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Last Updated: April 26, 2024

Claims for Patent: 7,132,260


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Summary for Patent: 7,132,260
Title:DNA encoding parathyroid hormone receptor
Abstract: DNA encoding a parathyroid hormone receptor; production and isolation of recombinant and synthetic parathyroid hormone receptor polypeptides and fragments; antibodies to parathyroid hormone receptors and receptor fragments; methods for screening candidate compounds for antagonistic or agonistic effects on parathyroid hormone receptor action; and diagnostic and therapeutic methods of these compounds are disclosed.
Inventor(s): Segre; Gino V. (Wayland, MA), Kronenberg; Henry M. (Belmont, MA), Abou-Samra; Abdul-Badi (Plainville, MA), Juppner; Harald (Boston, MA), Potts, Jr.; John T. (West Newton, MA), Schipani; Ernestina (Boston, MA)
Assignee: The General Hospital Corporation (Boston, MA)
Application Number:10/267,730
Patent Claims:1. An isolated DNA comprising a nucleic acid sequence that encodes a polypeptide comprising an amino acid sequence at least 75% identical to SEQ ID NO:20, wherein the polypeptide binds parathyroid hormone or parathyroid hormone-related protein.

2. The isolated DNA of claim 1, wherein the nucleic acid sequence encodes substantially all of SEQ ID NO: 18.

3. The isolated DNA of claim 1, wherein the nucleic acid sequence encodes substantially all of SEQ ID NO: 19.

4. The isolated DNA of claim 1, wherein the nucleic acid sequence encodes substantially all of SEQ ID NO: 20.

5. The isolated DNA of claim 1, wherein the nucleic acid sequence encodes substantially all of SEQ ID NO: 21.

6. A cell in culture containing the isolated DNA of claim 1.

7. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 1.

8. The isolated DNA of claim 1, wherein the DNA is single-stranded.

9. The single-stranded isolated DNA of claim 8, wherein the DNA is detectably labeled.

10. A vector comprising the isolated DNA of claim 1.

11. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 1; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

12. A cell in culture containing the isolated DNA of claim 5.

13. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 5.

14. The isolated DNA of claim 5, wherein the DNA is single-stranded.

15. The single-stranded isolated DNA of claim 14, wherein the DNA is detectably labeled.

16. A vector comprising the isolated DNA of claim 5.

17. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 5; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

18. An isolated DNA comprising a sequence that hybridizes under conditions of high stringency to a probe the sequence of which consists of the coding sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or a sequence complementary to the coding sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, wherein the DNA encodes a polypeptide that binds to parathyroid hormone or parathyroid hormone-related protein, and wherein conditions of high stringency include hybridizing at 42.degree. C. for 18 24 h in a solution comprising 50% formamide, 4.times. saline sodium citrate (SSC), 2.times. Denhardt's solution, 10% Dextran sulphate and 100 .mu.g/ml salmon sperm DNA and washing with 2.times.SSC/0.1% SDS for 30 minutes at room temperature and then with 1.times.SSC/0.1% SDS for 30 minutes at 45.degree. C.

19. A cell in culture containing the isolated DNA of claim 18.

20. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 18.

21. The isolated DNA of claim 18, wherein the DNA is single-stranded.

22. The single-stranded isolated DNA of claim 21, wherein the DNA is detectably labeled.

23. A vector comprising the isolated DNA of claim 18.

24. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 18; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

25. An isolated DNA comprising a sequence that hybridizes under conditions of high stringency to a probe the sequence of which consists of the coding sequence of SEQ ID NO: 4, or a sequence complementary to the coding sequence of SEQ ID NO: 4, wherein the DNA encodes a polypeptide that binds to parathyroid hormone or parathyroid hormone-related protein, and wherein conditions of high stringency include hybridizing at 42.degree. C. for 18 24 h in a solution comprising 50% formamide, 4.times. saline sodium citrate (SSC), 2.times. Denhardt's solution, 10% Dextran sulphate and 100 .mu.g/ml salmon sperm DNA and washing with 2.times.SSC/0.1% SDS for 30 minutes at room temperature and then with 1.times.SSC/0.1% SDS for 30 minutes at 45.degree. C.

26. A cell in culture containing the isolated DNA of claim 25.

27. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 25.

