Antisense modulation of estrogen receptor alpha expression

• US 6,617,162 B2
• Filed: 12/18/2001
• Issued: 09/09/2003
• Est. Priority Date: 12/18/2001
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Roach, Mark P., Dobie, Kenneth W.
• Primary Examiner(s): McGarry, Sean
• Assistant Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US10/027,983
• Publication Number:
  US 20030139360A1
• Time in Patent Office: 630 Days
• Field of Search: 536/24.5, 536/24.33, 536/23.1, 536/24.3, 435/325, 435/375, 435/455, 435/6, 514/44, 424/450
• 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 15/1138 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 2310/3341 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 estrogen receptor alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding estrogen receptor alpha. Methods of using these compounds for modulation of estrogen receptor alpha expression and for treatment of diseases associated with expression of estrogen receptor alpha are provided.

Claims

1. A compound 8 to 30 nucleobases in length targted to nucleobases 802 throuqh 821 or nucleobases 993 through 1012 of a coding region of a nucleic acid molecule of SEQ ID NO:

3 encoding estrogen receptor alpha, wherein said compound specifically hybridizes with one of said regions and inhibits the expression of estroqen receptor alpha.

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

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

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

5. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

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

-O—

methoxyethyl sugar moiety.

7. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

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

9. The compound of claim 2 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 further comprising a colloidal dispersion system.

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

13. A method of inhibiting the expression of estrogen receptor alpha in cells or tissues in vitro comprising contacting said cells or tissues with the compound of claim 1 so that expression of estrogen receptor alpha is inhibited.