Antibodies Directed to Angiopoietin-2 and Uses Thereof
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 immunoglobin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementary determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3. Hybridomas or other cell lines expressing such immunoglobin molecules and monoclonal antibodies.
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 . An antagonist according to claim 26 wherein the Angiopoietin-1 antagonist activity and the Angiopoietin-2 antagonist activity is comprised within one molecule.
28 . An antagonist according to claim 26 wherein the Angiopoietin-1 antagonist activity and the Angiopoietin-2 antagonist activity is comprised within more than one molecule.
29 . An antagonist according to claim 26 wherein the antagonist binds to the Tie-2 receptor.
30 . An antagonist according to claim 26 wherein the antagonist binds to Angiopoietin-1 and Angiopoietin-2.
31 . An antagonist according to claim 26 wherein the antagonist is an antibody.
32 . An antagonist according to claim 31 wherein the antagonist is a monoclonal antibody.
33 . An antagonist according to claim 32 wherein the antagonist is a fully human monoclonal antibody.
34 . An antagonist according to claim 33 wherein the antagonist is 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).
35 . An antagonist according to 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).
36 . Use of the targeted binding agent of claim 1 in the preparation of a medicament for the treatment of a malignant tumor.
37 . The use of claim 36 , 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.
38 . The use of claim 36 , wherein said targeted binding agent is a monoclonal antibody.
39 . The use of claim 38 , wherein said antibody is a fully human monoclonal antibody.
40 . The use of claim 39 , wherein said fully human monoclonal antibody is a fully human 3.19.3 antibody (ATCC Accession Number PTA-7260) or 3.3.2 (ATCC Accession Number PTA-7258) or 5.88.3 (ATCC Accession Number PTA-7259).