Antibody Drug Conjugates

Abstract

The present disclosure relates to antibody drug conjugates (ADCs) comprising an antibody or antigen-binding fragment thereof covalently linked to two pharma- ceutically active drugs via a dual linker. Linker-drug conjugates comprising a dual linker and a pharma- ceutically active drug are also disclosed. Such linkers are a conventional way to deliver two (e.g., two different or the same) drugs bound to a single antibody. Such linkers may be particularly useful for improving the solubility of antibody drug conjugates (ADCs) that contain one or more hydrophobic drug compounds.

Description

[Technical field]

[0001] The present disclosure relates to antibody drug conjugates (ADCs) comprising an antibody or antigen-binding fragment thereof covalently linked to two pharma- ceutically active drugs via a dual linker. Linker-drug conjugates comprising a dual linker and a pharma- ceutically active drug are also disclosed. Such linkers are a conventional way to deliver two (e.g., two different or the same) drugs bound to a single antibody. Such linkers may be particularly useful for improving the solubility of antibody drug conjugates (ADCs) that contain one or more hydrophobic drug compounds. [Background technology]

[0002] One aspect in the design of antibody drug conjugates (ADCs) is the design of the chemical linker that links the drug moiety to the targeting moiety. Typically, ADCs use hydrophobic drug moieties, but when such drug moieties are used in combination with relatively hydrophobic linkers, solubility problems can arise that can affect the biocompatibility and pharmaceutical efficacy of the ADC.

[0003] To overcome these challenges, hydrophilic linkers incorporating polyethylene glycol (see R.P. Lyon, T.D. Bovee, S.O. Doronina, P.J. Burke, J.H. Hunter, H.D. Neff-LaFord, M. Jonas, M.E. Anderson, J.R. Setter, P.D. Center, Nat. Biotechnol., 2015, 33, 733-735, and WO 2015057699), sulfonate linkers (R.Y. Zhao, S.D. Wilhelm, C. Audette, G. Jones, B.A. Lee, and others) have been developed. It has been reported that linker strategies have been attempted in the design of linkers with carbohydrate backbones (FSEkholm, H. Pynnoenen, A. Vilkman, V. Pitkaenen, J. Helin, J. Saarinen, T. Satomaa, ChemMedChem., 2016,11(22):2501-2505) and linkers with carbohydrate backbones (FSEkholm, H. Pynnoenen, A. Vilkman, V. Pitkaenen, J. Helin, J. Saarinen, T. Satomaa, ChemMedChem., 2016,11(22):2501-2505).

[0004] There remains a need for antibody-drug conjugate formats that allow for targeted delivery of pharmacologic active drugs, particularly hydrophobic drugs, with improved pharmacokinetic and pharmacodynamic properties, and in particular the delivery of two pharmacologic active drugs via a dual linker. Summary of the Invention

[0005] The present invention provides compounds and conjugates that achieve the delivery of two pharma- ceutical active drugs via dual linkers while simultaneously achieving high levels of solubility.The use of such linkers not only allows the delivery of two different drug molecules by a single monoclonal antibody, if necessary, but also allows the delivery of twice the number of drug moieties attached to the same antibody compared to antibody drug conjugates known in the art (2, 4, 6 or 8 drugs can be delivered per monoclonal antibody depending on the specific conjugation technology used).The compounds and conjugates described herein allow the delivery of 4, 8, 12 or 16 drug molecules per monoclonal antibody.Various embodiments of the present invention are described herein.

[0006] According to a first aspect of the present invention, the present invention provides a compound represented by formula (A-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’ are each independently a linker; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof.

[0007] According to a second aspect of the present invention, the present specification provides a compound represented by formula (B-1): [ka] (In the formula, R 1 is a linking group; L 1is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently an enzyme cleavage element or a hydrophilic moiety (e.g., E 1 and E 2 are enzyme cleavage elements, respectively); V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof.

[0008] According to a third aspect of the present invention, the present specification provides a compound represented by formula (C-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A 1 and A 2 are each independently a bond, -OC(=O)-*, [ka] , -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(R a ) 2 C(R a ) 2 N(CH 3 )C(=O)-*, Each R a are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3 are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. or a pharma- ceutically acceptable salt thereof.

[0009] According to a fourth aspect of the invention, there is provided herein a conjugate. In one embodiment of this aspect, the conjugate comprises an antibody or antigen-binding fragment thereof covalently linked to two pharmaceutically active drugs via a dual linker, the dual linker having one attachment point attached to the antibody and two attachment points to the two pharmaceutically active drugs, with the proviso that neither pharmaceutically active drug is a BH3 mimetic.

[0010] In another embodiment of this aspect, provided herein is a compound of formula (A-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’ are each independently a linker; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. A conjugate of the formula:

[0011] According to a fifth aspect of the present invention, there is provided herein a compound represented by formula (B-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently an enzyme cleavage element or a hydrophilic moiety (e.g., E 1 and E 2 are enzyme cleavage elements, respectively); V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. A conjugate of the formula:

[0012] According to a sixth aspect of the present invention, there is provided herein a compound represented by formula (C-2): [ka] (In the formula, Ab is an antibody or an antigen-binding fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; a is an integer from 1 to 16; A 1 and A 2 are each independently a bond, -OC(=O)-*, [ka] , -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(R a ) 2 C(R a ) 2 N(CH 3 )C(=O)-*, Each R a are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. A conjugate of the formula:

[0013] According to a seventh aspect of the invention, there is provided herein a pharmaceutical composition comprising a conjugate according to the fourth, fifth or sixth aspect of the invention and a pharma- ceutically acceptable carrier.

[0014] According to an eighth aspect of the present invention, there is provided herein a method of treating a subject having or suspected of having cancer, the method comprising administering to the subject a therapeutically effective amount of a conjugate of the fourth, fifth or sixth aspect of the present invention, or a pharmaceutical composition of the seventh aspect of the present invention.

[0015] According to a ninth aspect of the invention, there is provided herein a method of reducing or inhibiting the growth of a tumour in a subject comprising administering to the subject a therapeutically effective amount of a conjugate of the fourth, fifth or sixth aspect of the invention, or a pharmaceutical composition of the seventh aspect of the invention.

[0016] According to a tenth aspect of the invention, there is provided herein a method of reducing or inhibiting a haematological cancer in a subject comprising administering to the subject a therapeutically effective amount of a conjugate of the fourth, fifth or sixth aspect of the invention, or a pharmaceutical composition of the seventh aspect of the invention.

[0017] According to an eleventh aspect of the present invention, there is provided herein a method of reducing or slowing the expansion of a cancer cell population in a subject comprising administering to the subject a therapeutically effective amount of a conjugate of the fourth, fifth or sixth aspect of the present invention, or a pharmaceutical composition of the seventh aspect of the present invention.

[0018] According to a twelfth aspect of the present invention, there is provided herein use of a conjugate of the fourth, fifth or sixth aspect of the present invention, or a pharmaceutical composition of the seventh aspect of the present invention, for the manufacture of a medicament for (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumour in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

[0019] According to a thirteenth aspect of the invention, there is provided herein an antibody drug conjugate of the fourth, fifth or sixth aspect of the invention, or a pharmaceutical composition of the seventh aspect of the invention, for use in (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumour in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject. [Brief description of the drawings]

[0020] [Figure 1] Dose response curves of Trastuzumab-Example 8 and Trastuzumab-Example 7 against representative cancer cell lines. [Diagram 2] Dose response curves of Trastuzumab-Example 5 against representative cancer cell lines. [Diagram 3] Dose response curves of Trastuzumab-Example 6 against representative cancer cell lines. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] The disclosed compositions and methods may be more readily understood by reference to the following detailed description in connection with the accompanying drawings, which form a part of this disclosure.

[0022] Throughout this specification, the description refers to compositions and methods of using the compositions. When the present disclosure describes or claims features or embodiments related to compositions, such features or embodiments also apply to methods of using the compositions. Similarly, when the present disclosure describes or claims features or embodiments related to methods of using the compositions, such features or embodiments also apply to the compositions.

[0023] When a range of values ​​is expressed, it includes embodiments using any specific value within that range. Moreover, reference to values ​​stated within a range includes each and every value within that range. All ranges are inclusive of their endpoints and are combinable. When values ​​are expressed as approximations by use of the antecedent "about," it will be understood that the specific value forms another embodiment. Reference to a specific numerical value includes at least that specific value unless the context clearly dictates otherwise. The use of "or" is intended to mean "and / or" unless specifically indicated otherwise in relation to its use. All references cited herein are incorporated by reference for any purpose. In the event of a conflict between the reference and the specification, the specification will control.

[0024] Unless otherwise indicated in the context of the description, e.g., in the absence of a symbol indicating a particular point of attachment, when a structure or fragment of a structure is depicted, it may be used by itself, may be attached to other components of the ADC, and may do so in any orientation, e.g., when an antibody is attached to a chemical moiety such as a linker-drug at any suitable attachment point. However, when shown, the components of the ADC are attached in the orientation shown in the given formula. For example, when formula (1) is [ka] It is described as [ka] but, [ka] When written as: the detailed structure of formula (1) is: [ka] It is. [ka] but, [ka] But no.

[0025] It will be understood that certain features of the disclosed compositions and methods that are described herein in the context of separate embodiments for clarity, may also be provided in combination in a single embodiment. Conversely, various features of the disclosed compositions and methods that are described in the context of a single embodiment for brevity, may also be provided separately or in any subcombination.

[0026] As used throughout the specification, antibody drug conjugates may be identified using a naming convention in the general format of "target antigen / antibody-payload-dual linker-payload". For example, if and only if an antibody drug conjugate is referred to as "target X-P1-L1-P2", such conjugate will comprise an antibody that binds to target X, a dual linker denoted as L1, and two payloads denoted as P1 and P2, respectively. Alternatively, if an antibody drug conjugate is referred to as "anti-target X-P1-L1-P2", such conjugate will comprise an antibody that binds to target X, a dual linker denoted as L1, and two payloads denoted as P1 and P2, respectively. In another alternative, if an antibody drug conjugate is referred to as "AbX-P1-L1-P2", such conjugate will comprise an antibody that binds to target X, a dual linker denoted as L1, and two payloads denoted as P1 and P2, respectively. A control antibody drug conjugate that includes a non-specific isotype control antibody may be referred to as "isotype control IgG1-P1-L1-P2" or "IgG1-P1-L1-P2."

[0027] Any formula provided herein is also intended to represent unlabeled and isotopically labeled forms of the compound. Isotopically labeled compounds have the structure depicted by the formula provided herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Isotopes that can be incorporated into the compounds of the present invention include, for example, 3 H, 11 C. 13 C. 14 C. 15 N, 18 F, and 36 Included are isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, and chlorine, such as Cl. Thus, the present disclosure includes, for example, 3 H and 14 Radioisotopes such as C, or 2 H and 13It should be understood that compounds incorporating one or more of any of the aforementioned isotopes are included, including those in which non-radioactive isotopes such as C are present. Such isotopically labeled compounds may be used in metabolic studies ( 14 C), reaction rate tests (e.g. 2 H or 3 3H), detection or imaging techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), including drug or substrate tissue distribution assays, or radiotherapy of patients. 18 F or labeled compounds may be particularly desirable for PET or SPECT studies. Isotopically labeled compounds can generally be prepared by conventional techniques known to those of skill in the art, for example by substituting an appropriate isotopically labeled reagent for a previously used non-labeled reagent.

[0028] According to one aspect of the present invention, the present invention relates to a compound of formula (A-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’ are each independently a linker; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof is disclosed.

[0029] In one embodiment, L 2’ and L 3’each comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0030] In one embodiment, L 2’ and L 3’ Each of the formulas comprises a peptide group and a self-immolative group.

[0031] In one embodiment, L 2’ and L 3’ each comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a sugar (e.g., glucuronamide) group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0032] In certain embodiments, the compound has the formula (B-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic moiety; V 1 and V 2 may independently comprise: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V 1 and V 2are each independently a self-immolative group; or iii) comprise a self-immolative group and an enzymatic cleavage element; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof. In one embodiment, the compound has the formula (B-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic moiety; V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof.

[0033] In certain embodiments, W is N or CH.

[0034] In one embodiment, E 1 and E 2 are each enzyme cleavage elements.

[0035] In one embodiment, V 1 and V 2 are each independently a self-immolative group.

[0036] In certain embodiments, (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; (iii) the cleavable linker is -O-CH 2 -, -NH-CH 2 or (iv) V, which contains a self-immolative group comprising -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium; or (iv) V, 1 and / or V 2 each independently comprises a group containing para-aminobenzyl phosphate or para-aminobenzyl pyrophosphate.

[0037] In certain embodiments, (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker is -O-CH 2 -, -NH-CH 2Self-immolative groups include -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

[0038] In one embodiment, the compound has the formula (C-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A 1 and A 2 are each independently a bond, -OC(=O)-*, [ka] , -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(R a )2 C(R a ) 2 N(CH 3 )C(=O)-*, Each R a are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3 are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. or a pharma- ceutically acceptable salt thereof.

[0039] In certain embodiments, W is N or CH.

[0040] In one embodiment, R 2 and R 3 are each a hydrophilic group.

[0041] In certain embodiments, the compound has the formula (D1-1), (D2-1), or (D3-1): [ka] or a pharma- ceutically acceptable salt thereof.

[0042] In one embodiment, the formula (D1-1), R 2 and R 3 are each independently a hydrophilic group, and in formula (D2-1), R 2 and R 3 are each independently an enzyme cleavage element; and with respect to formula (D3-1), R 2 is a hydrophilic group, and R 3 is an enzyme cleavage element; or a pharma- ceutically acceptable salt thereof.

[0043] In one embodiment, R 1 teeth, [ka] , -ONH 2 , -NH 2 , [ka] , -N 3 , [ka] , -SH, -SR 11 , -SSR 12 , -S(=O) 2 (CH=CH 2 ), -(CH 2 ) 2 S(=O) 2 (CH=CH 2 ), -NHS(=O) 2 (CH=CH 2 ), -NR 11 C(=O)CH 2 Br, e.g. -NHC(=O)CH 2 Br, -NR 11 C(=O)CH 2 I, e.g. -NHC(=O)CH 2 I, [ka] , -C(O)NHNH 2 , [ka] (In the formula, Each R 11 are independently H and C 1 ~C 6 alkyl; Each R 12 is 2-pyridyl or 4-pyridyl; Each R 13 are independently H, C 1 ~C 6 selected from alkyl, F, Cl and -OH; Each R 14 are independently H, C 1 ~C 6 Alkyl, F, Cl, -NH 2 , -OCH 3 , -OCH 2 CH 3 , -N(CH 3 ) 2 , -CN, -NO 2 and -OH; and Each R 15 are independently H, C 1 ~C 6 Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH 1 ~C 4 Alkoxy and -C(=O)OH substituted C 1 ~C 4 alkyl) is selected from the group consisting of:

[0044] In one embodiment, R 1 teeth, [ka] , -ONH 2 , [ka] , NHC(=O)CH 2 Br and -NHC(=O)CH 2 I is selected from the group consisting of

[0045] In one embodiment, R 1 teeth, [ka] It is.

[0046] In one embodiment, (1) L 1 teeth, [ka] or *-CH(OH)CH(OH)CH(OH)CH(OH)-** (wherein each n is an integer from 1 to 12). Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (2)L 1 teeth, [ka] and n is an integer from 1 to 12, or n is 1, or n is 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (3) L 1 teeth, [ka] and n is an integer from 1 to 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (4) L 1 teeth, [ka] Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; or (5) L 1 is *-C(=O)(CH 2 ) m O(CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)(CH 2 ) m -**;*-C(=O)NH((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)O(CH 2 ) m SSC(R L1 ) 2 (CH 2 ) m C(=O)NR L1 (CH 2 ) m NR L1 C(=O)(CH 2 ) m -**;*-C(=O)O(CH 2 ) m C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) n C(=O)-**;*-C(=O)(CH 2 ) m X 1 (CH 2 ) m-**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m C(R L1 ) 2 -** or *-C(=O)(CH 2 ) m C(=O)NH(CH 2 ) m -** (In the formula, L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1indicating a direct or indirect (e.g., direct) point of attachment to; X 1 teeth, [ka] and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R L1 are independently H and C 1 ~C 6 alkyl) is a bridging spacer comprising:

[0047] In one embodiment, L 1 teeth, [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8), and L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 (Indicating a direct or indirect point of attachment to The part represented by

[0048] In one embodiment, n is an integer from 4 to 8.

[0049] In certain embodiments, n is 4 or 8.

[0050] In one embodiment, L 1 is the formula [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L 1 The * in indicates the direct point of attachment to W, and L 1 The ** is R 1 (Indicates the direct attachment point to It is represented by:

[0051] In one embodiment, n is an integer from 4 to 8.

[0052] In certain embodiments, n is 4 or 8.

[0053] In one embodiment, x is an integer from 0 to 2.

[0054] In certain embodiments, x is 0 or 2.

[0055] In one embodiment, z is an integer from 0 to 2.

[0056] In certain embodiments, n is 0 or 2.

[0057] In one embodiment, L 1 teeth, [ka] is selected from the group consisting of:

[0058] In one embodiment, L 2 and L 3 are each independently [ka] (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 (## indicates the direct or indirect point of attachment to W) is a linking spacer comprising a portion represented by:

[0059] In one embodiment, L 2 and L 3 are each independently [ka] [ka] (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R L23 is hydrogen or C 1 ~C 6 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; If W is N, then L 2 and L 3 (provided that it is not (L2c), (L2d), (L2f) or (L2k)) is a linking spacer selected from the group consisting of:

[0060] In one embodiment, L 2 and L 3 are each independently [ka] [ka] [ka] (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R L23 is hydrogen or C 1 ~C 3 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; if W is N, then L 2 and L 3 (provided that it is not (L2FF), (L2MM), (L2NN), (L2OO) or (L2PP)) is a linking spacer selected from the group consisting of:

[0061] In one embodiment, L 2and L 3 is, independently, [ka] [ka] (In the formula, L 2 Or L 3 # is E 1 Or E 2 indicates the direct attachment point to L 2 Or L 3 ## indicates the direct attachment point to W; R L is hydrogen or -C(O)-R H and R H teeth, [ka] and D is an integer from 20 to 30 (e.g., 25). is a linking spacer selected from the group consisting of:

[0062] In one embodiment, d is 25.

[0063] In certain embodiments, each peptide group independently comprises 1-4, 1-3, or 1-2 amino acid residues.

[0064] In certain embodiments, each peptide group independently comprises two amino acid residues.

[0065] In one embodiment, each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr), and β-alanine (β-Ala).

[0066] In certain embodiments, each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly, and sulfo-Ala-Val-Ala.

[0067] In one embodiment, E 1 and / or E 2 are each independently [ka] (Wherein, E1-1 or E1-2 is V in formula (B) 1 Or V 2 or the direct point of attachment to the -NH- group in formulas (C) and (D); and E1-1 or E1-2 ^^ respectively represent L 2 Or L 3 indicates the direct point of attachment to 1 and E 2 are peptide groups independently selected from (E1-1) and (E1-2). is a peptide group selected from the group consisting of:

[0068] In one embodiment, E 1 and E 2 are each a peptide group independently selected from (E1-1) and (E1-2).

[0069] In one embodiment, E 1 and / or E 2 are each independently [ka] (In the formula, R E is a hydrophilic group R H is) is a peptide group represented by:

[0070] In one embodiment, the hydrophilic group RH teeth, [ka] (wherein e is an integer of 20 to 30 (e.g., 25)) It is.

[0071] In one embodiment, e is 25.

[0072] In one embodiment, E 1 and E 2 are respectively [ka] It is.

[0073] In one embodiment, A 1 and A 2 are independently a bond and -OC(=O)-* (wherein * represents D 1 Or D 2 (indicating the point of attachment to the

[0074] In one embodiment, A 1 and A 2 are independent, combined, [ka] and -OC(=O)-* (wherein * represents D 1 Or D 2 (indicating the point of attachment to the

[0075] In one embodiment, A 1 and A 2 are bonds.

[0076] In one embodiment, A 1 and A 2 are both -OC(=O)-*.

[0077] In one embodiment, A 1 and A 2One of the groups is OC(=O)-* and A 1 and A 2 The other is a bond.

[0078] In one embodiment, A 1 and A 2 is independently a bond, or [ka] (In the formula, * represents D 1 Or D 2 (Indicates the attachment point to It is.

[0079] In one embodiment, A 1 and A 2 On the other hand, [ka] And A 1 and A 2 The other is a bond.

[0080] In one embodiment, A 1 and A 2 Both [ka] It is.

[0081] In one embodiment, A 1 and A 2 On the other hand, [ka] And A 1 and A 2 The other is OC(=O)-*.

[0082] In one embodiment, (i) A 1 and A 2 is -OC(=O)-*; (ii)A 1 and A 2 teeth, [ka] or (iii)A 1 is -OC(=O)-*, and A 2 is a bond, (iv)A 1 is -OC(=O)-*, and A 2 teeth, [ka] or (v)A 1 is a bond, and A 2 teeth, [ka] or (vi) A 1 is a bond, and A 2 is -OC(=O)-* (wherein * is D 1 Or D 2 (showing the attachment point to the

[0083] In one embodiment, i) L 4 and L 5 are each independently [ka] (In the formula, Z is -O-, -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR L45 -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NRL45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45 -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is a bond, triazolyl or -CH 2 -triazolyl-, X is R 2 or R 3 (connected to or a spacer moiety having the structure (ii) L 4 and L 5 is, independently, [ka] (In the formula, Z is -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR b -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45-, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n where each n is independently 1, 2, or 3; X is R 2 or R 3 (connected to It is a spacer portion having the structure:

[0084] In certain embodiments, Z is -O-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH- or -CH 2 X is a bond, triazolyl or -CH 2 -triazolyl-; and R L45 is, at each occurrence, independently H or C 1 ~C 3 It is an alkyl.

[0085] In one embodiment, L 4 and L 5 are each independently [ka] (In the formula, L 4 Or L 5 @ indicates the direct point of attachment to the phenyl group, and L 4 Or L 5 @@ is R 2 or R 3 (Indicates the direct attachment point to is a spacer moiety selected from the group consisting of:

[0086] In one embodiment, R 2 and R 3 Each of the hydrophilic groups represented by the formula (I) is independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 [ka] C replaced with 2 ~C 6 Alkyl or -OC(=O)NHS(O) 2 NHCH 2 CH 2 OCH 3 , -NHC(=O)C 1 ~C 4 Alkylene-P(O)(OCH 2 CH 3 ) 2and C substituted with 1 to 2 substituents independently selected from -COOH groups. 2 ~C 6 Contains alkyl.

[0087] In one embodiment, R 2 or / and R 3 are each independently [ka] (wherein n is an integer of 1 to 6). [ka] is selected from the group consisting of:

[0088] In one embodiment, R 2 or / and R 3 is, independently, (i) the following part: [ka] (In the formula, f is an integer from 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) Polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by Includes.

[0089] In one embodiment, R 2 or / and R 3 are each independently [ka] (In the formula, g and h are independently an integer of 20 to 30 (e.g., 23 or 24). is selected from the group consisting of:

[0090] In one embodiment, R 2 or / and R 3 teeth, [ka] Includes.

[0091] In one embodiment, R 2 or R 3 Each hydrophilic group represented by the formula: (i) the following part: [ka] (In the formula, f is an integer of 3 to 25; R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) or polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) Contains polyethylene glycol.

[0092] In one embodiment, R 2 and R 3 are each independently represented by the formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) Contains polyethylene glycol.

[0093] In one embodiment, D 1 and D. 2 is the same.

[0094] In one embodiment, D 1 and D. 2 is different.

[0095] In one embodiment, D 1 and D. 2 are each independently selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant.

[0096] In one embodiment, D 1 and D. 2 are each independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

[0097] In one embodiment, D 1 and D. 2 are each independently [ka] [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof. [ka] It should be understood that when an N atom bearing an * in an otherwise trivalent compound such as is attached to a linker, a cationic structure will result (cations are not depicted with respect to the molecular fragments herein).

[0098] In one embodiment, i) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iv) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; v)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vi)D 1teeth, [ka] and D 2 teeth, [ka] Is it; vii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; viii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; x)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xi) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvi)D 1 teeth, [ka] and D2 teeth, [ka] Is it; xxxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xli)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; il)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; l)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; li)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxiii)D 1 teeth, [ka] and D 2 teeth, [ka] or lxiv)D 1 teeth, [ka] and D 2 teeth, [ka] where the * indicates the point of attachment to the rest of the molecule.

[0099] In one embodiment, A 1 -D 1 and A 2 -D 2 is, independently, [ka] where * indicates the point of attachment to the rest of the molecule. is selected from the group consisting of:

[0100] In one embodiment, i)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iv) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; v)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; viii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ix) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; x)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xix)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xl)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xli)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; l)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; li)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxiii)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] or lxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] where the * indicates the point of attachment to the rest of the molecule.

[0101] In one embodiment, D 1 and / or D. 2 is an auristatin.

[0102] In one embodiment, D 1 and D. 2 Both are auristatins.

[0103] In one embodiment, D 1 and / or D. 2 is a topoisomerase 1 inhibitor.

[0104] In one embodiment, D 1 and D. 2 Both are topoisomerase 1 inhibitors.

[0105] In one embodiment, D 1 and D. 2 one of which is an auristatin and D 1 and D. 2 The other is a topoisomerase 1 inhibitor.

[0106] In one embodiment, D 1 is an auristatin, D 2 is a topoisomerase 1 inhibitor.

[0107] In one embodiment, D 1 is a topoisomerase 1 inhibitor, D 2 is an auristatin.

[0108] In one embodiment, D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0109] In one embodiment, D 1 and D. 2 is, independently, [ka] is selected from the group consisting of:

[0110] In one embodiment, D 1 and D. 2 is, independently, [ka] is selected from the group consisting of:

[0111] In one embodiment, D1 and D2 are each independently [ka] is selected from.

[0112] In one embodiment, D 1 and D. 2are each independently selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapeutic sensitizers, topoisomerase inhibitors, and / or vinca alkaloids.

[0113] In one embodiment, D 1 and D. 2 are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; 1 Also D 2 provided that the compound is not a BH3 mimetic.

