Anti-b7-h3 antibody

Abstract

ANTI-B7-H3 ANTIBODY In some aspects, an anti-B7-H3 antibody or its use is provided.

Description

ANTI-B7-H3 ANTIBODY Technical Field

[0001] In some aspects, the present invention relates to ananti-B7-H3 antibody or its use.Background Art

[0002] It is widely expected that the development of abiomarker which enables the prognosis of the efficacy orsafety, for example, of a therapeutic drug would lead tosignificant improvements in treatment for a wide variety of diseases and conditions. Thus, a great deal of effort has been taken to find such biomarker.

[0003] An anti-B7-H3 antibody or an anti-B7-H3 antibody- drug conjugate (ADC) which targets cancer cells expressing B7-H3 is known in the art. For example, an antibody-drug conjugate in which an exatecan derivative (a DNA topoisomerase I inhibitor) is conjugated to ananti-B7-H3 antibody (i.e. a targeting anti-B7-H3antibody) has been reported to show promising anti-tumoreffects (Patent Reference 1).Citation List Patent Literature 14833176-2

[0004] Patent Reference 1: WO2014 / 057687Summary of Invention Technical Problem

[0005] One possible biomarker for prognosing the efficacyor safety, for example, of an anti-tumor drug thattargets cancer cells expressing human B7-H3 may be human B7-H3 itself. Therefore, in some aspects, to elucidate the correlation between human B7-H3 expression level and the efficacy, for example, of an anti-B7-H3 ADC, it would be advantageous to develop and validate an anti-B7-H3 antibody (i.e. a detecting anti-B7-H3 antibody) that isable to measure or quantify with sufficient sensitivitythe presence and / or amount of human B7-H3 or human B7-H3in a complex in or on a cell or tumor sample containingcells expressing human B7-H3.Solution to Problem

[0006] In some aspects, the present inventors, as a resultof diligent studies, successfully identified andvalidated an anti-B7-H3 antibody which meets the above purpose. 14833176-2

[0007] Thus, in some embodiments, the present invention provides the following:

[0008] [1] An anti-B7-H3 antibody or an antigen-binding fragmentthereof, comprising: (1) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 31 to 35 of SEQ ID NO: 3; (2) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 50 to 65 of SEQ ID NO: 3; (3) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 98 to 107 of SEQ ID NO: 3; (4) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 24 to 39 of SEQ ID NO: 4; (5) CDRL2 consisting of an amino acid sequence consisting of amino acid residues 55 to 61 of SEQ ID NO: 4; and (6) CDRL3 consisting of an amino acid sequence consistingof amino acid residues 94 to 102 of SEQ ID NO: 4.[2] The anti-B7-H3 antibody or the antigen-bindingfragment thereof according to [1], wherein the anti-B7-H3antibody or the antigen-binding fragment thereofspecifically binds the IgC1 domain of human B7-H3.[3] The anti-B7-H3 antibody or the antigen-bindingfragment thereof according to [1] or [2], wherein theanti-B7-H3 antibody comprisesa heavy chain variable region comprising the amino acidsequence of SEQ ID NO: 3; and 14833176-2a light chain variable region comprising the amino acidsequence of SEQ ID NO: 4. [4] A method of measuring and / or quantifying the presence and / or amount of human B7-H3 or human B7-H3 in a complex in a sample, the method comprising (a) contacting the anti-B7-H3 antibody or the antigen- binding fragment thereof according to any one of [1] to[3] with the sample; and(b) allowing the anti-B7-H3 antibody or the antigen- binding fragment thereof to bind to the human B7-H3 orhuman B7-H3 in a complex in the sample and therebydetermining the presence and / or amount of human B7-H3 orhuman B7-H3 in a complex in the sample.[5] The method according to [4], wherein the sample is atumor sample. [6] The method according to [4] or [5], wherein thepresence and / or amount of human B7-H3 is determined byimmunohistochemistry. [7] A pharmaceutical composition for use in treating or preventing cancer, comprising a therapeutically effectiveamount of an anti-B7-H3 antibody-drug conjugate in whicha drug-linker is conjugated to a targeting anti-B7-H3 antibody or a functional fragment thereof, wherein the subject is pre-determined to have thelikelihood of responsiveness to the anti-B7-H3 antibody-drug conjugate by determining the presence and / or amountof human B7-H3 or human B7-H3 in a complex in a tumor 14833176-2sample from the subject using a detecting anti-B7-H3antibody, which is the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of[1] to [3], andwherein preferably, the targeting anti-B7-H3 antibody orthe functional fragment thereof comprises(i) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 50 to 54 of SEQ ID NO: 1; (ii) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 69 to 85 of SEQ ID NO: 1; (iii) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 118 to 130 of SEQ ID NO: 1; (iv) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 44 to 53 of SEQ ID NO: 2; (v) CDRL2 consisting of an amino acid sequence consistingof amino acid residues 69 to 75 of SEQ ID NO: 2; and(vi) CDRL3 consisting of an amino acid sequence consisting of amino acid residues 108 to 116 of SEQ ID NO: 2. [8] The pharmaceutical composition for use according to [7], wherein the targeting anti-B7-H3 antibody or thefunctional fragment thereof comprises14833176-2a heavy chain variable region consisting of an amino acid sequence consisting of amino acid residues 20 to 141 ofSEQ ID NO: 1; anda light chain variable region consisting of an amino acid sequence consisting of amino acid residues 21 to 128 of SEQ ID NO: 2. [9] The pharmaceutical composition for use according to [7] or [8], wherein the targeting anti-B7-H3 antibodyconsists ofa heavy chain consisting of an amino acid sequence consisting of amino acid residues 20 to 471 of SEQ ID NO:1; anda light chain consisting of an amino acid sequence consisting of amino acid residues 21 to 233 of SEQ ID NO: 2.

[0010] The pharmaceutical composition for use according to [9], wherein a lysine residue is deleted from each of the carboxyl termini of both of the heavy chains of the targeting anti-B7-H3 antibody.

[0011] The pharmaceutical composition for use according to any one of [7] to

[0010] , wherein the drug-linker represented by the following formula is conjugated to the targeting anti-B7-H3 antibody or the functional fragment thereof via a thioether bond: 14833176-2wherein “A” in the formula represents a connectingposition to the targeting anti-B7-H3 antibody or the functional fragment thereof.

