Fully human antibodies that bind to vascular endothelial growth factor receptor 2 (VEGFR2)
There is disclosed compositions and methods relating to anti-VEGFR2 antibodies. More specifically, there is disclosed fully human antibodies that bind VEGFR2, VEGFR2-binding fragments and derivatives of such antibodies, and VEGFR2-binding polypeptides comprising such fragments. Further still, there is disclosed antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having various cancers.
1. A recombinant fully human anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody, or an antigen binding fragment thereof, that binds to VEGFR2 comprising complementarity determining regions (CDRs) as set forth in a heavy chain variable domain amino acid sequence selected from the group consisting of SEQ ID NO. 9, SEQ ID NO. 23, SEQ ID NO. 51, SEQ ID NO. 63, SEQ ID NO. 73 and SEQ ID NO. 77, and comprising CDRs as set forth in a light chain variable domain amino acid sequence selected from the group consisting of SEQ ID NO. 10, SEQ ID NO. 24, SEQ ID NO. 52, SEQ ID NO. 64, SEQ ID NO. 78, and SEQ ID NO. 81.
2. The recombinant fully human anti-VEGFR2 antibody, or antigen-binding fragment thereof, of claim 1 , comprising a heavy chain/light chain variable domain amino acid sequence selected from the group consisting of SEQ ID NO. 9/SEQ ID NO. 10, SEQ ID NO. 23/SEQ ID NO. 24, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 63/SEQ ID NO. 64, SEQ ID NO. 73/SEQ ID NO. 74, SEQ ID NO. 77/SEQ ID NO. 78, and SEQ ID NO. 77/SEQ ID NO. 81.
3. The recombinant anti-VEGFR2 antibody or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is classified as an isotype selected from the group consisting of: IgG, IgM, IgD, IgA, and IgE.
4. The recombinant anti-VEGFR2 antibody, or antigen-binding fragment thereof, of claim 3 , wherein the antibody is an IgG1 or an IgG4.
5. The recombinant anti-VEGFR2 antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is a monoclonal antibody, a Fab, a Fab′, a F(ab′) 2 , a Fv, a domain antibody (dAb), a single-chain antibody (scFv), a chimeric antibody, a diabody, a triabody or a tetrabody.
6. The recombinant anti-VEGFR2 antigen binding fragment of claim 5 , which is a scFv.
7. The recombinant anti-VEGFR2 antigen binding fragment of claim 5 , which is a Fab.
8. The recombinant anti-VEGFR2 antibody, or an antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of:
a) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 9 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 9, and a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 10 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 10;
b) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 23 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 23, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 24 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 24;
c) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 51 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 51, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 52 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 52;
d) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 63 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 63, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 64 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 64;
e) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 73 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 73, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 74 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 74;
f) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 77 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 77, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 78 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 78; and
g) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 77 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 77, and comprising a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 81 and which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO. 81.
9. The recombinant anti-VEGR2 antigen-binding fragment of claim 8 , which is a Fab or a scFv.
10. A pharmaceutical composition comprising the recombinant anti-VEGFR2 antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier.
11. A method of treating cancer in a human subject in need thereof, the method comprising the step of administering an effective amount of the recombinant anti-VEGFR2 antibody, or antigen-binding fragment thereof, of claim 1 to the subject, such that the cancer is treated.
12. The method of claim 11 , wherein the cancer is selected from the group consisting of leukemia, bladder cancer, bone cancer, brain cancer, breast cancer, cartilage cancer, colon cancer, kidney cancer, liver cancer, lung cancer, lymph node cancer, nervous tissue cancer, ovary cancer, pancreatic cancer, prostate cancer, skeletal muscle cancer, skin cancer, spinal cord cancer, spleen cancer, stomach cancer, testes cancer, thymus cancer, thyroid cancer, trachea cancer, urogenital tract cancer, ureter cancer, urethra cancer, uterus cancer, and vaginal cancer.