Anti-CDH17 binding molecules

Abstract

Disclosed herein are anti-cadherin 17 (CDH17) binding molecules, methods for using thereof for treating, preventing, and diagnosing cancer. Further disclosed are antibody-drug conjugates (ADC) targeting CDH17 expressing cells.

Description

ANTI-CDH17 BINDING MOLECULESSEQUENCE LISTING

[0001] A Sequence Listing conforming to the rules of WIPO Standard ST.26 is hereby incorporated by reference. Said Sequence Listing has been filed as an electronic document via PatentCenter encoded as XML in UTF-8 text. The electronic document, created on June 5, 2024, is entitled “P-634360-USP_ST26.xml”, and is 311,745 bytes in size.FIELD OF DISCLOSURE

[0002] Disclosed herein are anti-cadherin 17 (CDH17) binding molecules, and methods for using thereof for treating, preventing, and diagnosing cancer. Further disclosed are antibodydrug conjugates (ADC) targeting CDH17 expressing cells.BACKGROUND

[0003] Cadherin 17 (CDH17) is a transmembrane glycoprotein belonging to the cadherin superfamily. CDH17 functions primarily as a cell adhesion molecule and contributes significantly to tissue morphogenesis and cellular differentiation during embryonic development. Recent research indicates CDH17’s role in carcinogenesis, and its implications in various malignancies. Among others, aberrant expression levels of CDH17 were reported in neoplastic transformations, including gastrointestinal and colorectal cancers. These findings suggest that CDH17 could be used as a biomarker for diagnostic and prognostic purposes. Further studies indicated a significant correlation between CDH17 expression levels and the pathological features of gastric malignancies.

[0004] CDH17 is characterized by an extracellular domain containing calcium- binding motifs that enable the adhesion between neighboring cells. Dysregulation of these adhesive properties were proposed to prompt tumor invasion and metastasis. Furthermore, CDH17 has been proposed as a putative target for cancer therapy due to its role in modulating cellular signaling pathways associated with proliferation, survival, and migration.

[0005] Several problems have been associated with anti-CDH17 cancer therapy. For example, CDH17 expression was shown to be heterogenous among cancer patients. Thus, the efficacy of the treatment is relatively low for patients with low CDH17 expression levels. Furthermore, CDH17 is expressed also in non-pathological tissues, which are targeted in a non-differentiated manner by anti-CDH17 therapies.

[0006] Drug-conjugated antibodies (ADC) play a central role in cancer therapy research, as they offer a precision-oriented approach to treatment. ADC are designed to selectively targetantigens present on the surface of cancer cells, and to deliver their cytotoxic drug payload directly to these cells, thus minimizing damage to surrounding healthy tissues. This drug delivery approach enhances the therapeutic index of potent cytotoxic agents, as it allows for a more concentrated and effective target of cancer cells while sparing non-cancerous cells from unnecessary exposure.

[0007] Thus, there is a clear need for new, more efficient anti-CDH17 binding molecules that would facilitate both cancer treatment and diagnostics.SUMMARY OF THE INVENTION

[0008] In some aspects, disclosed herein is an isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101 , 111, 121, 131, 141 , 151, 161, 171, 181, 191, 201, 211, or 221 ; a second CDR (CDRH2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, or 222; and a third CDR (CDRH3) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 1 13, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, or 223; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, or 224; a second CDR (CDRL2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, or 225; and a third CDR (CDRL3) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146, 156, 166, 176, 186, 196, 206, 216, or 226.

[0009] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 1 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 2, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 3, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 4, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 5, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 6.

[0010] In some related aspects, the CDRH1 comprises an amino acid sequence having at least80% homology to SEQ ID NO: 11; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 12, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 13, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 14, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 15, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 16.

[0011] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 21 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 22, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 23, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 24, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 25, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 26.

[0012] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 31; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 32, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 33, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 34, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 35, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 36.

[0013] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 41 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 42, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 43, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 44, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 45, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 46.

[0014] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 51 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 52, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 53, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 54, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 55, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 56.

[0015] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 61 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 62, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 63, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 64, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 65, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 66.

[0016] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 71 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 72, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 73, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 74, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 75, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 76.

[0017] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 81 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 82, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 83, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 84, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 85, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 86.

[0018] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 91; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 92, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 93, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 94, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 95, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 96.

[0019] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 101 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 102, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 103, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 104, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 105, and said CDRL3 comprisesan amino acid sequence having at least 80% homology to SEQ ID NO: 106.

[0020] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 111 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 112, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 113, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 114, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 115, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 1 16.

[0021] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 121; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 122, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 123, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 124, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 125, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 126.100221 In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 131 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 132, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 133, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 134, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 135, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 136.

[0023] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 141; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 142, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 143, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 144, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 145, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 146.

[0024] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 151 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 152, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 153, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 154, said CDRL2 comprises an aminoacid sequence having at least 80% homology to SEQ ID NO: 155, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 156.

[0025] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 161 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 162, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 163, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 164, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 165, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 166.

[0026] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 171; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 172, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 173, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 174, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 175, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 176.

[0027] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 181; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 182, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 183, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 184, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 185, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 186.

[0028] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 191 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 192, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 193, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 194, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 195, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 196.

[0029] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 201; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 202, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 203, said CDRL1 comprises an amino acidsequence having at least 80% homology to SEQ ID NO: 204, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 205, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 206.

[0030] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 211; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 212, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 213, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 214, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 215, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 216.

[0031] In some related aspects, said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 221 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 222, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 223, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 224, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 225, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 226.

[0032] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 7 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 8.

[0033] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 17 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 18.

[0034] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 27 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 28.

[0035] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 37 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 38.

[0036] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 47 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 48.

[0037] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 57 and said light chain variable regioncomprises an amino acid sequence having at least 80% homology to SEQ ID NO: 58.

[0038] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 67 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 68.

[0039] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 77 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 78.

[0040] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 87 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 88.

[0041] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 97 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 98.

[0042] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 107 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 108.

[0043] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 117 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 118.

[0044] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 127 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 128.

[0045] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 137 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 138.

[0046] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 147 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 148.

[0047] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 157 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 158.

[0048] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 167 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 168.

[0049] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 177 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 178.

[0050] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 187 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 188.

[0051] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 197 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 198.

[0052] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 207 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 208.

[0053] In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 217 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 218. [0054| In some related aspects, said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 227 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 228.

[0055] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 9, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 10.

[0056] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 19, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 20.

[0057] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 29, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 30.

[0058] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 39, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 40.

[0059] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 49, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 50.

[0060] In some related aspects, said heavy chain region comprises an amino acid sequencehaving at least 80% homology to SEQ ID NO: 59, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 60.

[0061] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 69, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 70.

[0062] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 79, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 80.

[0063] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 89, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 90.

[0064] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 99, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 100.

[0065] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 109, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 110.

[0066] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 119, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 120.

[0067] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 129, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 130.

[0068] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 139, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 140.

[0069] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 149, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 150.

[0070] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 159, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 160.

[0071] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 169, and said light chain region comprises anamino acid sequence having at least 80% homology to SEQ ID NO: 170.

[0072] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 179, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 180.

[0073] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 189, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 190.

[0074] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 199, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 200.

[0075] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 209, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 210.

[0076] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 219, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 220.

[0077] In some related aspects, said heavy chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 229, and said light chain region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 230.

[0078] In some related aspects, the binding molecule comprises an IgG, a Fv, a scFv, a Fab, a F(ab')2, a minibody, a diabody, a triabody, a nanobody, a bispecific antibody, a single domain antibody, a monoclonal antibody, or a chimeric antigen receptor. In some related aspects, said IgG is IgGl, IgG2, IgG3, or IgG4.

[0079] In some aspects, disclosed herein is a polynucleotide sequence encoding the anti- CDH17 binding molecule described above. In some aspects, disclosed herein is an expression vector comprising the polynucleotide described above. In some aspects, disclosed herein is a host cell comprising the expression vector disclosed above.

[0080] In some aspects, disclosed herein is an antibody-drug conjugate (ADC) comprising the anti-Cadherin 17 (CDH17) binding molecule described above; and a drug conjugate comprising a cleavable linker and a cytotoxic payload.

[0081] In some related aspects, the drug conjugate comprises duarcomycin (DMDM). In some related aspects, the drug conjugate comprises exatecan. In some related aspects, the drug conjugate comprises deruxtecan. In some related aspects, the drug conjugate comprises MMAE. In some related aspects, the cleavable linker moiety is a hydrazone linker, a disulphidelinker, or a peptide linker.

[0082] In some related aspects, the peptide linker is a dipeptide linker selected from the group consisting of valine-citrulline (Val-Cit), valine-alanine (Vai-Ala) and alanine-alanine (Ala- Ala). In some related aspects, the dipeptide linker is joined to the cytotoxic payload by the spacer unit ra-amirH)benzyloxycarbonyl (PABC).

[0083] In some related aspects, the peptide linker is a tripeptide linker comprising a glutamic acid-valine-citrulline (EVCit). In some related aspects, the glutamic acid-valine-citrulline (EVCit) tripeptide linker is joined to a meta-amid / wa-aminobenzyl carbamate (MA-PABC) group. In some related aspects, the drug-to-antibody ratio (DAR) is 2.

[0084] In some related aspects, the drug-to-antibody ratio (DAR) is 8 or 4.

[0085] In some aspects, disclosed herein is a pharmaceutical composition comprising the anti- CDH17 binding molecule described above, or the antibody-drug conjugate described above, and a pharmaceutically acceptable carrier.

[0086] In some aspects, disclosed herein is a method of treating a disease associated with CDH17, comprising a step of administering to the subject the pharmaceutical composition described above.

[0087] In some related aspects, the disease is cancer. In some related aspects, the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, colon cancer, and colorectal cancer.

[0088] In some aspects, the ADC is administered in a dosage of 3, 5, 7, or 10 mg per kg. In some aspects, the ADC is administered once every 7 days, or once every 14 days.

[0089]

[0090] In some aspects, disclosed herein is a method of diagnosing a disease associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule described above.

