Human anti-VEGFR-2/KDR antibodies
The invention relates to antibodies that bind to VEGFR-2. The antibodies are used for treating neoplastic diseases, hyperproliferative disorders, and angiogenic disorders and can be used alone or in combination with other agents.
1. An isolated antibody or antigen binding fragment thereof that binds to human VEGFR2, comprising a heavy chain variable domain, which comprises a CDR1H, a CDR2H, and a CDR3H sequence, and a light chain variable domain, which comprises a CDR1L, a CDR2L, and a CDR3L sequence wherein:
(i) the CDR1H sequence is GFTFSWYVMG (SEQ ID NO: 237);
(ii) the CDR2H sequence is SIYPQGGATSYADSVKG (SEQ ID NO: 238);
(iii) the CDR3H sequence is GNYFDY (SEQ ID NO: 241);
(iv) the CDR1L sequence is RASQSVSSNYFG (SEQ ID NO: 245);
(v) the CDR2L sequence is GASSRAT (SEQ ID NO: 246); and
(vi) the CDR3L sequence is QQFDSLPLT (SEQ ID NO: 247).
2. The antibody or antigen binding fragment of claim 1 , wherein the heavy chain variable domain has a sequence that is SEQ ID NO: 200, and wherein the light chain variable domain has a sequence that is SEQ ID NO: 204.
3. The antibody or antigen binding fragment of claim 1 , which has isotype IgG.
4. The antibody or antigen binding fragment of claim 1 , which is an scFv, Fv, Fab′, Fab, F(ab′)2, or diabody.
5. The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment binds to human VEGFR2 and murine hVEGFR2.
6. The antibody or antigen binding fragment of claim 1 , wherein the heavy chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 200, and wherein the light chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 204.
7. A composition comprising an antibody or antigen binding fragment of claim 1 , and a pharmaceutically acceptable carrier.
8. A method of neutralizing activation of human VEGFR2 or murine VEGFR2 comprising contacting a cell with an effective amount of an antibody or antigen binding fragment of claim 1 .
9. A method of inhibiting angiogenesis associated with tumor growth in a subject in need thereof, the method comprising administering to the subject an effective amount of an antibody or antigen binding fragment of claim 1 .
10. A method of reducing tumor growth in a subject in need thereof, the method comprising administering to the subject an effective amount of an antibody or antigen binding fragment of claim 1 .
11. The method of claim 10 , the method further comprising administering to the subject an antineoplastic agent.
12. The method of claim 10 , the method further comprising administering to the subject an anti-inflammatory agent or an immunosuppressant.
13. A method of treating a neoplastic disease in a subject, the method comprising administering to the subject an effective amount of an antibody or antigen binding fragment of claim 1 , wherein the neoplastic diseases is selected from the group consisting of lung cancer, colorectal cancer, renal cell carcinoma, glioblastoma, ovarian cancer, bladder cancer, gastric cancer, multiple myeloma, non-small cell lung cancer, and pancreatic cancer.