Human anti-VEGFR-2/KDR antibodies
View Patent ↗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 polynucleotide encoding an antibody or fragment thereof that binds to human VEGFR2, the antibody or fragment thereof comprising a heavy chain variable domain comprising a CDR-1H, CDR-2H, and CDR-3H sequence and a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein:
(i) the CDR-1H sequence consists of residues 26 to 35 of SEQ ID NO: 4;
(ii) the CDR-2H sequence consists of residues 50 to 66 of SEQ ID NO: 4;
(iii) the CDR-3H sequence is SEQ ID NO:3;
(iv) the CDR-1L, CDR-2L, and CDR-3L sequences are selected from the group consisting of:
SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7;
SEQ ID NO:21, SEQ ID NO:22, and SEQ ID NO:23;
SEQ ID NO:25, SEQ ID NO:26, and SEQ ID NO:27;
SEQ ID NO:29, SEQ ID NO:30, and SEQ ID NO:31;
SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35;
SEQ ID NO:37, SEQ ID NO:38, and SEQ ID NO:39;
SEQ ID NO:41, SEQ ID NO:42, and SEQ ID NO:43; and
SEQ ID NO:45; SEQ ID NO:46, and SEQ ID NO:47.
2. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:5, the CDR-2L sequence is SEQ ID NO:6, and the CDR-3L sequence is SEQ ID NO:7.
3. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:21, the CDR-2L sequence is SEQ ID NO:22, and the CDR-3L sequence is SEQ ID NO:23.
4. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:25, the CDR-2L sequence is SEQ ID NO:26, and the CDR-3L sequence is SEQ ID NO:27.
5. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:29, the CDR-2L sequence is SEQ ID NO:30, and the CDR-3L sequence is SEQ ID NO:31.
6. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:33, the CDR-2L sequence is SEQ ID NO:34, and the CDR-3L sequence is SEQ ID NO:35.
7. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:37, the CDR-2L sequence is SEQ ID NO:38, and the CDR-3L sequence is SEQ ID NO:39.
8. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:41, the CDR-2L sequence is SEQ ID NO:42, and the CDR-3L sequence is SEQ ID NO:43.
9. The An isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein the CDR-1L sequence is SEQ ID NO:45, the CDR-2L sequence is SEQ ID NO:46, and the CDR-3L sequence is SEQ ID NO:47.
10. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain sequence is SEQ ID NO:4 or a sequence that is at least 95% identical to SEQ ID NO:4 and the light chain variable domain sequence is selected from the group consisting of:
SEQ ID NO:8, a sequence that is at least 95% identical to SEQ ID NO:8,
SEQ ID NO:24, a sequence that is at least 95% identical to SEQ ID NO:24,
SEQ ID NO:28, a sequence that is at least 95% identical to SEQ ID NO:28,
SEQ ID NO:32, a sequence that is at least 95% identical to SEQ ID NO:32,
SEQ ID NO:36, a sequence that is at least 95% identical to SEQ ID NO:36,
SEQ ID NO:40, a sequence that is at least 95% identical to SEQ ID NO:40,
SEQ ID NO:44, a sequence that is at least 95% identical to SEQ ID NO:44,
SEQ ID NO:48, and a sequence that is at least 95% identical to SEQ ID NO:48.
11. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:8 and a sequence that is at least 95% identical to SEQ ID NO:8.
12. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:24 and a sequence that is at least 95% identical to SEQ ID NO:24.
13. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:28 and a sequence that is at least 95% identical to SEQ ID NO:28.
14. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:32 and a sequence that is at least 95% identical to SEQ ID NO:32.
15. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:36 and a sequence that is at least 95% identical to SEQ ID NO:36.
16. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:40 and a sequence that is at least 95% identical to SEQ ID NO:40.
17. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:44 and a sequence that is at least 95% identical to SEQ ID NO:44.
18. The isolated polynucleotide of claim 1 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a light chain variable domain, wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:48 and a sequence that is at least 95% identical to SEQ ID NO:48.
19. An isolated polynucleotide encoding an antibody or fragment thereof that binds to human VEGFR2, the antibody or fragment thereof comprising a heavy chain variable domain comprising a CDR-1H, CDR-2H, and CDR-3H sequence and a light chain variable domain comprising a CDR-1L, CDR-2L, and CDR-3L sequence, wherein:
(i) the CDR-1H sequence consists of residues 26 to 35 of SEQ ID NO: 12;
(ii) the CDR-2H sequence consists of residues 50 to 66 of SEQ ID NO: 12;
(iii) the CDR-3H sequence is SEQ ID NO:11;
(iv) the CDR-1L sequence is SEQ ID NO:13;
(v) the CDR-2L sequence is SEQ ID NO:14; and
(vi) the CDR-3L sequence is SEQ ID NO:15.
20. The isolated polynucleotide of claim 19 , wherein the polynucleotide encodes an antibody or fragment thereof comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain sequence is selected from the group consisting of SEQ ID NO:12 and a sequence that is at least 95% identical to SEQ ID NO:12, and wherein the light chain variable domain sequence is selected from the group consisting of SEQ ID NO:16 and a sequence that is at least 95% identical to SEQ ID NO:16.