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EP-4741420-A1 - PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING OBESITY COMPRISING GLP ANALOGUE AS ACTIVE INGREDIENT

EP4741420A1EP 4741420 A1EP4741420 A1EP 4741420A1EP-4741420-A1

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating obesity, the composition comprising a glucagon-like peptide (GLP) analogue as an active ingredient. The GLP analogue of the present invention is an analog of GLP-1 and GLP-2 and has an extended duration of in vivo activity due to having an increased half-life, and thus was found to have an excellent effect in preventing or treating metabolic diseases. Specifically, the peptide of the present invention reduces the body weight and fat of an individual, reduces the levels of blood fat factors such as blood glucose, total blood cholesterol, high-density lipoproteins, low-density lipoproteins, and triglycerides, and reduces hepatic ASL and AST levels, liver weight, hepatic steatosis levels, and hepatic triglycerides levels, and thus can be effectively used as an excellent agent for preventing or treating metabolic diseases.

Inventors

  • LIM, CHAE YOUNG
  • KIM, DONG HWAN
  • KWON, OH CHAN

Assignees

  • Huonslab Co., Ltd.

Dates

Publication Date
20260513
Application Date
20240628

Claims (20)

  1. A peptide represented by Formula I below: [Formula I] HX 2 EGX 5 FTX 8 DX 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 X 20 X 21 FIX 24 X 25 LX 27 X 28 X 29 X 30 X 31 X 32 X 33 X 34 X 35 X 36 X 37 X 38 X 39 X 40 X 41 X 42 X 43 In Formula I, X 2 is Gly or Aib; X 5 is Thr or Ser; X 8 is Ser or Asp; X 10 is Leu or Val; X 11 is Ser or Asn; X 12 is Thr or Ser; X 13 is Tyr or Ile; X 14 is Leu or Met; X 15 is Asp or Glu; X 16 is any one selected from the group consisting of Ala, Gly, and Asn; X 17 is Leu or Gln; X 18 and X 19 are Ala, or His; X 20 is Arg, or Cys; X 21 is Asp or Glu; X 24 is Asn or Lys; X 25 is Trp or Thr; X 27 is Ile or Val; X 28 is Gln or Lys; X 29 is Thr or Gly; X 30 is Lys or Arg; X 31 is Ile or absent; X 32 is Thr or absent; X 33 is Asp or absent; and X 34 to X 43 are absent or Lys.
  2. The peptide of claim 1, wherein X 5 is Thr; X 8 , and X 11 are Ser; X 12 is Thr; X 13 is Tyr; X 14 is Leu; X 15 is Asp; X 16 is Ala; X 17 is Leu; X 19 is Ala; X 21 is Asp; X 25 is Trp; X 27 is Ile; X 28 is Gln; X 29 is Thr; X 30 is Lys; X 31 is Ile; X 32 is Thr; X 33 is Asp, X 34 to X 43 , or X 36 to X 43 are absent.
  3. The peptide of claim 1 or 2, wherein X 10 is Leu, X 18 is Ala, and X 34 and X 35 are Lys.
  4. The peptide of any one of claims 1 to 3, wherein when X 20 is Cys, Cys is conjugated with polyethylene glycol (PEG).
  5. The peptide of any one of claims 1 to 4, wherein a fatty acid binds to any one or more amino acids selected from the group consisting of X 24 and X 35 to X43.
  6. The peptide of claim 5, wherein the fatty acid is a C 16 to C 20 fatty acid.
  7. The peptide of claim 6, wherein the fatty acid is any one selected from the group consisting of palmitic acid, octadecanedioic acid, eicosanedioic acid, margaric acid, heptadecanedioic acid, hexadecanedioic acid, stearic acid, nonadecylic acid, nonadecanedioic acid, and arachidic acid.
  8. The peptide of any one of claims 1 to 7, wherein the peptide comprises any one selected from the group consisting of amino acid sequences represented by SEQ ID NOs: 1 to 9.
  9. A pharmaceutical composition for preventing or treating a metabolic disease, comprising the peptide of any one of claims 1 to 8 as an active ingredient.
  10. The pharmaceutical composition of claim 9, wherein the metabolic disease is any one or more selected from the group consisting of obesity, diabetes, non-alcoholic fatty liver disease, hepatic steatosis, dyslipidemia, atherosclerosis, insulin resistance syndrome, and their complications.
  11. The pharmaceutical composition of claim 9 or 10, wherein the peptide has a long-acting form.
  12. The pharmaceutical composition of any one of claims 9 to 11, wherein the composition is administered by any one route selected from the group consisting of subcutaneous, intravenous, and oral administrations.
  13. The pharmaceutical composition of any one of claims 9 to 12, wherein the composition activates GLP-1 and GLP-2.
  14. The pharmaceutical composition of any one of claims 9 to 13, wherein the composition is characterized by any one or more selected from the group consisting of the following: a) reducing the body weight and fat of an individual; b) lowering blood glucose, total blood cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides; and c) decreasing hepatic ASL and AST levels, liver weight, a hepatic steatosis grade, and a hepatic triglyceride level.
  15. A kit for preventing or treating a metabolic disease, comprising a composition comprising the peptide of any one of claims 1 to 8 as an active ingredient; and instructions.
  16. A food composition for preventing or improving a metabolic disease, comprising the peptide of any one of claims 1 to 8 as an active ingredient.
  17. The food composition of claim 16, wherein the food is a health functional food.
  18. A cosmetic composition for preventing or improving obesity, comprising the peptide of any one of claims 1 to 8 as an active ingredient.
  19. A method of preventing, alleviating, or treating a metabolic disease, comprising: administering a pharmaceutically effective amount of a composition comprising the peptide of any one of claims 1 to 8 as an active ingredient to an individual in need thereof.
  20. A use of a composition comprising the peptide of any one of claims 1 to 8 as an active ingredient for preventing, alleviating, or treating a metabolic disease.

