Novel Anti-STN antibodies and methods of use

Abstract

Provided are novel anti-sTn antibodies and immunoconjugates thereof as well as methods of using such anti-sTn antibodies and immunoconjugates to treat cancer.

Description

[0001] Atorney Docket No. T107777 1050WO (00010)

[0002] NOVEL ANTI-STN ANTIBODIES AND METHODS OF USE

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 699,590, filed on September 26, 2024. The entire contents of the foregoing application is hereby incorporated herein by reference.

[0005] SEQUENCE LISTING

[0006] The instant application contains a Sequence Listing which has been filed electronically in extensible Markup Language (XML) format and is hereby incorporated by reference in its entirety. Said XML copy, created on September 17, 2025, is named T107777_1050WO_SL.xml and is 360,018 bytes in size.

[0007] FIELD OF DISCLOSURE

[0008] This application generally relates to novel anti-sTn antibodies or immunoreactive fragments thereof and compositions, including immunoconjugates such as antibody drug conjugates (ADCs), immunocytokines, chimeric antigen receptor (CAR) cells, and bispecific antibodies, comprising the same for the treatment, diagnosis or prophylaxis of cancer and / or any recurrence or metastasis thereof

[0009] BACKGROUND

[0010] Differentiation and proliferation of stem cells and progenitor cells are normal ongoing processes that act in concert to support tissue growth during organogenesis, cell repair and cell replacement. The system is tightly regulated to ensure that only appropriate signals are generated based on the needs of the organism. Cell proliferation and differentiation normally occur only as necessary for the replacement of damaged or dying cells or for growth. However, disruption of these processes can be triggered by many factors including the under- or overabundance of various signaling chemicals, the presence of altered microenvironments, genetic mutations or a combination thereof. Disruption of normal cellular proliferation and / or differentiation can lead to various disorders including proliferative diseases such as cancer.

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[0012] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0013] Conventional therapeutic treatments for cancer include chemotherapy, radiotherapy and immunotherapy. Often these treatments are ineffective and surgical resection may not provide a viable clinical alternative. Limitations in the current standard of care are particularly evident in those cases where patients undergo first line treatments and subsequently relapse. In such cases refractory tumors, often aggressive and incurable, frequently arise. The overall survival rates for many tumors have remained largely unchanged over the years due, at least in part, to the failure of existing therapies to prevent relapse, tumor recurrence and metastasis. There remains therefore a great need to develop more targeted and potent therapies for proliferative disorders. The current disclosure addresses this need.

[0014] SUMMARY

[0015] In a broad aspect the present invention provides antibodies, and corresponding immunoconjugates such as antibody drug conjugates (ADCs) (e g., wherein the conjugated drug is a cytotoxin, diagnostic agent, or cytokine (i.e. an immunocytokine)), chimeric antigen receptor (CAR) cells (e.g., CAR-T cells), bispecific antibodies, or compositions thereof, which bind to sTn determinants in humans and other mammalian species. The sTn determinant may be expressed on (i.e. attached to) various carrier proteins, such as, for example, mucins, or other proteins which contribute to the disease state. In certain aspects, the sTn determinant is expressed on cancer cells (i.e. atached to a protein or proteins expressed on the cell surface of cancer cells). This expression may encompass most or all tumor cells in a patient or in an individual tumor, or this expression may be limited to a subpopulation of tumor cells within a patient or individual tumor. For example, in some aspects, the sTn determinant may be expressed on cancer stem cells or on tumor initiating cells. In other aspects, the antibodies of the invention bind to an sTn glycan or sTn carrier protein and compete for binding with an antibody that binds to an epitope on sTn or an sTn carrier protein.

[0016] According to an aspect of the invention, an antibody that binds to a sialyl-Thomsen- nouveau antigen (sTn) comprises (a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; or (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising

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[0018] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 78 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 82.

[0019] The antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 85, an amino acid sequence set forth as SEQ ID NO: 86, and an amino acid sequence set forth as SEQ ID NO: 87; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 88, an amino acid sequence set forth as SEQ ID NO: 89, and an amino acid sequence set forth as SEQ ID NO: 90.

[0020] The antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 91, an amino acid sequence set forth as SEQ ID NO: 92, and an amino acid sequence set forth as SEQ ID NO: 93; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 94, an amino acid sequence LMS, and an amino acid sequence set forth as SEQ ID NO: 96.

[0021] The antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and

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[0023] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 74, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 97, an amino acid sequence set forth as SEQ ID NO: 98, and an amino acid sequence set forth as SEQ ID NO: 99; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 100, an amino acid sequence set forth as SEQ ID NO: 101, and an amino acid sequence set forth as SEQ ID NO: 102.

[0024] According to particular aspects of the above antibody, the antibody comprises (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (b)three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 74, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

[0025] The antibody may comprise (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; or (c) a heavy chain variable region comprising an

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[0027] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) amino acid sequence set forth as SEQ ID NO: 78 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 82.

[0028] According to particular aspects of the above antibody, the antibody comprises a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56.

[0029] The antibody may be a chimeric, CDR grafted, humanized, or human antibody, or the antibody may be an immunoreactive fragment thereof.

[0030] According to an aspect of the invention, a humanized antibody that binds to a sialyl- Thomsen-nouveau antigen (sTn) comprises (a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable

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[0032] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 165; (i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (1) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (s) three

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[0034] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (w) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (x) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (y) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (z) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (aa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (bb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (cc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an

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[0036] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (dd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (ee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (ft) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (gg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (hh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ii) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (jj) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (kk) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (11) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (mm) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable

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[0038] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 138; (nn) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (oo) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (pp) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (qq) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (rr) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ss) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (tt) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (uu) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (vv) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (ww) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (xx) three

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[0040] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (yy) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (zz) three complementanty-determimng regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (aaa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (bbb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ccc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (ddd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (eee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (fff) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (ggg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or (hhh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an

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[0042] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) amino acid sequence set forth as SEQ ID NO: 1 17 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

[0043] The humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as

[0044] Page 11 of 347

[0045] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0046] SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (h) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (i) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (j) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (k) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (1) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (m) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or (n) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142,

[0047] Page 12 of 347

[0048] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

[0049] The humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38.

[0050] The humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or (e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs

[0051] Page 13 of 347

[0052] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

[0053] The antibody may comprise (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (1) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region

[0054] Page 14 of 347

[0055] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) comprising an amino acid sequence set forth as SEQ ID NO: 163; (o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (w) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (x) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (y) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (z) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (aa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (bb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (cc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID

[0056] Page 15 of 347

[0057] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0058] NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (dd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (ee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (ff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (gg) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (hh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ii) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (jj) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (kk) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (11) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (mm) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (nn) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (oo) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (pp) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (qq) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (rr) a heavy chain variable region comprising

[0059] Page 16 of 347

[0060] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ss) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (tt) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (uu) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (vv) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (ww) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (xx) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (yy) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (zz) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (aaa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (bbb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ccc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (ddd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (eee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (fff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence

[0061] Page 17 of 347

[0062] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) set forth as SEQ ID NO: 136; (ggg) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or (hhh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

[0063] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In a specific embodiment, the antibody is TM06.02.13. In one embodiment, the humanized antibody is conjugated to a payload.

[0064] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID

[0065] Page 18 of 347

[0066] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0067] NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61 ; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In one embodiment, the humanized antibody is conjugated to a payload.

[0068] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ

[0069] Page 19 of 347

[0070] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0071] ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In one embodiment, the humanized antibody is conjugated to a payload.

[0072] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In one embodiment, the humanized antibody is conjugated to a payload.

[0073] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID

[0074] Page 20 of 347

[0075] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0076] NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64. In one embodiment, the humanized antibody is conjugated to a payload.

[0077] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0078] Page 21 of 347

[0079] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0080] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0081] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising

[0082] Page 22 of 347

[0083] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0084] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0085] In one embodiment, the humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn) comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising

[0086] Page 23 of 347

[0087] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In another embodiment, the humanized antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0088] According to an aspect of the invention, a humanized antibody that binds to a sialyl- Thomsen-nouveau antigen (sTn), wherein the antibody comprises: (a) three complementaritydetermining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an

[0089] Page 24 of 347

[0090] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (1) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable

[0091] Page 25 of 347

[0092] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 264; (q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; or (v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239. In one embodiment, the humanized antibody is conjugated to a payload.

[0093] In one embodiment, the humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0094] Page 26 of 347

[0095] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0096] In one embodiment, the humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 244; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 236, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 237; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0097] In one embodiment, the humanized antibody may comprise (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 245, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 238, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38. In one embodiment, the humanized antibody is conjugated to a payload.

[0098] In one embodiment, the humanized antibody may comprise (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO:

[0099] Page 27 of 347

[0100] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0101] 268; (d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (1) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino

[0102] Page 28 of 347

[0103] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) acid sequence set forth as SEQ ID NO: 268; (s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; or (v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239. In one embodiment, the humanized antibody is conjugated to a payload.

[0104] In one aspect, the present invention provides an antibody that preferentially binds to a mono sTn epitope. In one embodiment, the antibody does not bind to a Tn epitope.

[0105] According to an aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises or competes for binding to a mono sTn epitope with an antibody comprising: (a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable

[0106] Page 29 of 347

[0107] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 157; (g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (1) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (q) three

[0108] Page 30 of 347

[0109] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; or (u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.

[0110] According to another aspect of the invention, an antibody that prefereintially binds to a mono sTn epitope the antibody comprises: (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid

[0111] Page 31 of 347

[0112] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) sequence set forth as SEQ ID NO: 61 ; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (h) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (i) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

[0113] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises: three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64.

[0114] Page 32 of 347

[0115] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0116] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises: (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 74, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

[0117] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises: (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (h) a heavy

[0118] Page 33 of 347

[0119] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (1) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; (q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157; (r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160; (s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163; (t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; or (u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.

[0120] Page 34 of 347

[0121] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0122] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises or competes for binding to a mono sTn epitope with an antibody comprising: (a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable

[0123] Page 35 of 347

[0124] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 264; (k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (1) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; or (u) three

[0125] Page 36 of 347

[0126] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268.

[0127] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises: (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 244; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64.

[0128] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 245, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

[0129] According to another aspect of the invention, an antibody that preferentially binds to a mono sTn epitope comprises: (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (f) a heavy

[0130] Page 37 of 347

[0131] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (1) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268 (p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; (r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; (s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264; (t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as

[0132] Page 38 of 347

[0133] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0134] SEQ ID NO: 266; or (u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268.

[0135] In one aspect, the invention provides an antibody that binds to sTn and Tn. In another aspect, the antibody binds to an epitope comprising one or more sTn glycans, one or more Tn glycans, or a combination of sTn and Tn glycans.

[0136] In another aspect, the antibody that binds to sTn and Tn comprises or competes for binding to sTn and / or Tn with an antibody comprising: (a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30; (b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (i) three

[0137] Page 39 of 347

[0138] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (1) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an

[0139] Page 40 of 347

[0140] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) amino acid sequence set forth as SEQ ID NO: 1 13 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (w) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (x) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (y) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (z) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (aa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (bb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (cc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable

[0141] Page 41 of 347

[0142] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 136; (dd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (ee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (ff) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (gg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (hh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (ii) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (jj) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (kk) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (11) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (mm) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (nn) three

[0143] Page 42 of 347

[0144] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or (oo) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

[0145] In another aspect, the antibody that binds to sTn and Tn comprises: (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as

[0146] Page 43 of 347

[0147] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0148] SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or (g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

[0149] In another aspect, the antibody that binds to sTn and Tn comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38.

[0150] In another aspect, the antibody that binds to sTn and Tn comprises: (a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; (b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or (c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

[0151] In another aspect, the antibody that binds to sTn and Tn comprises: (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109

[0152] Page 44 of 347

[0153] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (1) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (r) a heavy chain variable region comprising an amino acid

[0154] Page 45 of 347

[0155] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) sequence set forth as SEQ ID NO: 1 13 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (w) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (x) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (y) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (z) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (aa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (bb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (cc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; (dd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140; (ee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120; (ff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124; (gg)

[0156] Page 46 of 347

[0157] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 1 17 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126; (hh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128; (ii) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130; (jj) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132; (kk) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134; (11) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136; (mm) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or (nn) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

[0158] In another aspect, the antibody that binds to sTn and Tn comprises or competes for binding to sTn and / or Tn with an antibody comprising:three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

[0159] In another aspect, the antibody that binds to sTn and Tn comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 236, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 237; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38.

[0160] In another aspect, the antibody that binds to sTn and Tn comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 238, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light

[0161] Page 47 of 347

[0162] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

[0163] In another aspect, the antibody that binds to sTn and Tn comprises a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

[0164] In one embodiment, the antibody is a recombinant antibody. In another embodiment, the antibody is an isolated antibody.

[0165] The antibody may be conjugated to a payload via any of numerous known techniques. In some aspects, the payload is conjugated to the antibody by a linker. In some aspects, the payload may be joined to the antibody by a linker comprising a sulfamide. In some aspects, the linker comprises a cleavable unit and a hydrophilic moiety. In other aspects, the payload may be conjugated to one or more naturally occurring glycans of the antibody. For example, the payload may be conjugated to an asparagine 297 residue in a constant region of a heavy chain of the antibody. The payload may be conjugated to an N-acetylglucosamine (GlcNAc). Representative payloads include SN-38, deruxtecan (DXd), exatecan, MMAE, MMAF, DM1, or DM4.

[0166] The antibody may be a bispecific or multispecific antibody. The bispecific or multispecific antibody may bind sTn on an antigen expressed on a tumor cell and an antigen expressed on a T cell, B cell, or NK cell selected from the group consisting of CD3, 4-1BB, CD16, NKp30, NKp46, NKG2D, and DNAM-1, and CD40.

[0167] According to another aspect of the invention, a pharmaceutical composition is provided which includes the antibody.

[0168] According to another aspect of the invention, a nucleic acid is provided which encodes a light chain variable region and / or a heavy chain variable region of the antibody. According to another aspect of the invention, a vector is provided which includes the nucleic acid. According to another aspect of the invention, a host cell is provided which contains the nucleic acid and / or the vector.

[0169] According to another aspect of the invention, an antibody drug conjugate (ADC) is provided comprising the antibody. The ADC has a formula of Ab-[L-D]n, wherein Ab is the anti- sTn antibody, D is a drug, L is an optional linker; and n is an integer from about 1 to about 20. The integer n may be an integer from about 1 to about 8.

[0170] Page 48 of 347

[0171] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0172] The drug may be a cytotoxic agent. The cytotoxic agent may be a toxin, a chemotherapeutic agent, an antibiotic, a radioactive isotope, or a nucleolytic enzyme. The drug may be a camptothecin, auristatin, dolastatin, maytansinoid, calicheamicin, pyrrolobenzodiazepine (PBD), benzodiazepine derivative, or amanitin, or the drug may be an analogue or derivative of any thereof. The drug may be SN-38, DXd, exatecan, MMAE, MMAF, DM1, or DM4.

[0173] The drug may be a cytokine. The cytokine may be interleukin-2 (IL2), interleukin- 12 (IL 12), tumor necrosis factor (TNF), interferon-alpha, and granulocyte-macrophage colonystimulating factor (GMCSF).

[0174] According to another aspect of the invention, the ADC has the structure: , wherein: (a) Z is a connecting group for conjugation to an antibody or an antigen-binding fragment thereof; (b) LBis a connector unit that covalently connects C1and Z; (c) CTis a cleavable linker; (d) R1and R2are coupling groups; (e) E is a hydrophilic moiety; and (f) D is a drug.

[0175] According to another aspect of the invention, the ADC has the structure: , wherein: (a) Z is a connecting group for conjugation to an antibody or an antigen-binding fragment thereof; (b) LBis a connector unit that covalently connects CL, Z, and E; (c) CLis a cleavable linker; (d) R1and R2are coupling groups; (e) E is a hydrophilic moiety; and (f) D is a drug.

[0176] In one embodiment, LBcomprises an amino acid.

[0177] In one embodiment, Z is selected from the group consisting of:

[0178] Page 49 of 347

[0179] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) wherein one wavy line indicates the site of covalent attachment to Ab and the other wavy line indicates the site of covalent attachment to LB; and where R5is H or Ci-Ce alkyl.

[0180] In another embodiment, LBcomprises an amino acid, and wherein the hydrophilic moiety (E) is coupled to LBthrough the amino group, through the carboxyl group, or through the side chain of the amino acid of the connector group.

[0181] In one embodiment, CLis a protease-cleavable peptide moiety, a glycosidase-cleavable sugar moiety, a pH sensitive moiety, or a hydrolysable moiety.

[0182] In another embodiment, CLis a protease-cleavable peptide moiety comprising valinealanine (VA), valine-cysteine (VC), phenylalanine-glycine (FG), phenylalanine-lysine (FK), alanine-alanine (AA), glycine-valine (GV), or glycine-cysteine (GC).

[0183] In one embodiment, each of R1and R2are, independently, selected from the group consisting of -C(O)-, -C(O)O-, -C(O)NH-, alkyl-O-, alkyl-NH-, alkyl-C(O)-, alkyl-C(O)-O-, alkyl-C(O)-NH-, alkyl-NH-C(O)-, alkyl-SCh-, alkyl-S-, alkyl-O-P(O)-O2-, alkyl-O-C(O)-NH-, or triazole.

[0184] In one embodiment, E comprises a polyethylene glycol (PEG), a polysarcosine (pSar), a poly lactic-co-glycolic acid (PLGA), a poly(glycerol) (PG), a poly(oxazolines) (POX), a poly(hydroxypropylmethacrylate) (PHPMA), a poly(2-hydroxyethyl methacrylate) (PHEMA), a poly(N-(2-hydroxypropyl)methacrylamide) (HPMA), a poly (vinylpyrrolidone) (PVP), a poly(N,N-dimethylacrylamide) (PDMA), a poly(N-acryloylmorpholine) (PAcM), or a saccharide.

[0185] Page 50 of 347

[0186] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0187] In another embodiment, E has the structure: where: (a) R3is -C(O)-, -O-, -S-, -NH-, -C(O)O-, alkyl-C(O)-NH-, alkyl-NH-C(O)-, alkyl-CCh-, alkyl-S sugar derivative, C1-C10 alkyl group,

[0188] C3-C10 cycloalkyl group, C2-C10 alkyl-NEE, C1-C10 alkyl-COOR, C2-C10 alkyl-NH(Ci-C3 alkyl), C2-C10 alkyl-N (C1-C3 alkyl)2, or sarcosine; and (c) n is an integer ranging from 2 to 72.

[0189] In one embodiment, Z is conjugated to one or more naturally occurring glycans associated with the antibody. In another embodiment, Z is conjugated to an N-acetylglucosamine (GlcNAc). In another embodiment, Z is conjugated to one or more amino acids of the antibody. In another embodiment, Z is conjugated to an asparagine 297 residue in a constant region of a heavy chain of the antibody.

[0190] According to another aspect of the invention, a pharmaceutical composition is provided which includes the ADC.

[0191] According to another aspect of the invention, a method of producing an ADC as described above comprises conjugating the antibody (Ab) with the drug (D).

[0192] According to another aspect of the invention, a chimeric antigen receptor (CAR) is provided which comprises the antibody. The CAR comprises i) an extracellular antigen binding domain that specifically binds to sTn and which comprises the antibody; ii) a transmembrane domain; and iii) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (IT AM). The intracellular signaling domain provides signal transduction activity.

[0193] According to another aspect of the invention, a nucleic acid is provided which encodes the CAR. According to another aspect of the invention, a vector is provided which includes the nucleic acid. According to another aspect of the invention, a host cell is provided which contains the nucleic acid and / or the vector. The cell may be an isolated T lymphocyte or an NK cell. According to another aspect of the invention, a pharmaceutical composition is provided which includes the cell.

[0194] Page 51 of 347

[0195] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0196] According to another aspect of the invention, a method of delivering a cytotoxin to a cell is provided. The method is performed by contacting the cell with an ADC of the invention. The contacting may be performed in vitro or in vivo.

[0197] According to another aspect of the invention, a method of treating cancer is provided. The method is performed by administering a pharmaceutical composition of the invention to a subject in need of treatment. The cancer may be a solid tumor cancer. The cancer may be an epithelial cell cancer. The cancer may be selected from the group consisting of gastric cancer, colorectal cancer, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, skin cancer, and bladder cancer. In particular aspects, the cancer is selected from the group consisting of gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, or lung cancer. The cancer may be an adenocarcinoma. The cancer may be a squamous cell carcinoma. Treating the cancer may further comprise administering a poly(ADP -ribose) polymerase (PARP) inhibitor to the subject. Treating the cancer may comprise administering an ADC to the subject. The ADC may comprise SN-38, DXd, or exatecan.

[0198] According to another aspect of the invention, a method of detecting, diagnosing, or monitoring cancer in a subject is provided. The method is performed by contacting cancer cells with an antibody or ADC of the invention and detecting the antibody on the tumor cells. The contacting may be performed in vitro or in vivo. The cancer may be a solid tumor cancer. The cancer may be an epithelial cell cancer. The cancer may be selected from the group consisting of gastric cancer, colorectal cancer, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, skin cancer, and bladder cancer. In particular aspects, the cancer is selected from the group consisting of gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, or lung cancer. The cancer may be an adenocarcinoma. The cancer may be a squamous cell carcinoma.

[0199] BRIEF DESCRIPTION OF THE FIGURES

[0200] FIG. 1 shows the immunoblotting with an sTn antibody of the immunogens used for generating novel sTn antibodies.

