Recombinant Alpha-Galactosidase A For Treatment Of Fabry Disease

Abstract

Described are compositions comprising α-galactosidase A enzymes with unique carbohydrate profiles, as well as methods for manufacturing and purifying such enzymes. Also described methods of treating, preventing, and/or ameliorating Fabry Disease by administering such enzymes to a subject in need thereof. Also described are compositions comprising migalastat in combination with such α-galactosidase A enzymes.

What is claimed is: 
     
         1 - 155 . (canceled) 
     
     
         156 . A method for treating Fabry disease, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising a human recombinant α-galactosidase A (rhα-Gal A), wherein the rhα-Gal A comprises a protein having at least 98% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the protein has less than 10% of total N-linked oligosaccharides that are neutral as measured by liquid chromatography. 
     
     
         157 . The method of  claim 156 , wherein the protein has 3.5 to 6 moles of mannose-6-phosphate (M6P) residues per mole of rhα-Gal A homodimer as measured by liquid chromatography. 
     
     
         158 . The method of  claim 156 , wherein the rhα-Gal A has one or more of:
 at least 17% of total N-linked oligosaccharides that contain a single sialic acid residue as measured by liquid chromatography; 
 at least 20% of total N-linked oligosaccharides that contain two sialic acid residues as measured by liquid chromatography; 
 at least 40% of total N-linked oligosaccharides that contain one or two sialic acid residues as measured by liquid chromatography; 
 or 
 at least 4 moles of sialic acid residues per mole of rhα-Gal A homodimer as measured by liquid chromatography. 
 
     
     
         159 . The method of  claim 156 , wherein the rhα-Gal A has at least 50% of total N-linked oligosaccharides that contain sialic acid as measured by liquid chromatography. 
     
     
         160 . The method of  claim 156 , wherein the rhα-Gal A has at least 25% of total N-linked oligosaccharides that are mono-mannose-6-phosphate and at least 6% of total N-linked oligosaccharides that are bis-mannose-6-phosphate as measured by liquid chromatography. 
     
     
         161 . The method of  claim 156 , wherein the rhα-Gal A has at least 7 moles of sialic acid residues per mole of rhα-Gal A homodimer as measured by liquid chromatography. 
     
     
         162 . The method of  claim 156 , wherein the rhα-Gal A has at least 22% of total N-linked oligosaccharides that contain two sialic acid residues as measured by liquid chromatography. 
     
     
         163 . The method of  claim 156 , wherein the rhα-Gal A has at least 14% of total N-linked oligosaccharides that are bis-mannose-6-phosphate as measured by liquid chromatography. 
     
     
         164 . The method of  claim 156 , further comprising administering a pharmacological chaperone for α-Gal A. 
     
     
         165 . The method of  claim 164 , wherein the pharmacological chaperone is migalastat or salt thereof. 
     
     
         166 . The method of  claim 165 , wherein the pharmacological chaperone is migalastat hydrochloride. 
     
     
         167 . The method of  claim 166 , wherein the patient is administered about 150 mg of migalastat hydrochloride. 
     
     
         168 . The method of  claim 167 , wherein the migalastat hydrochloride is administered orally. 
     
     
         169 . The method of  claim 156 , wherein the rhα-Gal A is administered at a dose of about 0.5 mg/kg to about 10 mg/kg. 
     
     
         170 . The method of  claim 166 , wherein the composition comprising rhα-Gal A is administered once a month to once a week. 
     
     
         171 . The method of  claim 156 , wherein the composition comprising rhα-Gal A is administered every other week. 
     
     
         172 . The method of  claim 171 , wherein the rhα-Gal A is administered at a dose of about 0.5 mg/kg to about 10 mg/kg. 
     
     
         173 . The method of  claim 156 , wherein the rhα-Gal A is co-formulated with a pharmacological chaperone for α-Gal A.