Dephosphorylated lysosomal storage disease proteins and methods of use thereof
AssigneeBioasis Technologies, Inc.
InventorsTimothy Z. Vitalis, Reinhard Gabathuler
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Abstract
Provided are substantially dephosphorylated forms of lysosomal storage disease (LSD) proteins, including dephosphorylated forms of iduronate-2-sulfatase (IDS, or I2D) and iduronidase (IDU), having increased ability to traverse or penetrate the blood brain barrier (BBB) relative to phosphorylated forms of the protein, and p97 conjugates thereof. Also provided are compositions comprising such dephosphorylated LSD proteins and p97 conjugates, and methods of use thereof, for instance, to treat any one or more lysosomal storage diseases, such as Hunter Syndrome (or MPS Type II).
Claims48
An isolated lysosomal storage disease (LSD) polypeptide that is substantially dephosphorylated, relative to a corresponding LSD protein expressed (or produced) in a mammalian cell.
3-4. (canceled)
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The isolated polypeptide of 16, where the one or more N-linked oligomannose glycans are at least 75% dephosphorylated.
20-21. (canceled)
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The isolated polypeptide of 27, where the N-linked oligomannose glycans are at least 75% dephosphorylated.
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A method of producing a substantially dephosphorylated human iduronate-2-sulfatase (IDS), comprising recombinantly producing the human IDS in a human cell line, and treating the recombinantly produced human IDS with a phosphatase for a time sufficient to reduce the mannose-6-phosphate (M6P) content of the human IDS by at least about 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99%, relative to untreated human IDS produced in the same human cell line.
An isolated human iduronate-2-sulfatase (IDS) polypeptide, where the human IDS polypeptide comprises or consists of the amino acid sequence of SEQ ID NO:2, or a variant thereof, and where the mannose-6-phosphate (M6P) content is less than about 1.2 pmol M6P/pmol IDS protein.
Dependencies are inferred from the claim text.