[0201] FIG. 2 depicts the O-glycan microarray layout; FIG. 2A lists the 94 separate features of the O-glycan microarray and FIG. 2B illustrates the structures of the 94 features; FIG. 2C depicts a graph of the TM06.02 antibody at 2ug / ml binding to the 03 and 04 probes, the sTn antigen

[0202] Page 52 of 347

[0203] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) attached to the amino acids serine and threonine, respectively; FIG. 2D illustrates the control antibody 2G12-2B2 at 2ug / mL binding to the 03 and 04 probes, but at lower affinity than the TM06.02 antibody; and FIG. 2E is a graph depicting the binding of different concentrations of the TM06.02 antibody to features 03 and 04 compared to the 2G12-2B2 control.

[0204] FIG. 3 shows the results of a MUC1 glycopeptide microarray; FIG. 3 A provides the array structures: array structures labeled 1-31 are Tn-containing peptides, array structures 32-62 are sTn- containing peptides, and array structure 63 is the non-glycosylated peptide. The array structures have the following SEQ ID NOs: array structure 1 (SEQ ID NO: 167), array structure 2 (SEQ ID NO: 168), array structure 3 (SEQ ID NO: 169), array structure 4 (SEQ ID NO: 170), array structure 5 (SEQ ID NO: 171), array structure 6 (SEQ ID NO: 172), array structure 7 (SEQ ID NO: 173), array structure 8 (SEQ ID NO: 174), array structure 9 (SEQ ID NO: 175), array structure 10 (SEQ ID NO: 176), array structure 11 (SEQ ID NO: 177), array structure 12 (SEQ ID NO: 178), array structure 13 (SEQ ID NO: 179), array structure 14 (SEQ ID NO: 180), array structure 15 (SEQ ID NO: 181), array structure 16 (SEQ ID NO: 182), array structure 17 (SEQ ID NO: 183), array structure 18 (SEQ ID NO: 184), array structure 19 (SEQ ID NO: 185), array structure 20 (SEQ ID NO: 186), array structure 21 (SEQ ID NO: 187), array structure 22 (SEQ ID NO: 188), array structure 23 (SEQ ID NO: 189), array structure 24 (SEQ ID NO: 190), array structure 25 (SEQ ID NO: 191), array structure 26 (SEQ ID NO: 192), array structure 27 (SEQ ID NO: 193), array structure 28 (SEQ ID NO: 194), array structure 29 (SEQ ID NO: 195), array structure 30 (SEQ ID NO: 196), array structure 31 (SEQ ID NO: 197), array structure 32 (SEQ ID NO: 198), array structure 33 (SEQ ID NO: 199), array structure 34 (SEQ ID NO: 200), array structure 35 (SEQ ID NO: 201), array structure 36 (SEQ ID NO: 202), array structure 37 (SEQ ID NO: 203), array structure 38 (SEQ ID NO: 204), array structure 39 (SEQ ID NO: 205), array structure 40 (SEQ ID NO: 206), array structure 41 (SEQ ID NO: 207), array structure 42 (SEQ ID NO: 208), array structure 43 (SEQ ID NO: 209), array structure 44 (SEQ ID NO: 210), array structure 45 (SEQ ID NO: 211), array structure 46 (SEQ ID NO: 212), array structure 47 (SEQ ID NO: 213), array structure 48 (SEQ ID NO: 214), array structure 49 (SEQ ID NO: 215), array structure 50 (SEQ ID NO: 216), array structure 51 (SEQ ID NO: 217), array structure 52 (SEQ ID NO: 218), array structure 53 (SEQ ID NO: 219), array structure 54 (SEQ ID NO: 220), array structure 55 (SEQ ID NO: 221), array structure 56 (SEQ ID NO: 222), array structure 57 (SEQ ID NO: 223), array structure 58 (SEQ ID NO: 224), array structure 59 (SEQ ID NO: 225), array structure 60 (SEQ ID

[0205] Page 53 of 347

[0206] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0207] NO: 226), array structure 61 (SEQ ID NO: 227), array structure 62 (SEQ ID NO: 228), and array structure 63 (SEQ ID NO: 229); FIG. 3B shows graphs depicting the binding of the TM06.01 antibody, the TM06.02 antibody, and the 2G12-2B2 antibody in the MUC1 glycopeptide microarray; FIG. 3C illustrates the MUC1 glycoproteins bound by the TM06.01 antibody; FIG. 3D illustrates the MUC1 glycopeptides bound by the TM06.02 antibody; and FIG. 3E illustrates the binding of the TM06.02.13, TM06.02.20, TM06.02.25, and TM06.02.56 humanized antibodies.

[0208] FIG. 4 illustrates the development of an immunohistochemistry assay for the TM06.02 antibody; FIG. 4A depicts immunohistochemistry on cells engineered to express sTn (BxPC-3 engineered cells); and FIG. 4B depicts immunohistochemistry staining in patient tumor tissues.

[0209] FIG. 5 shows the results of an internalization assay for humanized antibodies TM06.02.13, TM06.02.25, TM06.02.50, and TM06.02.86, and a comparator antibody 2G12-2B2. MOPC21 was used as a negative control antibody.

[0210] DETAILED DESCRIPTION

[0211] The present invention may be embodied in many different forms. Disclosed herein are nonlimiting, illustrative aspects of the invention that exemplify the principles thereof. Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. For the purposes of the instant invention all identifying sequence accession numbers may be found in the NCBI Reference Sequence (RefSeq) database and / or the NCBI GenBank archival sequence database unless otherwise noted.

[0212] It has been found that certain glycans, including Tn and sTn, provide useful cancer markers which may be exploited in the treatment of related diseases. In this regard, the present invention provides novel anti-glycan antibodies and antibody drug conjugates comprising an anti-glycan antibody targeting agent and cytotoxic payload. The disclosed anti-glycan antibodies and anti- glycan immunoconjugates may be effective at eliminating tumorigenic cells and therefore useful for the treatment and prophylaxis of certain proliferative disorders or the progression or recurrence thereof.

[0213] Anti-glycan immunoconjugates, including anti-sTn immunoconjugates such as those disclosed herein, may advantageously be used in the treatment and / or prevention of selected proliferative (e g., neoplastic) disorders or progression or recurrence thereof, such as, for example,

[0214] Page 54 of 347

[0215] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) ovarian cancer, melanoma, bladder cancer, esophageal cancer, kidney cancer, cholangiocarcinoma, liver cancer, cervical cancer, endometrial cancer, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, lung cancer, or other solid tumor cancers. It will be appreciated that, while examples will be discussed extensively below, particularly in terms of particular proteins, regions or epitopes or in the context of particular types of cancer cells and their interactions with the disclosed antibody drug conjugates, those skilled in the art will appreciate that the scope of the instant invention is not limited by such aspects.

[0216] I. Glycan Physiology

[0217] Various pathophysiological processes associated with tumor development and cancer progression, including cell-cell adhesion, cell-matrix interaction, epithelial-to-mesenchymal transition, tumor proliferation, invasion, metastasis, and angiogenesis, are regulated by glycosylation. Glycosylation is a complex form of post-translational modification, affecting over 50% of cell proteins and constituting a key regulator of many eukaryotic processes. The extracellular domains of most membrane anchored proteins are glycosylated, often at multiple sites, creating a dense network of carbohydrate chains at the cell surface (the glycocalyx). The various glycosylation patterns are abundant and diverse. Cancerous glycoproteomes exhibit varied density and distribution of glycosites and / or glycan chains structures. Interactions between the glycocalyx and tumor microenvironments, which may promote sustained proliferative signaling, resistance to cell death, deregulated cellular energetics, evasion of growth suppressors, genome instability and mutations, replicative immortality, angiogenesis, invasion and metastasis, tumorpromoting inflammation, and immune escape are detailed further in Peixoto et al., Front Oncol. 2019 May 14;9:380 (doi: 10.3389 / fonc.2019.00380), which is herein incorporated by reference in its entirety.

[0218] Aberrant glycosylation patterns can result in tumor-associated carbohydrate antigens (TACAs) that are suitable for targeting in oncotherapies, including cancer-targeted immunotherapies. TACAs can induce immunosuppressive signals by interacting with antigen- presenting cells via glycan-binding receptors, such as SIGLECs, MGL, and DC-SIGN. The best characterized TACAs are truncated O-glycans (Tn, sialyl-Tn (sTn), and TF antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GMl), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis antigens, and polysialic acid. TACAs are generally considered poorly immunogenic, eliciting

[0219] Page 55 of 347

[0220] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) weak humoral responses, and effective approaches to inducing of T-cell-dependent immune responses have typically required conjugation to carrier proteins or chemical modifications. As disclosed herein, immunogens generated in genetically modified cells, altered to prevent the extension to Core 1 O-glycans, increase the density of O-glycans, and supplemented with the ST6GalNAc-I enzyme to increase the production of sTn, were able to generate monoclonal antibodies with high affinity and high specificity against proteins carrying the sTn glycan.

[0221] Tn and sTn are classified as ( -GalNAc mucin-type glycans. (9-glycosylation occurs in approximately 85% of surface presented or secreted proteins. See, Romer et al., Br J Cancer. 2021 Oct; 125(9): 1239-1250 (doi: 10.1038 / s41416-021-01530-7), which is herein incorporated by reference in its entirety. Simple (truncated) mucin-type O-glycosylated TACAs are attractive targets for anticancer therapies because they are detected in most carcinomas and are usually absent in healthy tissues, although no FDA-approved drugs presently target truncated O-glycans. Overexpression of truncated O-glycans has been suggested to be an early and sustained event during cancer development that provides a permissive environment for malignant evolution during the progression to metastasis. They have been indicated in onogenesis, metastasis and immune- suppresion, specifically.

[0222] Mucin-type GalNAc O-glycans are built up by a sequential step-by-step process in the Golgi apparatus, starting with the addition of a N-acetyl-galactosamine (GalNAc) to a serine or a threonine residue, resulting in the core GalNAc-O-Ser / Thr antigen, known as the Thomsen- nouveau (Tn) antigen (also known as CD175). This initial key step of the O-glycosylation process is catalyzed by the UDP-GalNAc:polypeptide-N-acetyl-galactosaminyl-transferases family (GalNAc-T), having 20 different transferases. The Tn antigen is then further elongated by other glycosyltransferases to generate complex O-glycans. Addition of sialic acid to the Tn antigen, catalyzed by the ST6GalNAc-I, results in the sialyl-Tn (sTn) antigen (Neu5Aca2-6GalNAca-O- Ser / Thr also known as CD175s). The sialylation of the Tn antigen blocks further elongation of the saccharide chain. These truncated O-glycan antigens are observed at the earliest stages of cellular malignant transformation and are significantly associated with tumor progression through various mechanisms affecting adhesion properties of cancer cells, stabilizing receptor expression on the cell surface allowing stronger signaling, and triggering immune suppression by binding to tolerogenic dendritic cells or modulating NK cells action by competitive lectin binding. Furthermore, the Tn antigen is the acceptor substrate for core 1 P3 -galactosyltransferase

[0223] Page 56 of 347

[0224] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0225] (CI GalTl), which generates the core 1 disaccharide O-glycan Gaipi-3GalNAca-O-Ser / Thr, known as the Thomsen-Friedenreich (TF) antigen (also known as the T antigen).

[0226] The expression of the truncated Tn and sTn O-glycans in cancers has been proposed to result from a number of different mechanisms, including altered expression of glycosyltransferases; somatic mutations or hypermethylation of core 1 133-Gal-T-specific molecular chaperone (COSMC), a private chaperone for CIGalTl required for mature elongated O-glycosylation; relocation of polypeptide GalNAc-transferases from Golgi to endoplasmic reticulum (ER), general reorganization of glycosyltransferase topology, and fluctuations in cellular pH. Genetic profiling of a large number of pancreatic cancers revealed no evidence of somatic mutations in glycosylation-related genes and that almost 40% of cancers exhibited epigenetic silencing via hypermethylation of the COSMC gene that correlated with the loss of CIGalTl expression and the expression of truncated O-glycans. Likewise, knockout of COSMC in pancreatic cancer cell lines induced enhanced growth and invasive properties in culture as well as xenografts and loss of COSMC in an organotypic epidermis tissue model disrupted epithelial tissue integrity and homeostasis by inducing traditional oncogenic features, including hyperproliferation, loss of tissue architecture and disruption of basement membrane adhesion, and invasive growth, suggesting truncated O-glycans affect multiple pathways that promote tumor formation. The role of COSMC on expression of truncated O-glycans is described in further detail in Rhadakrishnan et al., Proc Natl Acad Sci U S A. 2014 Sep 30; 11 l(39):E4066-75 (doi: 10.1073 / pnas.1406619111), which is herein incorporated by reference in its entirety. Similarly, gastric cancer cells engineered to overexpress ST6GalNAc-I, leading to overexpression of sTn antigen, displayed enhanced in vitro invasion capacity, increased metastatic ability in mice, and markedly reduced homotypic cell-cell aggregation, but increased adhesion to extracellular matrix components such as collagen and fibronectin. See, Fernandes et al., Theranostics. 2020 Mar 31;10(l l):4903-4928 (doi: 10.7150 / thno.42480), which is herein incorporated by reference in its entirety.

[0227] Tumor glycan antigens, such as Tn and sTn, are described in further detail in Berois et al., Cancers (Basel). 2022 Jan 27;14(3):645 (doi: 10.3390 / cancersl4030645), which is herein incorporated by reference in its entirety. The Tn antigen has been characterized as a pan-cancer marker in human cancers. Different physiological mechanisms can cause the cumulative expression of the Tn antigen in cancerous cells. While the antigen’s chemical structure is defined, some known antibodies require more complex epitopes than the single Tn glycan, including, for

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[0229] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) example, additional amino acids. Thus, the neighboring peptide backbone may modulate the Tn epitope structure. Other known antibodies have required at least two consecutive Tn glycans for binding, consistent with the fact that the antigen is known to be clustered on native mucins. Other studies have shown increased efficacy of antibodies generated with immunogens comprising multiple (e.g., three) Tn glycans or additional peptide epitopes. Additional evidence suggests that for some anti-Tn antibodies, antibody binding is dependent on the amino acid carrier of the GalNAc (Ser vs. Thr), which may be important to specificity of cancer cell recognition. Accordingly, the Tn antigen may be a necessary but insufficient condition for some anti-Tn antibodies. Anti-Tn antibodies have been shown in vivo to reduce tumor growth via various mechanisms, which may be antibody-specific, including antibody-dependent cellular cytotoxicity (ADCC); antibody-induced complement-dependent cytotoxicity (CDC); inhibition of cancer cell adhesion to lymphatic endothelium; and direct blocking of receptor signaling, such as epidermal growth factor receptor and insulin-like growth factor I receptor. Tn antigen has also been shown to induce immune tolerance responses, including, for example, signaling through macrophage galactose C-type lectin (MGL) expressed on dendritic cells and macrophages, suppressing T-cell immunity, promoting angionesis, and potentially explaining the failure of some Tn-based vaccines. sTn is often coexpressed with Tn and exhibits a similar expression profile, including null- to-low expression in normal tissues (depending on the detection antibody). Aberrant sTn expression is also associated with dysregulation of O-glycosylation machinery. De novo sTn expression has been linked to changes in tumor malignant phenotype, aggressive cancer cell behavior, decreasing cell-cell aggregation, increasing tumor growth, extracellular matrix adhesion, migration, invasion, and metastases. sTn-expressing cancers cells have also been shown to impair dendritic cell maturation, limiting their capacity to trigger antitumor T-cell responses. sTn expression has been broadly associated with malignant phenotypes, poor prognosis, and decreased overall survival in patients. See, Loureiro et al., Sci Rep. 2018 Aug 15;8(1): 12196 (doi: 10.1038 / s41598-018-30421-w); Miles et al., Br J Cancer. 1994 Dec;70(6): 1272-5 (doi: 10.1038 / bjc.1994.486), each of which is herein incorporated by reference in its entirety. Studies have suggested that sTn antigen may interact with the lectin Siglec-15 expressed on tumor associated macrophages (TAMs) in the tumor microenvironment to promote tumor metastasis by coupling tumor cell recognition with the DAP12-Syk signal transduction pathway to induce TGF- B secretion. See, Takamiya et al., Glycobiology. 2013 Feb;23(2): 178-87 (doi:

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[0232] 10.1093 / glycob / cwsl39), which is herein incorporated by reference in its entirety. Hypoxia has also been found to induce sTn overexpression, particularly on integrins and cadherins, in bladder cancer cell lines via hypoxia inducible factor-la (HIF-la), which exhibits oxygen-dependent transcriptional activity and activates angiogenic, anti-apoptotic and growth factor genes, as well as a shift from aerobic to anaerobic metabolism, leading to enhanced cell migration and invasion. See, Peixoto et al., Oncotarget. 2016 Sep 27;7(39):63138-63157 (doi: 10.18632 / oncotarget.11257), which is herein incorporated by reference in its entirety. sTn has also been shown to protect cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 (gal-3), a B-galactoside-binding protein, and increasing gal-3 ’s intracellular accumulation. See, Santos et al., Oncotarget. 2016 Dec 13;7(50):83570-83587 (doi: 10.18632 / oncotarget.13192), which is herein incorporated by reference in its entirety. A subset of ovarian cancer cells were found to coexpress sTn and CD133, a marker of tumor-initiating cells, with sTn+cells already replicating some properties of tumorinitiating cells and targeting of sTn1cells demonstrating reduced tumor-initiating cell frequency. See, Starbuck et al., Oncotarget. 2018 May l;9(33):23289-23305 (doi: 10.18632 / oncotarget.25289). sTn expression has been found in metastases of various models and circulating tumor cells, supporting a role in metastases development. Fernandes et al, supra.

[0233] Various anti-sTn monoclonal antibodies (e.g., L2A5, B72.3, CC49, TKH2, 3F1, and 3P9), having various isotypes and exhibiting different binding patterns and functions, have been developed using various immunogens (e.g., different types of mucins, whole cell extracts, purified glycoproteins from cancer tissue) conjugated to various adjuvants. Loreiro, supra; Prendergast et al., MAbs. 2017 May / Jun;9(4): 615-627 (doi: 10.1080 / 19420862.2017.1290752), each of which is herein incorporated by reference in its entirety. Like some anti-Tn antibodies, some anti-sTn antibodies have exhibited better recognition and binding of clustered sTn antigen and some amino acid carrier (Ser vs. Thr) specificity. Some, but not all, anti-sTn antibodies have displayed crossreactivity with Tn antigen. B72.3 and CC49, while described as specific to the sTn-gly coprotein TAG-72, were clinically tested and shown to also cross react with Tn antigen. Oncoscint® (B72.3 antibody conjugated to indium-111) was approved by FDA as a diagnostic in 1992 for whole body imaging for recurrences of ovarian and colorectal cancers. The regulatory approval and strong safety profile of Oncoscint® led to the development of the second generation TAG-72 murine antibody CC49, which was evaluated for efficacy in Phase 2 clinical trials that evaluated an

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[0235] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) interferon adjuvant to enhance tumor antigen expression and131I-labeled CC49 to target both soft tissue and bone metastases in hormone-resistant metastatic prostate cancer patients. While the experimental therapy was generally well tolerated, the results were modest, and disease progression was not delayed for more than 6 months. Prendergast et al., supra. The L2A5 antibody has demonstrated high specificity toward tumor tissue, but the specificity may stem from crossreactivity with other sialylated TACAs rather than affinity for low-density sTn antigen. Loureiro et al., supra. L2A5 has also been used to engineer UniCAR T cells which were shown to effectively eradicate sTn-expressing breast and bladder cancer tumor cells in vitro and in vivo. Loureiro et al., Blood Cancer J. 2018 Aug 22;8(9):81 (doi: 10.1038 / s41408-018-0113-4), which is herein incorporated by reference in its entirety. Humanized anti-sTn ADCs were found to inhibit the growth of cancer cell lines and patient derived ovarian xenograft models in mice, and only mild MMAE toxicity was observed in cynomolgus monkeys. See, Eavarone et al., PloS One. 2018 Jul 27;13(7):e0201314 (doi: 10.1371 / journal. pone.0201314); Starbuck et al., supra, each of which is herein incorporated by reference in its entirety. Additional anti-sTn antibodies have been developed which are reported to target the sTn glycan itself, rather than a specific glycopeptide, offering broad potential to bind multiple sTn-glycosylated proteins on the surface of cancer cells. sTn-specific reactivity across a wide array of solid epithelial tumor types was observed, with reduced tumor volumes in multiple in vivo models. Prendergast et al., supra. Anti-sTn antibodies are also described in Kjeldsen et al., Cancer Res. 1988 Apr 15;48(8):2214-20; US 9879,087 to DeSander et al., issued Jan 30, 2018; and WO 2019 / 147152 to Videira et al., published Aug. 1, 2019, each of which is herein incorporated by reference in its entirety.

[0236] The Theratope® anti-cancer vaccine consisting of a synthetic construct of sTn disaccharide conjugated to an engineered Keyhole limpet haemocyanin (KLH) for immunogenicity has been the most studied sTn-targeting therapeutic. However, despite promising responses in murine mammary carcinoma models as well as improved survival and anti-sTn humoral responses in human patients, no overall benefit was observed in phase III clinical trials of metastatic breast cancer patients and only modest clinical efficacy was observed in metastatic breast cancer patients receiving concurrent endocrine therapy, possibly due to broad variability of sTn expression in breast cancer tissues.

