Anti-CUB domain-containing protein 1 (CDCP1) antibody, antibody-drug conjugate, and method of use thereof.

Abstract

This invention provides anti-CDCP1 antibodies and ADCs that can be used for therapeutic purposes in the treatment of cancer. [Solution] In certain embodiments, the present invention provides an anti-CDCP1 antibody and an antibody-drug conjugate (ADC). In certain embodiments of the present invention, the antibody or its antigen-binding moiety binds to the extracellular domain of CDCP1 (e.g., the amino acid sequence provided in GenBank accession number NP_073753.3 and / or the amino acid sequence provided in NP_835488.1; the entire contents of each of these are incorporated herein by reference).

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 435,509 filed on 16 December 2016, U.S. Provisional Patent Application No. 62 / 488,445 filed on 21 April 2017, and U.S. Provisional Patent Application No. 62 / 588,516 filed on 20 November 2017. The entire contents of the said applications are incorporated herein by reference.

[0002] Sequence List This application is filed electronically in ASCII format and includes a sequence listing which is incorporated herein by reference in its entirety. The ASCII copy was created on November 29, 2017, has the filename 127913-00920_SL.txt, and is 213,669 bytes in size. [Background technology]

[0003] CDCP1, also known as "CUB Domain-Containing Protein 1," "CD318," "Transmembrane and Associated with Src Kinases" ("TRASK"), and "SIMA135," is an 836-amino acid type I transmembrane protein consisting of a 29-amino acid signal peptide, a 636-amino acid large extracellular domain with three highly glycosylated regions having low homology to C1r / C1s and sea urchin embryo growth factor, and a bone morphogenetic protein 1 (CUB) domain, with 21 and 150-amino acid transmembrane and cytoplasmic domains, respectively. The cytoplasmic domain of CDCP1 contains five conserved tyrosine residues that act as substrates for Src family kinases (SFKs), such as Src, Fyn, and Yes, which are subsequently phosphorylated.

[0004] CDCP1 is widely expressed in human epithelial tissue. While CDCP1 functions in the tyrosine phosphorylation-dependent regulation of cellular events involved in tumor invasion and metastasis, its phosphorylation is observed only in cells that have detached or fallen off after pedunculation, consistent with CDCP1's role in the negative regulation of cell adhesion. CDCP1 phosphorylation is found in numerous cancers, including some pre-invasive cancers, as well as in invasive tumors and tumor metastases.

[0005] Recent clinical and commercial successes of anti-cancer antibodies have aroused significant interest in antibody-based therapies. Because antibodies can target specific antigens present on cancer cells, antibody-based therapies may be more effective in treating cancer and exhibit lower toxicity compared to commonly used chemotherapy. Therefore, there is a need to develop anti-cancer antibodies for use in various antibody-based therapies to treat cancer.

[0006] Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents that contain antibodies conjugated to cytotoxic drugs via a chemical linker. The therapeutic concept of ADCs is to combine the binding ability of an antibody with a drug, using the antibody to deliver the drug to tumor cells by binding to a target surface antigen. [Overview of the project] [Problems that the invention aims to solve]

[0007] Therefore, there remains a need in this field for anti-CDCP1 antibodies and ADCs that can be used for therapeutic purposes in the treatment of cancer. [Means for solving the problem]

[0008] In certain embodiments of the present invention, the present invention provides anti-CDCP1 antibodies and antibody-drug conjugates (ADCs). In certain embodiments of the present invention, the antibody or its antigen-binding moiety binds to the extracellular domain of CDCP1 (e.g., the amino acid sequence provided in GenBank accession number NP_073753.3 and / or the amino acid sequence provided in NP_835488.1; the entire contents of each of these are incorporated herein by reference) or CDCP1. In one embodiment, the antibody of the present invention or its antigen-binding portion is approximately 2,000 nM or less, approximately 1,000 nM or less, approximately 500 nM or less, approximately 200 nM or less, approximately 100 nM or less, approximately 75 nM or less, approximately 25 nM or less, approximately 21 nM or less, approximately 12 nM or less, approximately 11 nM or less, approximately 10 nM or less, approximately 9 nM or less, approximately 8 nM or less, approximately 7 nM or less, approximately 6 nM or less, approximately 5 nM or less, approximately 4 nM or less, approximately 3 nM or less, approximately 2 nM or less, approximately 1 nM or less, approximately 0.5 nM or less, approximately 0.3 nM or less, approximately 0.1 nM or less, or approximately 0.01 nM or less K d It then binds to CDCP1.

[0009] In yet another embodiment of the present invention, the anti-CDCP1 antibody-drug conjugate (ADC) of the present invention (e.g., the CDCP1 antibody of the present invention conjugated with a toxin) is capable of internal transfer. In yet another embodiment, the anti-CDCP1 antibody-drug conjugate (ADC) of the present invention is capable of inducing cell death in cells endogenously expressing CDCP1.

[0010] In one aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding moiety comprises a heavy chain variable region comprising CDR3 having the amino acid sequence of SEQ ID NO: 157, and a light chain variable region comprising CDR3 having the amino acid sequence of SEQ ID NO: 160. In some embodiments, the antibody or its antigen-binding moiety further comprises a heavy chain variable region comprising CDR2 having the amino acid sequence of SEQ ID NO: 156, and a light chain variable region comprising CDR2 having the amino acid sequence of SEQ ID NO: 159. In another embodiment, the antibody or its antigen-binding moiety comprises a heavy chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO: 155, and a light chain variable region comprising CDR1 having any of the amino acid sequences of SEQ ID NO: 158.

[0011] In one aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding portion comprises a heavy chain variable region comprising CDR3 having the amino acid sequence of SEQ ID NO: 37, and a light chain variable region comprising CDR3 having the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody or its antigen-binding portion further comprises a heavy chain variable region comprising CDR2 having the amino acid sequence of SEQ ID NO: 36, and a light chain variable region comprising CDR2 having the amino acid sequence of SEQ ID NO: 39. In another embodiment, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO: 35, and a light chain variable region comprising CDR1 having any of the amino acid sequences of SEQ ID NO: 38.

[0012] In one aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding moiety comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 87, and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 90. In some embodiments, the antibody or its antigen-binding moiety comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 86, and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 89. In other embodiments, the antibody or its antigen-binding moiety comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 85, and a light chain variable region comprising a CDR1 having any of the amino acid sequences of SEQ ID NO: 88.

[0013] In yet another aspect of the present invention, the present disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 107, and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 106, and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 109. In another embodiment, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 105, and a light chain variable region comprising a CDR1 having any of the amino acid sequences of SEQ ID NO: 108.

[0014] In another aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 127, and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 130. In some embodiments, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 126, and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 129. In another embodiment, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 125, and a light chain variable region comprising a CDR1 having any of the amino acid sequences of SEQ ID NO: 128.

[0015] In one aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 47, and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 50. In some embodiments, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 46, and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 49. In other embodiments, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 45, and a light chain variable region comprising a CDR1 having any of the amino acid sequences of SEQ ID NO: 48.

[0016] In another aspect of the present invention, the disclosure provides an isolated antibody or its antigen-binding capability that binds to human CDCP1, wherein the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 77, and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 80. In some embodiments, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 76, and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 79. In another embodiment, the antibody or its antigen-binding portion comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 75, and a light chain variable region comprising a CDR1 having any of the amino acid sequences of SEQ ID NO: 78.

[0017] In some embodiments, the antibody or its antigen-binding moiety is an IgG isotype.

[0018] In some embodiments, the antibody or its antigen-binding moiety is 200 nM or lower K D It has.

[0019] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 156, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 155, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 160, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 159, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 158.

[0020] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 37, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 36, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 35, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 40, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 39, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 38.

[0021] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 87, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 86, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 85, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 90, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 89, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 88.

[0022] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 107, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 106, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 105, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 110, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 109, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 108.

[0023] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 127, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 126, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 125, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 130, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 129, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 128.

[0024] In one aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 47, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 46, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 45, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 50, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 49, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 48.

[0025] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 76, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 75, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 80, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 79, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 78.

[0026] In some embodiments, the antibody or its antigen-binding moiety is an IgG isotype.

[0027] In some embodiments, the antibody or its antigen-binding moiety is 200 nM or lower K D It has.

[0028] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 151 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 152.

[0029] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 151, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 151, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 152, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 152.

[0030] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.

[0031] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 31, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 31, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 32, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 32.

[0032] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 82.

[0033] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 81, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 81, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 82, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 82.

[0034] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 101 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 102.

[0035] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 101, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 101, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 102, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 102.

[0036] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 121 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 122.

[0037] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 121, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 121, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 12, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 122.

[0038] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 42.

[0039] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 41, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 41, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 42, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 42.

[0040] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 71 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 72.

[0041] In another aspect of the present invention, the present disclosure provides an anti-CDCP1 antibody or its antigen-binding moiety comprising a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 71, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 71, and / or a light chain comprising the amino acid sequence shown in SEQ ID NO: 72, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 72.

[0042] In one aspect of the present invention, the present disclosure provides an anti-CUB domain-containing protein 1 (-CDCP1) antibody or an antigen-binding moiety thereof, wherein the antibody or the antigen-binding moiety comprises a heavy chain variable region containing a CDR3 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20, and a light chain variable region containing a CDR3 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20.

[0043] In one embodiment, the heavy chain variable region further comprises a CDR2 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20, and the light chain variable region further comprises a CDR2 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20.

[0044] In another embodiment, the heavy chain variable region further comprises a CDR1 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20, and the light chain variable region further comprises a CDR1 having an amino acid sequence selected from the group consisting of any one of the amino acid sequences in Figures 15, 18, or 20.

[0045] In another aspect of the present invention, the disclosure provides an antibody or an antigen-binding moiety that binds to the same epitope as the antibody or its antigen-binding moiety described herein.

[0046] In another aspect of the present invention, the disclosure provides isolated nucleic acids encoding an antibody or its antigen-binding moiety as described herein.

[0047] In another aspect of the present invention, the disclosure provides a pharmaceutical composition comprising an antibody or its antigen-binding moiety as described herein and a pharmaceutically acceptable carrier.

[0048] In another aspect of the present invention, the disclosure provides an antibody or its antigen-binding moiety, as described herein, conjugated to at least one drug.

[0049] In some embodiments, at least one drug is selected from the group consisting of anti-apoptotic agents, mitotic inhibitors, antitumor antibiotics, immunomodulators, nucleic acids for gene therapy, anti-angiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormone agents, corticosteroids, phototherapeutic agents, oligonucleotides, radionuclides, radiosensitizers, topoisomerase inhibitors, and tyrosine kinase inhibitors. In other embodiments, at least one drug is conjugated to an antibody or its antigen-binding moiety via a linker. In yet another embodiment, the linker is a cleavable linker. In yet another embodiment, the linker is a non-cleavable linker.

[0050] In one embodiment, the anti-CUB domain-containing protein 1 (anti-CDCP1) antibody of the present invention or its antigen-binding moiety is a bispecific antibody. In another embodiment, the anti-CUB domain-containing protein 1 (anti-CDCP1) antibody of the present invention or its antigen-binding moiety is a multispecific antibody.

[0051] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 156, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 155, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 160, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 159, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 158.

[0052] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 37, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 36, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 35, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 40, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 39, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 38.

[0053] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 87, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 86, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 85, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 90, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 89, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 88.

[0054] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 107, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 106, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 105, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 110, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 109, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 108.

[0055] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 127, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 126, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 125, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 130, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 129, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 128.

[0056] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 47, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 46, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 45, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 50, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 49, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 48.

[0057] In another aspect of the present invention, the present disclosure provides a drug conjugate (ADC) comprising an antibody or antigen-binding parity conjugated to at least one drug, wherein the antibody or antigen-binding parity comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 76, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 75, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 80, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 79, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 78.

[0058] In another aspect of the present invention, the disclosure provides an antibody or its antigen-binding moiety, as described herein, conjugated to at least one drug.

[0059] In some embodiments, at least one drug is selected from the group consisting of anti-apoptotic agents, mitotic inhibitors, antitumor antibiotics, immunomodulators, nucleic acids for gene therapy, anti-angiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormone agents, corticosteroids, phototherapeutic agents, oligonucleotides, radionuclides, radiosensitizers, topoisomerase inhibitors, and tyrosine kinase inhibitors. In other embodiments, at least one drug is conjugated to an antibody or its antigen-binding moiety via a linker. In another embodiment, the linker is a cleavable linker. In yet another embodiment, the linker is a non-cleavable linker.

[0060] In some embodiments, at least one drug is conjugated via a linker. In another embodiment, the linker is a cleavable linker. In yet another embodiment, the linker is a non-cleavable linker.

[0061] In some embodiments, the antibody or its antigen-binding moiety is an IgG1 isotype.

[0062] In another aspect of the present invention, the disclosure provides a pharmaceutical composition comprising an ADC mixture containing a plurality of ADCs as described herein and a pharmaceutically acceptable carrier.

[0063] In some embodiments, the ADC mixture has a mean drug-antibody ratio (DAR) of 0 to 8.

[0064] In another aspect of the present invention, the present disclosure provides a method for treating cancer, comprising administering a therapeutically effective amount of an antibody or antigen-binding moiety thereof as described herein, or a bispecific antibody or ADC as described herein, to a subject in need.

[0065] In some embodiments, the cancer is selected from the group consisting of breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer. In one embodiment, the cancer is breast cancer, for example, triple-negative breast cancer. In one embodiment, the cancer is colon cancer. In one embodiment, the cancer is lung cancer, for example, non-small cell lung cancer (NSCLC).

[0066] In another embodiment, the present invention provides a method for inhibiting or reducing solid tumor growth in a subject having a solid tumor. The method comprises administering a therapeutically effective amount of an antibody or antigen-binding moiety thereof as described herein, or a bispecific antibody or ADC as described herein, to a subject having a solid tumor to inhibit or reduce solid tumor growth.

[0067] In some embodiments, the cancer is selected from the group consisting of breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer. In one embodiment, the cancer is breast cancer, for example, triple-negative breast cancer. In one embodiment, the cancer is colon cancer. In one embodiment, the cancer is lung cancer, for example, non-small cell lung cancer (NSCLC).

[0068] In one embodiment, an antibody or its antigen-binding moiety, or a bispecific antibody as described herein, or an ADC, is administered in combination with an additional agent or additional therapy. In one embodiment, the additional agent is an immune checkpoint inhibitor, such as an antibody selected from the group consisting of anti-PD1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody. In one embodiment, the additional therapy is radiation. In one embodiment, the additional agent is a chemotherapeutic agent.

[0069] In one embodiment, cancer or tumors are characterized by having CDCP1 expression or overexpression.

[0070] In another aspect of the present invention, the present disclosure provides a method for treating cancer, comprising administering a therapeutically effective amount of an antibody or antigen-binding moiety thereof as described herein, or a bispecific antibody or ADC as described herein, and an anti-anti-PD-L1 antibody to a target in need to inhibit or reduce solid tumor growth.

[0071] In some embodiments, the cancer is selected from the group consisting of breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer. In one embodiment, the cancer is breast cancer, for example, triple-negative breast cancer. In one embodiment, the cancer is colon cancer. In one embodiment, the cancer is lung cancer, for example, non-small cell lung cancer (NSCLC).

[0072] In another embodiment, the present invention provides a method for inhibiting or reducing solid tumor growth in a subject having a solid tumor. The method comprises administering a therapeutically effective amount of an antibody or antigen-binding moiety thereof as described herein, or a bispecific antibody or ADC as described herein, and an anti-anti-PD-L1 antibody to a subject having a solid tumor to inhibit or reduce solid tumor growth.

[0073] In some embodiments, the cancer is selected from the group consisting of breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer. In one embodiment, the cancer is breast cancer, for example, triple-negative breast cancer. In one embodiment, the cancer is colon cancer. In one embodiment, the cancer is lung cancer, for example, non-small cell lung cancer (NSCLC).

[0074] In one embodiment, an antibody or its antigen-binding moiety, or a bispecific antibody as described herein, or an ADC, is administered in combination with an additional agent or additional therapy. In one embodiment, the additional agent is an immune checkpoint inhibitor, such as an antibody selected from the group consisting of anti-PD1 antibodies and anti-CTLA-4 antibodies. In one embodiment, the additional therapy is radiation. In one embodiment, the additional agent is a chemotherapeutic agent.

[0075] In one embodiment, cancer or tumors are characterized by having CDCP1 expression or overexpression.

[0076] In some embodiments, the present disclosure provides a method for inhibiting or reducing solid tumor growth in a subject having a solid tumor, the method comprising administering an effective amount of an antibody or antigen-binding moiety thereof as described herein, or an ADC as described herein, to a subject having a solid tumor to inhibit or reduce solid tumor growth.

[0077] In some embodiments, the antibody or its antigen-binding moiety, or the ADC, is administered in combination with an additional agent or additional therapy. In other embodiments, the additional agent is an immune checkpoint inhibitor. In yet another embodiment, the immune checkpoint inhibitor is an antibody. In yet another embodiment, the antibody is selected from the group consisting of anti-PD1 antibody, anti-PD-L1 antibody, or anti-CTLA-4 antibody. In yet another embodiment, the additional therapy is radiation. In yet another embodiment, the additional agent is a chemotherapeutic agent. In some embodiments, the cancer or tumor is characterized by having CDCP1 expression or overexpression.

[0078] In another aspect, the disclosure relates to a polynucleotide linked to a heterogeneous nucleic acid, wherein the polynucleotide is selected from the group consisting of: (a) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof, comprising a heavy chain variable region (VH) having the amino acid sequence shown in Figure 20, which, when paired with a corresponding light chain variable region (VL) as shown in Figure 15, binds to the CDCP1 protein; (b) a VL comprising CDR1, 2, and 3 having the amino acid sequence shown in Figure 20, which, when paired with a corresponding VH as shown in Figure 15, binds to the CDCP1 protein. (c) A polynucleotide encoding an immunoglobulin light chain or fragment thereof, comprising a VL that binds to 1; (i) an immunoglobulin heavy chain or fragment thereof comprising a VH comprising CDR1, 2, and 3 having the amino acid sequences shown in Figure 20; and (ii) a polynucleotide encoding an immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, 2, and 3 having the amino acid sequences shown in Figure 20; and (d) a polynucleotide encoding an immunoglobulin heavy chain or fragment thereof comprising a VH having the amino acid sequence shown in Figure 18, which binds to CDCP1 when paired with the corresponding VL as shown in Figure 15.

[0079] In one embodiment, the present disclosure features an expression vector comprising a heterogeneous promoter operably ligated to a polynucleotide encoding a polypeptide disclosed herein.