[0012] The pharmaceutical composition for use according to

[0011] , wherein the average number of units of the drug- linker conjugated per antibody molecule in the anti-B7-H3antibody-drug conjugate is in the range from 3 to 5, andmore preferably from 3.5 to 4.5.

[0013] The pharmaceutical composition for use according to

[0011] or

[0012] , wherein the anti-B7-H3 antibody-drug conjugate is represented by the following formula:14833176-2wherein ‘Antibody’ in the formula represents the targeting anti-B7-H3 antibody or the functional fragment thereof conjugated to the drug-linker via a thioether bond, and n represents drug-to-antibody ratio.

[0014] The pharmaceutical composition for use according toany one of [7] to

[0013] , wherein the anti-B7-H3 antibody-drug conjugate is ifinatamab deruxtecan.

[0015] The pharmaceutical composition for use according toany one of [7] to

[0014] , wherein the cancer is cancer expressing B7-H3, preferably selected from the groupconsisting of esophageal cancer (including esophagealsquamous cell carcinoma), bladder cancer, gallbladdercancer, urothelial cancer, kidney cancer, ovarian cancer,pancreatic cancer, colorectal cancer (also called colon and rectal cancer, and including colon cancer and rectalcancer), liver cancer, stomach cancer, melanoma,osteosarcoma, glioblastoma multiforme, endometrialcancer, prostate cancer (including castrate-resistantprostate cancer), neuroendocrine tumor, Rhabdomyosarcoma, Wilms tumor, neuroblastoma, head and neck cancer (including head and neck squamous cell carcinoma), vulval cancer, mesothelioma, skin cancer, bile duct cancer,stromal tumor, breast cancer, lung cancer (includingsmall cell lung cancer (SCLC) and non-small cell lungcancer (NSCLC)), hepatocellular carcinoma, pancreaticadenocarcinoma, sarcoma, gastric cancer (also calledgastric adenocarcinoma), cervical cancer, uterine cancer,14833176-2salivary gland cancer, gastroesophageal junctionadenocarcinoma, gastrointestinal cancer, Paget disease,peritoneal cancer, thyroid cancer, penile cancer,leukemia, malignant lymphoma, plasmacytoma, myeloma, nerve epithelial tissue tumor, nerve sheath tumor, throat cancer, and pharyngeal cancer.

[0016] The pharmaceutical composition for use according toany one of [7] to

[0015] , wherein the presence and / oramount of human B7-H3 or human B7-H3 in a complex isdetermined by immunohistochemistry.

[0017] A method of treating or preventing cancer in a subject with cancer or suspected cancer, comprising administering a therapeutically effective amount of the anti-B7-H3 antibody-drug conjugate as defined in any oneof [7] to

[0014] to a subject in need thereof,wherein the subject is pre-determined to have thelikelihood of responsiveness to the anti-B7-H3 antibody-drug conjugate by determining the presence and / or amount of human B7-H3 or human B7-H3 in a complex in a tumor sample from the subject using the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any oneof [1] to [3], optionally by immunohistochemistry, andwherein the cancer is optionally as defined in

[0015] .

[0018] A method of determining whether a subject withcancer or suspected cancer is likely to respond totreatment with the anti-B7-H3 antibody-drug conjugate asdefined in any one of [7] to

[0014] , comprising measuring 14833176-2and / or quantifying the presence and / or amount of humanB7-H3 or human B7-H3 in a complex in a tumor sample fromthe subject using a detecting anti-B7-H3 antibody whichis the anti-B7-H3 antibody or the antigen-bindingfragment thereof according to any one of [1] to [3],optionally by immunohistochemistry, and wherein the cancer is optionally as defined in

[0015] .

[0019] A diagnostic kit comprising the anti-B7-H3 antibody or the antigen-binding fragment thereof according to anyone of [1] to [3].

[0020] A pharmaceutical composition for use in treating or preventing cancer, comprising a therapeutically effectiveamount of the anti-B7-H3 antibody-drug conjugate asdefined in any one of [7] to

[0014] , wherein the pharmaceutical composition is for use in combination with the diagnostic kit according to

[0019] , wherein the cancer is optionally as defined in

[0015] .

[0021] A method of selecting a subject for treatment or prevention of cancer by administration of atherapeutically effective amount of the anti-B7-H3antibody-drug conjugate as defined in any one of [7] to

[0014] , comprising measuring and / or quantifying thepresence and / or amount of human B7-H3 or human B7-H3 in acomplex in a tumor sample from the subject using adetecting anti-B7-H3 antibody, which is the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of [1] to [3], optionally by 14833176-2immunohistochemistry, and wherein the cancer is optionally as defined in

[0015] .

[0022] The pharmaceutical composition according to any one of [7] to

[0010] , wherein a drug in the anti-B7-H3 antibody-drug conjugate is a topoisomerase I inhibitor,wherein the cancer is optionally as defined in

[0015] andwherein the presence and / or amount of human B7-H3 isoptionally determined by immunohistochemistry.

[0023] The pharmaceutical composition according to

[0022] , wherein the drug represented by the following formula is released to express an antitumor activity:.

[0024] The pharmaceutical composition according to

[0022] , wherein an antitumor compound represented by thefollowing formula is conjugated to the targeting anti-B7-H3 antibody or the functional fragment thereof as definedin any one of [7] to

[0010] through a linker with the nitrogen atom of the amino group at position 1 as the connecting position: 14833176-2.

[0025] The pharmaceutical composition according to

[0024] , wherein the antitumor compound is conjugated to the targeting anti-B7-H3 antibody or the functional fragmentthereof as defined in any one of [7] to

[0010] through thelinker via a thioether bond which is formed at a disulfide bond moiety present in the targeting anti-B7-H3antibody or the functional fragment thereof.

[0026] The pharmaceutical composition according to

[0024] or

[0025] , wherein the linker comprises a tetrapeptide residue of -Gly-Gly-Phe-Gly-.

