Immunoglobulin formulation and method of preparation thereof

Abstract

A stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, polysorbate 80, a buffer which inhibits polysorbate oxidation is described along with methods of making the preparation. Also described are formulations with high antibody concentrations which maintain fixed volumes and which may be used on patients of variable weight.

1 - 42 . (canceled) 
     
     
         43 . A stable, aqueous pharmaceutical formulation comprising from about 20 mg/ml to about 50 mg/ml of natalizumab, polysorbate 80 in an amount of about 0.02% (w/v), sodium chloride, and a buffer in the concentration range of 2 to 50 mM to provide buffering in the pH range of 3.0 to 7.0. 
     
     
         44 . The pharmaceutical formulation of  claim 43 , wherein the formulation has a pH between about 5.0 and about 6.5. 
     
     
         45 . The pharmaceutical formulation of  claim 44 , wherein the formulation has a pH of about 6.0±0.5. 
     
     
         46 . The pharmaceutical formulation according to  claim 43 , wherein the formulation is isotonic. 
     
     
         47 . The pharmaceutical formulation of any one of  claims 43 - 46 , wherein the buffer is selected from the group consisting of phosphate, histidine, citrate, acetate and succinate. 
     
     
         48 . The pharmaceutical formulation of  claim 47 , wherein the buffer comprises phosphate and/or histidine. 
     
     
         49 . The pharmaceutical formulation according to  claim 43 , further comprising a polyol, a sugar, and/or an amino acid. 
     
     
         50 . The pharmaceutical formulation according to  claim 49 , wherein said polyol is sorbitol and/or mannitol. 
     
     
         51 . The pharmaceutical formulation according to  claim 49 , wherein said sugar is sucrose and/or trehalose. 
     
     
         52 . The pharmaceutical formulation according to  claim 49 , wherein said amino acid is glycine. 
     
     
         53 . A stable, lyophilized pharmaceutical formulation comprising from about 20 mg/ml to about 50 mg/ml of natalizumab, polysorbate 80 in an amount of about 0.02% (w/v), and a buffer selected from the group consisting of histidine, citrate and succinate in the concentration range of 2 to 50 mM to provide buffering in the pH range of 3.0 to 7.0. 
     
     
         54 . The pharmaceutical formulation of  claim 53 , further comprising a polyol, a sugar, or combinations thereof to provide for stability and adjustment of tonicity. 
     
     
         55 . The pharmaceutical formulation according to  claim 53 , further comprising an amino acid such as glycine at levels of 10-1000 mM to prevent aggregation. 
     
     
         56 . The pharmaceutical formulation of  claim 53 , wherein the formulation has a pH between about 5.0 and about 6.5. 
     
     
         57 . The pharmaceutical formulation of  claim 56 , wherein the formulation has a pH of about 6.0±0.5. 
     
     
         58 . The pharmaceutical formulation of any one of  claims 53 - 57 , wherein the buffer is histidine. 
     
     
         59 . The pharmaceutical formulation of  claim 54 , wherein said formulation comprises 5 mM histidine, 20 mg/mL sucrose and 0.02% polysorbate 80, at pH 6. 
     
     
         60 . A method of treatment, comprising intravenously administering to a patient with multiple sclerosis or Crohn's disease a therapeutic amount of a stable, aqueous pharmaceutical formulation according to  claim 43 . 
     
     
         61 . A method of treatment, comprising reconstituting a therapeutic amount of a lyophilized pharmaceutical formulation according to  claim 53  in sterile water for injection and administering to a patient with multiple sclerosis or Crohn's disease.