[0080] In another embodiment, the present disclosure provides an expression vector, for example, a plasmid, phage, or virus, comprising: a first polynucleotide encoding a first polypeptide comprising an immunoglobulin heavy chain or fragment thereof, comprising a heavy chain variable region (VH) comprising VH complementarity-determining regions (CDRs) 1, 2, and 3 having the amino acid sequence shown in Figure 20; and a second polynucleotide encoding a second polypeptide comprising an immunoglobulin light chain or fragment thereof, comprising a light chain variable region (VL) comprising VL CDRs 1, 2, and 3 having the amino acid sequence shown in Figure 20, wherein the immunoglobulin heavy chain or fragment, when paired with the immunoglobulin light chain or fragment, forms an anti-CDCP1 antibody or a CDCP1-binding fragment thereof.

[0081] In some embodiments, the complementarity-determining region (CDR) sequences of the heavy-chain variable region and the light-chain variable region include or consist of a CDR sequence as shown in Figure 20. In some embodiments, the CDR sequences of the heavy-chain variable region and the light-chain variable region are at least 80%, 90%, 92%, 95%, 97%, 98%, 99%, or 100% identical to the CDR sequence shown in Figure 20. In some embodiments, the CDR sequences of the heavy-chain variable region and the light-chain variable region differ from the CDR sequence in Figure 20 by one, two, three, four, or five amino acids. In some embodiments, the CDR in Figure 20 is substituted with one, two, three, four, or five conserved amino acids.

[0082] In another embodiment, the disclosure features a composition comprising at least one antibody disclosed herein conjugated to a therapeutic agent, such as a cytotoxic agent or a radioisotope, and / or a reporter group. In some embodiments, the antibody conjugated to the therapeutic agent is administered to a subject to induce cell death in cancer cells, such as cancer cells that express or overexpress the CDCP1 protein or have the CDCP1 protein on their cell surface.

[0083] In some embodiments, the antibody is conjugated to a detectable marker. The conjugate is administered to a subject to detect cancer cells expressing the CDCP1 protein, and / or cancer cells having detectable and / or elevated levels of the CDCP1 protein.

[0084] In some embodiments, antibodies are linked to a surface (e.g., a microfluidic device, chromatographic resin, array, polymer, or beads) (e.g., covalently, by hydrogen, or ionic bonds).

[0085] In further embodiments, the Disclosure features a composition comprising at least one of the antibodies disclosed herein and a pharmaceutically acceptable excipient. In some embodiments, the Disclosure features a dry (e.g., lyophilized) composition comprising one or more antibodies disclosed herein and optionally one or more pharmaceutically acceptable excipients.

[0086] In other embodiments, the disclosure features a polynucleotide, such as DNA, encoding any polypeptide chain, such as an antibody heavy chain or light chain, of any of the antibodies disclosed herein. For example, the polynucleotide may contain a sequence disclosed herein. In some embodiments, the polynucleotide, such as DNA, does not contain introns. The disclosure also features vectors containing the polynucleotide, such as recombinant vectors and expression vectors, and cells containing the polynucleotide and / or vector, such as isolated cells, such as recombinant cells or hybridomas. In some embodiments, the vector is stably integrated into the chromosome of a cell, such as a mammalian cell, a bacterial cell, or a yeast cell. In some embodiments, the disclosure features a method for producing an antibody, comprising culturing a cell, such as an isolated cell, under conditions in which the antibody is expressed, and a method for collecting the antibody.

[0087] This disclosure features antibodies, nucleic acids, compositions, and cells disclosed herein, as well as their use for treating, preventing, imaging, and / or diagnosing cancer. In some embodiments, the compositions are formulated for intravenous administration. In some embodiments, the cancer expresses (e.g., overexpresses) CDCP1 or has CDCP1 on its cell surface. In some embodiments, the cancer is characterized by the presence of CDCP1 and / or elevated levels of CDCP1 protein produced by the cancer cells (e.g., compared to a reference level, e.g., CDCP1 protein levels produced by a healthy subject). In a further embodiment, the Disclosure provides a method for treating cancer (e.g., cancer characterized by overexpression of CDCP1 in cancer cells, or cancer characterized by having CDCP1 on the surface of cancer cells) (e.g., breast cancer, triple-negative breast cancer, carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, or hematological malignancies), comprising administering an antibody, nucleic acid, composition, or cell disclosed herein to a subject having cancer in a therapeutically effective dose.

[0088] In another aspect, the Disclosure features a method comprising administering an antibody or composition disclosed herein, e.g., a cell composition, an antibody-drug conjugate, or an antibody-radioisotope conjugate, to a subject in need, e.g., a cancer characterized by overexpression of CDCP1 in cancer cells, or a cancer characterized by having CDCP1 on the surface of cancer cells, e.g., breast cancer, triple-negative breast cancer, carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, colon cancer, or hematological malignancy cells, or a subject identified or diagnosed as having such cells.

[0089] In some embodiments, a subject is identified, for example, as a subject expressing CDCP1, using one of the methods described herein, or as a subject having a level of CDCP1 protein elevated compared to a threshold level of CDCP1 protein indicating that the antibody described herein should be administered to the subject, for example, a reference level, e.g., a CDCP1 protein level in a healthy subject, a non-cancerous level, e.g., a CDCP1 protein level in a primary cell, or a determined level of CDCP1 protein higher than that value.

[0090] In yet another embodiment, the Disclosure features a method for cancer prevention or for reducing the risk to a subject of developing cancer characterized by the expression, e.g., overexpression, of the CDCP1 protein in cancer cells, or cancer characterized by having CDCP1 on the surface of cancer cells, e.g., breast cancer (e.g., triple-negative breast cancer), carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, or hematological malignancies (e.g., compared to a subject at risk of developing cancer but not receiving treatment or receiving different treatment). The method comprises administering an antibody, nucleic acid, composition, or cell disclosed herein to a subject in need in a prophylactically effective dose. In some embodiments, the cancer expresses the CDCP1 protein. In some embodiments, the cancer cells have CDCP1 on their cell surface. In some embodiments of these methods, subjects have been identified as being at high risk of developing cancer.

[0091] In another embodiment, the Disclosure features a method for detecting the CDCP1 protein (e.g., CDCP1 protein) in a sample (e.g., a biopsy sample). The method includes contacting the sample with an antibody disclosed herein and detecting the binding of the activator to the sample, thereby detecting the CDCP1 protein in the sample. Some embodiments further include recording the detection or non-detection of the CDCP1 protein in the clinical record of the subject from whom the sample was obtained. In some embodiments, the clinical record is stored in a tangible computer-readable medium, such as a disk, magnetic tape, or computer memory.

[0092] In some embodiments of the methods described herein, the antibodies described herein may be brought into contact with a sample and / or cells, and the antibodies against CDCP1 may be used in immunoassays (e.g., enzyme-linked immunosorbent assays), fluorescence-assisted cell sorting, microfluidics, and chromatography.

[0093] In one embodiment, the present invention provides an antibody or an antigen-binding fragment thereof that binds to CUB domain-containing protein 1 (CDCP1). The antibody or its antigen-binding portion comprises a heavy chain variable region (VH) including complementarity-determining regions (CDRs) 1, 2, and 3, wherein the CDR1 region contains an amino acid sequence that is at least 80% identical to the selected VH CDR1 amino acid sequence, the CDR2 region contains an amino acid sequence that is at least 80% identical to the selected VH CDR2 amino acid sequence, and the CDR3 region contains an amino acid sequence that is at least 80% identical to the selected VH CDR3 amino acid sequence, and a light chain variable region (VL) including CDRs 1, 2, and 3, wherein the CDR1 region contains an amino acid sequence that is at least 80% identical to the selected VL CDR1 amino acid sequence, the CDR2 region contains an amino acid sequence that is at least 80% identical to the selected VL CDR2 amino acid sequence, and the CDR3 region contains an amino acid sequence that is at least 80% identical to the selected VL CDR3 amino acid sequence, where the selected VH CDR1, 2, and 3 amino acid sequences and the selected VL The amino acid sequences of CDR1, 2, and 3 are one of the following: (1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 5, 6, and 7 respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 8, 9, and 10 respectively; (2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 15, 16, and 17 respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 18, 19, and 20 respectively; (3) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 25, 26, and 27 respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 28, 29, and 30 respectively; (4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 35, 36, and 37 respectively, and the selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 38, 39, and 40, respectively; (5) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 45, 46, and 47, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 48, 49, and 50, respectively;(6) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 55, 56, and 57, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 58, 59, and 60, respectively; (7) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 65, 66, and 67, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 68, 69, and 70, respectively; (8) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 75, 76, and 77, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 78, 79, and 80, respectively; (9) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 85, 86, and 87, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 88, 89, and 90, respectively; (10) Selected VH The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 95, 96, and 97, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 98, 99, and 100, respectively; (11) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 105, 106, and 107, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 108, 109, and 110, respectively; (12) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 115, 116, and 117, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 118, 119, and 120, respectively; (13) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 125, 126, and 127, respectively, and the selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 128, 129, and 130, respectively; (14) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 135, 136, and 137, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 138, 139, and 140, respectively; (15) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 145, 146, and 147, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 148, 149, and 150, respectively;(16) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 155, 156, and 157, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 158, 159, and 160, respectively; (17) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 165, 166, and 167, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 168, 169, and 170, respectively; (18) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 175, 176, and 177, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 178, 179, and 180, respectively; (19) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 185, 186, and 187, respectively, and the selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 188, 189, and 190, respectively; (20) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 195, 196, and 197, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 198, 199, and 200, respectively; (21) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 205, 206, and 207, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 208, 209, and 210, respectively; (22) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 215, 216, and 217, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 218, 219, and 220, respectively; (23) Selected VH The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 225, 226, and 227, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 228, 229, and 230, respectively; (24) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 235, 236, and 237, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 238, 239, and 240, respectively;(25) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 245, 246, and 247, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 248, 249, and 250, respectively; (26) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 255, 256, and 257, respectively, and the selected VL; The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 258, 259, and 260, respectively; (27) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 265, 266, and 267, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 268, 269, and 270, respectively; (28) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 275, 276, and 277, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 278, 279, and 280, respectively; (29) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 285, 286, and 287, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 288, 289, and 290, respectively; (30) Selected VH The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 295, 296, and 297, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 298, 299, and 300, respectively; (31) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 305, 306, and 307, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 308, 309, and 310, respectively; (32) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 315, 316, and 317, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 318, 319, and 320, respectively; (33) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 325, 326, and 327, respectively, and the selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 328, 329, and 330, respectively; (34) Selected VH The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 335, 336, and 337, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 338, 339, and 340, respectively; (35) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 345, 346, and 347, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 348, 349, and 350, respectively; (36) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 355, 356, and 357, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 358, 359, and 360, respectively; (37) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 365, 366, and 367, respectively, and the selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 368, 369, and 370, respectively; (38) The amino acid sequences of selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 375, 376, and 377, respectively, and the amino acid sequences of selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 378, 379, and 380, respectively; (39) The amino acid sequences of selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 385, 386, and 387, respectively, and the amino acid sequences of selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 388, 389, and 390, respectively; and (40) The amino acid sequences of selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 395, 396, and 397, respectively, and the amino acid sequences of selected VL The amino acid sequences of CDR1, 2, and 3 are shown in SEQ ID NOs. 398, 399, and 400, respectively, where the antibody or its antigen-binding portion specifically binds to CUB domain-containing protein 1 (CDCP1).

[0094] In one embodiment, the antibody or its antigen-binding fragment specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1. In one embodiment, the antibody or its antigen-binding fragment has a dissociation constant (K) for human CDCP1. d ) is less than 10 nM, and / or K against cynomolgus monkey CDCP1 dHowever, it is less than 10 nM. In one embodiment, the antibody or its antigen-binding fragment is a humanized antibody or its antigen-binding fragment.

[0095] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively.

[0096] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 15, 16, and 17, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 18, 19, and 20, respectively.

[0097] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 25, 26, and 27, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 28, 29, and 30, respectively.

[0098] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 35, 36, and 37, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively.

[0099] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 45, 46, and 47, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively.

[0100] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 58, 59, and 60, respectively.

[0101] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 65, 66, and 67, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 68, 69, and 70, respectively.

[0102] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively.

[0103] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively.

[0104] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 98, 99, and 100, respectively.

[0105] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 105, 106, and 107, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 108, 109, and 110, respectively.

[0106] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 115, 116, and 117, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 118, 119, and 120, respectively.

[0107] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 125, 126, and 127, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 128, 129, and 130, respectively.

[0108] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 135, 136, and 137, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 138, 139, and 140, respectively.

[0109] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 145, 146, and 147, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 148, 149, and 150, respectively.

[0110] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 155, 156, and 157, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 158, 159, and 160, respectively.

[0111] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 165, 166, and 167, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively.

[0112] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 175, 176, and 177, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 178, 179, and 180, respectively.

[0113] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively.

[0114] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 195, 196, and 197, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs: 198, 199, and 200, respectively.

[0115] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 205, 206, and 207, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 208, 209, and 210, respectively.

[0116] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 215, 216, and 217, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively.

[0117] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively.

[0118] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 235, 236, and 237, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 238, 239, and 240, respectively.

[0119] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 245, 246, and 247, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively.

[0120] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively.

[0121] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 268, 269, and 270, respectively.

[0122] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 275, 276, and 277, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 278, 279, and 280, respectively.

[0123] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively.

[0124] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 295, 296, and 297, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively.

[0125] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 305, 306, and 307, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 308, 309, and 310, respectively.

[0126] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 315, 316, and 317, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively.

[0127] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 328, 329, and 330, respectively.

[0128] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 335, 336, and 337, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 338, 339, and 340, respectively.

[0129] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 345, 346, and 347, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively.

[0130] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 355, 356, and 357, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively.

[0131] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 365, 366, and 367, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively.

[0132] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 375, 376, and 377, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 378, 379, and 380, respectively.

[0133] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 385, 386, and 387, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 388, 389, and 390, respectively.

[0134] In one embodiment, the VH of the antibody or its antigen-binding portion comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 395, 396, and 397, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively.

