Methods of treating cardiovascular disorders with lectin-like oxidized LDL receptor 1 antibodies

Patent metadata

Field	Value
Publication number	US-9988455-B2
Application number	US-201615390067-A
Country	US
Kind code	B2
Filing date	Dec 23, 2016
Priority date	Jun 21, 2013
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The present invention relates to monoclonal antibodies binding to human lectin-like oxidized LDL (low density lipoprotein) receptor 1 (hereinafter, sometimes referred to as “LOX-1”), and pharmaceutical compositions and methods of treatment comprising the same.

First claim

The invention claimed is:

1. A method of treating a subject afflicted with a lectin-type oxidized low density lipoprotein receptor 1 (LOX-1)-disorder that is a cardiovascular disorder, the method comprising administering to the subject an effective amount of an isolated antibody or antigen binding fragment thereof comprising a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO:309; and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO:319.

2. The method of claim 1 , wherein the subject is afflicted with one or more of intermittent claudication and Rutherford Class II/III Claudication.

3. The method of claim 1 , wherein the subject is afflicted with angina.

4. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:311 and a light chain comprising the amino acid sequence of SEQ ID NO:321.

5. The method of claim 1 , wherein the antibody is a monoclonal antibody.

6. The method of claim 1 , wherein the antibody is a human antibody.

7. A method of treating a subject afflicted with a LOX-1-disorder that is a cardiovascular disorder, the method comprising administering to the subject an effective amount of an isolated antibody or antigen binding fragment thereof comprising a VH comprising complementarity determining regions HCDR1, HCDR2, and HCDR3 and a VL comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:303; the HCDR2 comprises the amino acid sequence of SEQ ID NO:304; the HCDR3 comprises the amino acid sequence of SEQ ID NO:305; the LCDR1 comprises the amino acid sequence of SEQ ID NO:313; the LCDR2 comprises the amino acid sequence of SEQ ID NO:314; and the LCDR3 comprises the amino acid sequence of SEQ ID NO:315.

8. The method of claim 7 , wherein the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:309, and wherein the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:319.

9. The method of claim 7 , wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:309, and wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:319.

10. The method of claim 7 , wherein the VH comprises the amino acid sequence of SEQ ID NO:309.

11. The method of claim 7 , wherein the VL comprises the amino acid sequence of SEQ ID NO:319.

12. The method of claim 7 , wherein the antibody is a monoclonal antibody.

13. The method of claim 7 , wherein the antibody is a human antibody.

14. The method of claim 7 , wherein the antibody or fragment thereof is a single chain antibody, Fab fragment, Fv fragment, F(ab)2 fragment, or scFv fragment.

15. The method of claim 7 , wherein the antibody or fragment thereof is an IgG1 isotype.

16. The method of claim 7 , wherein the subject is afflicted with one or more of intermittent claudication and Rutherford Class II/III Claudication.

17. The method of claim 7 , wherein the subject is afflicted with angina.

18. A method of treating a subject afflicted with a LOX-1-disorder that is a cardiovascular disorder, the method comprising administering to the subject an effective amount of an isolated antibody or antigen binding fragment thereof comprising a VH comprising complementarity determining regions HCDR1, HCDR2, and HCDR3, and a VL comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:306; the HCDR2 comprises the amino acid sequence of SEQ ID NO:307; the HCDR3 comprises the amino acid sequence of SEQ ID NO:308; the LCDR1 comprises the amino acid sequence of SEQ ID NO:316; the LCDR2 comprises the amino acid sequence of SEQ ID NO:317; and the LCDR3 comprises the amino acid sequence of SEQ ID NO:318.

19. The method of claim 18 , wherein the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:309, and wherein the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:319.

20. The method of claim 18 , wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:309, and wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:319.

21. The method of claim 18 , wherein the VH comprises the amino acid sequence of SEQ ID NO:309.

22. The method of claim 18 , wherein the VL comprises the amino acid sequence of SEQ ID NO:319.

23. The method of claim 18 , wherein the antibody is a monoclonal antibody.

24. The method of claim 18 , wherein the antibody is a human antibody.

25. The method of claim 18 , wherein the antibody or fragment thereof is a single chain antibody, Fab fragment, Fv fragment, F(ab)2 fragment, or scFv fragment.

26. The method of claim 18 , wherein the antibody or fragment thereof is an IgG1 isotype.

27. The method of claim 18 , wherein the subject is afflicted with one or more of intermittent claudication and Rutherford Class II/III Claudication.

28. The method of claim 18 , wherein the subject is afflicted with angina.

Assignees

• Novartis Ag

Inventors

• Heldwein Kurt Alex
• Brogdon Jennifer
• Dole William
• Trauger John
• Tang Yuting
• Neugebauer Julia
• Schmid Annika

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/2851 Primary

  against the lectin superfamily, e.g. CD23, CD72 · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title