[0114] In some embodiments, compounds or compounds allowed for pharmaceutical science are P1-L1-P1、P1-L1-P2、P1-L1-P3、P1-L1-P4、P1-L1-P5、P1-L1-P6、P1-L1-P7、P1-L1-P8、P1-L2-P1、P1-L2-P2、P1-L2- P3、P1-L2-P4、P1-L2-P5、P1-L2-P6、P1-L2-P7、P1-L2-P8、P1-L3-P1、P1-L3 -P2、P1-L3-P3、P1-L3-P4、P1-L3-P5、P1-L3-P6、P1-L3-P7、P1-L3-P8、P1-L4 -P1、P1-L4-P2、P1-L4-P3、P1-L4-P4、P1-L4-P5、P1-L4-P6、P1-L4-P7、P1-L 4-P8、P1-L5-P1、P1-L5-P2、P1-L5-P3、P1-L5-P4、P1-L5-P5、P1-L5-P6、P1- L5-P7、P1-L5-P8、P1-L6-P1、P1-L6-P2、P1-L6-P3、P1-L6-P4、P1-L6-P5、P1 -L6-P6、P1-L6-P7、P1-L6-P8、P1-L7-P1、P1-L7-P2、P1-L7-P3、P1-L7-P4、P1 -L7-P5、P1-L7-P6、P1-L7-P7、P1-L7-P8、P1-L8-P1、P1-L8-P2、P1-L8-P3、P 1-L8-P4、P1-L8-P5、P1-L8-P6、P1-L8-P7、P1-L8-P8、P1-L9-P1、P1-L9-P2、 P1-L9-P3、P1-L9-P4、P1-L9-P5、P1-L9-P6、P1-L9-P7、P1-L9-P8、P1-L10-P 1、P1-L10-P2、P1-L10-P3、P1-L10-P4、P1-L10-P5、P1-L10-P6、P1-L10-P7、P 1-L10-P8、P1-L11-P1、P1-L11-P2、P1-L11-P3、P1-L11-P4、P1-L11-P5、P1- L11-P6、P1-L11-P7、P1-L11-P8、P1-L12-P1、P1-L12-P2、P1-L12-P3、P1-L1 2-P4、P1-L12-P5、P1-L12-P6、P1-L12-P7、P1-L12-P8、P1-L13-P1、P1-L13-P2、P1-L13-P3、P1-L13-P4、P1-L13-P5、P1-L13-P6、P1-L13-P7、P1-L13-P8、P1-L14-P1、P1-L14-P2、P1-L14-P3、P1-L14-P4、P1-L14-P5、P1-L14-P6、P1 -L14-P7、P1-L14-P8、P1-L15-P1、P1-L15-P2、P1-L15-P3、P1-L15-P4、P1-L1 5-P5、P1-L15-P6、P1-L15-P7、P1-L15-P8、P1-L16-P1、P1-L16-P2、P1-L16-P3、P1-L16-P4、P1-L16-P5、P1-L16-P6、P1-L16-P7、P1-L16-P8、P1-L17-P1、 P1-L17-P2、P1-L17-P3、P1-L17-P4、P1-L17-P5、P1-L17-P6、P1-L17-P7、P1 -L17-P8、P1-L18-P1、P1-L18-P2、P1-L18-P3、P1-L18-P4、P1-L18-P5、P1-L1 8-P6、P1-L18-P7、P1-L18-P8、P1-L19-P1、P1-L19-P2、P1-L19-P3、P1-L19-P4、P1-L19-P5、P1-L19-P6、P1-L19-P7、P1-L19-P8、P1-L20-P1、P1-L20-P2、 P1-L20-P3、P1-L20-P4、P1-L20-P5、P1-L20-P6、P1-L20-P7、P1-L20-P8、P1 -L21-P1、P1-L21-P2、P1-L21-P3、P1-L21-P4、P1-L21-P5、P1-L21-P6、P1-L2 1-P7、P1-L21-P8、P1-L22-P1、P1-L22-P2、P1-L22-P3、P1-L22-P4、P1-L22- P5、P1-L22-P6、P1-L22-P7、P1-L22-P8、P1-L23-P1、P1-L23-P2、P1-L23-P3、 P1-L23-P4、P1-L23-P5、P1-L23-P6、P1-L23-P7、P1-L23-P8、P1-L24-P1、P1-L24-P2、P1-L24-P3、P1-L24-P4、P1-L24-P5、P1-L24-P6、P1-L24-P7、P1-L2 4-P8、P1-L25-P1、P1-L25-P2、P1-L25-P3、P1-L25-P4、P1-L25-P5、P1-L25-P6、P1-L25-P7、P1-L25-P8、P1-L26-P1、P1-L26-P2、P1-L26-P3、P1-L26-P4、<h2 style=";text-align:left;direction:ltr">P1-L26-P5、P1-L26-P6、P1-L26-P7、P1-L26-P8、P1-L27-P1、P1-L27-P2、P1 -L27-P3、P1-L27-P4、P1-L27-P5、P1-L27-P6、P1-L27-P7、P1-L27-P8、P1-L 28-P1、P1-L28-P2、P1-L28-P3、P1-L28-P4、P1-L28-P5、P1-L28-P6、P1-L28 -P7、P1-L28-P8、P1-L29-P1、P1-L29-P2、P1-L29-P3、P1-L29-P4、P1-L29-P 5、P1-L29-P6、P1-L29-P7、P1-L29-P8、P1-L30-P1、P1-L30-P2、P1-L30-P3、 P1-L30-P4、P1-L30-P5、P1-L30-P6、P1-L30-P7、P1-L30-P8、P1-L31-P1、P1 -L31-P2、P1-L31-P3、P1-L31-P4、P1-L31-P5、P1-L31-P6、P1-L31-P7、P1-L 31-P8、P1-L32-P1、P1-L32-P2、P1-L32-P3、P1-L32-P4、P1-L32-P5、P1-L32 -P6、P1-L32-P7、P1-L32-P8、P1-L33-P1、P1-L33-P2、P1-L33-P3、P1-L33-P 4、P1-L33-P5、P1-L33-P6、P1-L33-P7、P1-L33-P8、P1-L34-P1、P1-L34-P2、 P1-L34-P3、P1-L34-P4、P1-L34-P5、P1-L34-P6、P1-L34-P7、P1-L34-P8、P1 -L35-P1、P1-L35-P2、P1-L35-P3、P1-L35-P4、P1-L35-P5、P1-L35-P6、P1-L 35-P7、P1-L35-P8、P1-L36-P1、P1-L36-P2、P1-L36-P3、P1-L36-P4、P1-L36 -P5、P1-L36-P6、P1-L36-P7、P1-L36-P8、P2-L1-P1、P2-L1-P2、P2-L1-P3、P 2-L1-P4, P2-L1-P5, P2-L1-P6, P2-L1-P7, P2-L1-P8, P2-L2-P1, P2-L2-P2, P2-L2-P3, P2-L2-P4, P2-L2-P5, P2-L2-P6, P2-L2-P7, P2-L2-P8, P2-L3-P1,<h2 style=";text-align:left;direction:ltr">P2-L3-P2, P2-L3-P3, P2-L3-P4, P2-L3-P5, P2-L3-P6, P2-L3-P7, P2-L3-P8, P2-L4-P1, P2-L4-P2, P2-L4-P3, P2-L4-P4, P2-L4-P5, P2-L4-P6, P2-L4-P 7, P2-L4-P8, P2-L5-P1, P2-L5-P2, P2-L5-P3, P2-L5-P4, P2-L5-P5, P2-L5-P6, P2-L5-P7, P2-L5-P8, P2-L6-P1, P2-L6-P2, P2-L6-P3, P2-L6-P4, P2-L6 -P5,P2-L6-P6,P2-L6-P7,P2-L6-P8,P2-L7-P1,P2-L7-P2,P2-L7-P3,P2-L7-P4,P2-L7-P5,P2-L7-P6,P2-L7-P7,P2-L7-P8,P2-L8-P1,P2-L8-P2,P2- L8-P3、P2-L8-P4、P2-L8-P5、P2-L8-P6、P2-L8-P7、P2-L8-P8、P2-L9-P1、P2 -L9-P2、P2-L9-P3、P2-L9-P4、P2-L9-P5、P2-L9-P6、P2-L9-P7、P2-L9-P8、P2 -L10-P1、P2-L10-P2、P2-L10-P3、P2-L10-P4、P2-L10-P5、P2-L10-P6、P2-L 10-P7、P2-L10-P8、P2-L11-P1、P2-L11-P2、P2-L11-P3、P2-L11-P4、P2-L11 -P5、P2-L11-P6、P2-L11-P7、P2-L11-P8、P2-L12-P1、P2-L12-P2、P2-L12-P 3、P2-L12-P4、P2-L12-P5、P2-L12-P6、P2-L12-P7、P2-L12-P8、P2-L13-P1、P 2-L13-P2、P2-L13-P3、P2-L13-P4、P2-L13-P5、P2-L13-P6、P2-L13-P7、P2- L13-P8、P2-L14-P1、P2-L14-P2、P2-L14-P3、P2-L14-P4、P2-L14-P5、P2-L1 4-P6、P2-L14-P7、P2-L14-P8、P2-L15-P1、P2-L15-P2、P2-L15-P3、P2-L15- P4、P2-L15-P5、P2-L15-P6、P2-L15-P7、P2-L15-P8、P2-L16-P1、P2-L16-P2、P2-L16-P3、P2-L16-P4、P2-L16-P5、P2-L16-P6、P2-L16-P7、P2-L16-P8、P2-L17-P1、P2-L17-P2、P2-L17-P3、P2-L17-P4、P2-L17-P5、P2-L17-P6、P2-L17-P7、P2-L17-P8、P2-L18-P1、P2-L18-P2、P2-L18-P3、P2-L18-P4、P2-L18-P5、P2-L18-P6、P2-L18-P7、P2-L18-P8、P2-L19-P1、P2-L19-P2、P2-L19-P3、P2-L19-P4、P2-L19-P5、P2-L19-P6、P2-L19-P7、P2-L19-P8、P2-L20-P1、P2-L20-P2、P2-L20-P3、P2-L20-P4、P2-L20-P5、P2-L20-P6、P2-L20-P7、P2-L20-P8、P2-L21-P1、P2-L21-P2、P2-L21-P3、P2-L21-P4、P2-L21-P5、P2-L21-P6、P2-L21-P7、P2-L21-P8、P2-L22-P1、P2-L22-P2、P2-L22-P3、P2-L22-P4、P2-L22-P5、P2-L22-P6、P2-L22-P7、P2-L22-P8、P2-L23-P1、P2-L23-P2、P2-L23-P3、P2-L23-P4、P2-L23-P5、P2-L23-P6、P2-L23-P7、P2-L23-P8、P2-L24-P1、P2-L24-P2、P2-L24-P3、P2-L24-P4、P2-L24-P5、P2-L24-P6、P2-L24-P7、P2-L24-P8、P2-L25-P1、P2-L25-P2、P2-L25-P3、P2-L25-P4、P2-L25-P5、P2-L25-P6、P2-L25-P7、P2-L25-P8、P2-L26-P1、P2-L26-P2、P2-L26-P3、P2-L26-P4、P2-L26-P5、P2-L26-P6、P2-L26-P7、P2-L26-P8、P2-L27-P1、P2-L27-P2、P2-L27-P3、P2-L27-P4、P2-L27-P5、P2-L27-P6、P2-L27-P7、P2-L27-P8、P2-L28-P1、P2-L28-P2、P2-L28-P3、P2-L28-P4、P2-L28-P5、P2-L28-P6、P2-L28-P7、P2-L28-P8、P2-L29-P1、P2-L29-P2、P2-L29-P3、P2-L29-P4、P2-L29-P5、P2-L29-P6、P2-L29-P7、P2-L29-P8、P2-L30-P1、P2-L30-P2、P2-L30-P3、P2-L30、 <h2 style=";text-align:left;direction:ltr">-P4、P2-L30-P5、P2-L30-P6、P2-L30-P7、P2-L30-P8、P2-L31-P1、P2-L31-P 2、P2-L31-P3、P2-L31-P4、P2-L31-P5、P2-L31-P6、P2-L31-P7、P2-L31-P8、P 2-L32-P1、P2-L32-P2、P2-L32-P3、P2-L32-P4、P2-L32-P5、P2-L32-P6、P2- L32-P7、P2-L32-P8、P2-L33-P1、P2-L33-P2、P2-L33-P3、P2-L33-P4、P2-L33 -P5、P2-L33-P6、P2-L33-P7、P2-L33-P8、P2-L34-P1、P2-L34-P2、P2-L34-P 3、P2-L34-P4、P2-L34-P5、P2-L34-P6、P2-L34-P7、P2-L34-P8、P2-L35-P1、P 2-L35-P2、P2-L35-P3、P2-L35-P4、P2-L35-P5、P2-L35-P6、P2-L35-P7、P2- L35-P8、P2-L36-P1、P2-L36-P2、P2-L36-P3、P2-L36-P4、P2-L36-P5、P2-L36 -P6,P2-L36-P7,P2-L36-P8,P3-L1-P1,P3-L1-P2,P3-L1-P3,P3-L1-P4,P3-L1-P5,P3-L1-P6,P3-L1-P7,P3-L1-P8,P3-L2-P1,P3-L2-P2,P3-L2-P3,P3 -L2-P4,P3-L2-P5,P3-L2-P6,P3-L2-P7,P3-L2-P8,P3-L3-P1,P3-L3-P2,P3-L3-P3,P3-L3-P4,P3-L3-P5,P3-L3-P6,P3-L3-P7,P3-L3-P8,P3-L4-P1,P 3-L4-P2、P3-L4-P3、P3-L4-P4、P3-L4-P5、P3-L4-P6、P3-L4-P7、P3-L4-P8、 P3-L5-P1、P3-L5-P2、P3-L5-P3、P3-L5-P4、P3-L5-P5、P3-L5-P6、P3-L5-P7、 P3-L5-P8, P3-L6-P1, P3-L6-P2, P3-L6-P3, P3-L6-P4, P3-L6-P5, P3-L6-P6, P3-L6-P7, P3-L6-P8, P3-L7-P1, P3-L7-P2, P3-L7-P3, P3-L7-P4, P3-L7-P5,P3-L7-P6、P3-L7-P7、P3-L7-P8、P3-L8-P1、P3-L8-P2、P3-L8-P3、P3-L8-P4、P3-L8-P5、P3-L8-P6、P3-L8-P7、P3-L8-P8、P3-L9-P1、P3-L9-P2、P3-L9-P3 、P3-L9-P4、P3-L9-P5、P3-L9-P6、P3-L9-P7、P3-L9-P8、P3-L10-P1、P3-L10-P2、P3-L10-P3、P3-L10-P4、P3-L10-P5、P3-L10-P6、P3-L10-P7、P3-L10-P8 、P3-L11-P1、P3-L11-P2、P3-L11-P3、P3-L11-P4、P3-L11-P5、P3-L11-P6、P 3-L11-P7、P3-L11-P8、P3-L12-P1、P3-L12-P2、P3-L12-P3、P3-L12-P4、P3-L 12-P5、P3-L12-P6、P3-L12-P7、P3-L12-P8、P3-L13-P1、P3-L13-P2、P3-L13 -P3、P3-L13-P4、P3-L13-P5、P3-L13-P6、P3-L13-P7、P3-L13-P8、P3-L14-P1 、P3-L14-P2、P3-L14-P3、P3-L14-P4、P3-L14-P5、P3-L14-P6、P3-L14-P7、P 3-L14-P8、P3-L15-P1、P3-L15-P2、P3-L15-P3、P3-L15-P4、P3-L15-P5、P3-L 15-P6、P3-L15-P7、P3-L15-P8、P3-L16-P1、P3-L16-P2、P3-L16-P3、P3-L16-P4、P3-L16-P5、P3-L16-P6、P3-L16-P7、P3-L16-P8、P3-L17-P1、P3-L17-P2 、P3-L17-P3、P3-L17-P4、P3-L17-P5、P3-L17-P6、P3-L17-P7、P3-L17-P8、P 3-L18-P1、P3-L18-P2、P3-L18-P3、P3-L18-P4、P3-L18-P5、P3-L18-P6、P3-L 18-P7、P3-L18-P8、P3-L19-P1、P3-L19-P2、P3-L19-P3、P3-L19-P4、P3-L19- P5、P3-L19-P6、P3-L19-P7、P3-L19-P8、P3-L20-P1、P3-L20-P2、P3-L20-P3、P3-L20-P4、P3-L20-P5、P3-L20-P6、P3-L20-P7、P3-L20-P8、P3-L21-P1、P3 -L21-P2、P3-L21-P3、P3-L21-P4、P3-L21-P5、P3-L21-P6、P3-L21-P7、P3-L2 1-P8、P3-L22-P1、P3-L22-P2、P3-L22-P3、P3-L22-P4、P3-L22-P5、P3-L22- P6、P3-L22-P7、P3-L22-P8、P3-L23-P1、P3-L23-P2、P3-L23-P3、P3-L23-P4、 P3-L23-P5、P3-L23-P6、P3-L23-P7、P3-L23-P8、P3-L24-P1、P3-L24-P2、P3 -L24-P3、P3-L24-P4、P3-L24-P5、P3-L24-P6、P3-L24-P7、P3-L24-P8、P3-L2 5-P1、P3-L25-P2、P3-L25-P3、P3-L25-P4、P3-L25-P5、P3-L25-P6、P3-L25-P7、P3-L25-P8、P3-L26-P1、P3-L26-P2、P3-L26-P3、P3-L26-P4、P3-L26-P5、 P3-L26-P6、P3-L26-P7、P3-L26-P8、P3-L27-P1、P3-L27-P2、P3-L27-P3、P3 -L27-P4、P3-L27-P5、P3-L27-P6、P3-L27-P7、P3-L27-P8、P3-L28-P1、P3-L2 8-P2、P3-L28-P3、P3-L28-P4、P3-L28-P5、P3-L28-P6、P3-L28-P7、P3-L28-P8、P3-L29-P1、P3-L29-P2、P3-L29-P3、P3-L29-P4、P3-L29-P5、P3-L29-P6、 P3-L29-P7、P3-L29-P8、P3-L30-P1、P3-L30-P2、P3-L30-P3、P3-L30-P4、P3 -L30-P5、P3-L30-P6、P3-L30-P7、P3-L30-P8、P3-L31-P1、P3-L31-P2、P3-L3 1-P3、P3-L31-P4、P3-L31-P5、P3-L31-P6、P3-L31-P7、P3-L31-P8、P3-L32- P1、P3-L32-P2、P3-L32-P3、P3-L32-P4、P3-L32-P5、P3-L32-P6、P3-L32-P7、P3-L32-P8、P3-L33-P1、P3-L33-P2、P3-L33-P3、P3-L33-P4、P3-L33-P5、P3-L33-P6、P3-L33-P7、P3-L33-P8、P3-L34-P1、P3-L34-P2、P3-L34-P3、P3-L34-P4、P3-L34-P5、P3-L34-P6、P3-L34-P7、P3-L34-P8、P3-L35-P1、P3-L35-P2、P3-L35-P3、P3-L35-P4、P3-L35-P5、P3-L35-P6、P3-L35-P7、P3-L35-P8、P3-L36-P1、P3-L36-P2、P3-L36-P3、P3-L36-P4、P3-L36-P5、P3-L36-P6、P3-L36-P7、P3-L36-P8、P4-L1-P1、P4-L1-P2、P4-L1-P3、P4-L1-P4、P4-L1-P5、P4-L1-P6、P4-L1-P7、P4-L1-P8、P4-L2-P1、P4-L2-P2、P4-L2-P3、P4-L2-P4、P4-L2-P5、P4-L2-P6、P4-L2-P7、P4-L2-P8、P4-L3-P1、P4-L3-P2、P4-L3-P3、P4-L3-P4、P4-L3-P5、P4-L3-P6、P4-L3-P7、P4-L3-P8、P4-L4-P1、P4-L4-P2、P4-L4-P3、P4-L4-P4、P4-L4-P5、P4-L4-P6、P4-L4-P7、P4-L4-P8、P4-L5-P1、P4-L5-P2、P4-L5-P3、P4-L5-P4、P4-L5-P5、P4-L5-P6、P4-L5-P7、P4-L5-P8、P4-L6-P1、P4-L6-P2、P4-L6-P3、P4-L6-P4、P4-L6-P5、P4-L6-P6、P4-L6-P7、P4-L6-P8、P4-L7-P1、P4-L7-P2、P4-L7-P3、P4-L7-P4、P4-L7-P5、P4-L7-P6、P4-L7-P7、P4-L7-P8、P4-L8-P1、P4-L8-P2、P4-L8-P3、P4-L8-P4、P4-L8-P5、P4-L8-P6、P4-L8-P7、P4-L8-P8、P4-L9-P1、P4-L9-P2、P4-L9-P3、P4-L9-P4、P4-L9-P5、P4-L9-P6、P4-L9-P7、P4-L9-P8、P4-L10-P1、P4-L10-P2、P4-L10-P3、P4-L10-P4、P4-L10-P5、P4-L10-P6、P4-L10-P7、P4-L10-P8、P4-L11-P1、P4-L11-P2、P4-L11-P3、P4-L11-P4、P4-L11-P5、P4-L11-P6、P4-L11-P7、P4-L11-P8、P4-L12-P1、P4-L12-P2、P4-L12-P3、P4-L12-P4、P4-L12-P5、P4-L12-P6、P4-L12-P7、P4-L12-P8、P4-L13-P1、P4-L13-P2、P4-L13-P3、P4-L13-P4、P4-L13-P5、P4-L13-P6、P4-L13-P7、P4-L13-P8、P4-L14-P1、P4-L14-P2、P4-L14-P3、P4-L14-P4、P4-L14-P5、P4-L14-P6、P4-L14-P7、P4-L14-P8、P4-L15-P1、P4-L15-P2、P4-L15-P3、P4-L15-P4、P4-L15-P5、P4-L15-P6、P4-L15-P7、P4-L15-P8、P4-L16-P1、P4-L16-P2、P4-L16-P3、P4-L16-P4、P4-L16-P5、P4-L16-P6、P4-L16-P7、P4-L16-P8、P4-L17-P1、P4-L17-P2、P4-L17-P3、P4-L17-P4、P4-L17-P5、P4-L17-P6、P4-L17-P7、P4-L17-P8、P4-L18-P1、P4-L18-P2、P4-L18-P3、P4-L18-P4、P4-L18-P5、P4-L18-P6、P4-L18-P7、P4-L18-P8、P4-L19-P1、P4-L19-P2、P4-L19-P3、P4-L19-P4、P4-L19-P5、P4-L19-P6、P4-L19-P7、P4-L19-P8、P4-L20-P1、P4-L20-P2、P4-L20-P3、P4-L20-P4、P4-L20-P5、P4-L20-P6、P4-L20-P7、P4-L20-P8、P4-L21-P1、P4-L21-P2、P4-L21-P3、P4-L21-P4、P4-L21-P5、P4-L21-P6、P4-L21-P7、P4-L21-P8、P4-L22-P1、P4-L22-P2、P4-L22-P3、P4-L22-P4、P4-L22-P5、P4-L22-P6、P4-L22-P7、P4-L22-P8、P4-L23-P1、P4-L23-P2、P4-L23-P3、P4-L23-P4、P4-L23-P5、P4-L23-P6、P4-L23-P7、P4-L23-P8、P4-L24-P1、P4-L24-P2、P、 4-L24-P3、P4-L24-P4、P4-L24-P5、P4-L24-P6、P4-L24-P7、P4-L24-P8、P4-L25-P1、P4-L25-P2、P4-L25-P3、P4-L25-P4、P4-L25-P5、P4-L25-P6、P4-L25-P7、P4-L25-P8、P4-L26-P1、P4-L26-P2、P4-L26-P3、P4-L26-P4、P4-L26-P5、P4-L26-P6、P4-L26-P7、P4-L26-P8、P4-L27-P1、P4-L27-P2、P4-L27-P3、P4-L27-P4、P4-L27-P5、P4-L27-P6、P4-L27-P7、P4-L27-P8、P4-L28-P1、P4-L28-P2、P4-L28-P3、P4-L28-P4、P4-L28-P5、P4-L28-P6、P4-L28-P7、P4-L28-P8、P4-L29-P1、P4-L29-P2、P4-L29-P3、P4-L29-P4、P4-L29-P5、P4-L29-P6、P4-L29-P7、P4-L29-P8、P4-L30-P1、P4-L30-P2、P4-L30-P3、P4-L30-P4、P4-L30-P5、P4-L30-P6、P4-L30-P7、P4-L30-P8、P4-L31-P1、P4-L31-P2、P4-L31-P3、P4-L31-P4、P4-L31-P5、P4-L31-P6、P4-L31-P7、P4-L31-P8、P4-L32-P1、P4-L32-P2、P4-L32-P3、P4-L32-P4、P4-L32-P5、P4-L32-P6、P4-L32-P7、P4-L32-P8、P4-L33-P1、P4-L33-P2、P4-L33-P3、P4-L33-P4、P4-L33-P5、P4-L33-P6、P4-L33-P7、P4-L33-P8、P4-L34-P1、P4-L34-P2、P4-L34-P3、P4-L34-P4、P4-L34-P5、P4-L34-P6、P4-L34-P7、P4-L34-P8、P4-L35-P1、P4-L35-P2、P4-L35-P3、P4-L35-P4、P4-L35-P5、P4-L35-P6、P4-L35-P7、P4-L35-P8、P4-L36-P1、P4-L36-P2、P4-L36-P3、P4-L36-P4、P4-L36-P5、P4-L36-P6、<h2 style=";text-align:left;direction:ltr">P4-L36-P7, P4-L36-P8, P5-L1-P1, P5-L1-P2, P5-L1-P3, P5-L1-P4, P5-L1-P5, P5-L1-P6, P5-L1-P7, P5-L1-P8, P5-L2-P1, P5-L2-P2, P5-L2-P3, P5-L2 -P4,P5-L2-P5,P5-L2-P6,P5-L2-P7,P5-L2-P8,P5-L3-P1,P5-L3-P2,P5-L3-P3,P5-L3-P4,P5-L3-P5,P5-L3-P6,P5-L3-P7,P5-L3-P8,P5-L4-P1,P5-L 4-P2、P5-L4-P3、P5-L4-P4、P5-L4-P5、P5-L4-P6、P5-L4-P7、P5-L4-P8、P5- L5-P1、P5-L5-P2、P5-L5-P3、P5-L5-P4、P5-L5-P5、P5-L5-P6、P5-L5-P7、P5- L5-P8, P5-L6-P1, P5-L6-P2, P5-L6-P3, P5-L6-P4, P5-L6-P5, P5-L6-P6, P5-L6-P7, P5-L6-P8, P5-L7-P1, P5-L7-P2, P5-L7-P3, P5-L7-P4, P5-L7-P5, P5 -L7-P6、P5-L7-P7、P5-L7-P8、P5-L8-P1、P5-L8-P2、P5-L8-P3、P5-L8-P4、P 5-L8-P5、P5-L8-P6、P5-L8-P7、P5-L8-P8、P5-L9-P1、P5-L9-P2、P5-L9-P3、 P5-L9-P4、P5-L9-P5、P5-L9-P6、P5-L9-P7、P5-L9-P8、P5-L10-P1、P5-L10- P2、P5-L10-P3、P5-L10-P4、P5-L10-P5、P5-L10-P6、P5-L10-P7、P5-L10-P8、 P5-L11-P1、P5-L11-P2、P5-L11-P3、P5-L11-P4、P5-L11-P5、P5-L11-P6、P5 -L11-P7、P5-L11-P8、P5-L12-P1、P5-L12-P2、P5-L12-P3、P5-L12-P4、P5-L1 2-P5、P5-L12-P6、P5-L12-P7、P5-L12-P8、P5-L13-P1、P5-L13-P2、P5-L13- P3、P5-L13-P4、P5-L13-P5、P5-L13-P6、P5-L13-P7、P5-L13-P8、P5-L14-P1、P5-L14-P2、P5-L14-P3、P5-L14-P4、P5-L14-P5、P5-L14-P6、P5-L14-P7、P5-L14-P8、P5-L15-P1、P5-L15-P2、P5-L15-P3、P5-L15-P4、P5-L15-P5、P5-L1 5-P6、P5-L15-P7、P5-L15-P8、P5-L16-P1、P5-L16-P2、P5-L16-P3、P5-L16- P4、P5-L16-P5、P5-L16-P6、P5-L16-P7、P5-L16-P8、P5-L17-P1、P5-L17-P2、 P5-L17-P3、P5-L17-P4、P5-L17-P5、P5-L17-P6、P5-L17-P7、P5-L17-P8、P5-L18-P1、P5-L18-P2、P5-L18-P3、P5-L18-P4、P5-L18-P5、P5-L18-P6、P5-L1 8-P7、P5-L18-P8、P5-L19-P1、P5-L19-P2、P5-L19-P3、P5-L19-P4、P5-L19- P5、P5-L19-P6、P5-L19-P7、P5-L19-P8、P5-L20-P1、P5-L20-P2、P5-L20-P3、 P5-L20-P4、P5-L20-P5、P5-L20-P6、P5-L20-P7、P5-L20-P8、P5-L21-P1、P5 -L21-P2、P5-L21-P3、P5-L21-P4、P5-L21-P5、P5-L21-P6、P5-L21-P7、P5-L2 1-P8、P5-L22-P1、P5-L22-P2、P5-L22-P3、P5-L22-P4、P5-L22-P5、P5-L22-P6、P5-L22-P7、P5-L22-P8、P5-L23-P1、P5-L23-P2、P5-L23-P3、P5-L23-P4、 P5-L23-P5、P5-L23-P6、P5-L23-P7、P5-L23-P8、P5-L24-P1、P5-L24-P2、P5 -L24-P3、P5-L24-P4、P5-L24-P5、P5-L24-P6、P5-L24-P7、P5-L24-P8、P5-L2 5-P1、P5-L25-P2、P5-L25-P3、P5-L25-P4、P5-L25-P5、P5-L25-P6、P5-L25- P7、P5-L25-P8、P5-L26-P1、P5-L26-P2、P5-L26-P3、P5-L26-P4、P5-L26-P5、<h2 style=";text-align:left;direction:ltr">P5-L26-P6, P5-L26-P7, P5-L26-P8, P5-L27-P1, P5-L27-P2, P5-L27-P3, P5-L27-P4, P5-L27-P5, P5-L27-P6, P5-L27-P7, P5-L27-P8, P5-L28-P1, P5-L2 8-P2、P5-L28-P3、P5-L28-P4、P5-L28-P5、P5-L28-P6、P5-L28-P7、P5-L28- P8、P5-L29-P1、P5-L29-P2、P5-L29-P3、P5-L29-P4、P5-L29-P5、P5-L29-P6、 P5-L29-P7、P5-L29-P8、P5-L30-P1、P5-L30-P2、P5-L30-P3、P5-L30-P4、P5 -L30-P5、P5-L30-P6、P5-L30-P7、P5-L30-P8、P5-L31-P1、P5-L31-P2、P5-L3 1-P3、P5-L31-P4、P5-L31-P5、P5-L31-P6、P5-L31-P7、P5-L31-P8、P5-L32- P1、P5-L32-P2、P5-L32-P3、P5-L32-P4、P5-L32-P5、P5-L32-P6、P5-L32-P7、 P5-L32-P8, P5-L33-P1, P5-L33-P2, P5-L33-P3, P5-L33-P4, P5-L33-P5, P5-L33-P6, P5-L33-P7, P5-L33-P8, P5-L34-P1, P5-L34-P2, P5-L34-P3, P5-L3 4-P4、P5-L34-P5、P5-L34-P6、P5-L34-P7、P5-L34-P8、P5-L35-P1、P5-L35- P2、P5-L35-P3、P5-L35-P4、P5-L35-P5、P5-L35-P6、P5-L35-P7、P5-L35-P8、 P5-L36-P1、P5-L36-P2、P5-L36-P3、P5-L36-P4、P5-L36-P5、P5-L36-P6、P5 -L36-P7、P5-L36-P8、P6-L1-P1、P6-L1-P2、P6-L1-P3、P6-L1-P4、P6-L1-P5、 P6-L1-P6, P6-L1-P7, P6-L1-P8, P6-L2-P1, P6-L2-P2, P6-L2-P3, P6-L2-P4, P6-L2-P5, P6-L2-P6, P6-L2-P7, P6-L2-P8, P6-L3-P1, P6-L3-P2, P6-L3-P3,<h2 style=";text-align:left;direction:ltr">P6-L3-P4、P6-L3-P5、P6-L3-P6、P6-L3-P7、P6-L3-P8、P6-L4-P1、P6-L4-P2 、P6-L4-P3、P6-L4-P4、P6-L4-P5、P6-L4-P6、P6-L4-P7、P6-L4-P8、P6-L5-P 1、P6-L5-P2、P6-L5-P3、P6-L5-P4、P6-L5-P5、P6-L5-P6、P6-L5-P7、P6-L5-P8、P6-L6-P1、P6-L6-P2、P6-L6-P3、P6-L6-P4、P6-L6-P5、P6-L6-P6、P6-L6- P7, P6-L6-P8, P6-L7-P1, P6-L7-P2, P6-L7-P3, P6-L7-P4, P6-L7-P5, P6-L7-P6, P6-L7-P7, P6-L7-P8, P6-L8-P1, P6-L8-P2, P6-L8-P3, P6-L8-P4, P6-L 8-P5、P6-L8-P6、P6-L8-P7、P6-L8-P8、P6-L9-P1、P6-L9-P2、P6-L9-P3、P6- L9-P4、P6-L9-P5、P6-L9-P6、P6-L9-P7、P6-L9-P8、P6-L10-P1、P6-L10-P2、P 6-L10-P3、P6-L10-P4、P6-L10-P5、P6-L10-P6、P6-L10-P7、P6-L10-P8、P6- L11-P1、P6-L11-P2、P6-L11-P3、P6-L11-P4、P6-L11-P5、P6-L11-P6、P6-L1 1-P7、P6-L11-P8、P6-L12-P1、P6-L12-P2、P6-L12-P3、P6-L12-P4、P6-L12- P5、P6-L12-P6、P6-L12-P7、P6-L12-P8、P6-L13-P1、P6-L13-P2、P6-L13-P3、 P6-L13-P4、P6-L13-P5、P6-L13-P6、P6-L13-P7、P6-L13-P8、P6-L14-P1、P6 -L14-P2、P6-L14-P3、P6-L14-P4、P6-L14-P5、P6-L14-P6、P6-L14-P7、P6-L1 4-P8、P6-L15-P1、P6-L15-P2、P6-L15-P3、P6-L15-P4、P6-L15-P5、P6-L15- P6、P6-L15-P7、P6-L15-P8、P6-L16-P1、P6-L16-P2、P6-L16-P3、P6-L16-P4、P6-L16-P5、P6-L16-P6、P6-L16-P7、P6-L16-P8、P6-L17-P1、P6-L17-P2、P6-L17-P3、P6-L17-P4、P6-L17-P5、P6-L17-P6、P6-L17-P7、P6-L17-P8、P6-L18、 -P1、P6-L18-P2、P6-L18-P3、P6-L18-P4、P6-L18-P5、P6-L18-P6、P6-L18-P 7、P6-L18-P8、P6-L19-P1、P6-L19-P2、P6-L19-P3、P6-L19-P4、P6-L19-P5、 P6-L19-P6、P6-L19-P7、P6-L19-P8、P6-L20-P1、P6-L20-P2、P6-L20-P3、P6-L20-P4、P6-L20-P5、P6-L20-P6、P6-L20-P7、P6-L20-P8、P6-L21-P1、P6-L 21-P2、P6-L21-P3、P6-L21-P4、P6-L21-P5、P6-L21-P6、P6-L21-P7、P6-L21-P8、P6-L22-P1、P6-L22-P2、P6-L22-P3、P6-L22-P4、P6-L22-P5、P6-L22-P 6、P6-L22-P7、P6-L22-P8、P6-L23-P1、P6-L23-P2、P6-L23-P3、P6-L23-P4、 P6-L23-P5、P6-L23-P6、P6-L23-P7、P6-L23-P8、P6-L24-P1、P6-L24-P2、P6- L24-P3、P6-L24-P4、P6-L24-P5、P6-L24-P6、P6-L24-P7、P6-L24-P8、P6-L2 5-P1、P6-L25-P2、P6-L25-P3、P6-L25-P4、P6-L25-P5、P6-L25-P6、P6-L25- P7、P6-L25-P8、P6-L26-P1、P6-L26-P2、P6-L26-P3、P6-L26-P4、P6-L26-P5、P6-L26-P6、P6-L26-P7、P6-L26-P8、P6-L27-P1、P6-L27-P2、P6-L27-P3、P 6-L27-P4、P6-L27-P5、P6-L27-P6、P6-L27-P7、P6-L27-P8、P6-L28-P1、P6-L28-P2、P6-L28-P3、P6-L28-P4、P6-L28-P5、P6-L28-P6、P6-L28-P7、P6-L2 8-P8、P6-L29-P1、P6-L29-P2、P6-L29-P3、P6-L29-P4、P6-L29-P5、P6-L29- P6、P6-L29-P7、P6-L29-P8、P6-L30-P1、P6-L30-P2、P6-L30-P3、P6-L30-P4、<h2 style=";text-align:left;direction:ltr">P6-L30-P5、P6-L30-P6、P6-L30-P7、P6-L30-P8、P6-L31-P1、P6-L31-P2、P6 -L31-P3、P6-L31-P4、P6-L31-P5、P6-L31-P6、P6-L31-P7、P6-L31-P8、P6-L 32-P1、P6-L32-P2、P6-L32-P3、P6-L32-P4、P6-L32-P5、P6-L32-P6、P6-L32 -P7、P6-L32-P8、P6-L33-P1、P6-L33-P2、P6-L33-P3、P6-L33-P4、P6-L33-P5 、P6-L33-P6、P6-L33-P7、P6-L33-P8、P6-L34-P1、P6-L34-P2、P6-L34-P3、P 6-L34-P4、P6-L34-P5、P6-L34-P6、P6-L34-P7、P6-L34-P8、P6-L35-P1、P6- L35-P2、P6-L35-P3、P6-L35-P4、P6-L35-P5、P6-L35-P6、P6-L35-P7、P6-L3 5-P8、P6-L36-P1、P6-L36-P2、P6-L36-P3、P6-L36-P4、P6-L36-P5、P6-L36-P 6, P6-L36-P7, P6-L36-P8, P7-L1-P1, P7-L1-P2, P7-L1-P3, P7-L1-P4, P7-L1-P5, P7-L1-P6, P7-L1-P7, P7-L1-P8, P7-L2-P1, P7-L2-P2, P7-L2-P3, P7- L2-P4, P7-L2-P5, P7-L2-P6, P7-L2-P7, P7-L2-P8, P7-L3-P1, P7-L3-P2, P7-L3-P3, P7-L3-P4, P7-L3-P5, P7-L3-P6, P7-L3-P7, P7-L3-P8, P7-L4-P1, P7 -L4-P2、P7-L4-P3、P7-L4-P4、P7-L4-P5、P7-L4-P6、P7-L4-P7、P7-L4-P8、P 7-L5-P1、P7-L5-P2、P7-L5-P3、P7-L5-P4、P7-L5-P5、P7-L5-P6、P7-L5-P7、P 7-L5-P8,P7-L6-P1,P7-L6-P2,P7-L6-P3,P7-L6-P4,P7-L6-P5,P7-L6-P6,P7-L6-P7,P7-L6-P8,P7-L7-P1,P7-L7-P2,P7-L7-P3,P7-L7-P4,P7-L7-P5,P7-L7-P6、P7-L7-P7、P7-L7-P8、P7-L8-P1、P7-L8-P2、P7-L8-P3、P7-L8-P4、P7-L8-P5、P7-L8-P6、P7-L8-P7、P7-L8-P8、P7-L9-P1、P7-L9-P2、P7-L9-P3、P7-L9-P4、P7-L9-P5、P7-L9-P6、P7-L9-P7、P7-L9-P8、P7-L10-P1、P7-L10-P2、P7-L10-P3、P7-L10-P4、P7-L10-P5、P7-L10-P6、P7-L10-P7、P7-L10-P8、P7-L11-P1、P7-L11-P2、P7-L11-P3、P7-L11-P4、P7-L11-P5、P7-L11-P6、P7-L11-P7、P7-L11-P8、P7-L12-P1、P7-L12-P2、P7-L12-P3、P7-L12-P4、P7-L12-P5、P7-L12-P6、P7-L12-P7、P7-L12-P8、P7-L13-P1、P7-L13-P2、P7-L13-P3、P7-L13-P4、P7-L13-P5、P7-L13-P6、P7-L13-P7、P7-L13-P8、P7-L14-P1、P7-L14-P2、P7-L14-P3、P7-L14-P4、P7-L14-P5、P7-L14-P6、P7-L14-P7、P7-L14-P8、P7-L15-P1、P7-L15-P2、P7-L15-P3、P7-L15-P4、P7-L15-P5、P7-L15-P6、P7-L15-P7、P7-L15-P8、P7-L16-P1、P7-L16-P2、P7-L16-P3、P7-L16-P4、P7-L16-P5、P7-L16-P6、P7-L16-P7、P7-L16-P8、P7-L17-P1、P7-L17-P2、P7-L17-P3、P7-L17-P4、P7-L17-P5、P7-L17-P6、P7-L17-P7、P7-L17-P8、P7-L18-P1、P7-L18-P2、P7-L18-P3、P7-L18-P4、P7-L18-P5、P7-L18-P6、P7-L18-P7、P7-L18-P8、P7-L19-P1、P7-L19-P2、P7-L19-P3、P7-L19-P4、P7-L19-P5、P7-L19-P6、P7-L19-P7、P7-L19-P8、P7-L20-P1、P7-L20-P2、P7-L20-P3、P7-L20-P4、P7-L20-P5、P7-L20-P6、P7-L20-P7、P7-L20-P8、P7-L21-P1、P7 -L21-P2、P7-L21-P3、P7-L21-P4、P7-L21-P5、P7-L21-P6、P7-L21-P7、P7-L2 1-P8、P7-L22-P1、P7-L22-P2、P7-L22-P3、P7-L22-P4、P7-L22-P5、P7-L22- P6、P7-L22-P7、P7-L22-P8、P7-L23-P1、P7-L23-P2、P7-L23-P3、P7-L23-P4、 P7-L23-P5、P7-L23-P6、P7-L23-P7、P7-L23-P8、P7-L24-P1、P7-L24-P2、P7 -L24-P3、P7-L24-P4、P7-L24-P5、P7-L24-P6、P7-L24-P7、P7-L24-P8、P7-L2 5-P1、P7-L25-P2、P7-L25-P3、P7-L25-P4、P7-L25-P5、P7-L25-P6、P7-L25- P7、P7-L25-P8、P7-L26-P1、P7-L26-P2、P7-L26-P3、P7-L26-P4、P7-L26-P5、 P7-L26-P6、P7-L26-P7、P7-L26-P8、P7-L27-P1、P7-L27-P2、P7-L27-P3、P7 -L27-P4、P7-L27-P5、P7-L27-P6、P7-L27-P7、P7-L27-P8、P7-L28-P1、P7-L2 8-P2、P7-L28-P3、P7-L28-P4、P7-L28-P5、P7-L28-P6、P7-L28-P7、P7-L28-P8、P7-L29-P1、P7-L29-P2、P7-L29-P3、P7-L29-P4、P7-L29-P5、P7-L29-P6、 P7-L29-P7、P7-L29-P8、P7-L30-P1、P7-L30-P2、P7-L30-P3、P7-L30-P4、P7 -L30-P5、P7-L30-P6、P7-L30-P7、P7-L30-P8、P7-L31-P1、P7-L31-P2、P7-L3 1-P3、P7-L31-P4、P7-L31-P5、P7-L31-P6、P7-L31-P7、P7-L31-P8、P7-L32- P1、P7-L32-P2、P7-L32-P3、P7-L32-P4、P7-L32-P5、P7-L32-P6、P7-L32-P7、<h2 style=";text-align:left;direction:ltr">P7-L32-P8, P7-L33-P1, P7-L33-P2, P7-L33-P3, P7-L33-P4, P7-L33-P5, P7-L33-P6, P7-L33-P7, P7-L33-P8, P7-L34-P1, P7-L34-P2, P7-L34-P3, P7-L 34-P4、P7-L34-P5、P7-L34-P6、P7-L34-P7、P7-L34-P8、P7-L35-P1、P7-L35 -P2、P7-L35-P3、P7-L35-P4、P7-L35-P5、P7-L35-P6、P7-L35-P7、P7-L35-P8 、P7-L36-P1、P7-L36-P2、P7-L36-P3、P7-L36-P4、P7-L36-P5、P7-L36-P6、P 7-L36-P7、P7-L36-P8、P8-L1-P1、P8-L1-P2、P8-L1-P3、P8-L1-P4、P8-L1-P5 P8-L1-P6, P8-L1-P7, P8-L1-P8, P8-L2-P1, P8-L2-P2, P8-L2-P3, P8-L2-P4, P8-L2-P5, P8-L2-P6, P8-L2-P7, P8-L2-P8, P8-L3-P1, P8-L3-P2, P8-L3-P 3、P8-L3-P4、P8-L3-P5、P8-L3-P6、P8-L3-P7、P8-L3-P8、P8-L4-P1、P8-L4- P2、P8-L4-P3、P8-L4-P4、P8-L4-P5、P8-L4-P6、P8-L4-P7、P8-L4-P8、P8-L5 -P1,P8-L5-P2,P8-L5-P3,P8-L5-P4,P8-L5-P5,P8-L5-P6,P8-L5-P7,P8-L5-P8,P8-L6-P1,P8-L6-P2,P8-L6-P3,P8-L6-P4,P8-L6-P5,P8-L6-P6,P8-L 6-P7,P8-L6-P8,P8-L7-P1,P8-L7-P2,P8-L7-P3,P8-L7-P4,P8-L7-P5,P8-L7-P6,P8-L7-P7,P8-L7-P8,P8-L8-P1,P8-L8-P2,P8-L8-P3,P8-L8-P4,P8- L8-P5、P8-L8-P6、P8-L8-P7、P8-L8-P8、P8-L9-P1、P8-L9-P2、P8-L9-P3、P8 -L9-P4、P8-L9-P5、P8-L9-P6、P8-L9-P7、P8-L9-P8、P8-L10-P1、P8-L10-P2、P8-L10-P3、P8-L10-P4、P8-L10-P5、P8-L10-P6、P8-L10-P7、P8-L10-P8、P8-L11 -P1、P8-L11-P2、P8-L11-P3、P8-L11-P4、P8-L11-P5、P8-L11-P6、P8-L11-P7、P、 8-L11-P8、P8-L12-P1、P8-L12-P2、P8-L12-P3、P8-L12-P4、P8-L12-P5、P8- L12-P6、P8-L12-P7、P8-L12-P8、P8-L13-P1、P8-L13-P2、P8-L13-P3、P8-L1 3-P4、P8-L13-P5、P8-L13-P6、P8-L13-P7、P8-L13-P8、P8-L14-P1、P8-L14-P2、P8-L14-P3、P8-L14-P4、P8-L14-P5、P8-L14-P6、P8-L14-P7、P8-L14-P8、 P8-L15-P1、P8-L15-P2、P8-L15-P3、P8-L15-P4、P8-L15-P5、P8-L15-P6、P8 -L15-P7、P8-L15-P8、P8-L16-P1、P8-L16-P2、P8-L16-P3、P8-L16-P4、P8-L1 6-P5、P8-L16-P6、P8-L16-P7、P8-L16-P8、P8-L17-P1、P8-L17-P2、P8-L17-P3、P8-L17-P4、P8-L17-P5、P8-L17-P6、P8-L17-P7、P8-L17-P8、P8-L18-P1、 P8-L18-P2、P8-L18-P3、P8-L18-P4、P8-L18-P5、P8-L18-P6、P8-L18-P7、P8 -L18-P8、P8-L19-P1、P8-L19-P2、P8-L19-P3、P8-L19-P4、P8-L19-P5、P8-L1 9-P6、P8-L19-P7、P8-L19-P8、P8-L20-P1、P8-L20-P2、P8-L20-P3、P8-L20- P4、P8-L20-P5、P8-L20-P6、P8-L20-P7、P8-L20-P8、P8-L21-P1、P8-L21-P2、 P8-L21-P3、P8-L21-P4、P8-L21-P5、P8-L21-P6、P8-L21-P7、P8-L21-P8、P8 -L22-P1、P8-L22-P2、P8-L22-P3、P8-L22-P4、P8-L22-P5、P8-L22-P6、P8-L2 2-P7、P8-L22-P8、P8-L23-P1、P8-L23-P2、P8-L23-P3、P8-L23-P4、P8-L23-P5、P8-L23-P6、P8-L23-P7、P8-L23-P8、P8-L24-P1、P8-L24-P2、P8-L24-P3、P8-L24-P4、P8-L24-P5、P8-L24-P6、P8-L24-P7、P8-L24-P8、P8-L25-P1、P8 -L25-P2、P8-L25-P3、P8-L25-P4、P8-L25-P5、P8-L25-P6、P8-L25-P7、P8-L2 5-P8、P8-L26-P1、P8-L26-P2、P8-L26-P3、P8-L26-P4、P8-L26-P5、P8-L26-P6、P8-L26-P7、P8-L26-P8、P8-L27-P1、P8-L27-P2、P8-L27-P3、P8-L27-P4、 P8-L27-P5、P8-L27-P6、P8-L27-P7、P8-L27-P8、P8-L28-P1、P8-L28-P2、P8 -L28-P3、P8-L28-P4、P8-L28-P5、P8-L28-P6、P8-L28-P7、P8-L28-P8、P8-L2 9-P1、P8-L29-P2、P8-L29-P3、P8-L29-P4、P8-L29-P5、P8-L29-P6、P8-L29-P7、P8-L29-P8、P8-L30-P1、P8-L30-P2、P8-L30-P3、P8-L30-P4、P8-L30-P5、 P8-L30-P6、P8-L30-P7、P8-L30-P8、P8-L31-P1、P8-L31-P2、P8-L31-P3、P8 -L31-P4、P8-L31-P5、P8-L31-P6、P8-L31-P7、P8-L31-P8、P8-L32-P1、P8-L3 2-P2、P8-L32-P3、P8-L32-P4、P8-L32-P5、P8-L32-P6、P8-L32-P7、P8-L32- P8、P8-L33-P1、P8-L33-P2、P8-L33-P3、P8-L33-P4、P8-L33-P5、P8-L33-P6、 P8-L33-P7、P8-L33-P8、P8-L34-P1、P8-L34-P2、P8-L34-P3、P8-L34-P4、P8 -L34-P5、P8-L34-P6、P8-L34-P7、P8-L34-P8、P8-L35-P1、P8-L35-P2、P8-L3 5-P3、P8-L35-P4、P8-L35-P5、P8-L35-P6、P8-L35-P7、P8-L35-P8、P8-L36- P1、P8-L36-P2、P8-L36-P3、P8-L36-P4、P8-L36-P5、P8-L36-P6、P8-L36-P7、P8-L36-P8.

