Search

EP-4737570-A1 - PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING SIRNA AS ACTIVE INGREDIENT

EP4737570A1EP 4737570 A1EP4737570 A1EP 4737570A1EP-4737570-A1

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating cancer, the composition comprising siRNA as an active ingredient. The pharmaceutical composition was found to significantly inhibit the cell proliferation effect of colorectal cancer or pancreatic cancer, thus having an excellent anticancer effect, and reduce the expression level of KRAS mRNA. In addition, the composition maintains the body weight of an individual even while reducing the size and weight of a tumor, and thus can be effectively used as an excellent anticancer therapeutic agent.

Inventors

  • CHUNG, JIHWA
  • KIM, HYO KYEONG
  • CHOI, YUJEONG

Assignees

  • Exollence Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240628

Claims (12)

  1. A pharmaceutical composition for preventing or treating cancer, comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29.
  2. The pharmaceutical composition of claim 1, wherein the group consisting of siRNAs below have a sense strand that is 19 to 25 nt long and an anti-sense strand that is 21 to 27 nt long: 1) siRNA having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 5; 2) siRNA having a nucleotide sequence represented by SEQ ID NO: 7; 3) siRNA having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 14, 15, and 17; and 4) siRNA having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 20, 23, and 26 to 28.
  3. The pharmaceutical composition of claim 1, wherein the group consisting of siRNA having a nucleotide sequence represented by SEQ ID NO: 12, siRNA having a nucleotide sequence represented by SEQ ID NO: 13, siRNA having a nucleotide sequence represented by SEQ ID NO: 18, siRNA having a nucleotide sequence represented by SEQ ID NO: 21, siRNA having a nucleotide sequence represented by SEQ ID NO: 24, and siRNA having a nucleotide sequence represented by SEQ ID NO: 29 has the following characteristics: a) having a sense strand that is 19 to 25 nt long and an anti-sense strand that is 21 to 27 nt long; b) having no tt overhang in a sense strand; c) having a 2'-OMe-chemically modified nucleotide at the 7 th position from the 5' end of a sense strand, and a nucleotide in an anti-sense strand binding to this position, which is not chemically modified with 2'-OMe; d) having a nucleotide at the 9 th position from the 5' end of the sense strand, which is not chemically modified with 2'-OMe; and e) having 2'-OMe-chemically modified nucleotides at the 18 th and 20 th positions from the 5' end of the anti-sense strand.
  4. The pharmaceutical composition of claim 1, wherein the group consisting of siRNA comprising the nucleotide sequence represented by SEQ ID NO: 6, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 8, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 9, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 10, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 11, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 16, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 19, siRNA comprising the nucleotide sequence represented by SEQ ID NO: 22, and siRNA comprising the nucleotide sequence represented by SEQ ID NO: 25 has the following characteristics: a) having a sense strand that is 19 to 25 nt long and an anti-sense strand that is 21 to 27 nt long; b) having a 2'-OMe-chemically modified nucleotide at the 7 th position from the 5' end of a sense strand, and a nucleotide in an anti-sense strand binding to this position, which is not chemically modified with 2'-OMe; c) having a nucleotide at the 9 th position from the 5' end of the sense strand, which is not chemically modified with 2'-OMe; and d) having 2'-OMe-chemically modified nucleotides at the 16 th , 18 th and 20 th positions from the 5' end of the anti-sense strand.
  5. The pharmaceutical composition of claim 1, wherein the cancer is one selected from the group consisting of pancreatic cancer, colorectal cancer, squamous cell carcinoma, lung cancer, adenocarcinoma of the lung, peritoneal cancer, skin cancer, skin or intraocular melanoma, rectal cancer, anal cancer, esophageal cancer, small intestinal cancer, endocrine cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, blood cancer, liver cancer, gastric cancer, glioblastoma, cervical cancer, ovarian cancer, bladder cancer, liver tumors, breast cancer, colon cancer, endometrial cancer, uterine cancer, salivary gland cancer, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancer, and brain cancer.
  6. The pharmaceutical composition of claim 1, wherein the composition inhibits the proliferation of cancer cells.
  7. The pharmaceutical composition of claim 1, wherein the composition reduces tumor size and weight.
  8. The pharmaceutical composition of claim 1, wherein the composition inhibits KRAS mRNA expression.
  9. A kit for preventing or treating cancer, comprising a composition comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient, and an instruction manual.
  10. A method of treating cancer, comprising: administering a pharmaceutically effective amount of a composition comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient to a subject in need thereof.
  11. A use of a composition comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient for preventing or treating cancer.
  12. A use of a composition comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient for preparing a formulation for preventing or treating cancer.

