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 an epitope on hPCSK9 comprising one or more of residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 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 is a human antibody.
4. The isolated monoclonal antibody of claim 2 , wherein the epitope comprises a structural epitope.
5. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue R207.
6. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue D208.
7. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue D162.
8. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue R164.
9. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue E167.
10. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue T132.
11. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue S351.
12. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue A390.
13. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue A413.
14. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue S123.
15. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue E129.
16. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue A311.
17. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue D313.
18. The isolated monoclonal antibody of claim 4 , wherein the epitope comprises residue D337.
19. The isolated monoclonal antibody of claim 1 , wherein the epitope comprises at least two of residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
20. The isolated monoclonal antibody of claim 1 , wherein the epitope comprises at least three of residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
21. The isolated monoclonal antibody of claim 1 , wherein the epitope comprises at least four of residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
22. The isolated human monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody was produced by a CHO cell.
23. The isolated human monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody binds to PCSK9 with a K D of less than or equal to 5×10 −9 M.
24. The isolated human monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody comprises a light chain region that comprises an amino acid sequence of SEQ ID NO: 157.
25. An isolated monoclonal neutralizing antibody specific for PCSK9 that binds at least one of amino acid residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
26. The isolated monoclonal neutralizing antibody of claim 25 , wherein the isolated monoclonal neutralizing antibody is human, and wherein the isolated monoclonal neutralizing antibody comprises a light chain that comprises the amino acid sequence of SEQ ID NO: 157.
27. The isolated monoclonal neutralizing antibody of claim 25 , wherein the isolated monoclonal antibody binds to at least two of amino acid residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
28. The isolated monoclonal neutralizing antibody of claim 25 , wherein the isolated monoclonal antibody binds to at least three of amino acid residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
29. The isolated monoclonal neutralizing antibody of claim 25 , wherein the isolated monoclonal antibody binds to at least four of amino acid residues 207, 208, 162, 164, 167, 132, 351, 390, 413, 123, 129, 311, 313, or 337 of SEQ ID NO:1.
30. The isolated monoclonal neutralizing antibody of claim 25 , wherein the isolated monoclonal antibody competes for binding to PCSK9 with an antibody comprising a heavy chain variable region having an amino acid sequence of SEQ ID NO: 49 and a light chain variable region having an amino acid sequence of SEQ ID NO: 23.