[0115] According to one aspect of the present invention, a conjugate is provided comprising an antibody or antigen-binding fragment thereof covalently linked to two pharma- ceutical active drugs via a dual linker, the dual linker having one attachment point attached to the antibody and two attachment points to the two pharma-ceutical active drugs, with the proviso that neither pharma-ceutical active drug is a BH3 mimetic. In one embodiment, the two pharma-ceutical active drugs are the same or different. In another embodiment, the pharma-ceutical active drug is selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant. In yet another embodiment, the pharma-ceutical active drug is selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid. In some embodiments, the pharma- ceutically active drug is an auristatin, hi some embodiments, the pharma- ceutically active drug is selected from an antitubulin agent, a tubulin inhibitor, a DNA minor groove binder, a DNA replication inhibitor, an alkylating agent, an antibiotic, an antifolate, an antimetabolite, a chemotherapy sensitizer, a topoisomerase inhibitor, and / or a vinca alkaloid. In another embodiment, the pharma- ceutically active drug is selected from Eg5 inhibitors, V-ATPase inhibitors, HSP90 inhibitors, IAP inhibitors, mTor inhibitors, microtubule stabilizing agents, microtubule destabilizing agents, auristatins, dolastatins, maytansinoids, MetAP (methionine aminopeptidase), inhibitors of nuclear export of protein CRM1, DPPIV inhibitors, inhibitors of phosphoryl transfer reactions in mitochondria, protein synthesis inhibitors, kinase inhibitors, CDK2 inhibitors, CDK9 inhibitors, proteasome inhibitors, kinesin inhibitors, HDAC inhibitors, DNA damaging agents, DNA alkylating agents, DNA interfering agents, DNA minor groove binders, RNA polymerase inhibitors, amanitin, spliceosome inhibitors, topoisomerase inhibitors, DHFR inhibitors, or pro-apoptotic agents.In further embodiments, the pharma- ceutically active drug is selected from a topoisomerase 1 inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative, and / or addition salt with a pharma- ceutically acceptable acid or base. In one embodiment, the pharma- ceutically active drug is a topoisomerase 1 inhibitor selected from topotecan, exatecan, deruxtecan, and SN-38. In yet another embodiment, the pharma-ceutically active drug is selected from a mitotic inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative, and / or addition salt with a pharma- ceutically acceptable acid or base. In a further embodiment, the mitotic inhibitor is monomethyl auristatin E (MMAE) or a taxane. In one embodiment, the taxane is selected from docetaxel, paclitaxel, or cabazitaxel. In another embodiment, the conjugate comprises any of the compounds disclosed herein or a pharma- ceutically acceptable salt thereof.

[0116] As described above, according to one embodiment of the present invention, a compound represented by formula (A-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’ are each independently a linker; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. A conjugate of the formula:

[0117] In one embodiment, L 2’and L 3’ each comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group (eg, a peptide group and a self-immolative group).

[0118] In one embodiment, L 2’ and L 3’ Each of the formulas comprises a peptide group and a self-immolative group.

[0119] In one embodiment, L 2’ and L 3’ each comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a sugar (e.g., glucuronamide) group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0120] In certain embodiments, the conjugate has the formula (B-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently an enzyme cleavage element or a hydrophilic moiety (e.g., E 1 and E 2 are enzyme cleavage elements, respectively); V 1 and V 2may independently comprise: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group) or iii) comprise a self-immolative group and an enzyme-cleavage element; D 1 and D. 2 are each independently a pharma- ceutically active drug, but D 1 Also D 2 is not a BH3 mimetic; and A is an integer from 1 to 16. It is of the following.

[0121] In certain embodiments, the conjugate has the formula (B-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic moiety; V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group; D 1 and D. 2are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. It is of the following.

[0122] In certain embodiments, W is N or CH.

[0123] In one embodiment, E 1 and E 2 are each enzyme cleavage elements.

[0124] In one embodiment, V 1 and V 2 are each independently a self-immolative group.

[0125] In certain embodiments, a is an integer from 1 to 8, or from 1 to 6 or 1 to 4, or a is 1 or 2.

[0126] In certain embodiments, a is determined by liquid chromatography-mass spectrometry (LC-MS).

[0127] In certain embodiments, (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker is -CH 2 -O-, -NH-CH 2 Self-immolative groups include -, -C(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

[0128] In certain embodiments, W is N or CH.

[0129] In one embodiment, R 2 and R 3 are each a hydrophilic group.

[0130] In certain embodiments, the conjugate has the formula (C-2): [ka] (In the formula, Ab is an antibody or an antigen-binding fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A 1 and A 2 are each independently a bond, -OC(=O)-*, [ka] , -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(R a ) 2 C(R a ) 2 N(CH 3 )C(=O)-*, Each Ra are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3 are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. It is of the following.

[0131] In certain embodiments, the conjugate has formula (D1-2), (D2-2) or (D3-2): [ka] It is of the following.

[0132] In certain embodiments, the conjugate is of formula (D1-2), where R 2 and R 3 are each independently a hydrophilic group, and in formula (D2-2), R 2 and R 3 are each independently an enzyme cleavage element; and with respect to formula (D3-2), R 2 is a hydrophilic group, and R 3 is an enzyme cleavage element.

[0133] In one embodiment, R100 teeth, [ka] [ka] [ka] [ka] [ka] Disulfides (In the formula, R 16 , H, C 1 ~C 4 alkyl, phenyl, pyrimidine or pyridine; R 18 , H, C 1 ~C 6 C substituted with alkyl, phenyl or 1 to 3 -OH groups 1 ~C 4 is alkyl; Each R 15 are independently H, C 1 ~C 6 Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH 1 ~C 4 Alkoxy and -C(=O)OH substituted C 1 ~C 4 alkyl; R 17 is independently selected from H, phenyl and pyridine; q is 0, 1, 2 or 3; R 19 is H or methyl; and R 20 -H, -CH 3 or phenyl) is selected from the group consisting of:

[0134] In one embodiment, R 100 teeth, [ka] (In the formula, R 100 (*** indicates the attachment point to Ab) is selected from the group consisting of:

[0135] In one embodiment, R 100 teeth, [ka] (In the formula, R 100 (*** indicates the attachment point to Ab) It is.

[0136] In one embodiment, (1) L 1 teeth, [ka] or *-CH(OH)CH(OH)CH(OH)CH(OH)-** (wherein each n is an integer from 1 to 12). Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (2)L 1 teeth, [ka] and n is an integer from 1 to 12, or n is 1, or n is 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (3) L 1 teeth, [ka] and n is an integer from 1 to 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (4) L 1 teeth, [ka] Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; or (5) L 1 is *-C(=O)(CH 2 ) m O(CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)(CH 2 ) m -**;*-C(=O)NH((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)O(CH 2 ) m SSC(R L1 ) 2 (CH 2 ) m C(=O)NR L1 (CH 2 ) m NR L1 C(=O)(CH 2 ) m -**;*-C(=O)O(CH 2 ) m C(=O)NH(CH 2 ) m -**;*-C(=O)(CH2 ) m NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) n C(=O)-**;*-C(=O)(CH 2 ) m X 1 (CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 )m C(R L1 ) 2 -** or *-C(=O)(CH 2 ) m C(=O)NH(CH 2 ) m -** (In the formula, L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicating a direct or indirect (e.g., direct) point of attachment to; X 1 teeth, [ka] and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R L1 are independently H and C 1 ~C 6 alkyl) is a bridging spacer comprising:

[0137] In one embodiment, L 1 teeth, [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8), and L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 (Indicating a direct or indirect point of attachment to The part represented by

[0138] In one embodiment, n is an integer from 4 to 8.

[0139] In certain embodiments, n is 4 or 8.

[0140] In one embodiment, L 1 is the formula [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L 1 The * in indicates the direct point of attachment to W, and L 1 The ** is R 1 (Indicates the direct attachment point to It is represented by:

[0141] In one embodiment, n is an integer from 4 to 8.

[0142] In certain embodiments, n is 4 or 8.

[0143] In one embodiment, x is an integer from 0 to 2.

[0144] In certain embodiments, x is 0 or 2.

[0145] In one embodiment, z is an integer from 0 to 2.

[0146] In certain embodiments, z is 0 or 2.

[0147] In one embodiment, L 1 teeth, [ka] is selected from the group consisting of:

[0148] In one embodiment, L 2 and L 3 are each independently [ka] (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 (## indicates the direct or indirect point of attachment to W) is a linking spacer comprising a portion represented by:

[0149] In one embodiment, L 2 and L 3 are each independently [ka] [ka] [ka] (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R L23 is hydrogen or C 1 ~C 6is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; If W is N, then L 2 and L 3 (provided that it is not (L2c), (L2d), (L2f) or (L2k)) is a linking spacer selected from the group consisting of:

[0150] In one embodiment, L 2 and L 3 are each independently [ka] [ka] [ka] (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R L23 is hydrogen or C 1 ~C 3 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E2 and L 2 Or L 3 ## indicates the direct point of attachment to W; if W is N, then L 2 and L 3 (provided that it is not (L2FF), (L2MM), (L2NN), (L2OO) or (L2PP)) is a linking spacer selected from the group consisting of:

[0151] In one embodiment, L 2 and L 3 is, independently, [ka] [ka] (In the formula, L 2 Or L 3 # is E 1 Or E 2 indicates the direct attachment point to L 2 Or L 3 ## indicates the direct attachment point to W; R L is hydrogen or -C(O)-R H and R H teeth, [ka] and D is an integer from 20 to 30 (e.g., 25). is a linking spacer selected from the group consisting of:

[0152] In one embodiment, d is 25.

[0153] In certain embodiments, each peptide group independently comprises 1-4, 1-3, or 1-2 amino acid residues.

[0154] In certain embodiments, each peptide group independently comprises two amino acid residues.

[0155] In one embodiment, each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr), and β-alanine (β-Ala).

[0156] In certain embodiments, each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly, and sulfo-Ala-Val-Ala.

[0157] In one embodiment, E 1 and / or E 2 are each independently [ka] (Wherein, E1-1 or E1-2 is V in formula (B) 1 Or V 2 or the direct point of attachment to the -NH- group in formulas (C) and (D); and E1-1 or E1-2 ^^ respectively represent L 2 Or L 3 indicates the direct point of attachment to 1 and E 2 are peptide groups independently selected from (E1-1) and (E1-2). is a peptide group selected from the group consisting of:

[0158] In one embodiment, E 1 and E 2 are each a peptide group independently selected from (E1-1) and (E1-2).

[0159] In one embodiment, E 1 and / or E 2 are each independently [ka] (In the formula, R E is a hydrophilic group R H is) is a peptide group represented by:

[0160] In one embodiment, the hydrophilic group R H teeth, [ka] (wherein e is an integer of 20 to 30 (e.g., 25)) It is.

[0161] In one embodiment, e is 25.

[0162] In one embodiment, E 1 and E 2 are respectively [ka] It is.

[0163] In one embodiment, A 1 and A 2 are independently a bond and -OC(=O)-* (wherein * represents D 1 Or D 2 (indicating the point of attachment to the

[0164] In one embodiment, A 1 and A 2 are independent, combined, [ka] and -OC(=O)-* (wherein * represents D 1 Or D 2 (indicating the point of attachment to the

[0165] In one embodiment, A 1 and A 2 is a bond.

[0166] In one embodiment, A 1 and A 2 is independently a bond, or [ka] (In the formula, * represents D 1 Or D 2 (Indicates the attachment point to It is.

[0167] In one embodiment, A 1 and A 2 On the other hand, [ka] And A 1 and A 2 The other is a bond.

[0168] In one embodiment, A 1 and A 2 Both [ka] It is.

[0169] In one embodiment, A 1 and A 2 On the other hand, [ka] And A 1 and A 2 The other is OC(=O)-*.

[0170] In one embodiment, (i) A 1 and A 2 is -OC(=O)-*; (ii)A 1 and A 2 teeth, [ka] Is it; (iii)A 1 is -OC(=O)-*, and A 2 is a bond; (iv)A 1 is -OC(=O)-*, and A 2 teeth, [ka] Is it; (v)A 1 is a bond, and A 2 teeth, [ka] or (vi) A 1 is a bond, and A 2 is -OC(=O)-* (wherein * is D 1 Or D 2 (showing the attachment point to the

[0171] In one embodiment, i) L 4 and L 5 are each independently [ka] (In the formula, Z is -O-, -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR L45 -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH2 NR L45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45 -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is a bond, triazolyl or -CH 2 -triazolyl-, X is R 2 or R 3 (connected to or a spacer moiety having the structure (ii) L 4 and L 5 is, independently, [ka] (In the formula, Z is -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR b -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45-, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n where each n is independently 1, 2, or 3; X is R 2 or R 3 (connected to It is a spacer portion having the structure:

[0172] In certain embodiments, Z is -O-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH- or -CH 2 X is a bond, triazolyl or -CH 2 -triazolyl-; and R L45 is, at each occurrence, independently H or C 1 ~C 3 It is an alkyl.

[0173] In one embodiment, L 4 and L 5 are each independently [ka] (In the formula, L 4 Or L 5 @ indicates the direct point of attachment to the phenyl group, and L 4 Or L 5 @@ is R 2 or R 3 (Indicates the direct attachment point to is a spacer moiety selected from the group consisting of:

[0174] In one embodiment, R 2 and R 3 Each of the hydrophilic groups represented by the formula (I) is independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 [ka] C replaced with 2 ~C 6 Alkyl or -OC(=O)NHS(O) 2 NHCH 2 CH 2 OCH 3 , -NHC(=O)C 1 ~C 4 Alkylene-P(O)(OCH 2 CH 3 ) 2and C substituted with 1 to 2 substituents independently selected from -COOH groups. 2 ~C 6 Contains alkyl.

[0175] In one embodiment, R 2 or / and R 3 are each independently [ka] (wherein n is an integer of 1 to 6). [ka] is selected from the group consisting of:

[0176] In one embodiment, R 2 or / and R 3 are each independently (i) the following part: [ka] (In the formula, f is an integer from 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) Polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by Contains:

[0177] In one embodiment, R 2 or R 3Each hydrophilic group represented by the formula: (i) the following part: [ka] (In the formula, f is an integer of 3 to 25; R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) or polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) Contains polyethylene glycol.

[0178] In one embodiment, R 2 and R 3 are each independently [ka] (In the formula, g and h are independently an integer of 20 to 30 (e.g., 23 or 24). is selected from the group consisting of:

[0179] In one embodiment, R 2 or / and R 3 teeth, [ka] Includes.

[0180] In one embodiment, R 2 and R 3 are each independently represented by the formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) Contains polyethylene glycol.

[0181] In one embodiment, D 1 and D. 2 is the same.

[0182] In one embodiment, D 1 and D. 2 is different.

[0183] In one embodiment, D 1 and D. 2 are each independently selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant.

[0184] In one embodiment, D 1 and D. 2 are each independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

[0185] In one embodiment, D 1 and D. 2 are each independently [ka] [ka] [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0186] In one embodiment, i)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iv) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; v)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; viii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; x)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xi) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvii)D1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xli)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; il)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; l)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; li)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxiii)D 1 teeth, [ka] and D 2 teeth, [ka] or lxiv)D 1 teeth, [ka] and D 2 teeth, [ka] It is.

[0187] In one embodiment, i)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iv) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; v)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; viii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ix) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; x)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxv)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xl)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xli)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlii)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] Is it; xliii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; l)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; li)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] or lxiv)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] where the * indicates the point of attachment to the rest of the molecule.

[0188] In one embodiment, D 1 and / or D. 2 is an auristatin.

[0189] In one embodiment, D 1 and D. 2 Both are auristatins.

[0190] In one embodiment, D 1 and / or D. 2 is a topoisomerase 1 inhibitor.

[0191] In one embodiment, D 1 and D. 2 Both are topoisomerase 1 inhibitors.

[0192] In one embodiment, D 1 and D. 2 one of which is an auristatin and D 1 and D. 2 The other is a topoisomerase 1 inhibitor.

[0193] In one embodiment, D 1 is an auristatin, D 2 is a topoisomerase 1 inhibitor.

[0194] In one embodiment, D 1 is a topoisomerase 1 inhibitor, D 2 is an auristatin.

[0195] In one embodiment, D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to is selected from the group consisting of:

[0196] In one embodiment, D 1 and D. 2 is, independently, [ka] is selected from the group consisting of:

[0197] In one embodiment, D 1 and D. 2 are each independently selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapeutic sensitizers, topoisomerase inhibitors, and / or vinca alkaloids.

[0198] In one embodiment, D 1 and D. 2 are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; 1 Also D 2 provided that the compound is not a BH3 mimetic.

[0199] In certain embodiments, the antibody or antigen-binding fragment binds to a target antigen on a cancer cell.

[0200] In certain embodiments, (i) the target antigen is selected from BCMA, CD33, HER2, CD38, CD48, CD79b, PCAD, CD74, CD138, SLAMF7, CD123, CLL1, FLT3, CD7, CKIT, CD56, SEZ6, DLL3, DLK1, B7-H3, EGFR, CD71, EphA2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, TROP2, LIV1, CD46, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; (ii) the target antigen is selected from EGFR, CD7, HER2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; or (iii) the target antigen is PCAD, CD48, CD74, EphA2, HER2, TROP2, B7-H3 or 5T4.

[0201] In certain embodiments, the target antigen is PCAD, CD48, CD74, EphA2, HER2, TROP2, B7-H3, or 5T4.

[0202] In certain embodiments, the antibody or antigen-binding fragment thereof is selected from Table D1.

[0203] In some embodiments, the antibody or antigen-binding fragment comprises i) three heavy chain CDR sequences and three light chain CDR sequences selected from an antibody in Tables D3 and D8, ii) a heavy chain variable region sequence and a light chain variable region sequence selected from an antibody in Tables D2 and D8, and / or iii) a heavy chain sequence and a light chain sequence selected from an antibody in Tables D4, D5 and D7.

[0204] In certain embodiments, the antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 268, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 269, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 263, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 6) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 7) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 215, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; and 8) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174 and three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0205] In one embodiment, the antibody or antigen-binding fragment is an anti-CD74 antibody comprising (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 262, or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 267.

[0206] In certain embodiments, the antibody or antigen-binding fragment comprises: (a) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 237, or a sequence at least 95% identical to SEQ ID NO: 237; (b) a heavy chain amino acid sequence of SEQ ID NO: 236, or a sequence at least 95% identical to SEQ ID NO: 236, and a light chain amino acid sequence of SEQ ID NO: 237, or a sequence at least 95% identical to SEQ ID NO: 237; or (c) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 239, or a sequence at least 95% identical to SEQ ID NO: 239. is an anti-CD74 antibody comprising

[0207] In certain embodiments, the antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 271, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 272, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 281, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 283; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 274, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 285, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 276, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 287, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 4) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 279, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 288, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 51, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 52, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 53; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 54, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 55, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 56 and three light chain CDRs selected from the group consisting of:

[0208] In one embodiment, the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:270 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:280; or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:14.

[0209] In one embodiment, the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: (a) a heavy chain amino acid sequence of SEQ ID NO:240, or a sequence that is at least 95% identical to SEQ ID NO:240, and a light chain amino acid sequence of SEQ ID NO:243, or a sequence that is at least 95% identical to SEQ ID NO:243; or (b) a heavy chain amino acid sequence of SEQ ID NO:242, or a sequence that is at least 95% identical to SEQ ID NO:242, and a light chain amino acid sequence of SEQ ID NO:243, or a sequence that is at least 95% identical to SEQ ID NO:243; c) a heavy chain amino acid sequence of SEQ ID NO:240, or a sequence that is at least 95% identical to SEQ ID NO:240, and a light chain amino acid sequence of SEQ ID NO:69, or a sequence that is at least 95% identical to SEQ ID NO:70.

[0210] In certain embodiments, the antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 289, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 290, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 297, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 299; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 292, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 293, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 294, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 295; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 302, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 39, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44 and three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0211] In one embodiment, the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:9 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:296.

[0212] In one embodiment, the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO:245, or a sequence at least 95% identical to SEQ ID NO:245, and a light chain amino acid sequence of SEQ ID NO:66, or a sequence at least 95% identical to SEQ ID NO:66.

[0213] In certain embodiments, the antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 304, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 305, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 312, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 314; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 307, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 309, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 317, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 310, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316 and three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0214] In one embodiment, the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:303 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:311.

[0215] In one embodiment, the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain amino acid sequence of SEQ ID NO:248, or a sequence at least 95% identical to SEQ ID NO:248, and a light chain amino acid sequence of SEQ ID NO:250, or a sequence at least 95% identical to SEQ ID NO:250.

[0216] In certain embodiments, the antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 319, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 320, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 330, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 332; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 322, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 324; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 325, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 326, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 327; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 336, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 328, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335 and three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0217] In one embodiment, the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:318 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:329.

[0218] In one embodiment, the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO:252, or a sequence at least 95% identical to SEQ ID NO:252, and a light chain amino acid sequence of SEQ ID NO:254, or a sequence at least 95% identical to SEQ ID NO:254.

[0219] In some embodiments, the antibody or antigen-binding fragment thereof comprises one or more cysteine ​​substitutions selected from E152C, S375C, or both E152C and S375C in the heavy chain of the antibody or antigen-binding fragment thereof, where positions are numbered according to the EU system.

[0220] In certain embodiments, the antibody or antigen-binding fragment thereof comprises one or more Fc-silencing mutations.

[0221] In one embodiment, the composition comprises multiple copies of the antibody drug conjugate of any one of claims 46 to 110, and the average a of the antibody drug conjugate in the composition is from about 1 to about 8, e.g., from about 1 to about 6, from about 1 to about 4, or from about 1 to about 2.

[0222] In certain embodiments, the compound, or a pharma- ceutically acceptable salt thereof, is represented by any one of the following formulas: [ka] [ka] [ka] [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30; o for each occurrence is independently an integer from 1 to 9; and and n is an integer from 1 to 12.

[0223] In one embodiment, A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the

[0224] In certain embodiments, the conjugate is represented by any one of the following formulas: [ka] [ka] [ka] [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30; o for each occurrence is independently an integer from 1 to 9; n is an integer from 1 to 12; and **--- indicates the point of attachment to Ab).

[0225] In one embodiment, A 1 and A 2 each independently represents a bond and OC(=O)-* (wherein A1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the

[0226] In one embodiment, the compound or a pharma- ceutically acceptable salt thereof has the formula (D5a-1): [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); and n is an integer from 1 to 12 (e.g., 5 to 10). It is of the following.

[0227] In one embodiment, A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the

[0228] In certain embodiments, the conjugate has formula (D5a-2): [ka] (In the formula, A 1 and A2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); n is an integer from 1 to 12 (e.g., 5 to 10); and **--- indicates the attachment point to Ab) It is of the following.

[0229] In one embodiment, A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the

[0230] In certain embodiments, the conjugate is represented by any one of the following formulas: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein * is D 1 Or D 2 **--- indicates point of attachment to Ab; and [ka] D 1 Or D 2 (Indicating a direct attachment point to the

[0231] In one embodiment, A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the

[0232] In some embodiments, the present disclosure provides, in part, novel antibody drug conjugate (ADC) compounds that have biological activity against cancer cells. The compounds may slow, inhibit, and / or reverse tumor growth in mammals and / or may be useful for treating human cancer patients. The present disclosure more specifically relates to ADC compounds that can bind to and kill cancer cells in some embodiments. In some embodiments, the ADC compounds disclosed herein include a dual linker that connects a full-length antibody or antigen-binding fragment with, optionally, two pharma- ceutically active drugs, provided that neither is a BH3 mimetic. In some embodiments, the ADC compounds can also be internalized into target cells after binding.

[0233] In some embodiments, the antibody or antigen-binding fragment binds to a target antigen on a cancer cell, hi some embodiments, the target antigen is BCMA, CD33, HER2, CD38, CD48, CD79b, PCAD, CD74, CD138, SLAMF7, CD123, CLL1, FLT3, CD7, CKIT, CD56, DLL3, DLK1, B7-H3, EGFR, CD71, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, TROP2, LIV1, CD46, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, or GPNMB. In some embodiments, the target antigen is EphA2, CD56, SEZ6, CD25, CCR8, CEACAM5, CEACAM6, 4-1BB, 5AC, 5T4, alpha-fetoprotein, angiopoietin 2, ASLG659, TCLI, BMPRIB, brevican BCAN, BEHAB, C242 antigen, C5, CA-125, CA-125 (mimetics), CA-IX (carbonic anhydrase 9), CCR4, CD140a, CD152, CD19, CD20, CD200, CD21 (C3DR)I), CD22 (B-cell receptor CD22-B isoform), CD221, CD23 (gE receptor), CD28, CD30 (TNFRSF8), CD37, CD4, CD40, CD44 v6, CD51, CD52, CD70, CD72 (Lyb-2, B-cell differentiation antigen CD72), CD79a, CD80, CEA, CEA-related antigen, ch4D5, CLDN18.2, CRIPTO (CR, CRI, CRGF, TDGF1), CTLA-4, CXCR5, DLL4, DR5, E16 (LATI, SLC7A5), EGFL7, EphB2R (DRT, ERK, Hek5, EPHT3, Tyro5), episialin, ERBB3, ETBR (endothelin type B receptor), FCRHI (Fc receptor-like protein I), FcRH2 (IFGP4, IRTA4, SPAPI, SPAP IB, SPAP IC), fibronectin extra domain-B, Frizzled receptor, GD2, GD3 ganglioside, GEDA, HER1, HER2 / neu, HER3, HGF, HLA-DOB, HLA-DR, human scatter factor receptor kinase, IGF-I receptor, IL-13, IL20R (ZCYTOR7), IL-6, ILGF2, ILFRIR, integrin u, IRTA2 (immunoglobulin superfamily receptor metastasis-associated 2), Lewis-Y antigen, LY64 (RP105), MCP-I, MDP (DPEPI), MPF, MSLN, SMR, mesothelin, megakaryocyte, PD-I, PDCDI, PDGF-Ru, prostate-specific membrane antigen, PSCA (prostate stem cell antigen precursor), PSCA hlg, RANKL, RON, SDCI, Sema Sb, STEAP I, STEAP2, PCANAP I, STAMP I, STEAP2, STMP, prostate cancer associated gene I, TAG-72, TEMI, tenascin-C, TENB2, (TMEFF2, tomoregulin, TPEF, HPPI, TR), TGF-IJ, TRAIL-E2, TRAIL-Rl, TRAIL-R2, T17M4 (BR22450, FLJ20041, TRPM4, TRPM4B, transient receptor potential cation channel subfamily M, member 4), TWEAK-R, TYRP I (glycoprotein 75), VEGF, VEGF-A, EGFR-I, VEGFR-2, or vimentin. In some embodiments, the target antigen is EGFR, CD7, HER2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, nectin4, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, or GPNMB. In some embodiments, the target antigen is PCAD, HER2, CD48, CD74, EphA2, TROP2, B7-H3, or 5T4.

[0234] In some embodiments, the antibody or antigen-binding fragment is selected from the group consisting of antibodies and antigen-binding fragments described in International Publication Nos. WO 2018 / 098306, WO 2016 / 179257, WO 2011 / 097627, WO 2017 / 214282, WO 2017 / 214301, WO 2017 / 214233, WO 201 and in U.S. Pat. No. 6,870,034 B2, and on the internet at go.drugbank.com / drugs / DB00002.

[0235] In some embodiments, the antibody or antigen-binding fragment is an anti-HER2 antibody or antigen-binding fragment (e.g., trastuzumab or Ab T). In some embodiments, the antibody or antigen-binding fragment is an anti-CD74 antibody or antigen-binding fragment (e.g., VHmilxVK1aNQAb or milatuzumab). In some embodiments, the antibody or antigen-binding fragment is an anti-CD48 antibody or antigen-binding fragment (e.g., SGN-CD48A (MEM / MEM102 or NY920). In some embodiments, the antibody or antigen-binding fragment is an anti-PCAD antibody or antigen-binding fragment (e.g., CQY679). In some embodiments, the antibody or antigen-binding fragment is an anti-EphA2 antibody or antigen-binding fragment (e.g., 1C1). In some embodiments, the antibody or antigen-binding fragment is an antibody or antigen-binding fragment having CDR sequences selected from those in Tables D3 and D8, or an antibody or antigen-binding fragment having variable regions selected from those in Tables D2 and D8, or an antibody or antigen-binding fragment having a full length selected from those in Tables D4, D5, and D7.

[0236] Also provided herein, in some embodiments, are compositions comprising multiple copies of an antibody drug conjugate (e.g., any of the exemplary antibody drug conjugates described herein). In some embodiments, the average p of the antibody drug conjugate in the composition is about 2 to about 4.

