NF-kappa-B p65 subunit are provided.

Claims

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

20, 23, 24, 26, 31, 32, or 42 wherein said antisense compound inhibits the expression of human NF-kappa-B p65 subunit.

2. A method of inhibiting expression of human NF-kappa-B p65 subunit in human cells or tissues comprising contacting said human cells or tissues in vitro with the antisense compound of claim 1 so that expression of human NF-kappa-B p65 subunit is inhibited.

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

4. The antisense compound of claim 3 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

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

6. The antisense compound of claim 3 wherein the antisense oligonucleotide comprises at least one modified sugar moiety. nucleobase.

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

8. The antisense compound of claim 3 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

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

10. The antisense compound of claim 3 wherein the antisense oligonucleotide is a chimeric oligonucleotide.