Methods and compositions for inhibiting PMP22 expression

Patent metadata

Field	Value
Publication number	US-11959080-B2
Application number	US-202117493112-A
Country	US
Kind code	B2
Filing date	Oct 4, 2021
Priority date	Mar 9, 2016
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present embodiments provide methods, compounds, and compositions useful for inhibiting PMP22 expression and for treating, preventing, or ameliorating a disease associated with PMP22.

First claim

The invention claimed is:

1. A method of reducing the amount or activity of a PMP22 transcript in a cell of an individual having, or at risk of having, a disease associated with PMP22 comprising contacting the cell with an oligomeric compound comprising a modified oligonucleotide, wherein the modified oligonucleotide comprises a complementary region of at least 12 contiguous nucleobases, wherein the nucleobase sequence of the complementary region is complementary to a target region of the PMP22 transcript, and wherein the disease associated with PMP22 is Charcot-Marie-Tooth Disease.

2. The method of claim 1 , wherein the cell is a nerve cell.

3. The method of claim 1 , wherein the cell is a Schwann cell.

4. The method of claim 1 , wherein the nucleobase sequence of the modified oligonucleotide is at least 80% complementary to the target region of the PMP22 transcript.

5. The method of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside.

6. The method of claim 5 , wherein at least one modified nucleoside comprises a modified sugar moiety.

7. The method of claim 6 , wherein at least one modified sugar moiety is a non-bicyclic, 2′-substituted sugar moiety.

8. The method of claim 7 , wherein the non-bicyclic, 2′-substituted sugar moiety is selected from among 2′-OMe, 2′-F, and 2′-MOE.

9. The method of claim 6 , wherein at least one modified sugar moiety is a bicyclic sugar moiety.

10. The method of claim 9 , wherein the bicyclic sugar moiety is selected from LNA and cEt.

11. The method of claim 6 , wherein at least one modified sugar moiety is a sugar surrogate.

12. The method of claim 1 , wherein the modified oligonucleotide comprises 16 linked nucleosides.

13. The method of claim 1 , wherein the modified oligonucleotide consists of 16 linked nucleosides.

14. The method of claim 1 , wherein the oligomeric compound comprises a conjugate group.

15. The method of claim 1 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.

16. The method of claim 15 , wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.

17. The method of claim 15 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

18. The method of claim 1 , wherein the oligomeric compound is single-stranded.

19. The method of claim 1 , wherein the oligomeric compound is paired with a second oligomeric compound to form a duplex.

20. The method of claim 1 , wherein the oligomeric compound is a pharmaceutically acceptable salt.

21. The method of claim 1 , wherein the oligomeric compound is administered in a pharmaceutically acceptable carrier or diluent.

22. The method of claim 1 , wherein the oligomeric compound is administered systemically.

23. The method of claim 1 , wherein the oligomeric compound is administered subcutaneously.

24. The method of claim 1 , wherein the Charcot-Marie-Tooth Disease is Type 1.

25. The method of claim 1 , wherein the d Charcot-Marie Tooth Disease is Type 1A.

26. The method of claim 1 , wherein the individual is a human.

27. An oligomeric compound comprising a modified oligonucleotide, wherein the modified oligonucleotide comprises a sequence selected from SEQ ID NOs: 9-16.

28. The oligomeric compound of claim 27 , wherein the nucleobase sequence of the modified oligonucleotide consists of a sequence selected from SEQ ID NOs: 9-16.

29. The oligomeric compound of claim 27 , wherein the modified oligonucleotide is a salt.

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Hung Gene
• Kordasiewicz Holly
• Zhao Hien Thuy
• Swayze Eric E

Classifications

• 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

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61P25/02

  for peripheral neuropathies · 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