[0237] In some embodiments, the antibody or antigen-binding fragment thereof is conjugated to a group selected from any one of: P1-L1-P1, P1-L1-P2, P1-L1-P3, P1-L1-P4, P1-L1-P5, P1-L1-P6, P1-L1-P7, P1-L1-P8, P1-L2-P1, P1-L2-P2, P1-L2-P3, P1-L2-P4, P1-L2-P5, P1-L2-P6, P1-L2-P7, P1-L2-P8, P1-L3-P1, P1-L3-P2, P1-L3-P3, P1-L3-P4, P1-L3-P5, P1-L3-P6, P1-L3-P7 , P1-L3-P8, P1-L4-P1, P1-L4-P2, P1-L4-P3, P1-L4-P4, P1-L4-P5, P1-L 4-P6, P1-L4-P7, P1-L4-P8, P1-L5-P1, P1-L5-P2, P1-L5-P3, P1-L5-P4, P1-L5-P5, P1-L5-P6, P1-L5-P7, P1-L5-P8, P1-L6-P1, P1-L6-P2, P1-L6 -P3, P1-L6-P4, P1-L6-P5, P1-L6-P6, P1-L6-P7, P1-L6-P8, P1-L7-P1, P1 -L7-P2, P1-L7-P3, P1-L7-P4, P1-L7-P5, P1-L7-P6, P1-L7-P7, P1-L7-P 8, P1-L8-P1, P1-L8-P2, P1-L8-P3, P1-L8-P4, P1-L8-P5, P1-L8-P6, P1- L8-P7, P1-L8-P8, P1-L9-P1, P1-L9-P2, P1-L9-P3, P1-L9-P4, P1-L9-P5 , P1-L9-P6, P1-L9-P7, P1-L9-P8, P1-L10-P1, P1-L10-P2, P1-L10-P3, P1 -L10-P4, P1-L10-P5, P1-L10-P6, P1-L10-P7, P1-L10-P8, P1-L11-P1, P 1-L11-P2, P1-L11-P3, P1-L11-P4, P1-L11-P5, P1-L11-P6, P1-L11-P7, P 1-L11-P8, P1-L12-P1, P1-L12-P2, P1-L12-P3, P1-L12-P4, P1-L12-P5, P1-L12-P6, P1-L12-P7, P1-L12-P8, P1-L13-P1, P1-L13-P2, P1-L13-P3,P1-L13-P4、P1-L13-P5、P1-L13-P6、P1-L13-P7、P1-L13-P8、P1-L14-P1、P1 -L14-P2、P1-L14-P3、P1-L14-P4、P1-L14-P5、P1-L14-P6、P1-L14-P7、P1-L1 4-P8、P1-L15-P1、P1-L15-P2、P1-L15-P3、P1-L15-P4、P1-L15-P5、P1-L15-P6、P1-L15-P7、P1-L15-P8、P1-L16-P1、P1-L16-P2、P1-L16-P3、P1-L16-P4、 P1-L16-P5、P1-L16-P6、P1-L16-P7、P1-L16-P8、P1-L17-P1、P1-L17-P2、P1 -L17-P3、P1-L17-P4、P1-L17-P5、P1-L17-P6、P1-L17-P7、P1-L17-P8、P1-L1 8-P1、P1-L18-P2、P1-L18-P3、P1-L18-P4、P1-L18-P5、P1-L18-P6、P1-L18- P7、P1-L18-P8、P1-L19-P1、P1-L19-P2、P1-L19-P3、P1-L19-P4、P1-L19-P5、 P1-L19-P6、P1-L19-P7、P1-L19-P8、P1-L20-P1、P1-L20-P2、P1-L20-P3、P1 -L20-P4、P1-L20-P5、P1-L20-P6、P1-L20-P7、P1-L20-P8、P1-L21-P1、P1-L2 1-P2、P1-L21-P3、P1-L21-P4、P1-L21-P5、P1-L21-P6、P1-L21-P7、P1-L21- P8、P1-L22-P1、P1-L22-P2、P1-L22-P3、P1-L22-P4、P1-L22-P5、P1-L22-P6、 P1-L22-P7、P1-L22-P8、P1-L23-P1、P1-L23-P2、P1-L23-P3、P1-L23-P4、P1 -L23-P5、P1-L23-P6、P1-L23-P7、P1-L23-P8、P1-L24-P1、P1-L24-P2、P1-L2 4-P3、P1-L24-P4、P1-L24-P5、P1-L24-P6、P1-L24-P7、P1-L24-P8、P1-L25-P1、P1-L25-P2、P1-L25-P3、P1-L25-P4、P1-L25-P5、P1-L25-P6、P1-L25-P7、P1-L25-P8、P1-L26-P1、P1-L26-P2、P1-L26-P3、P1-L26-P4、P1-L26-P5、P1-L26-P6、P1-L26-P7、P1-L26-P8、P1-L27-P1、P1-L27-P2、P1-L27-P3、P1-L 27-P4、P1-L27-P5、P1-L27-P6、P1-L27-P7、P1-L27-P8、P1-L28-P1、P1-L28-P2、P1-L28-P3、P1-L28-P4、P1-L28-P5、P1-L28-P6、P1-L28-P7、P1-L28-P8 、P1-L29-P1、P1-L29-P2、P1-L29-P3、P1-L29-P4、P1-L29-P5、P1-L29-P6、P1-L29-P7、P1-L29-P8、P1-L30-P1、P1-L30-P2、P1-L30-P3、P1-L30-P4、P1-L 30-P5、P1-L30-P6、P1-L30-P7、P1-L30-P8、P1-L31-P1、P1-L31-P2、P1-L31 -P3、P1-L31-P4、P1-L31-P5、P1-L31-P6、P1-L31-P7、P1-L31-P8、P1-L32-P1 、P1-L32-P2、P1-L32-P3、P1-L32-P4、P1-L32-P5、P1-L32-P6、P1-L32-P7、P 1-L32-P8、P1-L33-P1、P1-L33-P2、P1-L33-P3、P1-L33-P4、P1-L33-P5、P1- L33-P6、P1-L33-P7、P1-L33-P8、P1-L34-P1、P1-L34-P2、P1-L34-P3、P1-L3 4-P4、P1-L34-P5、P1-L34-P6、P1-L34-P7、P1-L34-P8、P1-L35-P1、P1-L35-P 2、P1-L35-P3、P1-L35-P4、P1-L35-P5、P1-L35-P6、P1-L35-P7、P1-L35-P8、 P1-L36-P1、P1-L36-P2、P1-L36-P3、P1-L36-P4、P1-L36-P5、P1-L36-P6、P1- L36-P7、P1-L36-P8、P2-L1-P1、P2-L1-P2、P2-L1-P3、P2-L1-P4、P2-L1-P5、 P2-L1-P6、P2-L1-P7、P2-L1-P8、P2-L2-P1、P2-L2-P2、P2-L2-P3、P2-L2-P4、<h2 style=";text-align:left;direction:ltr">P2-L2-P5, P2-L2-P6, P2-L2-P7, P2-L2-P8, P2-L3-P1, P2-L3-P2, P2-L3-P3, P2-L3-P4, P2-L3-P5, P2-L3-P6, P2-L3-P7, P2-L3-P8, P2-L4-P1, P2-L4-P2 、P2-L4-P3、P2-L4-P4、P2-L4-P5、P2-L4-P6、P2-L4-P7、P2-L4-P8、P2-L5-P 1、P2-L5-P2、P2-L5-P3、P2-L5-P4、P2-L5-P5、P2-L5-P6、P2-L5-P7、P2-L5-P 8, P2-L6-P1, P2-L6-P2, P2-L6-P3, P2-L6-P4, P2-L6-P5, P2-L6-P6, P2-L6-P7, P2-L6-P8, P2-L7-P1, P2-L7-P2, P2-L7-P3, P2-L7-P4, P2-L7-P5, P2-L7- P6, P2-L7-P7, P2-L7-P8, P2-L8-P1, P2-L8-P2, P2-L8-P3, P2-L8-P4, P2-L8-P5, P2-L8-P6, P2-L8-P7, P2-L8-P8, P2-L9-P1, P2-L9-P2, P2-L9-P3, P2-L9 -P4、P2-L9-P5、P2-L9-P6、P2-L9-P7、P2-L9-P8、P2-L10-P1、P2-L10-P2、P2 -L10-P3、P2-L10-P4、P2-L10-P5、P2-L10-P6、P2-L10-P7、P2-L10-P8、P2-L1 1-P1、P2-L11-P2、P2-L11-P3、P2-L11-P4、P2-L11-P5、P2-L11-P6、P2-L11- P7、P2-L11-P8、P2-L12-P1、P2-L12-P2、P2-L12-P3、P2-L12-P4、P2-L12-P5、 P2-L12-P6、P2-L12-P7、P2-L12-P8、P2-L13-P1、P2-L13-P2、P2-L13-P3、P2 -L13-P4、P2-L13-P5、P2-L13-P6、P2-L13-P7、P2-L13-P8、P2-L14-P1、P2-L1 4-P2、P2-L14-P3、P2-L14-P4、P2-L14-P5、P2-L14-P6、P2-L14-P7、P2-L14- P8、P2-L15-P1、P2-L15-P2、P2-L15-P3、P2-L15-P4、P2-L15-P5、P2-L15-P6、P2-L15-P7、P2-L15-P8、P2-L16-P1、P2-L16-P2、P2-L16-P3、P2-L16-P4、P2-L16-P5、P2-L16-P6、P2-L16-P7、P2-L16-P8、P2-L17-P1、P2-L17-P2、P2-L17-P3、P2-L17-P4、P2-L17-P5、P2-L17-P6、P2-L17-P7、P2-L17-P8、P2-L18-P1、P2-L18-P2、P2-L18-P3、P2-L18-P4、P2-L18-P5、P2-L18-P6、P2-L18-P7、P2-L18-P8、P2-L19-P1、P2-L19-P2、P2-L19-P3、P2-L19-P4、P2-L19-P5、P2-L19-P6、P2-L19-P7、P2-L19-P8、P2-L20-P1、P2-L20-P2、P2-L20-P3、P2-L20-P4、P2-L20-P5、P2-L20-P6、P2-L20-P7、P2-L20-P8、P2-L21-P1、P2-L21-P2、P2-L21-P3、P2-L21-P4、P2-L21-P5、P2-L21-P6、P2-L21-P7、P2-L21-P8、P2-L22-P1、P2-L22-P2、P2-L22-P3、P2-L22-P4、P2-L22-P5、P2-L22-P6、P2-L22-P7、P2-L22-P8、P2-L23-P1、P2-L23-P2、P2-L23-P3、P2-L23-P4、P2-L23-P5、P2-L23-P6、P2-L23-P7、P2-L23-P8、P2-L24-P1、P2-L24-P2、P2-L24-P3、P2-L24-P4、P2-L24-P5、P2-L24-P6、P2-L24-P7、P2-L24-P8、P2-L25-P1、P2-L25-P2、P2-L25-P3、P2-L25-P4、P2-L25-P5、P2-L25-P6、P2-L25-P7、P2-L25-P8、P2-L26-P1、P2-L26-P2、P2-L26-P3、P2-L26-P4、P2-L26-P5、P2-L26-P6、P2-L26-P7、P2-L26-P8、P2-L27-P1、P2-L27-P2、P2-L27-P3、P2-L27-P4、P2-L27-P5、P2-L27-P6、P2-L27-P7、P2-L27-P8、P2-L28-P1、P2-L28-P2、P2-L28-P3、P2-L28-P4、P2-L28-P5、P2-L28-P6、P2-L28-P7、P2-L28-P8、P2-L29-P1、P2-L29-P2、P2-L29-P3、P2-L29-P4、P2-L29-P5、P2-L29-P6、P2-L、 <h2 style=";text-align:left;direction:ltr">29-P7、P2-L29-P8、P2-L30-P1、P2-L30-P2、P2-L30-P3、P2-L30-P4、P2-L30 -P5、P2-L30-P6、P2-L30-P7、P2-L30-P8、P2-L31-P1、P2-L31-P2、P2-L31-P 3、P2-L31-P4、P2-L31-P5、P2-L31-P6、P2-L31-P7、P2-L31-P8、P2-L32-P1、 P2-L32-P2、P2-L32-P3、P2-L32-P4、P2-L32-P5、P2-L32-P6、P2-L32-P7、P2- L32-P8, P2-L33-P1, P2-L33-P2, P2-L33-P3, P2-L33-P4, P2-L33-P5, P2-L33-P6, P2-L33-P7, P2-L33-P8, P2-L34-P1, P2-L34-P2, P2-L34-P3, P2-L34-P 4、P2-L34-P5、P2-L34-P6、P2-L34-P7、P2-L34-P8、P2-L35-P1、P2-L35-P2、 P2-L35-P3、P2-L35-P4、P2-L35-P5、P2-L35-P6、P2-L35-P7、P2-L35-P8、P2- L36-P1、P2-L36-P2、P2-L36-P3、P2-L36-P4、P2-L36-P5、P2-L36-P6、P2-L3 6-P7、P2-L36-P8、P3-L1-P1、P3-L1-P2、P3-L1-P3、P3-L1-P4、P3-L1-P5、P3- L1-P6, P3-L1-P7, P3-L1-P8, P3-L2-P1, P3-L2-P2, P3-L2-P3, P3-L2-P4, P3-L2-P5, P3-L2-P6, P3-L2-P7, P3-L2-P8, P3-L3-P1, P3-L3-P2, P3-L3-P3, P3 -L3-P4、P3-L3-P5、P3-L3-P6、P3-L3-P7、P3-L3-P8、P3-L4-P1、P3-L4-P2、P 3-L4-P3、P3-L4-P4、P3-L4-P5、P3-L4-P6、P3-L4-P7、P3-L4-P8、P3-L5-P1、P 3-L5-P2, P3-L5-P3, P3-L5-P4, P3-L5-P5, P3-L5-P6, P3-L5-P7, P3-L5-P8, P3-L6-P1, P3-L6-P2, P3-L6-P3, P3-L6-P4, P3-L6-P5, P3-L6-P6, P3-L6-P7,P3-L6-P8、P3-L7-P1、P3-L7-P2、P3-L7-P3、P3-L7-P4、P3-L7-P5、P3-L7-P6、P3-L7-P7、P3-L7-P8、P3-L8-P1、P3-L8-P2、P3-L8-P3、P3-L8-P4、P3-L8-P5、P3-L8-P6、P3-L8-P7、P3-L8-P8、P3-L9-P1、P3-L9-P2、P3-L9-P3、P3-L9-P4、P3-L9-P5、P3-L9-P6、P3-L9-P7、P3-L9-P8、P3-L10-P1、P3-L10-P2、P3-L10-P3、P3-L10-P4、P3-L10-P5、P3-L10-P6、P3-L10-P7、P3-L10-P8、P3-L11-P1、P3-L11-P2、P3-L11-P3、P3-L11-P4、P3-L11-P5、P3-L11-P6、P3-L11-P7、P3-L11-P8、P3-L12-P1、P3-L12-P2、P3-L12-P3、P3-L12-P4、P3-L12-P5、P3-L12-P6、P3-L12-P7、P3-L12-P8、P3-L13-P1、P3-L13-P2、P3-L13-P3、P3-L13-P4、P3-L13-P5、P3-L13-P6、P3-L13-P7、P3-L13-P8、P3-L14-P1、P3-L14-P2、P3-L14-P3、P3-L14-P4、P3-L14-P5、P3-L14-P6、P3-L14-P7、P3-L14-P8、P3-L15-P1、P3-L15-P2、P3-L15-P3、P3-L15-P4、P3-L15-P5、P3-L15-P6、P3-L15-P7、P3-L15-P8、P3-L16-P1、P3-L16-P2、P3-L16-P3、P3-L16-P4、P3-L16-P5、P3-L16-P6、P3-L16-P7、P3-L16-P8、P3-L17-P1、P3-L17-P2、P3-L17-P3、P3-L17-P4、P3-L17-P5、P3-L17-P6、P3-L17-P7、P3-L17-P8、P3-L18-P1、P3-L18-P2、P3-L18-P3、P3-L18-P4、P3-L18-P5、P3-L18-P6、P3-L18-P7、P3-L18-P8、P3-L19-P1、P3-L19-P2、P3-L19-P3、P3-L19-P4、P3-L19-P5、P3-L19-P6、P3-L19-P7、P3-L19-P8、P3-L20-P1、P3-L20-P2、P3-L20-P3、P3 -L20-P4、P3-L20-P5、P3-L20-P6、P3-L20-P7、P3-L20-P8、P3-L21-P1、P3-L2 1-P2、P3-L21-P3、P3-L21-P4、P3-L21-P5、P3-L21-P6、P3-L21-P7、P3-L21-P8、P3-L22-P1、P3-L22-P2、P3-L22-P3、P3-L22-P4、P3-L22-P5、P3-L22-P6、 P3-L22-P7、P3-L22-P8、P3-L23-P1、P3-L23-P2、P3-L23-P3、P3-L23-P4、P3 -L23-P5、P3-L23-P6、P3-L23-P7、P3-L23-P8、P3-L24-P1、P3-L24-P2、P3-L2 4-P3、P3-L24-P4、P3-L24-P5、P3-L24-P6、P3-L24-P7、P3-L24-P8、P3-L25- P1、P3-L25-P2、P3-L25-P3、P3-L25-P4、P3-L25-P5、P3-L25-P6、P3-L25-P7、 P3-L25-P8、P3-L26-P1、P3-L26-P2、P3-L26-P3、P3-L26-P4、P3-L26-P5、P3 -L26-P6、P3-L26-P7、P3-L26-P8、P3-L27-P1、P3-L27-P2、P3-L27-P3、P3-L2 7-P4、P3-L27-P5、P3-L27-P6、P3-L27-P7、P3-L27-P8、P3-L28-P1、P3-L28-P2、P3-L28-P3、P3-L28-P4、P3-L28-P5、P3-L28-P6、P3-L28-P7、P3-L28-P8、 P3-L29-P1、P3-L29-P2、P3-L29-P3、P3-L29-P4、P3-L29-P5、P3-L29-P6、P3 -L29-P7、P3-L29-P8、P3-L30-P1、P3-L30-P2、P3-L30-P3、P3-L30-P4、P3-L3 0-P5、P3-L30-P6、P3-L30-P7、P3-L30-P8、P3-L31-P1、P3-L31-P2、P3-L31- P3、P3-L31-P4、P3-L31-P5、P3-L31-P6、P3-L31-P7、P3-L31-P8、P3-L32-P1、P3-L32-P2、P3-L32-P3、P3-L32-P4、P3-L32-P5、P3-L32-P6、P3-L32-P7、P3-L32-P8、P3-L33-P1、P3-L33-P2、P3-L33-P3、P3-L33-P4、P3-L33-P5、P3-L33-P6、P3-L33-P7、P3-L33-P8、P3-L34-P1、P3-L34-P2、P3-L34-P3、P3-L34-P4、P3-L34-P5、P3-L34-P6、P3-L34-P7、P3-L34-P8、P3-L35-P1、P3-L35-P2、P3-L35-P3、P3-L35-P4、P3-L35-P5、P3-L35-P6、P3-L35-P7、P3-L35-P8、P3-L36-P1、P3-L36-P2、P3-L36-P3、P3-L36-P4、P3-L36-P5、P3-L36-P6、P3-L36-P7、P3-L36-P8、P4-L1-P1、P4-L1-P2、P4-L1-P3、P4-L1-P4、P4-L1-P5、P4-L1-P6、P4-L1-P7、P4-L1-P8、P4-L2-P1、P4-L2-P2、P4-L2-P3、P4-L2-P4、P4-L2-P5、P4-L2-P6、P4-L2-P7、P4-L2-P8、P4-L3-P1、P4-L3-P2、P4-L3-P3、P4-L3-P4、P4-L3-P5、P4-L3-P6、P4-L3-P7、P4-L3-P8、P4-L4-P1、P4-L4-P2、P4-L4-P3、P4-L4-P4、P4-L4-P5、P4-L4-P6、P4-L4-P7、P4-L4-P8、P4-L5-P1、P4-L5-P2、P4-L5-P3、P4-L5-P4、P4-L5-P5、P4-L5-P6、P4-L5-P7、P4-L5-P8、P4-L6-P1、P4-L6-P2、P4-L6-P3、P4-L6-P4、P4-L6-P5、P4-L6-P6、P4-L6-P7、P4-L6-P8、P4-L7-P1、P4-L7-P2、P4-L7-P3、P4-L7-P4、P4-L7-P5、P4-L7-P6、P4-L7-P7、P4-L7-P8、P4-L8-P1、P4-L8-P2、P4-L8-P3、P4-L8-P4、P4-L8-P5、P4-L8-P6、P4-L8-P7、P4-L8-P8、P4-L9-P1、P4-L9-P2、P4-L9-P3、P4-L9-P4、P4-L9-P5、P4-L9-P6、P4-L9-P7、P4-L9-P8、P4-L10-P1、P4-L10-P2、P4-L10-P3、P4-L10-P4、P4-L10-P5、P4-L10-P6、P4-L10-P7、P4-L10-P8、P4-L11-P1、P4-L11-P2、P4-L11-P3、P4-L11-P4、P4-L11-P5、P4-L11-P6、P4-L11-P7、P4-L11-P8、P4-L12-P1、P4-L12-P2、P4-L12-P3、P4-L12-P4、P4-L12-P5、P4-L12-P6、P4-L12-P7、P4-L12-P8、P4-L13-P1、P4-L13-P2、P4-L13-P3、P4-L13-P4、P4-L13-P5、P4-L13-P6、P4-L13-P7、P4-L13-P8、P4-L14-P1、P4-L14-P2、P4-L14-P3、P4-L14-P4、P4-L14-P5、P4-L14-P6、P4-L14-P7、P4-L14-P8、P4-L15-P1、P4-L15-P2、P4-L15-P3、P4-L15-P4、P4-L15-P5、P4-L15-P6、P4-L15-P7、P4-L15-P8、P4-L16-P1、P4-L16-P2、P4-L16-P3、P4-L16-P4、P4-L16-P5、P4-L16-P6、P4-L16-P7、P4-L16-P8、P4-L17-P1、P4-L17-P2、P4-L17-P3、P4-L17-P4、P4-L17-P5、P4-L17-P6、P4-L17-P7、P4-L17-P8、P4-L18-P1、P4-L18-P2、P4-L18-P3、P4-L18-P4、P4-L18-P5、P4-L18-P6、P4-L18-P7、P4-L18-P8、P4-L19-P1、P4-L19-P2、P4-L19-P3、P4-L19-P4、P4-L19-P5、P4-L19-P6、P4-L19-P7、P4-L19-P8、P4-L20-P1、P4-L20-P2、P4-L20-P3、P4-L20-P4、P4-L20-P5、P4-L20-P6、P4-L20-P7、P4-L20-P8、P4-L21-P1、P4-L21-P2、P4-L21-P3、P4-L21-P4、P4-L21-P5、P4-L21-P6、P4-L21-P7、P4-L21-P8、P4-L22-P1、P4-L22-P2、P4-L22-P3、P4-L22-P4、P4-L22-P5、P4-L22-P6、P4-L22-P7、P4-L22-P8、P4-L23-P1、P4-L23-P2、P4-L23-P3、P4-L23-P4、P4-L23-P5、 、P4-L23-P6、P4-L23-P7、P4-L23-P8、P4-L24-P1、P4-L24-P2、P4-L24-P3、P4-L24-P4、P4-L24-P5、P4-L24-P6、P4-L24-P7、P4-L24-P8、P4-L25-P1、P4-L25-P2、P4-L25-P3、P4-L25-P4、P4-L25-P5、P4-L25-P6、P4-L25-P7、P4-L25-P8、P4-L26-P1、P4-L26-P2、P4-L26-P3、P4-L26-P4、P4-L26-P5、P4-L26-P6、P4-L26-P7、P4-L26-P8、P4-L27-P1、P4-L27-P2、P4-L27-P3、P4-L27-P4、P4-L27-P5、P4-L27-P6、P4-L27-P7、P4-L27-P8、P4-L28-P1、P4-L28-P2、P4-L28-P3、P4-L28-P4、P4-L28-P5、P4-L28-P6、P4-L28-P7、P4-L28-P8、P4-L29-P1、P4-L29-P2、P4-L29-P3、P4-L29-P4、P4-L29-P5、P4-L29-P6、P4-L29-P7、P4-L29-P8、P4-L30-P1、P4-L30-P2、P4-L30-P3、P4-L30-P4、P4-L30-P5、P4-L30-P6、P4-L30-P7、P4-L30-P8、P4-L31-P1、P4-L31-P2、P4-L31-P3、P4-L31-P4、P4-L31-P5、P4-L31-P6、P4-L31-P7、P4-L31-P8、P4-L32-P1、P4-L32-P2、P4-L32-P3、P4-L32-P4、P4-L32-P5、P4-L32-P6、P4-L32-P7、P4-L32-P8、P4-L33-P1、P4-L33-P2、P4-L33-P3、P4-L33-P4、P4-L33-P5、P4-L33-P6、P4-L33-P7、P4-L33-P8、P4-L34-P1、P4-L34-P2、P4-L34-P3、P4-L34-P4、P4-L34-P5、P4-L34-P6、P4-L34-P7、P4-L34-P8、P4-L35-P1、P4-L35-P2、P4-L35-P3、P4-L35-P4、P4-L35-P5、P4-L35-P6、P4-L35-P7、P4-L35-P8、P4-L36-P1、<h2 style=";text-align:left;direction:ltr">P4-L36-P2、P4-L36-P3、P4-L36-P4、P4-L36-P5、P4-L36-P6、P4-L36-P7、P4 -L36-P8、P5-L1-P1、P5-L1-P2、P5-L1-P3、P5-L1-P4、P5-L1-P5、P5-L1-P6、 P5-L1-P7, P5-L1-P8, P5-L2-P1, P5-L2-P2, P5-L2-P3, P5-L2-P4, P5-L2-P5, P5-L2-P6, P5-L2-P7, P5-L2-P8, P5-L3-P1, P5-L3-P2, P5-L3-P3, P5-L3-P4 P5-L3-P5, P5-L3-P6, P5-L3-P7, P5-L3-P8, P5-L4-P1, P5-L4-P2, P5-L4-P3, P5-L4-P4, P5-L4-P5, P5-L4-P6, P5-L4-P7, P5-L4-P8, P5-L5-P1, P5-L5-P 2、P5-L5-P3、P5-L5-P4、P5-L5-P5、P5-L5-P6、P5-L5-P7、P5-L5-P8、P5-L6-P1、P5-L6-P2、P5-L6-P3、P5-L6-P4、P5-L6-P5、P5-L6-P6、P5-L6-P7、P5-L6- P8, P5-L7-P1, P5-L7-P2, P5-L7-P3, P5-L7-P4, P5-L7-P5, P5-L7-P6, P5-L7-P7, P5-L7-P8, P5-L8-P1, P5-L8-P2, P5-L8-P3, P5-L8-P4, P5-L8-P5, P5-L 8-P6、P5-L8-P7、P5-L8-P8、P5-L9-P1、P5-L9-P2、P5-L9-P3、P5-L9-P4、P5- L9-P5、P5-L9-P6、P5-L9-P7、P5-L9-P8、P5-L10-P1、P5-L10-P2、P5-L10-P3、 P5-L10-P4、P5-L10-P5、P5-L10-P6、P5-L10-P7、P5-L10-P8、P5-L11-P1、P5 -L11-P2、P5-L11-P3、P5-L11-P4、P5-L11-P5、P5-L11-P6、P5-L11-P7、P5-L1 1-P8、P5-L12-P1、P5-L12-P2、P5-L12-P3、P5-L12-P4、P5-L12-P5、P5-L12- P6、P5-L12-P7、P5-L12-P8、P5-L13-P1、P5-L13-P2、P5-L13-P3、P5-L13-P4、P5-L13-P5、P5-L13-P6、P5-L13-P7、P5-L13-P8、P5-L14-P1、P5-L14-P2、P5-L14-P3、P5-L14-P4、P5-L14-P5、P5-L14-P6、P5-L14-P7、P5-L14-P8、P5-L1 5-P1、P5-L15-P2、P5-L15-P3、P5-L15-P4、P5-L15-P5、P5-L15-P6、P5-L15- P7、P5-L15-P8、P5-L16-P1、P5-L16-P2、P5-L16-P3、P5-L16-P4、P5-L16-P5、 P5-L16-P6、P5-L16-P7、P5-L16-P8、P5-L17-P1、P5-L17-P2、P5-L17-P3、P5-L17-P4、P5-L17-P5、P5-L17-P6、P5-L17-P7、P5-L17-P8、P5-L18-P1、P5-L1 8-P2、P5-L18-P3、P5-L18-P4、P5-L18-P5、P5-L18-P6、P5-L18-P7、P5-L18-P8、P5-L19-P1、P5-L19-P2、P5-L19-P3、P5-L19-P4、P5-L19-P5、P5-L19-P6、 P5-L19-P7、P5-L19-P8、P5-L20-P1、P5-L20-P2、P5-L20-P3、P5-L20-P4、P5 -L20-P5、P5-L20-P6、P5-L20-P7、P5-L20-P8、P5-L21-P1、P5-L21-P2、P5-L2 1-P3、P5-L21-P4、P5-L21-P5、P5-L21-P6、P5-L21-P7、P5-L21-P8、P5-L22-P1、P5-L22-P2、P5-L22-P3、P5-L22-P4、P5-L22-P5、P5-L22-P6、P5-L22-P7、 P5-L22-P8、P5-L23-P1、P5-L23-P2、P5-L23-P3、P5-L23-P4、P5-L23-P5、P5 -L23-P6、P5-L23-P7、P5-L23-P8、P5-L24-P1、P5-L24-P2、P5-L24-P3、P5-L2 4-P4、P5-L24-P5、P5-L24-P6、P5-L24-P7、P5-L24-P8、P5-L25-P1、P5-L25- P2、P5-L25-P3、P5-L25-P4、P5-L25-P5、P5-L25-P6、P5-L25-P7、P5-L25-P8、<h2 style=";text-align:left;direction:ltr">P5-L26-P1、P5-L26-P2、P5-L26-P3、P5-L26-P4、P5-L26-P5、P5-L26-P6、P5 -L26-P7、P5-L26-P8、P5-L27-P1、P5-L27-P2、P5-L27-P3、P5-L27-P4、P5-L 27-P5、P5-L27-P6、P5-L27-P7、P5-L27-P8、P5-L28-P1、P5-L28-P2、P5-L28 -P3、P5-L28-P4、P5-L28-P5、P5-L28-P6、P5-L28-P7、P5-L28-P8、P5-L29-P1 、P5-L29-P2、P5-L29-P3、P5-L29-P4、P5-L29-P5、P5-L29-P6、P5-L29-P7、P 5-L29-P8、P5-L30-P1、P5-L30-P2、P5-L30-P3、P5-L30-P4、P5-L30-P5、P5- L30-P6、P5-L30-P7、P5-L30-P8、P5-L31-P1、P5-L31-P2、P5-L31-P3、P5-L3 1-P4、P5-L31-P5、P5-L31-P6、P5-L31-P7、P5-L31-P8、P5-L32-P1、P5-L32-P 2、P5-L32-P3、P5-L32-P4、P5-L32-P5、P5-L32-P6、P5-L32-P7、P5-L32-P8、P5-L33-P1、P5-L33-P2、P5-L33-P3、P5-L33-P4、P5-L33-P5、P5-L33-P6、P5 -L33-P7,P5-L33-P8,P5-L34-P1,P5-L34-P2,P5-L34-P3,P5-L34-P4,P5-L34-P5,P5-L34-P6,P5-L34-P7,P5-L34-P8,P5-L35-P1,P5-L35-P2,P5-L35- P3, P5-L35-P4, P5-L35-P5, P5-L35-P6, P5-L35-P7, P5-L35-P8, P5-L36-P1, P5-L36-P2, P5-L36-P3, P5-L36-P4, P5-L36-P5, P5-L36-P6, P5-L36-P7, P5 -L36-P8,P6-L1-P1,P6-L1-P2,P6-L1-P3,P6-L1-P4,P6-L1-P5,P6-L1-P6,P6-L1-P7,P6-L1-P8,P6-L2-P1,P6-L2-P2,P6-L2-P3,P6-L2-P4,P6-L2-P5,<h2 style=";text-align:left;direction:ltr">P6-L2-P6, P6-L2-P7, P6-L2-P8, P6-L3-P1, P6-L3-P2, P6-L3-P3, P6-L3-P4, P6-L3-P5, P6-L3-P6, P6-L3-P7, P6-L3-P8, P6-L4-P1, P6-L4-P2, P6-L4-P3 、P6-L4-P4、P6-L4-P5、P6-L4-P6、P6-L4-P7、P6-L4-P8、P6-L5-P1、P6-L5-P 2、P6-L5-P3、P6-L5-P4、P6-L5-P5、P6-L5-P6、P6-L5-P7、P6-L5-P8、P6-L6-P 1、P6-L6-P2、P6-L6-P3、P6-L6-P4、P6-L6-P5、P6-L6-P6、P6-L6-P7、P6-L6-P8、P6-L7-P1、P6-L7-P2、P6-L7-P3、P6-L7-P4、P6-L7-P5、P6-L7-P6、P6-L7- P7、P6-L7-P8、P6-L8-P1、P6-L8-P2、P6-L8-P3、P6-L8-P4、P6-L8-P5、P6-L8 -P6、P6-L8-P7、P6-L8-P8、P6-L9-P1、P6-L9-P2、P6-L9-P3、P6-L9-P4、P6-L9 -P5、P6-L9-P6、P6-L9-P7、P6-L9-P8、P6-L10-P1、P6-L10-P2、P6-L10-P3、P 6-L10-P4、P6-L10-P5、P6-L10-P6、P6-L10-P7、P6-L10-P8、P6-L11-P1、P6-L 11-P2、P6-L11-P3、P6-L11-P4、P6-L11-P5、P6-L11-P6、P6-L11-P7、P6-L11 -P8、P6-L12-P1、P6-L12-P2、P6-L12-P3、P6-L12-P4、P6-L12-P5、P6-L12-P6 、P6-L12-P7、P6-L12-P8、P6-L13-P1、P6-L13-P2、P6-L13-P3、P6-L13-P4、P 6-L13-P5、P6-L13-P6、P6-L13-P7、P6-L13-P8、P6-L14-P1、P6-L14-P2、P6-L 14-P3、P6-L14-P4、P6-L14-P5、P6-L14-P6、P6-L14-P7、P6-L14-P8、P6-L15- P1、P6-L15-P2、P6-L15-P3、P6-L15-P4、P6-L15-P5、P6-L15-P6、P6-L15-P7、P6-L15-P8、P6-L16-P1、P6-L16-P2、P6-L16-P3、P6-L16-P4、P6-L16-P5、P6-L16-P6、P6-L16-P7、P6-L16-P8、P6-L17-P1、P6-L17-P2、P6-L17-P3、P6-L、 17-P4、P6-L17-P5、P6-L17-P6、P6-L17-P7、P6-L17-P8、P6-L18-P1、P6-L18 -P2、P6-L18-P3、P6-L18-P4、P6-L18-P5、P6-L18-P6、P6-L18-P7、P6-L18-P 8、P6-L19-P1、P6-L19-P2、P6-L19-P3、P6-L19-P4、P6-L19-P5、P6-L19-P6、P6-L19-P7、P6-L19-P8、P6-L20-P1、P6-L20-P2、P6-L20-P3、P6-L20-P4、P6- L20-P5、P6-L20-P6、P6-L20-P7、P6-L20-P8、P6-L21-P1、P6-L21-P2、P6-L21-P3、P6-L21-P4、P6-L21-P5、P6-L21-P6、P6-L21-P7、P6-L21-P8、P6-L22- P1、P6-L22-P2、P6-L22-P3、P6-L22-P4、P6-L22-P5、P6-L22-P6、P6-L22-P7 、P6-L22-P8、P6-L23-P1、P6-L23-P2、P6-L23-P3、P6-L23-P4、P6-L23-P5、P6 -L23-P6、P6-L23-P7、P6-L23-P8、P6-L24-P1、P6-L24-P2、P6-L24-P3、P6-L24-P4、P6-L24-P5、P6-L24-P6、P6-L24-P7、P6-L24-P8、P6-L25-P1、P6-L25 -P2、P6-L25-P3、P6-L25-P4、P6-L25-P5、P6-L25-P6、P6-L25-P7、P6-L25-P8、P6-L26-P1、P6-L26-P2、P6-L26-P3、P6-L26-P4、P6-L26-P5、P6-L26-P6、P 6-L26-P7、P6-L26-P8、P6-L27-P1、P6-L27-P2、P6-L27-P3、P6-L27-P4、P6- L27-P5、P6-L27-P6、P6-L27-P7、P6-L27-P8、P6-L28-P1、P6-L28-P2、P6-L2 8-P3、P6-L28-P4、P6-L28-P5、P6-L28-P6、P6-L28-P7、P6-L28-P8、P6-L29-P1、P6-L29-P2、P6-L29-P3、P6-L29-P4、P6-L29-P5、P6-L29-P6、P6-L29-P7、<h2 style=";text-align:left;direction:ltr">P6-L29-P8、P6-L30-P1、P6-L30-P2、P6-L30-P3、P6-L30-P4、P6-L30-P5、P6 -L30-P6、P6-L30-P7、P6-L30-P8、P6-L31-P1、P6-L31-P2、P6-L31-P3、P6-L 31-P4、P6-L31-P5、P6-L31-P6、P6-L31-P7、P6-L31-P8、P6-L32-P1、P6-L32 -P2、P6-L32-P3、P6-L32-P4、P6-L32-P5、P6-L32-P6、P6-L32-P7、P6-L32-P 8、P6-L33-P1、P6-L33-P2、P6-L33-P3、P6-L33-P4、P6-L33-P5、P6-L33-P6、 P6-L33-P7、P6-L33-P8、P6-L34-P1、P6-L34-P2、P6-L34-P3、P6-L34-P4、P6 -L34-P5、P6-L34-P6、P6-L34-P7、P6-L34-P8、P6-L35-P1、P6-L35-P2、P6-L 35-P3、P6-L35-P4、P6-L35-P5、P6-L35-P6、P6-L35-P7、P6-L35-P8、P6-L36 -P1、P6-L36-P2、P6-L36-P3、P6-L36-P4、P6-L36-P5、P6-L36-P6、P6-L36-P 7、P6-L36-P8、P7-L1-P1、P7-L1-P2、P7-L1-P3、P7-L1-P4、P7-L1-P5、P7-L1 -P6,P7-L1-P7,P7-L1-P8,P7-L2-P1,P7-L2-P2,P7-L2-P3,P7-L2-P4,P7-L2-P5,P7-L2-P6,P7-L2-P7,P7-L2-P8,P7-L3-P1,P7-L3-P2,P7-L3-P3,P7- L3-P4, P7-L3-P5, P7-L3-P6, P7-L3-P7, P7-L3-P8, P7-L4-P1, P7-L4-P2, P7-L4-P3, P7-L4-P4, P7-L4-P5, P7-L4-P6, P7-L4-P7, P7-L4-P8, P7-L5-P1, P 7-L5-P2, P7-L5-P3, P7-L5-P4, P7-L5-P5, P7-L5-P6, P7-L5-P7, P7-L5-P8, P7-L6-P1, P7-L6-P2, P7-L6-P3, P7-L6-P4, P7-L6-P5, P7-L6-P6, P7-L6-P7,<h2 style=";text-align:left;direction:ltr">P7-L6-P8, P7-L7-P1, P7-L7-P2, P7-L7-P3, P7-L7-P4, P7-L7-P5, P7-L7-P6, P7-L7-P7, P7-L7-P8, P7-L8-P1, P7-L8-P2, P7-L8-P3, P7-L8-P4, P7-L8-P 5、P7-L8-P6、P7-L8-P7、P7-L8-P8、P7-L9-P1、P7-L9-P2、P7-L9-P3、P7-L9- P4、P7-L9-P5、P7-L9-P6、P7-L9-P7、P7-L9-P8、P7-L10-P1、P7-L10-P2、P7- L10-P3、P7-L10-P4、P7-L10-P5、P7-L10-P6、P7-L10-P7、P7-L10-P8、P7-L1 1-P1、P7-L11-P2、P7-L11-P3、P7-L11-P4、P7-L11-P5、P7-L11-P6、P7-L11- P7、P7-L11-P8、P7-L12-P1、P7-L12-P2、P7-L12-P3、P7-L12-P4、P7-L12-P5 、P7-L12-P6、P7-L12-P7、P7-L12-P8、P7-L13-P1、P7-L13-P2、P7-L13-P3、P7 -L13-P4、P7-L13-P5、P7-L13-P6、P7-L13-P7、P7-L13-P8、P7-L14-P1、P7-L 14-P2、P7-L14-P3、P7-L14-P4、P7-L14-P5、P7-L14-P6、P7-L14-P7、P7-L14 -P8、P7-L15-P1、P7-L15-P2、P7-L15-P3、P7-L15-P4、P7-L15-P5、P7-L15-P 6、P7-L15-P7、P7-L15-P8、P7-L16-P1、P7-L16-P2、P7-L16-P3、P7-L16-P4、P 7-L16-P5、P7-L16-P6、P7-L16-P7、P7-L16-P8、P7-L17-P1、P7-L17-P2、P7- L17-P3、P7-L17-P4、P7-L17-P5、P7-L17-P6、P7-L17-P7、P7-L17-P8、P7-L1 8-P1、P7-L18-P2、P7-L18-P3、P7-L18-P4、P7-L18-P5、P7-L18-P6、P7-L18- P7、P7-L18-P8、P7-L19-P1、P7-L19-P2、P7-L19-P3、P7-L19-P4、P7-L19-P5、P7-L19-P6、P7-L19-P7、P7-L19-P8、P7-L20-P1、P7-L20-P2、P7-L20-P3、P7 -L20-P4、P7-L20-P5、P7-L20-P6、P7-L20-P7、P7-L20-P8、P7-L21-P1、P7-L2 1-P2、P7-L21-P3、P7-L21-P4、P7-L21-P5、P7-L21-P6、P7-L21-P7、P7-L21- P8、P7-L22-P1、P7-L22-P2、P7-L22-P3、P7-L22-P4、P7-L22-P5、P7-L22-P6、 P7-L22-P7、P7-L22-P8、P7-L23-P1、P7-L23-P2、P7-L23-P3、P7-L23-P4、P7 -L23-P5、P7-L23-P6、P7-L23-P7、P7-L23-P8、P7-L24-P1、P7-L24-P2、P7-L2 4-P3、P7-L24-P4、P7-L24-P5、P7-L24-P6、P7-L24-P7、P7-L24-P8、P7-L25- P1、P7-L25-P2、P7-L25-P3、P7-L25-P4、P7-L25-P5、P7-L25-P6、P7-L25-P7、 P7-L25-P8、P7-L26-P1、P7-L26-P2、P7-L26-P3、P7-L26-P4、P7-L26-P5、P7 -L26-P6、P7-L26-P7、P7-L26-P8、P7-L27-P1、P7-L27-P2、P7-L27-P3、P7-L2 7-P4、P7-L27-P5、P7-L27-P6、P7-L27-P7、P7-L27-P8、P7-L28-P1、P7-L28-P2、P7-L28-P3、P7-L28-P4、P7-L28-P5、P7-L28-P6、P7-L28-P7、P7-L28-P8、 P7-L29-P1、P7-L29-P2、P7-L29-P3、P7-L29-P4、P7-L29-P5、P7-L29-P6、P7 -L29-P7、P7-L29-P8、P7-L30-P1、P7-L30-P2、P7-L30-P3、P7-L30-P4、P7-L3 0-P5、P7-L30-P6、P7-L30-P7、P7-L30-P8、P7-L31-P1、P7-L31-P2、P7-L31- P3、P7-L31-P4、P7-L31-P5、P7-L31-P6、P7-L31-P7、P7-L31-P8、P7-L32-P1、<h2 style=";text-align:left;direction:ltr">P7-L32-P2, P7-L32-P3, P7-L32-P4, P7-L32-P5, P7-L32-P6, P7-L32-P7, P7-L32-P8, P7-L33-P1, P7-L33-P2, P7-L33-P3, P7-L33-P4, P7-L33-P5, P7-L 33-P6、P7-L33-P7、P7-L33-P8、P7-L34-P1、P7-L34-P2、P7-L34-P3、P7-L34 -P4、P7-L34-P5、P7-L34-P6、P7-L34-P7、P7-L34-P8、P7-L35-P1、P7-L35-P 2、P7-L35-P3、P7-L35-P4、P7-L35-P5、P7-L35-P6、P7-L35-P7、P7-L35-P8、 P7-L36-P1、P7-L36-P2、P7-L36-P3、P7-L36-P4、P7-L36-P5、P7-L36-P6、P7 -L36-P7,P7-L36-P8,P8-L1-P1,P8-L1-P2,P8-L1-P3,P8-L1-P4,P8-L1-P5,P8-L1-P6,P8-L1-P7,P8-L1-P8,P8-L2-P1,P8-L2-P2,P8-L2-P3,P8-L2-P 4、P8-L2-P5、P8-L2-P6、P8-L2-P7、P8-L2-P8、P8-L3-P1、P8-L3-P2、P8-L3-P3、P8-L3-P4、P8-L3-P5、P8-L3-P6、P8-L3-P7、P8-L3-P8、P8-L4-P1、P8-L4 -P2、P8-L4-P3、P8-L4-P4、P8-L4-P5、P8-L4-P6、P8-L4-P7、P8-L4-P8、P8-L 5-P1、P8-L5-P2、P8-L5-P3、P8-L5-P4、P8-L5-P5、P8-L5-P6、P8-L5-P7、P8- L5-P8, P8-L6-P1, P8-L6-P2, P8-L6-P3, P8-L6-P4, P8-L6-P5, P8-L6-P6, P8-L6-P7, P8-L6-P8, P8-L7-P1, P8-L7-P2, P8-L7-P3, P8-L7-P4, P8-L7-P5, P 8-L7-P6、P8-L7-P7、P8-L7-P8、P8-L8-P1、P8-L8-P2、P8-L8-P3、P8-L8-P4、 P8-L8-P5、P8-L8-P6、P8-L8-P7、P8-L8-P8、P8-L9-P1、P8-L9-P2、P8-L9-P3、P8-L9-P4、P8-L9-P5、P8-L9-P6、P8-L9-P7、P8-L9-P8、P8-L10-P1、P8-L10-P2、P8-L10-P3、P8-L10-P4、P8-L10-P5、P8-L10-P6、P8-L10-P7、P8-L10-P8、P8-L11-P1、P8-L11-P2、 、P8-L11-P3、P8-L11-P4、P8-L11-P5、P8-L11-P6、P8-L11-P7、P8-L11-P8、P 8-L12-P1、P8-L12-P2、P8-L12-P3、P8-L12-P4、P8-L12-P5、P8-L12-P6、P8-L 12-P7、P8-L12-P8、P8-L13-P1、P8-L13-P2、P8-L13-P3、P8-L13-P4、P8-L13-P5、P8-L13-P6、P8-L13-P7、P8-L13-P8、P8-L14-P1、P8-L14-P2、P8-L14-P3 、P8-L14-P4、P8-L14-P5、P8-L14-P6、P8-L14-P7、P8-L14-P8、P8-L15-P1、P 8-L15-P2、P8-L15-P3、P8-L15-P4、P8-L15-P5、P8-L15-P6、P8-L15-P7、P8-L 15-P8、P8-L16-P1、P8-L16-P2、P8-L16-P3、P8-L16-P4、P8-L16-P5、P8-L16 -P6、P8-L16-P7、P8-L16-P8、P8-L17-P1、P8-L17-P2、P8-L17-P3、P8-L17-P4 、P8-L17-P5、P8-L17-P6、P8-L17-P7、P8-L17-P8、P8-L18-P1、P8-L18-P2、P 8-L18-P3、P8-L18-P4、P8-L18-P5、P8-L18-P6、P8-L18-P7、P8-L18-P8、P8-L 19-P1、P8-L19-P2、P8-L19-P3、P8-L19-P4、P8-L19-P5、P8-L19-P6、P8-L19 -P7、P8-L19-P8、P8-L20-P1、P8-L20-P2、P8-L20-P3、P8-L20-P4、P8-L20-P5 、P8-L20-P6、P8-L20-P7、P8-L20-P8、P8-L21-P1、P8-L21-P2、P8-L21-P3、P 8-L21-P4、P8-L21-P5、P8-L21-P6、P8-L21-P7、P8-L21-P8、P8-L22-P1、P8-L 22-P2、P8-L22-P3、P8-L22-P4、P8-L22-P5、P8-L22-P6、P8-L22-P7、P8-L22-P8、P8-L23-P1、P8-L23-P2、P8-L23-P3、P8-L23-P4、P8-L23-P5、P8-L23-P6、P8-L23-P7、P8-L23-P8、P8-L24-P1、P8-L24-P2、P8-L24-P3、P8-L24-P4、P8 -L24-P5、P8-L24-P6、P8-L24-P7、P8-L24-P8、P8-L25-P1、P8-L25-P2、P8-L2 5-P3、P8-L25-P4、P8-L25-P5、P8-L25-P6、P8-L25-P7、P8-L25-P8、P8-L26-P1、P8-L26-P2、P8-L26-P3、P8-L26-P4、P8-L26-P5、P8-L26-P6、P8-L26-P7、 P8-L26-P8、P8-L27-P1、P8-L27-P2、P8-L27-P3、P8-L27-P4、P8-L27-P5、P8 -L27-P6、P8-L27-P7、P8-L27-P8、P8-L28-P1、P8-L28-P2、P8-L28-P3、P8-L2 8-P4、P8-L28-P5、P8-L28-P6、P8-L28-P7、P8-L28-P8、P8-L29-P1、P8-L29-P2、P8-L29-P3、P8-L29-P4、P8-L29-P5、P8-L29-P6、P8-L29-P7、P8-L29-P8、 P8-L30-P1、P8-L30-P2、P8-L30-P3、P8-L30-P4、P8-L30-P5、P8-L30-P6、P8 -L30-P7、P8-L30-P8、P8-L31-P1、P8-L31-P2、P8-L31-P3、P8-L31-P4、P8-L3 1-P5、P8-L31-P6、P8-L31-P7、P8-L31-P8、P8-L32-P1、P8-L32-P2、P8-L32- P3、P8-L32-P4、P8-L32-P5、P8-L32-P6、P8-L32-P7、P8-L32-P8、P8-L33-P1、 P8-L33-P2、P8-L33-P3、P8-L33-P4、P8-L33-P5、P8-L33-P6、P8-L33-P7、P8 -L33-P8、P8-L34-P1、P8-L34-P2、P8-L34-P3、P8-L34-P4、P8-L34-P5、P8-L3 4-P6、P8-L34-P7、P8-L34-P8、P8-L35-P1、P8-L35-P2、P8-L35-P3、P8-L35- P4、P8-L35-P5、P8-L35-P6、P8-L35-P7、P8-L35-P8、P8-L36-P1、P8-L36-P2、Selected from the group consisting of P8-L36-P3, P8-L36-P4, P8-L36-P5, P8-L36-P6, P8-L36-P7 and P8-L36-P8.