[0135] In another embodiment, the present invention relates to (1) an immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively, wherein the VH, when paired with a light chain variable region (VL) having amino acid sequences shown in SEQ ID NOs. 2, binds to CDCP1; and (2) an immunoglobulin light chain or fragment thereof comprising a VL containing CDRs 1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively, wherein the VL is (3) an immunoglobulin light chain or fragment thereof, which, when paired with a VH having the amino acid sequence shown in SEQ ID NO: 1, binds to CDCP1; (4) an immunoglobulin heavy chain or fragment thereof comprising a VH comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 15, 16, and 17, respectively, wherein the VH is an immunoglobulin heavy chain or fragment thereof, which, when paired with a VL having the amino acid sequence shown in SEQ ID NO: 12, binds to CDCP1; (5) a VL comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 18, 19, and 20, respectively (5) An immunoglobulin light chain or fragment thereof, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO: 11, binds to CDCP1; (6) An immunoglobulin heavy chain or fragment thereof, comprising a VH having the amino acid sequences shown in SEQ ID NOs: 25, 26, and 27, respectively, wherein the VH, when paired with a VL having the amino acid sequence shown in SEQ ID NO: 22, binds to CDCP1; (7) As shown in SEQ ID NOs: 28, 29, and 30, respectively (7) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequence shown in SEQ ID NO: 21, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 21, binds to CDCP1; (7) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NO: 35, 36, and 37, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 32, binds to CDCP1;(8) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 31, binds to CDCP1; (9) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 45, 46, and 47, respectively, wherein the VH, when paired with a VL having the amino acid sequence shown in SEQ ID NOs. 42 (10) An immunoglobulin light chain or fragment thereof that binds to CDCP1, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 41, binds to CDCP1; (11) An immunoglobulin light chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively. (12) an immunoglobulin light chain or fragment comprising a VL containing CDR1, 2, 3 having amino acid sequences shown in SEQ ID NO: 58, 59, and 60, wherein the VH is an immunoglobulin heavy chain or fragment that binds to CDCP1 when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 51; (13) an immunoglobulin light chain or fragment comprising a VL containing CDR1, 2, 3 having amino acid sequences shown in SEQ ID NO: 65, 66, and 67, respectively (14) An immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, 2, and 3, wherein the VH, when paired with a VL having the amino acid sequence shown in SEQ ID NO: 62, binds to CDCP1; (14) An immunoglobulin light chain or fragment thereof comprising a VL having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 68, 69, and 70, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO: 61, binds to CDCP1;(15) An immunoglobulin heavy chain or fragment thereof comprising VH comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NOs. 72, binds to CDCP1; (16) An immunoglobulin light chain or fragment thereof comprising VL comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively, wherein the VL, when paired with VH having the amino acid sequence shown in SEQ ID NOs. 71 (17) An immunoglobulin light chain or fragment thereof that, when paired, binds to CDCP1; (18) An immunoglobulin light chain or fragment thereof comprising a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively, wherein the VH, when paired with a VL having the amino acid sequence shown in SEQ ID NO. 82, binds to CDCP1; (19) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively. (19) an immunoglobulin light chain or fragment thereof comprising a VL which, when paired with a VH which contains the amino acid sequence shown in SEQ ID NO: 81, binds to CDCP1; (20) an immunoglobulin heavy chain or fragment thereof comprising a VH which contains CDR1, 2, 3 which have the amino acid sequences shown in SEQ ID NOs: 95, 96, and 97, respectively, wherein the VH which, when paired with a VL which contains the amino acid sequence shown in SEQ ID NO: 92, binds to CDCP1; (3) an immunoglobulin heavy chain or fragment thereof which has the amino acid sequences shown in SEQ ID NOs: 98, 99, and 100, respectively (21) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 91, binds to CDCP1; (21) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 105, 106, and 107, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 102, binds to CDCP1;(22) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 108, 109, and 110, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 101, binds to CDCP1; (23) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 115, 116, and 117, respectively, wherein the VH has the amino acid sequence shown in SEQ ID NOs. 112 (24) An immunoglobulin heavy chain or fragment thereof that, when paired with L, binds to CDCP1; (25) An immunoglobulin light chain or fragment thereof comprising VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 118, 119, and 120, respectively, wherein VL, when paired with VH having the amino acid sequence shown in SEQ ID NOs. 111, binds to CDCP1; (26) An immunoglobulin heavy chain or fragment thereof comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 125, 126, and 127, respectively. (26) An immunoglobulin heavy chain or fragment thereof, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 122, binds to CDCP1; (27) An immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 128, 129, and 130, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 121, binds to CDCP1; (28) An immunoglobulin light chain or fragment thereof, wherein the amino acid sequences shown in SEQ ID NOs: 135, 136, and 137, respectively (28) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the sequence, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 132, binds to CDCP1; (28) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NO: 138, 139, and 140, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 131, binds to CDCP1;(29) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 145, 146, and 147, respectively; (30) an immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 148, 149, and 150, respectively, wherein the VL contains an immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 148, 149, and 150, respectively, wherein the VL contains an immunoglobulin light chain or fragment thereof comprising a VH containing the amino acid sequence shown in SEQ ID NO: 141, respectively, and binds to CDCP1; (31) SEQ ID NOs: 155, 156, and 157 (32) An immunoglobulin heavy chain or fragment thereof comprising VH comprising CDR1, 2, and 3 having the amino acid sequences shown respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO: 152, binds to CDCP1; (32) An immunoglobulin light chain or fragment thereof comprising VL comprising CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 158, 159, and 160 respectively, wherein the VL, when paired with VH having the amino acid sequence shown in SEQ ID NO: 151 (33) An immunoglobulin light chain or fragment thereof that binds to CDCP1 when paired with a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 165, 166, and 167, respectively, wherein the VH binds to CDCP1 when paired with a VL containing the amino acid sequence shown in SEQ ID NOs. 162; (34) An immunoglobulin light chain or fragment thereof that includes a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively, wherein the VL binds to CDCP1 when paired with a VH containing the amino acid sequence shown in SEQ ID NOs. 161; (35) An immunoglobulin heavy chain or fragment thereof that includes a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 175, 176, and 177, respectively, wherein the VH binds to CDCP1 when paired with a VL containing the amino acid sequence shown in SEQ ID NOs. 172;(36) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 178, 179, and 180, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 171, binds to CDCP1; (37) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively, wherein the VH has the amino acid sequence shown in SEQ ID NOs. 182 (38) An immunoglobulin heavy chain or fragment thereof that, when paired with L, binds to CDCP1; (39) An immunoglobulin light chain or fragment thereof comprising VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively, wherein VL, when paired with VH having the amino acid sequence shown in SEQ ID NOs. 181, binds to CDCP1; (39) An immunoglobulin heavy chain or fragment thereof comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 195, 196, and 197, respectively. (40) An immunoglobulin heavy chain or fragment thereof, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 192, binds to CDCP1; (41) An immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 198, 199, and 200, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 191, binds to CDCP1; (42) Amino acids shown in SEQ ID NOs: 205, 206, and 207, respectively (42) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the sequence, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 202, binds to CDCP1; (42) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NO: 208, 209, and 210, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 201, binds to CDCP1;(43) An immunoglobulin heavy chain or fragment thereof comprising VH comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 215, 216, and 217, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NOs. 212, binds to CDCP1; (44) An immunoglobulin light chain or fragment thereof comprising VL comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively, wherein the VL comprises V (45) An immunoglobulin light chain or fragment thereof that, when paired with H, binds to CDCP1; (46) An immunoglobulin heavy chain or fragment thereof comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NOs. 222, binds to CDCP1; (47) An immunoglobulin light chain or fragment thereof comprising VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively. (47) An immunoglobulin light chain or fragment thereof comprising a VL which, when paired with a VH having the amino acid sequence shown in SEQ ID NO: 221, binds to CDCP1; (48) An immunoglobulin heavy chain or fragment thereof comprising a VH having the amino acid sequences shown in SEQ ID NOs: 235, 236, and 237, respectively, wherein the VH which, when paired with a VL having the amino acid sequence shown in SEQ ID NO: 232, binds to CDCP1; (49) Amino acids shown in SEQ ID NOs: 238, 239, and 240, respectively (49) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the sequence, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 231, binds to CDCP1; (49) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 245, 246, and 247, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 242, binds to CDCP1;(50) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 241, binds to CDCP1; (51) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively, wherein the VH has the amino acid sequence shown in SEQ ID NOs. 252 (52) An immunoglobulin heavy chain or fragment thereof that, when paired with L, binds to CDCP1; (53) An immunoglobulin light chain or fragment thereof comprising VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively, wherein VL, when paired with VH having the amino acid sequence shown in SEQ ID NOs. 251, binds to CDCP1; (54) An immunoglobulin heavy chain or fragment thereof comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively. (54) An immunoglobulin light chain or fragment comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 268, 269, and 270, respectively, wherein the VL contains CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 261, respectively, and binds to CDCP1; (55) Amino acids shown in SEQ ID NO: 275, 276, and 277, respectively (56) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the sequence, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 272, binds to CDCP1; (56) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 278, 279, and 280, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 271, binds to CDCP1;(57) An immunoglobulin heavy chain or fragment thereof comprising VH comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NOs. 282, binds to CDCP1; (58) An immunoglobulin light chain or fragment thereof comprising VL comprising CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively, wherein the VL comprises V (59) An immunoglobulin light chain or fragment thereof that, when paired with H, binds to CDCP1; (60) An immunoglobulin light chain or fragment thereof that includes VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 295, 296, and 297, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NOs. 292, binds to CDCP1; (60) An immunoglobulin light chain or fragment thereof that includes VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively. (61) An immunoglobulin light chain or fragment thereof, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 291, binds to CDCP1; (62) An immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 305, 306, and 307, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 302, binds to CDCP1; (62) Amino acids shown in SEQ ID NOs: 308, 309, and 310, respectively (63) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the sequence, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 301, binds to CDCP1; (63) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 315, 316, and 317, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 312, binds to CDCP1;(64) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 311, binds to CDCP1; (65) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively; (66) an immunoglobulin light chain or fragment comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 328, 329, and 330, wherein the VL contains an immunoglobulin light chain or fragment comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NO: 328, 329, and 330, respectively, wherein the VL contains an immunoglobulin light chain or fragment comprising a VH containing the amino acid sequence shown in SEQ ID NO: 321, respectively, and binds to CDCP1; (67) SEQ ID NOs: 335, 336, and 337 (68) An immunoglobulin heavy chain or fragment thereof comprising VH comprising CDR1, 2, and 3 having the amino acid sequences shown respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO: 332, binds to CDCP1; (68) An immunoglobulin light chain or fragment thereof comprising VL comprising CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 338, 339, and 340 respectively, wherein the VL, when paired with VH having the amino acid sequence shown in SEQ ID NO: 331 (69) An immunoglobulin light chain or fragment thereof that binds to CDCP1 when paired with a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 345, 346, and 347, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NOs. 342, binds to CDCP1; (70) An immunoglobulin light chain or fragment thereof that includes a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NOs. 341, binds to CDCP1; (71) An immunoglobulin heavy chain or fragment thereof that includes a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 355, 356, and 357, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NOs. 352, binds to CDCP1;(72) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 351, binds to CDCP1; (73) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 365, 366, and 367, respectively, wherein the VH has the amino acid sequence shown in SEQ ID NOs. 362 (74) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively, wherein the VL is an immunoglobulin light chain or fragment thereof comprising a VH containing the amino acid sequence shown in SEQ ID NOs. 361, respectively, and which binds to CDCP1 when paired with a VH having the amino acid sequence shown in SEQ ID NOs. 361; (75) An immunoglobulin heavy chain or thereof comprising a VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 375, 376, and 377, respectively. (76) An immunoglobulin heavy chain or fragment thereof, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 372, binds to CDCP1; (77) An immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs: 378, 379, and 380, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 371, binds to CDCP1; (78) Amino acids shown in SEQ ID NOs: 385, 386, and 387, respectively (78) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the sequence, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NO: 382, ​​binds to CDCP1; (78) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 388, 389, and 390, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 381, binds to CDCP1;(79) An immunoglobulin heavy chain or fragment thereof comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 395, 396, and 397, respectively, wherein the VH, when paired with a VL containing the amino acid sequence shown in SEQ ID NOs. 392, binds to CDCP1; or (80) A cDNA comprising a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively, wherein the VL, when paired with a VH containing the amino acid sequence shown in SEQ ID NOs. 391, binds to CDCP1.

[0136] In some embodiments, when paired with VL, VH specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1, and when paired with VH, VL specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1.

[0137] In some embodiments, the immunoglobulin heavy chain or fragment thereof is a humanized immunoglobulin heavy chain or fragment thereof, and the immunoglobulin light chain or fragment thereof is a humanized immunoglobulin light chain or fragment thereof.

[0138] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively.

[0139] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively.

[0140] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 15, 16, and 17, respectively.

[0141] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 18, 19, and 20, respectively.

[0142] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 25, 26, and 27, respectively.

[0143] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 28, 29, and 30, respectively.

[0144] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 35, 36, and 37, respectively.

[0145] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively.

[0146] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 45, 46, and 47.

[0147] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively.

[0148] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively.

[0149] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 58, 59, and 60, respectively.

[0150] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 65, 66, and 67, respectively.

[0151] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 68, 69, and 70, respectively.

[0152] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively.

[0153] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively.

[0154] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively.

[0155] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively.

[0156] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, respectively.

[0157] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 98, 99, and 100, respectively.

[0158] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 105, 106, and 107.

[0159] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 108, 109, and 110, respectively.

[0160] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 115, 116, and 117, respectively.

[0161] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 118, 119, and 120, respectively. In another embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 125, 126, and 127, respectively.

[0162] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 128, 129, and 130, respectively.

[0163] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 135, 136, and 137, respectively.

[0164] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 138, 139, and 140, respectively.

[0165] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 145, 146, and 147.

[0166] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 148, 149, and 150, respectively.

[0167] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 155, 156, and 157, respectively.

[0168] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 158, 159, and 160, respectively.

[0169] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 165, 166, and 167.

[0170] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively.

[0171] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 175, 176, and 177.

[0172] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 178, 179, and 180, respectively.

[0173] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively.

[0174] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively.

[0175] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 195, 196, and 197.

[0176] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 198, 199, and 200, respectively.

[0177] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 205, 206, and 207.

[0178] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 208, 209, and 210, respectively.

[0179] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 215, 216, and 217.

[0180] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively.

[0181] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively.

[0182] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively.

[0183] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 235, 236, and 237, respectively.

[0184] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 238, 239, and 240, respectively.

[0185] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 245, 246, and 247.

[0186] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively.

[0187] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively.

[0188] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively.

[0189] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively.

[0190] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 268, 269, and 270, respectively.

[0191] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 275, 276, and 277, respectively.

[0192] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 278, 279, and 280, respectively.

[0193] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively.

[0194] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively.

[0195] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 295, 296, and 297.

[0196] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively.

[0197] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 305, 306, and 307.

[0198] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 308, 309, and 310, respectively.

[0199] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 315, 316, and 317, respectively.

[0200] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively.

[0201] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH including CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively.

[0202] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 328, 329, and 330, respectively.

[0203] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 335, 336, and 337.

[0204] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, including a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 338, 339, and 340, respectively.

[0205] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 345, 346, and 347.

[0206] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively.

[0207] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 355, 356, and 357.

[0208] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively.

[0209] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 365, 366, and 367.

[0210] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively.

[0211] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs. 375, 376, and 377.

[0212] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 378, 379, and 380, respectively.

[0213] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having the amino acid sequences shown in SEQ ID NOs. 385, 386, and 387, respectively.

[0214] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 388, 389, and 390, respectively.

[0215] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a heavy chain or fragment thereof containing a VH having amino acid sequences CDR1, 2, and 3, respectively, as shown in SEQ ID NOs: 395, 396, and 397.

[0216] In one embodiment, the cDNA comprises a polynucleotide encoding a polypeptide comprising a light chain or fragment thereof, which includes a VL containing CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively.

[0217] In one embodiment, the present invention provides an antibody that binds to CDCP1 or an antigen-binding moiety thereof, comprising a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are as follows: (1) The selected VH sequence is SEQ ID NO: 1 and the selected VL sequence is SEQ ID NO: 2; (2) The selected VH sequence is SEQ ID NO: 11 and the selected VL sequence is SEQ ID NO: (3) The selected VH sequence is sequence number 21 and the selected VL sequence is sequence number 22; (4) The selected VH sequence is sequence number 31 and the selected VL sequence is sequence number 32; (5) The selected VH sequence is sequence number 41 and the selected VL sequence is sequence number 42; (6) The selected VH sequence is sequence number 51 and the selected VL sequence is sequence number 52; (7) The selected VH sequence is sequence number 61 and the selected VL sequence is sequence number 62; (8) The selected VH sequence is sequence number 71 (9) The selected VL sequence is sequence number 81 and the selected VL sequence is sequence number 82; (10) The selected VH sequence is sequence number 91 and the selected VL sequence is sequence number 92; (11) The selected VH sequence is sequence number 101 and the selected VL sequence is sequence number 102; (12) The selected VH sequence is sequence number 111 and the selected VL sequence is sequence number 112; (13) The selected VH sequence is sequence number 121 and the selected VL sequence is sequence number (14) The selected VH sequence is sequence number 131 and the selected VL sequence is sequence number 132; (15) The selected VH sequence is sequence number 141 and the selected VL sequence is sequence number 142; (16) The selected VH sequence is sequence number 151 and the selected VL sequence is sequence number 152; (17) The selected VH sequence is sequence number 161 and the selected VL sequence is sequence number 162; and (18) The selected VH sequence is sequence number 171 and the selected VL sequence is sequence number 172;(19) The selected VH sequence is sequence number 181 and the selected VL sequence is sequence number 182; (20) The selected VH sequence is sequence number 191 and the selected VL sequence is sequence number 192; (21) The selected VH sequence is sequence number 201 and the selected VL sequence is sequence number 202; (22) The selected VH sequence is sequence number 211 and the selected VL sequence is sequence number 212; (23) The selected VH sequence is sequence number 221 and the selected VL sequence is sequence number 222; (24) The selected VH The sequence is sequence number 231, and the selected VL sequence is sequence number 232; (25) The selected VH sequence is sequence number 241, and the selected VL sequence is sequence number 242; (26) The selected VH sequence is sequence number 251, and the selected VL sequence is sequence number 252; (27) The selected VH sequence is sequence number 261, and the selected VL sequence is sequence number 262; (28) The selected VH sequence is sequence number 271, and the selected VL sequence is sequence number 272; (29) The selected VH sequence is sequence number 281 (30) The selected VL sequence is sequence number 291 and the selected VL sequence is sequence number 292; (31) The selected VH sequence is sequence number 301 and the selected VL sequence is sequence number 302; (32) The selected VH sequence is sequence number 311 and the selected VL sequence is sequence number 312; (33) The selected VH sequence is sequence number 321 and the selected VL sequence is sequence number 322; (34) The selected VH sequence is sequence number 331 and the selected VL sequence (35) The selected VH sequence is sequence number 341 and the selected VL sequence is sequence number 342; (36) The selected VH sequence is sequence number 351 and the selected VL sequence is sequence number 352; (37) The selected VH sequence is sequence number 361 and the selected VL sequence is sequence number 362; (38) The selected VH sequence is sequence number 371 and the selected VL sequence is sequence number 372; (39) The selected VH sequence is sequence number 381 and the selected VL sequence is sequence number 382;(40) The selected VH sequence is one of sequence numbers 391 and the selected VL sequence is sequence number 392, where the antibody or its antigen-binding moiety specifically binds to CUB domain-containing protein 1 (CDCP1).

[0218] In one embodiment, the antibody or its antigen-binding fragment specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1.

[0219] In one embodiment, the antibody or its antigen-binding fragment has a dissociation constant (K) for human CDCP1. d ) is less than 10 nM, and / or the dissociation constant (K) for cynomolgus monkey CDCP1 d ) is less than 10 nM.

[0220] In one embodiment, the antibody or its antigen-binding fragment is a humanized antibody or its antigen-binding fragment.

[0221] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 1, and the VL portion includes the sequence of SEQ ID NO: 2.

[0222] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 11, and the VL portion includes the sequence of SEQ ID NO: 12.

[0223] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 21, and the VL portion includes the sequence of SEQ ID NO: 22.

[0224] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 31, and the VL portion includes the sequence of SEQ ID NO: 32.

[0225] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 41, and the VL portion includes the sequence of SEQ ID NO: 42.

[0226] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 51, and the VL comprises the sequence of SEQ ID NO: 52.

[0227] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 61, and the VL comprises the sequence of SEQ ID NO: 62.

[0228] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 71, and the VL comprises the sequence of SEQ ID NO: 72.

[0229] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 81, and the VL comprises the sequence of SEQ ID NO: 82.

[0230] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 91, and the VL comprises the sequence of SEQ ID NO: 92.

[0231] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 101, and the VL comprises the sequence of SEQ ID NO: 102.

[0232] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 111, and the VL comprises the sequence of SEQ ID NO: 112.

[0233] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 121, and the VL comprises the sequence of SEQ ID NO: 122.

[0234] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 131, and the VL comprises the sequence of SEQ ID NO: 132.

[0235] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 141, and the VL comprises the sequence of SEQ ID NO: 142.

[0236] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 151, and the VL portion includes the sequence of SEQ ID NO: 152.

[0237] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 161, and the VL portion includes the sequence of SEQ ID NO: 162.

[0238] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 171, and the VL portion includes the sequence of SEQ ID NO: 172.

[0239] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 181, and the VL portion includes the sequence of SEQ ID NO: 182.

[0240] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 191, and the VL portion includes the sequence of SEQ ID NO: 192.

[0241] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 201, and the VL portion includes the sequence of SEQ ID NO: 202.

[0242] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 211, and the VL portion includes the sequence of SEQ ID NO: 212.

[0243] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 221, and the VL portion includes the sequence of SEQ ID NO: 222.

[0244] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 231, and the VL portion includes the sequence of SEQ ID NO: 232.

[0245] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 241, and the VL portion includes the sequence of SEQ ID NO: 242.

[0246] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 251, and the VL comprises the sequence of SEQ ID NO: 252.

[0247] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 261, and the VL comprises the sequence of SEQ ID NO: 262.

[0248] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 271, and the VL comprises the sequence of SEQ ID NO: 272.

[0249] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 281, and the VL comprises the sequence of SEQ ID NO: 282.

[0250] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 291, and the VL comprises the sequence of SEQ ID NO: 292.

[0251] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 301, and the VL comprises the sequence of SEQ ID NO: 302.

[0252] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 311, and the VL comprises the sequence of SEQ ID NO: 312.

[0253] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 321, and the VL comprises the sequence of SEQ ID NO: 322.

[0254] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 331, and the VL comprises the sequence of SEQ ID NO: 332.

[0255] In one embodiment, the VH of the antibody or its antigen-binding portion comprises the sequence of SEQ ID NO: 341, and the VL comprises the sequence of SEQ ID NO: 342.

[0256] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 351, and the VL portion includes the sequence of SEQ ID NO: 352.

[0257] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 361, and the VL portion includes the sequence of SEQ ID NO: 362.

[0258] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 371, and the VL portion includes the sequence of SEQ ID NO: 372.

[0259] In one embodiment, the VH portion of the antibody or its antigen-binding portion includes the sequence of SEQ ID NO: 381, and the VL portion includes the sequence of SEQ ID NO: 382.

