# US 10,119,142 B2 · Pharmaceutical composition for treating Charcot Marie Tooth disease

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- Number: US 10,119,142 B2
- Document ID: US10119142B2
- Status: Granted
- Kind: B2
- Application number: 15/690,478
- Filed: 2017-08-30
- Published: 2018-03-08
- Granted: 2018-11-06
- Earliest claimed: 2016-09-05
- Assignees: Samsung Life Public Welfare Foundation
- Applicants: Samsung Life Public Welfare Foundation
- Inventors: Byung-Ok Choi; Young Bin Hong
- Web page: https://patentgrep.com/patent/US10119142B2

## CPC

- C12N 15/113: 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)}
- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/34: Allele or polymorphism specific uses
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

An siRNA for specifically targeting a PMP22 mutant gene and a pharmaceutical composition for preventing or treating Charcot Marie Tooth disease, which includes the same, are provided. According to the present invention, it is confirmed that selective suppression of a PMP22 mutant allele by a non-viral delivery system of siRNA may improve demyelinating neuropathic symptoms of CMT in vivo, enhance a motor ability and increase a volume of muscle. Therefore, the siRNA may be used in a useful method for treating various dominantly inherited peripheral neuropathies including CMT.

## Claims

### Claim 1

A method of treating Charcot Marie Tooth disease in a subject in need thereof, comprising:
administering to the subject an effective amount of a pharmaceutical composition comprising an expression inhibitor of a peripheral myelin protein 22 (PMP22) mutant gene as an active ingredient,
wherein the expression inhibitor is a small interfering RNA (siRNA) haying a sense strand selected from the group consisting of SEQ ID NOs: 2, 3, and 4, and an antisense strand consisting of a sequence complementary to the sense strand.

### Claim 2 (depends on 1)

The method of claim 1, wherein the PMP22 mutant gene is characterized by thymine, which is a base at position 47 of a wild-type PMP22 gene, being replaced with cytosine.

### Claim 3 (depends on 2)

The method of claim 2, wherein the PMP22 mutant gene consists of a base sequence set forth in SEQ ID NO: 1.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition further comprises a lipid polymer as an siRNA delivery system.

### Claim 5

An siRNA having a sense strand selected from the group consisting of SEQ ID NOs: 2, 3, and 4 and an antisense strand consisting of a sequence complementary to the sense strand and binding to a PMP22 mutant gene to suppress expression of the PMP22 mutant gene.

### Claim 6 (depends on 5)

The siRNA of claim 5, wherein the PMP22 mutant gene is characterized by thymine, which is a base at position 47 of a wild-type PMP22 gene, being replaced with cytosine.

### Claim 7 (depends on 6)

The siRNA of claim 6, wherein the PMP22 mutant gene consists of a base sequence set forth in SEQ ID NO: 1.

### Claim 8 (depends on 5)

A recombinant vector comprising the siRNA defined in claim 5.

### Claim 9 (depends on 5)

A method of treating Charcot Marie Tooth disease in a subject in need thereof, comprising administering the siRNA of claim 5 to the subject.

### Claim 10 (depends on 5)

A method of suppressing expression of a target gene in cells, comprising: introducing the siRNA of claim 5 into the cells in vitro.

### Claim 11 (depends on 10)

The method of claim 10, wherein the target gene is a PMP22 mutant gene.

### Claim 12 (depends on 11)

The method of claim 11, wherein the PMP22 mutant gene consists of a base sequence set forth in SEQ ID NO: 1.