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 human monoclonal antibody that binds to an epitope on PSCK9, wherein the epitope comprises at least one of amino acid residues S123, E129, A311, D313, or D337 of SEQ ID NO: 1, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
2. The isolated human monoclonal antibody of claim 1 , wherein the epitope comprises at least two of amino acid residues S123, E129, A311, D313, or D337 of SEQ ID NO: 1.
3. The isolated human monoclonal antibody of claim 1 , wherein the epitope comprises at least three of amino acid residues S123, E129, A311, D313, or D337 of SEQ ID NO: 1.
4. The isolated human monoclonal antibody of claim 3 , wherein the isolated human monoclonal antibody is a neutralizing antibody.
5. The isolated human monoclonal antibody of claim 4 , wherein the isolated human monoclonal antibody was produced by a CHO cell.
6. The isolated human monoclonal antibody of claim 3 , wherein the isolated human monoclonal antibody binds to PCSK9 with a K D of less than or equal to 5×10 −9 M.
7. The isolated human monoclonal antibody of claim 3 , wherein the isolated human monoclonal antibody comprises a light chain region that comprises an amino acid sequence of SEQ ID NO: 157.
8. The isolated human monoclonal antibody of claim 3 , wherein the epitope is a functional epitope.
9. The isolated human monoclonal antibody of claim 3 , wherein the epitope is a structural epitope.
10. The isolated human monoclonal antibody of claim 3 , wherein the epitope is an epitope on a native PCSK9 protein.
11. The isolated human monoclonal antibody of claim 3 , wherein the epitope comprises at least residue 123 of SEQ ID NO: 1.
12. The isolated human monoclonal antibody of claim 3 , wherein the epitope comprises at least residue 129 of SEQ ID NO: 1.
13. The isolated human monoclonal antibody of claim 3 , wherein the epitope comprises at least residue 311 of SEQ ID NO: 1.
14. The isolated human monoclonal antibody of claim 3 , wherein the epitope comprises at least residue 313 of SEQ ID NO: 1.
15. The isolated human monoclonal antibody of claim 3 , wherein the epitope comprises at least residue 337 of SEQ ID NO: 1.
16. An isolated human 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 S123, E129, A311, D313, or D337 of SEQ ID NO: 1, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
17. The isolated human monoclonal antibody of claim 16 , wherein the isolated human monoclonal antibody binds to at least two of amino acid residues S123, E129, A311, D313, or D337 of SEQ ID NO: 1.
18. The isolated human monoclonal antibody of claim 16 , wherein the isolated human monoclonal antibody binds to at least three of amino acid residues S123, E129, A311, D313, or D337 of SEQ ID NO: 1.
19. The isolated human monoclonal antibody of claim 18 , wherein the isolated human monoclonal antibody is a neutralizing antibody.
20. The isolated human monoclonal antibody of claim 18 , wherein the isolated human monoclonal antibody was produced by a CHO cell.
21. The isolated human monoclonal antibody of claim 18 , wherein the isolated human monoclonal antibody binds to PCSK9 with a K D of less than or equal to 5×10 −9 M.
22. The isolated human monoclonal antibody of claim 16 , wherein the isolated human monoclonal antibody comprises a light chain region that comprises an amino acid sequence of SEQ ID NO: 157.
23. The isolated human monoclonal antibody of claim 17 , wherein the isolated human monoclonal antibody further binds at least one of amino acid residues 132, 351, 390, or 413 of SEQ ID NO: 1.
24. The isolated human monoclonal antibody of claim 17 , wherein the isolated human monoclonal antibody further binds at least one of amino acid residues 123, 164, 344, 347, or 349 of SEQ ID NO: 1.
25. The isolated human monoclonal antibody of claim 16 , wherein the isolated human monoclonal antibody competes for binding to PCSK9 with an antibody comprising a heavy chain amino acid sequence comprising an amino acid sequence of SEQ ID NO: 467 and a light chain amino acid sequence comprising an amino acid sequence of SEQ ID NO: 469.