Stabilized liquid anti-RSV antibody formulations
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 process for the preparation of a high concentration stable aqueous palivizumab formulation, comprising diafiltering about 70 mg/mL, about 80 mg/mL, about 90 mg/mL, about 100 mg/mL or about 150 mg/mg/mL of palivizumab or an antigen-binding fragment thereof into a formulation buffer comprising about 1 mM to about 100 mM of histidine and less than 100 mM of glycine, wherein the palivizumab or palivizumab antigen-binding fragment is in an aqueous phase during the preparation of the stable aqueous palivizumab formualtion.
2. The process of claim 1 , wherein the formulation buffer comprises about 10 mM to about 50 mM of histidine, about 20 mM to about 30 mM of histidine, about 23 mM to about 27 mM of histidine, or about 25 mM histidine.
3. The process of claim 1 , wherein the formulation buffer comprises less than 150 mM glycine, less than 100 mM glycine, less than 50 mM glycine, less than 3 mM glycine, less than 2 mM glycine, or 1.6 mM of glycine.
4. The process of claim 2 , wherein the formulation buffer comprises less than 150 mM glycine, less than 100 mM glycine, less than 50 mM glycine, less than 3 mM glycine, less than 2 mM glycine, or 1.6 mM of glycine.
5. The process of claim 1 , wherein the stable aqueous 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.
6. The process of claim 2 , wherein the stable aqueous 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.
7. The process of claim 3 , wherein the stable aqueous formulation has a pH of about 5.5 to about 6.5, about 5.8 to about 6.2, or about 6.0.
8. The process of claim 4 , wherein the stable aqueous formulation has a pH of about 5.5 to about 6.5, about 5.8 to about 6.2, or about 6.0.
9. The process of claim 1 , wherein the process further comprises sterilization of the high concentration stable aqueous palivizumab formulation.
10. The process of claim 2 , wherein the process further comprises sterilization of the high concentration stable aqueous palivizumab formulation.
11. The process of claim 1 , wherein the process comprises purification of palivizumab or palivizumab antigen-binding fragment from conditioned medium and concentration of the palivizumab or palivizumab antigen-binding fragment before diafiltering the palivizumab or palivizumab antigen-binding fragment into the formulation buffer.
12. The process of claim 2 , wherein the process comprises purification of palivizumab or palivizumab antigen-binding fragment from conditioned medium and concentration of the palivizumab or palivizumab antigen-binding fragment before diafiltering the palivizumab or palivizumab antigen-binding fragment into the formulation buffer.
13. The process of claim 1 , wherein the palivizumab or palivizumab antigen-binding fragment is diafiltrated into 1 mL of the formulation buffer.
14. The process of claim 2 , wherein the palivizumab or palivizumab antigen-binding fragment is diafiltrated into 1 mL of the formulation buffer.
15. The process of claim 1 , wherein the high concentration stable aqueous palivizumab formulation contains no more than 3% aggregation by weight protein as measured by HPSEC.
16. The process of claim 2 , wherein the high concentration stable aqueous palivizumab formulation contains no more than 3% aggregation by weight protein as measured by HPSEC.
17. The process of claim 1 , wherein the high concentration stable aqueous palivizumab formulation contains equal to or more than 98% of the total protein in a single peak as determined by HSPEC and contains no other single peaks having more than 2% of total protein each.
18. The process of claim 2 , wherein the high concentration stable aqueous palivizumab formulation contains equal to or more than 98% of the total protein in a single peak as determined by HSPEC and contains no other single peaks having more than 2% of total protein each.
19. The process of claim 1 , which does not involve a drying step.
20. The process of claim 2 , which does not involve a drying step.