Compositions and methods of using angiopoietin-like 4 protein

• US 20070054856A1
• Filed: 09/28/2006
• Published: 03/08/2007
• Est. Priority Date: 07/20/2004
• Status: Abandoned Application

• Current Assignee: Hanspeter Gerber, Stuart Bunting, Xiao Liang
• Original Assignee: Hanspeter Gerber, Stuart Bunting, Xiao Liang
• Inventors: Gerber, Hanspeter, Liang, Xiao, Bunting, Stuart
• Application Number:
  US11/540,430
• Publication Number:
  US 20070054856A1
• Time in Patent Office: Days
• US Class Current: 514/13.300
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/515 : Angiogenesic factors; Angiogenin
• CPC Class Codes: C07K 16/22 : against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/2839 : against the integrin superfamily
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 2710/10343 : viral genome or elements thereof as genetic vector

Abstract

ANGPTL4 compositions and methods of using such compositions, and agonists or antagonists thereof, for the diagnosis and treatment of diseases or disorders are included, including methods to modulate cell proliferation, cell adhesion, and cell migration.

Claims

1. A method of stimulating proliferation of hepatocytes, the method comprising:

administering an effective amount of an angiopoietin-like 4 protein (ANGPTL4) to a population of hepatocytes or pre-hepatocytes thereby stimulating proliferation.

2. The method of claim 1, wherein the hepatocytes are in a subject.

3. The method of claim 2, wherein the subject is a human.

4. The method of claim 1, wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.

5. The method of claim 1, wherein the ANGPTL4 comprises amino acid residues 184 to 406 of human ANGPTL4.

6. The method of claim 1, wherein administration step comprises administering a nucleic acid sequence than encodes for the ANGPTL4.

7. A method of stimulating proliferation of hepatocytes, the method comprising:

administering an effective amount of an agent that stimulates production of an ANGPTL4 in hepatocytes or pre-hepatocytes, thereby stimulating proliferation.

8. A method of inhibiting proliferation of hepatocytes, the method comprising administering an effective amount of an ANGPTL4 antagonist to a population of hepatocytes or pre-hepatocytes.

9. The method of claim 8, wherein the antagonist is an agent that inhibits ANGPTL4 protein production in the hepatocyte.

10. The method of claim 8, wherein the agent is an antisense or ribozyme molecule.

11. The method of claim 8, wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.

12. The method of claim 8, wherein the ANGPTL4 antagonist is an anti-α

Vβ

5 antibody.

13. A method of inducing cell adhesion of hepatocytes, the method comprising:

administering an effective amount of a composition comprising an ANGPTL4 to a population of hepatocytes, thereby inducing the cell adhesion of hepatocytes.

14. The method of claim 13, wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.

15. The method of claim 13, wherein the ANGPTL4 comprises amino acids residues 185 to 406 of human ANGPTL4.

16. The method of claim 13, wherein the composition comprises the ANGPTL4 with a carrier.

17. A method of inhibiting cell adhesion of hepatocytes, the method comprising:

administering an effective amount of a composition comprising an ANGPTL4 antagonist to a population of hepatocytes, thereby inhibiting the cell adhesion of the hepatocytes.

18. The method of claim 17, wherein the antagonist is an anti-ANGPTL4 antibody.

19. The method of claim 17, wherine the antagonist is an anti-α

Vβ

5 antibody.

20. A method of stimulating proliferation of pre-adipocytes, the method comprising:

administering an effective amount of a composition comprising an ANGPTL4 or agonist to a population of preadipocytes, thereby inducing the proliferation of pre-adipocytes.

21. The method of claim 20, wherein the preadipocytes are in a subject.

22. The method of claim 20, wherein the subject is a human.

23. The method of claim 20, wherein the composition comprises the ANGPTL4 with a carrier.

24. The method of claim 20, wherein the ANGPTL4 comprises amino acid residues 23 to 406 of human ANGPTL4.

25. The method of claim 24, wherein the ANGPTL4 comprises amino acid residues from about 23 to about 162.

26. A method of inhibiting the proliferation of pre-adipocytes, the method comprising administering an effective amount of a composition comprising an ANGPTL4 antagonist to a population of preadipocytes.

27. The method of claim 26, wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.

28. A method of inhibiting a biological activity of ANGPTL4, the method comprising administering an ANGPTL4 antagonist that binds to C-terminal of ANGPTL4.

29. The method of claim 28, wherein the ANGPTL4 antagonist is an anti-ANGPTL4 antibody.

30. The method of claim 28, wherein the ANGPTL4 antagonist is an anti-α

Vβ

5 antibody.

31. The method of claim 28, wherein the ANGPTL4 antagonist blocks Angptl4 from binding to α

Vβ

5.

32. The method of claim 28, wherein the biological activity comprises inducing cell proliferation or cell differentiation.

34. The antibody of claim 32, wherein the antibody is a neutralizing antibody.

33. An antibody that binds to C-terminal of ANGPTL4.

35. A composition comprising a variant of ANGPTL4, wherein the variant ANGPTL4 is not proleolytically processed.

36. The composition of claim 35, wherein the variant of ANGPTL4 comprises an alteration of amino acid 162 and/or 164.

37. The composition of claim 36, wherein the alteration is a substitution.

38. The composition of claim 37, wherein the substitution is at position 162 and at position 164.