[0091] In some related aspects, the disease is cancer. In some related aspects, the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, colon cancer, and colorectal cancer. In some related aspects, the tissue comprises blood and / or a tumor tissue.BRIEF DESCRIPTION OF THE DRAWINGS

[0092] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0093] Figures 1A-1W show intrinsic binding affinity of DM-9464 (Figure 1A), DM- 9476(Figure IB), DM-9491 (Figure 1C), DM-9509 (Figure ID), DM-9558 (Figure IE), DM- 9580 (Figure IF), DM-9591 (Figure 1G), DM-9597 (Figure 1H), DM-9616 (Figure II), DM-9620 (Figure 1 J), DM-9621 (Figure IK), DM-9628 (Figure IL), DM-9648 (Figure IM), DM- 9649 (Figure IN), DM-9701 (Figure 10), DM-9706 (Figure IP), DM-9746 (Figure IQ), DM- 9762 (Figure 1R), DM-9773 (Figure IS), DM-9780 (Figure IT), DM-9787 (Figure 1U), (Figure IV), DM-9814 DM-9832 (Figure 1W) anti-CDH17 antibodies, as measured by surface plasmon resonance (SPR) using soluble human CDH17 was passed over the captured antibody.

[0094] Figure 2 is a table summarizing the experiments showing intrinsic binding affinity of anti-CDH17 antibodies as measured by SPR using soluble human and monkey CDH17.

[0095] Figures 3A-3W show binding of DM-9464 (Figure 3A), DM-9476(Figure 3B), DM- 9491 (Figure 3C), DM-9509 (Figure 3D), DM-9558 (Figure 3E), DM-9580 (Figure 3F), DM- 9591 (Figure 3G), DM-9597 (Figure 3H), DM-9616 (Figure 31), DM-9620 (Figure 3J), DM-9621 (Figure 3K), DM-9628 (Figure 3L), DM-9648 (Figure 3M), DM-9649 (Figure 3N), DM- 9701 (Figure 30), DM-9706 (Figure 3P), DM-9746 (Figure 3Q), DM-9762 (Figure 3R), DM- 9773 (Figure 3S), DM-9780 (Figure 3T), DM-9787 (Figure 3U), (Figure 3V), DM-9814 DM- 9832 (Figure 3W) anti-CDH17 antibodies to cells expressing CDH17.

[0096] Figures 4A-4E show the cytotoxic effects of DM-9509 (Figure 4A), DM-9832 (Figure 4B), DM-9491 (Figure 4C), DM-9648 (Figure 4D), and DM-9787 (Figure 4E) conjugated to duarcomycin (DMDM) on CDH17 expressing SNU-16 cells.

[0097] Figure 5 shows the cytotoxic effects of DMDM-conjugated DM-9832 (Tool) and DM- 9648 (Lead) antibodies on SNU-16 cells.

[0098] Figures 6A and 6B show the cytotoxic effects of Exatecan-conjugated DM-9832 in cells (Figure 6A) and in a AsPC-1 xenograft model (Figure 6B).

[0099] Figures 7A-7F show tumor growth inhibition (TGI) efficiency of ADCs comprising DM-9648 in colorectal PDX. Mice implanted with CTG-2351 (Figure 7A), CTG-0063 (Figure 7B), CTG-0923 (Figure 7C), CTG-0652 (Figure 7D), and CTG-0864 (Figure 7E) were treated with CO-ADC-005, CO-ADC-009, or CO-ADC-010, and the volume of the tumors measured. Figure 7F shows TGI efficiency of CO-ADC-010 and CO-ADC-09 across all models.DETAILED DESCRIPTION OF THE INVENTIONAnti-CDH17 Binding Molecules

[0100] In some embodiments, disclosed herein is an isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101 , 111, 121, 131, 141 , 151, 161, 171, 181, 191, 201, 211, or 221 ; a second CDR (CDRH2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, or 222; and a third CDR (CDRH3) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 1 13, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, or 223; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, or 224; a second CDR (CDRL2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145,155, 165, 175, 185, 195, 205, 215, or 225; and a third CDR (CDRL3) comprising an amino acid sequence of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146,156, 166, 176, 186, 196, 206, 216, or 226.

[0101] In some embodiments, disclosed herein is an isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid as set forth in SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141, 151, 161, 171, 181, 191, 201, 211, or 221; a second CDR (CDRH2) comprising an amino acid sequence as set forth in SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, or 222; and a third CDR (CDRH3) comprising an amino acid sequence as set forth in SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, or 223; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence as set forth in SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, or 224; a second CDR (CDRL2) comprising an amino acid sequence as set forth in SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, or 225; and a third CDR (CDRL3) comprising an amino acid sequence as set forth in SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136,146, 156, 166, 176, 186, 196, 206, 216, or 226.

[0102] An artisan would appreciate that the term "homology" refers to the similarity between two or more polynucleotide or polypeptide sequences. This similarity is often measured by comparing nucleotide sequences using algorithms such as BLAST (Basic Local Alignment Search Tool) or sequence alignment methods like Needleman-Wunsch or Smith-Waterman. Thus, at least 80% homology implies that when the two sequences (DNA, RNA, or protein) are aligned and compared by any of those methods, at least 80% of their positions exhibit identical or similar nucleotides or amino acids.

[0103] An artisan would appreciate that the 80% homology threshold is considered robust enough to infer a meaningful relationship between two sequences. Sequences having homology of at least 80% comprises sequences that are 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% homologous. Further, an artisan would appreciate that an homology score comprises both identical matches and similar matches, i.e., conservative substitutions. In some embodiments, the terms “homology” and “identity” are used herein interchangeably. However, “homology” can be also understood to “similarity”, meaning that the positions are either the same or similar enough to have the same function and structure. Sequence alignment algorithms use scoring matrices like PAM or BLOSUM assess similarity, where similar amino acids receive positive scores.

[0104] In some embodiments, disclosed herein is an isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 1; a second CDR (CDRH2) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 2; and a third CDR (CDRH3) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 3; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 4; a second CDR (CDRL2) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 5; and a third CDR (CDRL3) comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 6. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9832, or DM-9832, having all the same features and limitations.

[0105] In some embodiments, ATX-9832, or DM-9832, comprises a heavy chain variableregion comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 8; or a heavy chain variable region comprising SEQ ID NO: 7 and a light chain variable region comprising SEQ ID NO: 8.

[0106] In some embodiments, ATX-9832, or DM-9832, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 9, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 10.

[0107] In some embodiments, disclosed herein is an isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 11; a second CDR (CDRH2) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 12; and a third CDR (CDRH3) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 13; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO:14; a second CDR (CDRL2) comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 15; and a third CDR (CDRL3) comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 16. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9464, or DM-9464, having all the same features and limitations.

[0108] In some embodiments, ATX-9464, or DM-9464, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 17 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 18; or a heavy chain variable region comprising SEQ ID NO: 17 and a light chain variable region comprising SEQ ID NO: 18.

[0109] In some embodiments, ATX-9464, or DM-9464, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 19, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 20.

[0110] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as setforth in, or having at least 80% homology to SEQ ID NO: 21 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 22; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 23 ; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 24; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 25; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 26. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9476, or DM-9476, having all the same features and limitations.

[0111] In some embodiments, ATX-9476, or DM-9476, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 27 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 28; or a heavy chain variable region comprising SEQ ID NO: 27 and a light chain variable region comprising SEQ ID NO: 28.

[0112] In some embodiments, ATX-9476, or DM-9476, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 29, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 30.

[0113] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 31 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 32; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 33; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 34; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 35; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 36. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9491, or DM-9491, having all the same features and limitations.

[0114] In some embodiments, ATX-9491 , or DM-9491 , comprises a heavy chain variableregion comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 37 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 38; or a heavy chain variable region comprising SEQ ID NO: 37 and a light chain variable region comprising SEQ ID NO: 38.

[0115] In some embodiments, ATX-9491 , or DM-9491 , comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 39, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 40.

[0116] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 41 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 42; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 43; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 44; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 45; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 46. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9509, or DM-9509, having all the same features and limitations.

[0117] In some embodiments, ATX-9509, or DM-9509, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 47 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 48; or a heavy chain variable region comprising SEQ ID NO: 47 and a light chain variable region comprising SEQ ID NO: 48.

[0118] In some embodiments, ATX-9509, or DM-9509, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 49, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 50.

[0119] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 51 ; a CDRH2 comprising an aminoacid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 52; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 53; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 54; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 55; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 56. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9558, or DM-9558, having all the same features and limitations.

[0120] In some embodiments, ATX-9558, or DM-9558, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 57 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 58; or a heavy chain variable region comprising SEQ ID NO: 57 and a light chain variable region comprising SEQ ID NO: 58.

[0121] In some embodiments, ATX-9558, or DM-9558, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 59, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 60.

[0122] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 61 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 62; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 63; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 64; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 65; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 66. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9580, or DM-9580, having all the same features and limitations.

[0123] In some embodiments, ATX-9580, or DM-9580, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 67and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 68; or a heavy chain variable region comprising SEQ ID NO: 67 and a light chain variable region SEQ ID NO: 68.

[0124] In some embodiments, ATX-9580, or DM-9580, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 69, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 70.

[0125] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 71 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 72; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 73 ; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 74; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 75; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 76. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9591, or DM-9591, having all the same features and limitations.

[0126] In some embodiments, ATX-9591, or DM-9591, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 77 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 78; or a heavy chain variable region comprising SEQ ID NO: 77 and a light chain variable region comprising SEQ ID NO: 78.

[0127] In some embodiments, ATX-9591, or DM-9591, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 79, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 80.

[0128] In some embodiments, disclosed herein is an anti-CDHl 7 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 81 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 82; and aCDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 83; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 84; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 85; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 86. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9597, or DM-9597, having all the same features and limitations.

[0129] In some embodiments, ATX-9597, or DM-9597, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 87 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 88; or a heavy chain variable region comprising SEQ ID NO: 87 and a light chain variable region comprising SEQ ID NO: 88.

