Antisense modulation of damage-specific DNA binding protein 1, p127 expression

• US 6,855,700 B2
• Filed: 12/06/2000
• Issued: 02/15/2005
• Est. Priority Date: 12/06/2000
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Wyatt, Jacqueline, Popoff, Ian
• Primary Examiner(s): McGarry, Sean
• Assistant Examiner(s): SCHULTZ, JAMES
• Application Number:
  US09/731,457
• Publication Number:
  US 20020103146A1
• Time in Patent Office: 1,532 Days
• Field of Search: 514/44, 536/24.5, 536/23.1, 435/6, 435/325, 435/375
• US Class Current: 514/44.00A
• 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 Damage-specific DNA binding protein 1, p127. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Damage-specific DNA binding protein 1, p127. Methods of using these compounds for modulation of Damage-specific DNA binding protein 1, p127 expression and for treatment of diseases associated with expression of Damage-specific DNA binding protein 1, p127 are provided.

Claims

1. An oligomeric compound up to 50 nucleobases in length comprising SEQ ID NO:

73, or a pharmaceutically acceptable salt thereof.

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

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

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

-O—

CH₂CH₂OCH₃, 2′

-O—

CH₃, or 2′

-F moiety.

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

-O—

CH₂CH₂OCH₃ moiety.

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

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

10. The compound of claim 2 wherein the oligonucleotide is a chimeric oligonucleotide.

11. The compound of claim 10 wherein the chimeric oligonucleotide comprises 2′

-O—

CH₂CH₂OCH₃ wings and a deoxy gap.

12. The compound of claim 1 wherein the pharmaceutically acceptable salt is a sodium salt or a potassium salt.

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

14. The composition of claim 13 wherein the oligomeric is an oligonucleotide.

15. The composition of claim 13 further comprising a colloidal dispersion system.

16. The composition of claim 14 further comprising another oligonucleotide.

17. A method of inhibiting the expression of damage-specific DNA binding protein 1, p127 in a cell or a tissue comprising contacting the cell or tissue in vitro with the compound of claim 1, wherein the expression of damage-specific DNA binding protein 1, p127 is inhibited.

18. A method of detecting the presence of damage-specific DNA binding protein 1, p127 in a cell or a tissue comprising contacting the cell or tissue in vitro with the compound of claim 1 and detecting the presence of the compound.

19. A kit comprising the compound of claim 1.