GLYCAN-INTERACTING COMPOUNDS AND METHODS OF USE
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 monoclonal antibodies, derivatives and fragments thereof as well as compositions and kits comprising them.
1 - 71 . (canceled)
72 . An isolated Group 1 antibody, wherein said Group 1 antibody is capable of binding glycated antigens having either:
N-acetylneuraminic sialy Tn (AcSTn), wherein said Group 1 antibody specifically binds an epitope of AcSTn consisting of:
a N-Acetyl group of N-acetylgalactosamine (GalNAc),
a galactosamine of GalNAc,
a neuraminic acid of N-acetylneuraminic acid (Neu5Ac),
a N-acetyl group of Neu5Ac, and
a O-linkage of STn, or
N-glycolylneuraminic sialyl Tn (GcSTn), wherein said Group 1 antibody specifically binds an epitope of GcSTn consisting of:
a N-Acetyl group of GalNAc,
a galactosamine of GalNAc,
a glycolylneuraminic acid of N-glycolylneuraminic acid (Neu5Gc),
a N-glycolyl group of Neu5Gc, and
a O-linkage of STn.
73 . The isolated Group 1 antibody of claim 72 having at least one variable domain with an amino acid sequence having at least 95% sequence identity to one or more of SEQ ID NOs: 1-5.
74 . The isolated Group 1 antibody of claim 73 , wherein said at least one variable domain comprises a variable domain pair, said variable domain pair comprising:
a heavy chain variable domain (VH) with at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 and 4; and
a light chain variable domain (VL,) with at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 3, and 5.
75 . The isolated Group 1 antibody of claim 72 comprising:
at least one VH complementarity determining region (CDR-H) having an amino acid sequence with at least 85% sequence identity to a CDR-H selected from one or more of SEQ ID NOs: 15, 16, 19, 20, 22, and 23; and
at least on VL complementarity determining region (CDR-L) having an amino acid sequence with at least 85% sequence identity to a CDR-L selected from one or more of SEQ ID NOs: 29, 31, 32, 33, 35, 36, and 40.
76 . The isolated Group 1 antibody of claim 75 having:
a VH comprising:
a CDR-H1 having an amino acid sequence with at least 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 15 and 16,
a CDR-H2 having an amino acid sequence with at least 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19 and 20, and
a CDR-H3 having an amino acid sequence with at least 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22 and 23, and
a VL comprising:
a CDR-L1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 29, 31, and 32,
a CDR-L2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 33 and 35, and
a CDR-L3 having an amino acid sequence with at least 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 36 and 40.
77 . The isolated Group 1 antibody of claim 76 , wherein said isolated Group 1 antibody is a humanized antibody.
78 . The isolated Group 1 antibody of claim 72 , wherein said isolated Group 1 antibody is an antibody-drug conjugate.
79 . The isolated Group 1 antibody of claim 78 , wherein said isolated Group 1 antibody is conjugated to a cytotoxic agent.
80 . A composition comprising:
an isolated Group 1 antibody, wherein said Group 1 antibody is capable of binding glycated antigens having either:
AcSTn, wherein said Group 1 antibody specifically binds an epitope of AcSTn consisting of:
an N-Acetyl group of GalNAc,
a galactosamine of GalNAc,
a neuraminic acid of Neu5Ac,
an N-acetyl group of Neu5Ac, and
an O-linkage of STn, or
GcSTn, wherein said Group 1 antibody specifically binds an epitope of GcSTn consisting of:
an N-Acetyl group of GalNAc,
a galactosamine of GalNAc,
a glycolylneuraminic acid of Neu5Gc,
an N-glycolyl group of Neu5Gc, and
an O-linkage of STn, and
an excipient.
81 . The composition of claim 80 , wherein said isolated Group 1 antibody is a humanized antibody.
82 . The composition of claim 80 , wherein said isolated Group 1 antibody is an antibody-drug conjugate.
83 . The composition of claim 82 , wherein said isolated Group 1 antibody is conjugated to a cytotoxic agent.
84 . A method of reducing tumor volume comprising administering an isolated Group 1 antibody to a subject in need thereof, wherein said Group 1 antibody is capable of binding glycated antigens having either:
AcSTn, wherein said Group 1 antibody specifically binds an epitope of AcSTn consisting of:
an N-Acetyl group of GalNAc,
a galactosamine of GalNAc,
a neuraminic acid of Neu5Ac,
an N-acetyl group of Neu5Ac, and
an O-linkage of STn, or
GcSTn, wherein said Group 1 antibody specifically binds an epitope of GcSTn consisting of:
an N-Acetyl group of GalNAc,
a galactosamine of GalNAc,
a glycolylneuraminic acid of Neu5Gc,
an N-glycolyl group of Neu5Gc, and
an O-linkage of STn.
85 . The method of claim 84 , wherein said isolated Group 1 antibody is a humanized antibody.
86 . The method of claim 84 , wherein said isolated Group 1 antibody is an antibody-drug conjugate.
87 . The method of claim 86 , wherein said isolated Group 1 antibody is conjugated to a cytotoxic agent.
88 . The method of claim 84 , wherein said isolated Group 1 antibody is administered at a dosage level sufficient to deliver from about 1 mg/kg to about 25 mg/kg of isolated Group 1 antibody to said subject in need thereof.
89 . The method of claim 88 , wherein said isolated Group 1 antibody is administered intravenously.
90 . The method of claim 89 , wherein said isolated Group 1 antibody is administered in multiple doses.
91 . The method of claim 84 , wherein immune-resistant tumor cell volume is reduced.
92 . The method of claim 91 , wherein dendritic cell (DC) and/or natural killer (NK) cell anti-tumor cell activity is increased.