Human G protein-coupled receptors

• US 7,816,492 B2
• Filed: 05/04/2006
• Issued: 10/19/2010
• Est. Priority Date: 11/20/1998
• Status: Expired due to Fees

• Current Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Original Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Inventors: Chen, Ruoping, Leonard, James N.
• Primary Examiner(s): Landsman; Robert
• Assistant Examiner(s): Chandra; Gyan
• Application Number:
  US11/417,708
• Publication Number:
  US 20070122878A1
• Time in Patent Office: 1,629 Days
• Field of Search: None
• US Class Current: 530/350
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/723 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor
• CPC Class Codes: G01N 2333/726 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to endogenous, human orphan G protein-coupled receptors.

Claims

1. An isolated G protein-coupled receptor comprising the amino acid sequence of SEQ ID NO:

8.

2. An isolated G protein-coupled receptor encoded by the nucleotide sequence of SEQ ID NO:

7.

3. An isolated G protein-coupled receptor comprising the amino acid sequence of a mutant of SEQ ID NO:

8 comprising a single substitution of lysine for leucine at amino acid position 224 of SEQ ID NO;

8.

4. A recombinant G protein-coupled receptor comprising the amino acid sequence of SEQ ID NO:

8.

5. A recombinant G protein-coupled receptor encoded by the nucleotide sequence of SEQ ID NO:

7.

6. A recombinant G protein-coupled receptor comprising the amino acid sequence of a mutant of SEQ ID NO:

8 comprising a single substitution of lysine for leucine at amino acid position 224 of SEQ ID NO;

8.

7. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor comprising the amino acid sequence of SEQ ID NO:

8 linked to a heterologous polypeptide.

8. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor encoded by the nucleotide sequence of SEQ ID NO:

7;

wherein said G protein-coupled receptor is linked to a heterologous polypeptide.

9. A G protein-coupled receptor fusion protein comprising the amino acid sequence of a mutant of SEQ ID NO:

8 comprising a single substitution of lysine for leucine at amino acid position 224 of SEQ ID NO;

8;

wherein said G protein-coupled receptor is linked to a heterologous polypeptide.

10. An isolated G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptors is capable of modulating insulin or glucagon levels.

14. The isolated G protein-coupled receptor according to any one of claims 10, 11, 12, and 13 wherein said isolated G protein-coupled receptor comprises a substitution of lysine for leucine at amino acid position 224 of SEQ ID NO:

8.

15. The isolated G protein-coupled receptor according to claim 14, wherein said isolated G protein-coupled receptor is a constitutively activated receptor.

16. The isolated G protein-coupled receptor according to claim 14 wherein said isolated G protein-coupled receptor is a human receptor.

17. The isolated G protein-coupled receptor according to any one of claims 10, 11, 12, and 13 wherein said isolated G protein-coupled receptor is a constitutively activated receptor.

18. The isolated G protein-coupled receptor according to any one of claims 10, 11, 12, and 13 wherein said isolated G protein-coupled receptor is a human receptor.

11. An isolated G protein-coupled receptor comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

12. An isolated G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

13. An isolated G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

19. A recombinant G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

23. The recombinant G protein-coupled receptor according to any one of claims 19, 20, 21, and 22, wherein said recombinant G protein-coupled receptor comprises a substitution of lysine for leucine at amino acid position 224 of SEQ ID NO:

8.

24. The recombinant G protein-coupled receptor according to claim 23, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor.

25. The recombinant G protein-coupled receptor according to claim 23, wherein said recombinant G protein-coupled receptor is a human receptor.

26. The recombinant G protein-coupled receptor according to any one of claims 19, 20, 21, and 22, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor.

27. The recombinant G protein-coupled receptor according to any one of claims 19, 20, 21, and 22, wherein said recombinant G protein-coupled receptor is a human receptor.

20. A recombinant G protein-coupled receptor comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

21. A recombinant G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

22. A recombinant G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

28. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor fusion protein is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

32. The G protein-coupled receptor fusion protein according to any one of claims 28, 29, 30, and 31, wherein said G protein-coupled receptor comprises a substitution of lysine for leucine at amino acid position 224 of SEQ ID NO:

8.

33. The G protein-coupled receptor fusion protein according to claim 32, wherein said heterologous polypeptide is a G protein.

34. The G protein-coupled receptor fusion protein according to claim 32, wherein said G protein-coupled receptor is a constitutively activated receptor.

35. The G protein-coupled receptor fusion protein according to claim 32, wherein said G protein-coupled receptor is a human G protein-coupled receptor.

36. The G protein-coupled receptor fusion protein according to any one of claims 28, 29, 30, and 31, wherein said heterologous polypeptide is a G protein.

37. The G protein-coupled receptor fusion protein according to any one of claims 28, 29, 30, and 31, wherein said G protein-coupled receptor is a constitutively activated receptor.

38. The G protein-coupled receptor fusion protein according to any one of claims 28, 29, 30, and 31, wherein said G protein-coupled receptor is a human G protein-coupled receptor.

29. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor fusion protein is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

30. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor fusion protein is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

31. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor fusion protein is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

39. An isolated G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said isolated G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

43. The isolated G protein-coupled receptor according to any one of claims 39, 40, 41, and 42, wherein said isolated G protein-coupled receptor is a human receptor.

40. An isolated G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said isolated G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

41. An isolated G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said isolated G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

42. An isolated G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said isolated G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

44. A recombinant G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

48. The recombinant G protein-coupled receptor according to any one of claims 44, 45, 46, and 47, wherein said isolated G protein-coupled receptor is a human receptor.

45. A recombinant G protein-coupled receptor comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO:

8, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

46. A recombinant G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

47. A recombinant G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said recombinant G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

49. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

53. The G protein-coupled receptor fusion protein according to any one of claims 49, 50, 51, and 52, wherein said heterologous polypeptide is a G protein.

54. The G protein-coupled receptor fusion protein according to claim 53, wherein said G protein-coupled receptor is a human G protein-coupled receptor.

55. The G protein-coupled receptor fusion protein according to any one of claims 49, 50, 51, and 52, wherein said G protein-coupled receptor is a human G protein-coupled receptor.

50. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO:

8, wherein said G protein-coupled receptor is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

51. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor encoded by a nucleotide sequence having at least 95% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.

52. A G protein-coupled receptor fusion protein comprising a G protein-coupled receptor encoded by a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO:

7, wherein said G protein-coupled receptor is linked to a heterologous polypeptide, and wherein said G protein-coupled receptor is a constitutively activated receptor, and wherein said G protein-coupled receptor is capable of modulating insulin or glucagon levels.