Composition, method, and kit for alpha-1 proteinase inhibitor

Abstract

The present invention provides compositions comprising API and at least one amino acid, in particular a liquid API formulation comprising amino acids, and methods and kits related thereto. These amino acids when incorporated into the API composition afford stability to the API formulation.

We claim: 
     
         1 . A composition comprising:
 (a) an alpha 1-proteinase inhibitor (API); and   (b) at least one amino acid.   
     
     
         2 . The composition of  claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient such that the API retains at least 50% of its activity when the composition is exposed to a temperature for a period of time. 
     
     
         3 . The composition of  claim 2 , wherein the temperature is about 5° C. to about 40° C. 
     
     
         4 . The composition of  claim 2 , wherein the time is at least about 6 months. 
     
     
         5 . The composition of  claim 1 , wherein the at least one amino acid is a neutral or a hydrophilic amino acid. 
     
     
         6 . The composition of  claim 1 , wherein the at least one amino acid is selected from the group consisting of alanine, threonine, serine, hydroxyproline, glycine, proline, leucine, and histidine. 
     
     
         7 . The composition of  claim 1 , wherein the amino acid is alanine. 
     
     
         8 . The composition of  claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount of about 0.01 M to about 3 M. 
     
     
         9 . The composition of  claim 1  further comprising one or more excipients. 
     
     
         10 . The composition of  claim 1 , wherein the one or more excipients is selected from the group consisting of: sucrose, mannitol, glycerol, sorbitol, dextran, trehalose, hydroxyethyl starch (HES), and 1,2-propanediol. 
     
     
         11 . The composition of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         12 . The composition of  claim 1 , wherein the composition is suitable for intravenous administration to a subject. 
     
     
         13 . The composition of  claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient to maintain total protein aggregation at less than about 5% following exposure of the composition to a temperature for a period of time. 
     
     
         14 . The composition of  claim 13 , wherein the temperature is about 25° C., wherein the period of time is about 6 months. 
     
     
         15 . The composition of  claim 13 , wherein the temperature is about 5° C., wherein the period of time is about 6 months. 
     
     
         16 . The composition of  claim 15 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient to maintain total protein aggregation at less than about 2% following exposure of the composition to the temperature for the period of time. 
     
     
         17 . The composition of  claim 13 , wherein the pH of the composition is about 6.3 to about 7.4. 
     
     
         18 . The composition of  claim 13 , wherein the pH of the composition is about 6.7 to about 7.1. 
     
     
         19 . The composition of  claim 1 , wherein the composition is in lyophilized form. 
     
     
         20 . A kit comprising the composition of  claim 1  as a pharmaceutical composition suitable for intravenous administration.