Claims for Patent: 11,162,500

Summary for Patent: 11,162,500

Title:	Stable liquid formulation of AMG 416 (etelcalcetide)
Abstract:	A liquid formulation comprising a peptide agonist of the calcium sensing receptor and method of preparing and using the formulation are provided.
Inventor(s):	Derek MacLean, Qun Yin
Assignee:	Amgen Inc
Application Number:	US16/430,322
Patent Claims:	1. A pharmaceutical formulation, comprising: etelcalcetide in aqueous solution, wherein the formulation has a pH of 2.0 to 5.0 and wherein etelcalcetide is present at a concentration of between 0.5 mg/mL to 15 mg/mL. 2. The pharmaceutical formulation of claim 1, wherein etelcalcetide at a concentration of between 1.0-10 mg/mL. 3. The pharmaceutical formulation of claim 2, wherein the formulation has a pH of 2.5 to 4.5. 4. The pharmaceutical formulation of claim 1, wherein the pH is maintained by a pharmaceutically acceptable buffer. 5. The pharmaceutical formulation of claim 4, wherein the buffer is succinate. 6. The pharmaceutical formulation of claim 4, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, histidine, acetate, ascorbate, glutamate, lactate, and phosphate. 7. The pharmaceutical formulation of claim 4, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer. 8. The pharmaceutical formulation of claim 7, wherein the pharmaceutically acceptable lactate buffer is sodium lactate, the pharmaceutically acceptable acetate buffer is sodium acetate and the pharmaceutically acceptable succinate buffer is sodium succinate. 9. The pharmaceutical formulation of claim 4, further comprising a pharmaceutically acceptable tonicity modifier. 10. The pharmaceutical formulation of claim 9, wherein the pharmaceutically acceptable tonicity modifier is selected from the group consisting of sodium chloride, potassium chloride, mannitol, glycerin, glycine, arginine, sucrose, dextrose, sorbitol, and sodium sulfate. 11. The pharmaceutical formulation of claim 9, wherein the tonicity modifier is sodium chloride. 12. The pharmaceutical formulation of claim 11, wherein the sodium chloride is present in the formulation at a concentration of between 7.0-10 mg/mL. 13. The pharmaceutical formulation of claim 9, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, malate, edentate, histidine, acetate, adipate, aconitate, ascorbate, benzoate, carbonate, bicarbonate, maleate, glutamate, lactate, phosphate, and tartarate. 14. The pharmaceutical formulation of claim 9, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, histidine, acetate, ascorbate, glutamate, lactate, and phosphate. 15. The pharmaceutical formulation of claim 9, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer. 16. The pharmaceutical formulation of claim 15, wherein the pharmaceutically acceptable lactate buffer is sodium lactate, the pharmaceutically acceptable acetate buffer is sodium acetate and the pharmaceutically acceptable succinate buffer is sodium succinate. 17. The pharmaceutical formulation of claim 16, wherein the pharmaceutically acceptable succinate buffer is sodium succinate. 18. The pharmaceutical formulation of claim 17, wherein the sodium succinate is present in the formulation at a concentration of between 1-20 mmol/L. 19. The pharmaceutical formulation of claim 1, wherein the etelcalcetide is present as etelcalcetide hydrochloride. 20. The pharmaceutical formulation of claim 19, further comprising a pharmaceutically acceptable buffer to maintain the pH. 21. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, malate, edentate, histidine, acetate, adipate, aconitate, ascorbate, benzoate, carbonate, bicarbonate, maleate, glutamate, lactate, phosphate, and tartarate. 22. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, histidine, acetate, ascorbate, glutamate, lactate, and phosphate. 23. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer. 24. The pharmaceutical formulation of claim 23, wherein the pharmaceutically acceptable lactate buffer is sodium lactate, the pharmaceutically acceptable acetate buffer is sodium acetate and the pharmaceutically acceptable succinate buffer is sodium succinate. 25. The pharmaceutical formulation of claim 24, wherein the pharmaceutically acceptable succinate buffer is sodium succinate. 26. The pharmaceutical formulation of claim 25, wherein the sodium succinate is present in the formulation at a concentration of between 1-20 mmol/L. 27. The pharmaceutical formulation of claim 19, further comprising a pharmaceutically acceptable tonicity modifier. 28. The pharmaceutical formulation of claim 27, wherein the tonicity modifier is selected from the group consisting of sodium chloride, potassium chloride, mannitol, glycerin, glycine, arginine, sucrose, dextrose, sorbitol, and sodium sulfate. 29. The pharmaceutical formulation of claim 28, wherein the tonicity modifier is sodium chloride. 30. The pharmaceutical formulation of claim 29, wherein the sodium chloride is present in the formulation at a concentration of between 7.0-10 mg/mL. 31. The pharmaceutical formulation of claim 19, further comprising a pharmaceutically acceptable buffer to maintain the pH and a pharmaceutically acceptable tonicity modifier. 32. The pharmaceutical formulation of claim 31, wherein the etelcalcetide hydrochloride is at a concentration of between 1.0-10 mg/mL. 33. The pharmaceutical formulation of claim 31, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer and wherein the pharmaceutically acceptable tonicity modifier is selected from the group consisting of sodium chloride, mannitol, glycine, arginine, and sodium sulfate. 34. The pharmaceutical formulation of claim 31, wherein the buffer is a succinate buffer comprising sodium succinate at a concentration of between 1-20 mmol/L and wherein the tonicity modifier is sodium chloride present in the formulation at a concentration of between 7.0-10 mg/mL. 35. The pharmaceutical formulation of claim 19, wherein the etelcalcetide hydrochloride is at a concentration of between 1.0-10 mg/mL. 36. The pharmaceutical formulation of claim 20 wherein the pharmaceutically acceptable buffer is a tartarate buffer. 37. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a citrate buffer. 38. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a malate buffer. 39. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is an edentate buffer. 40. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a histidine buffer. 41. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is an acetate buffer. 42. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is an adipate buffer. 43. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is an aconitate buffer. 44. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is an ascorbate buffer. 45. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a benzoate buffer. 46. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a carbonate buffer. 47. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a bicarbonate buffer. 48. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a maleate buffer. 49. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a glutamate buffer. 50. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a lactate buffer. 51. The pharmaceutical formulation of claim 20, wherein the pharmaceutically acceptable buffer is a phosphate buffer. 52. The pharmaceutical formulation of claim 1, further comprising a pharmaceutically acceptable tonicity modifier. 53. The pharmaceutical formulation of claim 52, wherein the tonicity modifier is NaCl. 54. A liquid pharmaceutical formulation, comprising: between 0.5 mg/mL to 15 mg/mL of etelcalcetide in aqueous solution, a pharmaceutically acceptable buffer that maintains at a pH of between about 2.5 to 5.0, and a pharmaceutically acceptable tonicity modifier. 55. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, malate, edentate, histidine, acetate, adipate, aconitate, ascorbate, benzoate, carbonate, bicarbonate, maleate, glutamate, lactate, phosphate, and tartarate. 56. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a buffer selected from the group consisting of succinate, citrate, histidine, acetate, ascorbate, glutamate, lactate, and phosphate. 57. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer. 58. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a succinate buffer. 59. The pharmaceutical formulation of claim 58, wherein the succinate buffer is sodium succinate. 60. The pharmaceutical formulation of claim 59, wherein the sodium succinate is present in the formulation at a concentration of between 1-20 mmol/L. 61. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable tonicity modifier is selected from the group consisting of sodium chloride, potassium chloride, mannitol, glycerin, glycine, arginine, sucrose, dextrose, sorbitol, and sodium sulfate. 62. The pharmaceutical formulation of claim 61, wherein the tonicity modifier is sodium chloride. 63. The pharmaceutical formulation of claim 62, wherein the sodium chloride is present in the formulation at a concentration of between 7.0-10 mg/mL. 64. The pharmaceutical formulation of claim 54, wherein etelcalcetide at a concentration of between 1.0-10 mg/mL. 65. The pharmaceutical formulation of claim 54, wherein the etelcalcetide is present as etelcalcetide hydrochloride. 66. The pharmaceutical formulation of claim 54, wherein the etelcalcetide hydrochloride is at a concentration of between 1.0-10 mg/mL. 67. The pharmaceutical formulation of claim 65, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer and wherein the pharmaceutically acceptable tonicity modifier is selected from the group consisting of sodium chloride, mannitol, glycine, arginine, and sodium sulfate. 68. The pharmaceutical formulation of claim 65, wherein the buffer is a succinate buffer comprising sodium succinate at a concentration of between 1-20 mmol/L and wherein the tonicity modifier is sodium chloride present in the formulation at a concentration of between 7.0-10 mg/mL. 69. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a lactate buffer, an acetate buffer or a succinate buffer and wherein the pharmaceutically acceptable tonicity modifier is selected from the group consisting of sodium chloride, mannitol, glycine, arginine, and sodium sulfate. 70. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a succinate buffer comprising sodium succinate at a concentration of between 1-20 mmol/L and wherein the pharmaceutically acceptable tonicity modifier is sodium chloride present in the formulation at a concentration of between 7.0-10 mg/mL. 71. The pharmaceutical formulation of claim 54, wherein the formulation has a pH of 2.5 to 4.5. 72. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a tartarate buffer. 73. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a citrate buffer. 74. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a malate buffer. 75. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is an edentate buffer. 76. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a histidine buffer. 77. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is an acetate buffer. 78. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is an adipate buffer. 79. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is an aconitate buffer. 80. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is an ascorbate buffer. 81. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a benzoate buffer. 82. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a carbonate buffer. 83. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a bicarbonate buffer. 84. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a maleate buffer. 85. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a glutamate buffer. 86. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a lactate buffer. 87. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a phosphate buffer. 88. The pharmaceutical formulation of claim 54, wherein the pharmaceutically acceptable buffer is a succinate buffer.