Fully human antibodies that bind to VEGFR2 and methods of use thereof
View Patent ↗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 fully human antibody of an IgG class that binds to a VEGFR2 [-] epitope, wherein the fully human antibody has a heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81.
2. The fully human antibody of claim 1 , wherein the antibody has a heavy chain/light chain variable domain 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. A fully human antibody Fab fragment, having a variable domain region from a heavy chain and a variable domain region from a light chain, wherein the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81.
4. The fully human antibody Fab fragment of claim 3 , wherein the antibody has a heavy chain/light chain variable domain 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.
5. A single chain human antibody, having a variable domain region from a heavy chain and a variable domain region from a light chain and a peptide linker connecting the heavy chain and light chain variable domain regions, wherein the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81.
6. The fully human single chain antibody of claim 5 , wherein the single chain fully human antibody has a heavy chain/light chain variable domain 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.
7. A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an anti-VEGFR2 polypeptide, wherein the anti-VEGFR2 polypeptide is selected from the group consisting of a fully human antibody of an IgG class that binds to a VEGFR2 epitope, a fully human antibody Fab fragment having a variable domain region from a heavy chain and a variable domain region from a light chain, a single chain human antibody having a variable domain region from a heavy chain and a variable domain region from a light chain and a peptide linker connecting the heavy chain and light chain variable domain regions;
wherein the fully human antibody has a heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81;
wherein the Fab fully human antibody fragment has the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81; and
wherein the single chain human antibody has the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81.
8. The method for treating a broad spectrum of mammalian cancers of claim 7 , wherein the fully human antibody has a heavy chain/light chain variable domain 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.
9. The method for treating a broad spectrum of mammalian cancers of claim 7 , wherein the fully human antibody Fab fragment has both a heavy chain variable domain region and a light chain variable domain region wherein the antibody has a heavy chain/light chain variable domain 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.
10. The method for treating a broad spectrum of mammalian cancers of claim 7 , wherein the fully human single chain antibody has both a heavy chain variable domain region and a light chain variable domain region, wherein the single chain fully human antibody has a heavy chain/light chain variable domain 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.
11. The method for treating a broad spectrum of mammalian cancers of claim 7 , wherein the mammalian cancer to be treated is selected from the group consisting of solid tumors, blood borne tumors, leukemias, hemangiomas, acoustic neuromas, neurofibromas, trachomas, and pyogenic granuloumas.
12. A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an anti-VEGFR2 polypeptide and an antineoplastic agent:
wherein the anti-VEGFR2 polypeptide is selected from the group consisting of a fully human antibody of an IgG class that binds to a VEGFR2 epitope, a fully human antibody Fab fragment having a variable domain region from a heavy chain and a variable domain region from a light chain, a single chain human antibody having a variable domain region from a heavy chain and a variable domain region from a light chain and a peptide linker connecting the heavy chain and light chain variable domain regions;
wherein the fully human antibody has a heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences 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 that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences 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. 74, SEQ ID NO. 78, and SEQ ID NO. 81;
wherein the antineoplastic agent is selected from the group consisting of anti-metabolites/anti-cancer agents, pyrimidine analogs, purine analogs, folate antagonists antiproliferative/antimitotic agents, vinca alkaloids, microtubule disruptors, taxane, vincristin, vinblastin, nocodazole, epothilones and navelbine, epidipodophyllotoxins actinomycin, amsacrine, anthracyclines, bleomycin, busulfan, camptothecin, carboplatin, chlorambucil, cisplatin, cyclophosphamide, cytoxan, dactinomycin, daunorubicin, doxorubicin, epirubicin, hexamethylmelamineoxaliplatin, iphosphamide, melphalan, merchlorehtamine, mitomycin, mitoxantrone, nitrosourea, plicamycin, procarbazine, taxol, taxotere, teniposide, triethylenethiophosphoramide, etoposide; antibiotics, dactinomycin (actinomycin D), daunorubicin, doxorubicin, idarubicin, anthracyclines, mitoxantrone, bleomycins, plicamycin, mitomycin; L-asparaginase; antiplatelet agents; antiproliferative/antimitotic alkylating agents, mechlorethamine, cyclophosphamide, melphalan, chlorambucil, ethylenimines, methylmelamines, alkyl sulfonates-busulfan, nitrosoureas, trazenes--dacarbazinine (DTIC); antiproliferative/antimitotic antimetabolites; platinum coordination complexes, procarbazine, hydroxyurea, mitotane, aminoglutethimide; hormones, hormone analogs, aromatase inhibitors; anticoagulants; fibrinolytic agents, aspirin, dipyridamole, ticlopidine, clopidogrel, abciximab; antimigratory agents; antisecretory agents; immunosuppressives anti-angiogenic compounds; angiotensin receptor blocker; nitric oxide donors; anti-sense oligonucleotides; antibodies; cell cycle inhibitors, differentiation inducers; mTOR inhibitors, topoisomerase inhibitors, corticosteroids; growth factor signal transduction kinase inhibitors; mitochondrial dysfunction inducers, caspase activators; and chromatin disruptors.F