Anti-RSPO1 antibodies
The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.
1. An isolated antibody that specifically binds human R-spondin 1 (RSPO1), wherein the antibody comprises:
(a) a heavy chain CDR1 comprising TGYTMH (SEQ ID NO:12), a heavy chain CDR2 comprising GINPNNGGTTYNQNFKG (SEQ ID NO:13), and a heavy chain CDR3 comprising KEFSDGYYFFAY (SEQ ID NO:14); and
(b) a light chain CDR1 comprising KASQDVIFAVA (SEQ ID NO:15), a light chain CDR2 comprising WASTRHT (SEQ ID NO:16), and a light chain CDR3 comprising QQHYSTPW (SEQ ID NO:17).
2. The antibody of claim 1 , which comprises:
(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:10, and a light chain variable region having at least 90% sequence identity to SEQ ID NO:11; or
(b) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:55, and a light chain variable region having at least 90% sequence identity to SEQ ID NO:59.
3. The antibody of claim 2 , which comprises:
(a) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:10; and
(b) a light chain variable region having at least 95% sequence identity to SEQ ID NO:11.
4. The antibody of claim 1 , which is a recombinant antibody, a monoclonal antibody, a chimeric antibody, a bispecific antibody, a humanized antibody, a human antibody, an IgG1 antibody, an IgG2 antibody, or an antibody fragment.
5. The antibody of claim 1 , which inhibits binding of RSPO1 to at least one leucine-rich repeat containing G protein coupled receptor (LGR).
6. The antibody of claim 5 , wherein the LGR is selected from the group consisting of LGR4, LGR5, and LGR6.
7. The antibody of claim 6 , wherein the LGR is LGR5.
8. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
9. An isolated monoclonal antibody that competes with the antibody of claim 1 for specific binding to RSPO1.
10. An isolated antibody that binds the same epitope on RSPO1 as the antibody of claim 1 .
11. An isolated monoclonal antibody that binds an epitope on RSPO1 that overlaps with the epitope on RSPO1 bound by the antibody of claim 1 .
12. An isolated antibody that specifically binds human R-spondin 1 (RSPO1), which comprises:
(a) a heavy chain variable region comprising SEQ ID NO:10; and
(b) a light chain variable region comprising SEQ ID NO:11.
13. A hybridoma cell line having ATCC deposit number PTA-11970.
14. An antibody produced by the cell line of claim 13 .
15. A humanized form of the antibody of claim 14 .