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. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.
1 - 7 . (canceled)
8 . An antibody comprising:
(a) a CDR-L1 selected from the group consisting of SEQ ID NOs: 100-114, and SEQ ID NOs: 159-167;
(b) a CDR-L2 selected from the group consisting of SEQ ID NOs: 115-126, and SEQ ID NOs: 168-170;
(c) a CDR-L3 selected from the group consisting of SEQ ID NOs: 127-142, and SEQ ID NOs: 171-173;
(d) a CDR-H1 selected from the group consisting of SEQ ID NOs: 81-83, SEQ ID NO: 143, and SEQ ID NO: 144;
(e) a CDR-H2 selected from the group consisting of SEQ ID NOs: 84-89, and SEQ ID NOs: 145-151; and
(f) a CDR-H3 selected from the group consisting of SEQ ID NOs: 90-99, and SEQ ID NOs: 152-158.
9 . The antibody of claim 8 , comprising a monoclonal antibody.
10 . The antibody of any of claim 8 , wherein said antibody comprises an IgG isotype.
11 - 16 . (canceled)
17 . The antibody of claim 10 , wherein said antibody comprises an antibody-drug conjugate.
18 . (canceled)
19 . The antibody of claim 17 , wherein said antibody-drug conjugate comprises a cytotoxic agent.
20 . (canceled)
21 . The antibody of claim 19 , wherein said cytotoxic agent is conjugated to said antibody via a linker.
22 - 23 . (canceled)
24 . The antibody of claim 21 , wherein said cytotoxic agent is a cytoskeletal inhibitor.
25 - 27 . (canceled)
28 . A method of treating cancer in a subject in need thereof, said method comprising administering to said subject the antibody of claim 22 .
29 . The method of claim 28 , wherein said cancer comprises an epithelial cancer.
30 . The method of claim 29 , wherein said epithelial cancer comprises breast, colon, lung, bladder, cervical, ovarian, stomach, prostate, and/or liver cancer.
31 - 62 . (canceled)
63 . A method of identifying cancerous cells in a tissue or organ comprising the use of the antibody of claim 1 .
64 . The method of claim 63 , wherein said tissue or organ is selected from the group consisting of breast, ovary, and pancreas.
65 - 75 . (canceled)
76 . The method of claim 63 , wherein said antibody comprises a variable domain pair selected from the group consisting of:
SEQ ID NO:15 and SEQ ID NO:16;
SEQ ID NO:17 and SEQ ID NO:18;
SEQ ID NO:19 and SEQ ID NO:20;
SEQ ID NO:21 and SEQ ID NO:22;
SEQ ID NO:23 and SEQ ID NO:24;
SEQ ID NO:25 and SEQ ID NO:26;
SEQ ID NO:27 and SEQ ID NO:28;
SEQ ID NO:29 and SEQ ID NO:30;
SEQ ID NO:31 and SEQ ID NO:32;
SEQ ID NO:35 and SEQ ID NO:36;
SEQ ID NO:37 and SEQ ID NO:38;
SEQ ID NO:39 and SEQ ID NO:40;
SEQ ID NO:42 and SEQ ID NO:32;
SEQ ID NO:44 and SEQ ID NO:45;
SEQ ID NO:46 and SEQ ID NO:32;
SEQ ID NO:47 and SEQ ID NO:32;
SEQ ID NO:48 and SEQ ID NO:50;
SEQ ID NO:48 and SEQ ID NO:49; and
SEQ ID NO:51 and SEQ ID NO:52.
77 . The method of claim 28 , wherein said antibody comprises at least one human framework region from a human donor antibody.
78 . The method of claim 28 , wherein said antibody is a humanized antibody.
79 . The method of claim 78 , wherein said antibody is prepared by CDR-grafting.
80 . The method of claim 78 , wherein said cytotoxic agent comprises monomethyl auristatin E (MMAE).