Beta klotho-binding proteins
The present disclosure provides binding proteins, such as antibodies, that bind beta klotho, including human beta klotho, and methods of their use.
1. An antibody or fragment thereof that binds human beta-klotho, which comprises
a heavy chain variable region comprising a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6.
2. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:26 and the light chain variable region has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:27.
3. The antibody or fragment thereof of claim 1 , which is a monoclonal antibody.
4. The antibody or fragment thereof of claim 1 , which is a humanized antibody.
5. The antibody or fragment thereof of claim 1 , wherein the fragment is a Fab, Fab′, F(ab′) 2 , Fv, scFv, (scFv) 2 , single chain antibody, dual variable region antibody, or linear antibody.
6. A pharmaceutical composition which comprises the antibody or fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
7. A method of activating a beta-klotho/FGF receptor complex in a cell, wherein the method comprises contacting the cell with the antibody or fragment thereof of claim 1 .
8. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:26 and the light chain variable region has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:27.
9. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence as set forth in SEQ ID NO:26 and the light chain variable region comprises the amino acid sequence as set forth in SEQ ID NO:27.
10. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NOs:56-78.
11. The antibody or fragment thereof of claim 1 , wherein the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NOs:80-90, 124, 132, 134, 137, or 146.
12. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NOs:56-78 and the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NOs:80-90, 124, 132, 134, 137, or 146.
13. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:69 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:134.
14. The antibody or fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:70 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:137.