Anti-Tie2 antibodies and uses thereof
The present invention provides antibodies that bind to Tie2 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Tie2 and block the interaction between Tie2 and one or more Tie2 ligands such as angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), angiopoietin 3 (Ang3) and/or angiopoietin 4 (Ang4). The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more Tie2 biological activities including angiogenesis.
1. A method for inhibiting the growth of a tumor in a patient, the method comprising administering to the patient a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds human Tie2 and blocks the interaction between Tie2 and a Tie2 ligand, wherein the antibody or antigen-binding fragment thereof interacts with amino acids 96-106 of SEQ ID NO:7, amino acids 139-152 of SEQ ID NO:7; and amino acids 166-175 of SEQ ID NO:7, as determined by hydrogen/deuterium exchange.
2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof specifically binds a rodent Tie2 and human Tie2.
3. The method of claim 2 , wherein the rodent Tie2 is mouse Tie2 or rat Tie2.
4. The method of claim 3 , wherein the antibody or antigen-binding fragment thereof specifically binds human, mouse and rat Tie2.
5. The method of claim 1 , wherein the Tie2 ligand is selected from the group consisting of angiopoietin 1 (Ang1), Ang2, Ang3 and Ang4.
6. A method for inhibiting the growth of a tumor in a patient, the method comprising administering to the patient a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds human Tie2 and blocks the interaction between Tie2 and a Tie2 ligand, wherein the antibody or antigen-binding fragment thereof comprises the complementarity determining regions (CDRs) of an antibody produced from a cell line deposited with the American Type Culture Collection (ATCC) under accession number PTA-12295 or PTA-12296.
7. The method of claim 6 , wherein the antibody or antigen-binding fragment thereof comprises the CDRs of an antibody produced from a cell line deposited with the ATCC under accession number PTA-12295, and blocks the interaction between Tie2 and all four of Ang1, Ang2, Ang3 and Ang4.
8. The method of claim 6 , wherein the antibody or antigen-binding fragment thereof is a human antibody having the variable regions of an antibody produced from a cell line deposited with the American Type Culture Collection under accession number PTA-12295.
9. The method of claim 8 , wherein the human antibody has a human IgG4 constant region.
10. The method of claim 6 , wherein the antibody or antigen-binding fragment thereof is a human antibody having the variable regions of an antibody produced from a cell line deposited with the American Type Culture Collection under accession number PTA-12296.
11. A method for inhibiting the growth of a tumor in a patient, the method comprising administering to the patient a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds human Tie2 and blocks the interaction between Tie2 and a Tie2 ligand, wherein the antibody or antigen-binding fragment thereof binds the same epitope on human Tie2 as an antibody produced from a cell line deposited with the American Type Culture Collection under accession number PTA-12295 or PTA-12296.
12. A method for inhibiting the growth of a tumor in a patient, the method comprising administering to the patient a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds human Tie2 and blocks the interaction between Tie2 and a Tie2 ligand, wherein the antibody or antigen-binding fragment thereof competes for binding to human Tie2 with an antibody produced from a cell line deposited with the American Type Culture Collection under accession number PTA-12295 or PTA-12296.