Antibodies to notch receptors
The present invention relates to Notch-binding agents and Notch antagonists and methods of using the agents and/or antagonists for treating diseases such as cancer. The present invention provides antibodies that specifically bind to a non-ligand binding region of the extracellular domain of one or more human Notch receptor, such as Notch2 and/or Notch3, and inhibit tumor growth. The present invention further provides methods of treating cancer, the methods comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.
1. An isolated antibody encoded by the polynucleotide deposited with ATCC as PTA-9547.
2. An isolated cell comprising or producing the antibody of claim 1 .
3. A pharmaceutical composition comprising the antibody of claim 1 .
4. An isolated antibody that specifically binds human Notch2 and/or Notch3, wherein the antibody comprises:
(a) a heavy chain CDR1 comprising SSSGMS (SEQ ID NO:5), a heavy chain CDR2 comprising VIASSGSNTYYADSVKG (SEQ ID NO:6), and a heavy chain CDR3 comprising SIFYTT (SEQ ID NO:51); and
(b) a light chain CDR1 comprising RASQSVRSNYLA (SEQ ID NO:8), a light chain CDR2 comprising GASSRAT (SEQ ID NO:9), and a light chain CDR3 comprising QQYSNFPI (SEQ ID NO:10).
5. The antibody of claim 4 , which is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or an antibody fragment.
6. An isolated cell comprising or producing the antibody of claim 4 .
7. A pharmaceutical composition comprising the antibody of claim 4 .
8. An isolated antibody that specifically binds human Notch2 and/or Notch3, wherein the antibody comprises:
(a) a heavy chain CDR1 comprising SSSGMS (SEQ ID NO:5), a heavy chain CDR2 comprising VIASSGSNTYYADSVKG (SEQ ID NO:6), and a heavy chain CDR3 comprising GIFFAI (SEQ ID NO:7); and
(b) a light chain CDR1 comprising RASQSVRSNYLA (SEQ ID NO:8), a light chain CDR2 comprising GASSRAT (SEQ ID NO:9), and a light chain CDR3 comprising QQYSNFPI (SEQ ID NO:10).
9. The antibody of claim 8 , which is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or an antibody fragment.
10. An isolated cell comprising or producing the antibody of claim 8 .
11. A pharmaceutical composition comprising the antibody of claim 8 .
12. An isolated antibody that specifically binds human Notch2 and/or Notch3, wherein the antibody comprises:
(a) a heavy chain variable region having at least about 90% sequence identity to SEQ ID NO:50, SEQ ID NO:14, or SEQ ID NO:20; and
(b) a light chain variable region having at least about 90% sequence identity to SEQ ID NO:13 or SEQ ID NO:19.
13. The antibody of claim 12 , which comprises:
(a) a heavy chain variable region having at least about 95% sequence identity to SEQ ID NO:50; and
(b) a light chain variable region having at least about 95% sequence identity to SEQ ID NO:13.
14. The antibody of claim 13 , which comprises:
(a) a heavy chain variable region comprising SEQ ID NO:50; and
(b) a light chain variable region comprising SEQ ID NO:13.
15. The antibody of claim 12 , which comprises:
(a) a heavy chain variable region having at least about 95% sequence identity to SEQ ID NO:14; and
(b) a light chain variable region having at least about 95% sequence identity to SEQ ID NO:13.
16. The antibody of claim 15 , which comprises:
(a) a heavy chain variable region comprising SEQ ID NO:14; and
(b) a light chain variable region comprising SEQ ID NO:13.
17. The antibody of claim 12 , which is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or an antibody fragment.
18. An isolated cell comprising or producing the antibody of claim 12 .
19. A pharmaceutical composition comprising the antibody of claim 12 .
20. An isolated polypeptide comprising a sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:49.
21. An isolated antibody encoded by the polynucleotide deposited with ATCC as PTA-10170.
22. An isolated cell comprising or producing the antibody of claim 21 .
23. A pharmaceutical composition comprising the antibody of claim 21 .