Antibodies directed to angiopoietin-2 and uses thereof

• US 20060246071A1
• Filed: 12/19/2005
• Published: 11/02/2006
• Est. Priority Date: 12/21/2004
• Status: Active Grant

• Current Assignee: MedImmune Ltd. (Astrazeneca PLC)
• Original Assignee: MedImmune Ltd. (Astrazeneca PLC)
• Inventors: Zhou, Qing, Green, Larry, Keyt, Bruce A., Yang, Xiao-Dong, Emery, Stephen Charles, Blakey, David Charles
• Granted Patent: US 7,973,140 B2
• Time in Patent Office: Days
• US Class Current: 424/145.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• 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 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• 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 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• 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

Antibodies directed to the antigen Ang-2 and uses of such antibodies are described. In particular, fully human monoclonal antibodies directed to the antigen Ang-2. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR'"'"'s), specifically from FR1 through FR4 or CDR1 through CDR3. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies.

Claims

1. A targeted binding agent that binds to Angiopoietin-2 with a Kd of less than 100 picomolar (pM).

2. The targeted binding agent of claim 1, wherein said targeted binding agent also binds to Angiopoietin-1.

3. The targeted binding agent of claim 1, wherein said targeted binding agent prevents Tie2 phosphorylation.

4. The targeted binding agent of claim 1, wherein said targeted binding agent binds Angiopoietin-2 with a Kd of less than 50 picomolar (pM).

5. The targeted binding agent of claim 1, wherein said targeted binding agent binds Angiopoietin-2 with a Kd of less than 20 picomolar (pM).

6. The targeted binding agent of claim 1, wherein said targeted binding agent binds Angiopoietin-2 with a Kd of less than 6 picomolar (pM).

7. The targeted binding agent, of claim 2, wherein said targeted binding agent binds Angiopoietin-1 with a Kd of less than 300 picomolar (pM).

8. The targeted binding agent of claim 2, wherein said targeted binding agent binds Angiopoietin-1 with a Kd of less than 160 picomolar (pM).

9. The targeted binding agent of claim 2, wherein said targeted binding agent binds Angiopoietin-1 with a Kd of less than 80 picomolar (pM).

10. The targeted binding agent of claim 2, wherein said targeted binding agent binds Angiopoietin-1 with a Kd of less than 40 picomolar (pM).

11. The targeted binding agent of claim 1, wherein said targeted binding agent is a monoclonal antibody.

12. The targeted binding agent of claim 11, wherein said targeted binding agent is a fully human monoclonal antibody.

13. The targeted binding agent of claim 12, wherein said targeted binding agent is mAb 3.19.3 (ATCC Accession Number PTA-7260) or mAb 3.3.2 (ATCC Accession Number PTA-7258) or mAb 5.88.3 (ATCC Accession Number PTA-7259).

14. The targeted binding agent of claim 1, in association with a pharmaceutically acceptable carrier.

15. A nucleic acid molecule encoding the targeted binding agent of claim 1.

16. A vector comprising the nucleic acid molecule of claim 15.

17. A host cell comprising the vector of claim 16.

18. A method of treating a malignant tumor in an animal, comprising administering to said animal in need thereof a therapeutically effective dose of the targeted binding agent of claim 1.

19. The method of claim 18, wherein said animal is human.

20. The method of claim 18, wherein said targeted binding agent is the monoclonal antibody 3.19.3 (ATCC Accession Number PTA-7260) or 3.3.2 (ATCC Accession Number PTA-7258) or 5.88.3 (ATCC Accession Number PTA-7259).

21. The method of claim 18, wherein said malignant tumor is selected from the group consisting of:

melanoma, small cell lung cancer, non-small cell lung cancer, glioma, hepatocellular (liver) carcinoma, thyroid tumor, gastric (stomach) cancer, prostate cancer, breast cancer, ovarian cancer, bladder cancer, lung cancer, glioblastoma, endometrial cancer, kidney cancer, colon cancer, pancreatic cancer, and epidermoid carcinoma.

22. A method of treating Angiopoietin-2 induced angiogenesis, comprising administering to an animal in need thereof a therapeutically effective dose of the targeted binding agent of claim 1.

23. The method of claim 22, wherein said animal is human.

24. The method of claim 22, wherein said targeted binding agent is a fully human monoclonal antibody.

25. The method of claim 22, wherein the targeted binding agent binds to Angiopoietin-1.

26. An antagonist of the biological activity of Angiopoietin-1 and Angiopoietin-2, wherein the antagonist does not bind to the ATP-binding site of Tie-2.

27. The antagonist of claim 26, wherein the Angiopoietin-1 antagonist activity and the Angiopoietin-2 antagonist activity is comprised within one molecule.

28. The antagonist of claim 26, wherein the Angiopoietin-1 antagonist activity and the Angiopoietin-2 antagonist activity is comprised within more than one molecule.

29. The antagonist of claim 26, wherein the antagonist binds to the Tie-2 receptor.

30. The antagonist of claim 26, wherein the antagonist binds to Angiopoietin-1 and Angiopoietin -2.

31. The antagonist of claims 26, wherein the antagonist is an antibody.

32. The antagonist of claim 31, wherein the antagonist is a monoclonal antibody.

33. The antagonist of claim 32, wherein the monoclonal antibody is a fully human monoclonal antibody.

34. The antagonist of claim 33, wherein the fully human monoclonal antibody is antibody 3.19.3 (ATCC Accession Number PTA-7260) or 3.3.2 (ATCC Accession Number PTA-7258) or 5.88.3 (ATCC Accession Number PTA-7259).

35. The antagonist of claim 32, wherein the antagonist is an antibody that binds to the same epitope as the fully human monoclonal antibody 3.19.3 (ATCC Accession Number PTA-7260) or 3.3.2 (ATCC Accession Number PTA-7258) or 5.88.3 (ATCC Accession Number PTA-7259).