Stable liquid pharmaceutical formulation of IgG antibodies

Abstract

This invention is directed to a stable liquid pharmaceutical formulation comprising a high concentration, e.g. 50 mg/ml or more, of antibody in about 20-60 mM succinate buffer or 30-70 mM histidine buffer, having pH from about pH 5.5 to about pH 6.5, about 0.01-0.1% polysorbate, and a tonicity modifier that contributes to the isotonicity of the formulation. This liquid formulation is stable at refrigerated temperature (2-8° C.) for at least 1 year, and preferably 2 years. This liquid formulation is suitable for subcutaneous injection. The preferred antibodies include Daclizumab, a humanized anti-IL-2 receptor monoclonal antibody; HAIL-12, a humanized anti-IL-12 monoclonal antibody; HuEP5C7, a humanized anti-L selectin monoclonal antibody; and Flintozumab, a humanized anti-gamma interferon monoclonal antibody.

What is claimed is:  
     
         1 . A stable liquid pharmaceutical formulation comprising: 
 about 20-60 mM succinate buffer having pH from about pH 5.5 to about pH 6.5,    about 0.01%-0.1% polysorbate,    a tonicity modifier that contributes to isotonicity of the formulation, and    greater than 50 mg/ml antibody.    
     
     
         2 . A stable liquid pharmaceutical formulation comprising: 
 about 30-70 mM histidine buffer having pH from about pH 5.5 to about pH 6.5,    about 0.01%-0.1% polysorbate,    a tonicity modifier that contributes to isotonicity of the formulation, and    greater than 50 mg/ml antibody.    
     
     
         3 . The liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said antibody concentration is greater than 100 mg/ml.  
     
     
         4 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said tonicity modifier is NaCl or MgCl 2 .  
     
     
         5 . The stable liquid pharmaceutical formulation according to  claim 4 , wherein said NaCl is at 75-150 mM.  
     
     
         6 . The stable liquid pharmaceutical formulation according to  claim 4 , wherein said MgCl 2  is at 1-100 mM.  
     
     
         7 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said pH is about pH 6.0 to 6.5.  
     
     
         8 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said polysorbate is at a concentration of about 0.02-0.04%.  
     
     
         9 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , further comprising 0.01 to 0.5% EDTA.  
     
     
         10 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said formulation is stable at about 2-8° C. for at least one year.  
     
     
         11 . The stable liquid pharmaceutical formulation according to  claim 1  or  2 , wherein said formulation is stable at about 23-27° C. for at least 6 months.  
     
     
         12 . A liquid pharmaceutical formulation comprising: 
 about 20-60 mM succinate buffer having pH of from about pH 5.5 to about pH 6.5,    about 0.01%-0.05% polysorbate,    about 75-150 mM sodium chloride, and    greater than 50 mg/ml antibody selected from the group consisting of Daclizumab, Flintozumab, HAIL-12, and HuEP5C7.    
     
     
         13 . A liquid pharmaceutical formulation comprising: 
 about 30-70 mM histidine buffer having pH of from about pH 5.5 to about pH 6.5,    about 0.01%-0.05% polysorbate,    about 75-150 mM sodium chloride, and    greater than 50 mg/ml antibody selected from the group consisting of Daclizumab, Flintozumab, HAIL-12, and HuEP5C7.