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US 2013/0095104 A1Published application
Anti-fzd10 monoclonal antibodies and methods for their use
AssigneeOmeros Corporation
InventorsW. Jason Cummings, Munehisa Yabuki, John B. Leppard, Christi L. Wood, Nancy Maizels, Daniel S. Allison, Larry W. Tjoelker
Life of this patent
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Abstract
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.
Claims34
A composition comprising an isolated anti-FZD10 antibody that is selected from:
- (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 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:9, 11, and 12, respectively;
- (c) the isolated antibody, or an antigen-binding fragment thereof, of (b), wherein the 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 domain 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 domain that comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:39;
- (k) the isolated antibody, or antigen-binding fragment thereof, of (i), further comprising a heavy chain variable domain 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 IgG1 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.
14 more elements
A composition comprising an isolated anti-FZD10 antibody that is selected from:
- (a) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a light chain variable region comprising any one of the amino acid sequences set forth in SEQ ID NOs:2, 3, and 4;
- (b) the isolated antibody of (a) wherein the light chain variable region comprises SEQ ID NO:2 and further comprising a heavy chain variable region comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:1;
- (c) the isolated antibody of (a) wherein the light chain variable region comprises SEQ ID NO:3 and further comprising a heavy chain variable region comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:1;
- and (d) the isolated antibody of (a) wherein the light chain variable region comprises SEQ ID NO:4 and further comprising a heavy chain variable region comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:1.
1 more element
A method for altering at least one of (i) survival, (ii) replication, (iii) differentiation and (iv) epithelial-to-mesenchymal cell transition of an FZD10-overexpressing cell, comprising contacting the cell with an anti-FZD10 antibody under conditions and for a time sufficient for specific binding of the antibody to the cell, wherein the anti-FZD10 antibody is selected from the group consisting of:
- (1) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a heavy chain variable domain 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 domain 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;
- (2) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:1;
- (3) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a light chain variable domain comprising any one of the amino acid sequences set forth in SEQ ID NOs:2, 3, and 4;
- and
- (4) an isolated antibody that competes with the antibody of (1), (2) or (3) for binding to FZD10.
3 more elements
A method for inhibiting tumor propagation by an FZD10-overexpressing cell, comprising:
- contacting an isolated FZD10-overexpressing tumor cell with an anti-FZD10 antibody under conditions and for a time sufficient for specific binding of the antibody to the cell,
- wherein said step of contacting takes place before, during or after transplantation of the tumor cell to an adoptive test host,
- wherein a level of tumor tissue that is established in the adoptive test host is decreased relative to the level of tumor tissue that is established in an adoptive control host into which the FZD10-overexpressing tumor cell is transplanted without being contacted with the anti-FZD10 antibody, and
- wherein the anti-FZD10 antibody is selected from the group consisting of:
- (1) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a heavy chain variable domain 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 domain comprising the VLCDR1, VLCDR2 and VLCDR3 amino acid sequences set forth in:
- SEQ ID NOs:9, 11 and 12, respectively, or SEQ ID NOs:10, 11 and 12, respectively;
- (2) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:1;
- (3) an isolated antibody, or an antigen-binding fragment thereof, that binds to human FZD10, comprising a light chain variable domain comprising any one of the amino acid sequences set forth in SEQ ID NOs:2, 3, and 4;
- and
- (4) an isolated antibody that competes with the antibody of (1), (2) or (3) for binding to FZD10.
7 more elements
Dependencies are inferred from the claim text.