[0237] Antibody mapping of truncated O-glycans has revealed high expression levels of Tn- antigen and sTn-antigen in epithelial tissue-derived cancers, such as tumors of the breast, colon,

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[0239] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) prostate, lung, pancreas, and skin, although variations existed between cancer types from the same organ. See, Romer et al., supra. sTn has been found to be highly overexpressed in advanced stage digestive tract tumors (esophageal, gastric, and colorectal tumors) where they are frequently associated with poor prognosis. Fernandes et al, supra; Cotton et al., Int J Mol Sci. 2021 Feb 7;22(4): 1664 (doi: 10.3390 / ijms22041664), each of which is herein incorporated by reference in its entirety. GLUTl-sTn overexpression, in particular, has been associated with esophageal squamous cell carcinomas (ESCCs) and sTn has been identified in esophageal-derived circulating tumor cells. Cotton et al., supra. sTn is expressed on ovarian cancer biomarkers including CA- 125 (MUC16) and MUC1, and elevated serum levels of sTn have been used for prognosing ovarian cancer patients. See, Eavarone et al., supra. In breast cancer, sTn overexpression has been associated with PD-L1 overexpression, and the coexpression was related to a high density of CD8+tumor-infiltrating lymphocytes (TILs), suggesting the triggering of immune evasion and tolerance. sTn / PD-Ll co-expression was significantly related to negative ER expression, positive HER-2 status and positive lymph node metastasis, and could be used as an independent prognostic factor for shorter progression free survival (PFS) and overall survival (OS). Both sTn and PD-L1 were more highly expressed in primary lesions than in metastatic lesions in breast cancer samples. See, Xu et al., Gland Surg. 2021 Jul;10(7):2159-2169 (doi: 10.21037 / gs-21-83).

[0240] Most tumors exhibited intra-tumor heterogeneity in expression patterns of Tn-antigen, sTn- antigen, and TF-antigen and many showed only partial positivity. Tn-antigen expression was correlated to both sTn-antigen and TF-antigen expression, although tumors demonstrated predominant expression of only one truncated O-glycan, likely due, in part, to the competitive elongation pathways for generating sTn-antigen and TF-antigen from Tn-antigen. In breast cancer, ductal carcinomas often expressed both Tn-antigen and sTn-antigen with less reactivity observed in medullary carcinomas. sTn is expressed in numerous human adenocarcinomas, including breast, ovarian, bladder, cervical, colon, pancreatic and lung cancers. Prendergast et al, supra. Adenocarcinomas and squamous cell carcinomas of the lung often expressed sTn-antigen, but rarely Tn-antigen. Pancreatic tumors almost exclusively expressed truncated O-glycans in adenocarcinomas and never in islet cell tumors. Only limited expression of truncated O-glycans was observed in central nervous system tumors, except for a subset of Tn-antigen positive glioblastomas, and no expression was observed in mesenchymal-tissue derived tumors. Tn-antigen and sTn-antigen expression decreased with increasing tumor grade, possibly suggesting truncation

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[0242] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) occurs at early stages of tumor development, whereas T-synthase levels may increase with tumor grade as accumulated mutations and dedifferentiation drives additional growth. In some cancer cells, CD44 and MUC1 are major carriers of the sTn antigen. See, Starbuck et al., supra.

[0243] In healthy tissue, no Tn-antigen expression was observed and sTn-antigen expression was only observed in the gastrointestinal tract (intracellular or localized to specific cell types). Normal adult tissue expression of sTn is rare and largely restricted to cell types specialized in secretion, generally on the apical surface, which would likely restrict the antigen’s accessibility to therapeutics administered in the blood. Prendergast et al, supra. Expression of Tn-antigen and sTn antigen in normal adult tissue is generally confined to immunologically privileged sites and is further described in Cao et al., Histochem Cell Biol. 1996 Aug; 106(2): 197-207 (doi: 10.1007 / BF02484401), which is herein incorporated by reference in its entirety. sTn expression is described in further detail in Julien et al., Biomolecules. 2012 Oct 11;2(4):435-66 (doi: 10.3390 / biom2040435), which is herein incorporated by reference in its entirety.

[0244] Mucins (MUC) are glycosylated proteins synthesized principally by epithelial cells, which provide protection against environmental insult and lubrication to the epithelial surfaces thereby maintaining homeostasis. The presence of highly O-glycosylated tandem repeat regions (TR) is a hallmark of mucins, consisting of proline, threonine, and serine (PTS) residues, which allow for clustering of O-glycans, such as sTn. Mucins can be classified into secreted (MUC2, MUC5AC, MUC5B, MUC6, MUC7, MUC8, and MUC 19) and membrane-bound (MUC1, MUC3A, MUC3B, MUC4, MUCH-13, MUC15-17, MUC20, MUC21, and MUC22) families. Structural attributes of membrane-bound mucins, such as extensive glycosylation and presence of growth factor-like C-terminal domains, modulate the microenvironment around the cell surface and mediate the interactions of mucins with other surface receptors.

[0245] The aberrant overexpression and glycosylation of mucins in various malignancies facilitate oncogenic events from inception to metastasis. Cellular transformation leads to the loss of polarity of the epithelial cells, which brings transmembrane mucins close to cell surface receptors that would otherwise be sequestered basolaterally in the polarized epithelium. In addition, altered mucins glycosylation paterns during malignant transformation enable their interaction with various receptors and thereby promote cancer cell differentiation, proliferation, invasion, and metastasis. Cancer cells exploit the immune-modulatory ability of mucins to evade immune surveillance. Mucins can interact with various inhibitory receptors like intercellular

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[0247] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) adhesion molecule-1 (ICAM-1) on T-cells, leading to their anergy and impaired antigen recognition, and with sialic-acid-binding immunoglobulin-like lectin receptors (siglecs) on antigen-presenting cells (APCs). Overexpression of mucins on cancer cells create steric hindrance and mask the detection of tumor-associated antigens (TAAs) and prevent specific and non-specific lysis of the tumor cells by immune cells.

[0248] Furthermore, mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC 1 -mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC 16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC 16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC 1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC 16 neoantigenspecific T cell clones and anti-MUCl antibodies in cancer patients suggests that mucins can serve as their own targets for cancer immunotherapy. Mucins, including aspects of their role in cancer and aberrant glycosylation (e g., with sTn), are described in further detail in Bhatia et al., Cancer Metastasis Rev. 2019 Jun;38(l-2):223-236 (doi: 10.1007 / sl 0555-018-09775-0), which is herein incorporated by reference in its entirety.

[0249] Given that mucins are particularly prone to aberrant sTn glycosylation, mucins may serve as suitable immunogens for developing sTn antibodies. According to preferred aspects of disclosure, sTn antibodies described herein may be used to target sTn glycans independent of the carrier protein, but including mucins with aberrant sTn glycosylation. Many other carrier proteins which express sTn are also themselves cancer-specific antigens and may be targeted by the sTn antibodies of the invention. According to certain aspects of the disclosure, sTn antibodies generated using mucin-derived immunogens may exhibit increased specificity and / or affinity for aberrantly glycosylated mucins or for epitopes having sTn anchor peptide sequences that exhibit homology to mucin peptide sequences, including those used for immunization.

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[0252] Generating antibodies to glycans is challenging, especially for achieving anti-glycan antibodies with high affinity and high specificity. The antibodies disclosed herein display suprising properties not previously accomplished in the field, including high specificity and high affinity (e.g., KD of < 5xlO'9M).

[0253] II. Antibodies

[0254] A. Antibody structure

[0255] The present invention provides sTn antibodies, which are exemplified by the antibodies having sequences shown in Tables 4-9, 12-34, and 36-47, and variants and described herein.

[0256] Antibodies and variants and derivatives thereof, including accepted nomenclature and numbering systems, have been extensively described, for example, in Abbas et al. (2010), Cellular and Molecular Immunology (6lhEd.), W.B. Saunders Company; or Murphey et al. (2011), Janeway ’s Immunobiology (8thEd.), Garland Science.

[0257] Conventional antibodies are tetrameric proteins comprising two heavy (H) and two light (L) polypeptide chains held together by covalent disulfide bonds and non-covalent interactions. Each light chain is composed of one variable domain (VL) and one constant domain (CL). Each heavy chain comprises one variable domain (VH) and a constant region, which in the case of IgG, IgA, and IgD antibodies, comprises three domains termed CHI, CH2, and CH3 (IgM and IgE have a fourth domain, CH4). In IgG, IgA, and IgD classes the CHI and CH2 domains are separated by a flexible hinge region, which is a proline and cysteine rich segment of variable length (from about 10 to about 60 amino acids in various IgG subclasses). The variable domains in both the light and heavy chains are joined to the constant domains by a “J” region of about 12 or more amino acids and the heavy chain also has a “D” region of about 10 additional amino acids. Each class of antibody further comprises inter-chain and intra-chain disulfide bonds formed by paired cysteine residues.

[0258] As used herein the term "antibody" includes polyclonal antibodies, multiclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, fully human antibodies, intrabodies, internalizing antibodies, multispecific antibodies such as bispecific antibodies, monovalent antibodies, multivalent antibodies, anti-idiotypic antibodies, recombinantly produced antibodies, and variants thereof. The term “antibody” also includes an antibody produced by recombinant techniques as described elsewhere herein and otherwise known in the art. The term

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[0261] “antibody” also includes immunospecific antibody fragments of any of the above-mentioned antibodies, such as Fd, Fab, F(ab')2, F(ab') fragments, single-chain fragments (e g. ScFv and ScFvFc) single domain antibodies and nanobodies, such as VHH fragments and VNAR fragments; and derivatives thereof including Fc fusions and other modifications. Unless dictated otherwise by contextual constraints the term “antibody” refers to all classes of antibodies (i.e. IgA, IgD, IgE, IgG, and IgM) and all subclasses (i.e., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2). Heavy chain constant domains that correspond to the different classes of antibodies are typically denoted by the corresponding lower case Greek letter a, 8, a, y, and p, respectively. Light chains of the antibodies from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (K) and lambda ( ), based on the amino acid sequences of their constant domains.

[0262] The variable domains of antibodies show considerable variation in amino acid composition from one antibody to another and are primarily responsible for antigen recognition and binding. Variable regions of each light / heavy chain (VL / VH) pair form the antibody binding site such that a conventional IgG antibody has two binding sites (i.e., it is bivalent). VH and VL regions comprise three regions of extreme variability, which are termed hypervariable regions, or more commonly, complementarity determining regions (CDRs), which are framed and separated by four less variable regions known as framework regions (FRs). Non-covalent association between the VH and the VL region forms the Fv fragment (for "fragment variable") which contains one of the two antigen-binding sites of the antibody.

[0263] As used herein, the assignment of amino acids to each domain, framework region and CDR may be in accordance with one of the schemes provided by Kabat et al. (1991) Sequences of Proteins of Immunological Interest (5thEd.), US Dept, of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242; Chothia et al., 1987, PMID: 3681981; Chothia et al, 1989, PMID: 2687698; MacCallum et al. ,1996, PMID: 8876650; Dubel, Ed. (2007) Handbook of Therapeutic Antibodies, 3rdEd., Wily-VCH Verlag GmbH and Co or AbM (Oxford Molecular / MSI Pharmacopia) orLefranc et al., 2003, Dev. Comp. Immunol. 27:55-77, unless otherwise noted. As is well known in the art variable region residue numbering is typically as set forth in Chothia or Kabat. Amino acid residues which comprise CDRs as defined by Kabat, Chothia, MacCallum (also known as Contact), AbM, and IMGT (also known as Lefranc) as obtained from the Abysis website database (infra.) are set out below in Table 1.

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[0266] Table 1: CDR Definitions

[0267] Variable regions and CDRs in an antibody sequence can be identified according to general rules that have been developed in the art (as set out above, such as, for example, the Kabat numbering system) or by aligning the sequences against a database of known variable regions. Methods for identifying these regions are described in Lefranc et al., 2003, Dev. Comp. Immunol. 2T.55-7T, Kontermann and Dubel, eds., Antibody Engineering, Springer, New York, NY, 2001 and Dinarello et al., Current Protocols in Immunology, John Wiley and Sons Inc., Hoboken, NJ, 2000. Representative databases of antibody sequences are described in, and can be accessed through, the “Abysis" website at www.bioinf.org.uk / abs (maintained by A.C. Martin in the Department of Biochemistry & Molecular Biology University College London, London, England) and the VBASE2 website at www.vbase2.org, as described in Retter et al., Nucl. Acids Res., 33 (Database issue): D671 -D674 (2005). For example, the Abysis database integrates sequence data from Kabat, IMGT and the Protein Data Bank (PDB) with structural data from the PDB (see Dr. Andrew C. R. Martin's book chapter Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Antibody Engineering Lab Manual (Ed.: Duebel, S. and Kontermann, R., Springer-Verlag, Heidelberg, ISBN-13: 978-3540413547, also available on the website bioinforg.uk / abs) and includes general rules that have been developed for identifying CDRs.

[0268] For heavy chain constant region amino acid positions discussed in the disclosure, numbering is according to the Eu index first described in Edelman et al., 1969, Proc. Natl. Acad. Sci. USA 63(1): 78-85 describing the amino acid sequence of the myeloma protein Eu, which reportedly was the first human IgGl sequenced. The Eu index of Edelman is also set forth in Kabat et al., 1991 (supraf Thus, the terms “Eu index as set forth in Kabat” or “Eu index of Kabat” or “Eu index” or “Eu numbering” in the context of the heavy chain refers to the residue numbering

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[0270] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) system based on the human TgGl Eu antibody of Edelman et al. as set forth in Kabat et al., 1991 (supra.) The numbering system used for the light chain constant region amino acid sequence is similarly set forth in Kabat et al., (supra.)

[0271] Exemplary human kappa and lambda light chain constant region amino acid sequences, including both naturally occurring or modified constant regions, are well known in the art and are readily used to prepare antibodies as disclosed herein (e.g., UniProtKB / Swiss-Prot: P01834.2 and P0CG04.1, respectively). Similarly, exemplary human heavy chain constant region amino acid sequences are well known in the art and may be substituted for the heavy chain constant regions of the antibodies disclosed herein, including, for example, the wild type heavy chain constant region of human IgG antibodies such as IgGl (e.g., GenBank: AXN93653.1), IgG2 (e.g., GenBank: AXN93663.2), or IgG4 (e.g., GenBank: CAC20457.1). The heavy chain and / or light chain constant region sequences disclosed in SEQ ID Nos: 103 and 104 may be substituted for the heavy chain and / or light chain constant regions, respectively, of the antibodies disclosed herein, e.g., to produce a chimeric antibody from an antibody derived from a non-human source, such as mouse.

[0272] Those of skill in the art will appreciate that such heavy and light chain constant region sequences, either wild-type or engineered as disclosed herein (e.g., to provide unpaired cysteines) may be operably associated with the disclosed heavy and light chain variable regions using standard molecular biology techniques to provide full-length antibodies that may be incorporated in the anti-sTn immunoconjugates (e.g., antibody drug conjugates) of the instant invention.

[0273] There are two types of disulfide bridges or bonds in immunoglobulin molecules: interchain and intrachain disulfide bonds. As is well known in the art the location and number of interchain disulfide bonds vary according to the immunoglobulin class and species. While this invention is not limited to any particular class or subclass of antibody, the IgGl immunoglobulin shall be used throughout the instant invention for illustrative purposes. In wild-type IgGl molecules there are twelve intrachain disulfide bonds (four on each heavy chain and two on each light chain) and four interchain disulfide bonds. Intrachain disulfide bonds are generally somewhat protected and relatively less susceptible to reduction than interchain bonds. Conversely, interchain disulfide bonds are located on the surface of the immunoglobulin, are accessible to solvent and are usually relatively easy to reduce. Two interchain disulfide bonds exist between the heavy chains and one from each heavy chain to its respective light chain. It has been demonstrated that interchain

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[0275] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) disulfide bonds are not essential for chain association. The IgGl hinge region contain the cysteines in the heavy chain that form the interchain disulfide bonds, which provide structural support along with the flexibility that facilitates Fab movement. The heavy / heavy IgGl interchain disulfide bonds are located at residues C226 and C229 (Eu numbering) while the IgGl interchain disulfide bond between the light and heavy chain of IgGl (heavy / light) are formed between C214 of the kappa or lambda light chain and C220 in the upper hinge region of the heavy chain.

[0276] B. Antibody generation and production

[0277] Antibodies of the invention can be produced using a variety of methods known in the art. In certain aspects the sTn ADCs of the invention will comprise an anti-sTn antibody as set forth in the appended Examples or an immunoreactive fragment thereof.

[0278] 1. Types of Antibodies

[0279] 1.1. Monoclonal antibodies

[0280] The present invention contemplates use of monoclonal antibodies. As known in the art, the term "monoclonal antibody" or “mAb” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible mutations (e g., naturally occurring mutations), that may be present in minor amounts.

[0281] Monoclonal antibodies can be prepared using a wide variety of techniques known in the art including hybridoma techniques, recombinant techniques, phage display technologies, transgenic animals (e.g., Alloy Therapeutics ATX-Gx" mice or a XenoMouse®) or some combination thereof. For example, monoclonal antibodies can be produced using hybridoma and biochemical and genetic engineering techniques such as described in more detail in An, Zhigiang (ed.) Therapeutic Monoclonal Antibodies: From Bench to Clinic, John Wiley and Sons, 1sted. 2009; Shire et. al. (eds.) Current Trends in Monoclonal Antibody Development and Manufacturing, Springer Science + Business Media LLC, 1sted. 2010; Dimitrov. Antony (ed.) Therapeutic Antibodies: Methods and Protocols, Humana Press; 2009; Harlow et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, 2nd ed. 1988; Hammerling, et al, in: Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, N.Y.,

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[0284] 1981). Following production of multiple monoclonal antibodies that bind specifically to a determinant, particularly effective antibodies may be selected through various screening processes, based on, for example, its affinity for the determinant or rate of internalization. Antibodies produced as described herein may be used as “source” antibodies and further modified to, for example, improve affinity for the target, improve its production in cell culture, reduce immunogenicity in vivo, create multispecific constructs, etc.

[0285] 1.2. Human antibodies

[0286] In some aspects of the invention, the antibodies may comprise fully human antibodies. The term “human antibody” refers to a non-naturally occurring antibody produced using any of the antibody engineering techniques for making human antibodies as known in the art.

[0287] For example, one technique involves generation of a display library of antibodies possessing amino acid sequences corresponding to human antibodies in phage or yeast, and then screened to identify those antibodies that bind to an antigen. Methods for preparing and screening such libraries are well known in the art and kits for generating phage display libraries are commercially available (e.g., the Pharmacia Recombinant Phage Antibody System, catalog no. 27- 9400-01; and the Stratagene SurfZAP™ phage display kit, catalog no. 240612). There also are other methods and reagents that can be used in generating and screening antibody display libraries (see, e.g., U.S.P.N. 5,223,409, U.S.P.N. 7,700,302; PCT Publication Nos. WO 92 / 18619, WO 91 / 17271, WO 92 / 20791, WO 92 / 15679, WO 93 / 01288, WO 92 / 01047, WO 92 / 09690; and Barbas et al., Proc. Natl. Acad. Sci. USA 88:7978-7982 (1991), Vaughan et al. Nature Biotechnology! 14:309-314 (1996): Sheets et al. Proc. Natl. Acad. Sci. USA 95:6157-6162 (1998)).

[0288] Human antibodies can also be made by introducing human immunoglobulin loci into transgenic cells or animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated and human immunoglobulin genes have been introduced (“humanized mice”). Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S.P.Ns. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and U.S.P.Ns. 6,075,181 and 6,150,584 regarding XenoMouse® technology; and Lonberg and Huszar, Intern. Rev. Immunol. 13:65-93 (1995). Alternatively, the human antibody may be prepared via immortalization of human B lymphocytes

[0289] Page 69 of 347

[0290] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) producing an antibody directed against a target antigen (such B lymphocytes may be recovered from an individual suffering from a neoplastic disorder or may have been immunized in vitro). See, e.g., Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boemer et al., J. Immunol, 147 (l):86-95 (1991); and U.S.P.N. 5,750,373.

[0291] 1.3. Chimeric and humanized antibodies

[0292] According to one aspect, the antibodies of the present invention are chimeric antibodies that are derived from protein segments from at least two different species or class of antibodies that have been covalently joined. The term "chimeric" antibody is directed to constructs in which a portion of the heavy and / or light chain is identical or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical or homologous to corresponding sequences in antibodies from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies (U.S.P.N. 4,816,567). According to some aspects, chimeric antibodies of the instant invention may comprise all or most of the selected murine heavy and light chain variable regions operably linked to human light and heavy chain constant regions. According to other selected aspects, anti-sTn antibodies may be derived from the mouse antibodies disclosed herein and comprise less than the entire heavy and light chain variable regions.

[0293] According to other aspects, chimeric antibodies of the invention are "CDR-grafted" antibodies, where the CDRs (as defined using Kabat, Chothia, McCallum, etc.) are derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the antibody is largely derived from an antibody from another species or belonging to another antibody class or subclass. For use in humans, one or more selected rodent CDRs (e.g., mouse CDRs) may be grafted into a human acceptor antibody, replacing one or more of the naturally occurring CDRs of the human antibody. These constructs generally have the advantages of providing full strength human antibody functions, e.g., complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) while reducing unwanted immune responses to the antibody by the subject. According to one aspect of the invention, the CDR grafted antibodies will comprise one or more CDRs obtained from a mouse incorporated in a human framework sequence.

