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Last Updated: December 15, 2024

Claims for Patent: 8,981,064


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Summary for Patent: 8,981,064
Title:Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract: 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.
Inventor(s): Jackson; Simon Mark (San Carlos, CA), Shan; Bei (Redwood City, CA), Shen; Wenyan (Palo Alto, CA), King; Chadwick Terence (North Vancouver, CA), Ketchem; Randal Robert (Snohomish, WA), Mehlin; Christopher (Seattle, WA), Carabeo; Teresa Arazas (New York, NY)
Assignee: Amgen Inc. (Thousand Oaks, CA)
Application Number:14/459,743
Patent Claims:1. A monoclonal antibody that binds to human PCSK9 at an epitope on PCSK9 that overlaps with an epitope that is bound by an antibody that comprises: a heavy chain variable region of the amino acid sequence in SEQ ID NO: 49; and a light chain variable region of the amino acid sequence in SEQ ID NO: 23, and wherein the epitope of said monoclonal antibody further overlaps with a site to which an EGFa domain of LDLR binds and thereby blocks binding between human PCSK9 and the EGFa domain of LDLR.

2. The monoclonal antibody of claim 1, wherein the monoclonal antibody further binds to human PCSK9 at an epitope on PCSK9 that overlaps with an epitope that is bound by a second antibody that comprises: a heavy chain variable region of the amino acid sequence in SEQ ID NO: 67; and a light chain variable region of the amino acid sequence in SEQ ID NO: 12.

3. The monoclonal antibody of claim 1, wherein said monoclonal antibody is a human or a humanized monoclonal antibody.

4. The monoclonal antibody of claim 1, wherein said monoclonal antibody is an IgG.

5. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises an intact immunoglobulin.

6. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a fragment of an intact immunoglobulin.

7. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a human kappa light chain.

8. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 157.

9. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a human lambda light chain.

10. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 156.

11. A monoclonal antibody that binds to human PCSK9 at an epitope on PCSK9 that overlaps with an epitope that is bound by an antibody that comprises: a heavy chain variable region of the amino acid sequence in SEQ ID NO: 67; and a light chain variable region of the amino acid sequence in SEQ ID NO: 12, and wherein the epitope of said monoclonal antibody further overlaps with a site to which an EGFa domain of LDLR binds and thereby blocks binding between human PCSK9 and the EGFa domain of LDLR.

12. The monoclonal antibody of claim 11, wherein said monoclonal antibody is a human or a humanized monoclonal antibody.

13. The monoclonal antibody of claim 11, wherein said monoclonal antibody is an IgG.

14. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises an intact immunoglobulin.

15. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises a fragment of an intact immunoglobulin.

16. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises a human kappa light chain.

17. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 157.

18. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises a human lambda light chain.

19. The monoclonal antibody of claim 11, wherein the monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 156.

20. A monoclonal antibody that binds to human PCSK9 at an epitope on PCSK9 that overlaps with an epitope that is bound by an antibody that comprises: a heavy chain variable region of the amino acid sequence in SEQ ID NO: 467; and a light chain variable region of the amino acid sequence in SEQ ID NO: 469, and wherein the epitope of said monoclonal antibody further overlaps with a site to which an EGFa domain of LDLR binds and thereby blocks binding between human PCSK9 and the EGFa domain of LDLR.

21. The monoclonal antibody of claim 20, wherein the monoclonal antibody is an IgG.

22. The monoclonal antibody of claim 20, wherein the monoclonal antibody is a human or humanized antibody.

23. The monoclonal antibody of claim 20, wherein the monoclonal antibody comprises a light chain that comprises the amino acid sequence of SEQ ID NO: 156.

24. The monoclonal antibody of claim 20, wherein the monoclonal antibody comprises a light chain that comprises the amino acid sequence of SEQ ID NO: 157.

25. A monoclonal antibody that binds to human PCSK9 at an epitope on PCSK9 that overlaps with an epitope that is bound by an antibody that comprises: a heavy chain variable region of the amino acid sequence in SEQ ID NO: 87; and a light chain variable region of the amino acid sequence in SEQ ID NO: 13, and wherein the epitope of said monoclonal antibody further overlaps with a site to which an EGFa domain of LDLR binds and thereby blocks binding between human PCSK9 and the EGFa domain of LDLR.

26. The monoclonal antibody of claim 25, wherein said monoclonal antibody is an IgG.

27. The monoclonal antibody of claim 25, wherein the monoclonal antibody is a human or a humanized antibody.

28. The monoclonal antibody of claim 25, wherein the monoclonal antibody comprises a light chain that comprises the amino acid sequence of SEQ ID NO: 156.

29. The monoclonal antibody of claim 25, wherein the monoclonal antibody comprises a light chain that comprises the amino acid sequence of SEQ ID NO: 157.

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