28. The isolated DNA of claim 25, wherein the DNA is single-stranded.

29. The single-stranded isolated DNA of claim 28, wherein the DNA is detectably labeled.

30. A vector comprising the isolated DNA of claim 25.

31. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 25; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

32. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20.

33. The isolated DNA of claim 32, wherein the nucleotide sequence comprises the coding sequence of SEQ ID NO:1.

34. The isolated DNA of claim 32, wherein the nucleotide sequence comprises the coding sequence of SEQ ID NO:2.

35. The isolated DNA of claim 32, wherein the nucleotide sequence comprises the coding sequence of SEQ ID NO: 3.

36. A cell in culture containing the isolated DNA of claim 32.

37. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 32.

38. The isolated DNA of claim 32, wherein the DNA is single-stranded.

39. The single-stranded isolated DNA of claim 38, wherein the DNA is detectably labeled.

40. A vector comprising the isolated DNA of claim 32.

41. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 32; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

42. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising SEQ ID NO: 21.

43. The isolated DNA of claim 42, wherein the nucleotide sequence comprises the coding sequence of SEQ ID NO:4.

44. A cell in culture containing the isolated DNA of claim 42.

45. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 42.

46. The isolated DNA of claim 42, wherein the DNA is single-stranded.

47. The single-stranded isolated DNA of claim 46, wherein the DNA is detectably labeled.

48. A vector comprising the isolated DNA of claim 42.

49. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 42; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

50. An isolated DNA comprising a nucleotide sequence encoding a polypeptide consisting of SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20.

51. A cell in culture containing the isolated DNA of claim 42.

52. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 50.

53. The isolated DNA of claim 50, wherein the DNA is single-stranded.

54. The single-stranded isolated DNA of claim 53, wherein the DNA is detectably labeled.

55. A vector comprising the isolated DNA of claim 50.

56. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 50; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

57. An isolated DNA comprising a nucleotide sequence encoding a polypeptide consisting of SEQ ID NO:21.

58. A cell in culture containing the isolated DNA of claim 57.

59. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 57.

60. The isolated DNA of claim 57, wherein the DNA is single-stranded.

61. The single-stranded isolated DNA of claim 60, wherein the DNA is detectably labeled.

62. A vector comprising the isolated DNA of claim 57.

63. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 57; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

64. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising an extracellular domain of SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20.

65. A cell in culture containing the isolated DNA of claim 64.

66. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 64.

67. The isolated DNA of claim 64, wherein the DNA is single-stranded.

68. The single-stranded isolated DNA of claim 67, wherein the DNA is detectably labeled.

69. A vector comprising the isolated DNA of claim 64.

70. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 64; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

71. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising an extracellular domain of SEQ ID NO:21.

72. A cell in culture containing the isolated DNA of claim 71.

73. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 71.

74. The isolated DNA of claim 71, wherein the DNA is single-stranded.

75. The single-stranded isolated DNA of claim 74, wherein the DNA is detectably labeled.

76. A vector comprising the isolated DNA of claim 71.

77. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 71; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

78. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising SEQ ID NO:18, SEQ ID NO:19 or SEQ ID NO:20 with at least one conservative amino acid substitution, wherein the polypeptide binds parathyroid hormone or parathyroid hormone-related protein.

79. A cell in culture containing the isolated DNA of claim 78.

80. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 78.

81. The isolated DNA of claim 78, wherein the DNA is single-stranded.

82. The single-stranded isolated DNA of claim 81, wherein the DNA is detectably labeled.

83. A vector comprising the isolated DNA of claim 78.

84. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 78; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

85. An isolated DNA comprising a nucleotide sequence encoding a polypeptide comprising SEQ ID NO:21 with at least one conservative amino acid substitution, wherein the polypeptide binds parathyroid hormone or parathyroid hormone-related protein.

86. A cell in culture containing the isolated DNA of claim 85.

87. An essentially homogenous population of cells in culture, each of which comprises the isolated DNA of claim 85.

88. The isolated DNA of claim 85, wherein the DNA is single-stranded.

89. The single-stranded isolated DNA of claim 88, wherein the DNA is detectably labeled.

90. A vector comprising the isolated DNA of claim 85.

91. A method of producing a polypeptide, the method comprising the steps of: (a) providing a cell comprising the isolated DNA of claim 85; and (b) culturing the cell under conditions that permit expression of a polypeptide from the isolated DNA, to thereby produce the polypeptide.

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