Modulation of huntingtin expression

Patent metadata

Field	Value
Publication number	US-10837016-B2
Application number	US-202016801431-A
Country	US
Kind code	B2
Filing date	Feb 26, 2020
Priority date	Sep 11, 2009
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof.

First claim

The invention claimed is:

1. A single-stranded modified oligonucleotide consisting of 18 linked nucleosides and having:
a gap segment consisting of eight linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides; and
a 3′ wing segment consisting of five linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment;
wherein each nucleoside of each wing segment comprises a 2′O-methoxyethyl sugar; and
wherein the nucleobase sequence of the oligonucleotide consists of the sequence recited in SEQ ID NO: 35,
or a pharmaceutically acceptable salt thereof.

2. The single-stranded modified oligonucleotide of claim 1 , wherein at least one nucleoside comprises a modified nucleobase.

3. The single-stranded modified oligonucleotide of claim 2 , wherein the modified nucleobase is a 5-methylcytosine.

4. The single-stranded modified oligonucleotide of claim 1 , wherein each cytosine is a 5-methylcytosine.

5. The single-stranded modified oligonucleotide of claim 1 , wherein at least one internucleoside linkage is a modified internucleoside linkage.

6. The single-stranded modified oligonucleotide of claim 1 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

7. The single-stranded modified oligonucleotide of claim 4 , wherein at least one internucleoside linkage is a modified internucleoside linkage.

8. The single-stranded modified oligonucleotide of claim 4 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

9. A composition comprising the single-stranded modified oligonucleotide or pharmaceutically acceptable salt thereof of claim 1 and at least one pharmaceutically acceptable carrier or diluent.

10. A composition comprising the single-stranded modified oligonucleotide or pharmaceutically acceptable salt thereof of claim 4 and at least one pharmaceutically acceptable carrier or diluent.

11. A composition comprising the single-stranded modified oligonucleotide or pharmaceutically acceptable salt thereof of claim 6 and at least one pharmaceutically acceptable carrier or diluent.

12. A composition comprising the single-stranded modified oligonucleotide or pharmaceutically acceptable salt thereof of claim 8 and at least one pharmaceutically acceptable carrier or diluent.

13. The single-stranded modified oligonucleotide of claim 1 , which is capable of inhibiting huntingtin expression.

14. The single-stranded modified oligonucleotide of claim 4 , which is capable of inhibiting huntingtin expression.

15. The single-stranded modified oligonucleotide of claim 6 , which is capable of inhibiting huntingtin expression.

16. The single-stranded modified oligonucleotide of claim 8 , which is capable of inhibiting huntingtin expression.

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Hung Gene
• Bennett C Frank
• Freier Susan M
• Kordasiewicz Holly
• Stanek Lisa
• Cleveland Don W
• Cheng Seng H
• Shihabuddin Lamya

Classifications

• C07H21/04

  with deoxyribosyl as saccharide radical · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/22

  Anxiolytics · CPC title