Methods and compositions for inhibiting PMP22 expression

Patent metadata

Field	Value
Publication number	US-12529055-B2
Application number	US-202418599942-A
Country	US
Kind code	B2
Filing date	Mar 8, 2024
Priority date	Mar 9, 2016
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

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 treating an individual exhibiting a symptom of Charcot-Marie-Tooth Disease and having a duplication of the peripheral myelin protein 22 (PMP22) gene, comprising:
determining whether the individual has a slowed motor nerve conduction velocity (MNCV), a reduced compound muscle action potential (CMAP), or a combination thereof; and administering to the individual a pharmaceutical composition comprising an antisense compound and a pharmaceutically acceptable diluent if the individual has a slowed MNCV, a reduced CMAP, or a combination thereof, wherein the antisense compound comprises an antisense oligonucleotide, and wherein the antisense oligonucleotide comprises at least 12 contiguous nucleobases complementary to a target region of the PMP22 transcript.

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

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

4 . The method of claim 3 , wherein the at least one modified nucleoside comprises a modified sugar moiety.

5 . The method of claim 4 , wherein the modified sugar moiety is a non-bicyclic, 2′-substituted sugar moiety.

6 . The method of claim 5 , wherein the non-bicyclic, 2′-substituted sugar moiety is selected from among 2′-OMe, 2′-F, and 2′-MOE.

7 . The method of claim 4 , wherein the modified sugar moiety is a bicyclic sugar moiety.

8 . The method of claim 7 , wherein the bicyclic sugar moiety is selected from LNA and cEt.

9 . The method of claim 4 , wherein the modified sugar moiety is a sugar surrogate.

10 . The method of claim 1 , wherein the antisense oligonucleotide consists of 16 linked nucleosides.

11 . The method of claim 1 , wherein the antisense compound comprises a conjugate group.

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

13 . The method of claim 12 , wherein the at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.

14 . The method of claim 12 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

15 . The method of claim 1 , wherein the antisense compound is a single-stranded antisense compound.

16 . The method of claim 1 , wherein the antisense compound is a double-stranded antisense compound.

17 . The method of claim 1 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS).

18 . The method of claim 1 , wherein the pharmaceutical composition is prepared for subcutaneous administration.

19 . The method of claim 1 , wherein the pharmaceutical composition is prepared for systemic administration.

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

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

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

Assignees

• Ionis Pharmaceuticals Inc

Inventors

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

Classifications

• C12N2310/322

  2'-R Modification · CPC title

• C12N2310/321

  2'-O-R Modification · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · 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

• A61P25/02

  for peripheral neuropathies · CPC title