[0027] The pharmaceutical composition according to any oneof [7] to

[0011] , wherein the number of units of the drug-linker conjugated per antibody molecule in the anti-B7-H3 antibody-drug conjugate is an integer in the range from 2 to 8, preferably 2, 4, 6, or 8, and most preferably 4,wherein the cancer is optionally as defined in

[0015] andwherein the presence and / or amount of human B7-H3 isoptionally determined by immunohistochemistry. 14833176-2

[0028] The pharmaceutical composition according to

[0011] or

[0012] , wherein the anti-B7-H3 antibody-drug conjugate is represented by the following formula:wherein ‘Antibody’ in the formula represents the targeting anti-B7-H3 antibody or the functional fragmentthereof as defined in any one of [7] to

[0010] conjugatedto the drug-linker via a thioether bond and n represents the average number of units of the drug-linker conjugated per antibody molecule in the anti-B7-H3 antibody-drug conjugate, wherein n is in the range from 3 to 5, whereinthe cancer is optionally as defined in

[0015] , and whereinthe presence and / or amount of human B7-H3 is optionallydetermined by immunohistochemistry.

[0029] The pharmaceutical composition according to

[0011] or

[0012] , wherein the anti-B7-H3 antibody-drug conjugate isrepresented by the formula shown in

[0028] , wherein‘Antibody’ in the formula is the targeting anti-B7-H3antibody or the functional fragment thereof as defined inany one of [7] to

[0010] and each drug-linker representedby the structure shown within the bracket in the formula 14833176-2is conjugated to the anti-B7-H3 antibody or thefunctional fragment thereof via a thioether bond, and nrepresents the average number of units of the drug-linker conjugated per antibody molecule in the anti-B7-H3 antibody-drug conjugate, wherein n is in the range from 3 to 5, wherein the cancer is optionally as defined in

[0015] , and wherein the presence and / or amount of human B7-H3 is optionally determined by immunohistochemistry. Advantageous Effects of Invention

[0009] In one aspect, the antibody or the antigen-bindingfragment thereof of the present invention can measure orquantify with sufficient sensitivity the presence and / oramount of human B7-H3 or human B7-H3 in a complex in a cell or tumor sample containing cells expressing human B7-H3. In another aspect, the antibody or the antigen-binding fragment thereof of the present invention can be used as a companion diagnostic to determine or prognosethe efficacy or safety, for example, of an anti-B7-H3antibody-drug conjugate. Brief Description of Drawings

[0010] [Figure 1] Figure 1 shows amino acid sequences of heavyand light chain variable regions of Anti-B7-H3 Ab (2).14833176-2[Figure 2] Figure 2 shows images of IHC staining by Anti-B7-H3 Ab (2) in human FFPE tissue sections ofhepatocellular carcinoma, breast cancer, and endometrialcancer at 20x magnification. Description of Embodiments

[0011] Hereinafter, preferred modes for carrying out thepresent invention are described. The embodiments described below are given merely for illustratingexamples of typical embodiments of the present inventionand are not intended to limit the scope of the present invention. Various embodiments or elements in relation to B7-H3 or its preparation, an anti-B7-H3 antibody-drug conjugate or a pharmaceutical composition comprising the anti-B7-H3 antibody-drug conjugate, including, but not limited to, adrug or its preparation, a drug-linker or its conjugationor preparation, an anti-B7-H3 antibody (i.e. a targetinganti-B7-H3 antibody) used in the anti-B7-H3 antibody-drugconjugate or its production, a drug-linker intermediatefor use in the production of the antibody-drug conjugate,or the production of the antibody-drug conjugate aredisclosed in WO2014 / 057687, which is incorporated hereinby reference. 1. Anti-B7-H3 antibody-drug conjugate 14833176-2

[0012] As used herein, the term "anti-B7-H3 antibody-drug conjugate" refers to an antibody-drug conjugate in which the antibody in the antibody-drug conjugate is an anti- B7-H3 antibody (i.e. a targeting anti-B7-H3 antibody) ora functional fragment thereof. In some embodiments, an“antibody-drug conjugate” is a construct comprising atargeting antibody or antigen binding fragment thereofwhich is associated with a drug. Typically, the antibody or antigen binding fragment thereof is associated with the drug by way of a linker that connects the targeting antibody or antigen binding fragment to the drug covalently. Exemplary anti-B7-H3 antibody-drug conjugates usedin the present invention are known in the art.

[0013] In some embodiments, the drug in the anti-B7-H3 antibody-drug conjugate is a topoisomerase I inhibitor. In particular embodiments, the drug represented by the following formula is released to express an antitumor activity: 14833176-2.

[0014] In some embodiments, an antitumor compound represented by the following formula is conjugated to thetargeting anti-B7-H3 antibody or the functional fragmentthereof through a linker with the nitrogen atom of theamino group at position 1 as the connecting position:. In particular, the antitumor compound may beconjugated to the targeting anti-B7-H3 antibody or thefunctional fragment thereof through a linker via athioether bond which is formed at a disulfide bond moietypresent in the targeting anti-B7-H3 antibody or thefunctional fragment thereof. An exemplary linkercomprises a tetrapeptide residue of -Gly-Gly-Phe-Gly-. 14833176-2

[0015] In some embodiments, the anti-B7-H3 antibody-drugconjugate is as described herein. In some preferredembodiments, the anti-B7-H3 antibody-drug conjugate is ifinatamab deruxtecan.

[0016] In some embodiments, in the anti-B7-H3 antibody-drug conjugate, the drug-linker represented by the followingformula is conjugated to a targeting anti-B7-H3 antibodyor a functional fragment thereof via a thioether bond:wherein “A” in the formula represents a connectingposition to the targeting anti-B7-H3 antibody or the functional fragment thereof. In further embodiments, the average number of unitsof the drug-linker conjugated per antibody molecule inthe anti-B7-H3 antibody-drug conjugate is preferably 2 to8, more preferably 3 to 5, even more preferably 3.5 to 4.5, and even more preferably about 4. 14833176-2In other embodiments, the number of drugs or drug-linkers conjugated per antibody molecule in the anti-B7-H3 antibody-drug conjugate is an integer in the range from preferably 2 to 8, more preferably selected from 2, 4, 6, or 8, and most preferably 4.

[0017] In some embodiments, the anti-B7-H3 antibody-drugconjugate used in the present invention can be represented by the following formula:nwherein the drug-linker is conjugated to the targetinganti-B7-H3 antibody or the functional fragment thereofvia a thioether bond. The meaning of n is the same aswhat is termed the average number of conjugated drugmolecules per antibody molecule (DAR; Drug-to-Antibody Ratio). In this context, n indicates the average number of units of the drug-linker conjugated per antibodymolecule, and, in one aspect, also refers to the averagenumber of drug molecules (or units of the drug-linker)conjugated per antibody molecule in a composition ofantibody-drug conjugates. Alternatively, in a different14833176-2context, n may represent the number of units of the drug-linker conjugated per antibody molecule in an anti-B7-H3antibody-drug conjugate.