Description

[Technical Field] The present invention relates to a pharmaceutical composition for preventing or treating cancer comprising siRNA as an active ingredient. This application claims priority to and the benefit of Korean Patent Application Nos. 10-2023-0083349, 10-2023-0083355, and 10-2023-0083360, each filed on June 28, 2023, the disclosure of which is incorporated herein by reference in its entirety. Additionally, this application claims priority to and the benefit of Korean Patent Application No. 10-2024-0084878, filed on June 27, 2024, the disclosure of which is incorporated herein by reference in its entirety. [Background Art] Cancer is a genetic disease that forms tumors through abnormal division, and when it worsens, it becomes a malignant tumor, metastasizes to surrounding tissue and threatens life. The main cause of cancer is the abnormal overexpression of genes related to cell growth and division, or mutations in genes that control them. There are various types of cancer depending on an organ in which cancer occurs, and according to statistical data from the Ministry of Health and Welfare, pancreatic cancer ranked eighth in all cancer cases occurring in 2017 and is known to have a poor prognosis because it is difficult to diagnose early and easily metastasizes to other organs. In addition, the 5-year survival rate for pancreatic cancer is approximately 12%, which is significantly lower than 76.5%, 75%, and 93% for stomach cancer, colon cancer, and breast cancer, respectively. Anticancer agents such as gemcitabine and radiation therapy, which are used today, can cause various side effects in the vascular system, nervous system, blood system and skin, so new treatments that minimize these side effects and have better therapeutic effects are needed. Colorectal cancer is a malignant tumor (adenocarcinoma) that occurs in the colon or rectum, and is cancer that mostly occurs in the mucosa. Depending on where cancer occurs, when occurring in the colon, it is called colon cancer, and when occurring in the rectum, it is called rectal cancer. These types of cancer are collectively called colorectal cancer. According to data from the Central Cancer Registry published in 2017, 214,701 cancer cases occurred in Korea in 2015. Among them, colorectal cancer was the second most common, with 26,790 cases in both men and women, accounting for 12.5% of all cancer cases. It was more prevalent in men, with a male-to-female ratio of 1.5:1. Particularly, colorectal cancer is known to be prevalent, with 15,911 cases in men, ranking third among cancers in men, and 10,879 cases in women, also ranking third among cancers in women. Meanwhile, gene therapy is a technology that uses genes to treat or prevent diseases and is actively being developed to treat intractable or incurable diseases such as cancer. Small interfering RNA (siRNA), one of the gene therapy technologies for cancer treatment, is a 21 to 23-bp long RNA duplex that suppresses gene expression by forming an RISC complex and cleaving mRNA. When the expression of genes essential for cancer development is suppressed using siRNA, cancer can be treated through the inhibition of cancer cell growth or death of cancer cells. Despite the above methods, few effective siRNA therapeutics for treating cancer have been reported to date. [Disclosure] [Technical Problem] An object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer, including one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient. Another object of the present invention is to provide a kit for preventing or treating cancer, comprising a composition including one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient, and an instruction manual. However, technical problems to be solved in the present invention are not limited to the above-described problems, and other problems which are not described herein will be fully understood by those of ordinary skill in the art from the following descriptions. [Technical Solution] The present invention provides a pharmaceutical composition for preventing or treating cancer, comprising one or more selected from the group consisting of siRNAs having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 29 as an active ingredient. In one embodiment of the present invention, the group consisting of siRNAs below may have a sense strand that is 19 to 25 nt long and an anti-sense strand that is 21 to 27 nt long, but is not limited thereto: 1) siRNA having any one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 5;2) siRNA having a nucleotide sequence represented by SEQ ID NO: 7;3) siRNA having any one nucleotide sequence selected from the group consi