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KR-20260064753-A - Novel polypeptides, polypeptide derivatives, and their uses

KR20260064753AKR 20260064753 AKR20260064753 AKR 20260064753AKR-20260064753-A

Abstract

This application relates to the field of biomedical technology and discloses a novel polypeptide, a polypeptide derivative, and its uses. Specifically, it relates to the specific sequence, discovery process, specific antitumor type, sustained modification method, and use of the novel polypeptide. The tumor includes one or more of glioma, neuroblastoma, head and neck cancer, esophageal cancer, thyroid cancer, lung cancer, liver cancer, kidney cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, colon cancer, small intestine cancer, ileocecal cancer, gastric cancer, bladder cancer, pancreatic cancer, prostate cancer, cholangiocarcinoma, melanoma, sarcoma, myeloma, lymphoma, and leukemia. The specific action includes inhibition of proliferation and/or metastasis of the aforementioned tumor cells, and due to its broad therapeutic range, it possesses significant therapeutic value in various tumors.

Inventors

  • 쉬, 한메이
  • 리, 멍웨이
  • 사라, 세트레라흐만

Assignees

  • 난징 안지 바이오테크놀러지 컴퍼니 리미티드

Dates

Publication Date
20260507
Application Date
20240927
Priority Date
20230808

Claims (14)