[0018] In some embodiments, the anti-B7-H3 antibody-drug conjugate used in the present invention can be produced with reference to WO2014 / 057687, WO2017 / 002776 or WO2022 / 014698, each of which is incorporated herein by reference. 2. B7-H3

[0019] The term "B7-H3" as used herein is preferably humanB7-H3 and is used with the same meaning as “B7-H3protein”. It also refers to B7-H3 variant 1 and / or B7-H3 variant 2. B7-H3 (also known as B cell antigen #7 homolog 3;PD-l3; or CD276) is a member of the B7 family expressedon antigen-presenting cells as a co-stimulatory molecule and is considered to act on a receptor on T cells to enhance or suppress immune activity. B7-H3 is a protein having a single-pass transmembrane structure and the N-terminal extracellulardomain of B7-H3 has two variants. The B7-H3 variant 1 (or4Ig-B7-H3) contains two V-like Ig domains (as IgV1 domainand IgV2 domain respectively) and two C-like Ig domains (as IgC1 domain and IgC2 domain respectively), and the 14833176-2B7-H3 variant 2 (2Ig-B7-H3) contains one V-like Ig domainand one C-like Ig domain (e.g. Steinberger, et al. JImmunol (2004) 172 (4): 2352–2359.). Under the definitionof UniProt accession number Q5ZPR3-1 (2004-11-23 v1), amino acid sequences of IgV1, IgC1, IgV2 and IgC2 domains correspond to amino acid residues 29-139, 145-238, 243- 357 and 363-456 of 4Ig-B7-H3, respectively. 3. Anti-B7-H3 antibody

[0020] As used herein, the term “anti-B7-H3 antibody”refers to an antibody which specifically binds to B7-H3,preferably human B7-H3. In this specification, the term “specifically binds”with reference to an antibody means that the antibody binds to the target antigen preferentially as compared with unrelated target antigens.

[0021] In some embodiments, an anti-B7-H3 antibodycomprises any constant region known in the art such asone originated or derived from any species such as ahuman, a rat, a mouse, or a rabbit, or a mutated onethereof. Such an anti-B7-H3 antibody may be a monoclonalor polyclonal antibody.

[0022] As used herein, a "functional fragment of anantibody" may also be called an "antigen-binding fragment14833176-2of an antibody" and each term is used to mean a partialfragment of an antibody having binding activity againstthe antigen thereof, and includes, but is not limited to,Fab, F(ab')2, scFv, a diabody, a linear antibody or amulti-specific antibody formed from antibody fragments. In some embodiments, Fab', which is a monovalent fragment of antibody variable regions obtained by treating F(ab')2under reducing conditions, is also included within theterm antigen-binding fragment of an antibody. Theantigen-binding fragment of an antibody is not limited to these molecules as long as the antigen-binding fragment has antigen-binding ability. These antigen-binding fragments include not only those obtained by treating a full-length molecule of an antibody protein with an appropriate enzyme, but also proteins produced in appropriate host cells using a genetically engineered antibody gene.

[0023] In some embodiments, modified variants of an anti-B7-H3 antibody or an antigen-binding fragment thereof arealso included and examples of such modified variants areexplained in further detail below. In some embodiments, an anti-B7-H3 antibody or anantigen-binding fragment thereof in which themodification of a glycan is regulated are also included.

[0024] 14833176-2It is known that a lysine residue at the carboxyl terminus of the heavy chain of an antibody produced in a cultured mammalian cell is deleted (Journal of Chromatography A, 705: 129-134 (1995)), and it is alsoknown that two amino acid residues (glycine and lysine)at the carboxyl terminus of the heavy chain of an antibody produced in a cultured mammalian cell are deleted and a proline residue newly located at the carboxyl terminus is amidated (Analytical Biochemistry, 360: 75-83 (2007)). However, such deletion and modification of the heavy chain sequence do not affect the antigen-binding affinity and the effector function of the antibody. Therefore, in some embodiments, anti-B7-H3antibodies subjected to such modification or functionalfragments thereof are also included. In otherembodiments, variants in which one or two amino acids have been deleted at either or both of the carboxyl terminus of the heavy chains, variants obtained by amidation of the deletion variants (for example, a heavy chain in which the carboxyl terminal proline residue has been amidated) are also included. The type of deletion variant having a deletion at the carboxyl terminus of the heavy chain of the anti-B7-H3 antibody or the functional fragment thereof is not limited to the above variants aslong as the antigen-binding affinity and the effectorfunction are conserved. In some preferred embodiments, ananti-B7-H3 antibody in which one amino acid residue at 14833176-2the carboxyl terminus has been deleted in both of the two heavy chains in the antibody can be exemplified.

[0025] It is to be understood that in embodiments of thepresent invention, there are provided a detecting anti- B7-H3 antibody and also a targeting anti-B7-H3 antibody. Although each antibody binds to B7-H3, the detecting anti-B7-H3 antibody and the targeting anti-B7-H3 antibodymay bind same, overlapping, or different epitopes thereofand have different sequences. Moreover, the targeting anti-B7-H3 antibody is conjugated to a drug-linker to form an antibody-drug conjugate.

[0026] In some embodiments, the detecting anti-B7-H3 antibody or the antigen-binding fragment thereof of thepresent invention is as exemplified herein. In furtherpreferred embodiments, it specifically binds the IgC1domain of human B7-H3. Considering the high sequencehomology between the IgC1 domain and the IgC2 domain ofhuman B7-H3, it is expected to bind the IgC2 domain aswell.

[0027] In some embodiments, the detecting anti-B7-H3 antibody or the antigen-binding fragment thereof comprises: (1) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 31 to 35 of SEQ ID NO: 3; 14833176-2(2) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 50 to 65 of SEQ ID NO: 3; (3) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 98 to 107 of SEQ ID NO: 3; (4) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 24 to 39 of SEQ ID NO: 4; (5) CDRL2 consisting of an amino acid sequence consisting of amino acid residues 55 to 61 of SEQ ID NO: 4; and (6) CDRL3 consisting of an amino acid sequence consistingof amino acid residues 94 to 102 of SEQ ID NO: 4.In preferred embodiments, the detecting anti-B7-H3antibody comprises: a heavy chain variable regioncomprising the amino acid sequence of SEQ ID NO: 3; anda light chain variable region comprising the amino acidsequence of SEQ ID NO: 4. In particular embodiments, the detecting anti-B7-H3antibody is Anti-B7-H3 Ab (2) as exemplified herein.