Description

[Technical Field] The present invention relates to a pharmaceutical composition for preventing or treating obesity, the composition comprising a GLP analog as an active ingredient. This application claims priority to and the benefit of Korean Patent Application No. 10-2023-0085302, filed on June 30, 2023, and Korean Patent Application No. 10-2024-0084869, filed on June 27, 2024, the disclosure of which is incorporated herein by reference in its entirety. [Background Art] Obesity, one of the chronic diseases of modern people, has emerged as one of the most serious global health issues, and in 1996, it was classified as a disease by the World Health Organization (WHO). Obesity is steadily increasing due to various reasons, such as dietary habits associated with industrialization and rising income levels, the westernization of eating patterns, and the increased consumption of processed food, and changes in lifestyle. Obesity is a condition in which metabolic disorders are induced by excessive accumulation of body fat. Although obesity itself may not pose a direct problem, it cannot be overlooked, as it can lead to secondary complications such as hyperlipidemia, hypertension, arteriosclerosis, diabetes, fatty liver, and cardiovascular diseases, as well as social problems resulting from excessive fat accumulation. For this reason, in 2013, the WHO identified obesity as a new epidemic in the 21st century. Afterwards, as health awareness grew, the world declared war on obesity, and multifaceted research is being conducted to develop obesity drugs, and the obesity treatment market is growing. The US Food and Drug Administration (FDA) approved sibutramine in 1997 and orlistat in 1999 as obesity drugs that can be used for more than 3 months. In 2006, rimonabant was licensed for use in European countries, including the United Kingdom. However, rimonabant was withdrawn from the market in 2009 due to psychiatric side effects such as suicide, and sibutramine was also withdrawn in 2010 due to concerns about cardiovascular adverse effects. After these incidents, anti-obesity drugs have been facing a period of stagnation. Meanwhile, glucagon-like peptide (GLP), an appetite control hormone, is a hormone secreted in the small intestine by eating, and it regulates appetite by increasing satiety and blood glucose by inducing insulin secretion in the pancreas. Therefore, various types of GLP analogs have been studied for the treatment of diabetes, etc. However, few have been reported on long-acting GLP analogs that exhibit significant anti-obesity effects. [Detailed Description of Invention] [Technical Problem] One object of the present invention is to provide a peptide represented by Formula I below:         HX2EGX5FTX8DX10X11X12X13X14X15X16X17X18X19X20X21FIX24X25LX27 X28X29X30X31X32X33X34X35X36X37X38X39X4oX41X42X43     [Formula I] In Formula I, X2 is Gly or Aib;X5 is Thr or Ser;X8 is Ser or Asp;X10 is Leu or Val;X11 is Ser or Asn;X12 is Thr or Ser;X13 is Tyr or Ile;X14 is Leu or Met;X15 is Asp or Glu;X16 is any one selected from the group consisting of Ala, Gly, and Asn;X17 is Leu or Gln;X18 and X19 are Ala, or His;X20 is Arg, or Cys;X21 is Asp or Glu;X24 is Asn or Lys;X25 is Trp or Thr;X27 is Ile or Val;X28 is Gln or Lys;X29 is Thr or Gly;X30 is Lys or Arg;X31 is Ile or absent;X32 is Thr or absent;X33 is Asp or absent; andX34 to X43 are absent or Lys. Another object of the present invention is to provide a pharmaceutical composition for preventing or treating a metabolic disease, the composition comprising the peptide as an active ingredient. Another object of the present invention is to provide a kit for preventing or treating a metabolic disease, the kit comprising a composition comprising the peptide as an active ingredient and instructions. Another object of the present invention is to provide a food composition for preventing or improving a metabolic disease, the composition comprising the peptide as an active ingredient. Another object of the present invention is to provide a cosmetic composition for preventing or improving obesity, the composition comprising the peptide as an active ingredient. 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 peptide represented by Formula I below:         HX2EGX5FTX8DX10X11X12X13X14X15X16X17X18X19X20X21FIX24X25LX27 X28X29X30X31X32X33X34X35X36X37X38X39X40X41X42X43     [Formula I] In Formula I, X2 is Gly or Aib;X5 is Thr or Ser;X8 is Ser or Asp;X10 is Leu or Val;X11 is Ser or Asn;X12 is Thr or Ser;X13 is Tyr or Ile;X14 is Leu or Met;X15 is Asp or Glu;X16 is any one selected from the group consisting of Ala, Gly, and Asn;X17 is Leu or Gln;X15 and X19 are Ala, or His;X20 is Arg, or Cys;X21 is Asp or Glu;X24 is Asn or Lys;X2