# US 11,439,657 B2 · Cancer stem cell growth inhibitor using miRNA

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- Number: US 11,439,657 B2
- Document ID: US11439657B2
- Status: Granted
- Kind: B2
- Application number: 16/498,986
- Filed: 2018-03-30
- Published: 2021-02-25
- Granted: 2022-09-13
- Earliest claimed: 2017-03-30
- Assignees: CancerStem Tech Inc.
- Applicants: CancerStem Tech Inc.
- Inventors: Xin Wu; Masaki Mori; Hirofumi Yamamoto
- Web page: https://patentgrep.com/patent/US11439657B2

## CPC

- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 9/0019: {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)}
- A61K 9/5115: {Inorganic compounds}
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12Y 207/11001: Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12N 2310/141: MicroRNAs, miRNAs
- 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)
- C12Y: ENZYMES

## Abstract

The purpose of the present invention is to provide a nucleic acid medication for cancer treatment, the medication being capable of suppressing the growth of cancer stem cells and thus effectively treating cancer. hsa-miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g, hsa-miR-181a-5p, hsa-miR-362-5p, and hsa-miR-608 have remarkably excellent growth inhibitory action on cancer stem cells and are thus useful as a nucleic acid medication for the treatment of various cancers.

## Claims

### Claim 1

A method of inhibiting proliferation of a cancer stem cell, the method comprising administering to the cancer stem cell:
(a) at least one miRNA as an active ingredient, wherein the at least one miRNA is:
(1) hsa miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g and/or hsa-miR-181a-5p delivered to pancreatic tumor cells;
(2) hsa-miR-136-5p, hsa-miR-3065-3p, and/or hsa-miR-181a-5p delivered to gastric tumor cells;
(3) hsa-miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g, hsa-miR-181a-5p, hsa-miR-362-5p, and/or hsa-miR-608 delivered to human large bowel cancer cells; or
(4) hsa-miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g, and/or hsa-miR-181a-5p delivered to esophageal cancer cells; and
(b) an miRNA transfer agent;
wherein the at least one miRNA and the miRNA transfer agent are administered simultaneously with an anticancer drug, or before and/or after administration of an anticancer drug.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the miRNA is a mature miRNA, pri-miRNA or pre-miRNA.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the miRNA transfer agent comprises carbonate apatite particles and the at least one miRNA is complexed to the carbonate apatite particles.

### Claim 4

A method for treating cancer, comprising a step of administering to a cancer patient a therapeutically effective amount of:
(a) at least one miRNA, wherein the at least one miRNA is:
(1) hsa miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g and/or hsa-miR-18 la-5p delivered to pancreatic tumor cells;
(2) hsa-miR-136-5p, hsa-miR-3065-3p, and/or hsa-miR-181a-5p delivered to gastric tumor cells;
(3) hsa-miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g, hsa-miR-181a-5p, hsa-miR-362-5p, and/or hsa-miR-608 delivered to human large bowel cancer cells; or
(4) hsa-miR-136-5p, hsa-miR-3065-3p, hsa-miR-4727-5p, hsa-miR-378g, and/or hsa-miR-181a-5p delivered to esophageal cancer cells; and
(b) an miRNA transfer agent.

### Claim 5 (depends on 4)

The method for treating cancer according to claim 4, wherein the miRNA is administered simultaneously with an anticancer drug, or before and/or after administration of an anticancer drug.