Insulin resistance improving agents

• US 20060014679A1
• Filed: 05/22/2003
• Published: 01/19/2006
• Est. Priority Date: 05/24/2002
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Sasada, Reiko, Tojo, Hideaki, Henta, Tsutomu
• Granted Patent: US 7,556,926 B2
• Time in Patent Office: Days
• US Class Current: 514/1.900
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 14/47 from mammals

Abstract

A compound or its salt inhibiting the activity of a protein having an amino acid sequence which is the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, an extracellular domain of the protein above, an antibody, an antisense polynucleotide, etc. are usable as insulin-sensitizing agents and preventives and/or remedies for diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension, heart disease, and so on.

Claims

1. An insulin-sensitizing agent which comprises a compound or its salt that inhibits the activity of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

4. The insulin-sensitizing agent according to claim 1, which is an agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease.

2. An insulin-sensitizing agent which comprises a compound or its salt that inhibits the expression of a gene for a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1.

3. An insulin-sensitizing agent which comprises a compound or its salt that inhibits the expression of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1.

5. An insulin-sensitizing agent which comprises an extracellular domain of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1;

or a salt thereof.

6. The insulin-sensitizing agent according to claim 5, wherein the extracellular domain is a partial peptide containing the 14-167 amino acid sequence in the amino acid sequence represented by SEQ ID NO:

1.

7. An agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises an extracellular domain of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1;

or a salt thereof.

8. An antisense polynucleotide containing the entire or part of a base sequence complementary or substantially complementary to a base sequence of a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence represented by SEQ ID NO:

1 or its partial peptide.

9. An insulin-sensitizing agent which comprises the antisense polynucleotide according to claim 8.

10. An agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises the antisense polynucleotide according to claim 8.

11. An insulin-sensitizing agent which comprises an antibody to a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

12. An agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises an antibody to a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

13. A diagnostic agent for insulin resistance, which comprises an antibody to a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

14. A diagnostic agent for diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises an antibody to a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

15. A diagnostic agent for insulin resistance, which comprises a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

16. A diagnostic agent for diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

17. A method of screening an insulin-sensitizing agent, which comprises using a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

24. The screening method according to claim 17, wherein substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1 is the amino acid sequence represented by SEQ ID NO;

2.

18. A method of screening an antagonist of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, or a salt of the protein, which comprises using (i) the protein, its partial peptide, or a salt thereof and (ii) a ligand to the protein, its partial peptide, or a salt thereof.

19. A method of screening an insulin-sensitizing agent, which comprises using (i) a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof and (ii) a ligand to the protein, its partial peptide, or a salt thereof.

20. A kit for screening an insulin-sensitizing agent, which comprises a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

21. A method of screening an insulin-sensitizing agent, which comprises using a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

22. A kit for screening an insulin-sensitizing agent which comprises a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

23. (canceled)

25. A method of screening an agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises using a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

26. A kit for screening an agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

27. A method of screening an agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises using a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

28. A kit for screening an agent for the prevention, treatment, or combination thereof, of diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, or its partial peptide.

29-33. -33. (canceled)

34. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of a compound or its salt that inhibits the activity of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt of the protein.

37. A method according to claim 34, which is a method of preventing and/or treating diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease.

35. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of a compound or its salt that inhibits the expression of a gene for a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1 or its partial peptide.

38. A method according to claim 35, which is a method of preventing and/or treating diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease.

36. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of a compound or its salt that inhibits the expression of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1 or its partial peptide.

39. A method according to claim 36, which is a method of preventing and/or treating diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease.

40. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of an extracellular domain of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1;

or a salt thereof.

41. The method according to claim 40, wherein the extracellular domain is a partial peptide containing the 14-167 amino acid sequence in the amino acid sequence represented by SEQ ID NO:

1.

42. A method of preventing and/or treating diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises administering to a mammal an effective amount of an extracellular domain of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1;

or a salt thereof.

43. The method according to claim 42, which is a method of preventing and/or treating diabetes.

44. The method according to claim 42, wherein the extracellular domain is a partial peptide containing the 14-167 amino acid sequence in the amino acid sequence represented by SEQ ID NO:

1.

45. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of an antisense polynucleotide containing the entire or part of a base sequence complementary or substantially complementary to a base sequence of a polynucleotide encoding a protein containing the same or substantially the same amino acid sequence represented by SEQ ID NO:

1 or its partial peptide.

46. A method of improving insulin resistance, which comprises administering to a mammal an effective amount of an antibody to a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt thereof.

47. A method of improving insulin resistance, which comprises inhibiting (i) the activity of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt of the protein, (ii) the expression of a gene for the protein or its partial peptide or (iii) the expression of the protein or its partial peptide.

48. A method of preventing and/or treating diabetes, obesity, hyperlipemia, arteriosclerosis, hypertension or heart disease, which comprises inhibiting (i) the activity of a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

1, its partial peptide, or a salt of the protein, (ii) the expression of a gene for the protein or its partial peptide or (iii) the expression of the protein or its partial peptide.