[0238] In accordance with one aspect of the present invention, provided herein is a pharmaceutical composition comprising a conjugate and a pharma- ceutically acceptable carrier.

[0239] According to certain aspects of the invention, provided herein is a method of treating a subject having or suspected of having cancer, comprising administering to the subject a therapeutically effective amount of a conjugate or pharmaceutical composition of the invention.

[0240] In some embodiments, the cancer expresses the target antigen.

[0241] In certain embodiments, the cancer is a tumor or blood cancer, optionally the cancer is breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, spleen cancer, pancreatic cancer, stomach cancer, colon cancer, or head and neck cancer.

[0242] According to certain aspects of the invention, provided herein is a method of reducing or inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate or pharmaceutical composition of the invention.

[0243] In certain embodiments, the tumor expresses a target antigen.

[0244] In certain embodiments, the tumor is breast cancer, gastric cancer, bladder cancer, brain cancer, cervical cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, melanoma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, stomach cancer, colon cancer, or head and neck cancer.

[0245] According to certain aspects of the invention, provided herein is a method of reducing or inhibiting hematological cancer in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate or pharmaceutical composition of the invention.

[0246] In certain embodiments, the hematological cancer expresses a target antigen.

[0247] In certain embodiments, the hematological cancer is chronic lymphocytic leukemia (CLL), follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), acute monocytic leukemia (AMoL), Hodgkin's lymphoma, non-Hodgkin's lymphoma, or myelodysplastic syndrome (MDS).

[0248] In certain embodiments, administration of the conjugate or pharmaceutical composition reduces or inhibits the growth of a tumor or hematological cancer by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

[0249] According to certain aspects of the invention, provided herein is a method of reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate or pharmaceutical composition of the invention.

[0250] In certain embodiments, the cancer cell population expresses a target antigen.

[0251] In certain embodiments, the cancer cell population is derived from a tumor or hematological cancer, optionally the cancer cell population is derived from breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, gastric cancer, colon cancer, or head and neck cancer.

[0252] In certain embodiments, administration of the conjugate or pharmaceutical composition reduces or slows the expansion of a cancer cell population by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

[0253] In some embodiments, the antibody drug conjugate is administered as a monotherapy. In other embodiments, the antibody drug conjugate is administered concomitantly with another therapeutic agent or radiation therapy. In some embodiments, the antibody drug conjugate is administered in an amount effective to sensitize tumor cells to one or more additional therapeutic agents and / or radiation therapy.

[0254] In certain embodiments, the method further comprises administering at least one additional therapeutic agent to a subject in need thereof.

[0255] In certain embodiments, the additional therapeutic agent is a taxane, a vinca alkaloid, a MEK inhibitor, an ERK inhibitor, a topoisomerase inhibitor, or a RAF inhibitor.

[0256] According to certain aspects of the invention, there is provided herein a use of a conjugate or pharmaceutical composition of the invention for the manufacture of a medicament for (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumor in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

[0257] According to certain aspects of the invention, there is provided herein an antibody drug conjugate or pharmaceutical composition of the invention for use in (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumor in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

[0258] Methods of producing the described ADC compounds and compositions are also disclosed. An exemplary embodiment is a method of producing an antibody drug conjugate by reacting an antibody or antigen-binding fragment with a cleavable dual linker attached or covalently linked to a pharma- ceutically active drug that is not a BH3 mimetic under conditions that allow for conjugation.

[0259] Accordingly, the present invention provides the following numbered embodiments: It will be appreciated that the features specified in each embodiment may be combined with other specified features to provide further embodiments of the present invention.

[0260] Embodiment 1. Formula (A-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’are each independently a linker; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof.

[0261] Embodiment 2.L 2’ and L 3’ or a pharma- ceutically acceptable salt thereof, according to embodiment 1, wherein each of said cleavable groups comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0262] Embodiment 2a.L 2’ and L 3’ or a pharma- ceutically acceptable salt thereof, according to embodiment 2, wherein each of

[0263] Embodiment 2b.L 2’ and L 3’ or a pharma- ceutically acceptable salt thereof, according to embodiment 1, wherein each of comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a sugar (e.g., glucuronamide) group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0264] Embodiment 3. Formula (B-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., Rw is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic moiety; V 1 and V 2 each independently represent: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group, or iii) comprise a self-immolative group and an enzymatic cleavage element; and D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof. A compound according to embodiment 1, embodiment 2 or embodiment 2a or a pharma- ceutically acceptable salt thereof.

[0265] Embodiment 3aa.V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group, a compound according to embodiment 3, or a pharma- ceutically acceptable salt thereof.

[0266] Embodiment 3a. A compound according to embodiment 3 or embodiment 3aa, or a pharma- ceutically acceptable salt thereof, wherein W is N or CH.

[0267] Embodiment 3b.E 1 and E 2 or a pharma- ceutically acceptable salt thereof, according to embodiment 3, embodiment 3aa or embodiment 3a, wherein each is an enzymatic cleavage element;

[0268] Embodiment 3c.V 1 and V 2 is each independently a self-immolative group; or a pharma- ceutically acceptable salt thereof.

[0269] Embodiment 4. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker is -O-CH 2 -, -NH-CH 2 or (iv) V, which contains a self-immolative group comprising -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium; or (iv) V, 1 and / or V 2 each independently comprises a group that comprises para-aminobenzyl-phosphate or para-aminobenzyl-pyrophosphate, or a pharma- ceutically acceptable salt thereof, according to embodiment 3, embodiment 3aa, embodiment 3a, embodiment 3b, or embodiment 3c.

[0270] Embodiment 4a. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker is -O-CH 2 -, -NH-CH 2The compound according to embodiment 4 or a pharma- ceutically acceptable salt thereof, comprising a self-immolative group comprising -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

[0271] Embodiment 5. Formula (C-1): [ka] (In the formula, R 1 is a linking group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A 1 and A 2 are each independently a bond, -OC(=O)-*, [ka] -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(Ra ) 2 C(R a ) 2 N(CH 3 )C(=O)-*, Each R a are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, and optionally D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3 are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. or a pharma- ceutically acceptable salt thereof. A compound according to embodiment 3, embodiment 4 or embodiment 4a or a pharma- ceutically acceptable salt thereof.

[0272] Embodiment 5a. A compound according to embodiment 5, or a pharma- ceutically acceptable salt thereof, wherein W is N or CH.

[0273] Embodiment 5b.R 2 and R 3 A compound according to embodiment 5 or embodiment 5a, or a pharma- ceutically acceptable salt thereof, wherein each is a hydrophilic group.

[0274] Embodiment 6. Formula (D1-1), (D2-1) or (D3-1): [ka] or a pharma- ceutically acceptable salt thereof. A compound according to embodiment 5, embodiment 5a, or embodiment 5b, or a pharma- ceutically acceptable salt thereof.

[0275] Embodiment 7. Regarding formula (D1-1), R 2 and R 3 are each independently a hydrophilic group, and in formula (D2-1), R 2 and R 3 are each independently an enzyme cleavage element; and with respect to formula (D3-1), R 2 is a hydrophilic group, and R 3 is an enzymatic cleavage element; or a pharma- ceutically acceptable salt thereof.

[0276] Embodiment 8.R 1 teeth, [ka] -ONH 2 , -NH 2 , [ka] , -N 3 , [ka] -SH, -SR 11 , -SSR 12 , -S(=O) 2 (CH=CH 2 ), -(CH 2 ) 2 S(=O) 2 (CH=CH 2 ), -NHS(=O) 2 (CH=CH 2 ), -NR 11 C(=O)CH 2 Br, e.g. -NHC(=O)CH 2 Br, -NR 11 C(=O)CH 2I, e.g. -NHC(=O)CH 2 I, [ka] -C(O)NHNH 2 , [ka] (In the formula, Each R 11 are independently H and C 1 ~C 6 alkyl; Each R 12 is 2-pyridyl or 4-pyridyl; Each R 13 are independently H, C 1 ~C 6 selected from alkyl, F, Cl and -OH; Each R 14 are independently H, C 1 ~C 6 Alkyl, F, Cl, -NH 2 , -OCH 3 , -OCH 2 CH 3 , -N(CH 3 ) 2 , -CN, -NO 2 and -OH; and Each R 15 are independently H, C 1 ~C 6 Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH 1 ~C 4 Alkoxy and -C(=O)OH substituted C 1 ~C 4 alkyl) or a pharma- ceutically acceptable salt thereof, according to any one of the preceding embodiments, selected from the group consisting of:

[0277] Embodiment 9.R 1 teeth, [ka] -ONH 2 , [ka] NHC(=O)CH 2 Br and -NHC(=O)CH 2 A compound according to any one of the preceding embodiments selected from the group consisting of I, or a pharma- ceutically acceptable salt thereof.

[0278] Embodiment 9a.R 1 teeth, [ka] -ONH 2 , [ka] or a pharma- ceutically acceptable salt thereof, according to any one of the preceding embodiments, selected from the group consisting of:

[0279] Embodiment 10.R 1 teeth, [ka] or a pharma- ceutically acceptable salt thereof, according to any one of the preceding embodiments.

[0280] Embodiment 11.(1)L 1 teeth, [ka] or *-CH(OH)CH(OH)CH(OH)CH(OH)-** (wherein each n is an integer from 1 to 12). Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (2)L 1 teeth, [ka] and n is an integer from 1 to 12, or n is 1, or n is 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (3) L 1 teeth, [ka] and n is an integer from 1 to 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (4) L 1 teeth, [ka] Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; or (5) L 1 is *-C(=O)(CH 2 ) m O(CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)(CH 2 ) m -**;*-C(=O)NH((CH 2 ) m O) t (CH2 ) n -**;*-C(=O)O(CH 2 ) m SSC(R L1 ) 2 (CH 2 ) m C(=O)NR L1 (CH 2 ) m NR L1 C(=O)(CH 2 ) m -**;*-C(=O)O(CH 2 ) m C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) n C(=O)-**;*-C(=O)(CH 2 ) m X 1 (CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n X 1 (CH 2 ) n-**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m C(R L1 ) 2 -** or *-C(=O)(CH 2 ) m C(=O)NH(CH 2 ) m -** (In the formula, L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicating a direct or indirect (e.g., direct) point of attachment to; X 1 teeth, [ka] and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R L1 are independently H and C 1 ~C 6 alkyl) or a pharma- ceutically acceptable salt thereof.

[0281] Embodiment 12.L 1 teeth, [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8), and L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 (Indicating a direct or indirect point of attachment to or a pharma- ceutically acceptable salt thereof.

[0282] Embodiment 12 A compound according to embodiment 12, wherein a.n is an integer from 4 to 8, or a pharma- ceutically acceptable salt thereof.

[0283] Embodiment 12b.n is a compound according to embodiment 12a, which is 4 or 8, or a pharma- ceutically acceptable salt thereof.

[0284] Embodiment 13.L 1 is the formula [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L 1 The * in indicates the direct point of attachment to W, and L 1 The ** is R 1 (Indicates the direct attachment point to or a pharma- ceutically acceptable salt thereof.

[0285] Embodiment 13: A compound according to embodiment 13, wherein a.n is an integer from 4 to 8, or a pharma- ceutically acceptable salt thereof.

[0286] Embodiment 13b.n is a compound according to embodiment 13a, which is 4 or 8, or a pharma- ceutically acceptable salt thereof.

[0287] Embodiment 13c. A compound according to embodiment 13, embodiment 13a or embodiment 13b, wherein x is an integer from 0 to 2, or a pharma- ceutically acceptable salt thereof.

[0288] Embodiment 13d. A compound according to embodiment 13c, wherein x is 0 or 2, or a pharma- ceutically acceptable salt thereof.

[0289]

[0043] Embodiment 13e.z is an integer from 0 to 2, a compound according to embodiment 13, embodiment 13a, embodiment 13b, embodiment 13c or embodiment 13d, or a pharma- ceutically acceptable salt thereof.

[0290] Embodiment 13f. A compound according to embodiment 13e, wherein z is 0 or 2, or a pharma- ceutically acceptable salt thereof.

[0291] Embodiment 14.L 1 teeth, [ka] or a pharma- ceutically acceptable salt thereof, according to any one of the preceding embodiments, selected from the group consisting of:

[0292] Embodiment 15.L 2 and L 3 are each independently [ka] (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 (## indicates the direct or indirect point of attachment to W) or a pharma- ceutically acceptable salt thereof.

[0293] Embodiment 16.L 2 and L 3 are each independently [ka] [ka] (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R L23 is hydrogen or C 1 ~C 6 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; If W is N, then L2 and L 3 (provided that it is not (L2c), (L2d), (L2f) or (L2k)) or a pharma- ceutically acceptable salt thereof according to any one of embodiments 3 to 15, wherein the linking spacer is selected from the group consisting of:

[0294] Embodiment 17.L 2 and L 3 are each independently [ka] [ka] (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R L23 is hydrogen or C 1 ~C 3 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; if W is N, then L 2 and L 3 (provided that it is not (L2FF), (L2MM), (L2NN), (L2OO) or (L2PP)) or a pharma- ceutically acceptable salt thereof, according to embodiment 16, wherein the linking spacer is selected from the group consisting of:

[0295] Embodiment 18.L 2 and L3 is, independently, [ka] [ka] (In the formula, L 2 Or L 3 # is E 1 Or E 2 indicates the direct attachment point to L 2 Or L 3 ## indicates the direct attachment point to W; R L is hydrogen or -C(O)-R H and R H teeth, [ka] and d is an integer from 20 to 30 (e.g., 25). or a pharma- ceutically acceptable salt thereof according to any one of embodiments 3 to 17, wherein the linking spacer is selected from the group consisting of:

[0296] Embodiment 18a.d is a compound according to embodiment 18, which is 25, or a pharma- ceutically acceptable salt thereof.

[0297] Embodiment 19. A compound according to any one of embodiments 5-18a, or a pharma- ceutically acceptable salt thereof, wherein each peptide group independently comprises 1-4, 1-3, or 1-2 amino acid residues.

[0298] Embodiment 19a. A compound according to embodiment 19, or a pharma- ceutically acceptable salt thereof, wherein each peptide group independently comprises two amino acid residues.

[0299] Embodiment 20. A compound according to embodiment 19 or embodiment 19a, or a pharma- ceutically acceptable salt thereof, wherein each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr) and β-alanine (β-Ala).

[0300] Embodiment 21. A compound or a pharma- ceutically acceptable salt according to any one of embodiments 5 to 19 and 20, wherein each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly and Sulfo-Ala-Val-Ala.

[0301] Embodiment 22.E 1 and / or E 2 are each independently [ka] (Wherein, E1-1 or E1-2 is V in formula (B) 1 Or V 2 or the direct point of attachment to the -NH- group in formulas (C) and (D); and E1-1 or E1-2 ^^ respectively represent L 2 Or L 3 indicates the direct point of attachment to 1 and E 2 are peptide groups independently selected from (E1-1) and (E1-2). The compound or pharma- ceutically acceptable salt according to any one of embodiments 3-19a, wherein the peptide group is selected from the group consisting of:

[0302] Embodiment 22a.E 1 and E2 is a peptide group independently selected from (E1-1) and (E1-2), or a pharma- ceutically acceptable salt thereof.

[0303] Embodiment 23.E 1 and / or E 2 are each independently [ka] (In the formula, R E is a hydrophilic group R H is) or a pharma- ceutically acceptable salt thereof according to any one of embodiments 3-19a, wherein R is a peptide group represented by:

[0304] The group R in embodiment 24 (E1-3) H teeth, [ka] (wherein e is an integer of 20 to 30 (e.g., 25)) 24. The compound according to embodiment 23, which is:

[0305] Embodiment 24a.e is a compound according to embodiment 24, which is 25, or a pharma- ceutically acceptable salt thereof.

[0306] Embodiment 25.E 1 and E 2 are respectively [ka] 23. The compound according to embodiment 22, or a pharma- ceutically acceptable salt thereof, wherein:

[0307] Embodiment 26.A 1 and A 2 are independently a bond and -OC(=O)-* (wherein * represents D 1 Or D 2or a pharma- ceutically acceptable salt according to any one of embodiments 5 to 25, selected from:

[0308] Embodiment 26a.A 1 and A 2 are independent, combined, [ka] and -OC(=O)-* (wherein * represents D 1 Or D 2 or a pharma- ceutically acceptable salt according to any one of embodiments 5 to 25, selected from:

[0309] Embodiment 27.A 1 and A 2 and R are each a bond.

[0310] Embodiment 27a.A 1 and A 2 or a pharma- ceutically acceptable salt thereof according to embodiment 26, wherein:

[0311] Embodiment 27b.A 1 and A 2 One of the groups is OC(=O)-* and A 1 and A 2 The compound or pharma- ceutically acceptable salt according to embodiment 26, wherein the other is a bond.

[0312] Embodiment 27c.A 1 and A 2 is independently a bond, or [ka] (In the formula, * represents D 1 Or D 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt according to embodiment 26a, which is

[0313] Embodiment 27d.A1 and A 2 On the other hand, [ka] And A 1 and A 2 The compound or pharma- ceutically acceptable salt according to embodiment 27c, wherein the other is a bond.

[0314] Embodiment 27e.A 1 and A 2 Both [ka] or a pharma- ceutically acceptable salt according to embodiment 27c, wherein:

[0315] Embodiment 27f.A 1 and A 2 On the other hand, [ka] And A 1 and A 2 and the other is OC(=O)-*.

[0316] Embodiment 27g.A 1 and A 2 is -OC(=O)-*; (ii)A 1 and A 2 teeth, [ka] Is it; (iii)A 1 is -OC(=O)-*, and A 2 is a bond or (iv)A 1 is -OC(=O)-*, and A 2 teeth, [ka] Is it; (v)A 1 is a bond, and A 2 teeth, [ka] or (vi) A 1 is a bond, and A 2 is -OC(=O)-* (wherein * is D 1 Or D 2 or a pharma- ceutically acceptable salt according to embodiment 26a, wherein:

[0317] Embodiment 28.i)L 4 and L 5 are each independently [ka] (In the formula, Z is -O-, -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR L45 -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45 -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C6 Alkyl and C 3 ~C 8 cycloalkyl); and X is a bond, triazolyl or -CH 2 -triazolyl-, X is R 2 or R 3 (connected to or a spacer moiety having the structure (ii) L 4 and L 5 is, independently, [ka] (In the formula, Z is -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR b -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH-, -CH 2 NR L45 C(=O)NR L45 -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is -CH 2 -Triazolyl-C1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n where each n is independently 1, 2, or 3; X is R 2 or R 3 (connected to or a pharma- ceutically acceptable salt thereof according to any one of embodiments 5 to 27b, wherein the spacer moiety has the structure:

[0318] Embodiment 29. Z is -O-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH- or -CH 2 X is a bond, triazolyl or -CH 2 -triazolyl-; and R L45 is, at each occurrence, independently H or C 1 ~C 329. The compound according to embodiment 28, or a pharma- ceutically acceptable salt thereof, wherein R is alkyl.

[0319] Embodiment 30.L 4 and L 5 are each independently [ka] (In the formula, L 4 Or L 5 @ indicates the direct point of attachment to the phenyl group, and L 4 Or L 5 @@ is R 2 or R 3 (Indicates the direct attachment point to 30. The compound or pharma- ceutically acceptable salt according to any one of embodiments 5 to 29, wherein the spacer moiety is selected from the group consisting of:

[0320] Embodiment 31.R 2 and R 3 Each of the hydrophilic groups represented by the formula (I) is independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 [ka] C replaced with 2 ~C 6 Alkyl or -OC(=O)NHS(O) 2 NHCH 2 CH 2 OCH 3 , -NHC(=O)C 1 ~C 4 Alkylene-P(O)(OCH 2 CH 3 ) 2 and C substituted with 1 to 2 substituents independently selected from -COOH groups. 2 ~C 6 The compound according to any one of embodiments 5 to 30, or a pharma- ceutically acceptable salt thereof, comprising alkyl.

[0321] Embodiment 32.R 2or / and R 3 are each independently [ka] (wherein n is an integer of 1 to 6). [ka] or a pharma- ceutically acceptable salt thereof, according to any one of embodiments 5 to 30, selected from the group consisting of:

[0322] Embodiment 33.R 2 or / and R 3 is, independently, (i) the following part: [ka] (In the formula, f is an integer from 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) Polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by The compound or pharma- ceutically acceptable salt according to any one of embodiments 5 to 30, comprising:

[0323] Embodiment 33a.R 2 or R 3 Each hydrophilic group represented by the formula: (i) the following part: [ka] (wherein f is an integer of 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) or polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by The compound or pharma- ceutically acceptable salt according to any one of embodiments 5 to 30, comprising:

[0324] Embodiment 34.R 2 or / and R 3 are each independently [ka] (In the formula, g and h are independently an integer of 20 to 30 (e.g., 23 or 24). A compound or a pharma- ceutically acceptable salt according to any one of embodiments 5 to 30, selected from the group consisting of:

[0325] Embodiment 35.R 2 or / and R 3 teeth, [ka] or a pharma- ceutically acceptable salt thereof.

[0326] Embodiment 35a.R 2 and R 3 are each independently represented by the formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or a pharma- ceutically acceptable salt thereof.

[0327] Embodiment 36.D 1 and D. 2 is the same.

[0328] Embodiment 37.D 1 and D. 2 is different, a compound or a pharma- ceutically acceptable salt according to any one of embodiments 1 to 35a.

[0329] Embodiment 38.D 1 and D. 2 or a pharma- ceutically acceptable salt thereof according to any one of the preceding embodiments, wherein each of the following is independently selected from a cytotoxic drug, a cytostatic agent, and an immunosuppressant.

[0330] Embodiment 39.D 1 and D. 2 or a pharmaceutically acceptable salt thereof according to any one of embodiments 1-37, wherein each of the formulas (I) and (II) is independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

[0331] Embodiment 39a.D 1 and D. 2 are each independently [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-37.

[0332] Embodiment 39b.i)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iv) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; v)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; viii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; x)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xi) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvi)D1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xli)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; il)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; l)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; li)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxiii)D 1 teeth, [ka] and D 2 teeth, [ka] or lxiv)D 1 teeth, [ka] and D 2 teeth, [ka] A compound or a pharma- ceutically acceptable salt according to embodiment 39a, wherein: and * indicates the point of attachment to the rest of the molecule.

[0333] Embodiment 39c.i)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iv) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; v)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; viii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ix) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; x)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiv)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xl)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xli)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] Is it; xlii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; l)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; li)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxiii)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] or lxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] and * indicates the point of attachment to the rest of the molecule.

[0334] Embodiment 40.D 1 and / or D. 2 The compound or pharma- ceutically acceptable salt according to any one of embodiments 1-37, wherein is an auristatin.

[0335] Embodiment 40a.D 1 and D. 2 or a pharma- ceutically acceptable salt thereof according to embodiment 40, wherein both of

[0336] Embodiment 40b.D 1 and / or D. 2 The compound or pharma- ceutically acceptable salt according to any one of embodiments 1-37, wherein is a topoisomerase 1 inhibitor.

[0337] Embodiment 40c.D 1 and D. 2 or a pharma- ceutically acceptable salt thereof according to embodiment 40b, wherein both of are topoisomerase 1 inhibitors.

[0338] Embodiment 40d.D 1 and D. 2 is an auristatin and D 1 and D. 2The compound or pharma- ceutically acceptable salt according to any one of embodiments 1 to 37, wherein the other is a topoisomerase 1 inhibitor.

[0339] Embodiment 40e.D 1 is an auristatin, and D 2 The compound or pharma- ceutically acceptable salt according to embodiment 40d, wherein is a topoisomerase 1 inhibitor.

[0340] Embodiment 40f.D 1 is a topoisomerase 1 inhibitor, and D 2 The compound or pharma- ceutically acceptable salt according to embodiment 40d, wherein is an auristatin.

[0341] Embodiment 41.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof according to any one of the preceding embodiments, selected from the group consisting of:

[0342] Embodiment 41a.D 1 and D. 2 is, independently, [ka] 42. A compound according to embodiment 41, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

[0343] Embodiment 41b.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0344] Embodiment 41c.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0345] Embodiment 42.D 1 and D. 2 or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-37, wherein each of the is independently selected from an antitubulin agent, a tubulin inhibitor, a DNA minor groove binder, a DNA replication inhibitor, an alkylating agent, an antibiotic, an antifolate, an antimetabolite, a chemotherapeutic sensitizer, a topoisomerase inhibitor, and / or a vinca alkaloid.

[0346] Embodiment 43.D 1 and D. 2 are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; 1 Also D 238. The compound or pharma- ceutically acceptable salt according to any one of embodiments 1-37, provided that said compound or pharma- ceutically acceptable salt is not a BH3 mimetic.

[0347] EMBODIMENT 44. [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of the preceding embodiments, selected from the group consisting of:

[0348] Embodiment 44a. [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of the preceding embodiments, selected from the group consisting of:

[0349] EMBODIMENT 45. [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of the preceding embodiments, selected from the group consisting of:

[0350] Embodiment 45a. [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-45, selected from the group consisting of:

[0351] Embodiment 45b. [ka] [ka] or a pharma- ceutically acceptable salt thereof. A compound according to embodiment 45a, selected from the group consisting of:

[0352] Embodiment 45c. [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-43, wherein the compound or a pharma- ceutically acceptable salt thereof is selected from:

[0353] Embodiment 45d. [ka] [ka] or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-43, wherein the compound or a pharma- ceutically acceptable salt thereof is selected from:

[0354] Embodiment 45e. [ka] or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-43, wherein the compound or a pharma- ceutically acceptable salt thereof is selected from:

[0355] Embodiment 45f. [ka] or a pharma- ceutically acceptable salt thereof according to any one of embodiments 1-43, wherein the compound or a pharma- ceutically acceptable salt thereof is selected from:

[0356] Embodiment 46. A conjugate comprising an antibody or antigen-binding fragment thereof covalently linked to two pharmaceutically active drugs via a dual linker, the dual linker having one point of attachment attached to the antibody and two points of attachment to the two pharmaceutically active drugs, provided that neither of the pharmaceutically active drugs is a BH3 mimetic.

[0357] Embodiment 46a. A conjugate according to embodiment 46, wherein the two pharma- ceutical active drugs are the same or different.

[0358] Embodiment 46b. A conjugate according to embodiment 46 or 46a, wherein the pharma- ceutically active drug is selected from cytotoxic drugs, cytostatic drugs and immunosuppressants.