[0130] In some embodiments, ATX-9597, or DM-9597, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 89, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 90.

[0131] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 91 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 92; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 93 ; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 94; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 95; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 96. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9616, or DM-9616, having all the same features and limitations.

[0132] In some embodiments, ATX-9616, or DM-9616, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 97 and a light chain variable region comprising an amino acid sequence having at least 80%homology to SEQ ID NO: 98; or a heavy chain variable region comprising SEQ ID NO: 97 and a light chain variable region comprising SEQ ID NO: 98.

[0133] In some embodiments, ATX-9616, or DM-9616, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 99, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 100.

[0134] In some embodiments, disclosed herein is an anti-CDHl 7 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 101 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 102; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 103; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 104; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 105; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 106. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9620, or DM-9620, having all the same features and limitations.

[0135] In some embodiments, ATX-9620, or DM-9620, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 107 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 108; or a heavy chain variable region comprising SEQ ID NO: 107 and a light chain variable region comprising SEQ ID NO: 108.

[0136] In some embodiments, ATX-9620, or DM-9620, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 109, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 110.

[0137] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 111 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 112; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homologyto SEQ ID NO: 113; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 114; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 115; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 116. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9621, or DM-9621, having all the same features and limitations.

[0138] In some embodiments, ATX-9620, or DM-9620, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 117 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 118; or a heavy chain variable region comprising SEQ ID NO: 117 and a light chain variable region comprising SEQ ID NO: 118.

[0139] In some embodiments, ATX-9620, or DM-9620, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 119, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 120.

[0140] In some embodiments, disclosed herein is an anti-CDHl 7 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 121 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 122; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 123; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 124; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 125; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 126. An anti-CDHl 7 binding molecule comprising said sequences is termed herein ATX-9628, or DM-9628, having all the same features and limitations.

[0141] In some embodiments, ATX-9628, or DM-9628, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 127 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 128; or a heavy chain variable region comprising SEQ ID NO: 127and a light chain variable region comprising SEQ ID NO: 128.

[0142] In some embodiments, ATX-9628, or DM-9628, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 129, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 130.

[0143] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 131 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 132; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 133; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 134; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 135; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 136. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9648, or DM-9648, having all the same features and limitations.

[0144] In some embodiments, ATX-9648, or DM-9648, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 137 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 138; or a heavy chain variable region comprising SEQ ID NO: 137 and a light chain variable region comprising SEQ ID NO: 138.

[0145] In some embodiments, ATX-9648, or DM-9648, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 139, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 140.

[0146] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 141 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 142; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 143; and a light chain variable region comprising a CDRL1 comprising anamino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 144; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 145; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 146. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9649, or DM-9649, having all the same features and limitations.

[0147] In some embodiments, ATX-9649, or DM-9649, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 147 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 148; or a heavy chain variable region comprising SEQ ID NO: 147 and a light chain variable region comprising SEQ ID NO: 148.

[0148] In some embodiments, ATX-9649, or DM-9649, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 149, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 150.

[0149] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 151 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 152; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 153; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 154; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 155; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 156. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9701 , or DM-9701 , having all the same features and limitations.

[0150] In some embodiments, ATX-9701, or DM-9701, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 157 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 158; or a heavy chain variable region comprising SEQ ID NO: 157 and a light chain variable region comprising SEQ ID NO: 158.

[0151] In some embodiments, ATX-9701, or DM-9701, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 159, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 160.

[0152] In some embodiments, disclosed herein is an anti-CDHl 7 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 161 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 162; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 163; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 164; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 165; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 166. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9706, or DM-9706, having all the same features and limitations.

[0153] In some embodiments, ATX-9706, or DM-9706, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 167 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 168; or a heavy chain variable region comprising SEQ ID NO: 167 and a light chain variable region comprising SEQ ID NO: 168.

[0154] In some embodiments, ATX-9706, or DM-9706, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 169, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 170.

[0155] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 171 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 172; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 173; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 174; aCDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 175; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 176. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9746, or DM-9746, having all the same features and limitations.

[0156] In some embodiments, ATX-9746, or DM-9746, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 177 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 178; or a heavy chain variable region comprising SEQ ID NO: 177 and a light chain variable region comprising SEQ ID NO: 178.

[0157] In some embodiments, ATX-9746, or DM-9746, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 179, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 180.

[0158] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 181 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 182; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 183; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 184; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 185; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 186. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9762, or DM-9762, having all the same features and limitations.

[0159] In some embodiments, ATX-9762, or DM-9762, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 187 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 188; or a heavy chain variable region comprising SEQ ID NO: 187 and a light chain variable region comprising SEQ ID NO: 188.

[0160] In some embodiments, ATX-9762, or DM-9762, comprises a heavy chain regioncomprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 189, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 190.

[0161] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 191 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 192; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 193; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 194; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 195; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 196. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9773, or DM-9773, having all the same features and limitations.

[0162] In some embodiments, ATX-9773, or DM-9773, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 197 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 198; or a heavy chain variable region comprising SEQ ID NO: 197 and a light chain variable region comprising SEQ ID NO: 198.

[0163] In some embodiments, ATX-9773, or DM-9773, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 199, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 200.

[0164] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 201 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 202; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 203; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 204; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homologyto SEQ ID NO: 205; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 206. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9780, or DM-9780, having all the same features and limitations.

[0165] In some embodiments, ATX-9780, or DM-9780, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 207 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 208; or a heavy chain variable region comprising SEQ ID NO: 207 and a light chain variable region comprising SEQ ID NO: 208.

[0166] In some embodiments, ATX-9780, or DM-9780, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 209, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 210.

[0167] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 211 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 212; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 213; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 214; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 215; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 216. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9787, or DM-9787, having all the same features and limitations.

[0168] In some embodiments, ATX-9787, or DM-9787, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 217 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 218; or a heavy chain variable region comprising SEQ ID NO: 217 and a light chain variable region comprising SEQ ID NO: 218.

[0169] In some embodiments, ATX-9787, or DM-9787, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQID NO: 219, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 220.

[0170] In some embodiments, disclosed herein is an anti-CDH17 binding molecule comprising a heavy chain variable region comprising a CDRH1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 221 ; a CDRH2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 222; and a CDRH3 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 223; and a light chain variable region comprising a CDRL1 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 224; a CDRL2 comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 225; and a CDRL3 comprising an amino acid sequence as set forth in, or of having at least 80% homology to SEQ ID NO: 226. An anti-CDH17 binding molecule comprising said sequences is termed herein ATX-9814, or DM-9814, having all the same features and limitations.

[0171] In some embodiments, ATX-9814, or DM-9814, comprises a heavy chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 227 and a light chain variable region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 228; or a heavy chain variable region comprising SEQ ID NO: 227 and a light chain variable region comprising SEQ ID NO: 228.

[0172] In some embodiments, ATX-9814, or DM-9814, comprises a heavy chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 229, and a light chain region comprising an amino acid sequence as set forth in, or having at least 80% homology to SEQ ID NO: 230.

[0173] Table 1 shows the polypeptide sequences referenced in regard to the anti-CDH17 binding molecules. The table further shows the names used herein to denominate the binding molecules having said sequences, which are used among others in the Examples section below.

[0174] Table 1. Sequences.

[0175] A skilled artisan would appreciate that the term “binding molecule” can be used interchangeably with the terms “antibody” and “immunoglobulin”, having all the same qualities and meanings. In some embodiments, a binding molecule comprises an antibody binding domain, an antigen binding site, a fragment of an antibody, or a genetically engineered product of one or more fragments of an antibody. In some embodiments, a binding molecule can be combined with molecules other than an antibody, as a chimeric antigen receptor (CAR).

[0176] The anti-CDH17 presented herein specifically binds CDH17, which means that the binding is selective for a CDH17 antigen, and it can be discriminated from unwanted or nonspecific interactions. For example, an binding molecule is said to specifically bind a CDH17 epitope when the equilibrium dissociation constant is < IO-5, 10"6, or 10‘7M. In some embodiments, the equilibrium dissociation constant may be < 10"8M or 10"9M. In some further embodiments, the equilibrium dissociation constant may be < IO-10M, 10’11M, or 1012M. In some embodiments, the equilibrium dissociation constant may be in the range of < 10sM to 10’12M.

[0177] “Epitope” or “antigenic determinant” refers to a site on an antigen to which an antibody binds. Epitopes can be formed both from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation.

[0178] In some embodiments, an anti-CDH17 binding molecule comprises an antibody or an antibody fragment or fragments with binding specificity including, but not limited to, IgG, heavy chain variable regions (VH), light chain variable regions (VL), Fab fragments, F(ab')2 fragments, scFv fragments, Fv fragments, a nanobody, minibodies, diabodies, triabodies, tetrabodies, and single domain antibodies. Also encompassed are humanized, primatized, and chimeric antibodies as these terms are generally understood in the art. Further, In some embodiments, the anti-CDH17binding molecule comprises a monoclonal antibody.

[0179] In some embodiments, the IgG is an IgGl. In some embodiments, the IgG is an IgG2. In some embodiments, the IgG is an IgG3. In some embodiments, the IgG is an IgG4.

[0180] As used herein, the term “heavy chain variable region” may be used interchangeably with the term “VH domain” or the term “VH”, having all the same meanings and qualities. As used herein, the term “light chain variable region” may be used interchangeably with the term “VL domain” or the term “VL”, having all the same meanings and qualities. A skilled artisan would recognize that a “heavy chain variable region” or “VH” with regard to an antibody encompasses the fragment of the heavy chain that contains three complementarity determining regions (CDRs) interposed between flanking stretches known as framework regions. The framework regions are more highly conserved than the CDRs, and form a scaffold to support the CDRs. Similarly, a skilled artisan would also recognize that a “light chain variable region” or “VL” with regard to an antibody encompasses the fragment of the light chain that contains three CDRs interposed between framework regions.