  1. In the use of a novel polypeptide or its derivative in the manufacture of drugs for the prevention or treatment of tumors, said novel polypeptide is, (1): A polypeptide formed by deleting three consecutive amino acids from the amino acid sequence represented by SEQ ID NO.1, and having the same or basically the same function; (2): A polypeptide formed by deleting any number of amino acids from 1 to 34 at the N-terminus of the polypeptide with the amino acid sequence represented by SEQ ID NO.1, and having the same or basically the same function; (3): A polypeptide having an amino acid sequence represented by SEQ ID NO.1 or a polypeptide formed by substituting one or more amino acids from (1) or (2) and having the same or basically the same function; any one selected from the use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors.
  2. In Article 1, In (1) above, the polypeptide of the amino acid sequence represented by SEQ ID NO.1 is formed by deleting three consecutive amino acids, the 3N-2, 3N-1, and 3Nth, and is a polypeptide having the same or basically the same function, where N=1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17; or In the above (2), 4, 9, 14, 19, 24, 29, or 34 amino acids are deleted from the N-terminus of the polypeptide of the amino acid sequence represented by SEQ ID NO.1, and the polypeptide is formed and has the same or basically the same function; or The use of a novel polypeptide or its derivative in the manufacture of a drug for tumor prevention or treatment, characterized in that the 2nd, 3rd, 8th, 9th, 10th, 11th, 12th, 13th, 17th, 19th, 20th, 21st, 22nd, 25th, 27th, 28th, 30th, 31st, 32nd, 40th, 41st, 42nd, 43rd, 44th, 45th, 48th, 49th, or 50th amino acid of the amino acid sequence represented by SEQ ID NO.1 in (3) above.
  3. In Article 2, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the amino acid sequence of the novel polypeptide is represented by any one of SEQ ID NO.2 to SEQ ID NO.53.
  4. In Paragraph 3, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the amino acid sequence of the novel polypeptide is represented as any one of SEQ ID NO.2~SEQ ID NO.4, SEQ ID NO.6~SEQ ID NO.10, SEQ ID NO.13, SEQ ID NO.15~SEQ ID NO.17, SEQ ID NO.19~SEQ ID NO.21, SEQ ID NO.26~SEQ ID NO.51, and SEQ ID NO.53.
  5. In any one of paragraphs 1 to 4, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the above derivative comprises a novel polypeptide modified and a derivative having the same or fundamentally the same function.
  6. In Article 5, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the above modification comprises one or more of N-terminal modifications, C-terminal modifications, side chain modifications, amino acid modifications, or skeletal modifications.
  7. In Article 6, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the above modification comprises one or more of modifications by polyethylene glycol, fatty acid linkage, Fc polypeptide fusion, binding with human serum albumin, non-natural amino acid substitution, polypeptide cyclization, or sustained-release modification of a higher formulation.
  8. In Article 7, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the above modification includes fatty acid linkage, wherein the fatty acid linkage includes C12-20 fatty acid linkage at the N-terminus or C12-20 fatty acid linkage using a linker.
  9. In Article 8, Use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the fatty acid linkage comprises a C18 fatty acid linkage at the N-terminus or a C18 fatty acid linkage using a linker, wherein the linker is a peptide fragment composed of amino acids with a length of less than 5.
  10. In any one of paragraphs 1 through 9, The use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the tumor comprises one or more of the following: glioma, neuroblastoma, head and neck cancer, esophageal cancer, thyroid cancer, lung cancer, liver cancer, kidney cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, colon cancer, small intestine cancer, ileocecal cancer, stomach cancer, bladder cancer, pancreatic cancer, prostate cancer, cholangiocarcinoma, melanoma, sarcoma, multiple myeloma, lymphoma, and leukemia.
  11. In Article 10, The use of a novel polypeptide or its derivative in the manufacture of a drug for tumor prevention or treatment, characterized in that the tumor prevention or treatment described above includes inhibiting the proliferation and/or metastasis of tumor cells.
  12. In Article 11, The above tumor prevention or treatment includes inhibiting the proliferation of tumor cells, and among the above tumor and cells, The cancer cells of the glioblastoma mentioned above contain U87-MG, and The above-mentioned neuroblastoma cancer cells contain SH-SY5Y, and The cancer cells of the head and neck cancer mentioned above include any one of oral epithelioid carcinoma cells KB, laryngeal epithelioid carcinoma cells HEp2, tongue squamous cell carcinoma cells CAL27, and nasopharyngeal carcinoma cells CNE-2Z, and The cancer cells of the above-mentioned esophageal cancer contain Eca-109 and/or TE-13, and The cancer cells of the above-mentioned thyroid cancer contain NPPA87-1, and The above-mentioned lung cancer cells include any one of 95-D, SK-MES-1, SPC-A1, and A549, or a combination thereof, and The above liver cancer cells contain HCCLM3 and/or HepG2, and The cancer cells of the above-mentioned kidney cancer contain Ketr-3 and/or 786-O, and The above-mentioned breast cancer cells include SK-BR-3 and/or MDA-MB-231, and The cancer cells of the above-mentioned cervical cancer include CaSki and/or HeLa, and The cancer cells of the above-mentioned uterine cancer include RL-952 and/or MS751, and The cancer cells of the above-mentioned ovarian cancer include ES-2 and/or SKOV3, and The cancer cells of the colon cancer mentioned above include HT29 and/or SW480, and The cancer cells of the above-mentioned small intestine cancer contain HIC, and The cancer cells of the above-mentioned ileocecal cancer include HCT-8, and The cancer cells of the above gastric cancer include MGC-803 and/or BGC-823, and The cancer cells of the bladder cancer mentioned above include T24 and/or EJ, and The cancer cells of the above-mentioned pancreatic cancer include ASPC-1 and/or PANC-1, and The cancer cells of the above-mentioned prostate cancer include 22RV1 and/or PC-3, and The cancer cells of the above-mentioned bile duct cancer include QBC939, and The cancer cells of the above-mentioned melanoma contain SK-mel-2 and/or A375, and The cancer cells of the above sarcoma include MG63 and/or HT-1080, and The cancer cells of the above-mentioned multiple myeloma contain LP-1, and The cancer cells of the above lymphoma include any one of Raji, RPMI 8226, U937, WSU-DLCL2, or a combination thereof, and Use of a novel polypeptide or its derivative in the manufacture of a drug for the prevention or treatment of tumors, characterized in that the cancer cells of the leukemia above comprise any one of CEM/C1, NB4, KG-1, K562, HL60, Jurkat, Clone E6-1 or a combination thereof.
  13. In Article 11, The above tumor prevention or treatment includes inhibiting the metastasis of tumor cells, and among the above tumors and cells, The cancer cells of the above-mentioned melanoma contain A375, and The cancer cells of the above-mentioned cervical cancer include HeLa, and The cancer cells of the above-mentioned ovarian cancer contain SKOV3, and The above liver cancer cells contain Hep3B, and The use of a novel polypeptide or its derivative in the manufacture of a drug for tumor prevention or treatment, characterized in that the cancer cells of the lung cancer described above contain A549.
  14. In a drug composition for the prevention or treatment of tumors, A drug composition for the prevention or treatment of tumors, characterized in that the above drug composition contains at least a novel polypeptide or derivative thereof according to any one of claims 1 to 9 and a pharmaceutically acceptable carrier, and the tumor comprises one or more of glioma, neuroblastoma, head and neck cancer, esophageal cancer, thyroid cancer, lung cancer, liver cancer, kidney cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, colon cancer, small intestine cancer, ileocecal cancer, stomach cancer, bladder cancer, pancreatic cancer, prostate cancer, cholangiocarcinoma, melanoma, sarcoma, multiple myeloma, lymphoma, and leukemia.

