Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
1. An isolated monoclonal antibody that binds to an epitope of PCSK9, wherein the epitope includes at least one of amino acid residues 311 to 313 of SEQ ID NO: 1, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
2. The isolated monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody is a neutralizing antibody.
3. The isolated monoclonal antibody of claim 2 , wherein the isolated monoclonal antibody was produced by a CHO cell.
4. The isolated monoclonal antibody of claim 3 , wherein the isolated monoclonal antibody binds to PCSK9 with a K D of less than or equal to 5×10 −9 M.
5. The isolated monoclonal antibody of claim 2 , wherein the isolated monoclonal antibody is a human antibody.
6. The isolated monoclonal antibody of claim 5 , wherein the isolated monoclonal antibody comprises a light chain region that comprises an amino acid sequence of SEQ ID NO: 157.
7. The isolated monoclonal antibody of claim 2 , wherein the epitope is a functional epitope.
8. The isolated monoclonal antibody of claim 2 , wherein the epitope is a structural epitope.
9. The isolated monoclonal antibody of claim 2 , wherein the epitope is an epitope on a native PCSK9 protein.
10. The isolated monoclonal antibody of claim 2 , wherein the epitope comprises at least residue 311 of SEQ ID NO: 1.
11. The isolated monoclonal antibody of claim 2 , wherein the epitope comprises at least residue 312 of SEQ ID NO: 1.
12. The isolated monoclonal antibody of claim 2 , wherein the epitope comprises at least residue 313 of SEQ ID NO: 1.
13. The isolated monoclonal antibody of claim 2 , wherein the epitope is a linear epitope of amino acid residues 311 to 313 of SEQ ID NO: 1.
14. The isolated monoclonal antibody of claim 2 , wherein the epitope comprises amino acid residues 311, 312, and 313 of SEQ ID NO: 1.
15. The isolated monoclonal antibody of claim 2 , wherein the isolated monoclonal antibody is a humanized antibody.
16. An isolated monoclonal antibody that binds to human PCSK9 having an amino acid sequence of SEQ ID NO: 1 at one or more of amino acid residues 311-313 of SEQ ID NO: 1, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
17. The isolated monoclonal antibody of claim 16 , wherein the isolated monoclonal antibody is a neutralizing antibody.
18. The isolated monoclonal antibody of claim 16 , wherein the isolated monoclonal antibody was produced by a CHO cell.
19. The isolated monoclonal antibody of claim 18 , wherein the isolated monoclonal antibody binds to PCSK9 with a K D of less than or equal to 5×10 −9 M.
20. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody is a human antibody.
21. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody comprises a light chain region that comprises an amino acid sequence of SEQ ID NO: 157.
22. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody binds at least amino acid residue 311 of SEQ ID NO: 1.
23. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody binds at least amino acid residue 312 of SEQ ID NO: 1.
24. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody binds at least amino acid residue 313 of SEQ ID NO: 1.
25. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody further binds at least one of amino acid residues 132, 351, 390, or 413 of SEQ ID NO: 1.
26. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody further binds at least one of amino acid residues 123, 129, or 337 of SEQ ID NO: 1.
27. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody further binds at least one of amino acid residues 123, 164, 208, 344, 347, or 349 of SEQ ID NO: 1.
28. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody further binds at least one of amino acid residues 337 or 352 of SEQ ID NO: 1.
29. The isolated monoclonal antibody of claim 17 , wherein the isolated monoclonal antibody is a humanized antibody.