Fibronectin based scaffold domain proteins that bind PCSK9
The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.
1. A method of treating hypercholesterolemia in a subject comprising administering an effective amount of a polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain wherein the 10 Fn3 has a BC, DE and FG loop, and wherein the BC loop comprises SEQ ID NO:14, the DE loop comprises SEQ ID NO:25 and the FG loop comprises SEQ ID NO:37, and wherein the polypeptide binds PCSK9.
2. A method of treating hypercholesterolemia in a subject comprising administering an effective amount of a polypeptide comprising a 10 Fn3 domain, wherein the polypeptide comprises SEQ ID NO:82, and wherein the polypeptide binds PCSK9.
3. The method of claim 1 , wherein the subject has atherosclerosis.
4. The method of claim 1 , wherein the polypeptide further comprises polyethylene glycol.
5. The method of claim 1 , wherein the polypeptide further comprises sialic acid.
6. The method of claim 1 , wherein the polypeptide further comprises Fc or a Fc fragment.
7. The method of claim 1 , wherein the polypeptide further comprises serum albumin or a serum albumin binding protein.
8. The method of claim 1 , wherein the polypeptide further comprises a serum immunoglobulin binding protein.
9. The method of claim 1 , wherein the administration is subcutaneous.
10. The method of claim 1 , wherein the administration is intravenous.
11. The method of claim 10 , wherein the intravenous administration is by a bolus.
12. The method of claim 10 , wherein the intravenous administration is by continuous infusion.
13. The method of claim 2 , wherein the subject has atherosclerosis.
14. The method of claim 2 , wherein the polypeptide further comprises polyethylene glycol.
15. The method of claim 2 , wherein the polypeptide further comprises sialic acid.
16. The method of claim 2 , wherein the polypeptide further comprises Fc or a Fc fragment.
17. The method of claim 2 , wherein the polypeptide further comprises serum albumin or a serum albumin binding protein.
18. The method of claim 2 , wherein the polypeptide further comprises a serum immunoglobulin binding protein.
19. The method of claim 2 , wherein the administration is subcutaneous.
20. The method of claim 2 , wherein the administration is intravenous.
21. The method of claim 20 , wherein the intravenous administration is by a bolus.
22. The method of claim 20 , wherein the intravenous administration is by continuous infusion.