[0181] As used herein, the term “complementarity determining region” or “CDR” refers to the hypervariable region(s) of a heavy or light chain variable region. Proceeding from the N-terminus, each of a heavy or light chain polypeptide has three CDRs denoted as “CDR1 ,” “CDR2,” and “CDR3”. Crystallographic analysis of a number of antigen-antibody complexes has demonstrated that the amino acid residues of CDRs form extensive contact with a bound antigen, wherein the most extensive antigen contact is with the heavy chain CDR3. Thus, the CDR regions are primarily responsible for the specificity of an antigen-binding site. In one embodiment, an antigenbinding site includes six CDRs, comprising the CDRs from each of a heavy and a light chain variable region. In some embodiments, a CDR of the heavy chain is termed herein CDRH. In some embodiments, a CDR of the light chain is termed herein CDRL.

[0182] In some embodiments, the anti-CDH17 binding molecule comprises a scFv, which is a fusion polypeptide comprising the variable heavy chain (VH) and variable light chain (VL) regions of an immunoglobulin, connected by a short linker peptide. The linker may have, for example, 10 to about 25 amino acids.

[0183] In some embodiments, the anti-CDH17 binding molecule comprises a Fab, which is a portion of an antibody consisting of a single light chain (both variable and constant regions) bound to the variable region and first constant region of a single heavy chain by a disulfide bond. In some embodiments, the anti-CDH17 binding molecule comprises a F(ab')2, which is a fragment of aheavy chain comprising a VH domain and a light chain comprising a VL domain.

[0184] In some embodiments, the anti-CDH17 binding molecule comprises a whole antibody molecules, including monoclonal and polyclonal antibodies. In some embodiments, the anti- CDH17 binding molecule comprises an antibody fragment or fragments that retain binding specificity including, but not limited to, variable heavy chain (VH) fragments, variable light chain (VL) fragments, Fab fragments, F(ab')2 fragments, scFv fragments, Fv fragments, minibodies, diabodies, triabodies, and tetrabodies.

[0185] In some embodiments, the anti-CDH17 binding molecule comprises a chimeric antibody. A “chimeric antibody” is an immunoglobulin molecule in which the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and / or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.

[0186] In some embodiments, the anti-CDH17 binding molecules of the present comprise humanized antibodies. A “humanized antibody” is an immunoglobulin molecule which contains minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody). In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In some embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin consensus sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. Methods for humanizing antibodies are disclosed in the art and therefore available to the artisan.

[0187] In some embodiments, the anti-CDH17 binding molecules of the present disclosure are bispecific (or multi-specific) antibodies. As it is generally known in the art, a bispecific antibody is a recombinant protein that includes antigen-binding fragments of two different monoclonal antibodies, and is thereby capable of binding two different antigens. In some embodiments, thebispecific antibodies are monoclonal, preferably human or humanized, and have binding specificities for at least one other antigen besides CDH17, or for different CDH17 epitopes. Similarly, a multi-specific antibody is a recombinant protein that includes antigen-binding fragments of at least two different monoclonal antibodies, such as two, three or four different monoclonal antibodies.

[0188] In another embodiment, one of ordinary skill in the art would readily use the anti-CDH17 binding molecule, or the VH, VL, and / or the CDRs disclosed herein to construct chimeric antigen receptor (CAR) that would have binding specificity to CDH17.

[0189] In one embodiment, the anti-CDH17 antibody or an antigen binding fragment thereof may comprise one or more Fc domain mutations that impair binding to the FcyR receptor (e.g. Fcyl, Fcylla, FcyITb,or FcyRIIIa). Any suitable Fc domain mutants can be used so that the resulting Fc domain binding to the FcyR receptor is reduced, e.g. by at least 50% relative to that with a nonmutated Fc domain. Fc mutations and truncations that can be made to reduce binding to the FcyR receptor can be made by those of skill in the art based on techniques well-known in the art.

[0190] In another embodiment, the anti- CDH17 binding molecules or anti- CDH17 antibodies of the present disclosure may be modified to extend half-life, such as by attaching at least one molecule to the antibody for extending serum half-life, including but not limited to a polyethlyene glycol (PEG) group, serum albumin, transferrin, transferrin receptor or the transferrin-binding portion thereof, or combinations thereof. As used herein, the word “attached” refers to a covalently or noncovalently conjugated substance. The conjugation may be by genetic engineering or by chemical means.

[0191] In some embodiments, disclosed herein is a polynucleotide encoding the anti-CD17 binding molecules. In some embodiments, disclosed herein is a polynucleotide encoding any of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 of the anti-CD17 binding molecules disclosed herein.

[0192] A skilled artisan would appreciate that, given the amino acid sequences as provided herein, it is possible to design a number of polynucleotide sequences encoding such sequences. In some embodiments, the whole anti-CDH17 is encoded by a single polynucleotide. In some embodiments, different parts of the anti-CDH17 are encoded by different polynucleotides.

[0193] In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9832. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9464. In some embodiments, disclosed herein is a vectorcomprising a polynucleotide encoding DM-9476. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9491. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9509.

[0194] In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9558. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9580. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9591. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9597. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9616.

[0195] In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9620. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9621. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9628. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9648. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9649.

[0196] In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9701. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9706. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9746. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9762. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9773. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9780. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM-9787. In some embodiments, disclosed herein is a vector comprising a polynucleotide encoding DM- 9814.

[0197] These vectors may include chemical conjugates which have a targeting moiety (e.g ., a ligand to a cellular surface receptor), and a nucleic acid binding moiety (e.g., poly lysine), viral vector (e.g., a DNA or RNA viral vector), fusion proteins containing a target moiety (e.g., an antibody specific for a target cell) and a nucleic acid binding moiety (e.g., a protamine), plasmids, phage, etc. The vectors can be chromosomal, non-chromosomal or synthetic.

[0198] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9832. In some embodiments, disclosed herein is a host cell comprising anexpression vector encoding DM-9464. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9476. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9491.

[0199] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9509. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9558. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9580. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9591.

[0200] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9597. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9616. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9620. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9621.

[0201] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9628. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9648. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9649. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9701.

[0202] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9706. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9746. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9762. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9773.

[0203] In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9780. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9787. In some embodiments, disclosed herein is a host cell comprising an expression vector encoding DM-9814.

[0204] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9832 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9464 and a drug conjugate comprising cleavable linker and a cytotoxic pay load. In some embodiments, disclosed herein is an antibody-drugconjugate (ADC) comprising the binding molecule DM-9476 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0205] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9491 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9509 and a drug conjugate comprising cleavable linker and a cytotoxic pay load. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9558 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0206] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9580 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9591 and a drug conjugate comprising cleavable linker and a cytotoxic pay load. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9597 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0207] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9616 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody -drug conjugate (ADC) comprising the binding molecule DM-9620 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9621 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0208] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9628 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody -drug conjugate (ADC) comprising the binding molecule DM-9648 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9649 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0209] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9701 and a drug conjugate comprising cleavable linkerand a cytotoxic payload. In some embodiments, disclosed herein is an antibody -drug conjugate (ADC) comprising the binding molecule DM-9706 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9746 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0210] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9762 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody -drug conjugate (ADC) comprising the binding molecule DM-9773 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9780 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0211] In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9787 and a drug conjugate comprising cleavable linker and a cytotoxic payload. In some embodiments, disclosed herein is an antibody-drug conjugate (ADC) comprising the binding molecule DM-9814 and a drug conjugate comprising cleavable linker and a cytotoxic payload.

[0212] A skilled artisan would appreciate that an ADC is usually composed of three main components: a monoclonal antibody, a cytotoxic pay load, and a cleavable linker moiety connecting the two. The cytotoxic payload with the cleavable linker are also termed herein the “drug conjugate”. The monoclonal antibody serves as a targeted vehicle, selectively binding to CDH17 expressed on cancer cell surface, thereby facilitating the specific delivery of the cytotoxic payload to malignant cells. This targeted approach minimizes off- target effects, reducing systemic toxicity and enhancing the therapeutic index of the ADC.

[0213] In some embodiments, the cytotoxic payload comprises a small molecule toxin, such as auristatins and maytansinoids. The linker connecting the antibody and the payload plays a pivotal role in controlling the release of the cytotoxic agent within the target cell. Cleavable linkers is usually sensitive to intracellular conditions. In some embodiments, the cleavable linker is sensitive to an enzymatic activity or the intracellular pH. When cleaved, the linker enables the efficient release of the payload upon internalization of the ADC by the cancer cell. In some embodiments, the ADC comprises a non-cleavable linkers, which may rely on lysosomal degradation for payload release.

[0214] In some embodiments, the ADC drug conjugate comprises exatecan. Exatecan, also known as DX-895H and Exa, is a potent chemotherapeutic agent belonging to the class of topoisomerase I inhibitors. Its mechanism of action involves the stabilization of the DNA- topoisomerase I complex, preventing the re-ligation of single-strand breaks during DNA replication. This interference leads to the accumulation of DNA damage, ultimately triggering apoptosis in rapidly dividing cancer cells. Exatecan has shown considerable efficacy in preclinical and clinical studies, particularly in the treatment of various solid tumors, including lung, breast, and gastrointestinal cancers.

[0215] In some embodiments, the ADC drug conjugate comprises tesirine. Tesirine is a novel and potent pyrrolobenzodiazepine (PBD) dimer, which has been used as a cytotoxic payload when conjugated for example to anti-CD19. In some embodiments, the tesirine conjugates to the anti-CDH17 antibody via a valine- alanine cleavable, maleimide linker. An artisan would appreciate that tesirine exerts its cytotoxic effects by binding to the minor groove of DNA, resulting in DNA cross-linking and subsequent inhibition of cell division. This distinctive mode of action imparts tesirine with remarkable potency against rapidly dividing cancer cells. In some embodiments, tesirine comprises the cytotoxic drug payload pyrrolobenzodiazepine dimer cytotoxic DNA-alkylating agent (SG3199).

