Composition comprising and method of using angiopoietin-like protein 3 Angptl3

• US 7,267,819 B2
• Filed: 11/15/2002
• Issued: 09/11/2007
• Est. Priority Date: 11/16/2001
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Ferrara, Napoleone, Gerber, Hans-Peter, Sherman, Daniel Eric, Pisabarro, Maria Teresa, Kowalski, Joe
• Primary Examiner(s): Spector; Lorraine
• Assistant Examiner(s): Shafer; Shulamith H.
• Application Number:
  US10/298,461
• Publication Number:
  US 20030215451A1
• Time in Patent Office: 1,761 Days
• Field of Search: 514/44
• US Class Current: 424/130.1
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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: 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 14/515 Angiogenesic factors; Angiogenin
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

Abstract

The present invention is directed to methods and means for making and using Angptl3 polypeptides. The invention specifically concerns the use of Angptl3 polypeptides in inducing liver regeneration and angiogenesis. Further methods include the use of Angptl3 polypeptides in the diagnosis and treatment of liver disease. Also provided herein are antibodies which bind to the polypeptides of the present invention.

Claims

1. A method of treating inflammatory disease in a liver, comprising administering to said liver an antibody or fragment thereof that binds Angptl3 and inhibits interaction of Angptl3 with α

vβ

3 integrin, thereby inhibiting the inflammatory disease in the liver.

2. The method of claim 1, wherein Angptl3 comprises an amino acid sequence of SEQ ID NO:

2.

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

4. The method of claim 1, wherein the inflammatory liver disease is liver cirrhosis, liver fibrosis, or toxic metabolic liver damage.

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

6. The method of claim 1, wherein the antibody fragment is a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

7. The method of claim 1, wherein the antibody is a single-chain antibody.

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

9. The method of claim 1, wherein the antibody is a humanized antibody.

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

11. A method for treating inflammatory liver disease in a mammalian subject, comprising administering to said mammalian subject an antibody or fragment thereof that binds to Angptl3 and inhibits interaction of Angptl3 with α

vβ

3 integrin, thereby treating the inflammatory liver disease.

12. The method of claim 11, wherein the mammalian subject is human.

13. The method of claim 11, wherein Angptl3 comprises an amino acid sequence of SEQ ID NO:

2.

14. The method of claim 11, wherein the inflammatory liver disease is liver cirrhosis, liver fibrosis, or toxic metabolic liver damage.

15. The method of claim 11, wherein the antibody is a single-chain antibody.

16. The method of claim 11, wherein the antibody is a monoclonal antibody.

17. The method of claim 11, wherein the antibody fragment is a Fab, Fab′

, F(ab′

)₂, or Fv fragment.