[0028] In other embodiments, the targeting anti-B7-H3antibody or the functional fragment thereof used in theanti-B7-H3 antibody-drug conjugate is also as exemplifiedherein.

[0029] In some embodiments, the targeting anti-B7-H3antibody or the functional fragment thereof comprises(i) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 50 to 54 of SEQ ID NO: 1; 14833176-2(ii) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 69 to 85 of SEQ ID NO: 1; (iii) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 118 to 130 of SEQ ID NO: 1; (iv) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 44 to 53 of SEQ ID NO: 2; (v) CDRL2 consisting of an amino acid sequence consistingof amino acid residues 69 to 75 of SEQ ID NO: 2; and(vi) CDRL3 consisting of an amino acid sequence consisting of amino acid residues 108 to 116 of SEQ ID NO: 2.

[0030] In preferred embodiments, the targeting anti-B7-H3antibody comprises: a heavy chain variable regionconsisting of an amino acid sequence consisting of aminoacid residues 20 to 141 of SEQ ID NO: 1; anda light chain variable region consisting of an amino acid sequence consisting of amino acid residues 21 to 128 of SEQ ID NO: 2.

[0031] In particularly preferred embodiments, the targeting anti-B7-H3 antibody comprises: 14833176-2a heavy chain consisting of an amino acid sequence consisting of amino acid residues 20 to 471 of SEQ ID NO:1; anda light chain consisting of an amino acid sequence consisting of amino acid residues 21 to 233 of SEQ ID NO: 2. In particular embodiments, the anti-B7-H3 antibody- drug conjugate is Anti-B7-H3 ADC (1) as exemplified herein.

[0032] As for isotypes of an anti-B7-H3 antibody (eitherthe detecting anti-B7-H3 antibody or the targeting anti-B7-H3 antibody) or an antigen-binding fragment thereof,IgG (IgG1, IgG2, IgG3, IgG4) can be exemplified, for example.

[0033] The term "CDR" as used herein refers to a complementarity determining region (CDR), and it is known that each heavy and light chain of an antibody molecule has three complementarity determining regions (CDRs). The CDR is also called the hypervariable region and is present in a variable region of each heavy and lightchain of an antibody. There are three separate CDRs inthe primary structure of each heavy and light polypeptide chain. As used herein, as for CDRs in an antibody or anantigen-binding fragment thereof, CDRs of the heavy chain 14833176-2are represented by CDRH1, CDRH2, and CDRH3 from the amino-terminus of the amino acid sequence of the heavy chain, and CDRs of the light chain are represented byCDRL1, CDRL2, and CDRL3 from the amino-terminus of theamino acid sequence of the light chain.3. Various uses of anti-B7-H3 antibody

[0034] In some aspects, the anti-B7-H3 antibody or the antigen-binding fragment thereof of the present invention(i.e. the detecting anti-B7-H3 antibody) can be used forvarious purposes. Such uses are exemplified herein. In some embodiments, it can be used for detecting, measuring or quantifying the presence and / or amount ofB7-H3 or B7-H3 in a complex in a sample. This is achievedby allowing the detecting anti-B7-H3 antibody or theantigen-binding fragment thereof to bind to the human B7-H3 or human B7-H3 in a complex in the sample therebycreating, releasing or facilitating the production of ameasurable signal. The sample may be a tumor sample,which may be obtained from a subject optionally with cancer or suspected cancer. In some embodiments, thephrase “human B7-H3 in a complex” means that the humanB7-H3 is in complex with any bound ligand. The presence and / or amount of B7-H3 can be checked by, for example, collecting tumor tissue from a cancer patient, and subjecting the formalin fixed paraffin 14833176-2embedded specimen (FFPE) to examination at a gene product(protein) level, such as an immunohistochemistry (IHC)method, flow cytometry, or a Western blot method. Inpreferred embodiments, the presence and / or amount of B7-H3 is determined by immunohistochemistry. In some embodiments, the anti-B7-H3 antibody or the antigen-binding fragment thereof of the present invention can be used to determine whether a subject with cancer or suspected cancer is likely to respond to treatment withan anti-B7-H3 antibody-drug conjugate by measuring and / orquantifying the presence and / or amount of human B7-H3 orhuman B7-H3 in a complex in a tumor sample. In thisspecification a subject with cancer or suspected cancer is considered to “respond to treatment” or to have “responsiveness” to a treatment when there is an improvement in his or her condition, symptoms or prognosis including, but not limited to, completeremission or an increase in progression free survivalterm.

[0035] In some embodiments, the anti-B7-H3 antibody or theantigen-binding fragment thereof of the present inventioncan be used to select a subject for treatment or preventionof cancer by administration of an anti-B7-H3 antibody-drugconjugate by measuring and / or quantifying the presenceand / or amount of human B7-H3 or human B7-H3 in a complex in a tumor sample from the subject. 14833176-2

[0036] In some embodiments, the anti-B7-H3 antibody or the antigen-binding fragment thereof of the present inventioncan be used in combination with an anti-B7-H3 antibody-drug conjugate or a pharmaceutical composition comprisingthe anti-B7-H3 antibody-drug conjugate.In some embodiments, the anti-B7-H3 antibody or the antigen-binding fragment thereof of the present inventioncan be used to determine the likelihood of responsivenessto an anti-B7-H3 antibody-drug conjugate by determiningthe presence and / or amount of human B7-H3 or human B7-H3in a complex in a tumor sample, before or during treatingor preventing cancer in a subject with cancer orsuspected cancer using such anti-B7-H3 antibody-drugconjugate. In some embodiments, the anti-B7-H3 antibody or the antigen-binding fragment thereof of the present inventioncan be used as a diagnostic kit. In particularembodiments, the kit comprises the detecting anti-B7-H3antibody or the antigen binding fragment thereof and oneor more other components selected from the following:instructions for use of the detecting anti-B7-H3antibody, a buffer, or the anti-B7-H3 antibody-drugconjugate as described herein. 4. Cancer

