Alpha1 -antitrypsin compositions and methods of treating autoimmune diseases

Abstract

The specification provides compositions comprising chimeric proteins comprising AAT conjugated to an Fc region of an immunoglobulin. Methods for treating autoimmune disease, e.g., diabetes, e.g., Type 1 and Type 2 diabetes, are also provided.

1 . A recombinant polypeptide comprising an α1-antitrypsin polypeptide (AAT) conjugated to an Fc region of an immunoglobulin. 
     
     
         2 . The recombinant polypeptide of  claim 1 , wherein the AAT comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:2. 
     
     
         3 . The recombinant polypeptide of  claim 1 , wherein the immunoglobulin is selected from the group consisting of IgG, IgA, IgD, IgE, and IgM. 
     
     
         4 . The recombinant polypeptide of  claim 1 , wherein the immunoglobulin is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. 
     
     
         5 . The recombinant polypeptide of  claim 1 , wherein the Fc region of the immunoglobulin comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:4 or 6. 
     
     
         6 . The recombinant polypeptide of  claim 1 , wherein polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:8, 10, 12, 14, 16, or 18. 
     
     
         7 . (canceled) 
     
     
         8 . A nucleic acid molecule encoding a recombinant polypeptide comprising an AAT conjugated to an Fc region of an immunoglobulin. 
     
     
         9 . The nucleic acid molecule of  claim 8 , wherein the AAT comprises an amino acid sequence that is least 90% identical to SEQ ID NO:2. 
     
     
         10 . The nucleic acid molecule of  claim 8 , wherein the nucleic acid sequence encoding AAT is at least 90% identical to SEQ ID NO:1. 
     
     
         11 . The nucleic acid molecule of  claim 8 , wherein the nucleic acid sequence encoding the Fc region of the immunoglobulin is at least 90% identical to SEQ ID NO:3 or 5. 
     
     
         12 . The nucleic acid molecule of  claim 8 , wherein the nucleic acid molecule comprises a nucleic acid sequence is at least 90% identical to SEQ ID NO:7, 9, 11, 13, 15, or 17. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . A cell comprising the vector of claim  13 . 
     
     
         16 . A method of purifying a recombinant polypeptide comprising an AAT conjugated to an Fc region of an immunoglobulin, the method comprising:
 providing the cell of  claim 15 ;   culturing the cell under conditions sufficient to produce the recombinant polypeptide; and   purifying the recombinant polypeptide from the cell using a purification reagent comprising methionine.   
     
     
         17 . The method of  claim 16 , wherein the cell is cultured in growth medium comprising at least 10 mM methionine. 
     
     
         18 . The method of  claim 16 , wherein the purification reagent is selected from the group consisting of extraction buffer, wash buffer, and elution buffer. 
     
     
         19 . The method of  claim 16 , wherein the purification reagent comprises at least 10 mM methionine. 
     
     
         20 . A method of treating an autoimmune disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a recombinant polypeptide comprising an AAT conjugated to an Fc region of an immunoglobulin, thereby treating the autoimmune disease in the subject. 
     
     
         21 . The method of  claim 20 , wherein the autoimmune disease is Type 1 or Type 2 diabetes. 
     
     
         22 . The method of  claim 20 , wherein the recombinant polypeptide is administered to the subject subcutaneously, intraperitoneally, intramuscularly, orally, or by infusion. 
     
     
         23 . The method of  claim 20 , wherein the subject is human.