Methods and compositions for cns delivery of iduronate-2-sulfatase

Abstract

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

1 - 61 . (canceled) 
     
     
         62 . A formulation for intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein at a concentration of at least 10 mg/ml and no greater than 5 mM phosphate. 
     
     
         63 . The formulation of  claim 62 , wherein the I2S protein is at a concentration of at least 30 mg/ml. 
     
     
         64 . The formulation of  claim 62 , wherein the I2S protein is at a concentration of at least 50 mg/ml. 
     
     
         65 . The formulation of  claim 62 , further comprising a surfactant. 
     
     
         66 . The formulation of  claim 65 , wherein the surfactant is a polysorbate. 
     
     
         67 . The formulation of  claim 65 , wherein the surfactant is polysorbate 20. 
     
     
         68 . The formulation of  claim 67 , wherein the polysorbate 20 is present in an amount at or less than 0.02%. 
     
     
         69 . The formulation of  claim 67 , wherein the polysorbate 20 is present in an amount at or less than 0.005%. 
     
     
         70 . The formulation of  claim 62 , further comprising a tonicifier. 
     
     
         71 . The formulation of  claim 70 , wherein the tonicifier is a salt. 
     
     
         72 . The formulation of  claim 71 , where the salt is NaCl. 
     
     
         73 . The formulation of  claim 72 , wherein the NaCl is present in an amount ranging from approximately 137 mM to approximately 154 mM. 
     
     
         74 . The formulation of  claim 62 , wherein the formulation has a pH of approximately 5.5 to 6.5. 
     
     
         75 . The formulation of  claim 62 , wherein the pH is approximately 6.0 
     
     
         76 . A container comprising a single dosage formulation for intrathecal administration, the formulation comprising at least 10 mg of I2S in a concentration of at least 10 mg/ml, and no greater than 5 mM phosphate. 
     
     
         77 . The container of  claim 76 , wherein the container is selected from an ampule, a vial, a cartridge, a reservoir, a lyo-ject, or a pre-filled syringe. 
     
     
         78 . A syringe comprising a formulation for intrathecal injection, wherein the formulation comprises at least 10 mg I2S, polysorbate 20 at a concentration of approximately 0.005%, NaCl at a concentration of approximately 154 mM, no greater than 5 mM phosphate, and has a pH of approximately 6.0. 
     
     
         79 . The syringe of  claim 78 , wherein the syringe is selected from a borosilicate glass syringe with baked silicone coating, borosilicate glass syringe with spayed silicone, or plastic resin syringe without silicone.