Claims for Patent: 7,294,336

Summary for Patent: 7,294,336

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:	11/362,267
Patent Claims:	1. A method of preventing a RSV infection or a symptom thereof in a human subject, said method comprising administering to the subject a prophylactically effective amount of 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 does not comprise mannitol. 2. A method of preventing a RSV infection or a symptom thereof in a human subject, said method comprising administering to the subject a prophylactically effective amount of an aqueous palivizumab formulation comprising, in an aqueous carrier: (a) at least 75 mg/mi 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 does not comprise mannitol. 3. A method of preventing a RSV infection or a symptom thereof in a subject, said method comprising administering to the subject a prophylactically effective amount of an aqueous palivizumab formulation comprising at least 40 mg/ml of 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. 4. The method 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 55 mg/mi, at least 60 mg/ml, at least 70 mg/ml, or at least 75 mg/ml. 5. The method of claim 1 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 75 mg/mi, at least 80 mg/mi or at least 85 mg/ml. 6. The method of claim 1 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 90 mg/mi, at least 95 mg/ml or at least 100 mg/ml. 7. The method of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is at a concentration of at least 125 mg/mi or at least 150 mg/ml. 8. The method of claim 1 or 3, wherein said formulation comprises histidine at a concentration of about 1 mM to about 100 mM. 9. The method of claim 1 or 3, wherein said formulation comprises histidine at a concentration of about 10 mM to about 50 mM. 10. The method of claim 1 or 3, wherein said formulation is substantially free of surfactants and inorganic salts. 11. The method of claim 2, wherein said formulation is substantially free of surfactants and inorganic salts. 12. The method of claim 10, wherein said formulation is substantially free of other excipients. 13. The method of claim 11, wherein said formulation is substantially free of other excipients. 14. The method of claim 1 or 3, wherein said formulation further comprises an excipient other than a surfactant. 15. The method of claim 10, wherein said formulation further comprises an excipient other than a surfactant. 16. The method of claim 2 or 11, wherein said formulation further comprises an excipient other than a surfactant. 17. The method of claim 14, wherein said excipient is glycine. 18. The method of claim 15, wherein said excipient is glycine. 19. The method of claim 17, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 20. The method of claim 18, wherein glycine is at a concentration of less than 150 mM, less than 100 mM or less than 50 mM. 21. The method of claim 19, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 22. The method of claim 20, wherein glycine is at a concentration of less than 3 mM or less than 2 mM. 23. The method of claim 1 or 3, wherein said formulation has a pH of between about 5.5 to about 7.0. 24. The method of claim 23, wherein said formulation has a pH of between about 5.5 to about 6.5. 25. The method of claim 2, wherein histidine is at a concentration of about 25 mM and glycine is at a concentration of 1.6 mM. 26. The method of claim 2, wherein said formulation has a pH of between about 5.5 to about 7.0. 27. The method of claim 2, wherein said formulation has a pH of about 5.5 to about 6.5. 28. The method of claim 2, wherein said formulation has a pH of about 6.0. 29. The method of claim 25, wherein said formulation has a pH of about 6.0. 30. The method of claim 14, wherein said excipient is a saccharide. 31. The method of claim 30, wherein said saccharide is sucrose. 32. The method of claim 14, wherein said excipient is a polyol other than mannitol. 33. The method of claim 32, wherein said polyol is polysorbate. 34. The method of claim 1, 2 or 3, wherein said aqueous carrier is distilled water. 35. The method of claim 28, wherein said aqueous carrier is distilled water. 36. The method of claim 29, wherein said aqueous carrier is distilled water. 37. The method of claim 1, 2 or 3, wherein said formulation is homogenous. 38. The method 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 High Performance Size Exclusion Chromatography (HPSEC). 39. The method 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 method of claim 1, 2 or 3, wherein said palivizumab or palivizumab antigen-binding fragment is stable at 40.degree. C. for at least 3 years as determined by HPSEC. 41. The method 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 method 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 method of claim 1 or 2, which has been prepared by a process that does not have a drying step. 44. The method of claim 1 or 2, which has been prepared by a process that does not have a lyophilization step. 45. The method of claim 10, wherein said formulation comprises histidine at a concentration of 1 mM to 100 mM. 46. The method of claim 45, wherein said formulation is substantially free of other excipients. 47. The method of claim 8, wherein said formulation has a pH of between about 5.5 to about 7.0. 48. The method of claim 45, wherein said formulation has a pH of between about 5.5 to about 7.0. 49. The method of claim 46, wherein said formulation has a pH of between about 5.5 to about 7.0. 50. The method of claim 29, wherein said formulation is substantially free of surfactants, inorganic salts and other excipients. 51. The method of claim 1, 2 or 3, wherein said formulation is administered parenterally or intranasally. 52. The method of claim 29, wherein said formulation is administered parenterally or intranasally. 53. The method of claim 51, wherein said prophylactically effective amount is a dose of 15 mg/kg. 54. The method of claim 52, wherein said prophylactically effective amount is a dose of 15 mg/kg. 55. The method of claim 53, further comprising administering another therapy. 56. The method of claim 54, further comprising administering another therapy. 57. The method of claim 1, 2, 3 or 29, wherein said human subject is a human in an nursing home, a human in an orphanage, a human with cystic fibrosis, bronchopulmonary dysplasia, congenital heart disease, congenital immunodeficiency or acquired immunodeficiency, or a human who has had a bone marrow transplant. 58. The method of claim 1, 2, 3 or 29, wherein said human subject is a human infant. 59. The method of claim 1, 2, 3 or 29, wherein said human subject is a human infant born prematurely or a human infant susceptible to an RSV infection. 60. The method of any one of claims 1, 2, 3 or 29, wherein said formulation is administered by a nebulizer or inhaler.

Details for Patent 7,294,336

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