[0294] Page 70 of 347

[0295] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0296] Also provided are “humanized” antibodies, in which a human antibody (acceptor antibody) comprises one or more amino acid sequences (e.g. CDR sequences) derived from one or more nonhuman antibodies (donor or source antibody). As is well known in the art, “back mutations” can be introduced into the humanized antibody, in which residues in one or more FRs of the variable region of the recipient human antibody are replaced by corresponding residues from the nonhuman species donor antibody. Such back mutations may help maintain the appropriate three- dimensional configuration of the grafted CDR(s) and thereby improve affinity and antibody stability. Antibodies from various donor species may be used including, without limitation, mouse, rat, rabbit, chicken, or non-human primate. Furthermore, humanized antibodies may comprise new residues that are not found in the recipient antibody or in the donor antibody to, for example, further refine antibody performance.

[0297] Various art-recognized techniques can be used to determine which human sequences to use as acceptor antibodies to provide humanized constructs in accordance with the instant invention. Compilations of compatible human germline sequences and methods of determining their suitability as acceptor sequences are disclosed, for example, in Dubel and Reichert (Eds.) (2014) Handbook of Therapeutic Antibodies, 2ndEdition, Wiley -Blackwell GmbH; Tomlinson, I. A. etal. (1992) J. Mol. Biol. 227:776-798; Cook, G. P. etal. (1995) Immunol. Today 16: 237-242; Chothia, D. et al. (1992) J. Mol. Biol. 227:799-817; and Tomlinson et al. (1995) EMBO J 14:4628-4638). The V-BASE directory (VBASE2 - Retter et al., Nucleic Acid Res. 33; 671-674, 2005) which provides a comprehensive directory of human immunoglobulin variable region sequences (compiled by Tomlinson, I. A. et al. MRC Centre for Protein Engineering, Cambridge, UK) may also be used to identify compatible acceptor sequences. Additionally, consensus human framework sequences described, for example, in U.S.P.N. 6,300,064 may also prove to be compatible acceptor sequences and can be used in accordance with the instant teachings. In general, human framework acceptor sequences are selected based on homology with the murine source framework sequences along with an analysis of the CDR canonical structures of the source and acceptor antibodies. The derived sequences of the heavy and light chain variable regions of the derived antibody may then be synthesized using art recognized techniques.

[0298] By way of example CDR grafted and humanized antibodies, and associated methods, are described in U.S.P.Ns. 6,180,370 and 5,693,762. For further details, see, e.g., Jones et al., 1986, (PMID: 3713831); and U.S.P.Ns. 6,982,321 and 7,087,409.

[0299] Page 71 of 347

[0300] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0301] Transgenic cells and animals (e.g., “humanized mice”) may be used to generate fully human antibodies, as described elsewhere herein, and / or may be used to generate chimeric antibodies. All portions of a “fully human” antibody are encoded by human immunoglobulin transgenes, but some or all non-coding genes may remain endogenous / non-human. Chimeric antibody structures are encoded by a combination of human and non-human / endogenous genes. The endogenous genes corresponding to the human transgenes may be inactivated (e.g., knocked out) in the transgenic cell or animal. According to certain aspects, the transgenic cell or animal (e g., a mouse or other rodent) comprises human immunoglobulin heavy chain V gene segments and / or human immunoglobulin light chain V gene segments (lambda V gene segments and / or kappa V gene segments). V gene segments may be selected for high expression level, stability, and ubiquity; high sequence diversity in CDRs; and / or low sequence diversity in framework regions. According to specific aspects of the invention, the transgenic mouse may have a heavy chain repertoire comprising at least 10, 15, 20, 25, 30, 35, 40, 45, or 50 heavy chain V gene segments. According to specific aspects of the invention, the transgenic mouse may have a light chain repertoire comprising at least 10, 15, 20, 25, 30, 35, 40, 45, or 50 lambda chain V gene segments and / or at least 10, 15, 20, 25, 30, 35, 40, 45, or 50 kappa chain V gene segments. According to certain aspects, the transgenic cell or animal comprises human immunoglobulin heavy chain J gene segments and / or human immunoglobulin light chain J gene segments. According to certain aspects, the transgenic cell or animal comprises human immunoglobulin heavy chain D gene segments. According to certain aspects, the transgenic animal is a transgenic mouse of one of the following parental strains: C57B1 / 6, SJL, FVB, 129, and BALB / c. According to certain aspects, the transgenic animal may be a transgenic mouse comprising one of the following MHC haplotypes: H-2b, H-2s, H-2q, and H-2d.

[0302] According to certain aspects, the transgenic animal comprises endogenous / non-human genes for the antibody heavy chain constant region. For example, the humanized antibody may comprise the heavy chain constant region of a rat or mouse IgGl, IgG2b, IgG2c, IgG3 antibody. According to certain aspects, the antibody heavy chain comprises a human variable region and a chimeric constant region. According to certain aspects, the antibody light chain comprises a human variable region and a chimeric constant region. The portions of the constant region most adjacent to the variable region (e.g., CHI or CHI and at least a portion of the hinge region) may

[0303] Page 72 of 347

[0304] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) be human to support the proper conformation of the adjacent human variable region, while the remaining portions of the constant region may be non-human / endogenous.

[0305] Transgenic animals can be used to generate diverse repertoires of in vivo affinity-matured antibodies with intrinsic drug-like properties necessary for successful development. For example, antibodies generated from humanized animals (e.g., mice) may demonstrate high potency, specificity, solubility, and manufacturability. Such antibodies can avoid the inconvenience of more complex humanization protocols and in vitro affinity maturation procedures. Antibodies having full-human variable regions (VH and VL) have low risk of immunogenicity, mitigating losses in efficacy that occur due to anti-drug responses when antibodies are reformatted as therapeutics. Antibody generation in humanized animals may provide for normal B cell development, productive rearrangement of functional human V, D, and J gene segments, normal human frequency of V, D, and J gene usage, normal human CDR-H3 length distribution, normal hypermutation and affinity maturation, and / or high expression of human antibodies. According to specific aspects, the antibody of the present invention may be produced by the methods described in U.S. Pat. No. 10,836,832 to Green et al., issued Nov. 17, 2020; U.S. Patent No. 10,638,736 to Green et al., issued May 5, 2020; U.S. Pat. App. Pub. No. 2005 / 0042664 to Wu et al., published Feb. 24, 2005; U.S. Pat. App. Pub. No. 2005 / 0048617 to Wu et al., published March 3, 2005; Briiggemann etal., Transplantation (2017) 101(8): 1770-1776; Briiggemann et al., Arch. Immunol. Ther. Exp. (2015) 63:101-108, or Lowitz et al. “Optimization of Therapeutic Discovery Strategies for Human Antibody Transgenic Animal Platforms” Poster presented at PEGS; 2019 Apr. 8-12; Boston, MA, each of which is herein incorporated by reference in its entirety. Multiple commercial platforms are available for antibody discovery using genetically modified mice that express fully- human heavy and light chain variable regions, including OmniMouse® (Ligand), Harbour Mice® (Harbour Biomed), Trianni Mouse® (Trianni), AlivaMab Mouse® (Ablexis), and Alloy GX Mouse® (Alloy Therapeutics). According to certain aspects of the invention, fully humanized antibodies may be generated using one of these transgenic mice antibody discovery platforms.

[0306] 1.4. Single domain antibodies

[0307] Single domain antibodies, also called nanobodies, are antibody fragments containing a single monomeric variable region. While most commonly produced from heavy chain variable regions, they can also be produced from light chain variable regions. Single domain antibodies

[0308] Page 73 of 347

[0309] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) can be produced by immunization of appropriate species (e.g., camels, llamas, alpacas or sharks), construction of an mRNA library, and use of screening techniques like phage display and ribosome display help to identify the clones that bind the antigen. Alternatively, single-domain antibodies can be derived from conventional antibodies (see e.g. Ward et al., Nature (1989) 341 (6242): 544- 546; Feng wt al, Antibody Therapeutics (2020) 3 (1): 10-17; and Holt et al., Trends in Biotechnology (2003) 21 (11): 484-490).

[0310] 1.5. Fragments

[0311] Regardless of which form of antibody (e.g. chimeric, humanized, etc.) is selected to practice the invention it will be appreciated that immunoreactive fragments, either by themselves or as part of an immunoconjugate (e.g., antibody drug conjugate), of the same may be used in accordance with the teachings herein. An “antibody fragment" comprises at least a portion of a conventional antibody. As used herein, the term "fragment" of an antibody molecule includes antigen-binding fragments of antibodies, and the term “antigen-binding fragment” refers to a polypeptide fragment of an immunoglobulin or antibody that immunospecifically binds or reacts with a selected antigen or immunogenic determinant thereof or competes with the conventional antibody from which the fragments were derived for specific antigen binding.

[0312] Exemplary immunoreactive fragments include: variable light chain fragments (VL), variable heavy chain fragments (VH), scFvs, F(ab')2 fragment, Fab fragment, Fd fragment, Fv fragment, single domain antibody fragments, diabodies, tribodies, tetrabodies, minibodies, linear antibodies, single-chain antibody molecules and multispecific antibodies formed from antibody fragments. Tn addition, an active site-specific fragment comprises a portion of the antibody that retains its ability to interact with the antigen / substrates or receptors and modify them in a manner similar to that of a conventional antibody (though maybe with somewhat less efficiency). Such antibody fragments may further be engineered to comprise one or more free cysteines as described herein.

[0313] According to some aspects, the sTn binding domain will comprise a scFv construct. As used herein, a “single chain variable fragment (scFv)” means a single chain polypeptide derived from an antibody which retains the ability to bind to an antigen. An example of the scFv includes an antibody polypeptide which is formed by a recombinant DNA technique and in which Fv regions of immunoglobulin heavy chain and light chain fragments are linked via a spacer sequence.

[0314] Page 74 of 347

[0315] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0316] Various methods for preparing a scFv are known, and include methods described in U.S.P.N. 4,694,778.

[0317] According to other aspects, an antibody fragment is one that comprises the Fc region and that retains at least one of the biological functions normally associated with the Fc region when present in a conventional antibody, such as FcRn binding, antibody half-life modulation, ADCC function and complement binding. According to one aspect of the invention, an antibody fragment is a monovalent antibody that has an in vivo half-life substantially similar to a conventional antibody. For example, such an antibody fragment may comprise an antigen binding arm linked to an Fc sequence comprising at least one free cysteine capable of conferring in vivo stability to the fragment.

[0318] As would be well recognized by those skilled in the art, fragments can be obtained by molecular engineering or via chemical or enzymatic treatment (such as papain or pepsin) of a conventional antibody or antibody chain or by recombinant means. See, e.g., Fundamental Immunology, W. E. Paul, ed., Raven Press, N.Y. (1999), for a more detailed description of antibody fragment.

[0319] According to select aspects, antibody fragments of the invention will comprise ScFv constructs which may be used in various configurations. For example, ScFv antibody fragments may be used to generate a chimeric antigen receptors (CAR) that immunoselectively react with sTn, as described elsewhere herein.

[0320] 1.6. Multivalent constructs

[0321] According to other aspects, the antibodies and immunoconjugates of the invention may be monovalent or multivalent (e.g., bivalent, trivalent, etc.). As used herein, the term "valency" refers to the number of potential target binding sites associated with an antibody. Each target binding site specifically binds one target molecule or specific position or locus on a target molecule. When an antibody is monovalent, each binding site of the molecule will specifically bind to a single antigen position or epitope. When an antibody comprises more than one target binding site (multivalent), each target binding site may specifically bind the same or different molecules (e.g., may bind to different ligands or different antigens, or different epitopes or positions on the same antigen). See, for example, U.S. Pat. App. Pub. No. 2009 / 0130105.

[0322] Page 75 of 347

[0323] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0324] According to one aspect of the invention, the antibodies are bi specific antibodies in which the two chains have different specificities, as described in Millstein et al., 1983, Nature, 305:537- 539. According to other aspects, the invention includes antibodies with additional specificities such as trispecific antibodies. Other more sophisticated compatible multispecific constructs and methods of their fabrication are set forth in U.S.P.N. 2009 / 0155255, as well as WO 94 / 04690; Suresh et al., 1986, Methods in Enzymology, 121 :210; and WO96 / 27011. According to certain aspects of the invention, a bispecific antibody comprising the sTn antigen-binding domains of the instant invention may be prepared and / or used as in Juntilla et al., Mol Cancer Ther 2021 Feb 3; molcanther.0490.2020 (doi: 10.1158 / 1535-7163.MCT-20-0490) or U.S. Patent No. 10,40,572 to Chen et al., issued May 5, 2020, each of which is herein incorporated by reference in its entirety.

[0325] Multivalent antibodies may immunospecifically bind to different epitopes of the desired target molecule or may immunospecifically bind to both the target molecule as well as a heterologous epitope, such as a heterologous polypeptide or solid support material. While selected antibodies of the invention may only bind two antigens (i.e. bispecific antibodies), antibodies with additional specificities such as trispecific antibodies are also encompassed by the instant invention. Bispecific antibodies also include cross-linked or "heteroconjugate" antibodies. For example, one of the antibodies in the heteroconjugate can be coupled to avidin, the other to biotin. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S.P.N. 4,676,980), and for treatment of HIV infection (WO 91 / 00360, WO 92 / 200373, and EP 03089). Heteroconjugate antibodies may be made using any convenient cross-linking methods. Suitable cross-linking agents are well known in the art, and are disclosed in U.S. P.N. 4,676,980, along with a number of cross-linking techniques.

[0326] Multivalent antibodies can be prepared as full length antibodies or as antibody fragments, including those described elsewhere herein which comprise multiple antigen binding sites (e.g., F(ab')2 bispecific antibodies). In one aspect of the invention, multivalent antibodies may bind to two different epitopes of the same antigen (e.g., sTn). In another aspect of the invention, multivalent antibodies may bind to different antigen moieties on the same protein (e.g., clustered sTn glycans expressed on the same protein). In another aspect of the invention, multivalent antibodies may bind to different antigen moieties on different proteins (e.g. sTn attached to one protein and to another antigen on a different protein (e.g. a protein epitope or a different glycan epitope. It is expressly contemplated that multivalent antibodies of the invention may further

[0327] Page 76 of 347

[0328] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) include a cell type-specific binding component, for example, T-cell or NK-cell binders. Such multivalent antibodies may also be used to localize cytotoxic agents to cells which express sTn. These antibodies possess an sTn-binding arm and an arm which binds a cytotoxic agent, such as, e.g., saporin, anti-interferon-a, vinca alkaloid, ricin A chain, methotrexate, radioactive isotope hapten, or any other cytotoxic agent described elsewhere herein. In yet another aspect of the invention, multivalent antibodies are configured to simultaneously bind cell surface antigens on cytotoxic cells and on cancer cells (e.g., sTn). Crosslinking cytotoxic cells and cancer cells may induce or facilitate the killing of the cancer cell by the bound cytotoxic cell.

[0329] According to one aspect of the invention, a multivalent antibody may redirect T-cells, by engaging both tumor antigen presenting cells and the T-cell receptor (TCR)-CD3 complexes, thereby redirecting T-cell cytotoxicity to malignant cells. Thus, the multivalent antibody may bind both sTn and CD3. In this approach, T-cell activation is independent of antigen specificity and a large proportion of the T cell pool is activated. A disadvantage to this approach is that activating a large pool of T cells may increase systemic toxicity. Also, CD3 will recruit T cells indiscriminately. Another approach to T-cell redirection is to engage costimulatory receptors such as 4- IBB found to be upregulated on tumor-specific tumor-infiltrating T cells. Such antigens may be more suitable for solid tumors, where tumor-infiltrating cells could be preferentially activated by a tumor-targeted immunomodulator acting on, for example, 4-1BB. T-cell redirecting therapies may be independent of costimulation through CD28 or IL-2.

[0330] According to another aspect of the invention, multivalent antibodies may redirect and activate NK cells. Several receptors capable of activating the cytotoxic function of NK cells have been described and may be targeted in combination with sTn by a multivalent antibody, including CD16 (FcyRIII), NKp30, NKp46, NKG2D, and DNAM-1. CD16A, or FcyRIIIA, is an FcyR expressed by NK cells and macrophages. Upon binding to the Fc domain of an antibody attached to its cognate antigen, CD16A induces antibody-dependent cellular cytotoxicity (ADCC) of the antigen-expressing cell.

[0331] According to one aspect of the invention, multivalent antibodies may act as tumor-targeted immunomodulators targeting a tumor antigen expressed by the malignant cell, and an immunomodulatory receptor expressed by tumor-infiltrating immune cells. By activation of the immunomodulatory receptor, the preexisting, tumor-specific immune response induced in the tumor environment by the interplay between antigen-presenting cells, T cells and tumor cells is

[0332] Page 77 of 347

[0333] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) stimulated. Tumor-targeted immunomodulators may either activate antigen presenting cells, for example via the CD40 pathway, stimulating their ability to induce a potent antitumor immune response, or they may act directly on tumor-specific T cells, for example by activation of 4-1BB. Thus, in some instances, a multivalent antibody may bind sTn and CD40. In some instances, a multivalent antibody may bind sTn and 4-1BB.

[0334] 2. Antibody Modifications

[0335] 2.1. Derived antibodies

[0336] The present invention also provides “source” antibodies (e.g., antibodies generated in nonhuman species) and derivatives thereof, including chimeric and humanized antibodies prepared by modification of the constant region and / or the variable region sequences of the source antibody. According to certain aspects, an antibody is “derived” from a source antibody if selected amino acids in the source antibody are altered through deletion, mutation, substitution, integration or combination. According to another aspect, a “derived” antibody is one in which fragments of the source antibody (e.g., one or more CDRs or domains or the entire heavy and light chain variable regions) are combined with or incorporated into an acceptor antibody sequence to provide the derivative antibody (e.g. chimeric, CDR grafted or humanized antibodies). These “derived” antibodies can be generated using genetic material from the antibody producing cell and standard molecular biological techniques as described below, such as, for example, to improve affinity for the determinant; to improve antibody stability; to improve production and yield in cell culture; to reduce immunogenicity in vivo, to reduce toxicity; to facilitate conjugation of an active moiety; or to create a multispecific antibody. Such antibodies may also be derived from source antibodies through modification of the mature molecule (e.g., glycosylation patterns or pegylation) by chemical means or post-translational modification.

[0337] 2.2. Constant region modifications

[0338] According to select aspects, the present invention may also comprise substitutions or modifications of the constant region (i.e., the Fc region), including without limitation, amino acid residue substitutions, mutations and / or modifications, which result in a compound with characteristics including, but not limited to: altered pharmacokinetics, increased serum half-life,

[0339] Page 78 of 347

[0340] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010) increased binding affinity, reduced immunogenicity, increased production, altered Fc ligand binding to an Fc receptor (FcR), enhanced or reduced ADCC or CDC, altered glycosylation and / or disulfide bonds and modified binding specificity.

[0341] Compounds with improved Fc effector functions can be generated, for example, through changes in amino acid residues involved in the interaction between the Fc domain and an Fc receptor (e.g., FcyRI, FcyRIIA and B, FcyRIII and FcRn), which may lead to increased cytotoxicity and / or altered pharmacokinetics, such as increased serum half-life (see, for example, Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas etal., J. Lab. Clin. Med. 126:330-41 (1995).

[0342] According to select aspects of the invention, antibodies with increased in vivo half-lives can be generated by modifying (e.g., substituting, deleting or adding) amino acid residues identified as involved in the interaction between the Fc domain and the FcRn receptor (see, e.g., International Publication Nos. WO 97 / 34631; WO 04 / 029207; U.S.P.N. 6,737,056 and U.S.P.N. 2003 / 0190311). With regard to such aspects, Fc variants may provide half-lives in a mammal, preferably a human, of greater than 5 days, greater than 10 days, greater than 15 days, preferably greater than 20 days, greater than 25 days, greater than 30 days, greater than 35 days, greater than 40 days, greater than 45 days, greater than 2 months, greater than 3 months, greater than 4 months, or greater than 5 months. The increased half-life results in a higher serum titer which thus reduces the frequency of the administration of the antibodies and / or reduces the concentration of the antibodies to be administered. Binding to human FcRn in vivo and serum half-life of human FcRn high affinity binding polypeptides can be assayed, e.g., in transgenic mice or transfected human cell lines expressing human FcRn, or in primates to which the polypeptides with a variant Fc region are administered. WO 2000 / 42072 describes antibody variants with improved or diminished binding to FcRns. See also, e.g., Shields et al. J. Biol. Chem. 9(2):6591-6604 (2001).

[0343] According to other aspects, Fc alterations may lead to enhanced or reduced ADCC or CDC activity. As in known in the art, CDC refers to the lysing of a target cell in the presence of complement, and ADCC refers to a form of cytotoxicity in which secreted Ig bound onto FcRs present on certain cytotoxic cells (e.g., Natural Killer cells, neutrophils, and macrophages) enables these cytotoxic effector cells to bind specifically to an antigen-bearing target cell and subsequently kill the target cell with cytotoxins. In the context of the instant invention, antibody variants may be provided with "altered" FcR binding affinity, which is either enhanced or diminished binding

[0344] Page 79 of 347

[0345] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) as compared to a parent or unmodified antibody or to an antibody comprising a native sequence FcR. Such variants which display decreased binding may possess litle or no appreciable binding, e.g., 0-20% binding to the FcR compared to a native sequence, e.g., as determined by techniques well known in the art. According to other aspects, the variant will exhibit enhanced binding as compared to the native immunoglobulin Fc domain. It will be appreciated that these types of Fc variants may advantageously be used to enhance the effective anti -neoplastic properties of the disclosed antibodies. According to yet other aspects, such alterations lead to increased binding affinity, reduced immunogenicity, increased production, altered glycosylation and / or disulfide bonds (e.g., for conjugation sites), modified binding specificity, increased phagocytosis; and / or down regulation of cell surface receptors (e.g. B cell receptor; BCR), etc.

