Epithelial cadherin-specific antibodies
AssigneeKling Biotherapeutics B.V.
InventorsTim Beaumont, Sabrina Julia Louisa Merat, Mark Jeroen Kwakkenbos, Martijn Kedde, Hergen Spits
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Abstract
The present invention relates to epithelial cadherin-specific antibodies, as well as uses thereof in the diagnosis and treatment of diseases such as cancer.
Claims27
A synthetic or recombinant IgG1 antibody or antigen binding fragment thereof that is able to bind O mannosylated E cadherin, wherein said antibody or antigen binding fragment comprises each of:
- a. a heavy chain variable region CDR1 comprising the amino acid sequence GFX1FSX2AW (SEQ ID NO:
- 59), wherein X1 is T or I and wherein X2 is N or Y;
- b. a heavy chain variable region CDR2 comprising the amino acid sequence IKSKIDG X1T X2 (SEQ ID NO:
- 60), wherein X1 is G or E and wherein X2 is T or I;
- c. a heavy chain variable region CDR3 comprising the amino acid sequence TPGVGX1NX2PYYFDR (SEQ ID NO:
- 61), wherein X1 is A or T and wherein X2 is D or N;
- d. a light chain variable region CDR1 comprising the amino acid sequence QSVLCRSNNKNC (SEQ ID NO:
- 62);
- e. a light chain variable region CDR2 comprising the amino acid sequence WAX1, wherein X1 is S or C;
- and
- f. a light chain variable region CDR3 comprising the amino acid sequence QQYSNTPQT (SEQ ID NO:
- 63).
A synthetic or recombinant antibody or antigen binding fragment thereof that is able to bind O mannosylated E cadherin, wherein said antibody or antigen binding fragment comprises each of:
- a. a heavy chain variable region CDR1 comprising the amino acid sequence GFX1FSX2AW (SEQ ID NO:
- 59), wherein X1 is T or I and wherein X2 is N or Y;
- b. a heavy chain variable region CDR2 comprising the amino acid sequence IKSKIDG X1T X2 (SEQ ID NO:
- 60), wherein X1 is G or E and wherein X2 is T or I;
- C. a heavy chain variable region CDR3 comprising the amino acid sequence TPGVGX1NX2PYYFDR (SEQ ID NO:
- 61), wherein X1 is A or T and wherein X2 is D or N;
- d. a light chain variable region CDR1 comprising the amino acid sequence QSVLCRSNNKNC (SEQ ID NO:
- 62);
- e. a light chain variable region CDR2 comprising the amino acid sequence WAX1, wherein X1 is S or C;
- and
- f. a light chain variable region CDR3 comprising the amino acid sequence QQYSNTPQT (SEQ ID NO:
- 63);
- and wherein the antibody or antigen binding fragment is afucosylated or hypergalactosylated or wherein said antibody or antigen binding fragment has a modified Fc region, and wherein said modified Fc region comprises an amino acid mutation selected from the group consisting of:
- S298A, E333A, K334A;
- S239D, I332E;
- S239D, I332E, A330L;
- L235V, F243L, R292P, Y300L, P396L;
- K326W;
- E333S;
- K326W, E333S;
- E345R;
- E345K;
- E430G;
- E345K, E430G;
- S267E, H268F, S324T;
- S267E, H268F, S324T, G236A, I332E;
- L235E;
- L234A, L235A;
- L234A, L235A, P329G;
- S228P, L235E;
- and
- S228P, L235E, P329G.
A synthetic or recombinant antibody or antigen binding fragment thereof that is able to bind O mannosylated E cadherin, wherein said antibody or antigen binding fragment comprises each of:
- a. a heavy chain variable region CDR1 comprising the amino acid sequence GFX1FSX2AW (SEQ ID NO:
- 59), wherein X1 is T or I and wherein X2 is N or Y;
- b. a heavy chain variable region CDR2 comprising the amino acid sequence IKSKIDG X1T X2 (SEQ ID NO:
- 60), wherein X1 is G or E and wherein X2 is T or I;
- C. a heavy chain variable region CDR3 comprising the amino acid sequence TPGVGX1NX2PYYFDR (SEQ ID NO:
- 61), wherein X1 is A or T and wherein X2 is D or N;
- d. a light chain variable region CDR1 comprising the amino acid sequence QSVLCRSNNKNC (SEQ ID NO:
- 62);
- e. a light chain variable region CDR2 comprising the amino acid sequence WAX1, wherein X1 is S or C;
- and
- f. a light chain variable region CDR3 comprising the amino acid sequence QQYSNTPQT (SEQ ID NO:
- 63);
- and wherein the antibody or antigen binding fragment is covalently linked to a cell-binding agent, a cytokine, a second antibody or antigen binding part thereof, a detectable label, a drug, a cytotoxic agent, a hormone, an enzyme, or a nucleic acid.
A synthetic or recombinant antibody or antigen binding fragment thereof that is able to bind O mannosylated E cadherin, wherein said antibody or antigen binding fragment comprises each of:
- a heavy chain variable region CDR1 comprising the amino acid sequence GFX1FSX2AW (SEQ ID NO:
- 59), wherein X1 is T or I and wherein X2 is N or Y;
- and
- a heavy chain variable region CDR2 comprising the amino acid sequence IKSKIDG X1T X2 (SEQ ID NO:
- 60), wherein X1 is G or E and wherein X2 is T or I;
- and
- a heavy chain variable region CDR3 comprising the amino acid sequence TPGVGX1NX2PYYFDR (SEQ ID NO:
- 61), wherein X1 is A or T and wherein X2 is D or N;
- and
- a light chain variable region CDR1 comprising the amino acid sequence QSVLCRSNNKNC (SEQ ID NO:
- 62);
- and
- a light chain variable region CDR2 comprising the amino acid sequence WAX1, wherein X1 is S or C;
- and
- and
- a light chain variable region CDR3 comprising the amino acid sequence QQYSNTPQT (SEQ ID NO:
- 63);
- and wherein the synthetic or recombinant antibody or antigen binding fragment thereof is a variant of antibody AT1636.
Dependencies are inferred from the claim text.