[0260] In one embodiment, the VH of the antibody or its antigen-binding fragment contains the sequence of SEQ ID NO: 391, and the VL contains the sequence of SEQ ID NO: 392, and the antibody or its antigen-binding fragment specifically binds to CUB domain-containing protein 1 (CDCP1).

[0261] In one embodiment, the antibody or its antigen-binding fragment binds to human CDCP1 and blocks the cleavage of human CDCP1 at residue 342. In one embodiment, the antibody or its antigen-binding fragment comprises VH containing CDR1, 2, 3 having the amino acid sequence shown in SEQ ID NOs. 85, 86, and 87, and VL containing CDR1, 2, 3 having the amino acid sequence shown in SEQ ID NOs. 88, 89, and 90. In one embodiment, the antibody or its antigen-binding fragment comprises VH containing CDR1, 2, 3 having the amino acid sequence shown in SEQ ID NOs. 95, 96, and 97, and VL containing CDR1, 2, 3 having the amino acid sequence shown in SEQ ID NOs. 98, 99, and 100.

[0262] In another aspect, this disclosure relates to antibody-drug conjugates having antibodies or antigen-binding fragments thereof and therapeutic agents disclosed herein.

[0263] In one embodiment, the antibody-drug conjugate comprises an antibody or its antigen-binding fragment and a therapeutic agent. In one embodiment, the therapeutic agent of the antibody-drug conjugate is a cytotoxic agent or a cell proliferation inhibitor. In one embodiment, the cytotoxic agent or cell proliferation inhibitor of the antibody-drug conjugate is a microtubule inhibitor or a DNA alkylator. In one embodiment, the cytotoxic agent or cell proliferation inhibitor of the antibody-drug conjugate is selected from the group consisting of DM4, MMAE, PDX, PDB, and IGN. In one embodiment, the agonist is DM4. In another embodiment, the agonist is MMAE. In one embodiment, the agonist is PDX. In one embodiment, the agonist is PDB. In one embodiment, the agonist is IGN. In one embodiment, the antibody or antigen-binding fragment of the antibody-drug conjugate is linked to the therapeutic agent by a linker.

[0264] In one embodiment, the linker in the antibody-drug conjugate is selected from the group consisting of cleavable peptides, charged hindered disulfides, and maleimide-caproyl-valine-citrulline.

[0265] In one embodiment, the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is D-Ala-L-Ala dpa.

[0266] In one embodiment, the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sSPDB).

[0267] In one embodiment, the therapeutic agent in the antibody-drug conjugate is MMAE, and the linker is maleimide-caproyl-valine-citrulline (MC-VC).

[0268] In one embodiment, the therapeutic agent in the antibody-drug conjugate is IGN, and the linker is D-Ala-L-Ala dpa.

[0269] One aspect of the present invention provides an antibody-drug conjugate having the formula Ab-[LD]n, where Ab comprises an antibody or an antigen-binding fragment thereof, L comprises a linker as needed, D is a therapeutic agent, and n is an integer from about 1 to about 20.

[0270] In one embodiment, a method is provided for treating a target cancer, comprising identifying a subject having cancer and administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an antibody-drug conjugate.

[0271] In one embodiment, the cancer is breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, or colon cancer.

[0272] In one embodiment, the cancer is triple-negative breast cancer. In one embodiment, the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is D-Ala-L-Ala dpa or sSPDB. In one embodiment, the therapeutic agent in the antibody-drug conjugate is MMAE, and the linker is MC-VC.

[0273] In one embodiment, the cancer is colon cancer. In one embodiment, the therapeutic agent in the antibody-drug conjugate is IGN, and the linker is D-Ala-L-Ala dpa. In one embodiment, the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is D-Ala-L-Ala dpa or sSPDB. In one embodiment, the therapeutic agent in the antibody-drug conjugate is MMAE, and the linker is MC-VC.

[0274] In one embodiment, the cancer is small cell lung cancer. In one embodiment, the therapeutic agent in the antibody-drug conjugate is IGN, and the linker is D-Ala-L-Ala dpa.

[0275] In another embodiment, the present invention provides a method for treating a target cancer, comprising identifying a subject having cancer and administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an antibody or an antigen-binding fragment thereof or a therapeutically effective amount of an antibody-drug conjugate.

[0276] In one embodiment, the cancer is breast cancer, triple-negative breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, or colon cancer.

[0277] In another aspect, the disclosure relates to a polynucleotide linked to a heterogeneous nucleic acid, wherein the polynucleotide is selected from the group consisting of: (a) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof, comprising a heavy chain variable region (VH) having the amino acid sequence shown in Figure 20, which, when paired with a corresponding light chain variable region (VL) as shown in Figure 15, binds to the CDCP1 protein; (b) a VL comprising CDR1, 2, and 3 having the amino acid sequence shown in Figure 20, which, when paired with a corresponding VH as shown in Figure 15, binds to the CDCP1 protein. (c) A polynucleotide encoding an immunoglobulin light chain or fragment thereof, comprising a VL that binds to 1; (i) an immunoglobulin heavy chain or fragment thereof comprising a VH comprising CDR1, 2, and 3 having the amino acid sequences shown in Figure 20; and (ii) a polynucleotide encoding an immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, 2, and 3 having the amino acid sequences shown in Figure 20; and (d) a polynucleotide encoding an immunoglobulin heavy chain or fragment thereof comprising a VH having the amino acid sequence shown in Figure 18, which binds to CDCP1 when paired with the corresponding VL as shown in Figure 15.

[0278] In one embodiment, the present invention features an expression vector comprising a heterogeneous promoter operably ligated to a polynucleotide encoding a polypeptide disclosed herein.

[0279] In another embodiment, the present disclosure provides an expression vector, for example, a plasmid, phage, or virus, comprising: a first polynucleotide encoding a first polypeptide comprising an immunoglobulin heavy chain or fragment thereof, comprising a heavy chain variable region (VH) comprising VH complementarity-determining regions (CDRs) 1, 2, and 3 having the amino acid sequence shown in Figure 20; and a second polynucleotide encoding a second polypeptide comprising an immunoglobulin light chain or fragment thereof, comprising a light chain variable region (VL) comprising VL CDRs 1, 2, and 3 having the amino acid sequence shown in Figure 20, wherein the immunoglobulin heavy chain or fragment, when paired with the immunoglobulin light chain or fragment, forms an anti-CDCP1 antibody or a CDCP1-binding fragment thereof.

[0280] In some embodiments, the complementarity-determining region (CDR) sequences of the heavy-chain variable region and the light-chain variable region include or consist of a CDR sequence as shown in Figure 20. In some embodiments, the CDR sequences of the heavy-chain variable region and the light-chain variable region are at least 80%, 90%, 92%, 95%, 97%, 98%, 99%, or 100% identical to the CDR sequence shown in Figure 20. In some embodiments, the CDR sequences of the heavy-chain variable region and the light-chain variable region differ from the CDR sequence in Figure 20 by one, two, three, four, or five amino acids. In some embodiments, the CDR in Figure 20 is substituted with one, two, three, four, or five conserved amino acids.

[0281] In another embodiment, the present invention provides a composition comprising at least one antibody disclosed herein conjugated to a therapeutic agent, such as a cytotoxic agent or a radioisotope, and / or a reporter group. In some embodiments, the antibody conjugated to the therapeutic agent is administered to a subject to induce cell death in cancer cells, for example, cancer cells that express or overexpress the CDCP1 protein or have the CDCP1 protein on their cell surface.

[0282] In some embodiments, the antibody is conjugated to a detectable marker. The conjugate is administered to a subject to detect cancer cells expressing the CDCP1 protein, and / or cancer cells having detectable and / or elevated levels of the CDCP1 protein.

[0283] In some embodiments, antibodies are linked to a surface (e.g., a microfluidic device, chromatographic resin, array, polymer, or beads) (e.g., covalently, by hydrogen, or ionic bonds).

[0284] In further embodiments, the present invention provides compositions comprising at least one of the antibodies disclosed herein and a pharmaceutically acceptable excipient. In some embodiments, the present disclosure features a dry (e.g., lyophilized) composition comprising one or more antibodies disclosed herein and optionally one or more pharmaceutically acceptable excipients.

[0285] In another embodiment, the present invention provides polynucleotides, such as DNA, that encode a polypeptide chain, such as an antibody heavy chain or light chain, of any of the antibodies disclosed herein. For example, the polynucleotide may contain a sequence disclosed herein. In some embodiments, the polynucleotide, such as DNA, does not contain introns. The disclosure also features vectors containing the polynucleotide, such as recombinant vectors and expression vectors, and cells containing the polynucleotide and / or vector, such as isolated cells, such as recombinant cells or hybridomas. In some embodiments, the vector is stably integrated into the chromosome of a cell, such as a mammalian cell, a bacterial cell, or a yeast cell. In some embodiments, the disclosure features a method for producing an antibody, comprising culturing a cell, such as an isolated cell, under conditions in which the antibody is expressed, and a method for collecting the antibody.

[0286] The present invention also provides antibodies, nucleic acids, compositions, and cells disclosed herein, as well as their use for treating, preventing, imaging, and / or diagnosing cancer. In some embodiments, the compositions are formulated for intravenous administration. In some embodiments, the cancer expresses (e.g., overexpresses) CDCP1 or has CDCP1 on its cell surface. In some embodiments, the cancer is characterized by the presence of CDCP1 and / or elevated levels of CDCP1 protein produced by the cancer cells (e.g., compared to a reference level, e.g., CDCP1 protein levels of CDCP1 protein produced by a healthy subject).

[0287] In a further embodiment, the present invention provides a method for treating cancer (for example, cancer characterized by overexpression of CDCP1 in cancer cells, or cancer characterized by having CDCP1 on the surface of cancer cells) (e.g., breast cancer, triple-negative breast cancer, carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, or hematological malignancies), comprising administering an antibody, nucleic acid, composition, or cell disclosed herein to a subject having cancer in a therapeutically effective dose.

[0288] In another aspect, the present invention provides a method comprising administering an antibody or composition disclosed herein, such as a cell composition, an antibody-drug conjugate, or an antibody-radioisotope conjugate, to a subject in need thereof, such as a cancer characterized by overexpression of CDCP1 in cancer cells, or a cancer characterized by having CDCP1 on the surface of cancer cells, such as breast cancer, triple-negative breast cancer, carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, colon cancer, or hematological malignancy cells.

[0289] In some embodiments, a subject is identified, for example, as a subject expressing CDCP1, using one of the methods described herein, or as a subject having a level of CDCP1 protein elevated compared to a threshold level of CDCP1 protein indicating that the antibody described herein should be administered to the subject, for example, a reference level, e.g., a CDCP1 protein level in a healthy subject, a non-cancerous level, e.g., a CDCP1 protein level in a primary cell, or a determined level of CDCP1 protein higher than that value.

[0290] In yet another aspect, the present invention provides a method for cancer prevention or for reducing the risk of a subject developing cancer characterized by the expression, e.g., overexpression, of the CDCP1 protein in cancer cells, or cancer characterized by having CDCP1 on the surface of cancer cells, e.g., breast cancer (e.g., triple-negative breast cancer), carcinoid cancer, cervical cancer, endometrial cancer, glioma, head and neck cancer, liver cancer, lung cancer, small cell lung cancer, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, gastric cancer, testicular cancer, thyroid cancer, bladder cancer, urethral cancer, colorectal cancer, or hematological malignancies (e.g., compared to a subject at risk of developing cancer but not receiving treatment or receiving different treatment). The method comprises administering an antibody, nucleic acid, composition, or cell disclosed herein to a subject in need in a prophylactically effective dose.

[0291] In some embodiments, cancer expresses the CDCP1 protein. In some embodiments, cancer cells have CDCP1 on their cell surface. In some implementations of any of these methods, subjects have been identified as being at high risk of developing cancer.

[0292] In another embodiment, the present invention provides a method for detecting the CDCP1 protein (e.g., CDCP1 protein) in a sample (e.g., a biopsy sample). The method comprises contacting the sample with an antibody disclosed herein and detecting the binding of the activator to the sample, thereby detecting the CDCP1 protein in the sample. Some embodiments further include recording the detection or non-detection of the CDCP1 protein in the clinical record of the subject from whom the sample was obtained. In some embodiments, the clinical record is stored in a tangible computer-readable medium, such as a disk, magnetic tape, or computer memory.

