# US 12,006,498 B2 · Composition for regulating expression of PROX1 or expression of telomerase reverse transcriptase comprising activity regulator or method for screening telomerase reverse transcriptase regulator

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- Number: US 12,006,498 B2
- Document ID: US12006498B2
- Status: Granted
- Kind: B2
- Application number: 16/761,151
- Filed: 2018-10-19
- Published: 2023-08-10
- Granted: 2024-06-11
- Earliest claimed: 2017-11-03
- Assignees: Korea Institute of Science and Technology; Industry-Academic Cooperation Foundation, Yonsei University
- Applicants: Korea Institute of Science and Technology; Industry-Academic Cooperation Foundation, Yonsei University
- Inventors: Sang Hoon Jung; Young-Joo Kim; Dae-geun Song; Young Nyun Park; Jeong Eun Yoo; Hyung Jin Rhee; Youngsic Jeon
- Web page: https://patentgrep.com/patent/US12006498B2

## 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 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 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 35/00: Antineoplastic agents
- C12Q 1/68: involving nucleic acids
- 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)
- G01N 33/575: for cancer
- C12N 2310/11: Antisense
- C12N 2310/12: catalytic nucleic acids, e.g. ribozymes
- C12N 2310/127: DNAzymes
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2310/3181: Peptide nucleic acid, PNA
- C12N 2310/531: Stem-loop; Hairpin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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

In the present specification, on the basis of the correlation between prospero homeobox protein 1 (PROX1) and telomerase reverse transcriptase (TERT), a composition for regulating expression of TERT, a method for screening a TERT expression regulator, a composition for diagnosing a TERT expression status, a diagnostic kit, a method for providing information for diagnosis, or a method for providing information for cancer diagnosis are disclosed. Specifically, in one aspect, the PROX1 of the present disclosure may bind to a TERT promoter, in particular a mutant TERT promoter in which base substitution occurs at the −124 or −146 bp position to regulate the expression of TERT, and the expression of TERT in non-hepatitis B virus-associated liver cancer can be inhibited specifically among liver cancers.

## Claims

### Claim 1

A method for regulating expression of telomerase reverse transcriptase (TERT), comprising administering a composition comprising a prospero homeobox protein 1 (PROX1) expression or activity regulator to a subject in need thereof;
wherein the PROX1 expression or activity regulator is a siRNA represented by SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, a sequence having 70% or higher homology to SEQ. ID. NO.: 1, or a sequence having 70% or higher homology to SEQ. ID. NO.: 2.

### Claim 2 (depends on 1)

The method for regulating expression of TERT according to claim 1, wherein the PROX1 expression or activity regulator is a PROX1 expression or activity inhibitor.

### Claim 3 (depends on 1)

The method for regulating expression of TERT according to claim 1, wherein the PROX1 expression or activity regulator is the siRNA represented by SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, a sequence having 80% or higher homology to SEQ. ID. NO.: 1, or a sequence having 80% or higher homology to SEQ. ID. NO.: 2.

### Claim 4 (depends on 1)

The method for regulating expression of TERT according to claim 1, wherein the siRNA is represented by SEQ. ID. NO.: 1 or SEQ. ID. NO.: 2.

### Claim 5 (depends on 1)

The method for regulating expression of TERT according to claim 1, wherein the composition is a pharmaceutical composition,
wherein the composition is for preventing or treating non-hepatitis B virus-associated liver cancer.

### Claim 6 (depends on 5)

The method for regulating expression of TERT according to claim 5, wherein the non-hepatitis B virus-associated liver cancer is one or more selected from a group consisting of hepatitis A virus-associated liver cancer, hepatitis C virus-associated liver cancer and alcoholic liver cancer.

### Claim 7 (depends on 1)

The method for regulating expression of TERT according to claim 1, wherein the PROX1 expression or activity regulator is the siRNA represented by SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, a sequence having 90% or higher homology to SEQ. ID. NO.: 1, or a sequence having 90% or higher homology to SEQ. ID. NO.: 2.