Methods and materials for treatment of Pompe's disease
AssigneeOxyrane UK Limited
InventorsWouter Vervecken, Kathleen Camilla Telesphore Alida Maria Piens, Jan Robert Ludo Stout, Gwenda Noëlla Pynaert
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Abstract
This document relates to molecular complexes having acid alpha glucosidase activity and at least one modification that results in enhanced ability of the molecular complex to be transported to the interior of a mammalian cell.
Claims10
A pharmaceutical composition comprising an isolated molecular complex having acid alpha glucosidase (GAA) activity and consisting of a GAA-derived protein consisting of two polypeptides, a first polypeptide having at least 85% sequence identity to amino acids 22 to 57 of SEQ ID NO:
- 1, and a second polypeptide having at least 85% sequence identity to amino acids 66-896 of SEQ ID NO:
- 1, with the proviso that the pharmaceutical composition does not include an isolated molecular complex having GAA activity and at least three or at least four polypeptides, wherein at least one of said two polypeptides includes a phosphorylated N-glycan such that said molecular complex has:
- the substantial ability to bind to a mannose-6-phosphate receptor on a mammalian cell and consequently, the ability to be transported to the interior of the mammalian cell;
- and
- a pharmaceutically acceptable carrier.
A method of transporting a molecular complex having GAA activity to the interior of a cell, said method comprising:
- contacting a mammalian cell with an isolated molecular complex having acid alpha glucosidase (GAA) activity and consisting of a GAA-derived protein consisting of two polypeptides, a first polypeptide having at least 85% sequence identity to amino acids 22 to 57 of SEQ ID NO:
- 1, and a second polypeptide having at least 85% sequence identity to amino acids 66-896 of SEQ ID NO:
- 1, with the proviso that the mammalian cell is not in contact with an isolated molecular complex having GAA activity and having at least three or at least four polypeptides, wherein at least one of the two polypeptides includes a phosphorylated N-glycan such that said molecular complex has:
- the substantial ability to bind to a mannose-6-phosphate receptor on a mammalian cell;
- and
- consequently, the ability to be transported to the interior of the mammalian cell.
An isolated fungal cell comprising a nucleic acid encoding a GAA protein having at least 85% sequence identity to the GAA amino acid sequence set forth in SEQ ID NO:1 and a nucleic acid encoding an alkaline protease having at least 85% sequence identity to the amino acid sequence set forth in SEQ ID NO:8, wherein said fungal cell produces a molecular complex having GAA activity and comprising two polypeptides, each polypeptide having at least 85% sequence identity to a segment of the amino acid sequence set forth in SEQ ID NO:
- 1, each segment being derived by proteolysis of the amino acid sequence set forth in SEQ ID NO:
- 1 at one or more sites between amino acid 50 and amino acid 74 by said alkaline protease.
Dependencies are inferred from the claim text.