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 . An antibody comprising:
a heavy chain variable domain (VH) with an amino acid sequence comprising at least 95% sequence identity to SEQ ID NO: 59; and
a light chain variable domain (VL) with an amino acid sequence comprising at least 95% sequence identity to SEQ ID NO: 60.
2 - 5 . (canceled)
6 . The antibody of claim 1 comprising a heavy chain with an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 63 and a light chain with an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 64.
7 . The antibody of claim 1 , wherein said antibody comprises an antibody-drug conjugate comprising one or more-therapeutic compound or one or more cytotoxic agent.
8 . The antibody of claim 7 , wherein said one or more therapeutic compound or one or more cytotoxic agent is conjugated to said antibody directly or via a linker.
9 . The antibody of claim 8 , wherein said antibody-drug conjugate comprises one or more cytotoxic agent and wherein said one or more cytotoxic agent comprises a cytoskeletal inhibitor or a DNA damaging agent.
10 . The antibody of claim 1 , wherein said antibody comprises a bispecific antibody comprising:
a. a first Fab region comprising the VH of SEQ ID NO: 59 and the VL of SEQ ID NO: 60; and
b. a second Fab region.
11 . (canceled)
12 . The antibody of claim 10 , wherein said second Fab region binds to a glycan.
13 . The antibody of claim 10 , wherein said second Fab region binds to a non-glycan.
14 . The antibody of claim 10 , wherein said second Fab region binds to a protein.
15 . The antibody of claim 1 , wherein said antibody comprises an intrabody.
16 . A method of killing or inhibiting the proliferation of a tumor cell comprising contacting said tumor cell with the antibody of claim 1 .
17 . The method of claim 16 , wherein said antibody induces antibody-dependent cell-mediated cytotoxicity (ADCC) and/or antibody-dependent cell phagocytosis (ADCP).
18 . The method of claim 16 , wherein said antibody is conjugated to a cytotoxic agent.
19 . The method of claim 18 , wherein said cytotoxic agent is conjugated using a linker and wherein said linker is selected from the group consisting of a cleavable linker and a non-cleavable linker.
20 . The method of claim 19 , wherein said cytotoxic agent is selected from the group consisting of monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF).
21 . (canceled)
22 . The method of claim 20 , comprising administration of said antibody to a subject with cancer.
23 . (canceled)
24 . The method of claim 22 , wherein said cancer comprises an epithelial cancer selected from the group consisting of breast, colon, lung, bladder, cervical, ovarian, stomach, prostate, and liver cancer.
25 . (canceled)
26 . The method of claim 22 , wherein tumor volume is reduced after administration of said antibody.
27 - 35 . (canceled)
36 . A construct comprising:
the nucleotide sequence of SEQ ID NO: 65 or a variant thereof with at least 95% sequence identity; and/or
the nucleotide sequence of SEQ ID NO: 66 or a variant thereof with at least 95% sequence identity.
37 - 42 . (canceled)
43 . The construct of claim 36 , wherein said construct is comprised by at least one of a cell and a virus.