[0037] 14833176-2In some embodiments, cancer detected, diagnosed,treated or prevented, for example, is cancer expressingB7-H3, preferably human B7-H3. Such cancer includes, butis not limited to, esophageal cancer (includingesophageal squamous cell carcinoma), bladder cancer,gallbladder cancer, urothelial cancer, kidney cancer,ovarian cancer, pancreatic cancer, colorectal cancer(also called colon and rectal cancer, and including coloncancer and rectal cancer), liver cancer, stomach cancer,melanoma, osteosarcoma, glioblastoma multiforme,endometrial cancer, prostate cancer (including castrate-resistant prostate cancer), neuroendocrine tumor, Rhabdomyosarcoma, Wilms tumor, neuroblastoma, head andneck cancer (including head and neck squamous cellcarcinoma), vulval cancer, mesothelioma, skin cancer,bile duct cancer, stromal tumor, breast cancer, lungcancer (including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)), hepatocellularcarcinoma, pancreatic adenocarcinoma, sarcoma, gastric cancer (also called gastric adenocarcinoma), cervicalcancer, uterine cancer, salivary gland cancer,gastroesophageal junction adenocarcinoma,gastrointestinal cancer, Paget disease, peritonealcancer, thyroid cancer, penile cancer, leukemia,malignant lymphoma, plasmacytoma, myeloma, nerve epithelial tissue tumor, nerve sheath tumor, throatcancer, or pharyngeal cancer.14833176-25. Pharmaceutical composition

[0038] In some embodiments, the pharmaceutical compositionand method of treatment or prevention of the presentinvention can be used for a mammal, preferably for a human.

[0039] In some embodiments, the pharmaceutical compositionof the present invention comprises the anti-B7-H3antibody-drug conjugate described herein. In someembodiments, the pharmaceutical composition of thepresent invention includes a pharmaceutical compositionfurther containing at least one pharmaceutically suitableingredient. The pharmaceutically suitable ingredient canbe suitably selected and applied from formulationadditives or the like that are generally used in the art,in accordance with the dosage, administrationconcentration or the like of an anti-B7-H3 antibody-drugconjugate. For example, the anti-B7-H3 antibody-drug conjugate can be administered as a pharmaceutical composition containing a buffer such as a histidinebuffer, an excipient such as sucrose or trehalose, adiluent such as physiological saline and a surfactantsuch as Polysorbate 80 or 20. Examples of the administration route which may beused to administer the pharmaceutical composition include14833176-2intravenous, intradermal, subcutaneous, intramuscular, or intraperitoneal routes.

[0040] In some embodiments, following administration of theanti-B7-H3 antibody-drug conjugate to a subject, theanti-B7-H3 antibody-drug conjugate circulates within thesubject and the targeting antibody or antigen binding fragment binds to its target, B7-H3. Due to its being conjugated to the targeting antibody or antigen binding fragment, the drug is likewise located adjacent to the B7-H3. Since B7-H3 is more highly expressed in many tumor cells, this results in the antibody-drug conjugate, and therefore the drug component thereof, being locatedadjacent to tumor cells where the drug is able to performits role (e.g. having a cytotoxic effect).

[0041] In some embodiments, the anti-B7-H3 antibody-drug conjugate can be administered to a human once at intervals of 1 to 180 days, and can be preferably administered once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks, and can be even more preferably administered once every 3 weeks. Also, in further embodiments, the anti-B7-H3 antibody-drug conjugate can be administered at a dose of about 0.001 to 100 mg / kg, and can be preferably administered at a doseof 0.8 mg / kg, 1.6 mg / kg, 3.2 mg / kg, 4.8 mg / kg, 6.4 mg / kg,8 mg / kg, 12 mg / kg, or 16 mg / kg, and can be more 14833176-2preferably administered at a dose of 8 to 12 mg / kg, preferably, 8 mg / kg or 12 mg / kg once every 3 weeks. In some embodiments, 8 to 12 mg / kg, preferably 12 mg / kg or 8 mg / kg, of the anti-B7-H3 antibody-drug conjugate is intravenously administered once every three weeks. 6. Sample

[0042] In some embodiments of the present invention, the presence and / or amount of human B7-H3 or human B7-H3 in acomplex within a sample is determined by a method of theinvention. The sample is a biological sample, such as a tumor sample, obtained from a subject. Examples of thebiological sample can include, but are not particularlylimited to, biopsied tumor, spinal fluid, pleural fluid, intra-abdominal fluid, lymph, skin sections, blood, urine, feces, sputum, the respiratory organs, the intestinal tract, the genitourinary tract, saliva, milk, the digestive organs, and cells collected therefrom.

[0043] In some embodiments, the tumor sample which is thesubject of the method is all of, or a portion of, theresected tissue obtained during surgery performed on a subject for the purpose or treating cancer. In other embodiments, the tumor sample is all of, or a portion of,the tissue collected by biopsy or the like from a subjectsuspected of having cancer. In still other embodiments, 14833176-2the tumor sample comprises cells derived from blood,pleural fluid, or intra-abdominal fluid from a subject.

[0044] As used herein, unless specifically stated otherwise and not limited in particular, and as long as it does not contradict technically in the context, a term written in the singular form is considered to include the plural form, and vice versa. Examples

[0045] In some embodiments, the present invention isspecifically described with reference to the examplesshown below. However, the present invention is not limited to these. Further, it is by no means to be interpreted in a limited way.

[0046] [Example 1] Production of Anti-B7-H3 ADC (1)In accordance with a production method described inWO2014 / 057687 or WO2022 / 014698 and using an anti-humanB7-H3 antibody (namely, an antibody comprising a heavychain consisting of an amino acid sequence consisting ofamino acid residues 20 to 471 of SEQ ID NO: 1 and a lightchain consisting of an amino acid sequence consisting of amino acid residues 21 to 233 of SEQ ID NO: 2 (hereinafter, referred to as "M30-H1-L4”)), an anti-human 14833176-2B7-H3 antibody-drug conjugate in which a drug-linker represented by the following formula:wherein A in the formula represents a connecting positionto the anti-human B7-H3 antibody, is conjugated to theanti-human B7-H3 antibody via a thioether bond(hereinafter, referred to as "Anti-B7-H3 ADC (1)", whichis also known as ifinatamab deruxtecan) was produced. The average number of units of the drug-linker conjugated perantibody molecule in Anti-B7-H3 ADC (1) was 4.0 asdetermined by a HPLC method.

