Subcutaneous administration of ADAMTS13
View Patent ↗This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.
1. A method for treating a bleeding episode associated with an increase in blood clotting activity associated with a specific indication in a mammal, the method comprising subcutaneously administering a therapeutically effective amount of a composition comprising isolated a disintegrin and metalloproteinase with thrombospondin type I motifs 13 (ADAMTS13) to the mammal in need thereof, wherein the ADAMTS13 has a bioavailability of at least 40% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
2. The method of claim 1 , wherein the specific indication is inherited thrombotic thrombocytopenic purpura (TTP) and the standard intravenous dose is from about 10 to about 80 activity units per kilogram body weight.
3. The method of claim 1 , wherein the specific indication is acquired TTP and the standard intravenous dose is from about 20 to about 1,000 activity units per kilogram body weight.
4. The method of claim 1 , wherein the specific indication is myocardial infarction, ischemia reperfusion injury, or both and the standard intravenous dose is about 20-2000 activity units per kilogram body weight.
5. The method of claim 1 , wherein the specific indication is cerebral infarction, ischemia reperfusion injury, or both and the standard intravenous dose is about 20-2000 activity units per kilogram body weight.
6. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of 50-80% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
7. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 50% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
8. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 55% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
9. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 60% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
10. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 65% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
11. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 70% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
12. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 75% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
13. The method of claim 1 , wherein the ADAMTS13 has a bioavailability of at least 80% after subcutaneous administration as compared to intravenous administration normalized for the same dose.
14. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection monthly.
15. The method of claim 1 , wherein the ADAMTS13 is recombinant.
16. The method of claim 1 , wherein the ADAMTS13 is plasma derived.
17. The method of claim 1 , wherein the mammal is a human.
18. The method of claim 1 , wherein the composition is a stable aqueous solution ready for administration.
19. The method of claim 1 , wherein the composition is lyophilized.
20. The method of claim 19 , wherein the composition is reconstituted with a pharmaceutically acceptable vehicle suitable for injection.
21. The method of claim 1 , wherein the specific indication is disseminated intravascular coagulation (DIC).
22. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every two weeks.
23. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection weekly.
24. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection twice a week.
25. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection daily.
26. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every 12 hours.
27. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every 8 hours.
28. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every six hours.
29. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every four hours.
30. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection every two hours.