Claims
- 1. A method for directly identifying a non-endogenous compound as a compound having an activity selected from the group consisting of: inverse agonists, parallel agonists, and partial agonists, to a non-endogenous, constitutively activated version of known G protein-coupled receptor, said receptor comprising a transmembrane-6 region and an intracellular region, comprising the steps of:
(a) selecting a non-endogenous version of a known GPCR having an amino acid sequence selected from the group consisting of SEQ.ID.NO.:425; 38SEQ.ID.NO.:427; SEQ.ID.NO.:429; SEQ.ID.NO.:431;SEQ.ID.NO.:433; SEQ.ID.NO.:435; SEQ.ID.NO.:437;SEQ.ID.NO.:439; SEQ.ID.NO.:441; SEQ.ID.NO.:443;SEQ.ID.NO.:445; SEQ.ID.NO.:447; SEQ.ID.NO.:449;SEQ.ID.NO.:451; SEQ.ID.NO.:453; SEQ.ID.NO.:455;SEQ.ID.NO.:457; SEQ.ID.NO.:459; SEQ.ID.NO.:461;SEQ.ID.NO.:463; SEQ.ID.NO.:465; SEQ.ID.NO.:467;SEQ.ID.NO.:469; SEQ.ID.NO.:471; SEQ.ID.NO.:473;SEQ.ID.NO.:475; SEQ.ID.NO.:477; SEQ.ID.NO.:479;SEQ.ID.NO.:481; SEQ.ID.NO.:483; SEQ.ID.NO.:485;SEQ.ID.NO.:487; SEQ.ID.NO.:489; SEQ.ID.NO.:491;SEQ.ID.NO.:493; SEQ.ID.NO.:495; SEQ.ID.NO.:497;SEQ.ID.NO.:499; SEQ.ID.NO.:501; SEQ.ID.NO.:503;SEQ.ID.NO.:505; SEQ.ID.NO.:507; SEQ.ID.NO.:347;SEQ.ID.NO.:509; SEQ.ID.NO.:351; SEQ.ID.NO.:355;SEQ.ID.NO.:359; SEQ.ID.NO.:363; SEQ.ID.NO.:367;SEQ.ID.NO.:371; SEQ.ID.NO.:375; SEQ.ID.NO.:379;SEQ.ID.NO.:383; SEQ.ID.NO.:387; SEQ.ID.NO.:391;SEQ.ID.NO.:511; SEQ.ID.NO.:513; SEQ.ID.NO.:515;SEQ.ID.NO.:517; SEQ.ID.NO.:519; SEQ.ID.NO.:521;SEQ.ID.NO.:523; SEQ.ID.NO.:525; SEQ.ID.NO.:527;SEQ.ID.NO.:529; SEQ.ID.NO.:531; SEQ.ID.NO.:533;SEQ.ID.NO.:535; SEQ.ID.NO.:537; SEQ.ID.NO.:539;SEQ.ID.NO.:541; SEQ.ID.NO.:543; SEQ.ID.NO.:545;SEQ.ID.NO.:547; SEQ.ID.NO.:549: SEQ.ID.NO.:551;SEQ.ID.NO.:553; SEQ.ID.NO.:555; SEQ.ID.NO.:557;SEQ.ID.NO.:559; SEQ.ID.NO.:561: SEQ.ID.NO.:563:SEQ.ID.NO.:565; SEQ.ID.NO.:567; SEQ.ID.NO.:569;SEQ.ID.NO.:571; SEQ.ID.NO.:573; SEQ.ID.NO.:575;SEQ.ID.NO.:577; SEQ.ID.NO.:395; SEQ.ID.NO.:399;SEQ.ID.NO.:403; SEQ.ID.NO.:407; SEQ.ID.NO.:411;SEQ.ID.NO.:415; SEQ.ID.NO.:419; SEQ.ID.NO.:423;SEQ.ID.NO.:579; and SEQ.ID.NO.:581;(b) confirming that the selected non-endogenous GPCR of step (a) is constitutively active; (c) contacting a non-endogenous candidate compound with the non-endogenous, constitutively activated GPCR of step of (b); and (d) determining, by measurement of the compound efficacy at said contacted receptor, whether said non-endogenous compound having inverse agonist activity as an inverse agonist or agonist activity is an agonist to said receptor of step (b).
- 2. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:425.
- 3. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:427
- 4. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:429.
- 5. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:431.
- 6. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:433.
- 7. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:435.
- 8. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:437.
- 9. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:439.
- 10. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:441.
- 11. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:443.
- 12. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:445.
- 13. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:447.
- 14. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:449.
- 15. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:451.
- 16. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:453.
- 17. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:455.
- 18. The method of claim 1 wherein the non-endogenous GPCR of step (b)is an amino acid sequence having the sequence of SEQ.ID.NO.:457.
- 19. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:459.
- 20. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:461.
- 21. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:463.
- 22. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:465.
- 23. The method of claim 1 wherein the non-endogenous GPCR of 467.
- 24. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:469.
- 25. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:471.
- 26. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:473.
- 27. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:475.
- 28. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:477.
- 29. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:479.
- 30. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:481.
- 31. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:483.
- 32. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:485.
- 33. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:487.
- 34. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:489.
- 35. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:491.
- 36. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:493.
- 37. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:495.
- 38. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:497.
- 39. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:499.
- 40. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:501.
- 41. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:503.
- 42. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:505.
- 43. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:507.
- 44. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:347.
- 45. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:509.
- 46. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:351.
- 47. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:355.
- 48. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:359.
- 49. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:361.
- 50. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:367.
- 51. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:371.
- 52. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:375.
- 53. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:379.
- 54. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:383.
- 55. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:387.
- 56. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:391.
- 57. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:511.
- 58. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:513.
- 59. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:515.
- 60. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:517.
- 61. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:519.
- 62. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:521.
- 63. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:523.
- 64. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:525.
- 65. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID).NO.:527.
- 66. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:529.
- 67. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:531.
- 68. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:533.
- 69. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:535.
- 70. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:537.
- 71. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:539.
- 72. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:541.
- 73. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:543.
- 74. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:545.
- 75. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:547.
- 76. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:549.
- 77. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:551.
- 78. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:553.
- 79. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:555.
- 80. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:557.
- 81. The method of claim 1 wherein the non-endogenous GPCR of step b is step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:559.
- 82. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:561.
- 83. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:563.
- 84. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:565.
- 85. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:567.
- 86. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:569.
- 87. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:571.
- 88. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:573.
- 89. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:575.
- 90. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:577.
- 91. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:395.
- 92. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:399.
- 93. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:403.
- 94. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:407.
- 95. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:411.
- 96. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:415.
- 97. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:419.
- 98. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:423.
- 99. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.ID.NO.:579.
- 100. The method of claim 1 wherein the non-endogenous GPCR of step (b) is an amino acid sequence having the sequence of SEQ.I).NO.:581.
- 101. The method of claim 1 further comprising the following step:
assessing, by using an endogenous ligand based assay, the impact of the non-endogenous compound of step (d) on the binding of an endogenous ligand for the known GPCR version of the non-endogenous version of said known GPCR of step (a) with said known GPCR.
- 102. The method of claim 101 wherein said non-endogenous compound is an allosteric modulator of said known GPCR.
Parent Case Info
[0001] This patent application claims priority from U.S. Provisional Application No. 60/195,747, filed with the United States Patent and Trademark Office on Apr. 7, 2000; and is related to U.S. Ser. No. 09/170,496, filed with the United States Patent and Trademark Office on Oct. 13, 1998, each of which is incorporated in its entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
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60195747 |
Apr 2000 |
US |