[0047] [Example 2] Acquisition of Anti-B7-H3 Ab (2)To obtain an anti-human B7-H3 mouse monoclonal antibody, BDF1 mice were immunized with the extracellular domain of human B7-H3 protein, and candidate clones wereobtained by methods known in the art. An anti-human B7-H3mouse monoclonal antibody (Anti-B7-H3 Ab (2)) was selected from these candidate clones by enzyme-linked 14833176-2immuno sorbent assay (ELISA) and immunohistochemistry (IHC) for B7-H3.

[0048] [Example 3] ELISA with Anti-B7-H3 Ab (2)M30-H1-L4 has been shown to bind the IgC1 domainand / or the IgC2 domain, each of which is a domain in theB7-H3 extracellular domain of human B7-H3 (seeWO2012 / 147713). The antibody part of Anti-B7-H3 ADC (1)has the same amino acid sequence as that of M30-H1-L4 andbinds the IgC1 domain and / or the IgC2 domain (seeWO2014 / 057687). The binding of the supernatant of Anti-B7-H3 Ab (2)-expressing hybridoma to a recombinant human B7-H3 IgC1domain protein (which includes an amino acid sequencecorresponding to amino acid residues 145-238 of UniProtaccession number Q5ZPR3-1 (2004-11-23 v1)) synthesized in-house was determined by a standard 2-step ELISA. The supernatant of the Anti-B7-H3 Ab (2)-expressing hybridomashowed optical density of 0.754 at 450 nm compared with0.074 of the culture medium alone. The result indicates that at least part of the Anti-B7-H3 Ab (2) binding site is located in the IgC1 domain.

[0049] [Example 4] IHC on FFPE cellsFor IHC, the human B7 family molecules were transiently expressed in CHO cells, and formalin-fixed paraffin embedded (FFPE) blocks of pellets of these cells 14833176-2and cancer cell lines endogenously expressing human B7-H3 (expression high: NCI-H322, medium: NCI-N87, low: MDA-MB- 231) were prepared. Thin sections were prepared from the blocks and stained for human B7-H3 with Anti-B7-H3 Ab (2)(5 μg / mL) on a Leica Bond-III automated stainer (LeicaBiosystems) using a standard staining protocol. The results of IHC on FFPE cells shown in Table 1 indicate that Anti-B7-H3 Ab (2) binds specifically to human B7-H3 and is sensitive enough to detect low level of human B7- H3 expression on MDA-MB-231 cells.

[0050] Table 1

[0051] [Example 5] IHC on FFPE human tumor tissue14833176-2FFPE tissue micro array of various human tumor tissue (CT565858, Origene) was purchased and stained withAnti-B7-H3 Ab (2) (1.5μg / mL) on an automated stainerLeica Bond-III using a standard staining protocol. As a result, as shown in Figure 2, specific B7-H3 staining was observed in the plasma membrane and cytoplasm of thetumor cells. Tumor and stromal tissues were able to bedistinguished by morphologic differences.

[0052] [REFERENCE] Nagase-Zembutsu A, Hirotani K, Yamato M, Yamaguchi J, Takata T, Yoshida M, Fukuchi K, Yazawa M, Takahashi S, Agatsuma T. Development of DS-5573a: A novel afucosylated mAb directed at B7-H3 with potent antitumor activity. Cancer Sci. 2016;107(5):674-681. 14833176-2

Claims

CLAIMS1. An anti-B7-H3 antibody or an antigen-binding fragmentthereof, comprising: (1) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 31 to 35 of SEQ ID NO: 3; (2) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 50 to 65 of SEQ ID NO: 3; (3) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 98 to 107 of SEQ ID NO: 3; (4) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 24 to 39 of SEQ ID NO: 4; (5) CDRL2 consisting of an amino acid sequence consisting of amino acid residues 55 to 61 of SEQ ID NO: 4; and (6) CDRL3 consisting of an amino acid sequence consistingof amino acid residues 94 to 102 of SEQ ID NO: 4.

2. The anti-B7-H3 antibody or the antigen-bindingfragment thereof according to claim 1, wherein the anti-B7-H3 antibody or the antigen-binding fragment thereofspecifically binds the IgC1 domain of human B7-H3.

3. The anti-B7-H3 antibody or the antigen-bindingfragment thereof according to claim 1 or 2, wherein theanti-B7-H3 antibody comprisesa heavy chain variable region comprising the amino acidsequence of SEQ ID NO: 3; and 14833176-2a light chain variable region comprising the amino acidsequence of SEQ ID NO:

4.

4. A method of measuring and / or quantifying the presence and / or amount of human B7-H3 or human B7-H3 in a complex in a sample, the method comprising (a) contacting the anti-B7-H3 antibody or the antigen- binding fragment thereof according to any one of claims 1to 3 with the sample; and(b) allowing the anti-B7-H3 antibody or the antigen- binding fragment thereof to bind to the human B7-H3 orhuman B7-H3 in a complex in the sample and therebydetermining the presence and / or amount of human B7-H3 orhuman B7-H3 in a complex in the sample.

5. The method according to claim 4, wherein the sample is a tumor sample.

6. The method according to claim 4 or 5, wherein thepresence and / or amount of human B7-H3 is determined byimmunohistochemistry.

