Anti-FZD10 monoclonal antibodies and methods for their use

摘要

The present invention relates generally to anti-FZD10 antibodies and to methods of using anti-FZD10 antibodies. In particular, the anti-FZD10 antibodies described herein are useful for altering one or more of survival, replication, differentiation and epithelial-to-mesenchymal cell transition of embryonic stem cells and/or for the treatment of diseases, such as a variety of cancers, associated with expression of FZD10, including as stand-alone therapies and in combination therapies with other agents.

主权项

1. A composition comprising an isolated anti-FZD10 antibody that is selected from the group consisting of:
(a) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a heavy chain variable region comprising the VHCDR1, VHCDR2 and VHCDR3 amino acid sequences set forth in SEQ ID NOs:5, 6 and 7, respectively, and a light chain variable region comprising the VLCDR1, VLCDR2 and VLCDR3 amino acid sequences set forth in: SEQ ID NOs:9, 11, 12, respectively, or SEQ ID NOs:10, 11, 12, respectively; (b) the isolated antibody, or an antigen-binding fragment thereof, of (a), wherein the heavy chain variable region comprises the VHCDR1, VHCDR2 and VHCDR3amino acid sequences set forth in SEQ ID NOs:5, 6, and 7, respectively, and the light chain variable region comprises the VLCDR1, VLCDR2 and VLCDR3 amino acid sequences set forth in SEQ ID NOs:9, 11, and 12, respectively; (c) the isolated antibody, or an antigen-binding fragment thereof, of (b), wherein he light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:3; (d) the isolated antibody, or an antigen-binding fragment thereof, of (b), wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:1; (e) the isolated antibody, or an antigen-binding fragment thereof, of (a), wherein the heavy chain variable region comprises the VHCDR1, VHCDR2 and VHCDR3 amino acid sequences set forth in SEQ ID) NOs:5, 6, and 7, respectively, and the light chain variable region comprises the VLCDR1, VLCDR2 and VLCDR3 amino acid sequences set forth in SEQ ID NOs:10, 11, and 12, respectively; (f) the isolated antibody, or an antigen-binding fragment thereof, of (e), wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:1; (g) the isolated antibody, or an antigen-binding fragment thereof, of (e), wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:4; (h) the isolated antibody, or an antigen-binding fragment thereof, of (a) wherein the antibody is humanized; (i) the isolated antibody, or antigen-binding fragment thereof, of (h) wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:37; (j) the isolated antibody, or antigen-binding fragment thereof, of (i), further comprising a heavy chain variable region that comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ NO:39; (k) the isolated antibody, or antigen-binding fragment thereof, of (i), further comprising a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:39; (l) the isolated antibody, or antigen-binding fragment thereof, of (k), further comprising a human lambda light chain constant region comprising the amino acid sequence set forth in SEQ ID NO:36; (m) the isolated antibody, or antigen-binding fragment thereof, of (l), further comprising a human IgGl constant region comprising the amino acid sequence set forth in SEQ ID NO:34; and (n) the isolated antibody, or antigen-binding fragment thereof, of (h), wherein the isolated antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO:29 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:31,