Selective antisense compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-12152244-B2
Application number	US-202217586175-A
Country	US
Kind code	B2
Filing date	Jan 27, 2022
Priority date	Oct 12, 2012
Publication date	Nov 26, 2024
Grant date	Nov 26, 2024

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 NOs: 251, 268, or 490-500, and wherein the modified oligonucleotide has a sugar motif selected from eeeee-d9-eeeee, ekk-d9-kke, eekk-d8-kkeee, ekek-d8-kekee, ekk-d8-kkeee, eeekk-d7-kkeee, or eekek-d7-kekee; 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 a eeeee-d9-eeeee sugar motif.

4. The compound of claim 1 , wherein the modified oligonucleotide has a ekk-d9-kke sugar motif.

5. The compound of claim 1 , wherein the modified oligonucleotide has a eekk-d8-kkeee sugar motif.

6. The compound of claim 1 , wherein the modified oligonucleotide has a ekek-d8-kekee sugar motif.

7. The compound of claim 1 , wherein the modified oligonucleotide has a ekk-d8-kkeee sugar motif.

8. The compound of claim 1 , wherein the modified oligonucleotide has a eeekk-d7-kkeee sugar motif.

9. The compound of claim 1 , wherein the modified oligonucleotide has a eekek-d7-kekee sugar motif.

10. The compound of claim 1 , wherein the modified oligonucleotide comprises at least one phosphorothioate internucleoside linkage.

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

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

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS).

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

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Oestergaard Michael
• Seth Punit P
• Swayze Eric E

Classifications

• C12N2310/313

  Phosphorodithioates · CPC title

• C12N2310/346

  having a combination of backbone and sugar modifications · CPC title

• C12N2310/3125

  Methylphosphonates · CPC title

• C12N2310/335

  Modified T or U · CPC title

• C07H21/02

  with ribosyl as saccharide radical · CPC title