[0346] 2.3. Site-specific antibodies

[0347] The antibodies of the instant invention may be engineered to facilitate conjugation to a cytotoxin or other anti-cancer agent (as discussed in more detail below). It may be advantageous for an immunoconjugate preparation such as an antibody drug conjugate (ADC) preparation to comprise a homogenous population of ADC molecules in terms of the position of the payload (e.g., cytotoxin) on the antibody and the drug to antibody ratio (DAR). Based on the instant invention one skilled in the art could readily fabricate site-specific engineered constructs as described herein. As used herein a “site-specific antibody” or “site-specific construct” means an antibody, or immunoreactive fragment thereof, wherein at least one amino acid in either the heavy or light chain is deleted, altered or substituted (preferably with another amino acid) to provide at least one reactive conjugation site (e.g., for forming an immunoconjugate). A conjugation site may be a free cysteine. Similarly, a “site-specific payload” or “site-specific conjugate” shall be understood to mean an ADC comprising a site-specific antibody and at least one cytotoxin or other compound (e.g., a reporter molecule) conjugated to the conjugation site (e.g., unpaired or free cysteine(s)). According to certain aspects, the unpaired cysteine residue will comprise an unpaired intrachain cysteine residue. According to other aspects, the free cysteine residue will comprise an unpaired interchain cysteine residue. According to still other aspects of the invention, the free cysteine may be engineered into the amino acid sequence of the antibody (e.g., in the CH3 domain). In any event, the site-specific antibody can be of various isotypes, for example, IgG, IgE, IgA or IgD; and within those classes the antibody can be of various subclasses, for example, IgGl, IgG2, IgG3 or

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[0349] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0350] IgG4. For IgG constructs the light chain of the antibody can comprise either a kappa or lambda isotype each incorporating a C214 that, according to select aspects of the invention, may be unpaired due to a lack of a C220 residue in the IgGl heavy chain.

[0351] Thus, as used herein, the terms “free cysteine” or “unpaired cysteine” may be used interchangeably unless otherwise dictated by context and shall mean any cysteine (or thiol containing) constituent (e.g., a cysteine residue) of an antibody, whether naturally present or specifically incorporated in a selected residue position using molecular engineering techniques, that is not part of a naturally occurring (or “native”) disulfide bond under physiological conditions. According to select aspects of the invention, the free cysteine may comprise a naturally occurring cysteine whose native interchain or intrachain disulfide bridge partner has been substituted, eliminated or otherwise altered to disrupt the naturally occurring disulfide bridge under physiological conditions thereby rendering the unpaired cysteine suitable for site-specific conjugation. According to certain aspects, the free or unpaired cysteine will comprise a cysteine residue that is selectively placed at a predetermined site within the antibody heavy or light chain amino acid sequences. It will be appreciated that, prior to conjugation, free or unpaired cysteines may be present as a thiol (reduced cysteine), as a capped cysteine (oxidized) or as part of a nonnative intra- or intermolecular disulfide bond (oxidized) with another cysteine or thiol group on the same or different molecule depending on the oxidation state of the system. As discussed in more detail below, mild reduction of the appropriately engineered antibody construct will provide thiols available for site-specific conjugation. Accordingly, the free or unpaired cysteines (whether naturally occurring or incorporated) may be subject to selective reduction and subsequent conjugation to provide homogenous DAR compositions.

[0352] In certain aspects the present invention preferably provides one or more predetermined unpaired (or free) cysteine sites by engineering the targeting antibody to disrupt one or more of the naturally occurring (i.e., “native”) interchain or intrachain disulfide bridges or to introduce a cysteine residue at any position. To this end it will be appreciated that, according to select aspects of the invention, a cysteine residue may be incorporated anywhere along the antibody (or immunoreactive fragment thereof) heavy or light chain or appended thereto using standard molecular engineering techniques. According to certain aspects, disruption of native disulfide bonds may be effected in combination with the introduction of a non-native cysteine (which will then comprise the free cysteine) that may then be used as a conjugation site.

[0353] Page 81 of 347

[0354] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0355] According to certain aspects, the engineered antibody comprises at least one amino acid deletion or substitution of an intrachain or interchain cysteine residue. As used herein “interchain cysteine residue” means a cysteine residue that is involved in a native disulfide bond either between the light and heavy chain of an antibody or between the two heavy chains of an antibody while an “intrachain cysteine residue” is one naturally paired with another cysteine in the same heavy or light chain. According to one aspect of the invention, the deleted or substituted interchain cysteine residue is involved in the formation of a disulfide bond between the light and heavy chain. According to another aspect, the deleted or substituted cysteine residue is involved in a disulfide bond between the two heavy chains. Due to the complementary structure of an antibody according to certain aspects of the invention, in which the light chain is paired with the VH and CHI domains of the heavy chain and wherein the CH2 and CH3 domains of one heavy chain are paired with the CH2 and CH3 domains of the complementary heavy chain, a mutation or deletion of a single cysteine in either the light chain or in the heavy chain would result in two unpaired cysteine residues in the engineered antibody.

[0356] According to some aspects, an interchain cysteine residue is deleted. According to other aspects, an interchain cysteine is substituted for another amino acid (e.g., a naturally occurring amino acid). For example, the amino acid substitution can result in the replacement of an interchain cysteine with a neutral (e.g. serine, threonine or glycine) or hydrophilic (e.g. methionine, alanine, valine, leucine or isoleucine) residue. According to select aspects of the invention, an interchain cysteine is replaced with a serine.

[0357] According to some aspects contemplated by the invention, the deleted or substituted cysteine residue is on the light chain (either kappa or lambda) thereby leaving a free cysteine on the heavy chain. According to other aspects, the deleted or substituted cysteine residue is on the heavy chain leaving the free cysteine on the light chain constant region. Upon assembly it will be appreciated that deletion or substitution of a single cysteine in either the light or heavy chain of a conventional antibody results in a site-specific antibody having two unpaired cysteine residues.

[0358] According to one aspect of the invention, the cysteine at position 214 (C214) of the IgG light chain (kappa or lambda) is deleted or substituted. According to another aspect, the cysteine at position 220 (C220) on the IgG heavy chain is deleted or substituted. According to further aspects, the cysteine at position 226 or position 229 on the heavy chain is deleted or substituted. According to one aspect of the invention, C220 on the heavy chain is substituted with serine

[0359] Page 82 of 347

[0360] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0361] (C220S) to provide the desired free cysteine in the light chain. According to another aspect, C214 in the light chain is substituted with serine (C214S) to provide the desired free cysteine in the heavy chain. As discussed above each of the heavy and light chain variants may be operably associated with the disclosed heavy and light chain variable regions (or derivatives thereof such as humanized or CDR grafted constructs) to provide site-specific anti-sTn antibodies as disclosed herein. Such engineered antibodies are particularly compatible for use in the disclosed ADCs.

[0362] With regard to the introduction or addition of a cysteine residue or residues to provide a free cysteine (as opposed to disrupting a native disulfide bond) compatible position(s) on the antibody or antibody fragment may readily be discerned by one skilled in the art. Accordingly, according to select aspects of the invention, the cysteine(s) may be introduced in the CHI domain, the CH2 domain or the CH3 domain or any combination thereof depending on the desired DAR, the antibody construct, the selected payload and the antibody target. According to certain aspects, the cysteines may be introduced into a kappa or lambda CL domain and, according to more select aspects, in the c-terminal region of the CL domain. In each case, other amino acid residues proximal to the site of cysteine insertion may be altered, removed or substituted to facilitate molecular stability, conjugation efficiency or provide a protective environment for the payload once it is attached. According to particular aspects, the substituted residues occur at any accessible sites of the antibody. By substituting such surface residues with cysteine, reactive thiol groups are thereby positioned at readily accessible sites on the antibody and may be selectively reduced as described further herein. According to particular aspects, the substituted residues occur at accessible sites of the antibody. By substituting those residues with cysteine, reactive thiol groups are thereby positioned at accessible sites of the antibody and may be used to selectively conjugate the antibody. According to certain aspects, any one or more of the following residues may be substituted with cysteine: V205 (Kabat numbering) of the light chain; Al 18 (Eu numbering) of the heavy chain; and S400 (Eu numbering) of the heavy chain Fc region. Additional substitution positions and methods of fabricating compatible site-specific antibodies are set forth in U.S.P.N. 7,521,541 which is incorporated herein in its entirety.

[0363] According to another aspect of the invention, site-specific antibodies may be engineered by modifying or replacing one or both of the two naturally-occurring glycan anchor points that exist on IgG antibodies. The Fc regions of IgGs bear a highly conserved N-glycosylation site at asparagine 297 in the constant region of the heavy chain. The naturally-occurring glycans at one

[0364] Page 83 of 347

[0365] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) or more glycan anchor sites may be trimmed and substituted or otherwise modified with appropriate functional groups for the conjugation techniques described in more detail elsewhere herein, including, for example, thiols or clickable moieties (e.g., azides).

[0366] According to another aspect of the invention, the antibody comprises an N- acetylglucosamine (GlcNAc) that is modified with one or more functional groups (e.g., one functional group) for conjugating to a payload, which may be any of the payloads described elsewhere herein, including drugs and linkers conjugated to drugs. According to certain aspects, the antibody comprises one, two, three, or four GlcNAc moieties. The GlcNAc moiety may be a core GlcNAc moiety (a GlcNAc-residue that is covalently bonded to the N-glycosylation site of an IgG antibody comprising one N-linked glycosylation site on the combination of a single heavy chain and single light chain via an N-glycosidic bond, preferably via Cl of the GlcNAc residue to an amide group in the side chain of an antibody amino acid). The GlcNAc moiety may be bonded to the antibody via an N-glycosidic bond to the amide nitrogen atom of the side chain of an asparagine amino acid of the antibody. The GlcNAc moiety may be present at a native glycosylation site of the antibody or may be introduced at a different site of the antibody. For example, the antibody may comprise a mutant N-linked glycosylation site as described in U.S Pat. App. Pub. No. 2016 / 0257764 to Van Delft et al., published on Sept. 8, 2016; or U.S. Pat. Pub. No. 2016 / 0235861 to Van Delft et al., published on Aug. 18, 2016, each of which is herein incorporated by reference in its entirety. The GlcNAc moiety may be a terminal GlcNAc of an oligosaccharide or polysaccharide glycan bonded to the antibody. The GlcNAc moiety may be fucosylated or may not be fucosylated. The functional group may be a clickable functional group. The functional group may be an azide, alkyne, and / or ketone functional group. See, e.g., U.S. Patent No. 10,745,488. The functional group may be an azido group, a keto group, or an aklynyl group. See, e.g., U.S. Patent No. 9,504,758. The functional group may be a thiol group or a precursor thereof, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group or a sulfonated hydroxyacetamido group. See, e.g., U.S. Patent No. 10,072,096.

[0367] The GlcNAc moiety may be modified by conjugating a sugar derivative comprising the functional group to the GlcNAc moiety. The sugar derivative may comprise one or more functional groups (e.g., 1, 2, 3, or 4 functional groups). The functionalized sugar derivative may be conjugated to the GlcNAc moiety using a galactosyltransferase (e.g., having a mutant catalytic domain). The functionalized sugar derivative substrate for the conjugation reaction may be joined

[0368] Page 84 of 347

[0369] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) to a nucleotide such as a diphosphate (e g., uridine diphosphate (UDP), guanosine diphosphate (GDP), and cytidine diphosphate (CDP)) which is removed from the functionalized sugar derivative during the conjugation of the sugar derivative to the antibody. The functional group may be any of the functional groups described elsewhere herein, including those suitable for click reaction conjugations to target payloads. According to certain aspects, the functionalized sugar derivative is reactive with a (hetero)cycloalkynyl group or terminal alkynyl group on the target payload. The functionalized GlcNAc moiety may provide efficient site-specific conjugations for the preparation of immunoconjugates, which avoids underconjugated antibodies (which may reduce immunoconjugate potency) and overconjugated antibodies (which may decrease circulatory half-lives, impair binding to antigens, and / or increase toxicity). The functionalized GlcNAc moiety may provide particularly homogenous immunoconjugate compositions in terms of DAR, described elsewhere herein. According to certain aspects, the antibody may be modified according to any of the methods disclosed in U.S. PatentNo. 10,745,488 to Van Delft et al., issued on Aug. 18, 2020; U.S. Patent No. 9,987,373 to Van Delft et al., issued on June 5, 2018; U.S. Patent No. 10,072,096 to Va Delft et al., issued on Sept. 11, 2018; U.S. Patent No. 9,504,758 to Van Delft et al., issued Nov. 29, 2016; U.S. Pat. App. Pub. No. 2019 / 0262468 to Van Berkel et al., published Aug. 29, 2019; U.S. Pat. App. Pub. No. 2019 / 0262466 to Van Berkel et al., published Aug. 29, 2019; U.S Pat. App. Pub. No. 2016 / 0257764 to Van Delft et al., published on Sept. 8, 2016; or U.S Pat. App. Pub. No. 2016 / 0257764 to Van Delft et al., published on Sept. 8, 2016, each of which is herein incorporated by reference in its entirety, and / or the antibody may be modified to comprise any of the functionalized sugars described therein. The antibodies may be modified via any of the galactosyltransferases described therein. Payloads may comprise appropriate reactive groups, including reactive counterpart reactive groups described therein. According to certain aspects, a glycan on the antibody may be functionalized with a sugar nucleotide such as those described elsewhere herein with a glycosyltransferase described in U.S. Patent No. 9,988,661 to Van Berkel et al., issued on June 5, 2018; or U.S. Pat. App. Pub. No. 2017 / 0226554 to Wasiel et al., published Aug. 10, 2017, each of which is herein incorporated by reference in its entirety, and / or the sugar nucleotide substrate used to modify the antibody may be any suitable sugar nucleotide described therein.

[0370] According to one aspect of the invention, site-specific modification may comprise trimming one or more glycans of the antibody. The glycans may be trimmed to liberate a core

[0371] Page 85 of 347

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[0373] GlcNAc. The glycans may be trimmed by one or more suitable enzymes or mutant enzymes (e.g., a mutant glycosidase). According to certain aspects, multiple different glycoforms may be trimmed in a single step. The antibody may comprise at least one high-mannose glycan prior to trimming. The antibody may comprise at least one complex glycan prior to trimming. The antibody may comprise at least one high-mannose glycan and at least one complex glycan prior to trimming. The antibody may comprise a hybrid glycan prior to trimming. According to certain aspects, one or more glycans of the antibody are trimmed by an enzyme described in U.S. Patent No. 10,858,641 to Geel et al., issued on Dec. 8, 2020, which is herein incorporated by reference in its entirety. The antibody comprising one or more trimmed glycans may be modified and / or functionalized according to any of the methods described elsewhere herein, including, for example, the functionalization of GlcNAc comprising antibodies.

[0374] According to one aspect of the invention, the antibody comprises an N- Acetylgalactosamine (GalNAc) moiety that is modified with one or more functional groups (e.g., one functional group) for conjugating to a payload, which may be any of the payloads described elsewhere herein, including drugs and linkers bound to drugs. The GalNAc moiety may be an N- acetylgalactosamine-(hetero)aryl moiety. The GalNAc moiety may be present at a native glycosylation site of the antibody or may be introduced at a different site of the antibody. The antibody may be modified by appending the GalNAc moiety to a GlcNAc moiety. The GlcNAc moiety may be a GlcNAc moiety described elsewhere herein, such a native GlcNAc moiety. The GlcNAc moiety may be a core GlcNAc moiety. The GlcNAc moiety may be a terminal GlcNAc moiety. The GlcNAc moiety may be the result of trimming one or more glucoforms from a glycan as described elsewhere herein. The GalNAc moiety may be functionalized with any of the same functional groups as the GlcNAc moiety described elsewhere herein. According to certain aspects, the GalNAc moiety comprises a 1,3-dipole functional group. The GalNAc moiety may be conjugated to the GlcNAc moiety using a galactosyltransferase (e.g., having a mutant catalytic domain). According to certain aspects, the GalNAc moiety may be joined to a GlcNAc moiety using a galactosyltransferase described in U.S. Pat. App. Pub. No. 2017 / 0009266 to Van Delft et al., published Jan. 12, 2017, which is herein incorporated by reference in its entirety, and / or the GalNAc moiety and / or GlcNAc moiety may be any of the suitable moieties described therein.

[0375] The strategy for generating antibody drug conjugates with defined sites and stoichiometries of drug loading, as disclosed herein, is broadly applicable to all anti-sTn antibodies as it primarily

[0376] Page 86 of 347

[0377] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) involves engineering of the conserved constant domains of the antibody. As the amino acid sequences and native disulfide bridges of each class and subclass of antibody are well documented, one skilled in the art could readily fabricate engineered constructs of various antibodies without undue experimentation and, accordingly, such constructs are expressly contemplated as being within the scope of the instant invention.

[0378] 2.4. Altered glycosylation

[0379] Still, according to other aspects, the invention comprises one or more engineered glycoforms, e.g., a site-specific antibody comprising an altered glycosylation pattern or altered carbohydrate composition that is covalently attached to the protein (e.g., in the Fc domain). See, for example, Shields, R. L. etal. (2002) J. Biol. Chem. 277:26733-26740. Engineered glycoforms may be useful for a variety of purposes, including but not limited to enhancing or reducing effector function, increasing the affinity of the antibody for a target or facilitating production of the antibody. According to certain aspects, where reduced effector function is desired, the molecule may be engineered to express an aglycosylated form. Substitutions that may result in elimination of one or more variable region framework glycosylation sites to thereby eliminate glycosylation at that site are well known (see, e.g., U.S.P.Ns. 5,714,350 and 6,350,861). Conversely, enhanced effector functions or improved binding may be imparted to the Fc-containing molecule by engineering in one or more additional glycosylation sites.

[0380] According to other aspects, the invention includes an Fc variant that has an altered glycosylation composition, such as a hypofucosylated antibody having reduced amounts of fucosyl residues or an antibody having increased bisecting GlcNAc structures. Such altered glycosylation patterns have been demonstrated to increase the ADCC ability of antibodies. Engineered glycoforms may be generated by any method known to one skilled in the art, for example by using engineered or variant expression strains, by co-expression with one or more enzymes (for example N-acetylglucosaminyltransferase III (GnTIII)), by expressing a molecule comprising an Fc region in various organisms or cell lines from various organisms or by modifying carbohydrate(s) after the molecule comprising Fc region has been expressed (see, for example, WO 2012 / 117002).

[0381] Page 87 of 347

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[0383] 2.5. Affinity maturation

[0384] Antibodies produced by any of the above-noted methods can be of moderate affinity (Kaof about 106to 107M'1), but affinity maturation can also be performed according to known techniques to increase affinity. For example, one or more mutations can be introduced at random in vitro by using error-prone polymerase (reported in Leung et al., Technique, 1 : 11-15 (1989)). Additionally, affinity maturation can be performed by randomly mutating one or more CDRs, e g. using PCR with primers carrying random sequence spanning the CDR of interest, in selected individual Fv clones and screening for higher-affinity clones. WO 9607754 described a method for inducing mutagenesis in a CDR of an immunoglobulin light chain to create a library of light chain genes. Another effective approach is to recombine the VH or VL domains repertoires of naturally occurring V domain variants obtained from unimmunized donors and to screen for higher affinity in several rounds of chain reshuffling as described in Marks et al., Biotechnol., 10: 779- 783 (1992). This technique allows the production of antibodies and antibody fragments with a dissociation constant KD (kotr / kon) of about 10'9M or less. Computational approaches including artificial intelligence / machine learning methods are also known in the art to aid in the discovery of mutations that enhance affinity.

[0385] 3. Nucleic acids encoding antibodies

[0386] Antibodies and fragments thereof may be produced or modified using genetic material obtained from antibody producing cells and recombinant technology (see, for example; Dubel and Reichert (Eds.) (2014) Handbook of Therapeutic Antibodies, 2ndEdition, Wiley-Blackwell GmbH; Sambrook and Russell (Eds.) (2000) Molecular Cloning: A Laboratory Manual (3rdEd.), NY, Cold Spring Harbor Laboratory Press; Ausubel et al. (2002) Short Protocols in Molecular Biology: A Compendium of Methods from Current Protocols in Molecular Biology, Wiley, John & Sons, Inc.; and U.S.P.N. 7,709,611).

[0387] Another aspect of the invention pertains to nucleic acid molecules that encode the disclosed antibodies. The nucleic acids may be present in whole cells, in a cell lysate, or in a partially purified or substantially pure form. A nucleic acid is “isolated” or rendered substantially pure when separated from other cellular components or other contaminants, e.g., other cellular nucleic acids or proteins, by standard techniques, including alkaline / SDS treatment, CsCl banding, column chromatography, agarose gel electrophoresis and others well known in the art. A nucleic acid of

[0388] Page 88 of 347

[0389] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010) the invention can be, for example, DNA (e.g. genomic DNA, cDNA), RNA and artificial variants thereof (e.g., peptide nucleic acids), whether single-stranded or double-stranded or RNA, RNA and may or may not contain introns. According to select aspects of the invention, the nucleic acid is a cDNA molecule.

