Monospecific anti-frizzled antibodies and methods of use
The present invention provides anti-Fzd monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of diseases.
1 . An isolated antibody, or an antigen-binding fragment thereof, that binds to Frizzled 1 (Fzd1), comprising a sequence comprising:
(i) CDRH1 of SEQ ID NO: 51, CDRH2 of SEQ ID NO: 747 and CDRH3 of SEQ ID NO: 1443; and
(ii) CDRL1 of SEQ ID NO: 2139, CDRL2 of SEQ ID NO: 2833 and CDRL3 of SEQ ID NO: 3527.
2 . The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is humanized.
3 . The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is a Fab or a Fab′ fragment.
4 . The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is a fusion protein.
5 . The isolated antibody, or antigen-binding fragment thereof, of claim 4 , wherein the antibody, or antigen-binding fragment thereof, is fused to a polypeptide sequence that binds LRP5 or LRP6.
6 . The isolated antibody or antigen binding fragment of claim 1 , comprising:
a) a variable light chain having at least 90% sequence identity to SEQ ID NO: 22; and
b) a variable heavy chain having at least 90% sequence identity to SEQ ID NO: 1523.
7 . The isolated antibody, or antigen-binding fragment thereof, of claim 1 , which modulates a Wnt signaling pathway in a cell, optionally a mammalian cell.
8 . 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 .
9 . 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 .
10 . The isolated antibody or antigen binding fragment thereof of claim 6 , comprising:
a) a polypeptide comprising SEQ ID NO: 22; and
b) a polypeptide comprising SEQ ID NO: 23.