Angiopoetin-like 4 (ANGPTL4) antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-9988443-B2
Application number	US-201514819700-A
Country	US
Kind code	B2
Filing date	Aug 6, 2015
Priority date	Aug 7, 2014
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The present invention relates to monoclonal antibodies binding to human angiopoetin-like protein 4 (hereinafter, sometimes referred to as “ANGPTL4”), and pharmaceutical compositions and methods of treatment comprising the same.

First claim

The invention claimed is:

1. An isolated anti-ANGPTL4 antibody or fragment thereof, wherein the antibody or fragment comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 313; and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 323.

2. An isolated anti-ANGPTL4 antibody or fragment thereof, wherein the antibody or fragment comprises a heavy chain variable region CDR1 of SEQ ID NO:307; CDR2 of SEQ ID NO:308; and CDR3 of SEQ ID NO:309; and a light chain variable region CDR1 of SEQ ID NO:317; CDR2 of SEQ ID NO:318; and CDR3 of SEQ ID NO:319 .

3. An isolated anti-ANGPTL4 antibody or fragment thereof, wherein the antibody or fragment comprises a heavy chain variable region CDR1 of SEQ ID NO:310; CDR2 of SEQ ID NO:311; and CDR3 of SEQ ID NO:312; and a light chain variable region CDR1 of SEQ ID NO:320; CDR2 of SEQ ID NO:321; and CDR3 of SEQ ID NO:322 .

4. The antibody or fragment of claim 1 , wherein the antibody or fragment is a monoclonal antibody, humanized antibody, single chain antibody, Fab fragment, Fv fragment, F(ab′)2 fragment, or scFv fragment.

5. The antibody or fragment of claim 1 , wherein the antibody or fragment is an IgG1 or IgG4 isotype.

6. The antibody or fragment of claim 1 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:315, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:325.

7. The antibody or fragment of claim 1 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:295, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:305.

8. A bispecific antibody comprising the antibody or fragment of claim 1 .

9. A pharmaceutical composition comprising the antibody or fragment of claim 1 and a pharmaceutically acceptable carrier.

10. The antibody or fragment of claim 2 , wherein the antibody or fragment is a monoclonal antibody, humanized antibody, single chain antibody, Fab fragment, Fv fragment, F(ab′)2 fragment, or scFv fragment.

11. The antibody or fragment of claim 2 , wherein the antibody or fragment is an IgG1 or IgG4 isotype.

12. The antibody or fragment of claim 2 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:315, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:325.

13. The antibody or fragment of claim 2 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:295, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:305.

14. A bispecific antibody comprising the antibody or fragment of claim 2 .

15. A pharmaceutical composition comprising the antibody or fragment of claim 2 and a pharmaceutically acceptable carrier.

16. The antibody or fragment of claim 2 , wherein the antibody or fragment comprises a heavy chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:313, and a light chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:323.

17. The antibody or fragment of claim 3 , wherein the antibody or fragment is a monoclonal antibody, humanized antibody, single chain antibody, Fab fragment, Fv fragment, F(ab′)2 fragment, or scFv fragment.

18. The antibody or fragment of claim 3 , wherein the antibody or fragment is an IgG1 or IgG4 isotype.

19. The antibody or fragment of claim 3 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:315, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:325.

20. The antibody or fragment of claim 3 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:295, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:305.

21. A bispecific antibody comprising the antibody or fragment of claim 3 .

22. A pharmaceutical composition comprising the antibody or fragment of claim 3 and a pharmaceutically acceptable carrier.

23. The antibody or fragment of claim 3 , wherein the antibody or fragment comprises a heavy chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:313, and a light chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:323.

24. An isolated anti-ANGPTL4 antibody or fragment thereof, wherein the antibody or fragment comprises heavy chain variable regions CDR1, CDR2, and CDR3 of a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:313; and light chain variable regions CDR1, CDR2, and CDR3 of a light chain variable domain comprising the amino acid sequence of SEQ ID NO:323.

25. The antibody or fragment of claim 24 , wherein the antibody or fragment is a monoclonal antibody, humanized antibody, single chain antibody, Fab fragment, Fv fragment, F(ab′)2 fragment, or scFv fragment.

26. The antibody or fragment of claim 24 , wherein the antibody or fragment is an IgG1 or IgG4 isotype.

27. The antibody or fragment of claim 24 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:315, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:325 .

28. The antibody or fragment of claim 24 , wherein the antibody or fragment comprises a heavy chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:295, and a light chain comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:305 .

29. A bispecific antibody comprising the antibody or fragment of claim 24 .

30. A pharmaceutical composition comprising the antibody or fragment of claim 24 and a pharmaceutically acceptable carrier.

31. The antibody or fragment of claim 24 , wherein the antibody or fragment comprises a heavy chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:313, and a light chain variable region comprising an amino acid sequence that has at least 90% identity to SEQ ID NO:323.

Assignees

• Trauger John
• Voznesensky Andrei Igorevich
• Neugebauer Julia
• Runz Steffen
• Novartis Ag

Inventors

• Trauger John
• Voznesensky Andrei Igorevich
• Neugebauer Julia
• Runz Steffen

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/92

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

• C07K16/22 Primary

  against growth factors {; against growth regulators} · CPC title