Stabilized liquid anti-RSV antibody formulations
View Patent ↗The present invention provides liquid formulations of SYNAGIS® 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® or an antigen-binding fragment thereof, even during long periods of storage. In particular, the present invention provides liquid formulations of SYNAGIS® 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.
1. A method for preventing a symptom of a respiratory syncytial virus (RSV) infection, comprising administering intramuscularly to a human infant 15 mg/kg of an aqueous palivizumab formulation comprising, in distilled water: (a) 103±3 mg/ml of palivizumab or an antigen-binding fragment thereof; (b) histidine at a concentration of about 25 mM, and (c) glycine at a concentration of about 1.6 mM, wherein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 2° C. to 8° C. for 15 months as determined by high performance size exclusion chromatography (HPSEC) and the formulation has a pH of about 6.0.
2. A method for preventing a symptom of a respiratory syncytial virus (RSV) infection, comprising administering intramuscularly to a human infant 15 mg/kg of an aqueous palivizumab formulation comprising, in distilled water: (a) about 100 mg/ml of palivizumab or an antigen-binding fragment thereof; (b) histidine at a concentration of about 25 mM, and (c) glycine at a concentration of about 1.6 mM, wherein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 38° C. to 42° C. for at least 60 days as determined by HPSEC.
3. The method of claim 1 or 2 , wherein the formulation is substantially free of surfactants and inorganic salts.
4. The method of claim 1 or 2 , wherein the formulation is substantially free of surfactants, inorganic salts and other excipients.
5. The method of claim 1 or 2 , wherein the formulation does not contain mannitol.
6. The method of claim 1 or 2 , herein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 20° C. to 24° C. for at least 1 year as determined by HPSEC.
7. The method of claim 1 , wherein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 38° C. to 42° C. for at least 60 days as determined by HPSEC.
8. The method of claim 2 or 7 , wherein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 38° C. to 42° C. for no more than 120 days as determined by HPSEC.
9. The method of claim 1 or 2 , wherein the palivizumab or palivizumab antigen-binding fragment in the formulation is stable at 2° C. to 8° C. for at least 3 year as determined by HPSEC.
10. The method of claim 1 or 2 , wherein the aqueous palivizumab formulation contains no more than 3% aggregation by weight protein as measured by HPSEC.
11. The method of claim 1 or 2 , wherein the stable aqueous palivizumab formulation contains equal to or more than 98% of the total protein in a single peak as determined by HPSEC and contains no other single peaks having more than 2% of total protein each.
12. The method of claim 1 or 2 , wherein the human infant is at high risk for hospitalization for a RSV infection.
13. The method of claim 1 or 2 , wherein the human infant has bronchopulmonary dysplasia or a congenital heart disease.
14. The method of claim 1 or 2 , wherein the aqueous palivizumab formulation is administered once prior to the RSV season.
15. The method of claim 1 or 2 , wherein the aqueous palivizumab formulation is administered once a month during the RSV season.