[0359] Embodiment 46c. A conjugate according to any one of embodiments 46-46b, wherein the pharma- ceutically active drug is selected from auristatins, camptothecins, duocarmycins, etoposide, maytansine, maytansinoids, taxanes, benzodiazepines or benzodiazepine-containing drugs (e.g., pyrrolo[1,4]-benzodiazepines (PBDs), indolinobenzodiazepines and oxazolidinobenzodiazepines) and vinca alkaloids.

[0360] Embodiment 46d. A conjugate according to embodiment 46c, wherein the pharma- ceutically active drug is an auristatin.

[0361] Embodiment 46e. A conjugate according to embodiment 46 or 46a, wherein the pharma- ceutically active drug is selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapy sensitizers, topoisomerase inhibitors and / or vinca alkaloids.

[0362] Embodiment 46f. A conjugate according to embodiment 46 or 46a, wherein the pharma- ceutically active drug is selected from Eg5 inhibitors, V-ATPase inhibitors, HSP90 inhibitors, IAP inhibitors, mTor inhibitors, microtubule stabilizing agents, microtubule destabilizing agents, auristatins, dolastatins, maytansinoids, MetAP (methionine aminopeptidase), inhibitors of nuclear export of protein CRM1, DPPIV inhibitors, inhibitors of phosphoryl transfer reactions in mitochondria, protein synthesis inhibitors, kinase inhibitors, CDK2 inhibitors, CDK9 inhibitors, proteasome inhibitors, kinesin inhibitors, HDAC inhibitors, DNA damaging agents, DNA alkylating agents, DNA interfering agents, DNA minor groove binders, RNA polymerase inhibitors, amanitin, spliceosome inhibitors, topoisomerase inhibitors, DHFR inhibitors or proapoptotic agents.

[0363] Embodiment 46g. A conjugate according to embodiment 46 or 46a, wherein the pharma- ceutically active drug is selected from a topoisomerase 1 inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or addition salt with a pharma- ceutically acceptable acid or base.

[0364] Embodiment 46h. A conjugate according to embodiment 46g, wherein the pharma- ceutically active drug, topoisomerase 1 inhibitor, is selected from topotecan, exatecan, deruxtecan and SN-38.

[0365] Embodiment 46i. A conjugate according to embodiment 46 or 46a, wherein the pharma- ceutically active drug is selected from a mitotic inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or addition salt with a pharma- ceutically acceptable acid or base.

[0366] Embodiment 46j. A conjugate according to embodiment 46i, wherein the mitotic inhibitor is monomethyl auristatin E (MMAE) or a taxane.

[0367] Embodiment 46k. A conjugate according to embodiment 46j, wherein the taxane is selected from docetaxel, paclitaxel, or cabazitaxel.

[0368] Embodiment 46l. A conjugate according to embodiment 46, wherein the conjugate comprises a compound according to any one of embodiments 1 to 45f or a pharma- ceutically acceptable salt thereof.

[0369] Embodiment 46m. Formula (A-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is a branching moiety; L 2’ and L 3’ are each independently a linker; D 1 and D. 2 are each independently a pharma- ceutically active drug, but D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. Conjugate of.

[0370] Embodiment 47.L 2’ and L 3’ each of which comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0371] Embodiment 47a.L 2’ and L 3’ Each of the above comprises a peptide group and a self-immolative group.

[0372] Embodiment 47b.L 2’ and L 3’ each of which comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a sugar (e.g., glucuronamide) group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

[0373] Embodiment 48. Formula (B-2): [ka] (In the formula, Ab is an antibody or fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently an enzyme cleavage element or a hydrophilic moiety (e.g., E 1 and E 2 are enzyme cleavage elements, respectively); V 1 and V 2 may independently comprise: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group, or iii) comprises a self-immolative group and an enzymatic cleavage element; D 1 and D. 2 are each independently a pharma- ceutically active drug, but D 1 Also D 2 is not a BH3 mimetic; and a is an integer from 1 to 16. The conjugate according to embodiment 46m, embodiment 47 or embodiment 47a.

[0374] Embodiment 48aa.V 1 and V 2 are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V 1 and V 2 are each independently a self-immolative group,

[0375] Embodiment 48a. A conjugate according to embodiment 48 or embodiment 48aa, wherein W is N or CH.

[0376] Embodiment 48b.E 1 and E 2 A conjugate according to embodiment 48, embodiment 48aa or embodiment 48a, wherein each of

[0377] Embodiment 48c.V 1 and V 2 A conjugate according to embodiment 48, embodiment 48aa, embodiment 48a or embodiment 48b, wherein each is independently a self-immolative group.

[0378] Embodiment 49. A conjugate according to any one of embodiments 46m to 48c, wherein a is an integer from 1 to 8, 1 to 6, 1 to 4, or a is 1 or 2.

[0379] Embodiment 49a.a is a conjugate according to embodiments 46m to 49, as determined by liquid chromatography-mass spectrometry (LC-MS).

[0380] Embodiment 50. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker is -CH 2 -O-, -NH-CH 2A conjugate according to any one of embodiments 46m to 49, comprising a self-immolative group comprising -, -C(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

[0381] Embodiment 50a. A conjugate according to embodiment 50, wherein W is N or CH.

[0382] Embodiment 50b.R 2 and R 3 A conjugate according to embodiment 50 or embodiment 50a, wherein each is a hydrophilic group.

[0383] Embodiment 51. Formula (C-2): [ka] (In the formula, Ab is an antibody or an antigen-binding fragment thereof; R 100 is a coupling group; L 1 is a bridging spacer; W is N or CR w and R w is H or C 1 ~C 6 is alkyl (e.g., R w is H); L 2 and L 3 are each independently a linking spacer; E 1 and E 2 are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A1 and A 2 are each independently a bond, -OC(=O)-*, [ka] -OC(=O)N(CH 3 )CH 2 CH 2 N(CH 3 )C(=O)-* or -OC(=O)N(CH 3 )C(R a ) 2 C(R a ) 2 N(CH 3 )C(=O)-*, Each R a are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl; A 1 Or A 2 * is D 1 Or D 2 Indicates the attachment point to; D 1 and D. 2 are each independently a pharma- ceutically active drug, but D 1 Also D 2 is not a BH3 mimetic; L 4 and L 5 are each independently a spacer moiety; R 2 and R 3 are each independently a hydrophilic group or an enzyme cleavage element (e.g., R 2 and R 3 are hydrophilic groups); and m and n are each independently 0 or 1. A conjugate according to any one of embodiments 46m to 50b.

[0384] Embodiment 52. Formula (D1-2), (D2-2) or (D3-2): [ka] The conjugate according to embodiment 51.

[0385] Embodiment 53. With respect to formula (D1-2), R 2 and R 3 are each independently a hydrophilic group, and in formula (D2-2), R 2 and R 3 are each independently an enzyme cleavage element; and with respect to formula (D3-2), R 2 is a hydrophilic group, and R 3 is an enzymatic cleavage element.

[0386] Embodiment 54.R 100 teeth, [ka] [ka] [ka] [ka] [ka] [ka] Disulfides (In the formula, R 16 , H, C 1 ~C 4 alkyl, phenyl, pyrimidine or pyridine; R 18 , H, C 1 ~C 6 C substituted with alkyl, phenyl or 1 to 3 -OH groups 1 ~C 4 is alkyl; Each R 15 are independently H, C 1 ~C 6Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH 1 ~C 4 Alkoxy and -C(=O)OH substituted C 1 ~C 4 alkyl; R 17 is independently selected from H, phenyl and pyridine; q is 0, 1, 2 or 3; R 19 is H or methyl; and R 20 -H, -CH 3 or phenyl) A conjugate according to any one of embodiments 46m to 53, selected from the group consisting of:

[0387] Embodiment 55.R 100 teeth, [ka] (In the formula, R 100 (*** indicates the attachment point to Ab) A conjugate according to any one of embodiments 46m to 54, selected from the group consisting of:

[0388] Embodiment 56.R 100 teeth, [ka] (In the formula, R 100 (*** indicates the attachment point to Ab) 56. The conjugate according to embodiment 55, wherein

[0389] Embodiment 57.(1)L 1 teeth, [ka] or *-CH(OH)CH(OH)CH(OH)CH(OH)-** (wherein each n is an integer from 1 to 12). Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (2)L 1 teeth, [ka] and n is an integer from 1 to 12, or n is 1, or n is 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (3) L 1 teeth, [ka] and n is an integer from 1 to 12; L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; (4) L 1 teeth, [ka] Including L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicates a direct or indirect (e.g., direct) point of attachment to; or (5) L 1 is *-C(=O)(CH 2 ) m O(CH 2 ) m -**;*-C(=O)((CH 2 )m O) t (CH 2 ) n -**;*-C(=O)(CH 2 ) m -**;*-C(=O)NH((CH 2 ) m O) t (CH 2 ) n -**;*-C(=O)O(CH 2 ) m SSC(R L1 ) 2 (CH 2 ) m C(=O)NR L1 (CH 2 ) m NR L1 C(=O)(CH 2 ) m -**;*-C(=O)O(CH 2 ) m C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m NH(CH 2 ) n C(=O)-**;*-C(=O)(CH 2 ) m X 1 (CH 2 ) m -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) nNHC(=O)(CH 2 ) n -**;*-C(=O)(CH 2 ) m NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n NHC(=O)(CH 2 ) n X 1 (CH 2 ) n -**;*-C(=O)((CH 2 ) m O) t (CH 2 ) n C(=O)NH(CH 2 ) m -**;*-C(=O)(CH 2 ) m C(R L1 ) 2 -** or *-C(=O)(CH 2 ) m C(=O)NH(CH 2 ) m -** (In the formula, L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 indicating a direct or indirect (e.g., direct) point of attachment to; X 1 teeth, [ka] and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R L1 are independently H and C 1 ~C 6 alkyl) The conjugate according to any one of embodiments 46m to 56, wherein the bridging spacer comprises:

[0390] Embodiment 58.L 1 teeth, [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8), and L 1 indicates a direct or indirect (e.g., direct) point of attachment to W, and L 1 The ** is R 1 (Indicating a direct or indirect point of attachment to A conjugate according to any one of embodiments 46m to 57, comprising a moiety represented by:

[0391] A conjugate according to embodiment 58, wherein n is an integer from 4 to 8.

[0392] Embodiment 58b.n is a conjugate according to embodiment 58a, wherein n is 4 or 8.

[0393] Embodiment 59.L 1 is the formula [ka] (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L 1 The * in indicates the direct point of attachment to W, and L 1 The ** is R 1 (Indicates the direct attachment point to A conjugate according to any one of embodiments 46m to 58b, represented by:

[0394] A conjugate according to embodiment 59, wherein n is an integer from 4 to 8.

[0395] Embodiment 59b.n is a conjugate according to embodiment 59a, wherein n is 4 or 8.

[0396] Embodiment 59c. A conjugate according to embodiment 59, embodiment 59a or embodiment 59b, wherein x is an integer from 0 to 2.

[0397] Embodiment 59d. A conjugate according to embodiment 59c, wherein x is 0 or 2.

[0398] Embodiment 59e.z is a conjugate according to embodiment 59, embodiment 59a, embodiment 59b, embodiment 59c or embodiment 59d, wherein R is an integer from 0 to 2.

[0399] Embodiment 59f. A conjugate according to embodiment 59e, wherein z is 0 or 2.

[0400] Embodiment 60.L 1 teeth, [ka] A conjugate according to any one of embodiments 46m to 59f, selected from the group consisting of:

[0401] Embodiment 61.L 2 and L 3 are each independently [ka] (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 (## indicates the direct or indirect point of attachment to W) A conjugate according to any one of embodiments 48 to 60, wherein the linking spacer comprises a moiety represented by:

[0402] Embodiment 62.L 2 and L 3 are each independently [ka] [ka] (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R L23 is hydrogen or C 1 ~C 6 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2and L 2 Or L 3 ## indicates the direct point of attachment to W; If W is N, then L 2 and L 3 (provided that it is not (L2c), (L2d), (L2f) or (L2k)) The conjugate according to any one of embodiments 48 to 60, wherein the linking spacer is selected from the group consisting of:

[0403] Embodiment 63.L 2 and L 3 are each independently [ka] [ka] (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R L23 is hydrogen or C 1 ~C 3 is alkyl; R L is hydrogen or -C(O)-R H and; R H is a hydrophilic group; and L 2 Or L 3 # is E 1 Or E 2 and L 2 Or L 3 ## indicates the direct point of attachment to W; if W is N, then L 2 and L 3 (provided that it is not (L2FF), (L2MM), (L2NN), (L2OO) or (L2PP)) 63. The conjugate according to embodiment 62, wherein the linking spacer is selected from the group consisting of:

[0404] Embodiment 64.L 2 and L 3 is, independently, [ka] [ka] (In the formula, L 2 Or L 3 # is E 1 Or E 2 indicates the direct attachment point to L 2 Or L 3 ## indicates the direct attachment point to W; R L is hydrogen or -C(O)-R H and R H teeth, [ka] and d is an integer from 20 to 30 (e.g., 25). The conjugate according to any one of embodiments 48 to 63, wherein the linking spacer is selected from the group consisting of:

[0405] Embodiment 64a.d is a conjugate according to embodiment 64, which is 25.

[0406] Embodiment 65. A conjugate according to any one of embodiments 51 to 64a, wherein each peptide group independently comprises 1 to 4, 1 to 3, or 1 to 2 amino acid residues.

[0407] Embodiment 65a. A conjugate according to embodiment 65, wherein each peptide group independently comprises two amino acid residues.

[0408] Embodiment 66. A conjugate according to embodiment 65 or embodiment 65a, wherein each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr) and β-alanine (β-Ala).

[0409] Embodiment 67. A conjugate according to any one of embodiments 51 to 65, wherein each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly and Sulfo-Ala-Val-Ala.

[0410] Embodiment 68.E 1 and / or E 2 are each independently [ka] (Wherein, E1-1 or E1-2 is V in formula (B) 1 Or V 2 or the direct point of attachment to the -NH- group in formulas (C) and (D); and E1-1 or E1-2 ^^ respectively represent L 2 Or L 3 indicates the direct point of attachment to 1 and E 2 are peptide groups independently selected from (E1-1) and (E1-2). 66. The conjugate according to any one of embodiments 48 to 65, wherein the peptide group is selected from the group consisting of:

[0411] Embodiment 68a.E 1 and E 2is a peptide group independently selected from (E1-1) and (E1-2), or a pharma- ceutically acceptable salt thereof.

[0412] Embodiment 69.E 1 and / or E 2 are each independently [ka] (In the formula, R E is a hydrophilic group R H is) The conjugate according to any one of embodiments 48 to 65, wherein the peptide group is represented by:

[0413] Hydrophilic group R in embodiment 70 (E1-3) H teeth, [ka] (wherein e is an integer of 20 to 30 (e.g., 25)) 70. The conjugate according to embodiment 69, wherein

[0414] Embodiment 70a.e is a conjugate according to embodiment 70, which is 25.

[0415] Embodiment 71.E 1 and E 2 are respectively [ka] 69. The conjugate according to embodiment 68, wherein

[0416] Embodiment 72.A 1 and A 2 are independently a bond and -OC(=O)-* (wherein * represents D 1 Or D 2 The conjugate according to any one of embodiments 51 to 71, wherein the conjugate is selected from the group consisting of:

[0417] Embodiment 72a.A 1 and A 2 are independent, combined, [ka] and -OC(=O)-* (wherein * represents D 1 Or D 2 The conjugate according to any one of embodiments 51 to 71, wherein the conjugate is selected from the group consisting of:

[0418] Embodiment 73.A 1 and A 2 The conjugate according to embodiment 72, wherein is a bond.

[0419] Embodiment 73a.A 1 and A 2 A conjugate according to embodiment 72, wherein both are -OC(=O)-*.

[0420] Embodiment 73b.A 1 and A 2 One of the groups is OC(=O)-* and A 1 and A 2 The conjugate according to embodiment 72, wherein the other is a bond.

[0421] Embodiment 73c.A 1 and A 2 is independently a bond, or [ka] (In the formula, * represents D 1 Or D 2 (Indicates the attachment point to The conjugate according to embodiment 72a,

[0422] Embodiment 73d.A 1 and A 2 On the other hand, [ka] And A 1 and A2 The conjugate according to embodiment 72a, wherein the other is a bond.

[0423] Embodiment 73e.A 1 and A 2 Both [ka] The conjugate according to embodiment 72a,

[0424] Embodiment 73f.A 1 and A 2 On the other hand, [ka] And A 1 and A 2 The conjugate according to embodiment 72a, wherein the other is OC(=O)-*.

[0425] Embodiment 73g.A 1 and A 2 is -OC(=O)-*; (ii)A 1 and A 2 teeth, [ka] or (iii)A 1 is -OC(=O)-*, and A 2 is a bond or (iv)A 1 is -OC(=O)-*, and A 2 teeth, [ka] or (v)A 1 is a bond, and A 2 teeth, [ka] or (vi) A 1 is a bond, and A 2 is -OC(=O)-* (wherein * is D 1 Or D 2 A conjugate according to embodiment 72a, wherein

[0426] Embodiment 74.i)L 4 and L 5 are each independently [ka] (In the formula, D 1 and D. 2 is independently selected from the group consisting of: X is a bond, triazolyl or -CH 2 -triazolyl-, X is R 2 or R 3 (connected to or a spacer moiety having the structure (ii) L 4 and L 5 is, independently, [ka] (In the formula, Z is -CH 2 -, -CH 2 O-, -CH 2 N(R L45 )C(=O)O-, -NHC(=O)C(R L45 ) 2 NHC(=O)O-, -NHC(=O)C(R L45 ) 2 NH-, -NHC(=O)C(R L45 ) 2 NHC(=O)-, -C(=O)NR b -, -C(=O)NH-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH-, -CH 2 NRL45 C(=O)NR L45 -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) 2 NH-, -NHS(O) 2 -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R L45 are independently H, C 1 ~C 6 Alkyl and C 3 ~C 8 cycloalkyl); and X is -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-, -(CH 2 CH 2 O) n -C(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -CH 2 -Triazolyl-C 1 ~C 4 Alkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n -, -C 4 ~C 6 Cycloalkylene-OC(O)NHS(O) 2 NH-(CH 2 CH 2 O) n where each n is independently 1, 2, or 3; X is R 2 or R 3 (connected to A conjugate according to any one of embodiments 51 to 73b, wherein the spacer moiety has the structure:

[0427] In embodiment 75, Z is -O-, -CH 2 NR L45 C(=O)-, -CH 2 NR L45 C(=O)NH- or -CH 2 X is a bond, triazolyl or -CH 2 -triazolyl-; and R L45 is, at each occurrence, independently H or C 1 ~C 3 The conjugate according to embodiment 74, wherein said alkyl is aryl.

[0428] Embodiment 76.L 4 and L 5 are each independently [ka] (In the formula, L 4 Or L 5 @ indicates the direct point of attachment to the phenyl group, and L 4 Or L 5 @@ is R 2 or R 3 (Indicates the direct attachment point to The conjugate according to any one of embodiments 51 to 75, wherein the spacer moiety is selected from the group consisting of:

[0429] Embodiment 77.R 2 and R 3 Each of the hydrophilic groups represented by the formula (I) is independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 [ka] C replaced with 2 ~C 6 Alkyl or -OC(=O)NHS(O) 2 NHCH 2 CH2 OCH 3 , -NHC(=O)C 1 ~C 4 Alkylene-P(O)(OCH 2 CH 3 ) 2 and C substituted with 1 to 2 substituents independently selected from -COOH groups. 2 ~C 6 The conjugate according to any one of embodiments 51 to 76, comprising an alkyl.

[0430] Embodiment 78.R 2 or / and R 3 are each independently [ka] (wherein n is an integer of 1 to 6). [ka] The conjugate according to any one of embodiments 51 to 76, selected from the group consisting of:

[0431] Embodiment 79.R 2 or / and R 3 are each independently (i) the following part: [ka] (In the formula, f is an integer from 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) Polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by The conjugate according to any one of embodiments 51 to 76, comprising:

[0432] Embodiment 79a.R 2 or R 3 Each hydrophilic group represented by the formula: (i) the following part: [ka] (wherein f is an integer of 3 to 25; and R 23 -H, -CH 3 or -CH 2 CH 2 C(=O)OH) or polysarcosine having (ii) Formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) or (iii) [ka] The part represented by The conjugate according to any one of embodiments 51 to 76, comprising:

[0433] Embodiment 80.R 2 and R 3 are each independently [ka] (In the formula, g and h are independently an integer of 20 to 30 (e.g., 23 or 24). The conjugate according to any one of embodiments 51 to 76, selected from the group consisting of:

[0434] Embodiment 81.R 2 or / and R 3 teeth, [ka] The conjugate according to embodiment 80, comprising:

[0435] Embodiment 81a.R 2 and R 3 are each independently represented by the formula: [ka] (In the formula, g and h are independently an integer of 2 to 30.) The conjugate according to embodiment 80, comprising a polyethylene glycol of

[0436] Embodiment 82.D 1 and D. 2 A conjugate according to any one of embodiments 46m to 81a, wherein:

[0437] Embodiment 83.D 1 and D. 2 is different, a conjugate according to any one of embodiments 46m to 81a.

[0438] Embodiment 84.D 1 and D. 2 The conjugate according to any one of embodiments 46m to 83, wherein each of the above is independently selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant.

[0439] Embodiment 85.D 1 and D. 2 The conjugate according to any one of embodiments 46m to 83, wherein each of said groups is independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

[0440] Embodiment 85a.D 1 and D. 2 is, independently, [ka] [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0441] Embodiment 85b.i)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iii) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; iv) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; v)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; viii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; ix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; x)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xi) D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxiv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xxxix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xli)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xliv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; vl)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; xlviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; il)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; l)D 1teeth, [ka] and D 2 teeth, [ka] Is it; li)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; liv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lv)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lvii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lviii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lix)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lx)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxi)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxii)D 1 teeth, [ka] and D 2 teeth, [ka] Is it; lxiii)D 1 teeth, [ka] and D 2 teeth, [ka] or lxiv)D 1 teeth, [ka] and D 2 teeth, [ka] A conjugate according to embodiment 85a, wherein * indicates the point of attachment to the rest of the molecule.

[0442] Embodiment 85c.i)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; iv) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; v)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; vii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; viii) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; ix) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; x)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xi) A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiii)A1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xxxix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xl)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] Is it; xli)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xliv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; xlix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; l)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; li)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; liv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lvii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lviii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lix)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lx)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxi)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] Is it; lxii)A 1 -D 1 teeth, [ka] and A 2 -D2 teeth, [ka] Is it; lxiii)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] or lxiv)A 1 -D 1 teeth, [ka] and A 2 -D 2 teeth, [ka] A conjugate according to any one of embodiments 46 to 85b, wherein * indicates the point of attachment to the rest of the molecule.

[0443] Embodiment 86.D 1 and / or D. 2 The conjugate according to any one of embodiments 46m to 83, wherein is an auristatin.

[0444] Embodiment 86a.D 1 and D. 2 The conjugate according to embodiment 86, wherein both of are auristatins.

[0445] Embodiment 86b.D 1 and / or D. 2 The conjugate according to any one of embodiments 46m to 83, wherein is a topoisomerase 1 inhibitor.

[0446] Embodiment 86c.D1 and D. 2 The conjugate according to embodiment 86b, wherein both of said compounds are topoisomerase 1 inhibitors.

[0447] Embodiment 86d.D 1 and D. 2 one of which is an auristatin and D 1 and D. 2 The conjugate according to any one of embodiments 46m to 83, wherein the other is a topoisomerase 1 inhibitor.

[0448] Embodiment 86e.D 1 is an auristatin, and D 2 The conjugate according to embodiment 86d, wherein is a topoisomerase 1 inhibitor.

[0449] Embodiment 86f.D 1 is a topoisomerase 1 inhibitor, and D 2 The conjugate according to embodiment 86d, wherein is an auristatin.

[0450] Embodiment 87.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to The conjugate according to embodiment 86, selected from the group consisting of:

[0451] Embodiment 87a.D 1 and D. 2 is, independently, [ka] 88. The conjugate according to embodiment 87, selected from the group consisting of:

[0452] Embodiment 87b.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0453] Embodiment 87c.D 1 and D. 2 is, independently, [ka] (In the formula, * represents A 1 Or A 2 (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

[0454] Embodiment 88.D 1 and D. 2 The conjugate according to any one of embodiments 46m to 83, wherein each of said groups is independently selected from an antitubulin agent, a tubulin inhibitor, a DNA minor groove binder, a DNA replication inhibitor, an alkylating agent, an antibiotic, an antifolate, an antimetabolite, a chemotherapeutic sensitizer, a topoisomerase inhibitor, and / or a vinca alkaloid.

[0455] Embodiment 89.D 1 and D. 2are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; 1 Also D 2 A conjugate according to any one of embodiments 46m to 83, with the proviso that neither is a BH3 mimetic.

[0456] Embodiment 90. A conjugate comprising an antibody or antigen-binding fragment bound to one or more (e.g., 1-16, such as 1-4) compounds independently selected from embodiment 44 or embodiment 45.

[0457] Embodiment 91. A conjugate according to any one of embodiments 46m to 90, wherein the antibody or antigen-binding fragment binds to a target antigen on a cancer cell.

[0458] Embodiment 92. (i) the target antigen is selected from BCMA, CD33, HER2, CD38, CD48, CD79b, PCAD, CD74, CD138, SLAMF7, CD123, CLL1, FLT3, CD7, CKIT, CD56, SEZ6, DLL3, DLK1, B7-H3, EGFR, CD71, EphA2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, TROP2, LIV1, CD46, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; (ii) the target antigen is selected from EGFR, CD7, HER2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; or (iii) The conjugate according to embodiment 91, wherein the target antigen is selected from PCAD, CD48, CD74, EphA2, TROP2, B7-H3, 5T4, and HER2.

[0459] Embodiment 92a. The conjugate of embodiment 91 or 92, wherein the antibody or antigen-binding fragment thereof is selected from Table D1.

[0460] Embodiment 93. A conjugate according to any one of embodiments 91 to 92a, wherein the antibody or antigen-binding fragment comprises i) three heavy chain CDR sequences and three light chain CDR sequences selected from Tables D3 and D8, ii) a heavy chain variable region sequence and a light chain variable region sequence selected from Tables D2 and D8, or iii) a heavy chain sequence and a light chain sequence selected from Tables D4, D5 and D7.

[0461] Embodiment 94. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 268, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 269, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 263, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 6) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 7) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 215, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; and 8) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174 92. The conjugate of embodiment 91, which is an anti-CD74 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0462] Embodiment 95. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-CD74 antibody comprising (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 262, or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 267.

[0463] Embodiment 96. The antibody or antigen-binding fragment comprises: (a) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 237, or a sequence at least 95% identical to SEQ ID NO: 237; (b) a heavy chain amino acid sequence of SEQ ID NO: 236, or a sequence at least 95% identical to SEQ ID NO: 236, and a light chain amino acid sequence of SEQ ID NO: 237, or a sequence at least 95% identical to SEQ ID NO: 237; or (c) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 239, or a sequence at least 95% identical to SEQ ID NO: 239. 92. The conjugate of embodiment 91, wherein the anti-CD74 antibody comprises

[0464] Embodiment 97. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 271, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 272, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 281, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 283; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 274, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 285, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 276, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 287, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 4) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 279, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 288, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 51, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 52, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 53; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 54, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 55, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 56 92. The conjugate of embodiment 91, which is an anti-CD48 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0465] Embodiment 98. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 270 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 280; or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 14.

[0466] Embodiment 99. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: (a) a heavy chain amino acid sequence of SEQ ID NO: 240 or a sequence that is at least 95% identical to SEQ ID NO: 240 and a light chain amino acid sequence of SEQ ID NO: 243 or a sequence that is at least 95% identical to SEQ ID NO: 243; or (b) a heavy chain amino acid sequence of SEQ ID NO: 242 or a sequence that is at least 95% identical to SEQ ID NO: 242 and a light chain amino acid sequence of SEQ ID NO: 243 or a sequence that is at least 95% identical to SEQ ID NO: 243; c) a heavy chain amino acid sequence of SEQ ID NO: 240 or a sequence that is at least 95% identical to SEQ ID NO: 240 and a light chain amino acid sequence of SEQ ID NO: 69 or a sequence that is at least 95% identical to SEQ ID NO: 70.

[0467] Embodiment 100. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 289, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 290, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 297, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 299; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 292, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 293, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 294, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 295; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 302, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 39, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44 92. The conjugate of embodiment 91, which is an anti-Her2 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0468] Embodiment 101. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:9 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:296.

[0469] Embodiment 102. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 245 or a sequence at least 95% identical to SEQ ID NO: 245 and a light chain amino acid sequence of SEQ ID NO: 66 or a sequence at least 95% identical to SEQ ID NO: 66.

[0470] Embodiment 103. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 304, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 305, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 312, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 314; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 307, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 309, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 317, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 310, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316 92. The conjugate of embodiment 91, which is an anti-PCAD antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0471] Embodiment 104. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 303 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 311.

[0472] Embodiment 105. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 248 or a sequence at least 95% identical to SEQ ID NO: 248 and a light chain amino acid sequence of SEQ ID NO: 250 or a sequence at least 95% identical to SEQ ID NO: 250.

[0473] Embodiment 106. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 319, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 320, and a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 330, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 332; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 322, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 324; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 325, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 326, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 327; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 336, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 328, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335 92. The conjugate of embodiment 91, which is an anti-EphA2 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

[0474] Embodiment 107. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 318 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 329.

[0475] Embodiment 108. The conjugate of embodiment 91, wherein the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 252 or a sequence at least 95% identical to SEQ ID NO: 252 and a light chain amino acid sequence of SEQ ID NO: 254 or a sequence at least 95% identical to SEQ ID NO: 254.

[0476] Embodiment 109. The conjugate of any one of embodiments 94 to 108, wherein the antibody or antigen-binding fragment thereof comprises one or more cysteine ​​substitutions selected from E152C, S375C or both E152C and S375C in the heavy chain of the antibody or antigen-binding fragment thereof, wherein the positions are numbered according to the EU system.

[0477] Embodiment 110. The conjugate of any one of embodiments 94 to 108, wherein the antibody or antigen-binding fragment thereof comprises one or more Fc-silencing mutations.

[0478] Embodiment 111. A composition comprising multiple copies of any one of embodiments 46m to 110, wherein the average a of the conjugate in the composition is from about 1 to about 8, for example from about 1 to about 6, from about 1 to about 4, or from about 1 to about 2.

[0479] Embodiment 112. A compound of the formula: [ka] [ka] [ka] [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., from 2 to 5); and n is an integer from 1 to 12 (e.g., 2 to 5). or a pharma- ceutically acceptable salt thereof.

[0480] Embodiment 112a.A 1 and A 2 each independently represents a bond and OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 or a pharma- ceutically acceptable salt thereof.

[0481] Embodiment 113. A compound of the formula: [ka] [ka] [ka] [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., from 2 to 5); n is an integer from 1 to 12 (e.g., from 2 to 5); and **--- indicates the attachment point to Ab) The conjugate according to any one of embodiments 46m to 110, represented by any one of:

[0482] Embodiment 113a.A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 The conjugate according to embodiment 113, wherein the conjugate is selected from the group consisting of:

[0483] Embodiment 114. Formula (D5a-1): [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); and n is an integer from 1 to 12 (e.g., 5 to 10). 44. A compound according to any one of embodiments 1 to 43, or a pharma- ceutically acceptable salt thereof.

[0484] Embodiment 114a.A 1 and A 2each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 or a pharma- ceutically acceptable salt thereof.

[0485] Embodiment 115. Formula (D5a-2): [ka] (In the formula, A 1 and A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 (indicating the point of attachment to the); g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); n is an integer from 1 to 12 (e.g., 5 to 10); and **--- indicates the attachment point to Ab) The conjugate according to any one of embodiments 46m to 110.

[0486] Embodiment 115a.A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 The conjugate according to embodiment 115, wherein the conjugate is selected from the group consisting of:

[0487] Embodiment 116. A compound of the formula: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] (In the formula, A 1 Or A 2 are each independently a bond, [ka] and -OC(=O)-* (wherein * is D 1 Or D 2 **--- indicates point of attachment to Ab; and [ka] D 1 Or D 2 (Indicates a direct attachment point to The conjugate according to any one of embodiments 46m to 110, represented by:

[0488] Embodiment 116a.A 1 and A 2 each independently represents a bond and -OC(=O)-* (wherein A 1 and A 2 The * in D 1 Or D 2 The conjugate according to embodiment 116, wherein the conjugate is selected from the group consisting of:

[0489] Embodiment 117. A pharmaceutical composition comprising the conjugate of any one of embodiments 46 to 110, 113, 115 and 116 and a pharma- ceutically acceptable carrier.

[0490] Embodiment 118. A method for treating a subject having or suspected of having cancer, comprising administering to the subject a therapeutically effective amount of a conjugate of any one of embodiments 46 to 110, 113, 115 and 116, or a pharmaceutical composition of embodiment 117.

[0491] Embodiment 119. The method of embodiment 118, wherein the cancer expresses the target antigen.

[0492] Embodiment 120. The method of embodiment 118 or embodiment 119, wherein the cancer is a tumor or blood cancer, optionally wherein the cancer is breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, spleen cancer, pancreatic cancer, gastric cancer, colon cancer or head and neck cancer.

[0493] Embodiment 121. A method for reducing or inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate of any one of embodiments 46 to 110, 113, 115 and 116, or a pharmaceutical composition of embodiment 117.

[0494] Embodiment 122. The method of embodiment 121, wherein the tumor expresses the target antigen.

[0495] Embodiment 123. The method of embodiment 121 or embodiment 122, wherein the tumor is breast cancer, gastric cancer, bladder cancer, brain cancer, cervical cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, melanoma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, stomach cancer, colon cancer or head and neck cancer.

[0496] Embodiment 124. A method for reducing or inhibiting a hematological cancer in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate of any one of embodiments 46 to 110, 113, 115 and 116, or a pharmaceutical composition of embodiment 117.

[0497] Embodiment 125. The method of embodiment 124, wherein the hematological cancer expresses the target antigen.

[0498] Embodiment 126. The method of embodiment 124 or embodiment 125, wherein the hematological cancer is chronic lymphocytic leukemia (CLL), follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), acute monocytic leukemia (AMoL), Hodgkin's lymphoma, non-Hodgkin's lymphoma or myelodysplastic syndrome (MDS).

[0499] Embodiment 127. The method of any one of embodiments 121-126, wherein administration of the conjugate or pharmaceutical composition reduces or inhibits the growth of the tumor or hematological cancer by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99%.

[0500] Embodiment 128. A method for reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate of any one of embodiments 46 to 110, 113, 115 and 116, or a pharmaceutical composition of embodiment 117.

[0501] Embodiment 129. The method of embodiment 128, wherein the cancer cell population expresses a target antigen.

[0502] Embodiment 130. The method of embodiment 128 or embodiment 129, wherein the cancer cell population is derived from a tumor or blood cancer, and optionally the cancer cell population is derived from breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, gastric cancer, colon cancer or head and neck cancer.

[0503] Embodiment 131. The method of any one of embodiments 128-130, wherein administration of the conjugate or pharmaceutical composition reduces the cancer cell population or slows the expansion of the cancer cell population by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

[0504] Embodiment 132. The method of any one of embodiments 118 to 131, wherein the conjugate is administered as monotherapy.

[0505] Embodiment 133. The method of any one of embodiments 118 to 131, wherein the conjugate is administered concomitantly with another therapeutic agent or radiation therapy.

[0506] Embodiment 134. The method of embodiment 133, wherein the conjugate is administered in an amount effective to sensitize tumor cells to one or more additional therapeutic agents and / or radiation therapy.

[0507] Embodiment 135. The method of any one of embodiments 118 to 131, further comprising administering at least one additional therapeutic agent to a subject in need thereof.

[0508] Embodiment 136. The method of embodiment 135, wherein one additional therapeutic agent is a taxane, a vinca alkaloid, a MEK inhibitor, an ERK inhibitor, a topoisomerase inhibitor, or a RAF inhibitor.

[0509] Embodiment 137. Use of a conjugate of any one of embodiments 46 to 110, 113, 115 and 116, or a pharmaceutical composition of embodiment 117, for the manufacture of a medicament for (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumor in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

[0510] Embodiment 138. A conjugate of any one of embodiments 46 to 113, 110, 115 and 116, or a pharmaceutical composition of embodiment 117, for use in (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumor in a subject, (iii) reducing or inhibiting a blood cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

[0511] definition Various terms relating to aspects of the present specification are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise specified. Other specifically defined terms are to be interpreted in a manner consistent with the definitions provided herein.

