Crystallized oxalate decarboxylase and methods of use

Abstract

Pharmaceutical compositions comprising spray-dried oxalate decarboxylase crystals are disclosed. Methods to treat a disorder associated with elevated oxalate concentration using compositions comprising spray-dried oxalate decarboxylase crystals are also disclosed.

1 . A pharmaceutical composition comprising a spray-dried oxalate decarboxylase crystal. 
     
     
         2 . The composition of  claim 1 , further comprising an excipient. 
     
     
         3 . The composition of  claim 2 , wherein the excipient is a sugar. 
     
     
         4 . The composition of  claim 3 , wherein the sugar is a disaccharide or a monosaccharide, 
     
     
         5 . The composition of  claim 4 , wherein the sugar is selected from trehalose, sucrose, and glucose. 
     
     
         6 . The composition of  claim 5 , wherein the sugar is trehalose. 
     
     
         7 . The composition of  claim 2 , wherein the excipient is selected from poly (acrylic acid), poly (cyanoacrylates), poly (amino acids), poly (anhydrides), poly (depsipeptide), poly (esters) such as poly (lactic acid) or PLA, poly (lactic-co-glycolic acid) or PLGA, poly (β-hydroxybutryate), poly (caprolactone) and poly (dioxanone); poly (ethylene glycol), poly ((hydroxypropyl)methacrylamide, poly [(organo)phosphazene], poly (ortho esters), poly (vinyl alcohol), poly (vinylpyrrolidone), maleic anhydride-alkyl vinyl ether copolymers, pluronic polyols, albumin, alginate, cellulose and cellulose derivatives, collagen, fibrin, gelatin, hyaluronic acid, oligosaccharides, glycaminoglycans, sulfated polysaccharides, blends and copolymers thereof. 
     
     
         8 - 38 . (canceled) 
     
     
         39 . The composition of  claim 1 , wherein the pharmaceutical composition is in the form of a capsule. 
     
     
         40 - 49 . (canceled) 
     
     
         50 . A method of reducing oxalate in a mammal, the method comprising administering a pharmaceutical composition comprising a spray-dried oxalate decarboxylase crystal to the mammal in an amount sufficient to reduce the level of oxalate in the urine or blood of the mammal and protect from loss of tissue function. 
     
     
         51 . The method of  claim 50 , wherein the pharmaceutical composition further comprises an excipient. 
     
     
         52 - 87 . (canceled) 
     
     
         88 . The method of  claim 50 , wherein the pharmaceutical composition is in the form of a capsule. 
     
     
         89 - 93 . (canceled) 
     
     
         94 . The method of  claim 50 , wherein said crystals are active and stable in the gastrointestinal tract of the mammal. 
     
     
         95 - 98 . (canceled) 
     
     
         99 . A method of treating a disorder associated with elevated oxalate concentration in a mammal, the method comprising administering a pharmaceutical composition according to  claim 1  to the mammal in an amount sufficient to reduce one or more symptoms associated with the disorder. 
     
     
         100 - 101 . (canceled) 
     
     
         102 . A method of preparing a pharmaceutical composition comprising oxalate decarboxylase crystals, wherein the method comprises spray-drying a suspension of oxalate decarboxylase crystals. 
     
     
         103 - 110 . (canceled) 
     
     
         111 . The composition of  claim 1 , wherein the oxalate decarboxylase comprises the amino acid sequence of SEQ ID NO:1, and wherein the thiol moiety of the cysteine residue at position 383 of the oxalate decarboxylase is protected by reaction with a thiol protecting group. 
     
     
         112 - 133 . (canceled)