[0293] In some embodiments of the methods described herein, the antibodies described herein may be brought into contact with a sample and / or cells, and the antibodies against CDCP1 may be used in immunoassays (e.g., enzyme-linked immunosorbent assays), fluorescence-assisted cell sorting, microfluidics, and chromatography. In embodiments of the present invention, for example, the following items are provided. (Item 1) A heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the CDR1 region includes an amino acid sequence that is at least 80% identical to the selected VH CDR1 amino acid sequence, the CDR2 region includes an amino acid sequence that is at least 80% identical to the selected VH CDR2 amino acid sequence, and the CDR3 region includes an amino acid sequence that is at least 80% identical to the selected VH CDR3 amino acid sequence, and A light chain variable region (VL) comprising CDR1, 2, and 3, wherein the CDR1 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR1 amino acid sequence, the CDR2 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR2 amino acid sequence, and the CDR3 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR3 amino acid sequence. An antibody or antigen-binding fragment thereof that binds to CUB domain-containing protein 1 (CDCP1), including, The selected VH CDR1,2,3 amino acid sequences and the selected VL CDR1,2,3 amino acid sequences are as follows: 1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 5, 6, and 7, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 8, 9, and 10, respectively; 2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 15, 16, and 17, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 18, 19, and 20, respectively; 3) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 25, 26, and 27, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 28, 29, and 30, respectively; 4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 35, 36, and 37, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 38, 39, and 40, respectively; 5) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 45, 46, and 47, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 48, 49, and 50, respectively; 6) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 55, 56, and 57, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 58, 59, and 60, respectively; 7) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 65, 66, and 67, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 68, 69, and 70, respectively; 8) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 75, 76, and 77, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 78, 79, and 80, respectively; 9) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 85, 86, and 87, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 88, 89, and 90, respectively; 10) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 95, 96, and 97, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 98, 99, and 100, respectively; 11) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 105, 106, and 107, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 108, 109, and 110, respectively; 12) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 115, 116, and 117, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 118, 119, and 120, respectively; 13) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 125, 126, and 127, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 128, 129, and 130, respectively; 14) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 135, 136, and 137, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 138, 139, and 140, respectively; 15) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 145, 146, and 147, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 148, 149, and 150, respectively; 16) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 155, 156, and 157, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 158, 159, and 160, respectively; 17) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 165, 166, and 167, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 168, 169, and 170, respectively; 18) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 175, 176, and 177, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 178, 179, and 180, respectively; 19) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 185, 186, and 187, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 188, 189, and 190, respectively; 20) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 195, 196, and 197, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 198, 199, and 200, respectively; 21) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 205, 206, and 207, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 208, 209, and 210, respectively; 22) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 215, 216, and 217, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 218, 219, and 220, respectively; 23) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 225, 226, and 227, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 228, 229, and 230, respectively; 24) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 235, 236, and 237, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 238, 239, and 240, respectively; 25) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 245, 246, and 247, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 248, 249, and 250, respectively; 26) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 255, 256, and 257, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 258, 259, and 260, respectively; 27) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 265, 266, and 267, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 268, 269, and 270, respectively; 28) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 275, 276, and 277, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 278, 279, and 280, respectively; 29) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 285, 286, and 287, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 288, 289, and 290, respectively; 30) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 295, 296, and 297, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 298, 299, and 300, respectively; 31) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 305, 306, and 307, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 308, 309, and 310, respectively; 32) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 315, 316, and 317, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 318, 319, and 320, respectively; 33) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 325, 326, and 327, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 328, 329, and 330, respectively; 34) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 335, 336, and 337, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 338, 339, and 340, respectively; 35) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 345, 346, and 347, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 348, 349, and 350, respectively; 36) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 355, 356, and 357, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 358, 359, and 360, respectively; 37) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 365, 366, and 367, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 368, 369, and 370, respectively; 38) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 375, 376, and 377, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 378, 379, and 380, respectively; 39) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 385, 386, and 387, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 388, 389, and 390, respectively; and 40) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 395, 396, and 397, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 398, 399, and 400, respectively, being one of the above, and the antibody or its antigen-binding fragment specifically binds to CUB domain-containing protein 1 (CDCP1). (Item 2) The antibody or its antigen-binding fragment according to item 1, which specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1. (Item 3) The dissociation constant (K d ) for human CDCP1 is less than 10 nM, and / or the K d for cynomolgus monkey CDCP1 is less than 10 nM, the antibody or its antigen-binding fragment according to item 1. (Item 4) The antibody or its antigen-binding fragment according to item 1, which is a humanized antibody or its antigen-binding fragment. (Item 5) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively. (Item 6) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 15, 16, and 17, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 18, 19, and 20, respectively. (Item 7) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 25, 26, and 27, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 28, 29, and 30, respectively. (Item 8) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 35, 36, and 37, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively. (Item 9) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 45, 46, and 47, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively. (Item 10) The antibody or antigen-binding fragment according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 58, 59, and 60, respectively. (Item 11) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 65, 66, and 67, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 68, 69, and 70, respectively. (Item 12) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively. (Item 13) The antibody or antigen-binding fragment according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively. (Item 14) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 98, 99, and 100, respectively. (Item 15) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 105, 106, and 107, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 108, 109, and 110, respectively. (Item 16) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 115, 116, and 117, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 118, 119, and 120, respectively. (Item 17) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 125, 126, and 127, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 128, 129, and 130, respectively. (Item 18) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 135, 136, and 137, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 138, 139, and 140, respectively. (Item 19) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 145, 146, and 147, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 148, 149, and 150, respectively. (Item 20) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 155, 156, and 157, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 158, 159, and 160, respectively. (Item 21) The antibody or antigen-binding fragment according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 165, 166, and 167, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively. (Item 22) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 175, 176, and 177, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 178, 179, and 180, respectively. (Item 23) The antibody or antigen-binding fragment according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively. (Item 24) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 195, 196, and 197, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 198, 199, and 200, respectively. (Item 25) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 205, 206, and 207, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 208, 209, and 210, respectively. (Item 26) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 215, 216, and 217, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively. (Item 27) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively. (Item 28) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 235, 236, and 237, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 238, 239, and 240, respectively. (Item 29) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 245, 246, and 247, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively. (Item 30) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively. (Item 31) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 268, 269, and 270, respectively. (Item 32) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 275, 276, and 277, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 278, 279, and 280, respectively. (Item 33) The antibody or antigen-binding fragment according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively. (Item 34) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 295, 296, and 297, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively. (Item 35) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 305, 306, and 307, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 308, 309, and 310, respectively. (Item 36) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 315, 316, and 317, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively. (Item 37) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 328, 329, and 330, respectively. (Item 38) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 335, 336, and 337, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 338, 339, and 340, respectively. (Item 39) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 345, 346, and 347, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively. (Item 40) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 355, 356, and 357, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively. (Item 41) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 365, 366, and 367, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively. (Item 42) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 375, 376, and 377, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 378, 379, and 380, respectively. (Item 43) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 385, 386, and 387, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 388, 389, and 390, respectively. (Item 44) The antibody or antigen-binding fragment thereof according to item 1, wherein the VH comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 395, 396, and 397, respectively, and the VL comprises CDR1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively. (Item 45) (1) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3 having amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively, wherein the VH, when paired with a light chain variable region (VL) containing the amino acid sequence shown in SEQ ID NO. 2, binds to CDCP1; (2) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 1, binds to CDCP1; (3) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 15, 16, and 17, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 12, binds to CDCP1; (4) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 18, 19, and 20, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 11, binds to CDCP1; (5) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 25, 26, and 27, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 22, binds to CDCP1; (6) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 28, 29, and 30, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 21, binds to CDCP1; (7) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 35, 36, and 37, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 32, binds to CDCP1; (8) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 31, binds to CDCP1; (9) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 45, 46, and 47, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 42, binds to CDCP1; (10) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 41, binds to CDCP1; (11) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 52, binds to CDCP1; (12) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 58, 59, and 60, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 51, binds to CDCP1; (13) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 65, 66, and 67, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 62, binds to CDCP1; (14) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 68, 69, and 70, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 61, binds to CDCP1; (15) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 72, binds to CDCP1; (16) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 71, binds to CDCP1; (17) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 82, binds to CDCP1; (18) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 81, binds to CDCP1; (19) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 92, binds to CDCP1; (20) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 98, 99, and 100, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 91, binds to CDCP1; (21) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 105, 106, and 107, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 102, binds to CDCP1; (22) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 108, 109, and 110, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 101, binds to CDCP1; (23) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 115, 116, and 117, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 112, binds to CDCP1; (24) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 118, 119, and 120, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 111, binds to CDCP1; (25) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 125, 126, and 127, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 122, binds to CDCP1; (26) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 128, 129, and 130, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 121, binds to CDCP1; (27) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 135, 136, and 137, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 132, binds to CDCP1; (28) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 138, 139, and 140, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 131, binds to CDCP1; (29) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 145, 146, and 147, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 142, binds to CDCP1; (30) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 148, 149, and 150, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 141, binds to CDCP1; (31) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 155, 156, and 157, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 152, binds to CDCP1; (32) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 158, 159, and 160, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 151, binds to CDCP1; (33) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 165, 166, and 167, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 162, binds to CDCP1; (34) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 161, binds to CDCP1; (35) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 175, 176, and 177, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 172, binds to CDCP1; (36) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 178, 179, and 180, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 171, binds to CDCP1; (37) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 182, binds to CDCP1; (38) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 181, binds to CDCP1; (39) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 195, 196, and 197, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 192, binds to CDCP1; (40) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 198, 199, and 200, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 191, binds to CDCP1; (41) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 205, 206, and 207, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 202, binds to CDCP1; (42) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 208, 209, and 210, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 201, binds to CDCP1; (43) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 215, 216, and 217, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 212, binds to CDCP1; (44) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 211, binds to CDCP1; (45) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 222, binds to CDCP1; (46) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 221, binds to CDCP1; (47) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 235, 236, and 237, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 232, binds to CDCP1; (48) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 238, 239, and 240, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 231, binds to CDCP1; (49) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 245, 246, and 247, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 242, binds to CDCP1; (50) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 241, binds to CDCP1; (51) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 252, binds to CDCP1; (52) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 251, binds to CDCP1; (53) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 262, binds to CDCP1; (54) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 268, 269, and 270, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 261, binds to CDCP1; (55) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 275, 276, and 277, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 272, binds to CDCP1; (56) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 278, 279, and 280, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 271, binds to CDCP1; (57) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 282, binds to CDCP1; (58) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 281, binds to CDCP1; (59) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 295, 296, and 297, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 292, binds to CDCP1; (60) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 291, binds to CDCP1; (61) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 305, 306, and 307, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 302, binds to CDCP1; (62) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 308, 309, and 310, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 301, binds to CDCP1; (63) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 315, 316, and 317, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 312, binds to CDCP1; (64) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 311, binds to CDCP1; (65) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 322, binds to CDCP1; (66) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 328, 329, and 330, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 321, binds to CDCP1; (67) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 335, 336, and 337, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 332, binds to CDCP1; (68) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 338, 339, and 340, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 331, binds to CDCP1; (69) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 345, 346, and 347, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 342, binds to CDCP1; (70) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 341, binds to CDCP1; (71) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 355, 356, and 357, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 352, binds to CDCP1; (72) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 351, binds to CDCP1; (73) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 365, 366, and 367, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 362, binds to CDCP1; (74) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 361, binds to CDCP1; (75) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 375, 376, and 377, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 372, binds to CDCP1; (76) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 378, 379, and 380, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 371, binds to CDCP1; (77) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 385, 386, and 387, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 382, ​​binds to CDCP1; (78) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 388, 389, and 390, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 381, binds to CDCP1; (79) An immunoglobulin heavy chain or fragment thereof comprising VH having CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 395, 396, and 397, respectively, wherein the VH, when paired with VL having the amino acid sequence shown in SEQ ID NO. 392, binds to CDCP1; or (80) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively, wherein the VL, when paired with a VH having the amino acid sequence shown in SEQ ID NO. 391, binds to CDCP1. cDNA containing polynucleotides that encode a polypeptide. (Item 46) The cDNA described in item 45, wherein VH, when paired with VL, specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1, and VL, when paired with VH, specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1. (Item 47) The cDNA described in item 45, wherein the immunoglobulin heavy chain or fragment thereof is a humanized immunoglobulin heavy chain or fragment thereof, and the immunoglobulin light chain or fragment thereof is a humanized immunoglobulin light chain or fragment thereof. (Item 48) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 5, 6, and 7, respectively. (Item 49) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 8, 9, and 10, respectively. (Item 50) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 15, 16, and 17, respectively. (Item 51) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 18, 19, and 20, respectively. (Item 52) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 25, 26, and 27, respectively. (Item 53) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 28, 29, and 30, respectively. (Item 54) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 35, 36, and 37, respectively. (Item 55) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 38, 39, and 40, respectively. (Item 56) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 45, 46, and 47, respectively. (Item 57) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 48, 49, and 50, respectively. (Item 58) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 55, 56, and 57, respectively. (Item 59) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 58, 59, and 60, respectively. (Item 60) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 65, 66, and 67, respectively. (Item 61) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 68, 69, and 70, respectively. (Item 62) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 75, 76, and 77, respectively. (Item 63) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 78, 79, and 80, respectively. (Item 64) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, respectively. (Item 65) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 88, 89, and 90, respectively. (Item 66) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, respectively. (Item 67) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 98, 99, and 100, respectively. (Item 68) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 105, 106, and 107, respectively. (Item 69) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 108, 109, and 110, respectively. (Item 70) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 115, 116, and 117, respectively. (Item 71) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 118, 119, and 120, respectively. (Item 72) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 125, 126, and 127, respectively. (Item 73) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 128, 129, and 130, respectively. (Item 74) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 135, 136, and 137, respectively. (Item 75) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 138, 139, and 140, respectively. (Item 76) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 145, 146, and 147, respectively. (Item 77) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 148, 149, and 150, respectively. (Item 78) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 155, 156, and 157, respectively. (Item 79) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 158, 159, and 160, respectively. (Item 80) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 165, 166, and 167, respectively. (Item 81) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 168, 169, and 170, respectively. (Item 82) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 175, 176, and 177, respectively. (Item 83) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 178, 179, and 180, respectively. (Item 84) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 185, 186, and 187, respectively. (Item 85) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 188, 189, and 190, respectively. (Item 86) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 195, 196, and 197, respectively. (Item 87) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 198, 199, and 200, respectively. (Item 88) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 205, 206, and 207, respectively. (Item 89) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 208, 209, and 210, respectively. (Item 90) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 215, 216, and 217, respectively. (Item 91) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 218, 219, and 220, respectively. (Item 92) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 225, 226, and 227, respectively. (Item 93) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 228, 229, and 230, respectively. (Item 94) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 235, 236, and 237, respectively. (Item 95) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 238, 239, and 240, respectively. (Item 96) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 245, 246, and 247, respectively. (Item 97) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 248, 249, and 250, respectively. (Item 98) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 255, 256, and 257, respectively. (Item 99) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 258, 259, and 260, respectively. (Item 100) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 265, 266, and 267, respectively. (Item 101) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 268, 269, and 270, respectively. (Item 102) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 275, 276, and 277, respectively. (Item 103) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 278, 279, and 280, respectively. (Item 104) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 285, 286, and 287, respectively. (Item 105) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 288, 289, and 290, respectively. (Item 106) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 295, 296, and 297, respectively. (Item 107) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 298, 299, and 300, respectively. (Item 108) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 305, 306, and 307, respectively. (Item 109) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 308, 309, and 310, respectively. (Item 110) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 315, 316, and 317, respectively. (Item 111) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 318, 319, and 320, respectively. (Item 112) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 325, 326, and 327, respectively. (Item 113) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 328, 329, and 330, respectively. (Item 114) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 335, 336, and 337, respectively. (Item 115) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 338, 339, and 340, respectively. (Item 116) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 345, 346, and 347, respectively. (Item 117) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 348, 349, and 350, respectively. (Item 118) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 355, 356, and 357, respectively. (Item 119) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 358, 359, and 360, respectively. (Item 120) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 365, 366, and 367, respectively. (Item 121) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 368, 369, and 370, respectively. (Item 122) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 375, 376, and 377, respectively. (Item 123) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, including VLs containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 378, 379, and 380, respectively. (Item 124) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 385, 386, and 387, respectively. (Item 125) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 388, 389, and 390, respectively. (Item 126) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin heavy chain or fragment thereof, comprising VH containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 395, 396, and 397, respectively. (Item 127) The cDNA described in item 45, comprising a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or fragment thereof, comprising a VL containing CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 398, 399, and 400, respectively. (Item 128) An antibody that binds to CDCP1 or an antigen-binding fragment thereof, The selected VH sequence comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to the selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to the selected VL sequence, wherein the selected VH sequence and the selected VL sequence are as follows: 1) The selected VH sequence is sequence number 1, and the selected VL sequence is sequence number 2; 2) The selected VH sequence is sequence number 11, and the selected VL sequence is sequence number 12; 3) The selected VH sequence is sequence number 21, and the selected VL sequence is sequence number 22; 4) The selected VH sequence is sequence number 31, and the selected VL sequence is sequence number 32; 5) The selected VH sequence is sequence number 41, and the selected VL sequence is sequence number 42; 6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 52; 7) The selected VH sequence is sequence number 61, and the selected VL sequence is sequence number 62; 8) The selected VH sequence is sequence number 71, and the selected VL sequence is sequence number 72; 9) The selected VH sequence is sequence number 81, and the selected VL sequence is sequence number 82; 10) The selected VH sequence is sequence number 91, and the selected VL sequence is sequence number 92; 11) The selected VH sequence is sequence number 101, and the selected VL sequence is sequence number 102; 12) The selected VH sequence is sequence number 111, and the selected VL sequence is sequence number 112; 13) The selected VH sequence is sequence number 121, and the selected VL sequence is sequence number 122; 14) The selected VH sequence is sequence number 131, and the selected VL sequence is sequence number 132; 15) The selected VH sequence is sequence number 141, and the selected VL sequence is sequence number 142; 16) The selected VH sequence is sequence number 151, and the selected VL sequence is sequence number 152; 17) The selected VH sequence is sequence number 161, and the selected VL sequence is sequence number 162; and 18) The selected VH sequence is sequence number 171, and the selected VL sequence is sequence number 172; 19) The selected VH sequence is sequence number 181, and the selected VL sequence is sequence number 182; 20) The selected VH sequence is sequence number 191, and the selected VL sequence is sequence number 192; 21) The selected VH sequence is sequence number 201, and the selected VL sequence is sequence number 202; 22) The selected VH sequence is sequence number 211, and the selected VL sequence is sequence number 212; 23) The selected VH sequence is sequence number 221, and the selected VL sequence is sequence number 222; 24) The selected VH sequence is sequence number 231, and the selected VL sequence is sequence number 232; 25) The selected VH sequence is sequence number 241, and the selected VL sequence is sequence number 242; 26) The selected VH sequence is sequence number 251, and the selected VL sequence is sequence number 252; 27) The selected VH sequence is sequence number 261, and the selected VL sequence is sequence number 262; 28) The selected VH sequence is sequence number 271, and the selected VL sequence is sequence number 272; 29) The selected VH sequence is sequence number 281, and the selected VL sequence is sequence number 282; 30) The selected VH sequence is sequence number 291, and the selected VL sequence is sequence number 292; 31) The selected VH sequence is sequence number 301, and the selected VL sequence is sequence number 302; 32) The selected VH sequence is sequence number 311, and the selected VL sequence is sequence number 312; 33) The selected VH sequence is sequence number 321, and the selected VL sequence is sequence number 322; 34) The selected VH sequence is sequence number 331, and the selected VL sequence is sequence number 332; 35) The selected VH sequence is sequence number 341, and the selected VL sequence is sequence number 342; 36) The selected VH sequence is sequence number 351, and the selected VL sequence is sequence number 352; 37) The selected VH sequence is sequence number 361, and the selected VL sequence is sequence number 362; 38) The selected VH sequence is sequence number 371, and the selected VL sequence is sequence number 372; 39) The selected VH sequence is sequence number 381, and the selected VL sequence is sequence number 382; and 40) The selected VH sequence is sequence number 391, and the selected VL sequence is sequence number 392. One of these, wherein the antibody or its antigen-binding fragment specifically binds to CUB domain-containing protein 1 (CDCP1). (Item 129) An antibody or antigen-binding fragment thereof, as described in item 128, that specifically binds to human CDCP1 and / or cynomolgus monkey CDCP1. (Item 130) Dissociation constant (K) for human CDCP1 d ) is less than 10 nM, and / or the dissociation constant (K) for cynomolgus monkey CDCP1 d An antibody or antigen-binding fragment described in item 128, wherein the concentration is less than 10 nM. (Item 131) A humanized antibody or its antigen-binding fragment, as described in item 128. (Item 132) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 1 and VL comprises the sequence of SEQ ID NO: 2. (Item 133) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 11 and VL comprises the sequence of SEQ ID NO: 12. (Item 134) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 21 and VL comprises the sequence of SEQ ID NO: 22. (Item 135) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 31 and VL comprises the sequence of SEQ ID NO: 32. (Item 136) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 41 and VL comprises the sequence of SEQ ID NO: 42. (Item 137) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 51 and VL comprises the sequence of SEQ ID NO: 52. (Item 138) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 61 and VL comprises the sequence of SEQ ID NO: 62. (Item 139) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 71 and VL comprises the sequence of SEQ ID NO: 72. (Item 140) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 81 and VL comprises the sequence of SEQ ID NO: 82. (Item 141) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 91 and VL comprises the sequence of SEQ ID NO: 92. (Item 142) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 101 and VL comprises the sequence of SEQ ID NO: 102. (Item 143) The antibody or antigen-binding fragment thereof according to item 128, wherein the VH comprises the sequence of sequence number 111 and the VL comprises the sequence of sequence number 112. (Item 144) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 121 and VL comprises the sequence of SEQ ID NO: 122. (Item 145) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 131 and VL comprises the sequence of SEQ ID NO: 132. (Item 146) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 141 and VL comprises the sequence of SEQ ID NO: 142. (Item 147) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 151 and VL comprises the sequence of SEQ ID NO: 152. (Item 148) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 161 and VL comprises the sequence of SEQ ID NO: 162. (Item 149) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 171 and VL comprises the sequence of SEQ ID NO: 172. (Item 150) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 181 and VL comprises the sequence of SEQ ID NO: 182. (Item 151) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 191 and VL comprises the sequence of SEQ ID NO: 192. (Item 152) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 201 and VL comprises the sequence of SEQ ID NO: 202. (Item 153) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 211 and VL comprises the sequence of SEQ ID NO: 212. (Item 154) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 221 and VL comprises the sequence of SEQ ID NO: 222. (Item 155) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 231 and VL comprises the sequence of SEQ ID NO: 232. (Item 156) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 241 and VL comprises the sequence of SEQ ID NO: 242. (Item 157) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 251 and VL comprises the sequence of SEQ ID NO: 252. (Item 158) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 261 and VL comprises the sequence of SEQ ID NO: 262. (Item 159) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 271 and VL comprises the sequence of SEQ ID NO: 272. (Item 160) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 281 and VL comprises the sequence of SEQ ID NO: 282. (Item 161) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 291 and VL comprises the sequence of SEQ ID NO: 292. (Item 162) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 301 and VL comprises the sequence of SEQ ID NO: 302. (Item 163) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 311 and VL comprises the sequence of SEQ ID NO: 312. (Item 164) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 321 and VL comprises the sequence of SEQ ID NO: 322. (Item 165) The antibody or its antigen-binding fragment according to item 128, wherein VH comprises the sequence of SEQ ID NO: 331 and VL comprises the sequence of SEQ ID NO: 332. (Item 166) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 341 and VL comprises the sequence of SEQ ID NO: 342. (Item 167) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 351 and VL comprises the sequence of SEQ ID NO: 352. (Item 168) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 361 and VL comprises the sequence of SEQ ID NO: 362. (Item 169) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 371 and VL comprises the sequence of SEQ ID NO: 372. (Item 170) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 381 and VL comprises the sequence of SEQ ID NO: 382. (Item 171) The antibody or antigen-binding fragment thereof according to item 128, wherein VH comprises the sequence of SEQ ID NO: 391 and VL comprises the sequence of SEQ ID NO: 392. (Item 172) An antibody or its antigen-binding fragment that binds to human CDCP1 and blocks the cleavage of human CDCP1 at residue 342. (Item 173) The antibody or antigen-binding fragment described in item 172, comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 85, 86, and 87, and VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 88, 89, and 90. (Item 174) The antibody or antigen-binding fragment described in item 172, comprising VH containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 95, 96, and 97, and VL containing CDR1, 2, 3 having the amino acid sequences shown in SEQ ID NOs. 98, 99, and 100. (Item 175) An antibody-drug conjugate comprising an antibody or its antigen-binding fragment and a therapeutic agent as described in any one of items 1-44 and 128-174. (Item 176) The aforementioned therapeutic agent is a cytotoxic agent or a cell proliferation inhibitor, an antibody-drug conjugate as described in item 175. (Item 177) The cytotoxic agent or cell proliferation inhibitor is a microtubule inhibitor or a DNA alkylator, as described in item 176, an antibody-drug conjugate. (Item 178) The cytotoxic agent or cell proliferation inhibitor is selected from the group consisting of DM4, MMAE, PDX, PDB, and IGN, and is an antibody-drug conjugate as described in item 177. (Item 179) The antibody-drug conjugate described in item 175, wherein the antibody or antigen-binding fragment is linked to the therapeutic agent by a linker. (Item 180) The linker is selected from the group consisting of cleavable peptides, charged hindered disulfides, and maleimide-caproyl-valine-citrulline, as described in item 179, for the antibody-drug conjugate. (Item 181) The antibody-drug conjugate described in item 179, wherein the therapeutic agent is DM4 and the linker is D-Ala-L-Ala dpa. (Item 182) The antibody-drug conjugate described in item 179, wherein the therapeutic agent is DM4 and the linker is N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sSPDB). (Item 183) The antibody-drug conjugate described in item 179, wherein the therapeutic agent is MMAE and the linker is maleimide-caproyl-valine-citrulline (MC-VC). (Item 184) The antibody-drug conjugate described in item 179, wherein the therapeutic agent is IGN and the linker is D-Ala-L-Ala dpa. (Item 185) An antibody-drug conjugate of formula Ab-[LD]n, In the formula, Ab comprises an antibody or its antigen-binding fragment as described in any one of items 1-44 and 128-174. L includes linkers as needed. D is a therapeutic agent, n is an integer between approximately 1 and approximately 20, representing an antibody-drug conjugate. (Item 186) A method for treating the target cancer, Identifying individuals with cancer, and The subject is administered a pharmaceutical composition containing an antibody-drug conjugate described in any one of items 175 to 185 of the items for therapeutically effective dose. A method that includes this. (Item 187) The method according to item 186, wherein the cancer is breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, or colon cancer. (Item 188) The cancer is triple-negative breast cancer, as described in item 186. (Item 189) The method according to item 188, wherein the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is D-Ala-L-Ala dpa or sSPDB. (Item 190) The method according to item 188, wherein the therapeutic agent in the antibody-drug conjugate is MMAE, and the linker is MC-VC. (Item 191) The cancer in question is colon cancer, as described in item 186. (Item 192) The method according to item 191, wherein the therapeutic agent in the antibody-drug conjugate is IGN, and the linker is D-Ala-L-Ala dpa. (Item 193) The method according to item 191, wherein the therapeutic agent in the antibody-drug conjugate is DM4, and the linker is D-Ala-L-Ala dpa or sSPDB. (Item 194) The method according to item 191, wherein the therapeutic agent in the antibody-drug conjugate is MMAE and the linker is MC-VC. (Item 195) The cancer is small cell lung cancer, as described in item 186. (Item 196) The method according to item 195, wherein the therapeutic agent in the antibody-drug conjugate is IGN, and the linker is D-Ala-L-Ala dpa. (Item 197) A method for treating the target cancer, Identifying individuals with cancer, and A method comprising administering to the subject a pharmaceutical composition containing an antibody or its antigen-binding fragment described in any one of items 1 to 44 and 128 to 174 of the therapeutically effective amount section, or an antibody-drug conjugate described in any one of items 175 to 185 of the therapeutically effective amount section. (Item 198) The method according to item 197, wherein the cancer is breast cancer, triple-negative breast cancer, lung cancer, small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, or colon cancer. [Brief explanation of the drawing]