[0512] As used herein, the singular forms "a," "an," and "the" include the plural unless the context clearly dictates otherwise. The terms "is," "includes," and "containing," such as in "comprising," "having," and "is of the formula," should be considered open terms (i.e., meaning "including, but not limited to") unless otherwise noted. Furthermore, whenever "comprising" or another open-ended term is used in an embodiment, it should be understood that the same embodiment may be more narrowly claimed using the intermediate term "consisting essentially of" or the limiting term "consisting of."

[0513] The term "about" or "approximately," when used in connection with numerical values ​​and ranges, refers to a value or range that is close to or near the recited value or range, such that an embodiment may be performed as intended, as would be apparent to one of ordinary skill in the art from the teachings contained herein. In some embodiments, about means plus or minus 20%, 15%, 10%, 5%, 1%, 0.5%, or 0.1% of a quantity. In one embodiment, the term "about" refers to a set of numerical values ​​that are greater than or less than 10% of a particular numerical value. In another embodiment, the term "about" refers to a set of numerical values ​​that are greater than or less than 5% of a particular numerical value. In another embodiment, the term "about" refers to a set of numerical values ​​that are greater than or less than 1% of a particular numerical value.

[0514] The terms "antibody drug conjugate," "antibody conjugate," "conjugate," "immunoconjugate," and "ADC" are used interchangeably and refer to one or more therapeutic compounds (not BH3 mimetics) linked to one or more antibodies or antigen-binding fragments. In some embodiments, an ADC has the general formula: [ka] (Formula 1), where Ab=antibody or antigen-binding fragment, L=dual linker moiety, and D 1 and D. 2 = a drug moiety that is not a BH3 mimetic, and A = D bound to each antibody or antigen-binding fragment. 1 and D.2 is the number of dual linker moieties having

[0515] The term "antibody" is used in the broadest sense to refer to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, carbohydrate, polynucleotide, lipid, or a combination of the above, through at least one antigen recognition site in the variable region of the immunoglobulin molecule. Antibodies can be polyclonal or monoclonal, multi-chain or single-chain or intact immunoglobulins, and can be from natural or recombinant sources. An "intact" antibody is a glycoprotein that typically comprises at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain is composed of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region contains three domains, CH1, CH2, and CH3. Each light chain is composed of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region is composed of one domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability called complementarity determining regions (CDRs), interspersed with more conserved regions called framework regions (FRs). Each VH and VL is composed of three CDRs and four FRs arranged from amino to carboxyl termini in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant regions of the antibody may mediate the binding of the immunoglobulin to host tissues or to various cells of the immune system (e.g., effector cells) and factors including the first component (C1q) of the classical complement system. The antibody may be a monoclonal antibody, a human antibody, a humanized antibody, a camelized antibody, or a chimeric antibody. The antibody can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. The antibody can be an intact antibody or an antigen-binding fragment thereof.

[0516] In some embodiments, the antibody or antibody fragment disclosed herein comprises modified or engineered amino acid residues, such as one or more cysteine ​​residues, as sites for conjugation to a drug moiety (Junutula JR, et al., Nat Biotechnol 2008,26:925-932). In one embodiment, the present disclosure provides modified antibodies or antibody fragments comprising substitutions of one or more amino acids with cysteine ​​at the positions described herein. The sites for cysteine ​​substitutions are in the constant region of the antibody or antibody fragment, and are therefore applicable to a variety of antibodies or antibody fragments, with the sites being selected to provide stable and uniform conjugates. The modified antibody or fragment can have one, two or more cysteine ​​substitutions, and these substitutions can be used in combination with other modification and conjugation methods as described herein. Methods for inserting cysteines at specific positions in an antibody are known in the art, see, e.g., Lyons et al, (1990) Protein Eng., 3:703-708, WO 2011 / 005481, WO 2014 / 124316, WO 2015 / 138615. In certain embodiments, the modified antibody comprises a substitution of one or more amino acids in its constant region selected from positions 117, 119, 121, 124, 139, 152, 153, 155, 157, 164, 169, 171, 174, 189, 191, 195, 197, 205, 207, 246, 258, 269, 274, 286, 288, 290, 292, 293, 320, 322, 326, 333, 334, 335, 337, 344, 355, 360, 375, 382, ​​390, 392, 398, 400 and 422 of the heavy chain of the antibody, wherein positions are numbered according to the EU system.In some embodiments, the modified antibody or antibody fragment comprises a substitution by cysteine ​​of one or more amino acids in its constant region selected from positions 107, 108, 109, 114, 129, 142, 143, 145, 152, 154, 156, 159, 161, 165, 168, 169, 170, 182, 183, 197, 199, and 203 of the light chain of the antibody or antibody fragment, positions numbered according to the EU system, and the light chain is a human kappa light chain. In certain embodiments, the modified antibody or antibody fragment thereof comprises a combination of substitution by cysteine ​​of two or more amino acids in its constant region, positions numbered according to the EU system, including substitution at position 375 of the antibody heavy chain, position 152 of the antibody heavy chain, position 360 of the antibody heavy chain, or position 107 of the antibody light chain, positions numbered according to the EU system. In certain embodiments, the modified antibody or antibody fragment thereof comprises a substitution of one amino acid by cysteine ​​in its constant region, which substitution is at position 375 of the antibody heavy chain, at position 152 of the antibody heavy chain, at position 360 of the antibody heavy chain, at position 107 of the antibody light chain, at position 165 of the antibody light chain or at position 159 of the antibody light chain, positions numbered according to the EU system, and the light chain is a kappa chain. In certain embodiments, the modified antibody or antibody fragment thereof comprises a combination of substitutions of two amino acids by cysteine ​​in its constant region, which combination comprises a substitution at position 375 of the antibody heavy chain and at position 152 of the antibody heavy chain, positions numbered according to the EU system. In certain embodiments, the modified antibody or antibody fragment thereof comprises a substitution of one amino acid by cysteine ​​at position 360 of the antibody heavy chain, positions numbered according to the EU system. In another particular embodiment, the modified antibody or antibody fragment thereof comprises a substitution of one amino acid at position 107 of the antibody light chain with a cysteine, where positions are numbered according to the EU system, and the light chain is a kappa chain.

[0517] The term "antibody fragment" or "antigen-binding fragment" or "functional antibody fragment" as used herein refers to at least a portion of an antibody that retains the ability to specifically interact with an epitope of an antigen (e.g., PCAD, HER2, CD48, CD74, EphA2, TROP2, B7-H3 or 5T4) (e.g., by binding, steric hindrance, stabilization / destabilization, spatial distribution). Antigen-binding fragments may also retain the ability to be internalized into antigen-expressing cells. In some embodiments, antigen-binding fragments also retain immune effector activity. The terms antibody, antibody fragment, antigen-binding fragment, and the like are intended to encompass the use of binding domains derived from antibodies in the context of larger macromolecules such as ADCs. It has been shown that fragments of full-length antibodies can perform the antigen-binding function of the full-length antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, Fv fragments, scFv antibody fragments, disulfide-linked Fvs (sdFv), Fd fragments consisting of VH and CH1 domains, linear antibodies, single domain antibodies (either VL or VH) such as sdAb, camelid VHH domains, multispecific antibodies formed from antibody fragments such as bivalent fragments comprising two Fab fragments linked by a disulfide bridge at the hinge region, and isolated CDRs or other epitope-binding fragments of antibodies. Antigen-binding fragments can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, bispecific or multispecific antibody constructs, ADCs, v-NARs, and bis-scFvs (e.g., Holliger and Hudson (2005) Nat Biotechnol. 23(9):1126-36). Antigen-binding fragments can also be grafted onto scaffolds based on polypeptides such as fibronectin type III (Fn3) (see US Pat. No. 6,703,199, which describes fibronectin polypeptide minibodies).The term "scFv" refers to a fusion protein comprising at least one antigen-binding fragment comprising a variable region of a light chain and at least one antigen-binding fragment comprising a variable region of a heavy chain, where the light chain variable region and the heavy chain variable region are closely linked, for example, via a synthetic linker, e.g., a short flexible polypeptide linker, and can be expressed as a single-chain polypeptide, and the scFv retains the specificity of the intact antibody from which it is derived. Unless otherwise specified, an scFv can have the VL and VH variable regions in any order, e.g., relative to the N-terminus and C-terminus of the polypeptide, and the scFv can comprise VL-linker-VH or VH-linker-VL. Antigen-binding fragments are obtained using conventional techniques known to those of skill in the art, and binding fragments are screened for utility (e.g., binding affinity, internalization) in the same manner as intact antibodies. Antigen-binding fragments can be prepared, for example, by cleavage of the intact protein, e.g., by protease or chemical cleavage.

[0518] As used herein, the term "complementarity determining region" or "CDR" refers to a sequence of amino acids in an antibody variable region that confers antigen specificity and binding affinity. For example, typically, there are three CDRs in each heavy chain variable region (e.g., HCDR1, HCDR2, and HCDR3) and three CDRs in each light chain variable region (LCDR1, LCDR2, and LCDR3). The exact amino acid sequence boundaries of a given CDR may be determined using any of a number of well-known schemes, including those described in Kabat et al. (1991), "Sequences of Proteins of Immunological Interest," 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD ("Kabat" numbering scheme); Al-Lazikani et al. (1997) J Mol Biol. 273(4):927-48 ("Chothia" numbering scheme); ImMunoGenTics (IMGT) numbering (Lefranc (2001) Nucleic Acids Res. 29(1):207-9; Lefranc et al. (2003) Dev Comp Immunol. 27(1):55-77) ("IMGT" numbering scheme); or a combination thereof. In a combination of the Kabat and Chothia numbering schemes for a given CDR region (e.g., HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, or LC CDR3), in some embodiments, the CDRs correspond to the amino acid residues defined as part of the Kabat CDRs along with the amino acid residues defined as part of the Chothia CDRs. As used herein, CDRs defined according to the "Chothia" numbering scheme are sometimes referred to as "hypervariable loops."

[0519] In some embodiments, under Kabat, the CDR amino acid residues in the heavy chain variable domain (VH) are numbered 31 to 35 (HCDR1) (e.g., an insertion after position 35), 50 to 65 (HCDR2), and 95 to 102 (HCDR3); and the CDR amino acid residues in the light chain variable domain (VL) are numbered 24 to 34 (LCDR1) (e.g., an insertion after position 27), 50 to 56 (LCDR2), and 89 to 97 (LCDR3). In some embodiments, under Chothia, the CDR amino acids in VH are numbered 26-32 (HCDR1) (e.g., insertion after position 31), 52-56 (HCDR2), and 95-102 (HCDR3); and the amino acid residues in VL are numbered 26-32 (LCDR1) (e.g., insertion after position 30), 50-52 (LCDR2), and 91-96 (LCDR3). Combining the CDR definitions of both Kabat and Chothia, in some embodiments, the CDRs comprise or consist of, for example, amino acid residues 26-35 (HCDR1), 50-65 (HCDR2), and 95-102 (HCDR3) in human VH and amino acid residues 24-34 (LCDR1), 50-56 (LCDR2), and 89-97 (LCDR3) in human VL. In some embodiments, under IMGT, the CDR amino acid residues in VH are numbered from about 26-35 (CDR1), 51-57 (CDR2), and 93-102 (CDR3), and the CDR amino acid residues in VL are numbered from about 27-32 (CDR1), 50-52 (CDR2), and 89-97 (CDR3). In some embodiments, under IMGT, the CDR regions of an antibody may be determined using the program IMGT / DomainGap Align.

[0520] The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies constituting the population are identical except for naturally occurring variants that may be present in minor amounts. Monoclonal antibodies are highly specific and directed against a single antigenic epitope. In contrast, conventional (polyclonal) antibody preparations usually contain a large number of antibodies directed against (or specific for) different epitopes. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous antibody population and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies to be used in accordance with the present disclosure may be produced by the hybridoma method first described by Kohler et al. (1975) Nature 256:495, or may be produced by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). Monoclonal antibodies can also be isolated from phage antibody libraries using, for example, the techniques described in Clackson et al. (1991) Nature 352:624-8, and Marks et al. (1991) J Mol Biol. 222:581-97. The term also includes preparations of antibody molecules of single molecular composition. A monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope.

[0521] The monoclonal antibodies described herein may be non-human, human, or humanized. The term specifically includes "chimeric" antibodies in which a portion of the heavy and / or light chain is identical or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chains are identical or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they specifically bind to the target antigen and / or exhibit the desired biological activity.

[0522] The term "human antibody" as used herein refers to an antibody produced by a human or an antibody having the amino acid sequence of an antibody produced by a human. This term includes antibodies having variable regions in which both the framework and CDR regions are derived from sequences of human origin. Furthermore, if the antibody contains a constant region, the constant region is also derived from such a human sequence, e.g., a human germline sequence or a variant of a human germline sequence, or an antibody containing a consensus framework sequence derived from human framework sequence analysis, e.g., as described in Knappik, et al. ((2000) J Mol Biol. 296(1):57-86). The structure and location of immunoglobulin variable domains, e.g., CDRs, can be defined using well-known numbering schemes, e.g., the Kabat numbering scheme, the Chothia numbering scheme, or a combination of Kabat and Chothia, and / or the ImMunoGenTics (IMGT) numbering. The human antibodies of the invention may include amino acid residues not encoded by human sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or somatic mutation in vivo, or conservative substitutions to facilitate stability or manufacturing). However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0523] As used herein, the term "recombinant human antibody" refers to a human antibody that is made, expressed, created or isolated by recombinant means, such as an antibody isolated from an animal (e.g., a mouse) transgenic or transchromosomal for human immunoglobulin genes or from a hybridoma made therefrom, an antibody isolated from a host cell transformed to express a human antibody, e.g., from a transfectoma, an antibody isolated from a recombinant combinatorial human antibody library, and an antibody made, expressed, created or isolated by any other means including splicing all or a portion of a human immunoglobulin gene sequence to other DNA sequences. Such recombinant human antibodies have variable regions in which the framework and CDR regions are derived from human germline immunoglobulin sequences. However, in some embodiments, such recombinant human antibodies may be subjected to in vitro mutagenesis (or, when animals transgenic for human Ig sequences are used, in vivo somatic mutagenesis) such that the amino acid sequences of the VH and VL regions of the recombinant antibodies are derived from and related to human germline VH and VL sequences, but are sequences that may not naturally exist within the human antibody germline repertoire in vivo.

[0524] The term "chimeric antibody" as used herein refers to an antibody in which the amino acid sequences of the immunoglobulin molecules are derived from two or more species. In some instances, the variable regions of both the heavy and light chains correspond to the variable regions of an antibody derived from one species having the desired specificity, affinity, and activity, while the constant regions are homologous to antibodies derived from another species (e.g., human) to minimize the immune response in the latter species.

[0525] As used herein, the term "humanized antibody" refers to a form of an antibody that contains sequences derived from a non-human (e.g., murine) antibody and a human antibody. Such antibodies are a type of chimeric antibody that contains minimal sequences derived from a non-human immunoglobulin. In general, a humanized antibody will contain substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are from human immunoglobulin sequences. A humanized antibody will optionally contain at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. A humanized antibody can be further modifi...

Claims

1. Formula (A-1): 【Chemistry 1】 (In the formula, R １ is a linking group; L １ is a bridging spacer; W is a branching moiety; L ２’ and L ３’ are each independently a linker; and D １ and D. ２ are each independently a pharma- ceutically active drug, and optionally D １ Also D ２ (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof.

2. L ２’ and L ３’ or a pharma- ceutically acceptable salt thereof.

3. L ２’ and L ３’ or a pharma- ceutically acceptable salt thereof.

3. The compound of claim 2, wherein each of comprises a peptide group and a self-immolative group.

4. L ２’ and L ３’ or a pharma- ceutically acceptable salt thereof.

5. Formula (B-1): 【Chemistry 2】 (In the formula, R １ is a linking group; L １ is a bridging spacer; W is N or CR ｗ and R ｗ is H or C １ ~C ６ is alkyl (e.g., R ｗ is H); L ２ and L ３ are each independently a linking spacer; E １ and E ２ are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic moiety; V １ and V ２ each independently represent: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V １ and V ２ are each independently a self-immolative group, or iii) comprise a self-immolative group and an enzymatic cleavage element; and D １ and D. ２ are each independently a pharma- ceutically active drug, and optionally D １ Also D ２ (Provided that the drug is not a BH3 mimetic) or a pharma- ceutically acceptable salt thereof, of the compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt thereof.

6. V １ and V ２ are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V １ and V ２ and each independently represents a self-immolative group, or a pharma- ceutically acceptable salt thereof.

7. 7. The compound of claim 5 or 6, or a pharma- ceutically acceptable salt thereof, wherein W is N or CH.

8. E １ and E ２ and each of the formula (I) and (II) is an enzyme cleavage element, or a pharma- ceutically acceptable salt thereof.

9. V １ and V ２ The compound according to any one of claims 5 to 8, or a pharma- ceutically acceptable salt thereof, wherein each of the groups is independently a self-immolative group.

10. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker comprises -O-CH ２ --NH-CH ２ or (iv) V comprises a self-immolative group comprising -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium; or (iv) V １ and / or V ２ Each of the formulas independently contains a group containing para-aminobenzyl phosphate or para-aminobenzyl pyrophosphate, or a pharma- ceutically acceptable salt thereof.

11. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker comprises -O-CH ２ --NH-CH ２ 11. The compound of claim 10, or a pharma- ceutically acceptable salt thereof, comprising a self-immolative group comprising -, -OC(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

12. Formula (C-1): 【Chemistry 3】 (In the formula, R １ is a linking group; L １ is a bridging spacer; W is N or CR ｗ and R ｗ is H or C １ ~C ６ is alkyl (e.g., R ｗ is H); L ２ and L ３ are each independently a linking spacer; E １ and E ２ are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A １ and A ２ each independently represents a bond, -OC(=O)-*, 【Chemistry 4】 , -OC(=O)N(CH ３ ) CH ２ CH ２ N (CH ３ )C(=O)-* or -OC(=O)N(CH ３ ) C(R ａ ) ２ C(R ａ ) ２ N (CH ３ )C(=O)-*, Each R ａ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl; A １ Or A ２ The * is D １ Or D ２ indicates the point of attachment to D １ and D. ２ are each independently a pharma- ceutically active drug, and optionally D １ Also D ２ is not a BH3 mimetic; L ４ and L ５ are each independently a spacer moiety; R ２ and R ３ are each independently a hydrophilic group or an enzymatic cleavage element (e.g., R ２ and R ３ are each a hydrophilic group; and m and n are each independently 0 or 1. or a pharma- ceutically acceptable salt thereof, of the compound according to any one of claims 5 to 11, or a pharma- ceutically acceptable salt thereof.

13. 13. The compound of claim 12, or a pharma- ceutically acceptable salt thereof, wherein W is N or CH.

14. R ２ and R ３ and R 1 and R 2 are each a hydrophilic group, or a pharma- ceutically acceptable salt thereof.

15. Formula (D1-1), (D2-1) or (D3-1): 【Chemistry 5】 or a pharma- ceutically acceptable salt thereof, of the compound according to any one of claims 12 to 14, or a pharma- ceutically acceptable salt thereof.

16. With respect to formula (D1-1), R ２ and R ３ are each independently a hydrophilic group, and in formula (D2-1), R ２ and R ３ are each independently an enzyme cleavage element; and with respect to formula (D3-1), R ２ is a hydrophilic group, and R ３ is an enzymatic cleavage element; or a pharma- ceutically acceptable salt thereof.

17. R １ teeth, 【Chemistry 6】 -ONH ２ 、-NH ２ 、 【Chemistry 7】 -N ３ 、 【Chemistry 8】 , -SH, -SR １１ , -SSR １２ , -S(=O) ２ (CH=CH ２ ), -(CH ２ ) ２ S(=O) ２ (CH=CH ２ ), -NHS(=O) ２ (CH=CH ２ ), -NR １１ C(=O)CH ２ Br, for example -NHC(=O)CH ２ Br, -NR １１ C(=O)CH ２ I, for example -NHC(=O)CH ２ I 【Chemistry 9】 -C(O)NHNH ２ 、 【Chemistry 10】 (In the formula, Each R １１ are independently H and C １ ~C ６ alkyl; Each R １２ is 2-pyridyl or 4-pyridyl; Each R １３ are independently H, C １ ~C ６ selected from alkyl, F, Cl and -OH; Each R １４ are independently H, C １ ~C ６ Alkyl, F, Cl, -NH ２ , -OCH ３ , -OCH ２ CH ３ , -N(CH ３ ) ２ , -CN, -NO ２ and -OH; and Each R １５ are independently H, C １ ~C ６ Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH １ ~C ４ Alkoxy and -C(=O)OH substituted C １ ~C ４ alkyl) The compound according to any one of claims 1 to 16, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

18. R １ teeth, 【Chemistry 11】 -ONH ２ 、 【Chemistry 12】 NHC(=O)CH ２ Br and -NHC(=O)CH ２ 18. The compound according to any one of claims 1 to 17, selected from the group consisting of: I, or a pharma- ceutically acceptable salt thereof.

19. R １ teeth, 【Chemistry 13】 -ONH ２ 、 【Chemistry 14】 The compound according to any one of claims 1 to 18, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

20. R １ teeth, 【Chemistry 15】 20. The compound according to any one of claims 1 to 19, wherein:

21. (1) L １ teeth, 【Chemistry 16】 or *-CH(OH)CH(OH)CH(OH)CH(OH)CH(OH)-** wherein each n is an integer from 1 to 12. Including L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (2) L １ teeth, 【Chemistry 17】 and n is an integer from 1 to 12, or n is 1, or n is 12; L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (3) L １ teeth, 【Chemistry 18】 and n is an integer from 1 to 12; L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (4) L １ teeth, 【Chemistry 19】 Including L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ or (5)L １ は、*-C(=O)(CH ２ ) ｍ O(CH ２ ) ｍ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ -**;*-C(=O)NH((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ -**;*-C(=O)O(CH ２ ) ｍ SSC(R Ｌ１ ) ２ (CH ２ ) ｍ C(=O)NR Ｌ１ (CH ２ ) ｍ NR Ｌ１ C(=O)(CH ２ ) ｍ -**;*-C(=O)O(CH ２ ) ｍ C(=O)NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ NH(CH ２ ) ｎ C(=O)-**;*-C(=O)(CH ２ ) ｍ X １ (CH ２ ) ｍ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ NHC(=O)(CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ NHC(=O)(CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ NHC(=O)(CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ NHC(=O)(CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ C(=O)NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ C(R Ｌ１ ) ２ -** or -C(=O)(CH ２ ) ｍ C(=O)NH(CH ２ ) ｍ - is a bridging spacer containing **, and L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to X １ teeth, 【Chemistry 20】 and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and Each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R Ｌ１ are independently H and C １ ~C ６ 21. The compound of any one of claims 1 to 20, or a pharma- ceutically acceptable salt thereof, wherein: R is selected from the group consisting of alkyl, aryl, aryl, arylsulfates, arylalkyl, arylsulfates ...

22. L １ teeth, 【Chemistry 21】 (wherein n is an integer from 1 to 12 (e.g., 4 to 8, e.g., 4 or 8), and L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ (Indicating the direct or indirect point of attachment to or a pharma- ceutically acceptable salt thereof.

22. The compound of any one of claims 1 to 21, comprising a moiety represented by:

23. 23. The compound according to claim 22, or a pharma- ceutically acceptable salt thereof, wherein n is an integer from 4 to 8.

24. 24. The compound of claim 23, or a pharma- ceutically acceptable salt thereof, wherein n is 4 or 8.

25. L １ is the formula 【Chemical 22】 (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, e.g., 0 to 2, e.g., 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L １ * indicates the direct point of attachment to W, and L １ The ** in the is R １ (Indicates the direct attachment point to The compound according to any one of claims 1 to 24, represented by: or a pharma- ceutically acceptable salt thereof.

26. 26. The compound according to claim 25, or a pharma- ceutically acceptable salt thereof, wherein n is an integer from 4 to 8.

27. 27. The compound of claim 26, or a pharma- ceutically acceptable salt thereof, wherein n is 4 or 8.

28. 28. The compound according to any one of claims 25 to 27, wherein x is an integer from 0 to 2, or a pharma- ceutically acceptable salt thereof.

29. 29. The compound of claim 28, or a pharma- ceutically acceptable salt thereof, wherein x is 0 or 2.

30. 30. The compound according to any one of claims 25 to 29, wherein z is an integer from 0 to 2, or a pharma- ceutically acceptable salt thereof.

31. 31. The compound of claim 30, or a pharma- ceutically acceptable salt thereof, wherein z is 0 or 2.

32. L １ teeth, 【Chemistry 23】 32. The compound according to any one of claims 1 to 31, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

33. L ２ and L ３ are each independently 【Chemistry 24】 (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L ２ Or L ３ The # in each １ Or E ２ indicates a direct or indirect point of attachment to ２ Or L ３ ## indicates the direct or indirect point of attachment to W. or a pharma- ceutically acceptable salt thereof.

33. The compound according to any one of claims 5 to 32, wherein the linking spacer comprises a moiety represented by:

34. L ２ and L ３ are each independently 【Chemistry 25】 【Chemistry 26】 【Chemical 27】 (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R Ｌ２３ is hydrogen or C １ ~C ６ is alkyl; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ is a hydrophilic group; and L ２ Or L ３ The # in each １ Or E ２ and L ２ Or L ３ ## indicates the direct point of attachment to W; When W is N, L ２ and L ３ (provided that it is not (L2c), (L2d), (L2f) or (L2k) The compound according to any one of claims 5 to 33, or a pharma- ceutically acceptable salt thereof, wherein the linking spacer is selected from the group consisting of:

35. L ２ and L ３ are each independently 【Chemistry 28】 【Chemical 29】 【Chemistry 30】 (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R Ｌ２３ is hydrogen or C １ ~C ３ is alkyl; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ is a hydrophilic group; and L ２ Or L ３ The # in each １ Or E ２ and L ２ Or L ３ indicates the direct point of attachment to W; when W is N, L ２ and L ３ (provided that the L2FF, L2MM, L2NN, L2OO, or L2PP is not the same) or a pharma- ceutically acceptable salt thereof.

36. L ２ and L ３ is, independently, 【Chemistry 31】 【Chemistry 32】 (In the formula, L ２ Or L ３ The # in each １ Or E ２ indicates a direct point of attachment to ２ Or L ３ ## indicates the direct point of attachment to W; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ teeth, 【Chemical 33】 and d is an integer from 20 to 30 (e.g., 25). The compound according to any one of claims 5 to 35, or a pharma- ceutically acceptable salt thereof, wherein the linking spacer is selected from the group consisting of:

37. 37. The compound of claim 36, or a pharma- ceutically acceptable salt thereof, wherein d is 25.

38. 38. The compound of any one of claims 12 to 37, or a pharma- ceutically acceptable salt thereof, wherein each peptide group independently comprises 1 to 4, 1 to 3, or 1 to 2 amino acid residues.

39. 40. The compound of claim 38, or a pharma- ceutically acceptable salt thereof, wherein each peptide group independently comprises two amino acid residues.

40. 40. The compound of claim 38 or 39, or a pharma- ceutically acceptable salt thereof, wherein each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr), and β-alanine (β-Ala).

41. 41. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 38 or 40, wherein each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly, and Sulfo-Ala-Val-Ala.

42. E １ and / or E ２ are each independently 【Chemical 34】 (In the formula, E1-1 or E1-2 is V in formula (B). １ Or V ２ or a direct point of attachment to the —NH— group in formulas (C) and (D); and ^ in E1-1 or E1-2 respectively represents L ２ Or L ３ indicates a direct point of attachment to １ and E ２ are peptide groups independently selected from (E1-1) and (E1-2) 40. The compound or pharma- ceutically acceptable salt according to any one of claims 5 to 39, wherein the peptide group is selected from the group consisting of:

43. E １ and E ２ is a peptide group independently selected from (E1-1) and (E1-2), or a pharma- ceutically acceptable salt thereof.

44. E １ and / or E ２ are each independently 【Chemistry 35】 (In the formula, R Ｅ is a hydrophilic group R Ｈ (It is) The compound according to any one of claims 5 to 39, which is a peptide group represented by:

45. The hydrophilic group R in (E1-3) Ｈ teeth, 【Chemical 36】 (wherein e is an integer from 20 to 30 (e.g., 25)).

45. The compound of claim 44, which is: or a pharma- ceutically acceptable salt thereof.

46. 46. ​​The compound of claim 45, or a pharma- ceutically acceptable salt thereof, wherein e is 25.

47. E １ and E ２ are respectively 【Chemical 37】 43. The compound of claim 42, or a pharma- ceutically acceptable salt thereof:

48. A １ and A ２ are independently a bond and -OC(=O)-* (wherein * represents D １ Or D ２ 48. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 47, selected from:

49. A １ and A ２ are independent, combined, 【Chemical Formula 38】 and -OC(=O)-* (wherein * represents D １ Or D ２ 49. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 48, selected from:

50. A １ and A ２ or a pharma- ceutically acceptable salt thereof, according to claim 48, wherein each is a bond.

51. A １ and A ２ or a pharma- ceutically acceptable salt thereof, according to claim 48, wherein:

52. A １ and A ２ One of the groups is OC(=O)-*, and A １ and A ２ or a pharma- ceutically acceptable salt thereof, according to claim 48, wherein the other of said groups is a bond.

53. A １ and A ２ is independently a bond, or 【Chemical 39】 (Wherein, * represents D １ Or D ２ (Indicates the attachment point to 50. The compound of claim 49, or a pharma- ceutically acceptable salt thereof, wherein:

54. A １ and A ２ On the other hand, 【Chemistry 40】 And A １ and A ２ or a pharma- ceutically acceptable salt thereof, according to claim 53, wherein the other of said groups is a bond.

55. A １ and A ２ Both 【Chemistry 41】 54. The compound of claim 53, or a pharma- ceutically acceptable salt thereof:

56. A １ and A ２ On the other hand, 【Chemistry 42】 And A １ and A ２ or a pharma- ceutically acceptable salt thereof according to claim 49, wherein the other is OC(=O)-*.

57. A １ and A ２ is OC(=O)-*; (ii) A １ and A ２ teeth, 【Chemistry 43】 or (iii) A １ is OC(=O)-*, and A ２ is a bond or (iv) A １ is OC(=O)-*, and A ２ teeth, 【Chemistry 44】 or (v) A １ is a bond, and A ２ teeth, 【Chemistry 45】 or (vi) A １ is a bond, and A ２ is OC(=O)-*, * is D １ Or D ２ 50. The compound of claim 49, or a pharma- ceutically acceptable salt thereof, showing a point of attachment to:

58. i) L ４ and L ５ are each independently 【Chemistry 46】 (In the formula, Z is -O-, -CH ２ --, --CH ２ O-, -CH ２ N (R Ｌ４５ )C(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NH-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)-, -C(=O)NR Ｌ４５ -, -C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)NR Ｌ４５ -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) ２ NH-, -NHS(O) ２ -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R Ｌ４５ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl) ； and X is a bond, triazolyl or -CH ２ -triazolyl-, X is R ２ Or R ３ (connected to or a spacer moiety having the structure (ii) L ４ and L ５ is, independently, 【Chemistry 47】 (In the formula, Z is -CH ２ --, --CH ２ O-, -CH ２ N (R Ｌ４５ )C(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NH-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)-, -C(=O)NR ｂ -, -C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)NR Ｌ４５ -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) ２ NH-, -NHS(O) ２ -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R Ｌ４５ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl); and X is -CH ２ -Triazolyl-C １ ~C ４ Alkylene-OC(O)NHS(O) ２ NH-, -C ４ ~C ６ Cycloalkylene-OC(O)NHS(O) ２ NH-, -(CH ２ CH ２ O) ｎ -C(O)NHS(O) ２ NH-, -(CH ２ CH ２ O) ｎ -C(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ --, --CH ２ -Triazolyl-C １ ~C ４ Alkylene-OC(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ -, -C ４ ~C ６ Cycloalkylene-OC(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ where each n is independently 1, 2, or 3; X is R ２ Or R ３ (connected to 58. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 57, wherein the spacer moiety has the structure:

59. Z is -O-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH- or -CH ２ X is a bond, triazolyl or -CH ２ -triazolyl-; and R Ｌ４５ is, at each occurrence, independently H or C １ ~C ３ 60. The compound of claim 58, or a pharma- ceutically acceptable salt thereof, wherein: R is an alkyl group;

60. L ４ and L ５ are each independently 【Chemistry 48】 (In the formula, L ４ Or L ５ @ indicates the direct point of attachment to the phenyl group, and L ４ Or L ５ The @@ in is R ２ Or R ３ (Indicates the direct attachment point to 60. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 59, wherein the spacer moiety is selected from the group consisting of:

61. R ２ and R ３ The hydrophilic groups represented by the formula (I) are each independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 【Chemistry 49】 C substituted with ２ ~C ６ Alkyl or -OC(=O)NHS(O) ２ N.H.C.H. ２ CH ２ OCH ３ , -NHC(=O)C １ ~C ４ Alkylene-P(O)(OCH ２ CH ３ ) ２ and C substituted with 1 to 2 substituents independently selected from —COOH groups. ２ ~C ６ 61. The compound of any one of claims 12 to 60, or a pharma- ceutically acceptable salt thereof, comprising an alkyl.

62. R ２ Or / and R ３ are each independently 【Chemistry 50】 (wherein n is an integer from 1 to 6). 【Chemistry 51】 61. The compound according to any one of claims 12 to 60, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

63. R ２ Or / and R ３ is, independently, (i) the part: 【Chemistry 52】 (In the formula, f is an integer from 3 to 25; and R ２３ is H, -CH ３ or -CH ２ CH ２ C(=O)OH) Polysarcosine having the formula: (ii) Formula: 【Chemistry 53】 (wherein g and h are independently an integer from 2 to 30). or (iii) 【Chemical 54】 The part represented by 61. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 60, comprising:

64. R ２ Or R ３ The hydrophilic groups represented by (i) the part: 【Chemistry 55】 where f is an integer from 3 to 25; and R ２３ is H, -CH ３ or -CH ２ CH ２ C(=O)OH) or polysarcosine having the formula (ii) Formula: 【Chemistry 56】 (wherein g and h are independently an integer from 2 to 30). or (iii) 【Chemistry 57】 The part represented by 61. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 60, comprising:

65. R ２ Or / and R ３ are each independently 【Chemistry 58】 (wherein g and h are independently an integer from 20 to 30 (e.g., 23 or 24).

61. The compound or pharma- ceutically acceptable salt of any one of claims 12 to 60, selected from the group consisting of:

66. R ２ Or / and R ３ teeth, 【Chemistry 59】 or a pharma- ceutically acceptable salt thereof.

67. R ２ and R ３ each independently represents the formula: 【Chemistry 60】 (wherein g and h are independently an integer from 2 to 30). or a pharma- ceutically acceptable salt thereof.

68. D １ and D. ２ and R are the same.

69. D １ and D. ２ and are different. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 67.

70. D １ and D. ２ or a pharma- ceutically acceptable salt thereof according to any one of claims 1 to 69, wherein each of said compounds is independently selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant.

