Glycan-interacting compounds and methods of use
AssigneeSeagen Inc.
InventorsDavid A. Eavarone, Jillian M. Prendergast, Jeffrey Behrens
Life of this patent
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Abstract
The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include humanized antibodies, derivatives and fragments thereof as well as related compositions and kits. Methods of using glycan-interacting antibodies for treatment and diagnosis are included.
Claims93
An isolated antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
An isolated nucleic acid that encodes an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236, wherein the antibody comprises an IgG1 or IgG3 constant region, and wherein the cancer comprises STn-positive cancer cells.
A method of selecting a subject with cancer for treatment with an anti-STn antibody, comprising contacting a sample from the subject with an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236;
- and detecting binding of the antibody to STn-expressing cancer cells.
An antibody-drug conjugate comprising an antibody conjugated to a therapeutic agent, wherein the antibody binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of an antibody-drug conjugate comprising an antibody conjugated to a cytotoxic agent, wherein the antibody binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236, and wherein the cancer comprises STn-positive cancer cells.
A method of making an antibody-drug conjugate, comprising contacting an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn) with maleimidocaproyl-valine-citruline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-γc-PAB-MMAE), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
An isolated nucleic acid that encodes a heavy chain variable domain of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the heavy chain variable domain (VH) comprises an amino acid sequence selected from SEQ ID NOs:
- 237-241.
An isolated nucleic acid that encodes a light chain variable domain of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the light chain variable domain (VL) comprises an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
An isolated host cell that comprises a first nucleic acid that encodes a heavy chain variable domain (VH) of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the VH comprises an amino acid sequence selected from SEQ ID NOs:
- 237-241, and a second nucleic acid that encodes a light chain variable domain (VL) of the antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the VL comprises an amino acid sequence selected from SEQ ID NOs:
- 235 and 236.
Dependencies are inferred from the claim text.