Antisense modulation of CoREST expression

• US 6,900,306 B2
• Filed: 08/01/2001
• Issued: 05/31/2005
• Est. Priority Date: 08/01/2001
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Freier, Susan M., Bennett, C. Frank
• Primary Examiner(s): McGarry, Sean
• Application Number:
  US09/920,671
• Publication Number:
  US 20030083283A1
• Time in Patent Office: 1,399 Days
• Field of Search: 435/375, 435/377, 536/24.1, 536/24.5, 514/44
• US Class Current: 536/24.5
• 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 2310/3341 5-Methylcytosine
• 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 CoREST. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CoREST. Methods of using these compounds for modulation of CoREST expression and for treatment of diseases associated with expression of CoREST are provided.

Claims

1. A compound 20 to 50 nucleobases in length targeted to a nucleic acid molecule encoding CoREST (SEQ ID NO:

11), wherein said compound specifically hybridizes with said nucleic acid molecule encoding CoREST (SEO ID NO;

11) and inhibits the expression of CoREST, wherein said compound is an antisense oligonucleotide and has a sequence comprising SEQ ID NO;

80.

2. The compound of claim 1 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

3. The compound of claim 2 wherein the modified internucleoside linkage is a phosphorothioate linkage.

4. The compound of claim 1 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

5. The compound of claim 4 wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

6. The compound of claim 1 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

7. The compound of claim 6 wherein the modified nucleobase is a 5 -methylcytosine.

8. The compound of claim 1 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

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

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

9. An antisense compound 20 to 50 nucleobase in length which specifically hybridizes with nucleobases 48225 to 48244 of a nucleic acid molecule encoding CoREST (SEQ ID NO:

11) and which inhibits expression of CoREST.