7. A pharmaceutical composition for use in treating or preventing cancer, comprising a therapeutically effectiveamount of an anti-B7-H3 antibody-drug conjugate in whicha drug-linker is conjugated to a targeting anti-B7-H3 antibody or a functional fragment thereof, 14833176-2wherein the subject is pre-determined to have thelikelihood of responsiveness to the anti-B7-H3 antibody-drug conjugate by determining the presence and / or amountof human B7-H3 or human B7-H3 in a complex in a tumorsample from the subject using a detecting anti-B7-H3antibody, which is the anti-B7-H3 antibody or theantigen-binding fragment thereof according to any one ofclaims 1 to 3, and wherein preferably, the targeting anti-B7-H3 antibody orthe functional fragment thereof comprises(i) CDRH1 consisting of an amino acid sequence consisting of amino acid residues 50 to 54 of SEQ ID NO: 1; (ii) CDRH2 consisting of an amino acid sequence consisting of amino acid residues 69 to 85 of SEQ ID NO: 1; (iii) CDRH3 consisting of an amino acid sequence consisting of amino acid residues 118 to 130 of SEQ ID NO: 1; (iv) CDRL1 consisting of an amino acid sequence consisting of amino acid residues 44 to 53 of SEQ ID NO: 2; (v) CDRL2 consisting of an amino acid sequence consistingof amino acid residues 69 to 75 of SEQ ID NO: 2; and(vi) CDRL3 consisting of an amino acid sequence consisting of amino acid residues 108 to 116 of SEQ ID 14833176-28. The pharmaceutical composition for use according to claim 7, wherein the targeting anti-B7-H3 antibody or thefunctional fragment thereof comprisesa heavy chain variable region consisting of an amino acid sequence consisting of amino acid residues 20 to 141 ofSEQ ID NO: 1; anda light chain variable region consisting of an amino acid sequence consisting of amino acid residues 21 to 128 of SEQ ID NO:

2.

9. The pharmaceutical composition for use according toclaim 7 or 8, wherein the targeting anti-B7-H3 antibodyconsists ofa heavy chain consisting of an amino acid sequence consisting of amino acid residues 20 to 471 of SEQ ID NO:1; anda light chain consisting of an amino acid sequence consisting of amino acid residues 21 to 233 of SEQ ID NO:

2.

10. The pharmaceutical composition for use according to claim 9, wherein a lysine residue is deleted from each of the carboxyl termini of both of the heavy chains of the targeting anti-B7-H3 antibody.

11. The pharmaceutical composition for use according toany one of claims 7 to 10, wherein the drug-linker14833176-2represented by the following formula is conjugated to the targeting anti-B7-H3 antibody or the functional fragment thereof via a thioether bond:wherein “A” in the formula represents a connectingposition to the targeting anti-B7-H3 antibody or the functional fragment thereof.

12. The pharmaceutical composition for use according to claim 11, wherein the average number of units of the drug-linker conjugated per antibody molecule in the anti-B7-H3 antibody-drug conjugate is in the range from 3 to5.

13. The pharmaceutical composition for use according to claim 11 or 12, wherein the anti-B7-H3 antibody-drug conjugate is represented by the following formula: 14833176-2wherein ‘Antibody’ in the formula represents the targeting anti-B7-H3 antibody or the functional fragment thereof conjugated to the drug-linker via a thioether bond, and n represents drug-to-antibody ratio.

14. The pharmaceutical composition for use according toany one of claims 7 to 13, wherein the anti-B7-H3antibody-drug conjugate is ifinatamab deruxtecan.

15. The pharmaceutical composition for use according to any one of claims 7 to 14, wherein the cancer is cancer expressing B7-H3, preferably selected from the groupconsisting of esophageal cancer (including esophagealsquamous cell carcinoma), bladder cancer, gallbladdercancer, urothelial cancer, kidney cancer, ovarian cancer,pancreatic cancer, colorectal cancer (also called colon and rectal cancer, and including colon cancer and rectalcancer), liver cancer, stomach cancer, melanoma,osteosarcoma, glioblastoma multiforme, endometrialcancer, prostate cancer (including castrate-resistant14833176-2prostate cancer), neuroendocrine tumor, Rhabdomyosarcoma, Wilms tumor, neuroblastoma, head and neck cancer (including head and neck squamous cell carcinoma), vulval cancer, mesothelioma, skin cancer, bile duct cancer,stromal tumor, breast cancer, lung cancer (includingsmall cell lung cancer (SCLC) and non-small cell lungcancer (NSCLC)), hepatocellular carcinoma, pancreaticadenocarcinoma, sarcoma, gastric cancer (also calledgastric adenocarcinoma), cervical cancer, uterine cancer,salivary gland cancer, gastroesophageal junctionadenocarcinoma, gastrointestinal cancer, Paget disease,peritoneal cancer, thyroid cancer, penile cancer,leukemia, malignant lymphoma, plasmacytoma, myeloma, nerve epithelial tissue tumor, nerve sheath tumor, throat cancer, and pharyngeal cancer.

16. The pharmaceutical composition for use according to any one of claims 7 to 15, wherein the presence and / oramount of human B7-H3 or human B7-H3 in a complex isdetermined by immunohistochemistry.

17. A method of treating or preventing cancer in asubject with cancer or suspected cancer, comprising administering a therapeutically effective amount of theanti-B7-H3 antibody-drug conjugate as defined in any oneof claims 7 to 14 to a subject in need thereof,14833176-2wherein the subject is pre-determined to have thelikelihood of responsiveness to the anti-B7-H3 antibody-drug conjugate by determining the presence and / or amount of human B7-H3 or human B7-H3 in a tumor sample from the subject using the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of claims 1to 3, optionally by immunohistochemistry, and wherein the cancer is optionally as defined in claim 15.

18. A method of determining whether a subject with canceror suspected cancer is likely to respond to treatmentwith the anti-B7-H3 antibody-drug conjugate as defined inany one of claims 7 to 14, comprising measuring and / orquantifying the presence and / or amount of human B7-H3 orhuman B7-H3 in a complex in a tumor sample from thesubject using a detecting anti-B7-H3 antibody which isthe anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of claims 1 to 3, optionally by immunohistochemistry, and wherein the cancer is optionally as defined in claim 15.

19. A diagnostic kit comprising the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of claims 1 to 3.

20. A pharmaceutical composition for use in treating or preventing cancer, comprising a therapeutically effective 14833176-2amount of the anti-B7-H3 antibody-drug conjugate asdefined in any one of claims 7 to 14, wherein the pharmaceutical composition is for use in combination with the diagnostic kit according to claim 19, wherein the cancer is optionally as defined in claim 15.

21. A method of selecting a subject for treatment or prevention of cancer by administration of atherapeutically effective amount of the anti-B7-H3antibody-drug conjugate as defined in any one of claims 7to 14, comprising measuring and / or quantifying thepresence and / or amount of human B7-H3 or human B7-H3 in acomplex in a tumor sample from the subject using adetecting anti-B7-H3 antibody, which is the anti-B7-H3 antibody or the antigen-binding fragment thereof according to any one of claims 1 to 3, optionally by immunohistochemistry, and wherein the cancer is optionally as defined in claim 15. 14833176-2

Images