[0294] [Figure 1] Figure 1A is a schematic diagram showing CDCP1 constructs expressing full-length CDCP1 (FL-CDCP1) or cleaved CDCP1 (Clv-CDCP1(N342)) (containing amino acids 343-836). Figure 1B is a graph showing flow cytometry analysis of two CDCP1 antibodies in live 293T, 293T / FL-CDCP1, and 293T / Clv N342 cells. Figure 1C is a Western blot image of lysates of 293T cells stably transfected with FL or two forms of Clv-CDCP1:R368(AA369-836) and N342:(AA343-836).

[0295] [Figure 2] Figure 2A is a schematic diagram showing the protocol for the R368 cleavage blockade assay. This figure discloses “8xHis” as Sequence ID No. 406. Figures 2B-2C are images of Western blots showing the results of the R368 cleavage blockade assay.

[0296] [Figure 3] Figure 3 is a graph showing that the 18C6 antibody binds to cleaved CDCP (AA343~836) (Clv-CDCP1(N342)) with higher affinity than full-length CDCP1.

[0297] [Figure 4] Figure 4 is a schematic diagram showing separate epitope bins for 18 selected recombinant human antibodies.

[0298] [Figure 5]Figures 5A-5E are graphs showing the in vitro killing effect of antibody vcMMAE conjugates against cells derived from BrCa cell lines MCF7, BT549, and MDA231, as well as cells derived from CRC cell lines SW48 and HCT116. The antibodies in the antibody vcMMAE conjugates are hlgG1, 47G7, 41A09, 38E11, 27H10, 18C6, and 03B11.

[0299] [Figure 6] Figures 6A-6C are graphs showing the antibody-dependent cell-mediated cytotoxicity (ADCC) effects of hlgG (control) and human CDCP1 antibodies 2F3, 10E2, 38E11, and 41A9 on cells derived from TNBC cell lines BT549 and MDA231, as well as cells derived from CRC cell line SW48.

[0300] [Figure 7ABC] Figures 7A-7G are graphs showing the complement-dependent cell-mediated cytotoxicity (CDC) effects of hlgG (control) and human CDCP1 antibodies 27H10, 38E11, 3B11, 47G7, 41A9, and 18C6 on BT549 cells. [Figure 7DEFG] Figures 7A-7G are graphs showing the complement-dependent cell-mediated cytotoxicity (CDC) effects of hlgG (control) and human CDCP1 antibodies 27H10, 38E11, 3B11, 47G7, 41A9, and 18C6 on BT549 cells.

[0301] [Figure 8] Figure 8A is a graph showing that the antibody vcMMAE conjugate (41A10-vcMMAE) inhibited tumor growth in mice xenografted with cells derived from the TNBC cell line MDA231 in vivo. Figure 8B is a graph showing body weight plots for mice with MDA231 tumors treated with the antibody vcMMAE conjugate (41A10-vcMMAE).

[0302] [Figure 9]Figure 9 is a graph showing that human CDCP1 antibodies conjugated with vcMMAE inhibited SW48 tumor growth in mice in vivo, where the antibodies conjugated with vcMMAE were hlgG1 (control), 47G7, 41A09, 38E11, 27H10, 18C6, and 03B11.

[0303] [Figure 10] Figure 10 is a graph showing that in vivo, human CDCP1 antibody conjugated with vcMMAE inhibited tumor growth in mice xenografted with cells derived from the TNBC cell line MDA231, where the conjugated antibodies were 18C6, 27H10, 38E11, 41A9, and hlgG1.

[0304] [Figure 11] Figure 11 is a graph showing that in vivo, human CDCP1 antibodies conjugated with vcMMAE induced regression of established SW48 tumors in mice, where the conjugated antibodies were 18C6, 27H10, 38E11, 41A9, and hlgG1.

[0305] [Figure 12] Figure 12 is a graph showing the survival plot for mice with SW48 tumors treated with the antibody vcMMAE conjugate shown in Figure 11.

[0306] [Figure 13A] Figure 13A is a graph showing the dose-dependent tumor growth inhibitory effect of 38E11-MMAE on SW48 tumors in mice.

[0307] [Figure 13B] Figure 13B is a graph showing the dose-dependent tumor growth inhibitory effect of 27H10-MMAE on SW48 tumors in mice.

[0308] [Figure 13C]Figure 13C is a graph showing the dose-dependent tumor growth inhibitory effect of 18C6-MMAE on SW48 tumors in mice.

[0309] [Figure 13D] Figure 13D is a graph showing the dose-dependent tumor growth inhibitory effect of 10E2-MMAE on SW48 tumors in mice.

[0310] [Figure 14A] Figure 14A is a graph showing the Kaplan-Meier analysis of SW48 tumor-bearing mice treated with PBS, 0.5, 1.5, or 5 mg / kg of hlgG1-MMAE, or 38E11-MMAE.

[0311] [Figure 14B] Figure 14B is a graph showing the Kaplan-Meier analysis of SW48 tumor-bearing mice treated with PBS, 0.5, 1.5, or 5 mg / kg of hlgG1-MMAE, or 27H10-MMAE.

[0312] [Figure 14C] Figure 14C is a graph showing the Kaplan-Meier analysis of SW48 tumor-bearing mice treated with PBS, 0.5, 1.5, or 5 mg / kg of hlgG1-MMAE, or 18C6-MMAE.

[0313] [Figure 14D] Figure 14D is a graph showing the Kaplan-Meier analysis of SW48 tumor-bearing mice treated with PBS, 0.5, 1.5, or 5 mg / kg of hlgG1-MMAE, or 10E2-MMAE.

[0314] [Figure 15-1] Figure 15 lists the sequence numbers for 40 anti-CDCP1 antibodies, including the nucleic acid sequences of the heavy and light chain variable regions, as well as the amino acid sequences of the heavy and light chain variable regions and the complementarity-determining region (CDR). [Figure 15-2]Figure 15 lists the sequence numbers for 40 anti-CDCP1 antibodies, including the nucleic acid sequences of the heavy and light chain variable regions, as well as the amino acid sequences of the heavy and light chain variable regions and the complementarity-determining region (CDR). [Figure 15-3] Figure 15 lists the sequence numbers for 40 anti-CDCP1 antibodies, including the nucleic acid sequences of the heavy and light chain variable regions, as well as the amino acid sequences of the heavy and light chain variable regions and the complementarity-determining region (CDR).

[0315] [Figure 16] Figure 16 shows the characteristics of 40 types of anti-CDCP1 antibodies.

[0316] [Figure 17] Figure 17 shows the characteristics of 18 anti-CDCP1 antibodies, which are a subset of the 40 anti-CDCP1 antibodies shown in Figure 16.

[0317] [Figure 18-1] Figure 18 lists the amino acid sequences of the heavy chain variable region (VH) and light chain variable region (VL) of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 18-2] Figure 18 lists the amino acid sequences of the heavy chain variable region (VH) and light chain variable region (VL) of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 18-3] Figure 18 lists the amino acid sequences of the heavy chain variable region (VH) and light chain variable region (VL) of the 40 anti-CDCP1 antibodies shown in Figure 15.

[0318] [Figure 19-1] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-2] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-3] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-4] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-5] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-6] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-7] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-8] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-9] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 19-10] Figure 19 lists the nucleotide sequences of the heavy chain variable region and light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15.

[0319] [Figure 20-1] Figure 20 lists the amino acid sequences of the complementarity-determining regions (VH CDR1, VH CDR2, VH CDR3) in the heavy chain variable region and the complementarity-determining regions (VL CDR1, VL CDR2, VL CDR3) in the light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15. [Figure 20-2] Figure 20 lists the amino acid sequences of the complementarity-determining regions (VH CDR1, VH CDR2, VH CDR3) in the heavy chain variable region and the complementarity-determining regions (VL CDR1, VL CDR2, VL CDR3) in the light chain variable region of the 40 anti-CDCP1 antibodies shown in Figure 15.

[0320] [Figure 21A]Figures 21A and 21B are graphs showing the in vitro killing effects of hIgG1-vcMMAE and 38E11-vcMMAE against prostate cancer cells. [Figure 21B] Figures 21A and 21B are graphs showing the in vitro killing effects of hIgG1-vcMMAE and 38E11-vcMMAE against prostate cancer cells.

[0321] [Figure 22A] Figures 22A and 22B are graphs showing the in vitro killing effects of hIgG1-PBD and 38E11-PBD against prostate cancer cells. [Figure 22B] Figures 22A and 22B are graphs showing the in vitro killing effects of hIgG1-PBD and 38E11-PBD against prostate cancer cells.

[0322] [Figure 23A] Figures 23A and 23B are graphs showing the in vitro toxic effects of hIgG1-vcMMAE and 38E11-vcMMAE on NSLC cells. [Figure 23B] Figures 23A and 23B are graphs showing the in vitro toxic effects of hIgG1-vcMMAE and 38E11-vcMMAE on NSLC cells.

[0323] [Figure 24A] Figures 24A and 24B are graphs showing the in vitro killing effects of hIgG1-PBD and 38E11-PBD on NSLC cells. [Figure 24B] Figures 24A and 24B are graphs showing the in vitro killing effects of hIgG1-PBD and 38E11-PBD on NSLC cells.

[0324] [Figure 25A] Figures 25A and 25B are graphs showing tumor growth in eight TNBC PDX models responding to 38E11-vcMMAE and hIgG-vcMMAE. [Figure 25B] Figures 25A and 25B are graphs showing tumor growth in eight TNBC PDX models responding to 38E11-vcMMAE and hIgG-vcMMAE.

[0325] [Figure 26A] Figures 26A and 26B are graphs showing body weight plots of eight TNBC PDX models responding to 38E11-vcMMAE and hIgG-vcMMAE. [Figure 26B] Figures 26A and 26B are graphs showing body weight plots of eight TNBC PDX models responding to 38E11-vcMMAE and hIgG-vcMMAE. [Modes for carrying out the invention]

[0326] Various aspects of this disclosure relate to anti-CUB domain-containing protein 1 (anti-CDCP1) antibodies and antibody fragments, anti-CDCP1 ADCs, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors, and host cells for producing such antibodies and fragments. Methods for using the antibodies and ADCs described herein to detect human CDCP1, to bind to and inhibit human CDCP1 in CDCP1-expressing cells, to inhibit CDCP1 signaling in vivo, and / or to treat CDCP1-related disorders, for example, but not limited to, breast cancer, e.g., triple-negative breast cancer, lung cancer, e.g., non-small cell lung cancer (NSCLC), liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer.

[0327] In one embodiment, the anti-CDCP1 antibody or ADC of the present invention is administered in combination with one or more immune checkpoint inhibitors (e.g., antibodies or small molecule immune checkpoint inhibitors) for treating cancer. In another embodiment of the present invention, the anti-CDCP1 antibody drug conjugate (ADC) of the present invention (e.g., the CDCP1 antibody of the present invention conjugated with a toxin) is internalized and induces cell death in cells endogenously expressing CDCP1.

[0328] In one embodiment, the anti-CDCP1 antibody, bispecific antibody, or ADC disclosed herein is administered in combination with a PARP (poly-ADP-ribose polymerase) inhibitor. PARP inhibitors are well known to those skilled in the art and include, but are not limited to, niraparib, olaparib, rucaparib, iniparib, talazoparib, veliparib, CEP9722, E7016, BGB-290, and 3-aminobenazamine.

[0329] I. Definition To make the present invention easier to understand, certain terms will first be defined. In addition, it should be noted that whenever a parameter value or range of values ​​is stated, intermediate values ​​and intermediate ranges of the stated values ​​are also considered part of the present invention.

[0330] In this specification, the terms “CUB domain-containing protein 1 antibody” or “anti-CDCP1 antibody,” as used synonymously, refer to antibodies that specifically bind to CDCP1, for example, human CDCP1. The antibody that “binds” to the target antigen, i.e., CDCP1, is capable of binding to that antigen with sufficient affinity so that the antibody is useful in targeting cells expressing the antigen. In preferred embodiments, the antibody specifically binds to human CDCP1 (hCDCP1). Examples of anti-CDCP1 antibodies are disclosed in the following examples. Unless otherwise specified, the term “anti-CDCP1 antibody” is intended to refer to antibodies that bind to wild-type CDCP1, a variant or isoform of CDCP1.

[0331] Alternative splicing results in at least two transcript variants of hCDCP1. The CDCP1 nucleotide and polypeptide sequences have been reported under accession numbers NM_022842.4 (transcript variant 1 mRNA), NP_073753.3 (isoform 1 polypeptide), and NM_178181.2 (transcript variant 2 mRNA), NP_835488.1 (isoform 2 polypeptide). CDCP1 contains a CUB domain at positions 225–297 of NP_073753.3. The extracellular domain of the protein described in NP_073753.3 contains amino acid residues 30–667.

[0332] When the term “specific binding” or “specifically binding” is used herein in relation to the interaction between a CDCP1 antibody or ADC and a second chemical species, it means that the interaction depends on the presence of a specific structure (e.g., an antigenic determinant or epitope) in that chemical species, for example, that the antibody recognizes and binds to a specific protein structure rather than the protein in general. If the antibody or ADC is specific to epitope “A”, then in a reaction involving label “A”, the presence of a molecule and antibody containing epitope A (or free, unlabeled A) will reduce the amount of label A bound to the antibody or ADC.

[0333] In one embodiment, the phrase "specifically binds to hCDCP1" or "specifically binds to hCDCP1" means, as used herein, about 2,000 nM or less, about 1,000 nM or less, about 500 nM or less, about 200 nM or less, about 100 nM or less, about 75 nM or less, about 25 nM or less, about 21 nM or less, about 12 nM or less, about 11 nM or less, about 10 nM or less Dissociation constants (K) lower than 9nM or lower, 8nM or lower, 7nM or lower, 6nM or lower, 5nM or lower, 4nM or lower, 3nM or lower, 2nM or lower, 1nM or lower, 0.5nM or lower, 0.3nM or lower, 0.1nM or lower, 0.01nM or lower, or 0.001nM or lower. D ) refers to the ability of an anti-CDCP1 antibody or ADC to interact with CDCP1 (human or cynomolgus monkey CDCP1). In another embodiment, the phrase “specifically binds to hCDCP1” or “specifically binds to hCDCP1” means, as used herein, that the anti-CDCP1 antibody or ADC has a dissociation constant (K) of about 1 pM (0.001 nM) to 2,000 nM, about 500 pM (0.5 nM) to 1,000 nM, about 500 pM (0.5 nM) to 500 nM, about 1 nM to 200 nM, about 1 nM to 100 nM, about 1 nM to 50 nM, about 1 nM to 20 nM, or about 1 nM to 5 nM. D ) refers to the ability to interact with hCDCP1. In one embodiment, K DThis is determined by surface plasmon resonance, bio-layer interferometry, or any other method known in the art. Bio-layer interferometry refers to an optical phenomenon that enables real-time analysis of bio-specific interactions by measuring the interference pattern of reflected white light, for example, using the Octet® system (ForteBio, Pall Corp., Fremont, CA). For further details of the Octet® system, see Li, B et al. (2011) J. Pharm. Biomed. Anal. Vol. 54 (No. 2): pp. 286-294 and Abdiche, YN et al. (2009) Anal. Biochem. Vol. 386 (No. 2): pp. 172-180. The contents of these documents are incorporated herein by reference.

[0334] The term "antibody," broadly speaking, refers to an immunoglobulin (Ig) molecule, which generally consists of four polypeptide chains, i.e., two heavy (H) chains and two light (L) chains, or any functional fragment, variant, variant, or derivative thereof that retains the essential target-binding characteristics of the Ig molecule. Such variant, variant, or derivative antibody forms are known in the art. Their non-limiting embodiments are discussed below.

