Polymers for delivery of factor viii and/or factor ix

Abstract

In some aspects, a composition comprising a pH-sensitive crosslinked copolymer of methacrylic acid and poly(ethylene glycol) monomethyl ether methacrylate and a therapeutic protein is provided. In some embodiments, the therapeutic protein is a high molecular weight protein such as factor VIII or factor IX. In some embodiments, the composition is orally administered to a patient to treat a disease or disorder such as, e.g., hemophilia.

1 . A composition comprising:
 (A) a therapeutic protein; wherein the therapeutic protein is factor IX or factor VIII; and   (B) a copolymer comprising methacrylic acid and poly(ethylene glycol) monomethyl ether monomethacrylate crosslinked with about 0.5-2.0% tetra(ethylene glycol) dimethacrylate (TEGDMA) or about 0.5-2.0% poly(ethylene glycol) dimethacrylate (PEGDMA) wherein the poly(ethylene glycol) component of the PEGDMA has an average molecular weight of about 100-1,000; or     .   
     
     
         2 . The composition of  claim 1 , wherein the therapeutic protein is factor IX. 
     
     
         3 . The composition of  claim 1 , wherein the therapeutic protein is factor VIII. 
     
     
         4 . The composition of  claim 1 , wherein the composition is comprised in a pharmaceutical preparation formulated for oral administration. 
     
     
         5 - 8 . (canceled) 
     
     
         9 . The composition of  claim 1 , wherein the ratio of the molar percentage of methacrylic acid (MAA) to poly(ethylene glycol) monomethyl ether monomethacrylate is from about 1:1 to about 60:1. 
     
     
         10 . The composition of  claim 9 , wherein the ratio of the molar percentage of methacrylic acid to poly(ethylene glycol) monomethyl ether monomethacrylate is from about 20:1 to about 40:1. 
     
     
         11 - 15 . (canceled) 
     
     
         16 . The composition of claim  15 , wherein the average molecular weight is from about 200 to about 600. 
     
     
         17 . The composition of  claim 16 , wherein the average molecular weight is about 400. 
     
     
         18 . The composition of  claim 1 , wherein the copolymer comprises from about 90 mol % to about 99 mol % methacrylic acid. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The composition of  claim 1 , wherein the copolymer comprises from about 1 mol % to about 10 mol % poly(ethylene glycol) monomethyl ether monomethacrylate. 
     
     
         22 - 25 . (canceled) 
     
     
         26 . The composition of  claim 1 , wherein the composition comprises greater than about 20 μg of therapeutic protein per mg of copolymer. 
     
     
         27 . The composition of  claim 26 , wherein the composition comprises greater than about 30 μg of therapeutic protein per mg of copolymer. 
     
     
         28 . The composition of  claim 1 , wherein the copolymer has a particle size less than 100 μm. 
     
     
         29 . (canceled) 
     
     
         30 . The composition of  claim 28 , wherein the particle size is less than 75 μm. 
     
     
         31 . (canceled) 
     
     
         32 . The composition of  claim 1 , wherein the copolymer begins swelling at a pH greater than about 5. 
     
     
         33 . (canceled) 
     
     
         34 . The composition of  claim 1 , wherein the composition releases greater than about 0.1 μg of therapeutic protein per mg of copolymer at pH 7.4. 
     
     
         35 . The composition of  claim 34 , wherein the composition releases greater than about 0.25 μg of therapeutic protein per mg of copolymer at pH 7.4. 
     
     
         36 - 41 . (canceled) 
     
     
         42 . A method of treating hemophilia in a patient comprising orally administering a pharmacologically effective amount of the composition of  claim 1  to a patient in need of such treatment. 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 42 , wherein the hemophilia is hemophilia B. 
     
     
         45 . The method of  claim 42 , wherein the hemophilia is hemophilia A. 
     
     
         46 - 67 . (canceled)