Ethanol dependence of alpha1 antitrypsin C-terminal Lys truncation by basic carboxypeptidases
View Patent ↗Methods of preparing alpha-1-antiproteinase inhibitor and controlling the amount of des-lys alpha-1-antiproteinase inhibitor in the preparation, and compositions comprising the same, as well as methods of treatment using the same are provided.
1. A method of making an alpha-1-proteinase inhibitor composition comprising des-lys alpha-1 proteinase inhibitor from human plasma, the method comprising the step of:
treating a plasma precipitate comprising alpha-1-proteinase inhibitor with ethanol at a concentration of at least 5% and less than 15%,
wherein the plasma precipitate is selected from the group consisting of a Cohn fraction IV-1 precipitate and a Cohn fraction IV-1+IV-4 precipitate.
2. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate with ethanol at a final concentration of less than 15% and more than 10%.
3. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate with ethanol at a final concentration of at least 5% and less than 10%.
4. The method of claim 1 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 2% of total alpha-1-proteinase inhibitor in the composition.
5. The method of claim 2 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 2% of total alpha-1-proteinase inhibitor in the composition.
6. The method of claim 3 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 2% of total alpha-1-proteinase inhibitor in the composition.
7. The method of claim 1 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 6% of total alpha-1-proteinase inhibitor in the composition.
8. The method of claim 2 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 6% of total alpha-1-proteinase inhibitor in the composition.
9. The method of claim 3 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 65% and more than 6% of total alpha-1-proteinase inhibitor in the composition.
10. The method of claim 3 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is less than 6% and more than 2% of total alpha-1-proteinase inhibitor in the composition.
11. The method of claim 1 , wherein the Cohn fraction IV-1 or IV-1+IV-4 precipitate is treated at a pH of at least 5.2 and less than pH 5.9.
12. The method of claim 2 , wherein the Cohn fraction IV-1 or IV-1+IV-4 precipitate is treated at a pH of at least 5.2 and less than pH 5.9.
13. The method of claim 3 , wherein the Cohn fraction IV-1 or IV-1+IV-4 precipitate is treated at a pH of at least 5.2 and less than pH 5.9.
14. The method of claim 1 , wherein the plasma precipitate is a Cohn fraction IV-1 precipitate.
15. The method of claim 2 , wherein the plasma precipitate is a Cohn fraction IV-1 precipitate.
16. The method of claim 3 , wherein the plasma precipitate is a Cohn fraction IV-1 precipitate.
17. The method of claim 1 , wherein the plasma precipitate is a Cohn fraction IV-1+IV-4 precipitate.
18. The method of claim 2 , wherein the plasma precipitate is a Cohn fraction IV-1+IV-4 precipitate.
19. The method of claim 3 , wherein the plasma precipitate is a Cohn fraction IV-1+IV-4 precipitate.