Selective antisense compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11236335-B2
Application number	US-202016793119-A
Country	US
Kind code	B2
Filing date	Feb 18, 2020
Priority date	Oct 12, 2012
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount, activity, or expression of the target nucleic acid in a cell. In certain embodiments, hybridization results in selective modulation of the amount, activity, or expression of a target Huntingtin gene or Huntingtin transcript in a cell.

First claim

What is claimed is:

1. A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide comprises at least 8 contiguous nucleobases of the nucleobase sequence recited in SEQ ID NO: 2, wherein the modified oligonucleotide has a sugar motif selected from ekek-d9-keke, kekk-d8-keke, ekkk-d8-kke, ekk-d8-kkke, ekekk-d8-keke, ekek-d8-kkeke, eekk-d8-kkeee, and eeekk-d8-kkee, wherein k is a cEt sugar moiety, e is a 2′-OCH 2 CH 2 OCH 3 ribosyl sugar moiety, and d is a 2′-deoxyribosyl sugar moiety.

2. The compound of claim 1 , wherein the nucleobase sequence of the modified oligonucleotide is 100% complementary to SEQ ID NO. 1.

3. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 5.

4. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 6.

5. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 27.

6. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 28.

7. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 29.

8. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 30.

9. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 38.

10. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 39.

11. The compound of claim 1 , wherein the modified oligonucleotide has the nucleobase sequence recited in SEQ ID NO: 46.

12. The compound of claim 3 , wherein the modified oligonucleotide has a ekek-d9-keke sugar motif.

13. The compound of claim 4 , wherein the modified oligonucleotide has a kekk-d8-keke sugar motif.

14. The compound of claim 5 , wherein the modified oligonucleotide has a ekkk-d8-kke sugar motif.

15. The compound of claim 6 , wherein the modified oligonucleotide has a ekk-d8-kkke sugar motif.

16. The compound of claim 7 , wherein the modified oligonucleotide has a ekekk-d8-keke sugar motif.

17. The compound of claim 8 , wherein the modified oligonucleotide has a ekek-d8-kkeke sugar motif.

18. The compound of claim 9 , wherein the modified oligonucleotide has a eekk-d8-kkeee sugar motif.

19. The compound of claim 10 , wherein the modified oligonucleotide has a eekk-d8-kkeee sugar motif.

20. The compound of claim 11 , wherein the modified oligonucleotide has a eeekk-d8-kkee sugar motif.

21. The compound of claim 1 , comprising at least one phosphorothioate internucleoside linkage.

22. A method of ameliorating a symptom of Huntington's disease, comprising administering the compound of claim 1 to a subject in need thereof.

23. The compound of claim 1 , wherein the compound is conjugated.

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

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Oestergaard Michael
• Seth Punit P
• Swayze Eric E

Classifications

• C07H21/02

  with ribosyl as saccharide radical · CPC title

• C12N2310/346

  having a combination of backbone and sugar modifications · CPC title

• C12N2310/335

  Modified T or U · CPC title

• C12N15/113 Primary

  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 title

• C12N2310/3231

  having an additional ring, e.g. LNA, ENA · CPC title