High concentration alpha-glucosidase compositions for the treatment of Pompe disease
View Patent ↗The present application provides for compositions comprising high concentrations of acid a-glucosidase in combination with an active site-specific chaperone for the acid α-glucosidase, and methods for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject such compositions. The present application also provides methods for increasing the in vitro and in vivo stability of an acid α-glucosidase enzyme formulation.
1. A composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and 500 mg/mL, and the active site-specific chaperone is present in an amount between about 20 mg/mL and about 200 mg/mL.
2. The composition of claim 1 , wherein the composition has less than about 5% aggregate protein.
3. The composition of claim 2 , wherein the composition has less than about 1% aggregate protein.
4. The composition of claim 1 , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and 250 mg/mL.
5. The composition of claim 4 , wherein the acid α-glucosidase is present in an amount between about 10 mg/mL and 200 mg/mL.
6. The composition of claim 1 , wherein the acid α-glucosidase is present in an amount of about 25 mg/mL.
7. The composition of claim 1 , wherein the composition is a liquid formulation.
8. The composition of claim 7 , wherein the composition has a pH ranging from about 7.0-7.5.
9. The composition of claim 7 , wherein the composition is in a frozen state.
10. The composition of claim 1 , further comprising an excipient.
11. The composition 10 , wherein the excipient is selected from the group consisting of polyethylene glycol 400, arginine, glutamic acid, proline, gammacyclodextrin and combinations thereof.
12. The composition of claim 1 , further comprising a buffer selected from the group consisting of citrate buffer, acetate buffer, bicarbonate buffer, phosphate buffer and combinations thereof.
13. The composition of claim 1 , wherein the active site-specific chaperone is n-butyldeoxynojirimycin or a pharmaceutically acceptable salt thereof.
14. The composition of claim 1 , wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
15. A method of treating Pompe disease in a subject comprising administering to the subject the composition of claim 1 .
16. The method of claim 15 , wherein the composition is administered by subcutaneous injection.
17. The method of claim 16 , wherein the composition is administered in a single subcutaneous dose of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 milliliters.
18. The method of claim 15 , wherein the composition is administered intravenously.
19. The method of claim 15 , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and 250 mg/mL.
20. The method of claim 19 , wherein the acid α-glucosidase is present in an amount between about 10 mg/mL and 200 mg/mL.