Claims for Patent: 7,132,100

Summary for Patent: 7,132,100

Title:	Stabilized liquid anti-RSV antibody formulations
Abstract:	The present invention provides liquid formulations of SYNAGIS.RTM. or an antigen-binding fragment thereof that immunospecifically bind to a respiratory syncytial virus (RSV) antigen, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of SYNAGIS.RTM. or an antigen-binding fragment thereof, even during long periods of storage. In particular, the present invention provides liquid formulations of SYNAGIS.RTM. or an antigen-binding fragment thereof which immunospecifically binds to a RSV antigen, which formulations are substantially free of surfactant, inorganic salts, and/or other common excipients. Furthermore, the invention provides method of preventing, treating or ameliorating symptoms associated with RSV infection utilizing liquid formulations of the present invention.
Inventor(s):	Oliver; Cynthia N. (N. Potomac, MD), Shane; Erica (McLean, VA), Isaacs; Benjamin S. (Andover, MA), Allan; Christian B. (Brookeville, MD), Chang; Stephen T. (Frederick, MD)
Assignee:	MedImmune, Inc. (Gaithersburg, MD)
Application Number:	10/461,904
Patent Claims:	1. An aqueous palivizumab formulation comprising, in an aqueous carrier: (a) at least 40 mg/ml of palivizumab, or an antigen-binding fragment thereof; and (b) histidine, wherein said formulation is substantially free of surfactants and inorganic salts. 2. An aqueous palivizumab formulation comprising, in an aqueous carrier: (a) at least 100 mg/ml of palivizumab, or an antigen-binding fragment thereof; (b) histidine at a concentration of about 20 mM to about 30 mM; and (c) glycine at a concentration of less than 2 mM, wherein said formulation is substantially free of surfactants, inorganic salts and other excipients. 3. An aqueous palivizumab formulation comprising palivizumab or an antigen-binding fragment thereof in an aqueous carrier, said formulation (i) having been prepared by a process in which, for each step of said process, said palivizumab or palivizumab-antigen-binding fragment is in an aqueous phase; and (ii) being suitable for injection in a human subject, and wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 40 mg/ml. 4. The formulation of claim 1 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 50 mg/ml, at least 60 mg/ml, at least 70 mg/ml, at least 80 mg/ml or at least 90 mg/ml. 5. The formulation of claim 1 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 6. The formulation of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 125 mg/ml. 7. The formulation of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 150 mg/ml. 8. The formulation of claim 1 or 3, wherein said formulation comprises histidine is at a concentration of about 1 mM to about 100 mM. 9. The formulation of claim 1 or 3, wherein said formulation comprises histidine is at a concentration of about 10 mM to about 50 mM. 10. The formulation of claim 1 or 3, wherein said formulation is substantially free of other excipients. 11. The formulation of claim 1 or 3, wherein said formulation further comprises an excipient other than a surfactant. 12. The formulation of claim 9, wherein said formulation further comprises an excipient other than a surfactant. 13. The formulation of claim 11, wherein the excipient is glycine. 14. The formulation of claim 12, wherein the excipient is glycine. 15. The formulation of claim 13, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 16. The formulation of claim 14, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 17. The formulation of claim 13, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 18. The formulation of claim 14, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 19. The formulation of claim 1 or 3, wherein said formulation has a pH of between about 5.5 to about 7.0. 20. The formulation of claim 19, wherein said formulation has a pH of between about 5.5 to about 6.5. 21. The formulation of claim 13, wherein said formulation has a pH of between about 5.5 to about 7.0. 22. The formulation of claim 14, wherein said formulation has a pH of between about 5.5 to about 7.0. 23. The formulation of claim 2, wherein histidine is at a concentration of about 25 mM and glycine is at a concentration of 1.6 mM. 24. The formulation of claim 2, wherein the formulation has a pH of between about 5.5 to about 7.0. 25. The formulation of claim 2, wherein the formulation has a pH of about 5.5 to about 6.5. 26. The formulation of claim 2, wherein the formulation has a pH of about 6.0. 27. The formulation of claim 11, wherein the excipient is a saccharide. 28. The formulation of claim 27, wherein the saccharide is sucrose. 29. The formulation of claim 28, wherein the sucrose is at a concentration of about 1% to about 20%. 30. The formulation of claim 11, wherein the excipient is a polyol other than mannitol. 31. The formulation of claim 30, wherein the polyol is polysorbate. 32. The formulation of claim 30, wherein the polyol is Tween, which is at a concentration of about 0.001% to about 1%. 33. The formulation of claim 1, 2 or 3, wherein the aqueous carrier is distilled water. 34. The formulation of claim 26, wherein the aqueous carrier is distilled water. 35. The formulation of claim 1 or 2, wherein the formulation is sterile. 36. The formulation of claim 26, wherein the formulation is sterile. 37. The formulation of claim 1 or 2, wherein the formulation is homogenous. 38. The formulation of claim 1, 2 or 3, wherein said palivizumab or an antigen-binding fragment thereof is stable at 40.degree. C. for at least 100 days as determined by HPSEC. 39. The formulation of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is stable at about ambient temperature for at least 1 year as determined by HPSEC. 40. The formulation of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is stable at 4.degree. C. for at least 3 years as determined by HPSEC. 41. The formulation of claim 1, 2 or 3, wherein less than 2% of said palivizumab or palivizumab antigen-binding fragment forms an aggregate as measured by HPSEC. 