# US 10,864,283 B2 · Composition for preventing or treating keloid or hypertrophic scars

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- Number: US 10,864,283 B2
- Document ID: US10864283B2
- Status: Granted
- Kind: B2
- Application number: 16/028,283
- Filed: 2018-07-05
- Published: 2018-11-15
- Granted: 2020-12-15
- Earliest claimed: 2016-01-05
- Assignees: Industry-University Cooperation Foundation Hanyang University
- Applicants: Industry-University Cooperation Foundation Hanyang University
- Inventors: Chae Ok Yun; Won Jai Lee
- Web page: https://patentgrep.com/patent/US10864283B2

## CPC

- A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/235: Adenoviridae
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- 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)}
- C12N 15/861: Adenoviral vectors
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2310/531: Stem-loop; Hairpin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to a pharmaceutical composition for preventing or treating a keloid disease or scars. The inventors of the present invention discovered that mortalin expression inhibition and the interaction between mortalin and p53 may be new targets for keloid treatment. In the present invention, apoptosis and an anti-fibrotic effect were verified by preparing a mortalin-specific shRNA (dE1-RGD/GFP/shMOT) and injecting same in a keloid spheroid. Thus, by reducing ECM expression and inducing apoptosis in a keloid spheroid, mortalin knockdown may be very usefully employed for keloid treatment.

## Claims

### Claim 1

A method of treating keloid diseases or scars, comprising:
administering a therapeutically effective amount of an inhibitor, which suppresses an expression of a mortalin gene or an activity of a mortalin protein, to a subject in need thereof,
wherein the inhibitor is shRNA, siRNA, miRNA, an antisense oligonucleotide, a ribozyme, a DNAzyme, a peptide nucleic acid, an antibody or an aptamer, and
wherein shRNA, siRNA, miRNA, the antisense oligonucleotide, the ribozyme, the DNAzyme or the peptide nucleic acid comprises a sequence complementary to mRNA or DNA of the mortalin gene and suppresses an expression of the mortalin gene, and the antibody or the aptamer specifically binds to the mortalin protein and suppresses the activity of the mortalin protein.

### Claim 2 (depends on 1)

The method of claim 1, wherein the inhibitor is shRNA, siRNA, miRNA, or an antisense oligonucleotide, which suppresses the expression of the mortalin gene.

### Claim 3 (depends on 1)

The method of claim 1, wherein the shRNA, siRNA, miRNA or antisense oligonucleotide comprises a sequence complementary to a sequence from 2,102th nucleotide to 2,120th nucleotide of SEQ ID NO: 2.

### Claim 4 (depends on 3)

The method of claim 3, wherein the shRNA has a sequence complementary to a nucleotide sequence of SEQ ID NO: 1.

### Claim 5 (depends on 4)

The method of claim 4, wherein the shRNA comprises a sequence of SEQ ID NO: 3 or SEQ ID NO: 4.

### Claim 6 (depends on 1)

The method of claim 1, wherein the keloid diseases or scars is postoperative scars, burn keloids, keloids, posttraumatic keloids, restenosis after percutaneous coronary angioplasty, or hypertrophic scar pannus.

### Claim 7

A method of treating keloid diseases or scars, comprising:
administering, to a subject in need thereof, a pharmaceutical composition, which comprises:
(a) a therapeutically effective amount of an adenovirus expressing an oligonucleotide for inhibiting an expression of a mortalin gene as an active ingredient; and
(b) a pharmaceutically acceptable carrier.

### Claim 8 (depends on 7)

The method of claim 7, wherein the adenovirus is a recombinant adenovirus comprising the following sequences:
(a) an inverted terminal repeat (ITR) sequence of the adenovirus;
(b) an oligonucleotide sequence for inhibiting the expression of a mortalin gene, which comprises a sequence complementary to a sequence from 2,102th nucleotide to 2,120th nucleotide of SEQ ID NO:2; and
(c) a promoter sequence located downstream of the oligonucleotide sequence.
