Methods for modulating angiogenesis by using the anti-angiogenic angiotensin-7 and polynucleotides encoding therefor

• US 6,835,381 B1
• Filed: 05/17/2002
• Issued: 12/28/2004
• Est. Priority Date: 07/02/1999
• Status: Expired due to Fees

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Bayer AG
• Inventors: Zubov, Dmitry, Dubois-Stringfellow, Nathalie, Friedrich, Gabi, Hagen, Gustav, Wick, Maresa
• Primary Examiner(s): Nickol, Gary B.
• Application Number:
  US10/018,386
• Time in Patent Office: 956 Days
• Field of Search: 424/184.1, 424/200.1, 514/2
• US Class Current: 424/184.1
• CPC Class Codes: A61K 38/1891 Angiogenesic factors; Angiogenin

Abstract

The present invention provides methods for modulating angiogenesis by administering anti-angiogenic Ang-7 polypeptides to a subject. Methods of modulating angiogenesis by administering an anti-angiogenic ANG-7 nucleic acid are also provided.

Claims

1. A method for inhibiting angiogenesis comprising administering to a mammal a therapeutically effective dose of an isolated Ang-7 polypeptide, wherein said polypeptide comprises SEQ ID NO:

2.

2. The method of claim 1, wherein the mammal is human.

3. The method of claim 1, wherein the administering is performed in vivo.

4. The method of claim 1, further comprising administering a pharmaceutical carrier.

5. The method of claim 1, wherein the administering is ex vivo.

6. The method of claim 1, wherein the Ang-7 polypeptide is recombinantly expressed.

7. The method of claim 6, wherein the Ang-7 polypeptide is recombinantly expressed by culturing a cell containing an ANG-7 nucleic acid under conditions which result in expression of the polypeptide, and recovering the Ang-7 polypeptide from the cell culture.

8. The method of claim 6, wherein the Ang-7 polypeptide is expressed in E. coli.

9. The method of claim 6, wherein the Ang-7 polypeptide is expressed in mammalian cells.

10. The method of claim 7, wherein the ANG-7 nucleic acid is operably linked to a promoter in an expression vector.

11. The method of claim 7, wherein the ANG-7 nucleic acid has the sequence of human ANG-7 (SEQ ID NO:

1).

12. A method of treating a tumor in a subject in need of anti-angiogenesis therapy comprising administering to a subject a therapeutically effective amount of an Ang-7 polypeptide, wherein said polypeptide comprises SEQ ID NO:

2.

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

14. The method of claim 12, wherein the administering is performed in vivo.

15. The method of claim 12, further comprising administering a pharmaceutical carrier.

16. The method of claim 12, wherein the administration is ex vivo.

17. The method of claim 12, wherein the Ang-7 polypeptide is recombinantly expressed.

18. The method of claim 17, wherein the Ang-7 polypeptide is recombinantly expressed by culturing a cell containing an ANG-7 nucleic acid under conditions which result in expression of the polypeptide, and recovering the Ang-7 polypeptide from the cell culture.

19. The method of claim 17, wherein the Ang-7 polypeptide is expressed in mammalian cells, yeast cells, bacterial cells, or insect cells.

20. The method of claim 17, wherein the Ang-7 polypeptide is expressed in mammalian cells.

21. The method of claim 18, wherein the ANG-7 nucleic acid is operably linked to a promoter in an expression vector.

22. The method of claim 18, wherein the expression vector is an adenoviral vector, a retroviral vector, or a lentiviral vector.

23. The method of claim 18, wherein the ANG-7 nucleic acid has the sequence of human ANG-7 (SEQ ID NO:

1).

24. A method of inhibiting endothelial tube formation comprising administering to an endothelial cell an effective amount of an Ang-7 polypeptide, wherein said polypeptide comprises SEQ ID NO:

2.

25. A method of inhibiting tumor cell growth comprising administering to a tumor cell an effect amount of an Ang-7 polypeptide, wherein said polypeptide comprises SEQ ID NO:

2.

26. A method of inhibiting tumor cell growth comprising administering to a tumor cell an effective amount of an Ang-7 polypeptide, or fragment, variant, derivative, analog or a pharmaceutically acceptable salt thereof.

27. The method of claim 26, wherein the Ang-7 polypeptide is human Ang-7.