[0390] Nucleic acids of the invention can be obtained using standard molecular biology techniques. For antibodies expressed by hybridomas (e.g., hybridomas prepared as described in the Examples below), cDNAs encoding the light and heavy chains of the antibody can be obtained by standard PCR amplification or cDNA cloning techniques. For antibodies obtained from an immunoglobulin gene library (e.g., using phage display techniques), nucleic acid molecules encoding the antibody can be recovered from the library.

[0391] DNA fragments encoding VH and VL segments can be further manipulated by standard recombinant DNA techniques, for example to convert the variable region genes to full-length antibody chain genes, to Fab fragment genes or to a scFv gene. In these manipulations, a VL- or VH-encoding DNA fragment is operatively linked to another DNA fragment encoding another protein, such as an antibody constant region or a flexible linker. The term “operatively linked”, as used in this context, means that the two DNA fragments are joined such that the amino acid sequences encoded by the two DNA fragments remain in-frame.

[0392] The isolated DNA encoding the VH region can be converted to a full-length heavy chain gene by operatively linking the VH-encoding DNA to another DNA molecule encoding heavy chain constant regions (CHI, CH2 and CH3 in the case of IgGl). The sequences of human heavy chain constant region genes are known in the art (see, e.g., Kabat, et al. (1991) (supra) and DNA fragments encompassing these regions can be obtained by standard PCR amplification. The heavy chain constant region can be an IgGl, IgG2, IgG3, IgG4, IgA, IgE, IgM or IgD constant region, but most preferably is an IgGl or IgG4 constant region. For a Fab fragment heavy chain gene, the VH-encoding DNA can be operatively linked to another DNA molecule encoding only the heavy chain CHI constant region.

[0393] Isolated DNA encoding the VL region can be converted to a full-length light chain gene (as well as a Fab light chain gene) by operatively linking the VL-encoding DNA to another DNA molecule encoding the light chain constant region, CL. The sequences of human light chain constant region genes are known in the art (see e.g., Kabat, et al. (1991) (supra)) and DNA fragments encompassing these regions can be obtained by standard PCR amplification. The light

[0394] Page 89 of 347

[0395] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) chain constant region can be a kappa or lambda constant region, but most preferably is a kappa constant region.

[0396] In each case the VH or VL domains may be operatively linked to their respective constant regions (CH or CL) where the constant regions are site-specific constant regions and provide sitespecific antibodies. According to select aspects of the invention, the resulting site-specific antibodies will comprise two unpaired cysteines on the heavy chains while According to other aspects, the site-specific antibodies will comprise two unpaired cysteines in the CL domain.

[0397] Contemplated herein are certain polypeptides (e.g., antigens or antibodies) that exhibit “sequence identity”, sequence similarity” or “sequence homology” to the polypeptides of the invention. For example, a derived humanized antibody VH or VL domain may exhibit a sequence similarity with the source (e.g., murine) or acceptor (e.g., human) VH or VL domain. A “homologous” polypeptide may exhibit 65%, 70%, 75%, 80%, 85%, or 90% sequence identity. According to other aspects, a “homologous” polypeptides may exhibit 93%, 95% or 98% sequence identity. As used herein, the percent homology between two amino acid sequences is equivalent to the percent identity between the two sequences. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions* 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm.

[0398] The percent identity between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci.,4A’ \- l (1988)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J. Mol. Biol. 48:444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0399] Additionally or alternatively, the protein sequences of the present invention can further be used as a “query sequence” to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the XBLAST program (version 2.0) of

[0400] Page 90 of 347

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[0402] Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to the antibody molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When using BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0403] Residue positions which are not identical may differ by conservative amino acid substitutions or by non-conservative amino acid substitutions. A “conservative amino acid substitution” is one in which an amino acid residue is substituted by another amino acid residue having a side chain with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity or degree of similarity may be adjusted upwards to correct for the conservative nature of the substitution. In cases where there is a substitution with a non-conservative amino acid, the polypeptide exhibiting sequence identity will retain the desired function or activity of the polypeptide of the invention (e.g., antibody .)

[0404] Also contemplated herein are nucleic acids that that exhibit “sequence identity”, sequence similarity” or “sequence homology” to the nucleic acids of the invention. A “homologous sequence” means a sequence of nucleic acid molecules exhibiting at least about 65%, 70%, 75%, 80%, 85%, or 90% sequence identity over the length of the reference nucleic acid. According to other aspects, a “homologous sequence” of nucleic acids may exhibit 93%, 95% or 98% sequence identity to the reference nucleic acid over the length of the reference nucleic acid.

[0405] The instant invention also provides vectors comprising such nucleic acids described above, which may be operably linked to a promoter (see, e.g., WO 86 / 05807; WO 89 / 01036; and U.S.P.N. 5,122,464); and other transcriptional regulatory and processing control elements of the eukaryotic secretory pathway. The invention also provides host cells harboring those vectors and hostexpression systems.

[0406] 4. Recombinant antibody production and screening

[0407] As used herein, the term “host-expression system” includes any kind of cellular system that can be engineered to generate either the nucleic acids or the polypeptides and antibodies of the

[0408] Page 91 of 347

[0409] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010) invention. Such host-expression systems include, but are not limited to microorganisms (e.g., E. coll or B. subtilis) transformed or transfected with recombinant bacteriophage DNA or plasmid DNA; yeast (e.g., Saccharomyces) transfected with recombinant yeast expression vectors; or mammalian cells (e.g., COS, CHO HEK293T, 3T3 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells or viruses (e.g., the adenovirus late promoter). The host cell may be co-transfected with two expression vectors, for example, the first vector encoding a heavy chain derived polypeptide and the second vector encoding a light chain derived polypeptide.

[0410] Methods of transforming mammalian cells are well known in the art. See, for example, U.S.P.N.s. 4,399,216, 4,912,040, 4,740,461, and 4,959,455. The host cell may also be engineered to allow the production of an antigen binding molecule with various characteristics (e.g., modified glycoforms or proteins having GnTIII activity).

[0411] For long-term, high-yield production of recombinant proteins stable expression is preferred. Accordingly, cell lines that stably express the selected antibody may be engineered using standard art recognized techniques and form part of the disclosure. Rather than using expression vectors that contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter or enhancer sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Any of the selection systems well known in the art may be used, including the glutamine synthetase gene expression system (the GS system) which provides an efficient approach for enhancing expression under selected conditions. The GS system is discussed in whole or part in connection with EP 0216 846, EP 0 256 055, EP 0 323 997 and EP 0 338 841 and U.S.P.N.s 5,591,639 and 5,879,936. Another compatible expression system for the development of stable cell lines is the Freedom™ CHO-S Kit (Life Technologies).

[0412] Once an antibody of the invention has been produced by recombinant expression or any other of the disclosed techniques, it may be purified or isolated by methods known in the art in that it is identified and separated and / or recovered from its natural environment and separated from contaminants that would interfere with diagnostic or therapeutic uses for the antibody or related immunoconjugate. Isolated antibodies include antibodies in situ within recombinant cells.

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[0414] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0415] These isolated preparations may be purified using various art-recognized techniques, such as, for example, ion exchange and size exclusion chromatography, dialysis, diafiltration, and affinity chromatography, particularly Protein A or Protein G affinity chromatography.

[0416] No matter how obtained, antibody producing cells (e.g., hybridomas, yeast colonies, etc.) may be selected, cloned and further screened for desirable characteristics including, for example, robust growth, high antibody production and desirable antibody characteristics such as high affinity for the antigen of interest. Hybridomas can be expanded in vitro in cell culture or in vivo in syngeneic immunocompromised animals. Methods of selecting, cloning and expanding hybridomas and / or colonies are well known to those of ordinary skill in the art. Once the desired antibodies are identified the relevant genetic material may be isolated, manipulated and expressed using common, art-recognized molecular biology and biochemical techniques.

[0417] The antibodies produced by naive libraries (either natural or synthetic) may be of moderate affinity (Kaof about 106to 107M'1). To enhance affinity, affinity maturation may be mimicked in vitro by constructing antibody libraries (e.g., by introducing random mutations in vitro by using error-prone polymerase) and reselecting antibodies with high affinity for the antigen from those secondary libraries (e.g. by using phage or yeast display). WO 9607754 describes a method for inducing mutagenesis in a CDR of an immunoglobulin light chain to create a library of light chain genes. Artificial intelligence / machine learning methods may also be used to select mutations that enhance affinity or improve antibody properties.

[0418] Various techniques can be used to select antibodies, including but not limited to, phage or yeast display in which a library of human combinatorial antibodies or scFv fragments is synthesized on phages or yeast, the library is screened with the antigen of interest or an antibodybinding portion thereof, and the phage or yeast that binds the antigen is isolated, from which one may obtain the antibodies or immunoreactive fragments (Vaughan et aL, 1996, PMID: 9630891; Sheets et al., 1998, PMID: 9600934; Boder et al., 1997, PMID: 9181578; Pepper et al., 2008, PMID: 18336206). Kits for generating phage or yeast display libraries are commercially available. There also are other methods and reagents that can be used in generating and screening antibody display libraries (see U.S.P.N. 5,223,409; WO 92 / 18619, WO 91 / 17271, WO 92 / 20791, WO 92 / 15679, WO 93 / 01288, WO 92 / 01047, WO 92 / 09690; and Barbas et al., 1991, PMID: 1896445). Such techniques advantageously allow for the screening of large numbers of candidate antibodies and provide for relatively easy manipulation of sequences (e.g., by recombinant shuffling).

[0419] Page 93 of 347

[0420] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0421] III. Characteristics of Antibodies

[0422] According to certain aspects, antibody-producing cells (e.g., hybridomas or yeast colonies) may be selected, cloned and further screened for favorable properties including, for example, robust growth, high antibody production and, as discussed in more detail below, desirable sitespecific antibody characteristics. In other cases, characteristics of the antibody may be imparted by selecting a particular antigen or antigens (e.g., a specific peptide with sTn attached at desired serine or threonine amino acid residues; or proteins expressed in mammalian cells genetically modified to attach the sTn glycan to serine or threonine amino acids within O-glycan-rich protein domains) or immunoreactive fragment of the target antigen for inoculation of the animal. According to still other aspects of the invention, the selected antibodies may be engineered as described above to enhance or refine immunochemical characteristics such as affinity or pharmacokinetics.

[0423] According to select aspects, the antibodies of the invention may be “antagonists” or “neutralizing” antibodies, meaning that the antibody may associate with a determinant and block or inhibit the activities of said determinant either directly or by preventing association of the determinant with a binding partner such as a ligand or a receptor, thereby interrupting the biological response that otherwise would result from the interaction of the molecules. A neutralizing or antagonist antibody will substantially inhibit binding of the determinant to its ligand or substrate when an excess of antibody reduces the quantity of binding partner bound to the determinant by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97%, 99% or more as measured, for example, by target molecule activity or in an in vitro competitive binding assay. It will be appreciated that the modified activity may be measured directly using art recognized techniques or may be measured by the impact the altered activity has downstream (e.g., oncogenesis or cell survival). It may readily be determined if an antibody of the invention is capable of blocking or inhibiting the binding of naturally occurring ligands of sTn (including ligands specific to sTn-conjugated proteins). Thus, according to some aspects, exemplary antibodies of the invention will block the binding of a ligand to sTn by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97%, 99% or more when measured as set forth below. As certain immunoconjugates comprising such antagonistic antibodies may be particularly effective in killing cancer cells such neutralizing or blocking antibodies may be particularly compatible for use in the disclosed immunoconjugates or in treating cancer as disclosed herein.

[0424] Page 94 of 347

[0425] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0426] Antibodies of the invention may also comprise internalizing antibodies such that the antibody will bind to a determinant and will be internalized (along with any conjugated pharmaceutically active payload) into a selected target cell including cancer cells. The number of antibody molecules internalized may be sufficient to kill an antigen-expressing cell. Depending on the potency of the antibody or, in some instances, antibody drug conjugate, the uptake of a single antibody molecule into the cell may be sufficient to kill the target cell to which the antibody binds. According to select aspects of the invention, such antibodies will be associated with, or conjugated to, one or more drugs that kill the cell upon internalization. According to some aspects, the ADCs of the instant invention will comprise an internalizing site-specific ADC.

[0427] As used herein, an antibody that “internalizes” is one that is taken up (along with any conjugated cytotoxin) by a target cell upon binding to an associated determinant. The number of such ADCs internalized will preferably be sufficient to kill the determinant-expressing cell. Depending on the potency of the cytotoxin or ADC as a whole, in some instances the uptake of a few antibody molecules into the cell is sufficient to kill the target cell to which the antibody binds. For example, certain drugs are so potent that the internalization of a few molecules of the toxin conjugated to the antibody is sufficient to kill the target cell. Whether an antibody internalizes upon binding to a mammalian cell can be determined by various art-recognized assays (e.g., saporin assays such as Mab-Zap and Fab-Zap; Advanced Targeting Systems). Methods of detecting whether an antibody internalizes into a cell are also described in U.S.P.N. 7,619,068.

[0428] According to other aspects, the antibodies of the invention are depleting antibodies. The term “depleting” antibody refers to an antibody that preferably binds to an antigen on or near the cell surface and induces, promotes or causes the death of the cell (e.g., by CDC, ADCC or introduction of a cytotoxic agent). According to some aspects, the selected depleting antibodies will be conjugated to a cytotoxin.

[0429] Preferably, a depleting antibody will be able to kill at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97%, or 99% of sTn-expressing cells in a defined cell population. The term “apparent IC50”, as used herein, refers to the concentration at which a primary antibody linked to a toxin kills 50 percent of the cells expressing the antigen(s) recognized by the primary antibody. The toxin can be directly conjugated to the primary antibody, or can be associated with the primary antibody via a secondary antibody or antibody fragment that recognizes the primary antibody, and which secondary antibody or antibody fragment is directly conjugated to a toxin.

[0430] Page 95 of 347

[0431] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0432] Preferably, a depleting antibody will have an IC50 of less than 5 pM, less than 1 pM, less than 100 nM, less than 50 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 5 nM, less than 2 nM or less than 1 nM. Standard biochemical techniques may be used to monitor and quantify the depletion of cancer cells in accordance with the teachings herein.

[0433] Antibodies of the invention may have a high binding affinity for sTn (or sTn-attached protein). Antibodies of the invention may bind more than one epitope of sTn or sTn-attached proteins with different affinities for each epitope. In one aspect, amino acids directly surrounding sTn alter the binding affinity of the antibody. Antibodies of the invention may display avidity wherein the binding properties of the antibody may be altered. In one aspect, antibodies of the invention may display higher avidity to sTn or sTn-attached proteins to allow the antibodies to bind their respective target or targets. Multivalent antibodies of the invention may include any combination of binding affinities and avidities of the component antibodies. All such antibodies are useful in the methods described herein.

[0434] The term “KD” refers to the dissociation constant or apparent affinity of a particular antibody-antigen interaction. An antibody of the invention can immunospecifically bind its target antigen when the dissociation constant KD (koff / kon) is < 10’7M. The antibody specifically binds antigen with high affinity when the Ko is < 5xlO’9M, and with very high affinity when the KD is < 5xl0’10M. In some aspects of the invention, antibodies have a KD (koff / kon) of less than 10’6M, less than 5xlO’6M, less than 10’7M, less than 5xlO’7M, less than 10’8M, less than 5xl0’8M, less than 10’9M, less than 5xl0’9M, less than 10’10M, less than 5xlO’loM, less than 10’nM, less than 5xl0’nM, less than 10’12M, less than 5xlO’12M, less than 10’13M, less than 5xlO’l3M, less than 10’14M, less than 5xlO’14M, less than 10’15M or less than 5xl0’15M.

[0435] According to certain aspects, an antibody of the invention that immunospecifically binds to a determinant (e.g., sTn) may have an association rate constant or ko» (or ka) rate (antibody + antigen (Ag)kon<— antibody-Ag) of at least 105M’1s’1, at least 2xlO:,M’1s’1, at least 5xlO5M’1s’1, at least 106M’1s’1, at least 5xlO6M’1s’1, at least 107M’1s’1, at least 5xlO7M’1s’1, or at least 108M’1s’1. According to another aspect, an antibody of the invention that immunospecifically binds to a determinant (e.g., sTn) may have a disassociation rate constant or koff (or kd) rate (antibody + antigen (Ag)koir<— antibody -Ag) of less than 10’1s’ *, less than 5x10’1s’ *, less than 10’2s’ *, less than 5xl0’2s’ *, less than 10’3s’ *, less than 5xl0’3s’ *, less than 10’4s’ *, less than 5xl04s’ *, less than 10’5

[0436] Page 96 of 347

[0437] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) s’1, less than 5x1 O’3s’1, less than 10’6s’1, less than 5x1 O’6s’1less than 1 O’7s’ *, less than 5x1 O’7s’1, less than 10’8s’1, less than 5xl0’8s’1, less than 10’9s’1, less than 5xlO’9s’1or less than IO’10s’1.

[0438] Binding affinity may be determined using various techniques known in the art, for example, surface plasmon resonance, bio-layer interferometry, dual polarization interferometry, static light scattering, dynamic light scattering, isothermal titration calorimetry, ELISA, analytical ultracentrifugation, and flow cytometry.

[0439] In some aspects, the antibody binding affinity is measured using shorter peptides or proteins with attached glycans, for example as in the working examples provided herein, or the peptide glycan epitopes are presented in a dense / high concentration on longer proteins such that both arms of the antibody molecule are expected to engage. Binding to the glycans on shorter proteins or peptide framents that does not engage both arms of the antibody may result in less binding (e.g., as a result of lower binding affinity) than when both arms of the antibody are engaged, such as may occur in an assay using a dense / high concentration of the peptide glycan epitopes and longer peptides or protein sequences.

[0440] In one aspect of the invention, the antibody specifically binds to an sTn glycan or sTn on a carrier protein. By “specifically binds to sTn” means the antibody binds sTn and the antibody has undetectable binding to Tn or less than 25%, less than 20%, less than 15%, less than 10%, less than 5%, less than 2%, or less than 1% binding to Tn. Non-limiting examples of antibodies that specifically bind to sTn are provided in Tables 8, 1 lb, 35b, 26-34, and 38-47.

[0441] An antibody of the present invention preferentially binds to a mono glycan epitope, for example as compared to a glycan epitope within consecutive or contiguous glycan-bearing amino acids residues. A mono glycan epitope can be a mono sTn epitope or a mono Tn epitope. A mono glycan epitope means that the glycan forming the epitope e.g., sTn or Tn) is attached to an amino acid residue that is not adjacent to, or consecutive or contiguous with, another glycan bearing residue (e.g., another sTn or Tn bearing residue). Alternatively stated, a mono glycan epitope means the glycan forming the epitope e.g., sTn or Tn) is attached to an amino acid residue that is adjacent to, or consecutive or contiguous with, on either side, residues lacking an attached glycan. In other aspects of the present invention, an antibody binds to both a mono glycan epitope and a consecutive glycan epitope, i.e., a glycan epitope wherein the glycan is attached to an amino acid residue that is consecutive or contiguous with one more glycan-bearing

[0442] Page 97 of 347

[0443] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) residues, without discernible preference for either epitope. Consecutive and contiguous are used interchangeably herein to refer to adjacent amino acids.

[0444] According to a specific aspect of the invention, an antibody as disclosed herein preferentially binds to a mono sTn epitope as compared to a mono Tn epitope and a consecutive glycan epitope. Preferential binding to a mono sTn epitope may include binding to an epitope formed by the mono sTn glycan and the underlying amino acid to which the sTn is attached. As described above, a mono sTn glycan is an sTn glycan attached to an amino acid that is not adjacent to, or consecutive or contiguous with, another gly can-bearing residue in a peptide sequence.

[0445] By preferentially binds to a mono glycan epitope, e.g., a mono sTn epitope, means the antibody has at least about a 1.5 fold preference, at least about a 2-fold preference, at least about a 2.5-fold preference, at least about a 3-fold preference, at least about a 4-fold preference, at least about a 5-fold preference, at least about a 10-fold preference, at least about a 20-fold preference, at least about a 30-fold preference, or more, for binding to the mono glycan epitope as compared to a consecutive glycan eptiope. Preferential binding indicates that an antibody, when used in an assay to determine binding to glycan targets, shows an increased signal for binding to one glycan over another, e.g., an increased measure of binding to a mono sTn epitope as compared to a measure of binding to a consecutive sTn epitope. A representative assay is described in Example 7. Non-limiting examples of antibodies that preferentially bind to a mono sTn epitope are provided in Tables 8, l ib, 35b, 26-34, and 38-47.

[0446] In some aspects of the invention, an antibody that preferentially binds to a mono sTn epitope does not bind or shows undetectable binding to a Tn epitope.

[0447] As disclosed herein, in some aspects of the invention, antibodies can bind to both sTn and Tn epitopes, including a combination of mono glycan epitopes and consecutive glycan epitopes. For example, in some aspects of the invention, the antibody binds to a consecutive glycan epitope comprising two or more sTn glycans, two or more Tn glycans, or a combination of sTn and Tn glycans. In another aspect, the antibody just described, which binds to a consecutive glycan epitope, also binds to a mono glycan epitope, e.g., a mono sTn glycan. Non-limiting examples of antibodies that bind to sTn and Tn include the antibodies provided in Tables 7, I la, 35a, 12-25, and 36-37.

[0448] Page 98 of 347

[0449] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0450] While not wishing to be bound by any theory, the epitope may include the underlying amino acid that is attached to the glycan, Tn or sTn. In some aspects, the epitope may be formed by the unique presentation of the glycan on a threonine residue and preferentially to the presentation of the glycan on a serine residue. In some aspects, the antibodies provided herein prefer binding to sTn that is attached to a serine over sTn attached to a threonine.

