Formulations of recombinant furin
View Patent ↗The present application provides stabilized formulations of furin (e.g., rfurin) containing a sugar, sugar alcohol, and/or non-ionic surfactant. As compared to non-stabilized compositions, the furin formulations disclosed herein retain greater amounts of furin activity and monomeric furin content, while reducing furin aggregation when stored and/or subjected to mechanical stress. Also provided are methods for stably diluting furin (e.g., rfurin) compositions.
1. A stabilized aqueous composition of recombinant furin (rfurin), the composition comprising:
(a) from 8,000 U/mL to 500,000 U/mL rfurin;
(b) from 190±10 mM of a pharmaceutically acceptable salt;
(c) from 0.5 mM to 2mM calcium;
(d) from 2% to 20% sugar or sugar alcohol;
(e) from 10 to 200 ppm non-ionic surfactant;
(f) from 10 to 200 mM buffering agent; and
(g) a pH from 5.5 to 7.5.
2. The composition of claim 1 , wherein the pharmaceutically acceptable salt is sodium chloride.
3. The composition of claim 1 , comprising 0.9±0.2 mM calcium.
4. The composition of claim 1 , comprising 10±2% sugar or sugar alcohol.
5. The composition of claim 1 , wherein the sugar or sugar alcohol is selected from the group consisting of sucrose, trehalose, mannitol, and a combination thereof.
6. The composition of claim 1 , comprising from 50 ppm to 100 ppm non-ionic surfactant.
7. The composition of claim 1 , wherein the non-ionic surfactant is polysorbate-80.
8. The composition of claim 1 , comprising 90±10 mM buffering agent.
9. The composition of claim 1 , wherein the buffering agent comprises acetate and HEPES.
10. The composition of claim 9 , comprising 45±5 mM acetate and 45±5 mM HEPES.
11. The composition of claim 1 , having a pH of 6.0±0.2.
12. A stabilized aqueous composition of recombinant furin (rfurin), the composition comprising:
(a) from 8,000 U/mL to 500,000 U/mL rfurin;
(b) 190 mM sodium chloride;
(c) 0.92 mM calcium;
(d) 10% trehalose;
(e) 75 ppm polysorbate 80;
(f) 45 mM acetic acid;
(g) 46 mM HEPES; and
(g) a pH from 5.5 to 7.5.
13. The composition of claim 12 , having a pH of 6.0±0.2.
14. The composition of claim 1 , comprising 0.9±0.2 mM calcium.
15. The composition of claim 1 , comprising 10±2% sugar or sugar alcohol.
16. The composition of claim 3 , comprising 10±2% sugar or sugar alcohol.
17. The composition of claim 1 , comprising from 50 ppm to 100 ppm non-ionic surfactant.
18. The composition of claim 3 , comprising from 50 ppm to 100 ppm non-ionic surfactant.
19. The composition of claim 4 , comprising from 50 ppm to 100 ppm non-ionic surfactant.
20. The composition of claim 1 , comprising 90±10 mM buffering agent.
21. The composition of claim 3 , comprising 90±10 mM buffering agent.
22. The composition of claim 4 , comprising 90±10 mM buffering agent.
23. The composition of claim 6 , comprising 90±10 mM buffering agent.
24. The composition of claim 1 , having a pH of 6.0±0.2.
25. The composition of claim 3 , having a pH of 6.0±0.2.
26. The composition of claim 4 , having a pH of 6.0±0.2.
27. The composition of claim 6 , having a pH of 6.0±0.2.
28. The composition of claim 8 , having a pH of 6.0±0.2.