Stabilized angiopoietin-2 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-10329345-B2
Application number	US-201615335610-A
Country	US
Kind code	B2
Filing date	Oct 27, 2016
Priority date	Jan 28, 2008
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

Stabilized antibodies directed to Angiopoeitin-2 and uses of such antibodies are described. Nucleic acid and amino acid sequences, hybridomas or other cell lines for expressing such antibodies are also provided.

First claim

We claim:

1. An isolated antibody that binds to angiopoietin-2 (Ang-2), wherein the antibody comprises a heavy chain variable region of SEQ ID No:7 (MEDI5) and a light chain variable region selected from the group consisting of:
a) SEQ ID No:3 (MEDI1);
b) SEQ ID No:4 (MEDI2);
c) SEQ ID No:5 (MEDI3);
d) SEQ ID No:6 (MEDI4); and
e) SEQ ID No:8 (MEDI6);
wherein the antibody is a full-length antibody or fragment thereof.

2. The antibody according to claim 1 , wherein the antibody comprises a light chain variable region of SEQ ID No:3 (MEDI1).

3. The antibody according to claim 1 , wherein the antibody, when produced, exhibits a production efficiency in a mammalian host cell equal to or greater than 2 times the production efficiency of an Ang-2 antibody comprising SEQ ID No: 1 and SEQ ID No: 2 (3.19.3).

4. The antibody according to claim 1 , wherein the antibody exhibits an aggregation rate that is at least 10% lower than the aggregation rate of an Ang-2 antibody comprising SEQ ID No: 1 and SEQ ID No: 2 (3.19.3).

5. The antibody according to claim 1 , wherein the antibody exhibits a melting temperature that is higher than the melting temperature of an Ang-2 antibody comprising SEQ ID No: 1 and SEQ ID No: 2 (3.19.3).

6. A pharmaceutical composition comprising: an isolated antibody according to claim 1 , wherein the antibody comprises a light chain variable region of SEQ ID No:3 (MEDI1) and a heavy chain variable region of SEQ ID No:7 (MEDI5); and an excipient.

7. A method of inhibiting angiogenesis of a cancer tumor in an human in need thereof, wherein the method comprises administering to the human a composition comprising: an isolated antibody of claim 1 ; and an excipient.

8. The method according to claim 7 , wherein the composition further comprises one or more other cancer therapeutic agents.

9. The method according to claim 7 , wherein the cancer is selected from the group consisting of melanoma, colon, colorectal, lung, small cell lung carcinoma, non-small cell lung carcinoma, breast, rectum, stomach, glioma, prostate, ovary, testes, thyroid, kidney, liver, hepatocellular carcinoma pancreas, brain, neck, glioblastoma, endometrial cancer, and central nervous system cancer.

10. The method according to claim 7 , wherein the composition is administered intravenously, subcutaneously, intratumorally, intramuscularly, parenterally, or orally.

11. A method of treating arthritis in a human in need thereof, wherein the method comprises administering a composition comprising: an isolated antibody of claim 1 ; and an excipient.

12. The method according to claim 11 , wherein the method further comprises administering one or more anti-inflammatory therapeutic agents.

13. The method according to claim 12 , wherein the anti-inflammatory therapeutic agent is a TNF-α antagonist.

14. The antibody according to claim 1 , wherein the antibody is a full-length antibody.

15. The antibody according to claim 1 , wherein the antibody is an antibody fragment.

Assignees

• Medimmune Ltd

Inventors

• Bedian Vahe
• Dall'Acqua William
• Wu Herren
• Bowen Michael
• Brown Jeffrey
• Minter Ralph
• Buchanan Andrew

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title