[0216] In some embodiments, the ADC drug conjugate comprises deruxtecan. Deruxtecan, that has been conjugated to an antibody targeting CDH17, comprises a linker molecule, and a cytotoxic payload. The cytotoxic payload is exatecan, a topoisomerase I inhibitor that induces double-strand DNA breaks in the cancer cell nucleus resulting in inhibition of cell proliferation. Deruxtecan further comprises a glycine-glycine-phenylalanine-glycine (GGFG) tetrapeptide- based linker and a self-immolative amino methylene spacer.

[0217] In some embodiments, the ADC drug conjugate comprises MMAE. MMAE, or Monomethyl Auristatin E, is a cytotoxic agent that can be used as the payload in ADCs. It is a synthetic analog of dolastatin 10, a natural product derived from marine organisms.

[0218] In some embodiments, the cleavable linker comprises a hydrazone linker. In some embodiments, the cleavable linker comprises a disulphide linker. In some embodiments, the cleavable linker comprises a peptide linker. In some embodiments, the cleavable linker comprises a dipeptide linker selected from the group consisting of valine-citrulline (Val-Cit), vaiine-alanine (Val-Ala), alanine-alanine (Ala-Ala), and a GGFG linker. In some embodiments, there is further the dipeptide linker is joined to the cytotoxic payload by thespacer unit / ?ara-aminobenzyloxycarbonyl (PABC). In some embodiments, the peptide linker is a tripeptide linker comprising a glutamic acid-valine-citrulline (EVCit). In some embodiments, the glutamic acid-valine-citrulline (EVCit) tripeptide linker is joined to a meta- amide pura-aminobenzyl carbamate (MA-PABC) group.

[0219] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9832 and a drug conjugate comprising duarcomycin (DMDM). In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM- 9832 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9464 and a drug conjugate comprising DMDM.

[0220] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9476 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9491 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9509 and a drug conjugate comprising DMDM.

[0221] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9558 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9580 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9591 and a drug conjugate comprising DMDM.

[0222] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9597 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDHl 7 binding molecule DM-9616 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9620 and a drug conjugate comprising DMDM.

[0223] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9621 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9628 and adrug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9648 and a drug conjugate comprising DMDM.

[0224] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9649 and a drug conjugate comprising DMDM. In some embodiments, disclosedherein is an ADC comprising the anti-CDH17 binding molecule DM-9701 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9706 and a drug conjugate comprising DMDM.

[0225] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9746 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9762 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti- CDH17 binding molecule DM-9773 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM- 9780 and a drug conjugate comprising DMDM.

[0226] In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9787 and a drug conjugate comprising DMDM. In some embodiments, disclosed herein is an ADC comprising the anti-CDH17 binding molecule DM-9814 and a drug conjugate comprising DMDM.

[0227] A skilled artisan would appreciate that the drug-to-antibody ratio (DAR), i.e. the average number of drug molecules conjugated to a single monoclonal antibody within the ADC construct, can he determined by methods known in the art to optimize the ADC. The DAR can be optimized to influence the pharmacokinetics, efficacy, and safety profile of the ADC. While a higher DAR enhances the cytotoxic pay load delivered to cancer cells, it may lead to compromised stability, increased off-target toxicity, and altered pharmacokinetics.

[0228] In some embodiments, the DAR is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the DAR is 2.1. In some embodiments, the DAR is 8.

[0229] In some embodiments, disclosed herein is an ADC comprising DM-9648 conjugated to Deruxtecan. In some embodiments, disclosed herein is an ADC comprising DM-9648 conjugated to MMAE. In some embodiments, the DAR between DM-9648 and Deruxtecan is 8. In some embodiments, the DAR between DM-9648 and Deruxtecan is 4.Pharmaceutical Compositions

[0230] In one embodiment, the present disclosure provides a composition comprising the anti- CDH17 binding molecules disclosed herein and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers of use are well-known in the art. For example, Remington's Pharmaceutical Sciences, by E.W. Martin, Mack Publishing Co., Easton, PA, 23rd Edition, 2020 describes compositions and formulations suitable for pharmaceutical delivery ofbinding molecules and antibodies disclosed herein.

[0231] In one embodiment, the pharmaceutical composition comprises DM-9832 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9464 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9476 and a pharmaceutically acceptable carrier.

[0232] In one embodiment, the pharmaceutical composition comprises DM-9491 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9509 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9558 and a pharmaceutically acceptable carrier.

[0233] In one embodiment, the pharmaceutical composition comprises DM-9580 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9591 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9597 and a pharmaceutically acceptable carrier.

[0234] In one embodiment, the pharmaceutical composition comprises DM-9616 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9620 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9621 and a pharmaceutically acceptable carrier.

[0235] In one embodiment, the pharmaceutical composition comprises DM-9628 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9648 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9649 and a pharmaceutically acceptable carrier.

[0236] In one embodiment, the pharmaceutical composition comprises DM-9701 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9706 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9746 and a pharmaceutically acceptable carrier.

[0237] In one embodiment, the pharmaceutical composition comprises DM-9762 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9773 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises DM-9780 and a pharmaceutically acceptable carrier.

[0238] In one embodiment, the pharmaceutical composition comprises DM-9787 and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical compositioncomprises DM-9814 and a pharmaceutically acceptable carrier.

[0239] In some embodiments, the pharmaceutical composition an ADC comprising DM-9832; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9464; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9476; and a pharmaceutically acceptable carrier.

[0240] In some embodiments, the pharmaceutical composition an ADC comprising DM-9491; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9509; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9558; and a pharmaceutically acceptable carrier.

[0241] In some embodiments, the pharmaceutical composition an ADC comprising DM-9580; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9591 ; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9597; and a pharmaceutically acceptable carrier.

[0242] In some embodiments, the pharmaceutical composition an ADC comprising DM-9616; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9620; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9621 ; and a pharmaceutically acceptable carrier.

[0243] In some embodiments, the pharmaceutical composition an ADC comprising DM-9628; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9648; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9649; and a pharmaceutically acceptable carrier.

[0244] In some embodiments, the pharmaceutical composition an ADC comprising DM-9701; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9706; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9746; and a pharmaceutically acceptable carrier.

[0245] In some embodiments, the pharmaceutical composition an ADC comprising DM-9762;and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9773; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9780; and a pharmaceutically acceptable carrier.

[0246] In some embodiments, the pharmaceutical composition an ADC comprising DM-9787; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition an ADC comprising DM-9814; and a pharmaceutically acceptable carrier.

[0247] In some embodiments, the ADC comprises exatecan, DMDM, deruxtecan, or MMAE. In some embodiments, the ADC comprises exatecan. In some embodiments, the ADC comprises DMDM. In some embodiments, the ADC comprises deruxtecan. In some embodiments, the ADC comprises MMAE.

[0248] One of ordinary skill in the art would readily incorporate the anti-CDH17 binding molecules disclosed herein into therapeutics that target cells expressing CDH17. Examples of such therapeutic modalities include, but are not limited to, monoclonal antibodies, antibody drug conjugates, chimeric antigen receptor T-cells, and chimeric antigen receptor natural killer cells.

[0249] A composition comprising an anti- CDH17 binding molecule or an antigen-binding fragment thereof as disclosed herein can be administered to a subject (e.g. a human or an animal) alone, or in combination with a carrier, i.e., a pharmaceutically acceptable carrier. By pharmaceutically acceptable is meant a material that is not biologically or otherwise undesirable, i.e., the material can be administered to a subject without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained. As would be well-known to one of ordinary skill in the art, the carrier is selected to minimize any degradation of the polypeptides disclosed herein and to minimize any adverse side effects in the subject. The pharmaceutical compositions may be prepared by methodologies well known in the pharmaceutical art.

[0250] In some embodiments, the present disclosure provides a composition comprising a polynucleotide sequence encoding the anti-CDH17 disclosed herein.

[0251] The compositions comprising the anti-CDH17 binding molecules or antibodies, or the polynucleotide sequences encoding thereof, can be administered (e.g., to a mammal, a cell, or a tissue) in any suitable manner depending on whether local or systemic treatment is desired. For example, the composition can be administered topically, ophthalmically, vaginally,rectally, intranasally, transdermally, orally, by inhalation, or parenterally, including by intravenous drip or subcutaneous, intracavity, intraperitoneal, intradermal, or intramuscular injection. Topical intranasal administration refers to delivery of the compositions into the nose and nasal passages through one or both of the nares. The composition can be delivered by a spraying mechanism or droplet mechanism, or through aerosolization. Alternatively, administration can be intratumoral, e.g. local or intravenous injection.

[0252] If the composition is to be administered parenterally, the administration is generally by injection. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for suspension in liquid prior to injection, or as emulsions. Additionally, parental administration can involve preparation of a slow-release or sustained- release system so as to maintain a constant dosage.Methods of Treatment

[0253] As used herein, the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0254] As used herein, “modulating” refers to “stimulating” or “inhibiting” an activity of a molecular target or pathway. For example, a composition modulates the activity of a molecular target or pathway if it stimulates or inhibits the activity of the molecular target or pathway by at least 10%, by at least about 20%, by at least about 25%, by at least about 30%, by at least about 40%, by at least about 50%, by at least about 60%, by at least about 70%, by at least about 75%, by at least about 80%, by at least about 90%, by at least about 95%, by at least about 98%, or by about 99% or more relative to the activity of the molecular target or pathway under the same conditions but lacking only the presence of the composition. In another example, a composition modulates the activity of a molecular target or pathway if it stimulates or inhibits the activity of the molecular target or pathway by at least 2-fold, at least 5 -fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold relative to the activity of the molecular target or pathway under the same conditions but lacking only the presence of the composition. The activity of a molecular target or pathway may be measured by any reproducible means. The activity of a molecular target or pathway may be measured in vitro or in vivo. For example, the activity of a molecular target or pathway may be measured in vitro or in vivo by an appropriate assay known in the art measuring the activity. Control samples(untreated with the composition) can be assigned a relative activity value of 100%.

[0255] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9832. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9464.

[0256] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9476. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9491.

[0257] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9509. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9558.

[0258] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9580. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9591.

[0259] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9597. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9616.

[0260] In some embodiments, the present disclosure provides a method of treating orpreventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9620. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9621.

