Augmented acid alpha-glucosidase for the treatment of pompe disease
AssigneeAmicus Therapeutics, Inc.
InventorsHung V. DO, Richie KHANNA, Russell GOTSCHALL
Life of this patent
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Abstract
A method for treating Pompe disease including administration of recombinant human acid α-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid α-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid α-glucosidase is provided.
Claims14
-21. (canceled)
A method of treating Pompe disease in a patient in need thereof, comprising administering miglustat to the patient in combination with a composition comprising recombinant human acid α-glucosidase (rhGAA) molecules,
- wherein the composition is administered intravenously at a dose of about 5 mg/kg to about 20 mg/kg and the miglustat is administered orally at a dose of about 260 mg or about 130 mg, and
- wherein the rhGAA molecules are produced in Chinese hamster ovary (CHO) cells, the rhGAA molecules comprise first, second, third, fourth, fifth, sixth, and seventh potential N-glycosylation sites at amino acid positions corresponding to N84, N177, N334, N414, N596, N826, and N869 of SEQ ID NO:
- 5, respectively, 40%-60% of the N-glycans on the rhGAA molecules are complex type N-glycans, and at least 50% of the rhGAA molecules bear a bis-mannose-6-phosphate (bis-M6P) unit at the first potential N-glycosylation site.
A kit comprising
- a pharmaceutically acceptable dosage form comprising miglustat configured for oral administration at a dose of about 260 mg or about 130 mg,
- a pharmaceutically acceptable dosage form comprising recombinant human acid α-glucosidase (rhGAA) molecules configured for intravenous administration at a dose of about 5 mg/kg to about 20 mg/kg, and
- instructions for administering the pharmaceutically acceptable dosage form comprising miglustat and the pharmaceutically acceptable dosage form comprising rhGAA molecules to a patient in need thereof,
- wherein
- the rhGAA molecules are produced in Chinese hamster ovary (CHO) cells,
- the rhGAA molecules comprise first, second, third, fourth, fifth, sixth, and seventh potential N-glycosylation sites at amino acid positions corresponding to N84, N177, N334, N414, N596, N826, and N869 of SEQ ID NO:
- 5, respectively,
- 40%-60% of the N-glycans on the rhGAA molecules are complex type N-glycans, and
- at least 50% of the rhGAA molecules bear a bis-mannose-6-phosphate (bis-M6P) unit at the first potential N-glycosylation site.
A kit comprising
- a pharmaceutically acceptable dosage form comprising recombinant human acid α-glucosidase (rhGAA) molecules configured for intravenous administration at a dose of about 5 mg/kg to about 20 mg/kg, and
- instructions for administering to a patient in need thereof the pharmaceutically acceptable dosage form comprising rhGAA molecules in combination with a pharmaceutically acceptable dosage form comprising miglustat,
- wherein
- the rhGAA molecules are produced in Chinese hamster ovary (CHO) cells,
- the rhGAA molecules comprise first, second, third, fourth, fifth, sixth, and seventh potential N-glycosylation sites at amino acid positions corresponding to N84, N177, N334, N414, N596, N826, and N869 of SEQ ID NO:
- 5, respectively,
- 40%-60% of the N-glycans on the rhGAA molecules are complex type N-glycans, and
- at least 50% of the rhGAA molecules bear a bis-mannose-6-phosphate (bis-M6P) unit at the first potential N-glycosylation site.
Dependencies are inferred from the claim text.