Description

Novel polypeptides, polypeptide derivatives, and their uses The present application relates to the field of biomedical technology, specifically to novel polypeptides, polypeptide derivatives, and their uses, and more specifically to novel polypeptides, polypeptide derivatives, and their uses in the prevention or treatment of tumors. Open reading frames (ORFs) coding for proteins consist of a series of meaningful codons starting from a start codon and ending at a stop codon. Due to limitations in existing computer algorithms and detection methods, most ORF prediction algorithms have set a minimum lower bound of 100 amino acids. With advancements in ribosome profiling sequencing, computational biology, and high-throughput omics technologies, an increasing number of studies have revealed that many non-coding RNAs actually contain small open reading frames (sORFs) less than 300 nt in length and can code for functional polypeptides—namely micropeptides—less than 100 amino acids in length. Transcriptological sources of micropeptides primarily include non-coding RNAs (lncRNAs, circRNAs, pri-miRNAs), ribosomal RNAs (rRNA), antisense transcripts, 5’UTRs, 3’UTRs, and intergenetic ORFs. Early research on micropeptides began in 1996 when German scientists discovered a 679 nt RNA that performs a non-coding function, transcribed from the ENOD40 (early nodulin 40) gene in legumes. Although it was classified as lncRNA at the time because its length exceeded 200 nt, it was later revealed that it could actually code for proteins and regulate plant growth. Specific research findings were published in the journal Science. In 2002, German researchers studied this RNA in greater detail and discovered that it contains two sORFs and definitely codes for micropeptides (one coding for 12 peptides and the other for 24 peptides), and also demonstrated that it interacts with sucrose synthase. Over the following 20 years, with the advancement of computational biology and multi-omics deep sequencing technologies (e.g., ribosomal footprint sequencing, polypeptide sequencing), scientists have discovered a large number of previously unannotated sORFs hidden in non-coding RNA in various species, including nematodes, fruit flies, zebrafish, plants, mice, and humans. They have also discovered that these can translate novel polypeptides involved in biological functions such as muscle development, mRNA modification, immune regulation, and tumor progression, which has provided a new perspective on proteomics research. Recently, some studies have reported that micropeptides encoded by ncRNA (e.g., SMIM22, HOXB-AS3, SMIM30, MP31, PINT87aa) can regulate the development and progression of various tumors, including breast cancer, colorectal cancer, glioma, liver cancer, melanoma, and esophageal squamous cell carcinoma, and that they can play a role in promoting or inhibiting tumor proliferation, metastasis, energy metabolism, and drug resistance, suggesting that micropeptides can be developed in depth as potential tumor diagnostic biomarkers or therapeutic targets. Chinese invention patent publication number CN112442116A describes the use of the micropeptide HMMW encoded by lncRNA in the detection and treatment of malignant tumors such as head and neck cancer, thyroid cancer, and kidney cancer, and HMMW is a completely new endogenous polypeptide sequence, specifically containing 51 amino acid residues, and the direct binding receptor is the AQP2 protein. Figure 1 shows the effect of micropeptide HMMW on the proliferation of tongue squamous cell carcinoma CAL27 cells according to the deletion type. Figure 2 shows the effect of different cleavage fragments of the micropeptide HMMW on the proliferation of tongue squamous cell carcinoma CAL27 cells. Figure 3 shows the sequence information of the alanine scanning mutation of the micropeptide HMMW. Figure 4 shows the effect of a single amino acid mutation sequence of the micropeptide HMMW on the proliferation of tongue squamous cell carcinoma CAL27 cells. Figure 5 shows the statistical results of the effects of the novel polypeptide and micropeptide HMMW on the metastatic activity of melanoma A375 cells. Figure 6 shows the statistical results regarding the effect of the novel polypeptide and micropeptide HMMW on the metastatic activity of cervical cancer HeLa cells. Figure 7 shows the statistical results of the effects of the novel polypeptide and micropeptide HMMW on the metastatic activity of ovarian cancer SKOV3 cells. Figure 8 shows the statistical results regarding the effect of the novel polypeptide and micropeptide HMMW on the metastatic activity of liver cancer Hep3B cells. Figure 9 shows the statistical results of the effects of the novel polypeptide and micropeptide HMMW on the metastatic activity of lung cancer A549 cells. Figure 10 shows the results of the novel polypeptide and micropeptide HMMW inhibiting the in vivo tumorigenic ability of human tongue squamous cell carcinoma CAL27 cells. Figur