Highly Concentrated Stabilized Igm Solution

Abstract

The present inventors discovered that stable and highly concentrated IgM solutions can be prepared by using, as an additive, a compound comprising a polyvalent cationic ion, such as magnesium chloride or arginine hydrochloride, to suppress IgM aggregation in solutions.

1 . A solution wherein a high concentration of immunoglobulin is stabilized, and wherein the immunoglobulin is IgM.  
     
     
         2 . The solution of  claim 1 , comprising IgM at a concentration higher than 1 mg/mL.  
     
     
         3 . The solution of  claim 1 , which is an aqueous solution.  
     
     
         4 . The solution of  claim 1 , which is a pharmaceutical formulation.  
     
     
         5 . The solution of  claim 1 , comprising a polyvalent cationic ion.  
     
     
         6 . The solution of  claim 5 , comprising the polyvalent cationic ion at a concentration of 1 mM to 1,000 mM.  
     
     
         7 . The solution of  claim 5 , wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.  
     
     
         8 . The solution of  claim 5 , further comprising sugars.  
     
     
         9 . The solution of  claim 1 , which is pH 5 to pH 8.  
     
     
         10 . The solution of  claim 1 , wherein the solution does not intrinsically comprise human-derived proteins other than IgM.  
     
     
         11 . The solution of  claim 1 , wherein the solution does not intrinsically comprise proteins other than IgM.  
     
     
         12 . A pharmaceutical formulation obtained by freezing or lyophilizing the solution of  claim 1 .  
     
     
         13 . A method for stabilizing a solution comprising a high concentration of immunoglobulin, wherein the immunoglobulin is IgM and wherein the method comprises adding a polyvalent cationic ion to the solution.  
     
     
         14 . The method of  claim 13 , wherein the solution comprises IgM at a concentration higher than 1 mg/mL.  
     
     
         15 . The method of  claim 13 , wherein the solution is an aqueous solution.  
     
     
         16 . The method of  claim 13 , wherein the solution is a pharmaceutical formulation.  
     
     
         17 . The method of  claim 13 , which comprises adding a polyvalent cationic ion to the solution such that the solution comprises the polyvalent cationic ion at a concentration of 1 mM to 1,000 mM.  
     
     
         18 . The method of  claim 13 , wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.  
     
     
         19 . The method of  claim 13 , further comprising addition of sugars.  
     
     
         20 . The method of  claim 13 , wherein the pH of the solution is 5 to 8.  
     
     
         21 . The method of  claim 13 , wherein the solution does not intrinsically comprise human-derived proteins other than IgM.  
     
     
         22 . The method of  claim 13 , wherein the solution does not intrinsically comprise proteins other than IgM.  
     
     
         23 . A method for stabilizing a pharmaceutical formulation, which comprises the steps of: 
 (a) performing the method of  claim 13;  and    (b) freezing or lyophilizing the solution stabilized in step (a).    
     
     
         24 . A method for producing a solution comprising a high concentration of stabilized immunoglobulin, wherein the immunoglobulin is IgM and wherein the method comprises the step of adding a polyvalent cationic ion to the solution.  
     
     
         25 . The method of  claim 24 , wherein the solution comprises IgM at a concentration higher than 1 mg/mL.  
     
     
         26 . The method of  claim 24 , wherein the solution is an aqueous solution.  
     
     
         27 . The method of  claim 24 , wherein the solution is a pharmaceutical formulation.  
     
     
         28 . The method of  claim 24 , which comprises the step of adding a polyvalent cationic ion to the solution such that the solution comprises the polyvalent cationic ion at a concentration of 1 mM to 1000 mM.  
     
     
         29 . The method of  claim 24 , wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.  
     
     
         30 . The method of  claim 24 , which further comprises the step of adding sugars.  
     
     
         31 . The method of  claim 24 , wherein the pH of the solution is 5 to 8.  
     
     
         32 . The method of  claim 24 , wherein the solution essentially does not comprise human-derived proteins other than IgM.  
     
     
         33 . The method of  claim 24 , wherein the solution essentially does not comprise proteins other than IgM.  
     
     
         34 . A solution which is produced by the method of  claim 24 .  
     
     
         35 . A method for producing a pharmaceutical formulation, wherein the method comprises the steps of: 
 (a) performing the method of  claim 24;  and    (b) freezing or lyophilizing the solution produced in step (a).