Hydroxyethyl starch-containing polypeptide compositions

Abstract

The invention provides compositions containing hydroxyethyl starch and polypeptides, including therapeutic polypeptides such as interleukin-11, that provide for enhanced stability of the polypeptide following storage at room temperature or elevated temperatures.

1 . A composition comprising a polypeptide, a disaccharide and a hydroxyethyl starch wherein said composition has a glass transition temperature of at least 60° C. 
     
     
         2 . The composition of  claim 1 , wherein said polypeptide does not include an N-linked glycosylation site. 
     
     
         3 . The composition of  claim 1 , wherein said polypeptide does not include a cysteine amino acid. 
     
     
         4 . The composition of  claim 1 , wherein said polypeptide has a basic pd. 
     
     
         5 . The composition of  claim 1 , wherein said composition has a glass transition temperature of at least 75° C. 
     
     
         6 . The composition of  claim 1 , wherein said disaccharide is selected from the group consisting of trehalose and sucrose. 
     
     
         7 . The composition of  claim 6 , wherein said disaccharide is present at a concentration of 0.5% to 6.0%. 
     
     
         8 . The composition of  claim 6 , wherein said disaccharide is present at a concentration of 1.5% to 6.0%. 
     
     
         9 . The composition of  claim 6 , wherein said disaccharide is present at a concentration of 2.5% to 5.0%. 
     
     
         10 . The composition of  claim 1 , wherein said hydroxyethyl starch is present at a concentration of 0.5% to 3.5%. 
     
     
         11 . The composition of  claim 1 , wherein said hydroxyethyl starch is present at a concentration of 2.5%. 
     
     
         12 . The composition of  claim 1 , wherein said composition is stable for at least 9 months when said composition is stored at 60° C. 
     
     
         13 . A composition comprising an IL-11 polypeptide, a disaccharide, and hydroxyethyl starch. 
     
     
         14 . The composition of  claim 13 , wherein said IL-11 polypeptide is stable for at least 9 months when said composition is stored at 60° C. 
     
     
         15 . The composition of  claim 13 , wherein said disaccharide is selected from the group consisting of trehalose and sucrose. 
     
     
         16 . The composition of  claim 13 , wherein said disaccharide is present in said composition is present at a concentration of 0.5% to 6.0%. 
     
     
         17 . The composition of  claim 13 , wherein said disaccharide is present in said composition at a concentration of 1.5 to 6.0%. 
     
     
         18 . The composition of  claim 13 , wherein said disaccharide is present in said composition at a concentration of about 2.5% to 5.0%. 
     
     
         19 . The composition of  claim 15 , wherein said disaccharide is trehalose. 
     
     
         20 . The composition of  claim 15 , wherein said disaccharide is sucrose. 
     
     
         21 . The composition of  claim 15 , wherein said hydroxyethyl starch is present in said composition at a concentration of 0.5% to 3.5%. 
     
     
         22 . The composition of  claim 15 , wherein said hydroxyethyl starch is present in said composition at a concentration of 1.5% to 3.5%. 
     
     
         23 . The composition of  claim 15 , wherein said hydroxyethyl starch is present in said composition at a concentration of 2.5%. 
     
     
         24 . The composition of  claim 13  wherein said sucrose is present in said composition at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present in said composition at a concentration of 2.5%. 
     
     
         25 . The composition of  claim 13  wherein said trehalose is present in said composition at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present in said composition at a concentration of 2.5%. 
     
     
         26 . A method of treating or preventing inflammation in a subject, the method comprising administering to said subject a composition comprising IL-11, a disaccharide, and hydroxyethyl starch. 
     
     
         27 . The method of  claim 26 , wherein said subject is a human. 
     
     
         28 . The method of  claim 26 , wherein said inflammation is associated with inflammatory bowel disease. 
     
     
         29 . The method of  claim 28 , wherein said inflammatory bowel disease is Crohn's disease. 
     
     
         30 . The method of  claim 26 , wherein said disaccharide is sucrose present at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present at a concentration of 2.5%. 
     
     
         31 . The method of  claim 26 , wherein said disaccharide is trehalose present at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present at a concentration of 2.5%. 
     
     
         32 . A method of enhancing an immune response in a subject, the method comprising administering to said subject a composition comprising IL-11, a disaccharide, and hydroxyethyl starch. 
     
     
         33 . The method of  claim 32 , wherein said subject is a human. 
     
     
         34 . The method of  claim 33 , wherein said composition is administered in a route selected from the group consisting of intramuscular, intravenous, intraarterial, intradermal, intraperitoneal and subcutaneous delivery. 
     
     
         35 . The method of  claim 32  wherein said disaccharide is sucrose present at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present at a concentration of 2.5%. 
     
     
         36 . The method of  claim 32  wherein said disaccharide is trehalose present at a concentration of 2.5% to 5.0%, and said hydroxyethyl starch is present at a concentration of 2.5%. 
     
     
         37 . A method of increasing platelet production in a subject, the method comprising administering a subject in need thereof a composition comprising a polypeptide, a disaccharide, and hydroxyethyl starch. 
     
     
         38 . The method of  claim 37 , wherein said subject is a human. 
     
     
         39 . The method of  claim 38 , wherein said subject has or is at risk for developing a tumor. 
     
     
         40 . The method of  claim 39 , wherein said tumor is a solid tumor or a lymphoma. 
     
     
         41 . The method of  claim 39 , wherein said subject is undergoing treatment for said tumor.