Highly potent acid alpha-glucosidase with enhanced carbohydrates

Patent metadata

Field	Value
Publication number	US-10208299-B2
Application number	US-201515515808-A
Country	US
Kind code	B2
Filing date	Sep 30, 2015
Priority date	Sep 30, 2014
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

Abstract

Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.

First claim

We claim:

1. A composition comprising recombinant human acid alpha-glucosidase (rhGAA) produced from Chinese hamster ovary (CHO) cells, wherein 40%-60% of the N-glycans on the rhGAA are complex type N-glycans; and wherein the rhGAA comprises 3.0-5.0 mol mannose-6-phosphate (M6P) residues per mol rhGAA.

2. The composition of claim 1 , wherein the rhGAA comprises 3.0 to 4.0 mol M6P per mol rhGAA.

3. The composition of claim 1 , wherein the rhGAA comprises 4.0 to 5.0 mol M6P per mol rhGAA.

4. The composition of claim 1 , wherein the rhGAA further comprises at least 4 mol sialic acid per mol rhGAA.

5. The composition of claim 1 , wherein the rhGAA further comprises 2.0 to 8.0 mol sialic acid residues per mol of rhGAA.

6. The composition of claim 1 , wherein the composition further comprises a pharmacological chaperone.

7. The composition of claim 1 , wherein the rhGAA comprises at least one bis-phosphorylated N-glycan per rhGAA.

8. The composition of claim 1 , wherein about 45%-55% of the N-glycans on the rhGAA are complex type N-glycans.

9. The composition of claim 1 , wherein 50% of the N-glycans on the rhGAA are complex type N-glycans.

10. The composition of claim 1 , wherein the rhGAA comprises 4 mol M6P per mol rhGAA, 4.5 mol sialic acid per mol rhGAA, and at least one bis-phosphorylated N-glycan per rhGAA.

11. The composition of claim 10 , wherein the composition further comprises the pharmacological chaperone N-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

12. A method for treating Pompe disease in a subject in need thereof, the method comprising administering the composition of claim 1 to the subject in an amount sufficient to treat Pompe disease.

13. The method of claim 12 , wherein said composition is administered to cardiac muscle of the subject.

14. The method of claim 12 , wherein said composition is administered to quadriceps, triceps, or other skeletal muscle of the subject.

15. The method of claim 12 , wherein said composition is administered to the diaphragm of the subject.

16. The method of claim 12 , wherein said composition is combined with a pharmacological chaperone, and wherein said composition and said pharmacological chaperone are either administered as a single pharmaceutical composition or administered separately.

17. The method of claim 12 , wherein said composition is combined with 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof, and wherein said composition and said 1-deoxynojirimycin or pharmaceutically acceptable salt thereof are either administered as a single pharmaceutical composition or administered separately.

18. The method of claim 12 , wherein said composition is combined with N-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof, and wherein said composition and said N-butyl-deoxynojirimycin or pharmaceutically acceptable salt thereof are either administered as a single pharmaceutical composition or administered separately.

Assignees

• Amicus Therapeutics Inc

Inventors

• Gotschall Russell
• Do Hung V

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• C12Y302/0102

  Alpha-glucosidase (3.2.1.20) · CPC title

• C12N2510/02

  Cells for production · CPC title

• A61K48/005

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title