[0261] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9628. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9648.

[0262] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9649. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9701.

[0263] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9706. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9746.

[0264] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9762. In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9773.

[0265] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9780. In some embodiments, thepresent disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9787.

[0266] In some embodiments, the present disclosure provides a method of treating or preventing a medical condition associated with CDH17 in a subject, comprising the step of administering to the subject a composition comprising DM-9814.

[0267] In one embodiment, the composition comprises antibody drug conjugates as disclosed herein. In one embodiment, the antibody drug conjugates comprise Exatecan. In one embodiment, the antibody drug conjugates comprise DMDM. In one embodiment, the antibody drug conjugates comprise Deruxtecan. In one embodiment, the antibody drug conjugates comprise MMAE.

[0268] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9832. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9464.

[0269] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9476. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9491.

[0270] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9509. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9558.

[0271] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9580. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9591.

[0272] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9597. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9616.

[0273] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9620. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9621.

[0274] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9628. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9648.

[0275] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9649. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9701.

[0276] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9706. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9746.

[0277] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9762. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9773.

[0278] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9780. In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9787.

[0279] In another embodiment, disclosed herein is a method of treating cancer in a subject, comprising the step of administering to the subject a composition comprising DM-9814.

[0280] In one embodiment, the disease comprises any cancer or tumor cells that express CDH17. In some embodiments, the cancer comprises gastric cancer. In some embodiments, the cancer comprises pancreatic cancer. In some embodiments, the cancer comprises colon cancer. In some embodiments, the cancer comprises colorectal cancer.

[0281] In another embodiment, the disease is a cancer selected from carcinoma, sarcoma,lymphoma, leukemia, germ cell tumor, blastoma, chondrosarcoma, Ewing’s sarcoma, malignant fibrous histiocytoma of bone, osteosarcoma, rhabdomyosarcoma, heart cancer, brain cancer, astrocytoma, glioma, medulloblastoma, neuroblastoma, breast cancer, medullary carcinoma, adrenocortical carcinoma, thyroid cancer, Merkel cell carcinoma, eye cancer, gastrointestinal cancer, colon cancer, colorectal cancer, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, hepatocellular cancer, pancreatic cancer, rectal cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, renal cell carcinoma, prostate cancer, testicular cancer, urethral cancer, uterine sarcoma, vaginal cancer, head cancer, neck cancer, nasopharyngeal carcinoma, hematopoetic cancer, Non-hodgkin lymphoma, skin cancer, basal-cell carcinoma, melanoma, small cell lung cancer, non-small cell lung cancer, or any combination thereof.

[0282] As used herein, the terms “treat”, “treatment”, or “therapy” (as well as different forms thereof) refer to therapeutic treatment, including prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological change associated with a disease or condition. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of the extent of a disease or condition, stabilization of a disease or condition (i.e., where the disease or condition does not worsen), delay or slowing of the progression of a disease or condition, amelioration or palliation of the disease or condition, and remission (whether partial or total) of the disease or condition, whether detectable or undetectable. Those in need of treatment include those already with the disease or condition as well as those prone to having the disease or condition or those in which the disease or condition is to be prevented.

[0283] The terms "subject," "individual," and "patient" are used interchangeably herein, and refer to human or non-human animals to whom treatment with a composition or formulation in accordance with the present disclosure is provided. The terms "non-human animals" and "non- human mammals" are used interchangeably herein and include all vertebrates, e.g., mammals, such as non-human primates (e.g. higher primates), sheep, dog, rodent (e.g. mouse or rat), guinea pig, goat, pig, cat, rabbits, cows, horses, or non-mammals such as reptiles, amphibians, chickens, and turkeys. The compositions described herein can be used to treat any suitable mammal, including primates, such as monkeys and humans, horses, cows, cats, dogs, rabbits, and rodents such as rats and mice. In one embodiment, the mammal to be treated is human. The human can be any human of any age. In one embodiment, the human is an adult. In another embodiment, the human is a child. The human can be male, female, pregnant, middle-aged, adolescent, or elderly.

[0284] Pharmaceutical compositions suitable for use in the methods disclosed herein include compositions wherein the anti- CDH17 binding molecules are contained in an amount effective to achieve the intended purpose. In one embodiment, a therapeutically effective amount means an amount of the anti-CDHl 7 binding molecules or antibodies effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art.

[0285] In one embodiment, the exact amount of the present polypeptides or compositions thereof required to elicit the desired effects will vary from subject to subject, depending on the species, age, gender, weight, and general condition of the subject, the particular polypeptides, the route of administration, and whether other drugs are included in the regimen. Thus, it is not possible to specify an exact amount for every composition. However, an appropriate amount can be determined by one of ordinary skill in the art using routine experimentation. Dosages can vary, and the polypeptides can be administered in one or more (e.g., two or more, three or more, four or more, or five or more) doses daily, for one or more days. Guidance in selecting appropriate doses for antibodies can be readily found in the literature.Diagnostic Methods

[0286] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9832. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9464.

[0287] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDHl 7 binding molecule DM-9476. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9491.

[0288] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9509. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9558.

[0289] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9580. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9591 .

[0290] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9597. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9616.

[0291] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9620. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9621.

[0292] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9628. In some embodiments, disclosed herein is a method of diagnosing a medicalcondition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9648.

[0293] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9649. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9701.

[0294] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9706. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9746.

[0295] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9762. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9773.

[0296] In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9780. In some embodiments, disclosed herein is a method of diagnosing a medical condition, or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9787.

[0297] In some embodiments, disclosed herein is a method of diagnosing a medical condition,or a disease, associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule DM-9814.

[0298] In some embodiments, CDH17 levels are measured by a biosensor equipped with the anti-CDH17 binding molecules. In some embodiments, CDH17 levels are measured by a fluorescence-based technique with anti-CDH17 binding molecules. In some embodiments, the CDH17 levels are measured by a employing anti-CDH17 binding molecule conjugated to magnetic nanoparticles followed by magnetic resonance imaging. In some embodiments, the CDH17 levels are measured by immobilizing the anti-CDH17 binding molecule on a solid support to capture and quantify the CDH17 from a biological sample. In some embodiments, the CDH17 levels are measured by an enzyme-linked immunosorbent assay (ELISA), wherein the anti-CD17 binding molecule is either the enzyme labeled antibody or the antibody attached to the solid surface. In some embodiments, the CDH17 levels are measured by using a microfluidic chip functionalized with the anti-CDH17 binding molecule for rapid and high- throughput detection of CDH17 levels in biological samples.

[0299] In some embodiments, the anti-CDH17 binding molecule is modified to facilitate its detection. In some embodiments, the anti-CDH17 binding molecule is conjugated to a fluorescent probe to enable detection through fluorescence-based assays. In some embodiments, the anti-CDH17 binding molecule is conjugated to a biotin moiety, allowing for facile detection through interaction with streptavidin-conjugated labels or immobilization on a solid support coated with avidin. In some embodiments, the anti-CDH17 binding molecule is modified by the incorporation of a radioisotope, facilitating sensitive detection through radioimmunoassays for quantifying CDH17 levels. In some embodiments, the anti-CDH17 binding molecule is modified by the conjugation of a paramagnetic tag, enabling the detection of CDH17 through magnetic resonance imaging or magnetic separation techniques. In some embodiments, the anti-CDH17 binding molecule is modified by the incoroporation of a nanomaterial such as gold nanoparticles attached, allowing for colorimetric detection by changes in absorbance or color providing a visual indication of binding events.

[0300] A medical condition associated with CDH17 is not to be interpreted only as a disease that is solely caused by CDH17, or even as a disease in which CDH17 is part of its etiology. A medical condition associated with CDH17 also includes any condition in which the expression or function of CDH17 in at least one tissue is altered.

[0301] The levels of CDH17 can be measured in any relevant tissue, not necessarily one with pathological features. In some embodiments, CDH17 levels are measured in blood. In some embodiments, CDH17 levels are measured in plasma. In some embodiments, CDH17 levels are measured in a tumor tissue. In some embodiments, CDH17 levels are measured in stomach tissue. In some embodiments, CDH17 levels are measured in pancreatic tissue. In some embodiments, CDH17 levels are measured in pancreatic juice. In some embodiments, CDH17 levels are measured in colon tissue. In some embodiments, CDH17 levels are measured in fecal material.

[0302] In some embodiments, disclosed herein is an integrated method for diagnosis and treating cancer, comprising a first steps of detecting the presence of CDH17 in a tumor tissue with an anti-CDH17 binding molecule, and a second step of administering an anti-CDH17 binding molecule to target the tumor tissue, wherein a positive diagnosis triggers the administration of a targeted therapy against CDH17-expressing cancer cells. In some embodiments, disclosed herein is a method comprising simultaneous cancer diagnosis and treatment, comprising a step of administering anti-CDH17 binding molecules conjugated to a detection moiety, wherein said anti-CDH17 binding molecules target a tumor tissue, and wherein simultaneously the presence of the conjugated detection moiety can be measured on the tissue.

[0303] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. Each literature reference or other citation referred to herein is incorporated herein by reference in its entirety.

[0304] Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise,” “comprising,” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”. In some embodiments, comprising means consisting of. Words using the singular or plural number also include the plural or singular number, respectively. Additionally, the words “herein”, “above”, and “below” and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of thisapplication. As used herein, the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. “And” as used herein is interchangeably used with “or” unless expressly stated otherwise.

[0305] In the description presented herein, each of the steps of the invention and variations thereof are described. This description is not intended to be limiting and changes in the components, sequence of steps, and other variations would be understood to be within the scope of the present invention.

