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 blood clotting disorder in a mammal, the method comprising subcutaneously administering a therapeutically effective amount of a composition comprising isolated ADAMTS13 to the mammal in need thereof, wherein the therapeutically effective amount of ADAMTS13 is from 20 to 4,000 activity units per kilogram body weight, and the bioavailability of the ADAMTS13 after subcutaneous administration is 50-80% as compared to intravenous administration normalized for the same dose, and thereby treating the blood clotting disorder in the mammal.
2. The method of claim 1 , wherein the blood clotting disorder is selected from the group consisting of inherited TTP, acquired TTP, cerebral infarction, myocardial infarction, ischemic/reperfusion injury, deep vein thrombosis, and sepsis-related disseminated intravasular coagulation.
3. The method of claim 1 , wherein the bioavailability of the ADAMTS13 after subcutaneous administration is 55-80% as compared to intravenous administration normalized for the same dose.
4. The method of claim 1 , wherein the bioavailability of the ADAMTS13 after subcutaneous administration is 60-80% as compared to intravenous administration normalized for the same dose.
5. The method of claim 1 , wherein the bioavailability of the ADAMTS13 after subcutaneous administration is 65-80% as compared to intravenous administration normalized for the same dose.
6. The method of claim 1 , wherein the bioavailability of the ADAMTS13 after subcutaneous administration is 70-80% as compared to intravenous administration normalized for the same dose.
7. The method of claim 1 , wherein the bioavailability of the ADAMTS13 after subcutaneous administration is 75-80% as compared to intravenous administration normalized for the same dose.
8. The method of claim 2 , wherein the blood clotting disorder is inherited TTP.
9. The method of claim 8 , wherein the therapeutically effective amount is from 20 to 160 activity units per kilogram body weight.
10. The method of claim 2 , wherein the blood clotting disorder is acquired TTP.
11. The method of claim 10 , wherein the therapeutically effective amount is from 40 to 2,000 activity units per kilogram body weight.
12. The method of claim 2 , wherein the blood clotting disorder is cerebral infarction or ischemia reperfusion injury.
13. The method of claim 12 , wherein the therapeutically effective amount is from 40 to 4,000 activity units per kilogram body weight.
14. The method of claim 2 , wherein the blood clotting disorder is myocardial infarction or ischemia reperfusion injury.
15. The method of claim 14 , wherein the therapeutically effective amount is from 40 to 2,000 activity units per kilogram body weight.
16. The method of claim 1 , wherein the ADAMTS13 is administered in a single bolus injection, monthly, every two weeks, weekly, twice a week, daily, every 12 hours, every 8 hours, every six hours, every four hours, or every two hours.
17. The method of claim 1 , wherein the ADAMTS13 is recombinant.
18. The method of claim 1 , wherein the ADAMTS13 is plasma derived.
19. The method of claim 1 , wherein the mammal is a human.
20. The method of claim 1 , wherein the composition is a stable aqueous solution ready for administration.
21. The method of claim 1 , wherein the composition is lyophilized.
22. The method of claim 21 , wherein the composition is reconstituted with a pharmaceutically acceptable vehicle suitable for injection.