[0335] In full-length antibodies, each heavy chain consists of a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region consists of one domain, CL. The VH and VL regions can be further subdivided into hypervariable regions called complementarity-determining regions (CDRs), which are scattered in more conserved regions and are named framework regions (FRs). Each VH and VL consists of three CDRs and four FRs, arranged in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from the amino terminus to the carboxy terminus. The immunoglobulin molecule may be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY) and class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) or subclass.

[0336] The term “antigen-binding portion” (or simply “antibody portion”) of an antibody, as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., hCDCP1). It has been shown that the antigen-binding function of an antibody can be carried out by fragments of a full-length antibody. Furthermore, such antibody embodiments may be bispecific, dual-specific, or multispecific, i.e., specifically binding to two or more different antigens. Examples of binding fragments included in the term "antigen-binding moiety" of an antibody include: (i) Fab fragments, i.e., monovalent fragments consisting of VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, i.e., bivalent fragments containing two Fab fragments linked by disulfide crosslinks in the hinge region; (iii) Fd fragments consisting of VH and CH1 domains; (iv) Fv fragments consisting of VL and VH domains of a single arm of the antibody; (v) dAb fragments containing a single variable domain (Ward et al., Nature 341, pp. 544-546, 1989; Winter et al., PCT Publication WO90 / 05144A1; these publications are incorporated herein by reference); and (vi) isolated complementarity-determining regions (CDRs). Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be joined using recombination via a synthetic linker that allows the VL and VH regions to pair up to form a single protein chain that forms a monovalent molecule (known as single-chain Fv (scFv); see, e.g., Bird et al. (1988) Science vol. 242: pp. 423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA vol. 85: pp. 5879-5883). Such single-chain antibodies are also intended to be included within the term "antigen-binding portion" of the antibody. In certain embodiments, the scFv molecule may be incorporated into a fusion protein. Other forms of single-chain antibodies, such as diabodies, are also included.Diabody is a bivalent, bispecific antibody in which the VH and VL domains are expressed on a single polypeptide chain, but a linker that is too short to allow pairing between the two domains on the same chain is used, thereby forcing the above domains to pair with a complementary domain on another chain, generating two antigen-binding sites (see, for example, Holliger, P. et al. (1993) Proc. Natl. Acad. Sci. USA Vol. 90: pp. 6444-6448; Poljak, RJ et al. (1994) Structure Vol. 2: pp. 1121-1123). Such antibody-binding moieties are known in the art (Kontermann and Dubel, eds., Antibody). Engineering (2001) Springer-Verlag, New York, 790 pages (ISBN3-540-41354-5).

[0337] The term “antibody construct,” as used herein, refers to a polypeptide comprising one or more antigen-binding moieties disclosed herein, linked to a linker polypeptide or an immunoglobulin constant domain. A linker polypeptide comprises two or more amino acid residues linked by a peptide bond and is used to link one or more antigen-binding moieties. Such linker polypeptides are well known in the art (see, for example, Holliger, P. et al. (1993) Proc. Natl. Acad. Sci. USA Vol. 90: pp. 6444–6448; Poljak, RJ et al. (1994) Structure Vol. 2: pp. 1121–1123). An immunoglobulin constant domain refers to a heavy chain or light chain constant domain. Antibody moieties, such as Fab and F(ab')2 fragments, can be prepared from whole antibodies using conventional techniques such as papain or pepsin digestion of the whole antibody, respectively. Furthermore, antibodies, antibody moieties, and immunoadhesion molecules can be obtained using standard recombinant DNA techniques as described herein.

[0338] As used herein, "isolated antibody" is intended to refer to an antibody that substantially does not contain other antibodies with different antigen specificities (for example, an isolated antibody that specifically binds to CDCP1 substantially does not contain antibodies that specifically bind to antigens other than CDCP1). However, an isolated antibody that specifically binds to CDCP1 may have cross-reactivity with other antigens, such as CDCP1 molecules from other species. Furthermore, an isolated antibody may not substantially contain other cellular material and / or chemical substances.

[0339] The term “humanized antibody” refers to an antibody that contains heavy and light chain variable region sequences derived from a non-human species (e.g., mouse), but in which at least a portion of the VH and / or VL sequences has been modified to be more “human-like,” i.e., more similar to human germline variable sequences. In particular, the term “humanized antibody” refers to an antibody, or a variant, derivative, analog, or fragment thereof, that immunospecifically binds to an antigen of interest and contains a framework (FR) region having substantially the amino acid sequence of a human antibody, and a complementation-determining region (CDR) having substantially the amino acid sequence of a non-human antibody. As used herein, the term “substantially” refers to a CDR having an amino acid sequence that is at least 80%, preferably at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to the amino acid sequence of a non-human antibody CDR. A humanized antibody contains substantially all of at least one, typically two, variable domains (Fab, Fab', F(ab')2, FabC, Fv), where all or substantially all of the CDR region corresponds to the CDR region of a non-human immunoglobulin (i.e., a donor antibody), and all or substantially all of the framework region is the framework region of the human immunoglobulin consensus sequence. Preferably, the humanized antibody also contains the immunoglobulin constant region (Fc), typically at least a portion of the constant region of a human immunoglobulin. In some embodiments, the humanized antibody contains both the light chain and at least the heavy chain variable domains. The antibody may also contain the CH1, hinge, CH2, CH3, and CH4 regions of the heavy chain. In some embodiments, the humanized antibody contains only the humanized light chain. In other embodiments, the humanized antibody contains only the humanized heavy chain. In certain embodiments, the humanized antibody contains only the humanized variable domains of the light chain and / or the humanized heavy chain.

[0340] Humanized antibodies can be selected from any class of immunoglobulin, including IgM, IgG, IgD, IgA, and IgE, and any isotype, including, but not limited to, IgG1, IgG2, IgG3, and IgG4. Humanized antibodies may contain sequences derived from more than one class or isotype, and specific constant domains can be selected to optimize desired effector function using techniques well known in the art.

[0341] The terms “Kabat numbering,” “Kabat definition,” and “Kabat notation” are used synonymously herein. These terms refer to a system recognized in the art for numbering amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody or its antigen-binding moiety (Kabat et al. (1971) Ann. NY Acad, Sci. Vol. 190: pp. 382–391, and Kabat, EA et al. (1991) Sequences of Proteins of Immunological Interest, 5th edition, US Department of Health and Human Services, NIH Publications 91-3242). In the case of the heavy chain variable region, the hypervariable region is the range of amino acids 31–35 in CDR1, amino acids 50–65 in CDR2, and amino acids 95–102 in CDR3. In the case of the light chain variable region, the hypervariable region is in the range of amino acids 24-34 in CDR1, in the range of amino acids 50-56 in CDR2, and in the range of amino acids 89-97 in CDR3.

[0342] As used herein, the term “CDR” refers to the complementarity-determining region within an antibody variable sequence. Each of the variable regions of the heavy chain (HC) and light chain (LC) contains three CDRs, each named CDR1, CDR2, and CDR3 (or, in particular, HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3). As used herein, the term “CDR set” refers to a group of three CDRs occurring in a single variable region capable of binding to an antigen. The precise boundaries of these CDRs are defined differently by different systems. One such system is described by Kabat et al. in *Sequences of Proteins of Immunological Interest* (National The Institutes of Health, Bethesda, Md. (1987 and 1991) not only provide a clear residue numbering system applicable to any variable region of an antibody, but also precise residue boundaries that define three CDRs. These CDRs are sometimes called Kabat CDRs. Chothia and collaborators (Chothia and Lesk, J. Mol. Biol. Vol. 196: pp. 901-917 (1987), and Chothia et al., Nature, Vol. 342: pp. 877-883 (1989)) found that certain subportions within Kabat CDRs adopt almost identical peptide skeletal conformations despite considerable diversity at the amino acid sequence level. These subportions are named L1, L2, and L3, or H1, H2, and H3, where "L" and "H" refer to the light chain and heavy chain regions, respectively. These regions are sometimes referred to as Chothia CDRs and have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs that overlap with Kabat CDRs are described by Padlan (FASEB J. Vol. 9: pp. 133-139 (1995)) and MacCallum (J mol Biol Vol. 262 (No. 5): pp. 732-745 (1996)). Further other CDR boundary definitions may not strictly follow one of the above systems, but they overlap with Kabat CDRs, although they may be shortened or extended in light of predictions or experimental findings that certain residues or groups of residues, or even the entire CDR, do not significantly affect antigen binding. The methods used herein may use CDRs defined according to any of these systems, but in preferred embodiments, CDRs defined by Kabat or Chothia are used.

[0343] As used herein, the term “framework” or “framework sequence” refers to the sequence remaining after removing the CDRs from the variable region. Since the precise definition of a CDR sequence can be determined by various systems, the meaning of the framework sequence is subject to correspondingly different interpretations. Furthermore, the six CDRs (CDR-L1, CDR-L2, and CDR-L3 of the light chain, and CDR-H1, CDR-H2, and CDR-H3 of the heavy chain) divide the framework regions of the light and heavy chains into four sub-regions (FR1, FR2, FR3, and FR4) of each chain, with CDR1 located between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. The framework region represents a combination of FRs within the variable region of a single naturally occurring immunoglobulin chain, without designating specific sub-regions as FR1, FR2, FR3, or FR4, as referred to elsewhere. As used herein, FR represents one of the four sub-regions, and FR represents two or more of the four sub-regions that constitute the framework region.

[0344] The framework and CDR regions of a humanized antibody do not need to correspond precisely to the parent sequence. For example, a donor antibody CDR or consensus framework may be mutagenic by substitution, insertion, and / or deletion of at least one amino acid residue such that the CDR or framework residue at that site does not correspond to either the donor antibody or the consensus framework. However, in preferred embodiments, such mutations are not extensive. Typically, at least 80%, preferably at least 85%, more preferably at least 90%, and most preferably at least 95% of the humanized antibody residues correspond to residues in the parent FR and CDR sequences. As used herein, the term “consensus framework” refers to the framework region of a consensus immunoglobulin sequence. As used herein, the term “consensus immunoglobulin sequence” refers to a sequence formed from the most frequently occurring amino acids (or nucleotides) in the family of relevant immunoglobulin sequences (see, e.g., Winnaker, From Genes to Clones (Verlagsgesellschaft, Weinheim, Germany, 1987)). In immunoglobulin families, each position in the consensus sequence is occupied by the amino acid that occurs most frequently at that position within the family. If two amino acids occur with equal frequency, both can be included in the consensus sequence.

[0345] The “amino acid sequence identity percentage (%)” for a peptide or polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues of a particular peptide or polypeptide sequence after aligning the sequences, introducing gaps where necessary to achieve the maximum sequence identity percentage, and without considering any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining the amino acid sequence identity percentage can be achieved in various ways within the art using publicly available computer software, such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring the alignment, including any algorithm required to achieve the maximum alignment over the entire length of the sequences being compared. In one embodiment, the present disclosure includes amino acid sequences having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of the amino acid sequences shown in SEQ ID NOs: 1-400 and 402-505.

[0346] The term “polyvalent antibody” is used herein to refer to an antibody containing two or more antigen-binding sites. In certain embodiments, a polyvalent antibody may be engineered to have three or more antigen-binding sites and is not generally a naturally occurring antibody.

[0347] The term "multispecific antibody" refers to an antibody that is capable of binding to two or more unrelated antigens.

[0348] The terms “dual variable domain” or “DVD” are used synonymously herein and refer to an antigen-binding protein that is a tetravalent or polyvalent binding protein containing two or more antigen-binding sites. Such a DVD may be monospecific, i.e., capable of binding to one antigen, or multispecific, i.e., capable of binding to two or more antigens. A DVD-binding protein containing two heavy-chain DVD polypeptides and two light-chain DVD polypeptides is called DVD Ig. Each half of DVD Ig contains a heavy-chain DVD polypeptide, a light-chain DVD polypeptide, and two antigen-binding sites. Each binding site contains a heavy-chain variable domain and a light-chain variable domain, and has a total of six CDRs per antigen-binding site that are involved in antigen binding. In one embodiment, the CDRs described herein are used for anti-CDCP1 DVDs.

[0349] The term "activity" includes the activity of an antibody or ADC against an antigen, such as the binding specificity / affinity of an anti-hCDCP1 antibody or ADC that binds to the CDCP1 antigen. In one embodiment, anti-CDCP1 antibody or anti-CDCP1 ADC activity includes, but is not limited to, the following: binding to CDCP1 in vitro; binding to CDCP1 in cells expressing CDCP1 in vivo; modulation (e.g., inhibition) of src and / or EGFR signaling; induction of cell death in cells expressing CDCP1, including breast cancer cells, e.g., triple-negative breast cancer cells, colon cancer cells, lung cancer cells, e.g., non-small cell lung cancer (NSCLC) cells, liver cancer cells, pancreatic cancer cells, ovarian cancer cells, and kidney cancer cells; inhibition of cancer cell invasion and metastasis; reduction or inhibition of cancer, e.g., breast cancer, e.g., triple-negative breast cancer, colon cancer, lung cancer, e.g., non-small cell lung cancer (NSCLC), liver cancer, pancreatic cancer, ovarian cancer, and kidney cancer; and reduction or inhibition of tumor cell proliferation or tumor growth in vivo. In one embodiment, an anti-CDCP1 antibody or ADC can be internally transported into cells expressing CDCP1 and / or induce cytotoxicity.

[0350] The term "epitope" refers to a region of an antigen to which an antibody, antibody fragment, or ADC binds. In certain embodiments, epitope determinants include chemically active surface groups of a molecule, such as amino acids, sugar side chains, phosphoryls, or sulfonyls, and in certain embodiments, they may have specific three-dimensional structural features and / or specific charge characteristics. In certain embodiments, an antibody is said to bind specifically to an antigen if it preferentially recognizes its target antigen in a complex mixture of proteins and / or macromolecules.

[0351] The term "surface plasmon resonance," as used herein, refers to an optical phenomenon that enables real-time analysis of biospecific interactions by detecting changes in protein concentration within a biosensor matrix, for example, using the BIAcore system (Pharmacia Biosensor AB, Uppsala, Sweden, and Piscataway, NJ). For further explanation, see Jonesson, U. et al. (1993) Ann. Biol. Clin. Vol. 51: pp. 19-26; Jonesson, U. et al. (1991) Biotechniques Vol. 11: pp. 620-627; Johnson, B. et al. (1995) J. Mol. Recognit. Vol. 8: pp. 125-131; and Johnson, B. et al. (1991) Anal. Biochem. Vol. 198: pp. 268-277.

[0352] The term "k" on " or "k a When used herein, " is intended to refer to the binding rate constant at which an antibody associates with an antigen to form an antibody / antigen complex.

[0353] The term "k" off " or "k d When used herein, " is intended to refer to the dissociation rate constant at which an antibody dissociates from an antibody / antigen complex.

[0354] The term “K DWhen used herein, " is intended to refer to the equilibrium dissociation constant of a particular antibody-antigen interaction. D is, k a / k d It is calculated by [this method]. In one embodiment, the antibody of the present invention has a K content of approximately 2,000 nM or less, approximately 1,000 nM or less, approximately 500 nM or less, approximately 200 nM or less, approximately 100 nM or less, approximately 75 nM or less, approximately 25 nM or less, approximately 21 nM or less, approximately 12 nM or less, approximately 11 nM or less, approximately 10 nM or less, approximately 9 nM or less, approximately 8 nM or less, approximately 7 nM or less, approximately 6 nM or less, approximately 5 nM or less, approximately 4 nM or less, approximately 3 nM or less, approximately 2 nM or less, approximately 1 nM or less, approximately 0.5 nM or less, approximately 0.3 nM or less, approximately 0.1 nM or less, approximately 0.01 nM or less, or approximately 0.001 nM or less. D It has.

[0355] As used herein, the term "competitive binding" refers to a situation in which a first antibody competes with a second antibody for the binding site of a third molecule, such as an antigen. In one embodiment, competitive binding between the two antibodies is determined using FACS analysis.

[0356] The term "competitive binding assay" refers to an assay used to determine whether two or more antibodies bind to the same epitope. In one embodiment, a competitive binding assay is a competitive fluorescence-activated cell sorting (FACS) assay used to determine whether two or more antibodies bind to the same epitope by determining whether the fluorescence signal of a labeled antibody is reduced by the introduction of an unlabeled antibody, where competition for the same epitope reduces the level of fluorescence.

[0357] The term “labeled antibody,” as used herein, refers to an antibody or its antigen-binding moiety having an incorporated label that provides identification of the binding protein, e.g., the antibody. Preferably, the label is a detectable marker, e.g., the incorporation of a radioisotope-labeled amino acid, or the binding of a biotinyl moiety to a polypeptide that can be detected by a labeled avidin (e.g., streptavidin containing a fluorescent marker or enzymatic activity that can be detected by optical or colorimetric methods). Examples of labels on polypeptides, but not limited to, include: radioisotopes or radionuclides (e.g., 3 H, 14 C, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 I, 177 Lu, 166 Ho, or 153 Sm); fluorescent labels (e.g., FITC, rhodamine, lanthanide phosphors), enzyme labels (e.g., horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; predetermined polypeptide epitopes recognized by secondary reporters (e.g., leucine zipper pair sequences, secondary antibody binding sites, metal-binding domains, epitope tags); and magnetic agents such as gadolinium chelates.

[0358] The term “antibody-drug conjugate” or “ADC” refers to a conjugating protein, such as an antibody or its antigen-binding fragment, chemically linked to one or more chemical drugs (also referred herein as agonists), which may optionally be therapeutic or cytotoxic agents. In preferred embodiments, an ADC comprises an antibody, a cytotoxic or therapeutic agent, and a linker that enables the conjugation or binding of the drug to the antibody. Typically, an ADC contains 2, 4, 6, or 8 drug-loaded species, with 1 to 8 drugs conjugated to the antibody. Non-limiting examples of drugs that may be included in an ADC are mitotic inhibitors, antitumor antibiotics, immunomodulators, vectors for gene therapy, alkylating agents, anti-angiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormone agents, corticosteroids, phototherapeutic agents, oligonucleotides, radionuclides, topoisomerase inhibitors, tyrosine kinase inhibitors, and radiosensitizers.

[0359] The term "antibody-drug conjugate" refers to an ADC in which an antibody or its antigen-binding moiety specifically binds to CDCP1, and the antibody is conjugated to one or more chemicals or payloads. In one embodiment, the chemical is linked to the antibody via a linker.

[0360] The term "drug-to-antibody ratio" or "DAR" refers to the number of drugs, such as IGN, auristatin, or maytansinoids, that are bound to the antibodies of an ADC. The DAR of an ADC can range from 1 to 8, but higher loadings, such as 10, are possible depending on the number of antibody binding sites. The term DAR may be used in relation to the number of drugs loaded onto individual antibodies, or it may be used in relation to the average or mean DAR of a group of ADCs.

