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 . A nucleic acid encoding an antibody or antigen binding fragment thereof that binds to human VEGFR2, the antibody or antigen binding fragment thereof 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:
(a) the CDR1H sequence is GFTFSWYVMS (amino acids 26-35 of SEQ ID NO: 208),
the CDR2H sequence is SIYPQGGATNYADSVKG (SEQ ID NO: 239),
the CDR3H sequence is GNYFDY (SEQ ID NO: 241),
the CDR1L sequence is RASQSVSSNYFG (SEQ ID NO: 245),
the CDR2L sequence is GASSRAT (SEQ ID NO: 246), and
the CDR3L sequence is QQHDSSPLS (SEQ ID NO: 248);
(b) the CDR1H sequence is GFTFSWYVMG (SEQ ID NO: 237),
the CDR2H sequence is SIYPSGGATNYADSVKG (SEQ ID NO: 240),
the CDR3H sequence is GNYLDY (SEQ ID NO: 242),
the CDR1L sequence is RASQSVSSNYFG (SEQ ID NO: 245),
the CDR2L sequence is GASSRAT (SEQ ID NO: 246), and
the CDR3L sequence is QQFDSSPLS (SEQ ID NO: 249);
(c) the CDR1H sequence is GFTFSWYVMG (SEQ ID NO: 237),
the CDR2H sequence is SIYPSGGATNYADSVKG (SEQ ID NO: 240),
the CDR3H sequence is GPYLDY (SEQ ID NO: 243),
the CDR1L sequence is RASQSVSSNYFG (SEQ ID NO: 245),
the CDR2L sequence is GASSRAT (SEQ ID NO: 246), and
the CDR3L sequence is QQFDSSPLT (SEQ ID NO: 250); or
(d) the CDR1H sequence is GFTFSWYVMG (SEQ ID NO: 237),
the CDR2H sequence is SIYPSGGATNYADSVKG (SEQ ID NO: 240),
the CDR3H sequence is GSYLDY (SEQ ID NO: 244),
the CDR1L sequence is RASQSVSSNYFG (SEQ ID NO: 245),
the CDR2L sequence is GASSRAT (SEQ ID NO: 246), and
the CDR3L sequence is QQFDSSPLT (SEQ ID NO: 250).
2 . The nucleic acid of claim 1 , wherein:
(a) the heavy chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 208, and the light chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 212;
(b) the heavy chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 216, and the light chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 220;
(c) the heavy chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 224, and the light chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 228; or
(d) the heavy chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 232, and the light chain variable domain has a sequence that is at least 85% identical to the sequence of SEQ ID NO: 236.
3 . The nucleic acid of claim 1 , wherein:
(a) the heavy chain variable domain has a sequence that is SEQ ID NO: 208, and the light chain variable domain has a sequence that is SEQ ID NO: 212;
(b) the heavy chain variable domain has a sequence that is SEQ ID NO: 216, and the light chain variable domain has a sequence that is SEQ ID NO: 220;
(c) the heavy chain variable domain has a sequence that is SEQ ID NO: 224, and the light chain variable domain has a sequence that is SEQ ID NO: 228; or
(d) the heavy chain variable domain has a sequence that is SEQ ID NO: 232, and the light chain variable domain has a sequence that is SEQ ID NO: 236.
4 . The nucleic acid of claim 1 , wherein the antibody or antigen binding fragment thereof has isotype IgG.
5 . The nucleic acid of claim 1 , wherein the antibody or antigen binding fragment thereof is an scFv, Fv, Fab′, Fab, F(ab′)2, or diabody.
6 . The nucleic acid of claim 1 , wherein the antibody or antigen binding fragment thereof binds to human VEGFR2 and murine VEGFR2.