Anti-LRP5/6 antibodies and methods of use
The present invention provides anti-LRP5/6 monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for treating diseases and disorders associated with Wnt pathway signaling.
1. An isolated antibody, or an antigen-binding fragment thereof, that binds to one or more LRP5 or LRP6 receptor, comprising a sequence comprising:
a CDRH1 sequence of SEQ ID NO:107, a CDRH2 sequence of SEQ ID NO:203 and a CDRH3 sequence of SEQ ID NO:452 or any one of SEQ ID NOs: 609-618.
2. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10.
3. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is humanized.
4. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is a single chain antibody, a scFv, a univalent antibody lacking a hinge region, a VHH, an sdAb, a Fab, a Fab′ fragment, or a minibody.
5. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises a fusion protein.
6. The isolated antibody, or antigen-binding fragment thereof, of claim 5 , wherein the antibody, or antigen-binding fragment thereof, is fused to a polypeptide sequence that binds one or more Frizzled (Fzd) receptors.
7. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , which modulates a Wnt signaling pathway in a cell.
8. A method for agonizing a Wnt signaling pathway in a cell, comprising contacting the cell with the isolated antibody, or antigen-binding fragment thereof, according to claim 7 , wherein the antibody, or antigen-binding fragment thereof, increases signaling via the Wnt signaling pathway in the cell.
9. An isolated polynucleotide encoding the isolated antibody, or an antigen-binding fragment thereof, according to claim 1 .
10. A pharmaceutical composition comprising a physiologically acceptable excipient, diluent, or carrier, and a therapeutically effective amount of the isolated antibody, or antigen-binding fragment thereof, according to claim 1 .