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 liquid palivizumab formulation comprising: (a) at least 15 mg/ml of palivizumab, or an antigen-binding fragment thereof; and (b) histidine, wherein the histidine concentration is about 1 mM to about 100 mM, in an aqueous carrier, wherein said formulation is substantially free of surfactant, inorganic salts or other excipients.
2. The formulation of claim 1 , wherein the aqueous carrier is distilled water.
3. The formulation of claim 1 , wherein the formulation is sterile.
4. The formulation of claim 1 , wherein the formulation has a pH of about 5.0 to about 7.0, about 5.5 to about 6.5, about 5.8 to about 6.2, or about 6.0.
5. The formulation of claim 1 , wherein histidine is at concentration of about 10 to about 30 mM.
6. The formulation of claim 1 further comprising glycine.
7. The formulation of claim 6 , wherein glycine is at a concentration of less than 3.0 mM.
8. A pharmaceutical unit dosage form suitable for parenteral administration to a human which comprises the formulation of claim 1 in a suitable container.
9. A pharmaceutical unit dosage form suitable for aerosol administration to a human which comprises the formulation of claim 1 in a suitable container.
10. A sealed container comprising the formulation of claim 1 .
11. The formulation of claim 1 comprising, at least 30 mg/ml of palivizumab or an antigen-binding fragment thereof.
12. The formulation of claim 1 , wherein the histidine concentration is about 10 mM to about 50 mM, about 20 mM to about 30 mM, about 23 mM to about 27 mM, or about 25 mM.
13. The formulation of claim 6 , wherein glycine is at a concentration of less than 150 mM, less than 100 mM, less than 50 mM, less than 3 mM, less than 2 mM, less than 1.8 mM, or about 1.6 mM.
14. The formulation of claim 13 , wherein the histidine concentration is about 10 mM to about 50 mM, about 20 mM to about 30 mM, about 23 mM to about 27 mM, or about 25 mM.
15. The formulation of claim 1 comprising at least 20 mg/ml of palivizumab, or an antigen-binding fragment thereof.
16. The formulation of claim 1 comprising at least 25 mg/ml of palivizumab, or an antigen-binding fragment thereof.
17. The formulation of claim 1 comprising at least 35 mg/ml of palivizumab, or an antigen-binding fragment thereof.