[0451] Representative desirable features of particularly effective antibodies include high affinity for the target, minimal off-target binding, efficient rate of internalization by target cells, efficiency and ease of expression / production, stability in vitro and / or in vivo, high solubility, high conformational stability, minimal aggregation, half-life, and / or low immunogenicity.

[0452] IV. Antibody conjugates / Immunoconjugates

[0453] The present invention also provides immunoconjugates comprising at least one of the antibodies disclosed herein (including variants and immunospecific antibody fragments) conjugated to an additional molecule providing functionality to the immunoconjugate in addition to the antigen-binding properties of the antibody. The antibody may be conjugated directly to the molecule or indirectly through an optional linker. The term “conjugate” is used broadly and means the covalent or non-covalent association of any moiety with an antibody of the instant invention regardless of the method of association.

[0454] Representative desirable features of particularly effective antibody drug conjugates include an antibody with high affinity, efficient rate of internalization by target cells, efficiency and ease of conjugation / production, linker stability, half-life, stability in vitro and / or in vivo, bioavailability, payload potency, effective payload to antibody ratio (DAR), and / or controlled payload release to minimize toxicity.

[0455] A. Antibody Drug Conjugates

[0456] According to some aspects, the antibodies of the invention may be conjugated with pharmaceutically active or diagnostic moieties to form an “antibody drug conjugate” (ADC) or “antibody conjugate”.

[0457] It will be appreciated that the ADCs of the instant invention may be used to selectively deliver therapeutic or diagnostic agents to the target location (e.g., cancer cells and / or cells expressing sTn). As set forth herein, the term “drug” will mean any biologically active (e.g., a

[0458] Page 99 of 347

[0459] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010) pharmaceutically active compound or therapeutic moiety) or detectable molecule or compound that has a physiological effect or reporter function when introduced into a subject. For the avoidance of doubt, such drugs include the anti-cancer agents or cytotoxins as described below. A “payload” may comprise a drug in combination with an optional linker compound (e.g., a therapeutic payload) that preferably provides a relatively stable pharmaceutical complex until the ADC reaches the target. The term “payload” may be used interchangeably with the term “conjugate” unless otherwise dictated by context. By way of example, the drug on the payload may comprise peptides, proteins or prodrugs that are metabolized to an active agent in vivo, polymers, nucleic acid molecules, small molecules, binding agents, mimetic agents, synthetic drugs, inorganic molecules, organic molecules and radioisotopes. In certain aspects, the drug will be covalently conjugated to the antibody through a linker. In other aspects, the drug (e.g., a radioisotope) will be directly conjugated to, or incorporated in, the antibody.

[0460] The disclosed ADCs may direct the bound payload (e.g., drug linker) to the target site in a relatively unreactive, non-toxic state before releasing and activating the drug. This targeted release of the drug may be achieved through stable conjugation of the payloads (e.g., via one or more cysteines or lysines on the antibody) and relatively homogeneous composition of the ADC preparations which minimize over- conjugated toxic ADC species. Coupled with drug linkers that are designed to largely release the drug upon delivery to a tumor site, the conjugates of the instant invention can substantially reduce undesirable non-specific toxicity. This advantageously provides for relatively high levels of the active cytotoxin at the tumor site or other target site while minimizing exposure of non-targeted cells and tissue thereby providing an enhanced therapeutic index.

[0461] It will be appreciated that, while some aspects of the invention comprise payloads incorporating therapeutic moieties (e.g., cytotoxins), other payloads incorporating diagnostic agents and biocompatible modifiers may benefit from the targeted delivery provided by the disclosed conjugates. Accordingly, any disclosure directed to exemplary therapeutic payloads is also applicable to payloads comprising diagnostic agents or biocompatible modifiers as discussed herein unless otherwise dictated by context. The selected payload may be covalently or non- covalently linked to the antibody and exhibit various stoichiometric molar ratios depending, at least in part, on the method used to effect the conjugation.

[0462] Page 100 of 347

[0463] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0464] Antibody drug conjugates of the instant invention may be generally represented by the formula:

[0465] Ab-[L-D]n wherein: a) Ab comprises an anti-sTn antibody; b) D comprises a drug; c) L comprises an optional linker; and d) n is an integer from about 1 to about 20.

[0466] Those of skill in the art will appreciate that antibody drug conjugates according to the aforementioned formula may be fabricated using a number of different linkers and drugs and that conjugation methodology will vary depending on the selection of components. As such, any drug or drug linker compound that associates with a reactive residue (e.g., cysteine or lysine) or a modified N-glycan of the disclosed antibodies are compatible with the teachings herein. Similarly, any reaction conditions that allow for conjugation (including site-specific conjugation) of the selected drug to an antibody are within the scope of the present invention. Notwithstanding the foregoing, selective site-specific conjugation of the drug or drug linker to the antibody may be preferred according to some aspects, as such reaction conditions tend to provide more homogeneous preparations with less non-specific conjugation and contaminants and correspondingly less toxicity.

[0467] 1. Drugs

[0468] 1.1. Therapeutic agents

[0469] As discussed, the antibodies of the instant invention may be conjugated, linked or fused to or otherwise associated with any pharmaceutically active compound comprising a therapeutic moiety or a drug such as an anti-cancer agent including, but not limited to, cytotoxic agents (or cytotoxins), cytostatic agents, anti-angiogenic agents, debulking agents, chemotherapeutic agents, radiotherapeutic agents, targeted anti-cancer agents, biological response modifiers, cancer vaccines, cytokines, hormone therapies, anti-metastatic agents, antibiotics, nucleolytic enzymes and immunotherapeutic agents.

[0470] Exemplary anti-cancer agents or cytotoxins (including homologs and derivatives thereof) include dolastatins and auristatins. Dolastatins are linear peptides that are mitotic inhibitors.

[0471] Page 101 of 347

[0472] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010)

[0473] Dolastatins inhibit microtubule assembly by interfering with tubulin formation and thereby disrupt cell division by mitosis. Dolastatins also induce apoptosis and Bcl-2 phosphorylation in several malignant cell types. Exemplary dolastatins include dolastatin 10 and dolastatin 15. Auristatins are synthetic analogues of dolastatin 10, which have significantly greater cytotoxicity compared to dolastatin. Exemplary auristatins include, but are not limited to, monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF).

[0474] According to certain aspects of the invention, the drug can be an inhibitor of topoisomerase I. According to certain aspects, the topoisomerase I inhibitor is camptothecin (CPT) or a derivative or analog thereof. Camptothecin and its derivatives are a class of potent antitumor agents. Camptothecin has shown remarkable anticancer activity in clinical trials, particularly against breast, ovarian, colon, lung, and stomach cancers. Camptothecins act by stabilizing topoisomerase I-DNA complex (the covalent complex) resulting in a ternary complex, and thereby stabilizing it. This prevents DNA re-ligation and therefore causes DNA damage which results in apoptosis. Irinotecan (also referred to as CPT-11), topotecan, belotecan, exatecan, and deruxtecan are CPT analogs that are effective anti-cancer agents. In certain aspects, the drug may be irinotecan. In certain aspects, the drug may be topotecan.

[0475] In certain aspects, the drug may be exatecan having a structure according to the formula:

[0476] Exatecan may be synthesized according to the methods described in U.S. Patent No. 5,834,476 to Terasawa et al., issued on Nov. 10, 1998, which is herein incorporated by reference in its entirety.

[0477] In certain aspects the drug may be a derivative of exatecan (having the following formula:

[0478] Page 102 of 347

[0479] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010)

[0480] In other aspects, the drug may be DX-8951f, which is a mesylate salt of exatecan (DX-8951):

[0481] In certain aspects, the drug may be SN-38. SN-38 is the active metabolite of the irinotecan (CPT-11), and other camptothecin analogues such as topotecan and 10-hydroxy-CPT. SN-38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1 Al . SN-38 has approximately 1,000 times more activity than irinotecan itself. SN-38 having a structure according to the following formula:

[0482] The drug may be incorporated into an antibody-drug conjugate, for example, as described in U.S. Patent No. 10,918,721 to Govindan et al., issued Sept. 26, 2017; U.S. Pat. No. 9,770,517 to Govindan et al., issued Sept. 26, 2017; WO 2020 / 245229 published Dec. 10, 2020; WO 2020 / 094670 to Wijdeven et al., published on May 14, 2020; or Ogitani etal., “DS-8201a, ANovel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising

[0483] Page 103 of 347

[0484] WBD (US) 4890-0662-1673 vl Atorney Docket No. T107777 1050WO (00010)

[0485] Antitumor Efficacy with Differentiation from T-DM1”, Clin Cancer Res 2016 Oct 15;22(20):5097-5108 (doi: 10.1158 / 1078-0432.CCR-15-2822), each of which is incorporated by reference in its entirety, and / or may be prepared and / or dosed according to the methods described therein.

[0486] According to certain aspects of the invention, the drug is an enediyne antitumor antibiotic. The drug may be a calicheamicin, which is derived from the bacterium Micromonospora echinospora, such as calicheamicin yl. Calicheamicins are extremely toxic to various cells. The approved drug inotuzumab ozogamicin uses a calicheamicin. Calicheamicins target DNA and cause strand scission. Calicheamicins bind with DNA in the minor groove, wherein they then undergo a reaction analogous to the Bergman cyclization to generate a diradical species. This diradical, 1,4-didehydrobenzene, then abstracts hydrogen atoms from the deoxyribose (sugar) backbone of DNA, which ultimately leads to strand scission. In certain aspects, the drug is esperamicin, a related enediyne. The calicheamicin may be n-acetyl calicheamicin. In certain aspects, calicheamicin may be modified to minimize release of toxic metabolities. For example, calicheamicin ADCs of the invention may lack acid-labile dimethylhydrazine (DMH) linkers to prevent release of cytotoxic DMH catabolites, as in ABBV-011. See e.g. Wiedmeyer et al., Mol. Cancer Ther. 2022, 21(6):986-998, which is hereby incorporated by reference in its entirety. According to other aspects, the drug may be any one of the enediynes described in U.S. Pat. App. Pub. No. 2020 / 0297861 to Verkade et al., published Sept. 24, 2020, which is hereby incorporated by reference in its entirety, with or without the described linkers and / or functional groups.

[0487] According to certain aspects of the invention, the drug is a cytotoxin which inhibits microtubule function. The drug may be an auristatin, such as monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), or auristatin- 101 (see e.g., WO / 2016 / 055907). These auristatins inhibit cell division by blocking the polymerisation of tubulin. The drug may be maytansine or maytansinoid (a derivative of maytansine) or another derivative of maytansine. Maytansine inhibits the assembly of microtubules by binding to tubulin at the rhizoxin binding site. In certain aspects, the drug may be ansamitocin, mertansine (DMl) / emtansine, or ravtansine (DM4) / soravtansine .

[0488] Additional representative toxins include 1 -dehydrotestosterone, anthramycins, actinomycin D, bleomycin, colchicin, cyclophosphamide, cytochalasin B, dactinomycin (formerly actinomycin), dihydroxy anthracin, dione, duocarmycin, emetine, epirubicin, ethidium bromide,

[0489] Page 104 of 347

[0490] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010) etoposide, glucocorticoids, gramicidin D, lidocaine, maytansinoids such as DM-1 and DM-4 (Immunogen), benzodiazepine derivatives (Immunogen), mithramycin, mitomycin, mitoxantrone, paclitaxel, procaine, propranolol, puromycin, tenoposide, tetracaine and pharmaceutically acceptable salts or solvates, acids or derivatives of any of the above.

[0491] Additional compatible cytotoxins include amanitins such as alpha-amanitin, beta-amanitin, gamma-amanitin or epsilon-amanitin (Heidelberg Pharma), DNA minor groove binding agents such as duocarmycin derivatives (Syntarga), alkylating agents such as modified or dimeric pyrrolobenzodiazepines (PBD), mechlorethamine, thioepa, chlorambucil, melphalan, carmustine (BCNU), lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C and cisdichlorodiamine platinum (II) (DDP) cisplatin, splicing inhibitors such as meayamycin analogs or derivatives (e.g., FR901464 as set forth in U.S.P.N. 7,825,267), tubular binding agents such as epothilone analogs and tubulysins, paclitaxel and DNA damaging agents such as calicheamicins and esperamicins, antimetabolites such as methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, and 5 -fluorouracil decarbazine, anti-mitotic agents such as vinblastine and vincristine and anthracyclines such as daunorubicin (formerly daunomycin) and doxorubicin and pharmaceutically acceptable salts or solvates, acids or derivatives of any of the above.

[0492] According to some aspects, the antibodies of the instant invention may be associated with anti-CD 16A bispecific or multispecific binding molecules that target NK cells or anti-CD3 binding molecules to recruit cytotoxic T-cells and have them target cancer cells, and possibly tumorigenic cells (BiTE technology; see, e.g., Fuhrmann et. al. (2010) Annual Meeting of AACR Abstract No. 5625).

[0493] According to some aspects, ADCs of the present invention may comprise cytotoxins comprising therapeutic radioisotopes conjugated using appropriate linkers. Exemplary radioisotopes that may be compatible with such aspects include, but are not limited to, iodine (131I,123I,123I,121I,), carbon (14C), copper (62Cu,64Cu,67Cu), sulfur (35S), radium (223R), tritium (3H), indium (115In,113In,112In,n iIn,), bismuth (212Bi,213Bi), technetium ("Tc), thallium (201Ti), gallium (68Ga,67Ga), palladium (103Pd), molybdenum (99Mo), xenon (133Xe), fluorine (18F),153Sm,177Lu,159Gd,149Pm,140La,175Yb,166Ho,90Y,47Sc,186Re,188Re,142Pr,105Rh,97Ru,68Ge,57Co,65Zn,85Sr,32P,153Gd,169Yb,51Cr,54Mn,75Se,113Sn,117Sn,76Br,211At and225Ac. Other radionuclides are also available as diagnostic and therapeutic agents, especially those in the energy range of 60 to 4,000 keV.

[0494] Page 105 of 347

[0495] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0496] In addition to the aforementioned agents, the antibodies of the present invention may also be conjugated to biological response modifiers. In certain instances, the biological response modifier will comprise interleukin 2, interferons, or various types of colony-stimulating factors (e.g., CSF, GM-CSF, G-CSF).

[0497] More generally, the associated drug moiety can be a polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, Onconase (or another cytotoxic rNase), pseudomonas exotoxin, cholera toxin, diphtheria toxin; an apoptotic agent such as tumor necrosis factor (e.g., TNF- a or TNF-P), a-interferon, 0-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, AIM I (WO 97 / 33899), AIM II (WO 97 / 34911), Fas Ligand (Takahashi et al., 1994, PMID: 7826947), and VEGI (WO 99 / 23105), a thrombotic agent, an anti-angiogenic agent (e.g., angiostatin or endostatin), a lymphokine (e.g., interleukin- 1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF)), or a growth factor (e.g., growth hormone (GH)).

[0498] According to some aspects of the invention, the drug component of an ADC may comprise a cytokine. Cytokines are small immunomodulating proteins, generally of masses from about 5 to about 20 kDa, that act on cell surface receptors and are involved in autocrine, paracrine and endocrine signaling. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors and are produced by a broad range of cells, including immune cells such as macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells. Cytokines help modulate the balance between humoral and cell-based immune responses and regulate the maturation, growth, and responsiveness of particular cell populations. Cytokines have been explored as therapeutic agents, particularly the use of pro- inflammatory cytokines for the treatment of malignancies. However, substantial side effects and unfavorable pharmacokinetic properties hampered the administration of therapeutically relevant doses. The systemic administration of cytokines has been associated with dose-dependent sideeffects such as hypotension, flu-like symptoms, nausea, capillary leak.

[0499] Immunocytokines are antibody-cytokine fusion proteins which can be designed to preferentially localize on tumor lesions and to activate targeted anticancer immunity at the site of disease. Immunocytokines, thus, comprise an antigen-binding domain and a cytokine domain.

[0500] Page 106 of 347

[0501] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0502] A number of antigen-binding domain formats are known and any suitable format may be used for the antigen-binding domain of the immunocytokine. The antigen-binding domain may be derived from an antibody of the present invention. The antigen-binding domain may be any of the antibodies or antibody fragments described elsewhere herein. In some instances, the immunocytokine may comprise two cytokine domains (e.g., derived from different cytokines) joined to a single antigen-binding domain.

[0503] According to one aspect of the invention, the antigen-binding domain is a conventional antibody, such as an IgG. An IgG generally comprises a molecular weight of at least 150 kDa. IgGs typically have a longer circulatory half-life (e.g., in the range of days) than smaller antibody fragments. Binding of the Fc domain to neonatal Fc receptors may prolong immunocytokine halflife, but the increased blood clearance time of immunocytokines can also have negative effects. Mutations may be introduced in the Fc domain to modulate receptor binding and blood clearance. IgGs are also expected to retain functional properties such as binding to Fc gamma receptors and binding to the complement cascade-initiating factor Clq. The tissue penetration of IgGs is expected to be relatively slow and heterogeneous in solid tumors which are characterized by high interstitial pressure relative to smaller fragments. However, because of their longer circulatory half-life, conventional immunoglobulins may nonetheless display a higher tumor uptake compared with antibody fragments. IgG-based immunocytokines are expected to be multifunctional, potentially leading to the crosslinking of cytokine receptor-positive cells with components of the immune system capable of interacting with the Fc portion of IgG. Conventional antibodies can trigger antibody-dependent cellular toxicity (ADCC) or complement dependent cytotoxicity against the cancer cell bound by the antibody.

[0504] Smaller antigen-binding domains (e.g., below 130 kDa), such as monomeric scFvs (approximately 28 kDa) may have better tumor penetration compared with IgGs. Smaller fragments, however, lack the avidity effects of bivalent antibodies and typically display short retention times at tumor sites. However, favorable tumor: organ ratios have been reported for fragment-based immunocytokines in various quantitative biodistribution studies performed in mouse models of cancer. Bivalent recombinant antibodies of intermediate size, such as dimeric scFv fragments (i.e., diabodies), scFv-Fc fusions, and minibodies (small immunoprotein [SIP]), may display long residence time at the site of disease as well as rapid blood clearance.

[0505] Page 107 of 347

[0506] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0507] According to another aspect of the invention, the antigen-binding domain is an scFv. The scFv may comprise a VH domain fused to a VL domain by a peptide linker. The VH domain may be the N terminal domain and the VL domain may be the C terminal domain. The linker may be a peptide sequence of about 5 to 10 aa as is known in the art.

[0508] According to another aspect, the antigen-binding domain may be a small immunoprotein (SIP) comprising a homodimer of two polypeptides, each polypeptide comprising an scFv fused to an antibody heavy chain constant domain (e.g., CH3 or CH4). The scFv may be connected to the constant domain via a linker peptide, such as those described elsewhere herein. Dimerisation of the constant domains forms the homodimer. The antigen-binding domain may be an SIP comprising a homodimer of scFv fused to a human CH4 domain of the secretory isoform S2 of human IgE. CH4 is the domain that allows dimerization in the IgE molecule and the sS2 isoform contains a cysteine at the carb oxy terminal end, which stabilizes the IgE dimer through an interchain disulphide bond. Thus, a covalent homodimer may be produced.

[0509] The cytokine domain may be joined to the antigen-binding domain at any suitable site. For instance, the cytokine domain may be joined to the N-terminus or C-terminus of the antigenbinding domain unless otherwise indicated by context. The cytokine domain may be joined to the antigen-binding domain by any suitable covalent or non-covalent means. The immunocytokine may be a fusion protein comprising the cytokine domain and the antigen-binding domain. For example, the cytokine domain may be fused to a VH domain or VL domain of the antigen-binding domain. Typically, the antigen-binding domain and cytokine domain are joined via a peptide linker (e g., a peptide of about 5-25, 10-20, or 15 residues). Suitable examples of peptide linkers are well known in the art and may comprise any of the spacers or linkers described elsewhere herein.

[0510] The cytokine domain may comprise a naturally occurring cytokine, a physiologically relevant fragment thereof, or a mutant cytokine derived from either. Cytokines suitable for use with the present invention include, but are not limited to, interleukin-2 (IL2), interleukin- 12 (IL 12), tumor necrosis factor (TNF), interferon-alpha, and granulocyte-macrophage colony-stimulating factor (GMCSF). Most pro-inflammatory cytokines mediate the influx of leukocytes at the site of disease, but their activity on specific types of immunocells may vary. Selection of some cytokines (e.g., those with heavy glycosylation or with extreme isoelectric points) may abrogate the tumor targeting potential of the antigen-binding domain.

[0511] Page 108 of 347

[0512] WBD (US) 4890-0662- 1673vl Atorney Docket No. T107777 1050WO (00010)

[0513] In one aspect of the invention, the cytokine domain is derived from IL2 (UniProt: P60568). IL2 is a secreted cytokine naturally produced by T-cells. The IL2 precursor comprises an N- terminal signal peptide which is removed in the mature form. IL2 stimulates the proliferation of T- and B-lymphocytes, monocytes, and NK cells in response to antigenic or mitogenic stimulation. IL2 has been shown to have a cytotoxic effect on tumour cells and recombinant human IL2 (aldesleukin: Proleukin®) has FDA approval for treatment of metastatic renal carcinoma and metastatic melanoma. Tumor-targeting immunocytokines based on IL2 have been shown to mediate a massive infiltration of leukocytes into the tumour mass, with NK cells as the main mediator of therapeutic activity. IL2 may be particularly beneficial for treatment of glioma (e.g. for treating glioblastoma). Although IL2 has been shown to have anti-tumor activity, high levels of IL2 lead to pulmonary toxicity, and the anti-tumor activity of IL2 is limited by a number of inhibitory feedback loops. Also, the systemic and untargeted application of IL2 may considerably compromise anti-tumor immunity via induction of Treg cells and activation-induced cell death (AICD) rendering activated T-cells susceptible to Fas-mediated apoptosis. Specifically, IL-2 is involved in the maintenance and expansion of peripheral CD4+CD25+Treg cells.

