Monoclonal antibodies against ANGPTL3

• US 20080177045A1
• Filed: 12/06/2007
• Published: 07/24/2008
• Est. Priority Date: 12/08/2006
• Status: Active Grant

• Current Assignee: Lexicon Pharmaceuticals, Inc. (The Invus Group LLC)
• Original Assignee: Lexicon Pharmaceuticals, Inc. (The Invus Group LLC)
• Inventors: Landes, Gregory, Hong, Seokjoo, Desai, Urvi, Powell, David, Lee, E-Chiang
• Granted Patent: US 7,935,796 B2
• Time in Patent Office: Days
• US Class Current: 530/388.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Monoclonal antibodies that specifically bind to ANGPTL3 are provided. Monoclonal antibodies that neutralize at least one activity of ANGPTL3 are provided. Methods of treating a disorder of lipid metabolism using neutralizing monoclonal antibodies are provided.

Claims

1. A monoclonal antibody that binds to ANGPTL3 and neutralizes at least one activity of ANGPTL3.

2. The monoclonal antibody of claim 1, wherein the monoclonal antibody is a mouse monoclonal antibody.

3. The monoclonal antibody of claim 1, wherein the monoclonal antibody is a humanized monoclonal antibody.

4. The monoclonal antibody of claim 1, wherein the monoclonal antibody is a human monoclonal antibody.

5. The monoclonal antibody of claim 1, wherein the monoclonal antibody decreases the level of at least one serum lipid in vivo.

6. The monoclonal antibody of claim 1, wherein the monoclonal antibody binds to an epitope of ANGPTL3 having the amino acid sequence of SEQ ID NO:

59.

7. The monoclonal antibody of claim 1, wherein the monoclonal antibody binds to an epitope of ANGPTL3 having the amino acid sequence of SEQ ID NO:

60.

8. The monoclonal antibody of claim 1, wherein the monoclonal antibody binds to an epitope of ANGPTL3 having the amino acid sequence of SEQ ID NO:

9.

9. The monoclonal antibody of claim 1, wherein the monoclonal antibody binds to an epitope of ANGPTL3 having the amino acid sequence of SEQ ID NO:

10.

10. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

28.

11. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

22 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

30.

12. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

24 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

32.

13. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

64 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

68.

14. The monoclonal antibody of claim 1, wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

66 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

70.

15. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 4.7.1.

16. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 4.8.3.

17. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 4.9.1.

18. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 1.315.1.

19. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 5.35.

20. The monoclonal antibody of claim 1, wherein the monoclonal antibody specifically binds to the same epitope as antibody 5.50.

21-64. -64. (canceled)

65. A monoclonal antibody that binds to ANGPTL3 and neutralizes at least one activity of ANGPTL3, wherein the antibody binds to a peptide having the amino acid sequence of SEQ ID NO:

9 with a K_D of less than 50 nM.

66. The monoclonal antibody of claim 65, wherein the antibody binds to a peptide having the amino acid sequence of SEQ ID NO:

9 with a K_D of less than 30 nM.

67. The monoclonal antibody of claim 65, wherein the antibody binds to a peptide having the amino acid sequence of SEQ ID NO:

9 with a K_D of less than 10 nM.

68. The monoclonal antibody of claim 65, wherein the antibody binds to a peptide having the amino acid sequence of SEQ ID NO:

9 with a K_D of less than 5 nM.

69-77. -77. (canceled)