[0306] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also he provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0307] Throughout this application, various embodiments of the present disclosure may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0308] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging / ranges between” a first indicate number and a second indicate number and “ranging / ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

[0309] When values are expressed as approximations, by use of the antecedent "about," it is understood that the particular value forms another embodiment. All ranges are inclusive and combinable. In one embodiment, the term “about” refers to a deviance of between 0.1-5% fromthe indicated number or range of numbers. In another embodiment, the term “about” refers to a deviance of between 1-10% from the indicated number or range of numbers. In another embodiment, the term “about” refers to a deviance of up to 20% from the indicated number or range of numbers. In one embodiment, the term “about” refers to a deviance of ± 10% from the indicated number or range of numbers. In another embodiment, the term “about” refers to a deviance of ± 5% from the indicated number or range of numbers.EXAMPLESExample 1 - mAbs Binding Affinity’ to Soluble Human CDH17

[0310] Objective: to determine the binding affinity of selected antibodies to soluble human cadherin 17 (CDH17).

[0311] Methods: Surface Plasmon Resonance (SPR) was used to identify intrinsic binding affinity. Kinetic experiments were performed on Carterra LSA with a running buffer of PBS pH 7.40, 1% BSA, 0.05% Tween20. Purified recombinant anti-CDH17 antibodies were captured in a bivalent format. For kinetics analysis, human or cynomolgus monkey CDH17 antibody were injected at different concentrations. Results were processed and analyzed in Carterra LSA Kinetics Software to determine association and dissociation kinetic rate constants (konand koff values). The ratio koff / konwas used to derive the KD value of each antigen / mAb interaction, i.e. KD= kOff / kon.

[0312] Results: The interactions of human CDH17 with DM-9464 (Figure 1A), DM- 9476(Figure IB), DM-9491 (Figure 1C), DM-9509 (Figure ID), DM-9558 (Figure IE), DM- 9580 (Figure IF), DM-9591 (Figure 1G), DM-9597 (Figure 1H), DM-9616 (Figure II), DM- 9620 (Figure 1 J), DM-9621 (Figure IK), DM-9628 (Figure IL), DM-9648 (Figure IM), DM- 9649 (Figure IN), DM-9701 (Figure 10), DM-9706 (Figure IP), DM-9746 (Figure IQ), DM- 9762 (Figure 1R), DM-9773 (Figure IS), DM-9780 (Figure IT), DM-9787 (Figure 1U), (Figure IV), DM-9814 DM-9832 (Figure 1W) were analyzed by SPR at 3 different concentrations.

[0313] All SPR curves exhibited a sharp rise, indicating successful interaction between the analyte and ligand. Some of the analyzed antibodies exhibited a stable plateau in which a state of equilibrium was reached, while in others there was a slight decline after the plateau, hinting at the onset of the dissociation phase (Figures 1A-1W and Figure 2).Example 2 - mAbs Binding to Cells Expressing CDH17

[0314] Objective: to determine the binding affinity of selected antibodies to a cell surface expressing cadherin 17 (CDH17).

[0315] Methods: To assess the binding affinity of monoclonal antibodies (mAbs) to cell surface antigens, a flow cytometry analysis was used with AsPC-1 human pancreatic cancer cell line. AsPC-1 cells were cultured under standard conditions. Prior to the assay, cells were washed and resuspended. Cells were incubated with either anti-CDH17 antibodies or control antibodies labeled with PE-H allowing sufficient time for binding while minimizing internalization. After incubation, cells were washed to remove unbound antibodies and resuspended in buffer. The fluorescence intensity of the bound antibodies was then measured using flow cytometry to quantify the level of mAh binding.

[0316] Results: The binding of PE-H labeled DM-9464 (Figure 3 A), DM-9476(Figure 3B), DM-9491 (Figure 3C), DM-9509 (Figure 3D), DM-9558 (Figure 3E), DM-9580 (Figure 3F), DM-9591 (Figure 3G), DM-9597 (Figure 3H), DM-9616 (Figure 31), DM-9620 (Figure 3J), DM-9621 (Figure 3K), DM-9628 (Figure 3L), DM-9648 (Figure 3M), DM-9649 (Figure 3N), DM-9701 (Figure 30), DM-9706 (Figure 3P), DM-9746 (Figure 3Q), DM-9762 (Figure 3R), DM-9773 (Figure 3S), DM-9780 (Figure 3T), DM-9787 (Figure 3U), (Figure 3V), DM-9814 DM-9832 (Figure 3W) to CDH17-expressing AsPC-1 was analyzed by flow cytometry. All antibodies showed higher binding than control antibodies.Example 3 - Cytotoxicity of DMDM-conjugated CDH17 mAbs

[0317] Objective: to determine the cytotoxicity of Duarcomycin (DMDM) conjugated anti- CDH17 antibodies.

[0318] Methods: Anti-CDH17 antibodies were incubated with an anti -human FC Fab fragment containing a duarcomycin (DMDM) conjugated to the Fab Fragment via a cleavable linker, creating a secondary drug conjugate. Secondary drug conjugates were then incubated with Parental SNU-16 cells or CDH17 knockdown (KD) SNU-16 cells for 5 days, and cell viability was measured using Cell Titre Gio.

[0319] Results: SNU-16 cells incubated with DMDM conjugated to DM-9509 (Figure 4A), DM-9832 (Figure 4B), DM-9491 (Figure 4C), DM-9648 (Figure 4D), or DM-9787 (Figure 4E) showed decreased viability compared to CDH17 knockdown (KD) SNU-16 receiving the sametreatment, or to cells not incubated with the secondary drug conjugate.

[0320] Table 2 shows the IC50 of different DMDM conjugated anti-CDH17 antibodies when incubated with SNU-16 cells.

[0321] Table 2. DMDM conjugated anti-CDH17 antibodies cytotoxicity.Example 4 — Cytotoxicity of DMDM-conjugated CDH17 mAbs

[0322] Objective: to determine the cytotoxicity of selected DMDM-conjugated anti-CDH17 antibodies.

[0323] Methods: DM-9832 (Tool) and DM-9648 (Lead) antibodies were incubated with an anti-human FC Fab fragment containing a duarcomycin (DMDM) conjugated to the Fab Fragment via a cleavable linker, creating a secondary drug conjugate having a drug-antibody ratio (DAR) of 8. Antibody drug conjugates were then incubated with SNU-16 cells, and cell viability was measured.

[0324] Results: DM-9832 (Tool) ADC demonstrated less cytotoxic activity in SNU-16 cells than DM-9648 (Lead), which exhibited significantly higher potency, reducing cell viability more effectively at lower concentrations (Figure 5).Example 5 -Efficiency of Exatecan-conjugated CDH17 mAbs

[0325] Objective: to determine the cytotoxicity of selected Exatecan (Exa)-conjugated DM- 9648 antibody.

[0326] Methods: DM-9648 antibodies were incubated with an anti-human FC Fab fragmentcontaining a Exatecan (Exa) conjugated to the Fab Fragment via a cleavable linker, creating a secondary drug conjugate having a drug-antibody.

[0327] To determine the sensitivity of different cell types, SNU-5, SNU-16 and AsPC-1 cells were incubated with the antibody drug conjugate at different concentrations.

[0328] For the in vivo experiment, AsPC-1 cell were used to establish xenograft models in mice. Mice were then administered a single 10 mg / kg dose of either the Exa-conjugated DM- 9648 or a control ADC. Tumor volumes were measured for 30 days following drug administration.

[0329] Results: AsPCl cells showed less sensitivity to Exa-conjugated DM-9648 than SNU- 16 and SNU-5 cells (Figure 6A).

[0330] AsPCl showed lower sensitivity to Exa-conjugated DM-9648 apparently since they express only ~5-fold less CDH17 than patient-derived xenografts. However, it was easier to established a xenograft model with AsPCl than with SNU-5 and SNU-16.

[0331] In mice inoculated with AsPCl cells, AsPCl tumors showed 70% tumor growth inhibition compared to a control ADC after a single 10 mg / kg dose (Figure 6B).Example 6 - In vivo Efficiency of ADCs Comprising DM-9648 in Colorectal Xenografts

[0332] Objective: to determine the in vivo efficacy of ADCs comprising a DM-9648 antibody.

[0333] Methods: The efficacy of 2 different ADCs comprising DM-9648 antibody (CO-ADC- 009 and CO-ADC-010) was compared with an ADC comprising a commercially available isotype antibody (CO-ADC-005). CO-ADC-009 comprises the DM-9648 antibody, conjugated to MMAE with a Drug-to-Antibody Ratio (DAR) of 4, through a valine-citrulline linker. CO- ADC-010 comprises the DM-9648 antibody, conjugated to Deruxtecan with a DAR of 8, through the GGFG linker. CO-ADC-05 comprises a commercially available isotype, conjugated to Deruxtecan with a DAR of 8, through the GGFG linker. Conjugations were performed using maleimide chemistry.

[0334] Patient-derived colorectal xenografts CTG-2351, CTG-0063, CTG-0923, CTG-0652, and CTG-0864 (Champions Oncology) were used to establish xenograft models in mice. CTG- 2351 PDX is derived from a stage IV colorectal tumor that metastasized to abdomen. The patient was pretreated and relapsed on 5-FU, Irinotecan, and Bevacizumab. CTG-0063 PDX is derived from a primary stage III colorectal tumor. The patient was not treated. CTG-0923 PDXis derived from a stage IV colorectal tumor that metastasized to the brain. The patient was pretreated and relapsed on 5-FU and Oxaliplatin. CTG-0864 is derived from a stage III colorectal tumor that metastasized to ovary. The patient was pretreated and relapsed on 5-FU, irinotecan, and oxaliplatin.

[0335] Mice were then administered with either CO- ADC-005, CO- ADC-010, or CO- ADC-009 according to the following dosing scheme. CO- ADC-005 and CO- ADC-010 were administered at 3, 7, or 10 mg per kg (MPK) i.v. in 2 doses at an interval of once every 14 days. CO- ADC-009 was administered at 1, 3, or 5 mg per kg (MPK) i.v. in 3 doses at an interval of once every 7 days.

[0336] Results: CO-ADC-010 administration induced over 90% tumor growth inhibition across all xenograft models, with full regression observed. A potent activity was observed even at extremely low dose levels. CO-ADC-010 overcame resistance to all standard of care treatments, including irinotecan, 5-FU, oxaliplatin, FOLFOX, and Cetuximab. CO-ADC-009 was more active in naive tumors (Figures 7A-7F).