42. The formulation of claim 1 or 2 which has been prepared by a process in which, for each step of said process, said palivizumab or palivizumab antigen-binding fragment is in an aqueous phase. 43. The formulation of claim 1 or 2 which has been prepared by a process that does not have a drying step. 44. The formulation of claim 1 or 2 which has been prepared by a process that does not have a lyophilization step. 45. A pharmaceutical unit dosage form comprising the formulation of claim 1, 2 or 3, which dosage form is suitable for parenteral administration to a human and is in a suitable container. 46. A pharmaceutical unit dosage form comprising the formulation of claim 26, which dosage form is suitable for parenteral administration to a human and is in a suitable container. 47. The pharmaceutical unit dosage form of claim 45, wherein the formulation is suitable for subcutaneous, intravenous or intramuscular administration. 48. The pharmaceutical unit dosage form of claim 46, wherein the formulation is suitable for subcutaneous, intravenous or intramuscular administration. 49. A pharmaceutical unit dosage form comprising the formulation of claim 1, 2 or 3, which dosage form is suitable for aerosol administration to a human and is in a suitable container. 50. A pharmaceutical unit dosage form comprising the formulation of claim 26, which dosage form is suitable for aerosol administration to a human and is in a suitable container. 51. A sealed container comprising the formulation of claim 1, 2 or 3. 52. A sealed container comprising the formulation of claim 26. 53. A method of preventing a RSV infection or one or more symptoms thereof in a subject, said method comprising administering to the subject a prophylactically effective amount of the formulation of claim 1, 2 or 3. 54. A method of preventing a RSV infection or one or more symptoms thereof in a subject, said method comprising administering to the subject a prophylactically effective amount of the formulation of claim 26. 55. The method of claim 53, wherein the formulation is administered parenterally. 56. The method of claim 54, wherein the formulation is administered parenterally. 57. The method of claim 53, wherein the formulation is administered intramuscularly, intravenously, subcutaneously or intranasally. 58. The method of claim 54, wherein the formulation is administered intramuscularly, intravenously, subcutaneously or intranasally. 59. The method of claim 53, wherein the subject is a human. 60. The method of claim 54, wherein the subject is a human. 61. The formulation of claim 3, wherein said formulation comprises histidine is at a concentration of about 1 mM to about 100 mM and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 62. The formulation of claim 3, wherein said formulation comprises histidine is at a concentration of about 10 mM to about 50 mM and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 63. The formulation of claim 3, wherein the formulation is substantially free of other excipients and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 64. The formulation of claim 3, wherein the formulation further comprises an excipient other than a surfactant and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 65. The formulation of claim 3, wherein said formulation comprises histidine is at a concentration of about 10 mM to about 50 mM and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml, and wherein said formulation further comprises an excipient other than a surfactant. 66. The formulation of claim 64, wherein the excipient is glycine. 67. The formulation of claim 65, wherein the excipient is glycine. 68. The formulation of claim 66, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 69. The formulation of claim 67, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 70. The formulation of claim 66, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 71. The formulation of claim 67, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 72. The formulation of claim 1 or 3, wherein the formulation has a pH of between about 5.5 to about 7.0 and the palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 100 mg/ml. 73. The formulation of claim 72, wherein said formulation has a pH of between about 5.5 to about 6.5. 74. The formulation of claim 66, wherein said formulation has a pH of between about 5.5 to about 7.0. 75. The formulation of claim 67, wherein said formulation has a pH of between about 5.5 to about 7.0. 76. The formulation of claim 23, wherein the formulation has a pH of about 6.0. 77. The formulation of claim 64, wherein the excipient is a saccharide. 78. The formulation of claim 77, wherein the saccharide is sucrose. 79. The formulation of claim 78, wherein the sucrose is at a concentration of about 1% to about 20%. 80. The formulation of claim 64, wherein the excipient is a polyol other than mannitol. 81. The formulation of claim 80, wherein the polyol is polysorbate. 82. The formulation of claim 80, wherein the polyol is Tween, which is at a concentration of about 0.001% to about 1%. 83. The formulation of claim 76, wherein the aqueous carrier is distilled water. 84. The formulation of claim 76, wherein the formulation is sterile. 85. A sealed container comprising the formulation of claim 76. 86. A method of preventing a RSV infection or one or more symptoms thereof in a subject, said method comprising administering to the subject a prophylactically effective amount of the formulation of claim 76. 87. The method of claim 86, wherein the formulation is administered parenterally. 88. The method of claim 86, wherein the formulation is administered intramuscularly, intravenously, subcutaneously or intranasally. 89. The method of claim 86, wherein the subject is a human.

Details for Patent 7,132,100

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	For Injection	103770	06/19/1998		2022-06-14
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	Injection	103770	07/23/2004		2022-06-14