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AssigneesUniversity of Copenhagen, Glycodisplay Aps
InventorsClaus Kristensen, Weihua Tian, Henrik Clausen, Zhang Yang, Sergey Vakhrushev
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The present invention relates to lysosomal enzymes modified by use of cell based methods, a compositions comprising a modified lysosomal enzyme, as well as methods for producing a modified lysosomal enzyme and therapeutic use of such modified lysosomal enzyme. In particular, the present disclosure relates to a modified lysosomal enzyme which has low Man6P and low exposed Mannose and high sialic acid content of alpha2,3 type enabling long circulation time and improved uptake into difficult-to-reach organs like heart, kidney and brain.
A modified recombinant lysosomal enzyme with increased circulation time in plasma as compared to an unmodified version of the same, wherein said enzyme comprises less than 10% mannose-6-phosphate (Man6P) and less than 0.3 mole exposed mannose (Man) per mole of enzyme, and wherein said enzyme comprises more than 4 moles alpha2,3 sialic acid (SA) per mole of enzyme, and wherein the modified recombinant lysosomal enzyme is Alpha-Galactosidase A (GLA) or Aspartvlglucoaminidase (AGA).
Dependencies are inferred from the claim text.