[0514] IL2 also plays a significant role in memory CD8+T-cell differentiation during primary and secondary expansion of CD8+T cells. IL2 seems to be responsible for optimal expansion and generation of effector functions fo...

Claims

1. Attorney Docket No. T107777 1050WO (00010)Claims:

1. An antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; or(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 78 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 82.

2. The antibody of claim 1, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 85, an amino acid sequence set forth as SEQ ID NO: 86, and an amino acid sequence set forth as SEQ ID NO: 87; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 88, an amino acid sequence set forth as SEQ ID NO: 89, and an amino acid sequence set forth as SEQ ID NO: 90.Page 283 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)3. The antibody of claim 1, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 91, an amino acid sequence set forth as SEQ ID NO: 92, and an amino acid sequence set forth as SEQ ID NO: 93; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 94, an amino acid sequence LMS, and an amino acid sequence set forth as SEQ ID NO: 96.

4. The antibody of claim 1, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 74, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 97, an amino acid sequence set forth as SEQ ID NO: 98, and an amino acid sequence set forth as SEQ ID NO: 99; and / or three light chain CDRs comprising an amino acid sequence set forth asPage 284 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)SEQ ID NO: 100, an amino acid sequence set forth as SEQ ID NO: 101 , and an amino acid sequence set forth as SEQ ID NO: 102.

5. The antibody of any one of claims 2-4, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56; or(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 78 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 82.

6. The antibody of claim 5, wherein the antibody comprises: a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56.

7. The antibody of any one of claims 1-6, wherein the antibody is a chimeric, CDR grafted, humanized, or a human antibody, or an immunoreactive fragment thereof.

8. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;Page 285 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(l) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;Page 286 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;Page 287 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(w) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(x) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(y) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(z) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(aa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(bb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(cc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(dd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(ee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(ft) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;Page 288 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(gg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(hh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ii) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(jj) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(kk) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(11) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(mm) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(nn) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(oo) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(pp) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;Page 289 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(qq) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(IT) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ss) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(tt) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(uu) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(vv) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(ww) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(xx) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(yy) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(zz) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;Page 290 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(aaa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(bbb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ccc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(ddd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(eee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(fff) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(ggg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or(hhh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

9. The humanized antibody of claim 8, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;Page 291 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;Page 292 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(h) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(i) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(j) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(k) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(l) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(m) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; orPage 293 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(n) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

10. The humanized antibody of claim 8, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38.

11. The humanized antibody of claim 8, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth asPage 294 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or(e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

12. The humanized antibody of any one of claims 9-11, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;Page 295 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(l) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;Page 296 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(w) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(x) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(y) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;Page 297 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(z) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(aa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(bb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(cc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(dd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(ee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(ff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(gg) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(hh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ii) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;Page 298 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(jj ) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(kk) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(11) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(mm) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(nn) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(oo) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(pp) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(qq) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(rr) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ss) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;Page 299 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(tt) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(uu) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(vv) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(ww) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(xx) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(yy) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(zz) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(aaa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(bbb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;(ccc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;Page 300 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(ddd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(eee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(fff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(ggg) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or(hhh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

13. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;Page 301 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(l) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;Page 302 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; or(v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

14. The antibody of claim 13, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; orPage 303 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

15. The antibody of claim 13, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 244; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 236, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 237; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence GAS, and an amino acid sequence set forth as SEQ ID NO: 38.

16. The antibody of claim 13, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 245, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 238, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth asPage 304 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

17. The antibody of any one of claims 13-16, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;Page 305 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. TI07777 1050WO (00010)(i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(l) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;Page 306 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268; or(v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

18. An antibody that preferentially binds to an eptitope comprising at least one mono sTn glycan.

19. The antibody of claim 18, wherein the antibody does not bind to a Tn epitope.

20. The antibody of claim 18 or 19, wherein the antibody comprises or competes for binding to a mono sTn epitope with an antibody comprising:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;Page 307 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(l) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;Page 308 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; or(u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.

21. The antibody of any one of claims 18-20, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 60, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;Page 309 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;Page 310 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(h) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or(i) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

22. The antibody of any one of claims 18-20, wherein the antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence DTS, and an amino acid sequence set forth as SEQ ID NO: 64.

23. The antibody of any one of claims 18-20, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 74, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth asPage 311 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

24. The antibody of any one of claims 18-23, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 52 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 56;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 143 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;Page 312 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(l) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;(p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165;(q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157;(r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160;(s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163;Page 313 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 165; or(u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 149 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.

25. The antibody of claim 18 or 19, wherein the antibody comprises or competes for binding to a mono sTn epitope with an antibody comprising:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;Page 314 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(l) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;Page 315 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; or(u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268.

26. The antibody of any one of claims 18, 19, or 25, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 244; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 243, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64.

27. The antibody of any one of claims 18, 19, or 25, wherein the antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 245, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 62, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.Page 316 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)28. The antibody of any one of claims 18, 19, or 25-27, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 241 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 246 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 249 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;Page 317 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. TI07777 1050WO (00010)(j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(l) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 252 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 255 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268(p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;(q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266;(r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 258 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268;(s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 264;Page 318 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 266; or(u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 261 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 268.

29. An antibody that binds to sTn and Tn.

30. The antibody of claim 29, wherein the antibody binds to an epitope comprising one or more sTn glycans, one or more Tn glycans, or a combination of sTn and Tn glycans.

31. The antibody of claim 29 or 30, wherein the antibody comprises or competes for binding to an sTn and / or Tn with an antibody comprising:(a) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 26 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 30;(b) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(c) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(d) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(e) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 319 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(f) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(g) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(h) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(i) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(j) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(k) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(l) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(m) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(n) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(o) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 320 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(p) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(q) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(r) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(s) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(t) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(u) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(v) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(w) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(x) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(y) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 321 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(z) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(aa) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(bb) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(cc) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(dd) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(ee) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(ff) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(gg) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(hh) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(ii) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 322 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(jj) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(kk) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(11) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(mm) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(nn) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or(oo) three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

32. The antibody of any one of claims 29-31, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO:33, an amino acid sequence set forth as SEQ ID NO: 34, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;Page 323 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(d) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(e) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(f) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or(g) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 119, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

33. The antibody of any one of claims 29-31, wherein the antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38.Page 324 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)34. The antibody of any one of claims 29-31, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 142, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

35. The antibody of any one of claims 29-34, wherein the antibody comprises:(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(b) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(c) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(d) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 325 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(e) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(f) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(g) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(h) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(i) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(j) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(k) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(l) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(m) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(n) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 326 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(o) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(p) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(q) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(r) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(s) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(t) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(u) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(v) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(w) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(x) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 327 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(y) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(z) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(aa) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(bb) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(cc) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138;(dd) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140;(ee) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120;(ff) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124;(gg) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126;(hh) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 128;Page 328 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(ii) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 130;(jj) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 132;(kk) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134;(11) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 136;(mm) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 138; or(nn) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 117 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 140.

36. The antibody of claim 29 or 30, wherein the antibody comprises or competes for binding to an sTn and / or Tn with an antibody comprising three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

37. The antibody of claim 29, 30, or 36, wherein the antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 236, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 237; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38.Page 329 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)38. The antibody of claim 29, 30, or 36, wherein the antibody comprises three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 238, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and / or three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 36, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

39. The antibody of claim 29, 30, or 36-38, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 233 and / or a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 239.

40. The antibody of any one of claims 1-39, wherein the antibody is conjugated to a payload.

41. The antibody of claim 40, wherein the payload is conjugated to the antibody by a linker.

42. The antibody of claim 41, wherein the linker comprisesa sulfamide.

43. The antibody of any one of claims 40-42, wherein the linker comprises a cleavable unit and a hydrophilic moiety.

44. The antibody of any one of claims 40-43, wherein the payload is conjugated to one or more naturally occurring glycans of the antibody.

45. The antibody of claim 44, wherein the payload is conjugated to an asparagine 297 residue in a constant region of a heavy chain of the antibody.

46. The antibody of any one of claims 40-42, wherein the payload is conjugated to an N- acetylglucosamine (GlcNAc).

47. The antibody of any one of claims 40-46, wherein the payload comprises SN-38, deruxtecan (DXd), exatecan, MMAE, MMAF, DM1, or DM4.Page 330 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)48. The antibody of any one of claims 1-47, wherein the antibody is a bispecific antibody.

49. The antibody of any one of claims 1-48, wherein(a) the antibody binds sTn on an antigen expressed on a tumor cell; or(b) the antibody is a multispecific antibody that binds (i) sTn on an antigen expressed on a tumor cell, and (ii) an antigen expressed on a T cell, B cell, or NK cell selected from the group consisting of CD3, 4-1BB, CD16, NKp30, NKp46, NKG2D, and DNAM-1, and CD40.

50. A pharmaceutical composition comprising the antibody of any one of claims 1-49.

51. A nucleic acid encoding a light chain variable region and / or a heavy chain variable region of the antibody of any one of claims 1-49.

52. A vector comprising the nucleic acid of claim 51.

53. A host cell comprising the nucleic acid of claim 51 or the vector of claim 52.

54. An antibody drug conjugate (ADC) of the formula Ab-[L-D]n wherein:(a) Ab comprises an anti-sTn antibody, wherein the antibody is the antibody of any one of claims 1-39;(b) D comprises a drug or payload;(c) L comprises an optional linker; and(d) n is an integer from about 1 to about 20.

55. The ADC of claim 54, wherein n is an integer from about 1 to about 8.

56. The ADC of claim 54 or 55, wherein D is a cytotoxic agent.

57. The ADC of claim 56, wherein the cytotoxic agent is selected from the group consisting of a cytotoxin, a chemotherapeutic agent, an antibiotic, a radioactive isotope, and a nucleolytic enzyme.Page 331 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)58. The ADC of any one of claims 54-57, wherein D comprises a compound selected from the group consisting of camptothecins, auristatins, dolastatins, maytansinoids, calicheamicins, pyrrolobenzodiazepines (PBDs), benzodiazepine derivatives, and amanitins, or analogues or derivatives thereof.

59. The ADC of any one of claims 54-58, wherein D comprises SN-38, DXd, exatecan, MMAE, MMAF, DM1, or DM4.

60. The ADC of any one of claims 54-59, wherein the ADC has the structure:, wherein:(a) Z is a connecting group for conjugation to an antibody or an antigen-binding fragment thereof;(b) LBis a connector unit that covalently connects CLand Z;(c) CLis a cleavable linker;(d) R1and R2are coupling groups;(e) E is a hydrophilic moiety; and(f) D is a drug.

61. The ADC of any one of claims 54-59, wherein the ADC has the structure:(a) Z is a connecting group for conjugation to an antibody or an antigen-binding fragment thereof;(b) LBis a connector unit that covalently connects CL, Z, and E;Page 332 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(c) CLis a cleavable linker;(d) R1and R2are coupling groups;(e) E is a hydrophilic moiety; and(f) D is a drug.

62. The ADC of claim 60 or 61, wherein LBcomprises an amino acid.

63. The ADC of any one of claims 60-62, wherein Z is selected from the group consisting of:wherein one wavy line indicates the site of covalent attachment to Ab and the other wavy line indicates the site of covalent attachment to LB; and where R5is H or Ci-Ce alkyl.

64. The ADC of any one of claims 60-63, wherein LBcomprises an amino acid, and wherein the hydrophilic moiety (E) is coupled to LBthrough the amino group, through the carboxyl group, or through the side chain of the amino acid of the connector group.

65. The ADC of any one of claims 60-64, wherein C1is a protease-cleavable peptide moiety, a glycosidase-cleavable sugar moiety, a pH sensitive moiety, or a hydrolysable moiety.

66. The ADC of any one of claims 60-64, wherein CLis a protease-cleavable peptide moiety comprising valine-alanine (VA), valine-cysteine (VC), phenyl al anine-glycine (FG), phenylalanine-lysine (FK), alanine-alanine (AA), glycine-valine (GV), or glycine-cysteine (GC).Page 333 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)67. The ADC of any one of claims 60-66, wherein each of R1and R2are, independently, selected from the group consisting of -C(O)-, -C(O)O-, -C(O)NH-, alkyl-O-, alkyl-NH-, alkyl-C(O)-, alkyl-C(O)-O-, alkyl-C(O)-NH-, alkyl-NH-C(O)-, alkyl-SCh-, alkyl-S-, alkyl-O-P(O)-O2-, alkyl-O-C(O)-NH-, or triazole.

68. The ADC of any one of claims 60-67, wherein E comprises a polyethylene glycol (PEG), a polysarcosine (pSar), a poly lactic-co-glycolic acid (PLGA), a poly(glycerol) (PG), a poly(oxazolines) (POX), a poly(hydroxypropylmethacrylate) (PHPMA), a poly(2 -hydroxyethyl methacrylate) (PHEMA), a poly(N-(2-hydroxypropyl)methacrylamide) (HPMA), a poly(vinylpyrrolidone) (PVP), a poly(N,N-dimethylacrylamide) (PDMA), a poly(N- acryloylmorpholine) (PAcM), or a saccharide.

69. The ADC of any one of claims 60-67, wherein E has the structure:- R3- (CH2CH2O)n - R4where:(a) R3is -C(O)-, -O-, -S-, -NH-, -C(O)O-, alkyl-C(O)-NH-, alkyl-NH-C(O)-, alkyl-CO2-, alkyl-S(b) R4is H, SO3H, PO3H2, a sugar derivative, C1-C10 alkyl group, C3-C10 cycloalkyl group, C2-C10 alkyl-NH2, C1-C10 alkyl-COOR, C2-C10 alkyl-NH(Ci-C3 alkyl), C2-C10 alkyl-N (C1-C3 alkyl)2, or sarcosine; and(c) n is an integer ranging from 2 to 72.

70. The ADC of any one of claims 60-69, wherein Z is conjugated to one or more naturally occurring glycans associated with the antibody.Page 334 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)71 . The ADC of claim 70, wherein Z is conjugated to an N-acetylglucosamine (GlcNAc).

72. The ADC of any one of claims 60-69, wherein Z is conjugated to one or more amino acids of the antibody.

73. The ADC of claim 72, wherein Z is conjugated to an asparagine 297 residue in a constant region of a heavy chain of the antibody.

74. The ADC of claim 54 or 55, wherein D is a cytokine.

75. The ADC of claim 74, wherein the cytokine is selected from the group consisting of interleukin-2 (IL2), interleukin- 12 (IL12), tumor necrosis factor (TNF), interferon-alpha, and granulocyte-macrophage colony-stimulating factor (GMCSF).

76. A pharmaceutical composition comprising the ADC of any one of claims 54-75.

77. A method of producing the ADC of any one of claims 54-75, the method comprising the step of conjugating the antibody (Ab) with the drug (D).

78. A chimeric antigen receptor (CAR) comprising: i) an extracellular antigen binding domain that binds to sTn, wherein the antigen binding domain comprises the antibody of one of claims 1- 39; ii) a transmembrane domain; and iii) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM), wherein the intracellular signaling domain provides signal transduction activity.

79. A nucleic acid encoding the CAR of claim 78.

80. A vector comprising the nucleic acid of claim 79.

81. A host cell comprising the nucleic acid of claim 79 or the vector of claim 80.Page 335 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)82. The host cell of claim 80, wherein the cell is an isolated T lymphocyte.

83. A pharmaceutical composition comprising the host cell of claim 81 or 82.

84. A method of delivering a cytotoxin to a cell comprising contacting the cell with an ADC of any one of claims 54-75.

85. The method of claim 84, wherein the contacting is performed in vitro.

86. The method of claim 84, wherein the contacting is performed in vivo.

87. A method of treating cancer comprising administering a pharmaceutical composition of any one of claims 50, 76, or 83 to a subject in need thereof.

88. The method of claim 87, wherein the cancer comprises a solid tumor.

89. The method of claim 87 or 88, wherein the cancer is an epithelial cell cancer.

90. The method of any one of claims 87-89, wherein the cancer is selected from the group consisting of gastric cancer, colorectal cancer, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, skin cancer, and bladder cancer.

91. The method of claim 90, wherein the cancer is selected from the group consisting of gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, and lung cancer.

92. The method of any one of claims 87-91, wherein the cancer is an adenocarcinoma.

93. The method of any one of claims 87-91, wherein the cancer is a squamous cell carcinoma.

94. The method of any one of claims 87-93, wherein treating the cancer further comprises administering a poly(ADP-ribose) polymerase (PARP) inhibitor to the subject.Page 336 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)95. The method of any one of claims 87-94, wherein treating the cancer comprises administering an ADC to the subject.

96. The method of claim 95, wherein the ADC comprises SN-38, DXd, or exatecan.

97. A method of detecting, diagnosing, or monitoring cancer in a subject, the method comprising the steps of (a) contacting cancer cells with the antibody of any one of claims 1-49 or the ADC of claim 54 or 55; and (b) detecting the antibody on the tumor cells.

98. The method of claim 97, wherein the contacting is performed in vitro.

99. The method of claim 97, wherein the contacting is performed in vivo.

100. The method of any one of claims 97-99, wherein the cancer comprises a solid tumor.

101. The method of any one of claims 97-100, wherein the cancer is an epithelial cell cancer.

102. The method of any one of claims 97-101, wherein the cancer is selected from the group consisting of gastric cancer, colorectal cancer, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, skin cancer, and bladder cancer.

103. The method of claim 102, wherein the cancer is selected from the group consisting of gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, and lung cancer.

104. The method of any one of claims 97-103, wherein the cancer is an adenocarcinoma.

105. The method of any one of claims 97-103, wherein the cancer is a squamous cell carcinoma.

106. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variablePage 337 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010) region comprising an amino acid sequence set forth as SEQ ID NO: 143 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157.

107. The humanized antibody of claim 106, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 145, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

108. The antibody of claim 106 or 107, wherein the antibody is conjugated to a payload.

109. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 146 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 157.

110. The humanized antibody of claim 109, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 148, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQPage 338 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 159, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

111. The humanized antibody of claim 109 or 110, wherein the antibody is conjugated to a payload.

112. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160.

113. The humanized antibody of claim 112, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQPage 339 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

114. The humanized antibody of claim 112 or 113, wherein the antibody is conjugated to a payload.

115. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 152 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 163.

116. The humanized antibody of claim 115, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 154, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQPage 340 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

117. The humanized antibody of claim 115 or 116, wherein the antibody is conjugated to a payload.

118. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 155 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 160.

119. The humanized antibody of claim 118, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 59, an amino acid sequence set forth as SEQ ID NO: 151, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 65, an amino acid sequence set forth as SEQ ID NO: 66, and an amino acid sequence set forth as SEQ ID NO: 67; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 68, an amino acid sequence set forth as DTS, and an amino acid sequence set forth as SEQ ID NO: 64; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 71, an amino acid sequence set forth as SEQ ID NO: 72, and an amino acid sequence set forth as SEQ ID NO: 61; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 162, an amino acid sequence set forth as SEQ ID NO: 63, and an amino acid sequence set forth as SEQ ID NO: 64.

120. The humanized antibody of claim 118 or 119, wherein the antibody is conjugated to a payload.Page 341 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)121 . A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 109 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126.

122. The humanized antibody of claim 121, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

123. The humanized antibody of claim 121 or 122, wherein the antibody is conjugated to a payload.

124. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 124.

125. The humanized antibody of claim 124, wherein the antibody comprises:Page 342 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

126. The humanized antibody of claim 124 or 125, wherein the antibody is conjugated to a payload.

127. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 113 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 126.

128. The humanized antibody of claim 127, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;Page 343 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

129. The humanized antibody of claim 127 or 128, wherein the antibody is conjugated to a payload.

130. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 120.

131. The humanized antibody of claim 130, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38; orPage 344 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.

132. The humanized antibody of claim 130 or 131, wherein the antibody is conjugated to a payload.

133. A humanized antibody that binds to a sialyl-Thomsen-nouveau antigen (sTn), wherein the antibody comprises three complementarity-determining regions (CDRs) of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 115 and three CDRs of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 134.

134. The humanized antibody of claim 133, wherein the antibody comprises:(a) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 33, an amino acid sequence set forth as SEQ ID NO: 112, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38;(b) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 39, an amino acid sequence set forth as SEQ ID NO: 40, and an amino acid sequence set forth as SEQ ID NO: 41; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 42, an amino acid sequence set forth as GAS, and an amino acid sequence set forth as SEQ ID NO: 38; or(c) three heavy chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 45, an amino acid sequence set forth as SEQ ID NO: 46, and an amino acid sequence set forth as SEQ ID NO: 35; and three light chain CDRs comprising an amino acid sequence set forth as SEQ ID NO: 123, an amino acid sequence set forth as SEQ ID NO: 37, and an amino acid sequence set forth as SEQ ID NO: 38.Page 345 of 347WBD (US) 4890-0662- 1673vlAttorney Docket No. T107777 1050WO (00010)135. The humanized antibody of claim 133 or 134, wherein the antibody is conjugated to a payload.Page 346 of 347WBD (US) 4890-0662- 1673vl

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