[0361] The term “CDCP1-related disorder,” as used herein, includes any disorder or disease (including proliferative disorders, e.g., cancer) that is marked, diagnosed, detected, or identified by phenotypic or genotypic abnormalities of the CDCP1 gene component or expression during the course or pathogenesis of the disease or disorder. In this regard, CDCP1 phenotypic abnormalities or determinants may include, for example, an increased or decreased level of CDCP1 protein expression in one cell population, e.g., a cancer cell population, compared to another cell population, e.g., a normal cell population, or an increased or decreased level of CDCP1 protein expression in a particular definable cell population, or an increased or decreased level of CDCP1 protein expression at an inappropriate phase or stage of the cell life cycle. It is also understood that CDCP1-related disorders can be classified or detected using similar expression patterns of CDCP1 genotypic determinants (e.g., mRNA transcription levels). In one embodiment, the CDCP1-related disorder is breast cancer, e.g., triple-negative breast cancer. In another embodiment, the CDCP1-related disorder is colon cancer. In another embodiment, the CDCP1-related disorder is lung cancer, for example, non-small cell lung cancer (NSCLC). In another embodiment, the CDCP1-related disorder is liver cancer. In another embodiment, the CDCP1-related disorder is pancreatic cancer. In another embodiment, the CDCP1-related disorder is ovarian cancer. In another embodiment, the CDCP1-related disorder is kidney cancer.

[0362] When used herein, the term “cancer” is intended to refer to or describe a physiological condition in mammals typically characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More specific examples of such cancers include, but are not limited to, breast cancer (luminal A, TNBC, tubular), prostate cancer, squamous cell tumors, squamous cell carcinomas (e.g., squamous cell lung cancer or squamous cell head and neck cancer), neuroendocrine tumors, urothelial carcinoma, vulvar cancer, mesothelioma, liver cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, cutaneous or intraocular melanoma, and kidney cancer. Uterine cancer, ovarian cancer, colorectal cancer, colon cancer, rectal cancer, anal cancer, stomach cancer, testicular cancer, uterine cancer, fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, non-Hodgkin lymphoma, esophageal cancer, small intestine cancer, endocrine cancer, parathyroid cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, solid tumors in children, lymphocytic lymphoma, bladder cancer, kidney or ureteral cancer, renal pelvis cancer, neoplasms of the central nervous system (CNS), primary C NS lymphoma, tumor angiogenesis, spinal axial tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, epidermal carcinoma, environmentally induced cancers including those induced by asbestos, such as multiple myeloma, B-cell lymphoma, Hodgkin lymphoma / primary mediastinal B-cell lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myeloproliferative disorder (MPD), Hematological malignancies including chronic lymphocytic leukemia, follicular lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, mycosis fungoides, anaplastic large cell lymphoma, T-cell lymphoma, and precursor T-lymphoblastic lymphoma, PVNS, acute myeloid leukemia, adrenocorticoplasmic carcinoma, bladder urothelial carcinomaCarcinoma, cervical squamous cell carcinoma, intracervical adenocarcinoma, diffuse large B-cell lymphoma, glioblastoma pleomorphism, chronic lymphocytic leukemia, low-grade cerebral glioma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, large squamous cell carcinoma, cutaneous melanoma, ovarian serous cystadenocarcinoma, gastric cancer, soft tissue sarcoma, testicular germ cell carcinoma, thymoma, thyroid cancer, endometrial cancer, uterine carcinosarcoma, renal clear cell carcinoma, and renal papillary cell carcinoma, and any combination of the above cancers. Furthermore, the present invention is applicable to the treatment of metastatic cancer.

[0363] In one embodiment, the antibody or ADC of the present invention is administered to a patient having a solid tumor, including a progressive solid tumor. In another embodiment, the antibody or ADC of the present invention is administered to a patient having leukemia. In yet another embodiment, administration of the antibody or ADC of the present invention induces cell death of CDCP1-expressing cells.

[0364] The term “CDCP1-expressing tumor” as used herein refers to a tumor that expresses the CDCP1 protein (including tumors containing tumor-infiltrating cells that express the CDCP1 protein). In one embodiment, CDCP1 expression in a tumor is determined using immunohistochemical staining of the tumor cell membrane, and any immunohistochemical staining higher than the background level in the tumor sample indicates that the tumor is a CDCP1-expressing tumor. In another embodiment, a CDCP1-expressing tumor is identified in a patient if more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, or more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more cells in the tumor sample are positive for CDCP1 expression. In another embodiment, CDCP1-positive expression is determined based on membrane staining, for example, determined by immunohistochemical (IHC) analysis.

[0365] CDCP1-expressing tumors are identified as having “elevated levels of CDCP1” or “expressing CDCP1 at elevated levels” if the level of CDCP1 is higher in the surrounding tissue. In some embodiments, “elevated levels of CDCP1” means that 5% or more of the cells in the tumor sample have membrane staining. In some embodiments, “high levels” of CDCP1 means that 5% or more of the cells in the tumor sample are stained, for example, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100% of the cells in the tumor sample are stained. In some embodiments, protein expression levels can be measured by IHC analysis.

[0366] CDCP1-expressing tumors are identified as having “low levels of CDCP1” or “expressing CDCP1 at low levels,” where 5% or fewer cells in the tumor sample have membrane staining. In some embodiments, “low levels” of CDCP1 are 5% or fewer staining, for example, 4.9%, 4.5%, 4, 3, 2, 1, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, or fewer cells in the tumor sample are stained. In some embodiments, protein expression levels can be measured by IHC analysis.

[0367] Cells that do not express CDCP1 may also be described as expressing "low levels of CDCP1." Therefore, the phrase "expressing low levels of CDCP1" encompasses the absence of CDCP1 expression. In some embodiments, low levels of CDCP1 are within the background staining level. In some embodiments, a CDCP1-negative sample either does not express CDCP1 or has low levels of CDCP1. In some embodiments, CDCP1 staining is negative if there is no membrane staining for CDCP1, or if less than 5%, 4%, 3%, 2%, or 1% of the cells have membrane staining for CDCP1.

[0368] As used herein, the term “tumor sample” refers to a tumor tissue or cell sample obtained from a solid tumor. The sample may contain both tumor cells and tumor-infiltrating cells, such as tumor-infiltrating immune cells.

[0369] As used herein, the terms “non-cancerous sample” or “normal sample” refer to a sample derived from normal tissue (e.g., lung or ovarian tissue sample or normal cell sample). In some embodiments, a non-cancerous sample is derived from a part of the same subject, but different from the one being tested. In some embodiments, a non-cancerous sample is derived from a tissue area surrounding or adjacent to a cancer. In some embodiments, a non-cancerous sample is a sample derived from a subject that is not derived from the subject being tested, but is known to have or not have the disorder in question (e.g., a specific cancer such as a CDCP1-associated disorder). In some embodiments, a non-cancerous sample is derived from the same subject, but from a point in time before the subject developed cancer. In some embodiments, a reference sample is derived from a benign cancer sample (e.g., a benign ovarian cancer sample) from the same or a different subject.

[0370] Methods for detecting CDCP1 expression in tumors are known in the art.

[0371] The terms “overexpression,” “overexpressed,” or “overexpressed” are synonymous with a gene that is transcribed or translated at a level typically detectable in cancer cells compared to normal cells. Therefore, overexpression refers to both protein and RNA overexpression (through increased transcription, post-transcriptional processing, translation, post-translational processing, stability changes, and proteolysis changes) and localized overexpression through altered protein transport patterns (increased nuclear localization) and enhanced functional activity, such as increased enzymatic hydrolysis of substrates. Thus, overexpression refers to either protein or RNA levels. Furthermore, overexpression may be 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or higher compared to normal or control cells. In certain embodiments, an anti-CDCP1 antibody or ADC is used to treat solid tumors that may overexpress CDCP1.

[0372] The term “administer” as used herein is intended to refer to the delivery of a substance (e.g., an anti-CDCP1 antibody or ADC) to achieve a therapeutic objective (e.g., treatment of a CDCP1-related disorder or inhibition or reduction of a tumor). Modes of administration may be parenteral, enteral, and topical. Parenteral administration is usually by injection and includes, but is not limited to, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intraspinal, and intrasternal injections and infusions.

[0373] The term “combination therapy,” as used herein, refers to the administration of two or more therapeutic substances, such as an anti-CDCP1 antibody or ADC, and an additional therapeutic agent. The additional therapeutic agent may be administered concurrently with, before, or after the administration of the anti-CDCP1 antibody or ADC. In one embodiment, the anti-CDCP1 antibody or ADC of the present invention is administered in combination with one or more immune checkpoint inhibitors (e.g., one or more antibodies or small molecule immune checkpoint inhibitors) for treating cancer. In one embodiment, the anti-CDCP1 antibody, bispecific antibody, or ADC disclosed herein is administered in combination with a PARP (poly-ADP-ribose polymerase) inhibitor. PARP inhibitors are well known to those skilled in the art and include, but are not limited to, niraparib, olaparib, lucaparib, iniparib, talazoparib, veliparib, CEP9722, E7016, BGB-290, and 3-aminobenzamide.

[0374] As used herein, the terms “effective dose” or “therapeutic effective dose” refer to a quantity of a drug, such as an antibody or ADC, sufficient to reduce or improve the severity and / or duration of a disorder, such as cancer, or one or more of its symptoms; prevent the progression of the disorder; cause regression of the disorder; prevent the recurrence, onset, initiation, or exacerbation of one or more symptoms associated with the disorder; detect the disorder; or enhance or improve the preventive or therapeutic effect (may be one or more) of another treatment (e.g., a prophylactic or therapeutic agent). An effective dose of an antibody or ADC may, for example, inhibit tumor growth (e.g., inhibit the increase of tumor volume), reduce tumor growth (e.g., reduce tumor volume), reduce the number of cancer cells, and / or alleviate one or more of the symptoms associated with cancer to some extent. An effective dose may, for example, improve disease-free survival (DFS), improve overall survival (OS), or reduce the likelihood of recurrence.

[0375] Various aspects of the present invention are described in further detail in the following subsections.

[0376] II. Anti-CDCP1 antibody One embodiment disclosed herein provides a humanized anti-CDCP1 antibody or its antigen-binding moiety. Another embodiment disclosed herein provides a human anti-CDCP1 antibody or its antigen-binding moiety. In one embodiment, the antibody disclosed herein binds to human CDCP1. In another embodiment, the antibody disclosed herein binds to cynomolgus monkey CDCP1. In yet another embodiment, the antibody disclosed herein binds to human CDCP1 expressed on tumor cells. Another embodiment disclosed herein features an antibody-drug conjugate (ADC) comprising an anti-CDCP1 antibody and at least one drug as described herein. The antibodies or ADCs disclosed herein, but are not limited to those herein, have features including binding to human CDCP1 in vitro, modulating, for example inhibiting, IL-1 signaling, inducing cell death in cells expressing CDCP1, including but not limited to leukemia cells, and reducing or inhibiting cancer, tumor cell proliferation or tumor growth, or tumor invasion and metastasis. In particular, the ADCs disclosed herein, but are not limited to those herein, have features including inducing cell death in cells expressing CDCP1, for example, leukemia cells expressing CDCP1. In one embodiment, the anti-CDCP1 antibody or ADC disclosed herein is capable of internal translocation into cells expressing CDCP1.

[0377] In one embodiment, an anti-CDCP1 antibody having the ability to bind to CDCP1 is disclosed, as described in the following examples. The novel antibody is collectively referred to herein as “CDCP1 antibody.” Anti-CDCP1 antibodies, ADCs, or their antigen-binding fragments can inhibit or reduce tumor growth in vivo. The tumor may be a CDCP1-negative tumor or a CDCP1-expressing tumor. In various embodiments, anti-CDCP1 antibodies, ADCs, or their antigen-binding fragments can modulate the biological function of CDCP1. In other embodiments of the above-described embodiments, the anti-CDCP1 antibody, ADC, or its antigen-binding fragment binds to CDCP1 on cells expressing CDCP1. Therefore, this disclosure includes anti-CDCP1 antibodies, ADCs, or their antigen-binding fragments that are effective in inhibiting or reducing tumor growth.

[0378] In addition, the inventors have shown that CDCP1 is expressed in a number of solid tumors, including breast cancer tumors, e.g., triple-negative breast cancer tumors, lung cancer tumors, e.g., non-small cell lung cancer tumors, liver cancer tumors, pancreatic cancer tumors, ovarian cancer tumors, kidney cancer tumors, and colon cancer tumors (see, for example, Examples 3-7). Therefore, anti-CDCP1 antibodies, ADCs, and their antigen-binding moieties can be used to treat target breast cancers, e.g., triple-negative breast cancer, lung cancers, e.g., non-small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer. In one embodiment, more than 1%, more than 2%, more than 3%, more than 4%, more than 5%, more than 6%, more than 7%, more than 8%, more than 9%, more than 10%, more than 15%, more than 20%, more than 25%, or more than 30%, more than 40%, more than 50%, more than 60%, more than 70%, more than 80%, more than 90%, or more cells in a tumor sample (e.g., breast cancer, e.g., triple-negative breast cancer, lung cancer, e.g., non-small cell lung cancer, liver cancer, pancreatic cancer, ovarian cancer, kidney cancer, and colon cancer) are positive for CDCP1 expression. In another embodiment, the tumor sample has high levels of CDCP1 expression. For example, in one embodiment, at least 5% or more of the cells in the tumor sample, for example, breast cancer tumors, e.g., triple-negative breast cancer tumors, lung cancer tumors, e.g., non-small cell lung cancer tumors, liver cancer tumors, pancreatic cancer tumors, ovarian cancer tumors, kidney cancer tumors, and colon cancer tumors, have membrane staining. In another embodiment, the tumor sample obtained from the subject shows low levels of CDCP1 expression. The CDCP1 expression level can be determined by any method known in the art. For example, the CDCP1 expression level can be determined by immunohistochemical analysis. In another embodiment, the cancer has been previously treated with another anticancer agent or anticancer treatment, e.g., chemotherapy. In one embodiment, the cancer is resistant to chemotherapy.

[0379] Antibodies having any combination of the above-described features are intended as embodiments of this disclosure. Furthermore, ADCs described in more detail below may have any of the above-described features.

[0380] One aspect of the present disclosure features an anti-human CDCP1 (anti-hCDCP1) antibody-drug conjugate (ADC) comprising an anti-hCDCP1 antibody conjugated to a drug via a linker. Exemplary anti-CDCP1 antibodies (and their sequences) that can be used in ADCs are described herein.

[0381] The anti-CDCP1 antibodies described herein have the ability to bind to CDCP1 and provide an ADC that can deliver the antibody-bound cytotoxic molecule to CDCP1-expressing cells, particularly CDCP1-expressing cancer cells.

[0382] Although the term “antibody” is used throughout this specification, it should be noted that antibody fragments (i.e., the antigen-binding portion of an anti-CDCP1 antibody) are also included in this disclosure and may be included in the embodiments (methods and compositions) described throughout this specification. For example, an anti-CDCP1 antibody fragment may be conjugated to a drug as described herein. In certain embodiments, the anti-CDCP1 antibody-binding portion may be Fab, Fab', F(ab')2, Fv, disulfide-linked Fv, scFv, a single-domain antibody, or a diabody.

[0383] Example 2 describes the production of a fully human CDCP1 antibody against the extracellular domain of human CDCP1. The heavy and light chain variable region (CDR) amino acid sequences of these human antibodies are shown in Figures 15, 18, and 20, and the nucleotide sequences encoding these heavy and light chain variable region amino acid sequences are shown in Figure 19.

[0384] Accordingly, in one embodiment, the present disclosure comprises a human anti-CDCP1 antibody or its antigen-binding moiety, from the group consisting of SEQ ID NOs: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141, 151, 161, 171, 181, 191, 201, 211, 221, 231, 241, 251, 261, 271, 281, 291, 301, 311, 321, 331, 341, 351, 361, 371, 381, and 391. A heavy chain variable region containing a selected amino acid sequence; and a light chain variable region containing an amino acid sequence selected from the group consisting of 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 152, 162, 172, 182, 192, 202, 222, 222, 232, 242, 252, 262, 272, 282, 292, 302, 322, 322, 332, 342, 352, 362, 372, 382, ​​and 392.

[0385] In one embodiment, the present disclosure is an HC selected from those shown in Figure 15 or 20. The antibody comprises a human anti-CDCP1 antibody or its antigen-binding moiety, including a CDR set (CDR1, CDR2, and CDR3) and an LC CDR set (CDR1, CDR2, and CDR3) selected from those shown in Figure 15 or 20.

[0386] In one embodiment, the anti-CDCP1 antibody or its antigen-binding moiety is the human antibody 38E11. The 38E11 antibody includes a heavy chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 157, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 156, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 155, and a light chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 160, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 159, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 158. In a further embodiment, an antibody having a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 151 and a light chain variable region containing the amino acid sequence of SEQ ID NO: 152 is described herein.

[0387] In some embodiments, the anti-CDCP1 antibody or its antigen-binding moiety includes a heavy chain containing the amino acid sequence shown in SEQ ID NO: 151, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 151, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 152, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 152.

[0388] In one embodiment, the anti-CDCP1 antibody or its antigen-binding moiety is the human antibody 27H10. The 27H10 antibody includes a heavy chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 37, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 36, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 35, and a light chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 40, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 39, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 38. In a further embodiment, an antibody having a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 31 and a light chain variable region containing the amino acid sequence of SEQ ID NO: 32 is described herein.

[0389] In some embodiments, the anti-CDCP1 antibody or its antigen-binding moiety includes a heavy chain containing the amino acid sequence shown in SEQ ID NO: 31, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 31, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 32, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 32.

[0390] In one embodiment, the anti-CDCP1 antibody or its antigen-binding moiety is the human antibody 18C6. The 18C6 antibody includes a heavy chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 87, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 86, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 85, and a light chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 90, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 89, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 88. In a further embodiment, an antibody having a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 81 and a light chain variable region containing the amino acid sequence of SEQ ID NO: 82 is described herein.

[0391] In some embodiments, the anti-CDCP1 antibody or its antigen-binding moiety includes a heavy chain containing the amino acid sequence shown in SEQ ID NO: 81, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 81, and / or a light chain containing the amino acid sequence shown in SEQ ID NO: 82, or a sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 82.

[0392] In one embodiment, the anti-CDCP1 antibody or its antigen-binding moiety is a human antibody 10E2. The 10E2 antibody includes a heavy chain variable region including a CDR3 domain containing the amino acid sequence of SEQ ID NO: 107, a CDR2 domain containing the amino acid sequence of SEQ ID NO: 106, and a CDR1 domain containing the amino acid sequence of SEQ ID NO: 105, and a light chain variable region including a CDR3 domain containing the amino acid sequ...

Claims

[Claim 1] The invention as shown in the drawings.

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