Claims

CLAIMS1. An isolated anti-Cadherin 17 (CDH17) binding molecule comprising a heavy chain variable region comprising a first CDR (CDRH1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 11 1, 121, 131, 141, 151, 161, 171, 181, 191, 201, 211, or 221 ; a second CDR (CDRH2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 212, or 222; and a third CDR (CDRH3) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, or 223; and a light chain variable region comprising a first CDR (CDRL1) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, or 224; a second CDR (CDRL2) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, or 225; and a third CDR (CDRL3) comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146, 156, 166, 176, 186, 196, 206, 216, or 226.

2. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 1 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 2, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 3, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 4, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 5, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 6.

3. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 11; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 12, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQID NO: 13, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 14, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 15, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 16.

4. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 21; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 22, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 23, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 24, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 25, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 26.

5. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 31; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 32, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 33, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 34, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 35, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 36.

6. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 41; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 42, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 43, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 44, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 45, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 46.

7. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 51; said CDRH2comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 52, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 53, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 54, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 55, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 56.

8. The anti-CDH17 binding molecule of claim 1 , wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 61; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 62, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 63, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 64, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 65, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 66.

9. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 71; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 72, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 73, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 74, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 75, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 76.

10. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 81; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 82, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 83, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 84, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 85, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 86.

11. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 91; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 92, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 93, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 94, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 95, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 96.

12. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 101; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 102, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 103, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 104, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 105, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 106.

13. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 111; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 112, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 113, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 114, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 115, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 116.

14. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 121; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 122, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 123, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 124, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 125, and said CDRL3 comprises an amino acidsequence having at least 80% homology to SEQ ID NO: 126.

15. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 131; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 132, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 133, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 134, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 135, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 136.

16. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 141; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 142, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 143, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 144, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 145, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 146.

17. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 151; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 152, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 153, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 154, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 155, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 156.

18. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 161; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 162, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 163, said CDRL1 comprises an amino acid sequence having at least 80%homology to SEQ ID NO : 164, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 165, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 166.

19. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 171; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 172, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 173, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 174, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 175, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 176.

20. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 181; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 182, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 183, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 184, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 185, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 186.

21. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 191; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 192, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 193, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 194, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 195, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 196.

22. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 201; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 202,said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 203, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 204, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 205, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 206.

23. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 21 1 ; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 212, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 213, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 214, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 215, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 216.

24. The anti-CDH17 binding molecule of claim 1, wherein said CDRH1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 221; said CDRH2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 222, said CDRH3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 223, said CDRL1 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 224, said CDRL2 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 225, and said CDRL3 comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 226.

25. The anti-CDH17 binding molecule of claim 2, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 7 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 8.

26. The anti-CDH17 binding molecule of claim 3, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 17 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 18.

27. The anti-CDH17 binding molecule of claim 4, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 27 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 28.

28. The anti-CDH17 binding molecule of claim 5, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 37 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 38.

29. The anti-CDH17 binding molecule of claim 6, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 47 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 48.

30. The anti-CDH17 binding molecule of claim 7, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 57 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 58.

31. The anti-CDH17 binding molecule of claim 8, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 67 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 68.

32. The anti-CDH17 binding molecule of claim 9, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 77 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 78.

33. The anti-CDH17 binding molecule of claim 10, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 87 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 88.

34. The anti-CDH17 binding molecule of claim 11, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 97 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 98.

35. The anti-CDH17 binding molecule of claim 12, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 107 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 108.

36. The anti-CDH17 binding molecule of claim 13, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 117 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 118.

37. The anti-CDH17 binding molecule of claim 14, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 127 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 128.

38. The anti-CDH17 binding molecule of claim 15, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 137 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 138.

39. The anti-CDH17 binding molecule of claim 16, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 147 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 148.

40. The anti-CDH17 binding molecule of claim 17, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 157 and said light chain variable region comprises an amino acid sequence havingat least 80% homology to SEQ ID NO: 158.

41. The anti-CDH17 binding molecule of claim 18, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 167 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 168.

42. The anti-CDH17 binding molecule of claim 19, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 177 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 178.

43. The anti-CDH17 binding molecule of claim 20, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 187 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 188.

44. The anti-CDH17 binding molecule of claim 21, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 197 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 198.

45. The anti-CDH17 binding molecule of claim 22, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 207 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 208.

46. The anti-CDH17 binding molecule of claim 23, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 217 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 218.

47. The anti-CDH17 binding molecule of claim 24, wherein said heavy chain variable region comprises an amino acid sequence having at least 80% homology to SEQ IDNO: 227 and said light chain variable region comprises an amino acid sequence having at least 80% homology to SEQ ID NO: 228.

48. The anti-CDH17 binding molecule of claims 2 and 25, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 9, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 10.

49. The anti-CDH17 binding molecule of claims 3 and 26, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 19, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 20.

50. The anti-CDH17 binding molecule of claims 4 and 27, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 29, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 30.

51. The anti-CDH17 binding molecule of claims 5 and 28, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 39, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 40.

52. The anti-CDH17 binding molecule of claims 6 and 29, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 49, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 50.

53. The anti-CDH17 binding molecule of claims 7 and 30, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 59, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 60.

54. The anti-CDH17 binding molecule of claims 8 and 31, comprising a heavy chainregion comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 69, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 70.

55. The anti-CDH17 binding molecule of claims 9 and 32, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 79, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 80.

56. The anti-CDH17 binding molecule of claims 10 and 33, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 89, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 90.

57. The anti-CDH17 binding molecule of claims 11 and 34, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 99, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 100.

58. The anti-CDH17 binding molecule of claims 12 and 35, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 109, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 110.

59. The anti-CDH17 binding molecule of claims 13 and 36, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 119, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 120.

60. The anti-CDH17 binding molecule of claims 14 and 37, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 129, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 130.

61. The anti-CDH17 binding molecule of claims 15 and 38, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 139, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 140.

62. The anti-CDH17 binding molecule of claims 16 and 39, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 149, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 150.

63. The anti-CDH17 binding molecule of claims 17 and 40, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 159, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 160.

64. The anti-CDH17 binding molecule of claims 18 and 41, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 169, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 170.

65. The anti-CDH17 binding molecule of claims 19 and 42, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 179, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 180.

66. The anti-CDH17 binding molecule of claims 20 and 43, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 189, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 190.

67. The anti-CDH17 binding molecule of claims 21 and 44, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 199, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 200.

68. The anti-CDH17 binding molecule of claims 22 and 45, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 209, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 210.

69. The anti-CDH17 binding molecule of claims 23 and 46, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 219, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 220.

70. The anti-CDH17 binding molecule of claims 24 and 47, comprising a heavy chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 229, and a light chain region comprising an amino acid sequence having at least 80% homology to SEQ ID NO: 230.

71. The anti-CDH17 binding molecule of claims 1-70, wherein the binding molecule comprises an IgG, a Fv, a scFv, a Fab, a F(ab')2, a minibody, a diabody, a triabody, a nanobody, a bispecific antibody, a single domain antibody, a monoclonal antibody, or a chimeric antigen receptor.

72. The anti-CDH17 binding molecule of claim 71, wherein said IgG is IgGl, IgG2, IgG3, or IgG4.

73. An isolated polynucleotide sequence encoding the anti-CDH17 binding molecule of any one of claims 1-72.

74. An expression vector comprising the polynucleotide sequence of claim 73.

75. A host cell comprising the expression vector of claim 74.

76. An antibody-drug conjugate (ADC) comprising the anti-Cadherin 17 (CDH17) binding molecule of any of claims 1-72; and a drug conjugate comprising a cleavable linker and a cytotoxic payload.

77. The ADC of claim 76, wherein the drug conjugate comprises duarcomycin (DMDM).

78. The ADC of claim 76, wherein the drug conjugate comprises exatecan.

79. The ADC of claim 76, wherein the drug conjugate comprises deruxtecan.

80. The ADC of claims 76-79, wherein the cleavable linker moiety is a hydrazone linker, a disulphide linker, or a peptide linker.

81. The ADC of claim 76-80, wherein the peptide linker is a dipeptide linker selected from the group consisting of valine-citrulline (Val-Cit), valine-alanine (Val-Ala). alaninealanine (Ala-Ala), and a GGFG linker.

82. The ADC of claim 81, wherein the dipeptide linker is joined to the cytotoxic pay load by the spacer unit para-aminobenzyloxycarbonyl (PABC).

83. The ADC of claim 81, wherein the peptide linker is a tripeptide linker comprising a glutamic acid-valine-citrulline (EVCit).

84. The ADC of claims 76-84, wherein the glutamic acid-valine-citrulline (EVCit) tripeptide linker is joined to a meta-amide para-aminobenzyl carbamate (MA-PABC) group.

85. The ADC of claims 76-84, wherein the drug-to-antibody ratio (DAR) is 2.

86. The ADC of claims 76-84, wherein the drug-to-antibody ratio (DAR) is 8 or 4.

87. A pharmaceutical composition comprising the anti-CDH17 binding molecule of any one of claims 1-72, or the antibody-drug conjugate of claims 76-86, and a pharmaceutically acceptable carrier.

88. A method of treating a disease associated with CDH17, comprising a step of administering to the subject the composition of claim 87.

89. The method of claim 88, wherein the disease is cancer.

90. The method of claim 89, wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, colon cancer, and colorectal cancer.

91. The method of claims 88-90, wherein said ADC is administered in a dosage of 3, 5, 7, or 10 mg per kg.

92. The method of claims 99-91, wherein said ADC is administered once every 7 days, or once every 14 days.

93. A method of diagnosing a disease associated with CDH17 in a subject in need thereof, comprising a step of measuring CDH17 levels in a tissue from said subject with the anti-CDH17 binding molecule of claims 1-72.

94. The method of claim 93, wherein said disease is cancer.

95. The method of claim 94, wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, colon cancer, and colorectal cancer.

96. The method of any one of claims 93-95, wherein said tissue comprises blood and / or a tumor tissue.

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