Stable lyophilized pharmaceutical formulation of IgG antibodies

Abstract

This invention is directed to a stable lyophilized pharmaceutical formulation prepared by lyophilizing an aqueous formulation comprising a high concentration, e.g. 50 mg/ml or more, of an IgG antibody in about 5-25 mM histidine buffer having pH from about 5.5 to about 6.5, about 0.005%-0.03% polysorbate, sucrose, and optionally serine, and/or mannitol. This lyophilized formulation is stable at room temperature for at least 6 months, and preferably 1 year. This lyophilized formulation has a short reconstitution time of less than 2 minutes, and is suitable for parenteral administration such as intravenous, intramuscular, intraperitoneal, or subcutaneous injection. This invention is exemplified by the anti-IL2 receptor antibody.

What is claimed is:  
     
         1 . A stable lyophilized formulation prepared by lyophilizing an aqueous formulation comprising: 
 about 5-25 mM histidine buffer having a pH from 5.5 to about 6.5,    about 0.005%-0.03% polysorbate,    about 100-300 mM sucrose, and    greater than 50 mg/ml IgG antibody,    wherein said formulation is reconstitutable with a liquid to a particle-free solution containing greater than 50 mg/ml IgG antibody concentration within about 2 minutes or less.    
     
     
         2 . The stable lyophilized formulation according to  claim 1 , wherein said sucrose concentration is about 100-200 mM.  
     
     
         3  A stable lyophilized formulation prepared by lyophilizing an aqueous formulation comprising: 
 about 5-25 mM histidine buffer having a pH from about 5.5 to about 6.5,  
 about 0.005%-0.03% polysorbate,  
 about 110-130 mM sucrose,  
 about 20-45 mM mannitol, and  
 greater than 50 mg/ml IgG antibody,  
 wherein said lyophilized formulation is reconstitutable with liquid to a particle-free solution containing greater than 50 mg/ml IgG antibody concentration within about 2 minutes or less.  
 
     
     
         4 . A stable lyophilized formulation prepared by lyophilizing an aqueous formulation comprising: 
 about 5-25 mM histidine buffer having a pH from about 5.5 to about 6.5,    about 0.005% -0.03% polysorbate,    about 80-130 mM sucrose,    about 7-55 mM serine,    about 10-55 mM mannitol, and    greater than 50 mg/ml IgG antibody,    wherein said lyophilized formulation is reconstitutable with liquid to a particle-free solution containing greater than 50 mg/ml IgG antibody concentration within about 2 minutes or less.    
     
     
         5 . A stable lyophilized formulation prepared by lyophilizing an aqueous formulation comprising: 
 about 5-25 mM histidine buffer having a pH from about 5.5 to about 6.5,    about 0.005%-0.03% polysorbate,    about 100-130 mM sucrose,    about 15-55 mM serine, and    greater than 50 mg/ml IgG antibody,    wherein said lyophilized formulation is reconstitutable with liquid to a particle-free solution containing greater than 50 mg/ml IgG antibody concentration within about 2 minutes or less.    
     
     
         6 . The stable lyophilized formulation according to  claim 1 ,  3 ,  4  or  5 , wherein said IgG antibody is an anti-IL2 receptor antibody.  
     
     
         7 . The stable lyophilized formulation according to  claim 1 ,  3 ,  4  or  5 , wherein said formulation is stable at about 22-28° C. for at least 3 months.  
     
     
         8 . The stabilized lyophilized formulation according to  claim 1 ,  3 ,  4  or  5 , wherein said formulation is stable at about 2-8° C. for at least 1 year.  
     
     
         9 . The stable lyophilized formulation according to  claim 1 ,  3 ,  4 , or  5 , wherein said formulation is suitable for subcutaneous injection.