C1-INH compositions and methods for the prevention and treatment of disorders associated with C1 esterase inhibitor deficiency

1. A method for prophylactic treatment of hereditary angioedema (HAE) comprising subcutaneously administering to a subject in need thereof a pharmaceutical composition comprising C1 esterase inhibitor, sodium citrate, and having a pH ranging from 6.5-8.0, wherein the C1 esterase inhibitor has a concentration of about 400-600 U/mL, and wherein the C1 esterase inhibitor comprises the amino acid sequence of residues 23 to 500 of SEQ ID NO: 1, and wherein the administration of the composition increases the level of the C1 esterase inhibitor in the blood of the subject to at least about 0.4 U/mL.

2. The method of claim 1 , wherein the pharmaceutical composition is reconstituted with water from at least one lyophilized powder comprising at least about 2000 U C1 esterase inhibitor and less than about 5000 U C1 esterase inhibitor.

3. The method of claim 1 , wherein the C1 esterase inhibitor is administered in a range of about 1500 U to about 2500 U.

4. The method of claim 1 , wherein at least about 2000 U of C1 esterase inhibitor is administered.

5. The method of claim 1 , wherein the C1 esterase inhibitor is administered at a dose of about 5000 U.

6. The method of claim 1 , wherein the C1 esterase inhibitor is administered in doses of at least about 2000 U and less than about 5000 U.

7. The method of claim 1 , wherein the composition is administered daily, every other day, or every three days.

8. The method of claim 1 , wherein the composition is administered one, two, or three times a week.

9. The method of claim 1 , wherein the composition is administered three or more times per week.

10. The method of claim 1 , wherein administration of the composition increases the level of functional C1 esterase inhibitor in the blood of the subject to or above 0.4 U/mL.

11. The method of claim 1 , wherein administration of the composition maintains the level of functional C1 esterase inhibitor in the blood of the subject at or above 0.4 U/mL for at least 50% of the time between administrations.

12. The method of claim 1 , wherein administration of the composition maintains the level of functional C1 esterase inhibitor in the blood of the subject at or above 0.4 U/mL for at least 75% of the time between administrations.

13. The method of claim 1 , wherein administration of the composition maintains the level of functional C1 esterase inhibitor in the blood of the subject at or above 0.4 U/mL for at least 90% of the time between administrations.

14. The method of claim 1 , wherein administration of the composition maintains the level of functional C1 esterase inhibitor in the blood of the subject at or above 0.4 U/mL for at least 95% of the time between administrations.

15. The method of claim 1 , wherein the functional C1 esterase inhibitor blood levels are maintained above 0.4 U/mL for at least 95% of the time between administrations.

16. The method of claim 1 , wherein the functional C1 esterase inhibitor blood levels are maintained above 0.4 U/mL for 100% of the time between administrations.

17. The method of claim 1 , wherein the method of treating HAE consists of subcutaneously administering said composition.

18. The method of claim 1 , wherein the method of prophylactic treatment consists of one or more subcutaneous administrations of said composition.

19. The method of claim 1 , wherein administration of the composition does not comprise an initial intravenously administered dose of C1 esterase inhibitor.

20. The method of claim 1 , wherein administration of the composition results in at least a reduction in the severity and/or number of HAE attacks.

21. The method of claim 1 , wherein the composition is reconstituted from a lyophilized powder prior to administration.

22. The method of claim 21 , wherein the lyophilized powder is reconstituted with sterile water.

23. The method of claim 1 , wherein the composition is administered by the subject.

24. The method of claim 1 , wherein the subject in need thereof is an adolescent human.

25. The method of claim 1 , wherein the pH is between about 6.5 to about 7.5.

26. The method of claim 1 , wherein the pH is between about 6.5 to about 7.0.

27. The method of claim 1 , wherein the sodium citrate is present at about 10 mM to about 30 mM.

28. The method of claim 1 , wherein the sodium citrate is present at 10 mM to 30 mM.

29. The method of claim 1 , wherein the sodium citrate is present at about 10 mM.

30. The method of claim 1 , wherein the pharmaceutical composition is a monoformulation of active pharmaceutical ingredient consisting essentially of C1 esterase inhibitor.