71. D １ and D. ２ or a pharmaceutically acceptable salt thereof, wherein each of said x and m is independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

72. D １ and D. ２ are each independently 【Chemistry 61】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to 70. The compound of any one of claims 1 to 69, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

73. i) D １ teeth, 【Chemistry 62】 and D ２ teeth, 【Chemistry 63】 Is it; ii) D １ teeth, 【Chemistry 64】 and D ２ teeth, 【Chemistry 65】 Is it; iii) D １ teeth, 【Chemistry 66】 and D ２ teeth, 【Chemistry 67】 Is it; iv) D １ teeth, 【Chemistry 68】 and D ２ teeth, 【Chemistry 69】 Is it; v) D １ teeth, 【Chemistry 70】 and D ２ teeth, 【Chemistry 71】 Is it; (vi)D １ は、 【Chemical Formula 72】 and D ２ teeth, 【Chemical 73】 Is it; vii) D １ teeth, 【Chemical 74】 and D ２ teeth, 【Chemistry 75】 Is it; viii) D １ teeth, 【Chemical Formula 76】 and D ２ teeth, 【Chemical 77】 Is it; ix) D １ teeth, 【Chemical 78】 and D ２ teeth, 【Chemical Formula 79】 Is it; x) D １ teeth, 【Chemistry 80】 and D ２ teeth, 【Chemistry 81】 Is it; xi) D １ teeth, 【Chemistry 82】 and D ２ teeth, 【Chemistry 83】 Is it; xii) D １ teeth, 【Chemistry 84】 and D ２ teeth, 【Chemistry 85】 Is it; xiii) D １ teeth, 【Chemistry 86】 and D ２ teeth, 【Chemistry 87】 Is it; xiv) D １ teeth, 【Chemistry 88】 and D ２ teeth, 【Chemistry 89】 Is it; xv) D １ teeth, 【Chemistry 90】 and D ２ teeth, 【Chemistry 91】 Is it; xvi) D １ teeth, 【Chemistry 92】 and D ２ teeth, 【Chemistry 93】 Is it; xvii) D １ teeth, 【Chemistry 94】 and D ２ teeth, 【Chemistry 95】 Is it; xviii)D １ は、 【Chemistry 96】 and D ２ teeth, 【Chemistry 97】 Is it; xix) D １ teeth, 【Chemistry 98】 and D ２ teeth, 【Chemistry 99】 Is it; xx)D １ teeth, 【Chemistry 100】 and D ２ teeth, 【Chemistry 101】 Is it; xxi) D １ teeth, 【Chemistry 102】 and D ２ teeth, 【Chemistry 103】 Is it; xxii) D １ teeth, 【Chemistry 104】 and D ２ teeth, 【Chemistry 105】 Is it; xxiii) D １ teeth, 【Chemistry 106】 and D ２ teeth, 【Chemistry 107】 Is it; xxiv) D １ teeth, 【Chemistry 108】 and D ２ teeth, 【Chemistry 109】 Is it; xxv) D １ teeth, 【Chemistry 110】 and D ２ teeth, 【Chemistry 111】 Is it; xxvi) D １ teeth, 【Chemistry 112】 and D ２ teeth, 【Chemistry 113】 Is it; xxvii) D １ teeth, 【Chemistry 114】 and D ２ teeth, 【Chemistry 115】 Is it; xxviii) D １ teeth, 【Chemistry 116】 and D ２ teeth, 【Chemistry 117】 Is it; xxix) D １ teeth, 【Chemistry 118】 and D ２ teeth, 【Chemistry 119】 Is it; xxx)D １ teeth, 【Chemistry 120】 and D ２ teeth, 【Chemistry 121】 Is it; xxxi)D １ teeth, 【Chemistry 122】 and D ２ teeth, 【Chemistry 123】 Is it; xxxii) D １ teeth, 【Chemical 124】 and D ２ teeth, 【Chemistry 125】 Is it; xxxiii) D １ teeth, 【Chemistry 126】 and D ２ teeth, 【Chemistry 127】 Is it; xxxiv) D １ teeth, 【Chemistry 128】 and D ２ teeth, 【Chemistry 129】 Is it; xxxv)D １ teeth, 【Chemistry 130】 and D ２ teeth, 【Chemistry 131】 Is it; xxxvi)D １ teeth, 【Chemistry 132】 and D ２ teeth, 【Chemistry 133】 Is it; xxxvii) D １ teeth, 【Chemistry 134】 and D ２ teeth, 【Chemistry 135】 Is it; xxxviii) D １ teeth, 【Chemistry 136】 and D ２ teeth, 【Chemistry 137】 Is it; xxxix)D １ teeth, 【Chemistry 138】 and D ２ teeth, 【Chemistry 139】 Is it; xl) D １ teeth, 【Chemistry 140】 and D ２ teeth, 【Chemistry 141】 Is it; xli) D １ teeth, 【Chemistry 142】 and D ２ teeth, 【Chemistry 143】 Is it; xlii) D １ teeth, 【Chemistry 144】 and D ２ teeth, 【Chemistry 145】 Is it; xliii) D １ teeth, 【Chemistry 146】 and D ２ teeth, 【Chemistry 147】 Is it; xliv) D １ teeth, 【Chemistry 148】 and D ２ teeth, 【Chemistry 149】 Is it; vl) D １ teeth, 【Chemistry 150】 and D ２ teeth, 【Chemistry 151】 Is it; xlviii) D １ teeth, 【Chemistry 152】 and D ２ teeth, 【Chemistry 153】 Is it; xlvii) D １ teeth, 【Chemistry 154】 and D ２ teeth, 【Chemistry 155】 Is it; xlviii) D １ teeth, 【Chemistry 156】 and D ２ teeth, 【Chemistry 157】 Is it; il)D １ は、 【Chemistry 158】 and D ２ teeth, 【Chemistry 159】 Is it; l) D １ teeth, 【Chemistry 160】 and D ２ teeth, 【Chemistry 161】 Is it; (li)D １ は、 【Chemistry 162】 and D ２ teeth, 【Chemistry 163】 Is it; lii) D １ teeth, 【Chemistry 164】 and D ２ teeth, 【Chemistry 165】 Is it; liiii) D １ teeth, 【Chemistry 166】 and D ２ teeth, 【Chemistry 167】 Is it; liv)D １ teeth, 【Chemistry 168】 and D ２ teeth, 【Chemistry 169】 Is it; lv) D １ teeth, 【Chemistry 170】 and D ２ teeth, 【Chemistry 171】 Is it; lviii)D １ teeth, 【Chemistry 172】 and D ２ teeth, 【Chemistry 173】 Is it; lvii) D １ teeth, 【Chemistry 174】 and D ２ teeth, 【Chemistry 175】 Is it; lviii) D １ teeth, 【Chemistry 176】 and D ２ teeth, 【Chemistry 177】 Is it; lix)D １ teeth, 【Chemistry 178】 and D ２ teeth, 【Chemistry 179】 Is it; lx)D １ teeth, 【Chemistry 180】 and D ２ teeth, 【Chemistry 181】 Is it; lxi)D １ teeth, 【Chemistry 182】 and D ２ teeth, 【Chemistry 183】 Is it; (lxii)D １ は、 【Chemistry 184】 and D ２ teeth, 【Chemistry 185】 Is it; lxiii) D １ teeth, 【Chemistry 186】 and D ２ teeth, 【Chemistry 187】 Is it; lxiv) D １ teeth, 【Chemistry 188】 and D ２ teeth, 【Chemistry 189】 73. The compound of claim 72, or a pharma- ceutically acceptable salt thereof, wherein: and * indicates the point of attachment to the remainder of the molecule.

74. i) A １ -D １ teeth, 【Chemistry 190】 and A ２ -D ２ teeth, 【Chemistry 191】 Is it; ii) A １ -D １ teeth, 【Chemistry 192】 and A ２ -D ２ teeth, 【Chemistry 193】 Is it; 2000 １ 10 １ は、 【Chemistry 194】 and A ２ -D ２ teeth, 【Chemistry 195】 Is it; iv) A １ -D １ teeth, 【Chemistry 196】 and A ２ -D ２ teeth, 【Chemistry 197】 Is it; v) A １ -D １ teeth, 【Chemistry 198】 and A ２ -D ２ teeth, 【Chemistry 199】 Is it; (vi)A １ -D １ は、 【Chemistry 200】 and A ２ -D ２ teeth, 【Chemistry 201】 Is it; vii) A １ -D １ teeth, 【Chemistry 202】 and A ２ -D ２ teeth, 【Chemistry 203】 Is it; viii)｡ １ -D １ は、 【Chemistry 204】 and A ２ -D ２ teeth, 【Chemistry 205】 Is it; ix)｡ １ -D １ は、 【Chemistry 206】 and A ２ -D ２ teeth, 【Chemistry 207】 Is it; x) A １ -D １ teeth, 【Chemistry 208】 and A ２ -D ２ teeth, 【Chemistry 209】 Is it; xi) A １ -D １ teeth, 【Chemistry 210】 and A ２ -D ２ teeth, 【Chemistry 211】 Is it; x)))? １ . １ は、 【Chemistry 212】 and A ２ -D ２ teeth, 【Chemistry 213】 Is it; xiii)｡ １ -D １ は、 【Chemistry 214】 and A ２ -D ２ teeth, 【Chemistry 215】 Is it; 90) １ 10 １ は、 【Chemistry 216】 and A ２ -D ２ teeth, 【Chemistry 217】 Is it; xv) A １ -D １ teeth, 【Chemistry 218】 and A ２ -D ２ teeth, 【Chemical 219】 Is it; xvi) A １ -D １ teeth, 【Chemistry 220】 and A ２ -D ２ teeth, 【Chemistry 221】 Is it; xvii)｡ １ -D １ は、 【Chemical 222】 and A ２ -D ２ teeth, 【Chemical 223】 Is it; xviii)｡ １ -D １ は、 【Chemical 224】 and A ２ -D ２ teeth, 【Chemistry 225】 Is it; xix) A １ -D １ teeth, 【Chemical 226】 and A ２ -D ２ teeth, 【Chemical 227】 Is it; xx) A １ -D １ teeth, 【Chemical 228】 and A ２ -D ２ teeth, 【Chemical 229】 Is it; xx))? １ . １ は、 【Chemistry 230】 and A ２ -D ２ teeth, 【Chemistry 231】 Is it; xx))? １ . １ は、 【Chemistry 232】 and A ２ -D ２ teeth, 【Chemistry 233】 Is it; 10.00 １ 10 １ は、 【Chemical 234】 and A ２ -D ２ teeth, 【Chemistry 235】 Is it; 2000) １ 10 １ は、 【Chemistry 236】 and A ２ -D ２ teeth, 【Chemistry 237】 Is it; xxv) A １ -D １ teeth, 【Chemical 238】 and A ２ -D ２ teeth, 【Chemical 239】 Is it; xxvi)A １ -D １ は、 【Chemistry 240】 and A ２ -D ２ teeth, 【Chemical Formula 241】 Is it; xxv))? １ . １ は、 【Chemical 242】 and A ２ -D ２ teeth, 【Chemical Formula 243】 Is it; xx)) １ . １ は、 【Chemical 244】 and A ２ -D ２ teeth, 【Chemistry 245】 Is it; xxix) A １ -D １ teeth, 【Chemical 246】 and A ２ -D ２ teeth, 【Chemical 247】 Is it; xxx)A １ -D １ teeth, 【Chemical 248】 and A ２ -D ２ teeth, 【Chemical 249】 Is it; xxxi)A １ -D １ は、 【Chemistry 250】 and A ２ -D ２ teeth, 【Chemistry 251】 Is it; xx)))? １ . １ は、 【Chemistry 252】 and A ２ -D ２ teeth, 【Chemistry 253】 Is it; xxxiii)! １ -D １ は、 【Chemical 254】 and A ２ -D ２ teeth, 【255】 Is it; xxxiv) A １ -D １ teeth, 【256】 and A ２ -D ２ teeth, 【Chemistry 257】 Is it; xxxv) A １ -D １ teeth, 【Chemistry 258】 and A ２ -D ２ teeth, 【Chemical 259】 Is it; 1000) １ 10 １ は、 【Chemistry 260】 and A ２ -D ２ teeth, 【Chemical 261】 Is it; xxxvii) A １ -D １ teeth, 【Chemical 262】 and A ２ -D ２ teeth, 【Chemical 263】 Is it; xxxv))))? １ . １ は、 【Chemical 264】 and A ２ -D ２ teeth, 【Chemistry 265】 Is it; xxxix) A １ -D １ teeth, 【Chemical 266】 and A ２ -D ２ teeth, 【Chemical 267】 Is it; xl) A １ -D １ teeth, 【Chemical 268】 and A ２ -D ２ teeth, 【Chemical 269】 Is it; xli) A １ -D １ teeth, 【Chemistry 270】 and A ２ -D ２ teeth, 【Chemical 271】 Is it; 2000 １ 10 １ は、 【Chemical 272】 and A ２ -D ２ teeth, 【Chemical 273】 Is it; xliii)｡ １ -D １ は、 【Chemical 274】 and A ２ -D ２ teeth, 【Chemistry 275】 Is it; xliv)｡ １ -D １ は、 【Chemical 276】 and A ２ -D ２ teeth, 【Chemical 277】 Is it; xlv) A １ -D １ teeth, 【Chemical 278】 and A ２ -D ２ teeth, 【Chemical 279】 Is it; 10.00 １ 10 １ は、 【Chemistry 280】 and A ２ -D ２ teeth, 【Chemistry 281】 Is it; xlvii) A １ -D １ teeth, 【Chemical 282】 and A ２ -D ２ teeth, 【Chemistry 283】 Is it; xlviii) A １ -D １ teeth, 【Chemical 284】 and A ２ -D ２ teeth, 【Chemistry 285】 Is it; 90 １ 10 １ は、 【Chemistry 286】 and A ２ -D ２ teeth, 【Chemistry 287】 Is it; l) A １ -D １ teeth, 【Chemistry 288】 and A ２ -D ２ teeth, 【Chemical 289】 Is it; (li)A １ -D １ は、 【Chemistry 290】 and A ２ -D ２ teeth, 【Chemical 291】 Is it; lii) A １ -D １ teeth, 【Chemical 292】 and A ２ -D ２ teeth, 【Chemical 293】 Is it; 2000 １ 10 １ は、 【Chemical 294】 and A ２ -D ２ teeth, 【Chemistry 295】 Is it; liv) A １ -D １ teeth, 【Chemical Formula 296】 and A ２ -D ２ teeth, 【Chemical 297】 Is it; lv) A １ -D １ teeth, 【Chemical 298】 and A ２ -D ２ teeth, 【Chemical 299】 Is it; lvi)A １ -D １ は、 【Chemistry 300】 and A ２ -D ２ teeth, 【Chemistry 301】 Is it; lvii) A １ -D １ teeth, 【Chemistry 302】 and A ２ -D ２ teeth, 【Chemistry 303】 Is it; lviii) A １ -D １ teeth, 【Chemistry 304】 and A ２ -D ２ teeth, 【Chemistry 305】 Is it; 00) １ 10 １ は、 【Chemistry 306】 and A ２ -D ２ teeth, 【Chemistry 307】 Is it; lx) A １ -D １ teeth, 【Chemistry 308】 and A ２ -D ２ teeth, 【Chemistry 309】 Is it; lxi)A １ -D １ teeth, 【Chemistry 310】 and A ２ -D ２ teeth, 【Chemistry 311】 Is it; (lxii)A １ -D １ は、 【Chemistry 312】 and A ２ -D ２ teeth, 【Chemistry 313】 Is it; lxiii)A １ -D １ は、 【Chemistry 314】 and A ２ -D ２ teeth, 【Chemistry 315】 or lxiv) A １ -D １ teeth, 【Chemistry 316】 and A ２ -D ２ teeth, 【Chemistry 317】 70. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 69, wherein * indicates the point of attachment to the remainder of the molecule.

75. D １ And / or D ２ 70. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 69, wherein is an auristatin.

76. D １ and D. ２ or a pharma- ceutically acceptable salt thereof, according to claim 75, wherein both of

77. D １ And / or D ２ 70. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 69, which is a topoisomerase 1 inhibitor.

78. D １ and D. ２ 78. The compound or pharma- ceutically acceptable salt of claim 77, wherein both of are topoisomerase 1 inhibitors.

79. D １ and D. ２ is an auristatin, and D １ and D. ２ The compound or pharma- ceutically acceptable salt of any one of claims 1 to 69, wherein the other is a topoisomerase 1 inhibitor.

80. D １ is an auristatin, and D ２ 80. The compound of claim 79, or a pharma- ceutically acceptable salt thereof, which is a topoisomerase 1 inhibitor.

81. D １ is a topoisomerase 1 inhibitor, and D ２ 80. The compound or pharma- ceutically acceptable salt of claim 79, wherein is an auristatin.

82. D １ and D. ２ is, independently, 【Chemistry 318】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to 82. The compound according to any one of claims 1 to 81, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

83. D １ and D. ２ is, independently, 【Chemical 319】 83. The compound of claim 82, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

84. D １ and D. ２ is, independently, 【Chemistry 320】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to 73. The compound or pharma- ceutically acceptable salt thereof of any one of claims 1 to 69 or 72, selected from the group consisting of:

85. D １ and D. ２ is, independently, 【Chemistry 321】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

86. D １ and D. ２ or a pharma- ceutically acceptable salt thereof, each independently selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapeutic sensitizers, topoisomerase inhibitors, and / or vinca alkaloids.

87. D １ and D. ２ are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of the nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; １ Also D ２ 70. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 69, provided that said compound or pharma- ceutically acceptable salt is not a BH3 mimetic.

88. D １ and D. ２ or a pharma- ceutically acceptable salt thereof, wherein each of the formulas (I) and (II) is independently selected from a topoisomerase 1 inhibitor or an enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or addition salt with a pharma- ceutically acceptable acid or base.

89. 89. The compound or pharma- ceutically acceptable salt of claim 88, wherein the topoisomerase 1 inhibitor is topotecan, exatecan, deruxtecan, or SN-38.

90. D １ and D. ２ is, independently, 【Chemistry 322】 where * indicates the point of attachment to the rest of the molecule.

89. The compound of claim 88, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

91. D １ and D. ２ or a pharma- ceutically acceptable salt thereof, wherein each of the formulas (I) and (II) is independently selected from a mitotic inhibitor or an enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or an addition salt with a pharma- ceutically acceptable acid or base.

92. 92. The compound or pharma- ceutically acceptable salt of claim 91, wherein the mitotic inhibitor is monomethylauristatin E (MMAE) or a taxane.

93. 93. The compound or pharma- ceutically acceptable salt of claim 92, wherein the taxane is selected from docetaxel, paclitaxel, or cabazitaxel.

94. 【Fig. 323】 【Chemical 324】 【Chemistry 325】 【Chemical 326】 【Chemical 327】 【Chemical 328】 【Chemical 329】 【Chemistry 330】 【Chemistry 331】 【Chemical 332】 【Chemical 333】 【Chemical 334】 【Chemical 335】 【Chemical 336】 【Chemical 337】 【Chemical 338】 【Chemical 339】 【Chemistry 340】 【Chemical 341】 【Chemical 342】 【Chemical 343】 【Chemical 344】 【Chemical 345】 【Chemical 346】 【Chemical 347】 【Chemical 348】 94. The compound according to any one of claims 1 to 93, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

95. 【Fig. 349】 【Chemistry 350】 【Chemistry 351】 【Chemical Formula 352】 【Chemical 353】 【Chemical 354】 【Chemistry 355】 【Chemical 356】 【Chemical 357】 【Chemical 358】 【Chemical 359】 【Hua360】 【Chemistry 361】 【Chemical 362】 or a pharma- ceutically acceptable salt thereof. The compound according to any one of claims 1 to 94, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

96. 【Chemical Formula 363】 【Hua364】 or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 95, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

97. 【Fig. 365】 【Chemistry 366】 or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 96, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

98. 【Fig. 367】 or a pharma- ceutically acceptable salt thereof.

98. The compound of claim 97, or a pharma- ceutically acceptable salt thereof, selected from the group consisting of:

99. 【Fig. 368】 【Chemical 369】 88. The compound of any one of claims 1 to 87, or a pharma- ceutically acceptable salt thereof, selected from:

100. 【Fig. 370】 【Chemical 371】 88. The compound of any one of claims 1 to 87, or a pharma- ceutically acceptable salt thereof, selected from:

101. 【Fig. 372】 88. The compound of any one of claims 1 to 87, or a pharma- ceutically acceptable salt thereof, selected from:

102. 【Fig. 373】 88. The compound of any one of claims 1 to 87, or a pharma- ceutically acceptable salt thereof, selected from:

103. A conjugate comprising an antibody or antigen-binding fragment thereof covalently linked to two pharmaceutically active drugs via a dual linker, said dual linker having one point of attachment attached to said antibody and two points of attachment to said two pharmaceutically active drugs, provided that neither of the pharmaceutically active drugs is a BH3 mimetic.

104. The conjugate of claim 103, wherein the two pharma- ceutical active drugs are the same or different.

105. 105. The conjugate of claim 103 or 104, wherein the pharma- ceutical active drug is selected from cytotoxic drugs, cytostatic drugs and immunosuppressants.

106. 106. The conjugate of any one of claims 103 to 105, wherein the pharma- ceutically active drug is selected from auristatins, camptothecins, duocarmycins, etoposide, maytansines, maytansinoids, taxanes, benzodiazepines or benzodiazepine-containing drugs (e.g., pyrrolo[1,4]-benzodiazepines (PBDs), indolinobenzodiazepines and oxazolidinobenzodiazepines) and vinca alkaloids.

107. The conjugate of claim 106, wherein the pharma- ceutical active drug is an auristatin.

108. The conjugate of claim 103 or 104, wherein the pharma- ceutically active drug is selected from antitubulin agents, tubulin inhibitors, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapy sensitizers, topoisomerase inhibitors and / or vinca alkaloids.

109. 105. The conjugate of claim 103 or 104, wherein the pharma- ceutically active drug is selected from Eg5 inhibitors, V-ATPase inhibitors, HSP90 inhibitors, IAP inhibitors, mTor inhibitors, microtubule stabilizing agents, microtubule destabilizing agents, auristatins, dolastatins, maytansinoids, MetAP (methionine aminopeptidase), inhibitors of nuclear export of protein CRM1, DPPIV inhibitors, inhibitors of phosphoryl transfer reactions in mitochondria, protein synthesis inhibitors, kinase inhibitors, CDK2 inhibitors, CDK9 inhibitors, proteasome inhibitors, kinesin inhibitors, HDAC inhibitors, DNA damaging agents, DNA alkylating agents, DNA interfering agents, DNA minor groove binders, RNA polymerase inhibitors, amanitin, spliceosome inhibitors, topoisomerase inhibitors, DHFR inhibitors or pro-apoptotic agents.

110. 105. The conjugate of claim 103 or 104, wherein the pharma- ceutically active drug is selected from a topoisomerase 1 inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or addition salt with a pharma- ceutically acceptable acid or base.

111. The conjugate of claim 110, wherein the pharma- ceutically active drug, the topoisomerase 1 inhibitor, is selected from topotecan, exatecan, deruxtecan, and SN-38.

112. The conjugate of claim 103 or 104, wherein the pharma- ceutically active drug is selected from a mitotic inhibitor or its enantiomer, diastereoisomer, atropisomer, deuterated derivative and / or addition salt with a pharma- ceutically acceptable acid or base.

113. The conjugate of claim 112, wherein the mitotic inhibitor is monomethyl auristatin E (MMAE) or a taxane.

114. 114. The conjugate of claim 113, wherein the taxane is selected from docetaxel, paclitaxel, or cabazitaxel.

115. 104. The conjugate of claim 103, comprising a compound according to any one of claims 1 to 102 or a pharma- ceutically acceptable salt thereof.

116. Formula (A-2): 【Chemical 374】 (In the formula, Ab is an antibody or fragment thereof; R １００ is a coupling group; L １ is a bridging spacer; W is a branching moiety; L ２’ and L ３’ are each independently a linker; D １ and D. ２ are each independently a pharma- ceutically active drug, while D １ Also D ２ is not a BH3 mimetic; and a is an integer from 1 to 16. Conjugate of.

117. L ２’ and L ３’ each of which comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

118. L ２’ and L ３’ The conjugate of claim 117, wherein each of comprises a peptide group and a self-immolative group.

119. L ２’ and L ３’ each comprises a cleavable group, and optionally at least one cleavable group comprises a phosphate group, a pyrophosphate group, a sugar (e.g., glucuronamide) group, a peptide group, and / or a self-immolative group (e.g., a peptide group and a self-immolative group).

120. Formula (B-2): 【Chemical 375】 (In the formula, Ab is an antibody or fragment thereof; R １００ is a coupling group; L １ is a bridging spacer; W is N or CR ｗ and R ｗ is H or C １ ~C ６ is alkyl (e.g., R ｗ is H); L ２ and L ３ are each independently a linking spacer; E １ and E ２ are each independently an enzyme cleavage element or a hydrophilic moiety (e.g., E １ and E ２ are each an enzyme cleavage element); V １ and V ２ independently represents: i) a self-immolative group; ii) an enzymatic cleavage element (e.g., V １ and V ２ are each independently a self-immolative group), or iii) comprise a self-immolative group and an enzymatic cleavage element; D １ and D. ２ are each independently a pharma- ceutically active drug, while D １ Also D ２ is not a BH3 mimetic; and a is an integer from 1 to 16. The conjugate according to any one of claims 116 to 118.

121. V １ and V ２ are each independently i) a self-immolative group, or ii) an enzymatic cleavage element (e.g., V １ and V ２ is each independently a self-immolative group.

122. 122. The conjugate of claim 120 or 121, wherein W is N or CH.

123. E １ and E ２ A conjugate according to any one of claims 120 to 122, wherein each of said is an enzymatic cleavage element.

124. V １ and V ２ The conjugate of any one of claims 120 to 123, wherein each is independently a self-immolative group.

125. 125. The conjugate of any one of claims 116 to 124, wherein a is an integer from 1 to 6 or 1 to 4, or a is 1 or 2.

126. The conjugate of any one of claims 116 to 125, wherein a is determined by liquid chromatography-mass spectrometry (LC-MS).

127. (i) the cleavable linker comprises a phosphate group, a pyrophosphate group, and / or a self-immolative group; (ii) the cleavable linker comprises a self-immolative group; or (iii) the cleavable linker comprises -CH ２ -O-, -NH-CH ２ 127. The conjugate of any one of claims 116 to 126, comprising a self-immolative group comprising -, -C(=O)-, para-aminobenzyl-carbamate, para-aminobenzyl-ammonium, para-amino-(sulfo)benzyl-ammonium, para-amino-(sulfo)benzyl-carbamate, para-amino-(alkoxy-PEG-alkyl)benzyl-carbamate, para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-carbamate or para-amino-(polyhydroxycarboxytetrahydropyranyl)alkyl-benzyl-ammonium.

128. The conjugate of claim 127, wherein W is N or CH.

129. R ２ and R ３ The conjugate of claim 127 or 128, wherein each of said groups is a hydrophilic group.

130. Formula (C-2): 【Chemical 376】 (In the formula, Ab is an antibody or antigen-binding fragment thereof; R １００ is a coupling group; L １ is a bridging spacer; W is N or CR ｗ and R ｗ is H or C １ ~C ６ is alkyl (e.g., R ｗ is H); L ２ and L ３ are each independently a linking spacer; E １ and E ２ are each independently a peptide group comprising 1 to 6 amino acids, said peptide group being optionally substituted with a hydrophilic group; A １ and A ２ each independently represents a bond, -OC(=O)-*, 【Chemical 377】 -OC(=O)N(CH ３ ) CH ２ CH ２ N (CH ３ )C(=O)-* or -OC(=O)N(CH ３ ) C(R ａ ) ２ C(R ａ ) ２ N (CH ３ )C(=O)-*, Each R ａ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl; A １ Or A ２ The * is D １ Or D ２ indicates the point of attachment to D １ and D. ２ are each independently a pharma- ceutically active drug, while D １ Also D ２ is not a BH3 mimetic; L ４ and L ５ are each independently a spacer moiety; R ２ and R ３ are each independently a hydrophilic group or an enzymatic cleavage element (e.g., R ２ and R ３ are each a hydrophilic group; and m and n are each independently 0 or 1. The conjugate according to any one of claims 116 to 129.

131. Formula (D1-2), (D2-2) or (D3-2): 【Chemical 378】 The conjugate of claim 130.

132. With respect to formula (D1-2), R ２ and R ３ are each independently a hydrophilic group, and in formula (D2-2), R ２ and R ３ are each independently an enzyme cleavage element; and with respect to formula (D3-2), R ２ is a hydrophilic group, and R ３ is an enzymatic cleavage element.

133. R １００ teeth, 【Chemical 379】 【Hua380】 【Chemistry 381】 【Chemical 382】 【Chemical 383】 【Chemical 384】 【Chemistry 385】 Disulfides (In the formula, R １６ is H, C １ ~C ４ alkyl, phenyl, pyrimidine or pyridine; R １８ is H, C １ ~C ６ C substituted with alkyl, phenyl or 1 to 3 -OH groups １ ~C ４ is alkyl; Each R １５ are independently H, C １ ~C ６ Alkyl, fluoro, benzyloxy substituted with -C(=O)OH, benzyl substituted with -C(=O)OH, C substituted with -C(=O)OH １ ~C ４ Alkoxy and -C(=O)OH substituted C １ ~C ４ alkyl; R １７ is independently selected from H, phenyl and pyridine; q is 0, 1, 2 or 3; R １９ is H or methyl; and R ２０ is H, -CH ３ or phenyl) The conjugate according to any one of claims 116 to 131, selected from the group consisting of:

134. R １００ teeth, 【Chemistry 386】 (In the formula, R １００ (*** indicates the binding point to Ab) The conjugate according to any one of claims 116 to 133, selected from the group consisting of:

135. R １００ teeth, 【Chemical 387】 (In the formula, R １００ (*** indicates the binding point to Ab) The conjugate of claim 134,

136. (1) L １ teeth, 【Chemistry 388】 or *-CH(OH)CH(OH)CH(OH)CH(OH)CH(OH)-** wherein each n is an integer from 1 to 12. Including L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (2) L １ teeth, 【Chemical 389】 and n is an integer from 1 to 12, or n is 1, or n is 12; L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (3) L １ teeth, 【Chemical 390】 and n is an integer from 1 to 12; L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to; (4) L １ teeth, 【Chemical 391】 Including L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ or (5)L １ は、*-C(=O)(CH ２ ) ｍ O(CH ２ ) ｍ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ -**;*-C(=O)NH((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ -**;*-C(=O)O(CH ２ ) ｍ SSC(R Ｌ１ ) ２ (CH ２ ) ｍ C(=O)NR Ｌ１ (CH ２ ) ｍ NR Ｌ１ C(=O)(CH ２ ) ｍ -**;*-C(=O)O(CH ２ ) ｍ C(=O)NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ NH(CH ２ ) ｎ C(=O)-**;*-C(=O)(CH ２ ) ｍ X １ (CH ２ ) ｍ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ NHC(=O)(CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ NHC(=O)(CH ２ ) ｎ -**;*-C(=O)(CH ２ ) ｍ NHC(=O)(CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ NHC(=O)(CH ２ ) ｎ X １ (CH ２ ) ｎ -**;*-C(=O)((CH ２ ) ｍ O) ｔ (CH ２ ) ｎ C(=O)NH(CH ２ ) ｍ -**;*-C(=O)(CH ２ ) ｍ C(R Ｌ１ ) ２ -** or -C(=O)(CH ２ ) ｍ C(=O)NH(CH ２ ) ｍ - is a bridging spacer containing **, and L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ indicates a direct or indirect (e.g., direct) point of attachment to X １ teeth, 【Chemical 392】 and each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and Each t is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30; and Each R Ｌ１ are independently H and C １ ~C ６ The conjugate of any one of claims 116 to 135, wherein the alkyl is selected from the group consisting of aryl, aryl, aryl and alkyl.

137. L １ teeth, 【Chemical 393】 (wherein n is an integer from 1 to 12 (e.g., 4 to 8, e.g., 4 or 8), and L １ indicates a direct or indirect (e.g., direct) point of attachment to W, and L １ The ** in the is R １ (Indicating the direct or indirect point of attachment to The conjugate of any one of claims 116 to 136, comprising a moiety represented by:

138. The conjugate of claim 137, wherein n is an integer from 4 to 8.

139. The conjugate of claim 138, wherein n is 4 or 8.

140. L １ is the formula 【Chemical 394】 (In the formula, n is an integer from 1 to 12 (e.g., 4 to 8, for example, 4 or 8); x is an integer from 0 to 6 (e.g., 0 to 4, e.g., 0 to 2, e.g., 0 or 2); y is 0 or 1; z is an integer from 0 to 6 (e.g., 0 to 4, for example, 0 to 2, for example, 0 or 2); u is 0 or 1; L １ * indicates the direct point of attachment to W, and L １ The ** in the is R １ (Indicates the direct attachment point to The conjugate according to any one of claims 116 to 110, represented by:

141. The conjugate of claim 140, wherein n is an integer from 4 to 8.

142. The conjugate of claim 141, wherein n is 4 or 8.

143. The conjugate of any one of claims 140 to 142, wherein x is an integer from 0 to 2.

144. The conjugate of claim 143, wherein x is 0 or 2.

145. The conjugate of any one of claims 140 to 144, wherein z is an integer from 0 to 2.

146. The conjugate of claim 145, wherein z is 0 or 2.

147. L １ teeth, 【Chemical 395】 The conjugate of any one of claims 116 to 146, selected from the group consisting of:

148. L ２ and L ３ are each independently 【Chemical 396】 (In the formula, k is an integer from 0 to 6; r is 0 or 1; o is an integer from 0 to 12; p is an integer from 0 to 6; L ２ Or L ３ The # in each １ Or E ２ and L ２ Or L ３ ## indicates the direct or indirect point of attachment to W. The conjugate of any one of claims 120 to 147, wherein the linking spacer comprises a moiety represented by:

149. L ２ and L ３ are each independently 【Chemical 397】 【Chemical 398】 【Chemical 399】 (In the formula, k in each occurrence is independently an integer from 0 to 4; r in each occurrence is independently 0 or 1; o in each occurrence is independently an integer from 0 to 10; p in each occurrence is independently an integer from 0 to 4; R Ｌ２３ is hydrogen or C １ ~C ６ is alkyl; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ is a hydrophilic group; and L ２ Or L ３ The # in each １ Or E ２ and L ２ Or L ３ ## indicates the direct point of attachment to W; When W is N, L ２ and L ３ (provided that it is not (L2c), (L2d), (L2f) or (L2k) The conjugate of any one of claims 120 to 147, wherein the linking spacer is selected from the group consisting of:

150. L ２ and L ３ are each independently 【Chemical 400】 【Chemistry 401】 【Chemistry 402】 (In the formula, k in each occurrence is independently an integer from 1 to 3; o in each occurrence is independently an integer from 1 to 9; p in each occurrence is independently an integer from 1 to 3; R Ｌ２３ is hydrogen or C １ ~C ３ is alkyl; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ is a hydrophilic group; and L ２ Or L ３ The # in each １ Or E ２ and L ２ Or L ３ indicates the direct point of attachment to W; when W is N, L ２ and L ３ (provided that the L2FF, L2MM, L2NN, L2OO, or L2PP is not the same) The conjugate of claim 149, wherein the linking spacer is selected from the group consisting of:

151. L ２ and L ３ is, independently, 【Chemistry 403】 【Chemistry 404】 (In the formula, L ２ Or L ３ The # in each １ Or E ２ indicates a direct point of attachment to ２ Or L ３ ## indicates the direct point of attachment to W; R Ｌ is hydrogen or -C(O)-R Ｈ and R Ｈ teeth, 【Chemistry 405】 and d is an integer from 20 to 30 (e.g., 25). The conjugate of any one of claims 120 to 150, wherein the linking spacer is selected from the group consisting of:

152. The conjugate of claim 151, wherein d is 25.

153. 153. The conjugate of any one of claims 130-152, wherein each peptide group independently comprises 1 to 4, 1 to 3, or 1 to 2 amino acid residues.

154. 154. The conjugate of claim 153, wherein each peptide group independently comprises two amino acid residues.

155. 155. The conjugate of claim 153 or 154, wherein each amino acid residue is independently selected from glycine (Gly), L-valine (Val), L-citrulline (Cit), L-cysteic acid (sulfo-Ala), L-lysine (Lys), L-isoleucine (Ile), L-phenylalanine (Phe), L-methionine (Met), L-asparagine (Asn), L-proline (Pro), L-alanine (Ala), L-leucine (Leu), L-tryptophan (Trp), L-tyrosine (Tyr) and β-alanine (β-Ala).

156. 154. The conjugate of any one of claims 130 to 153, wherein each peptide group is independently selected from Val-Cit, Phe-Lys, Val-Ala, Val-Lys, Leu-Cit, Cit-(β-Ala), Gly-Gly-Gly, Gly-Gly-Phe-Gly, and Sulfo-Ala-Val-Ala.

157. E １ and / or E ２ are each independently 【Chemistry 406】 (In the formula, E1-1 or E1-2 is V in formula (B). １ Or V ２ or a direct point of attachment to the —NH— group in formulas (C) and (D); and ^ in E1-1 or E1-2 respectively represents L ２ Or L ３ indicates a direct point of attachment to １ and E ２ are peptide groups independently selected from (E1-1) and (E1-2) The conjugate of any one of claims 120 to 153, wherein the peptide group is selected from the group consisting of:

158. E １ and E ２ is a peptide group independently selected from (E1-1) and (E1-2).

159. E １ and / or E ２ are each independently 【Chemistry 407】 (In the formula, R Ｅ is a hydrophilic group R Ｈ (It is) The conjugate of any one of claims 120 to 153, wherein the peptide group is represented by:

160. The hydrophilic group R in (E1-3) Ｈ teeth, 【Chemistry 408】 (wherein e is an integer from 20 to 30 (e.g., 25)). The conjugate of claim 159,

161. The conjugate of claim 160, wherein e is 25.

162. E １ and E ２ are respectively 【Chemistry 409】 The conjugate of claim 157,

163. A １ and A ２ are independently a bond and -OC(=O)-* (wherein * represents D １ Or D ２ The conjugate of any one of claims 130 to 162, wherein

164. A １ and A ２ are independent, bonded, 【Chemistry 410】 and -OC(=O)-* (wherein * represents D １ Or D ２ The conjugate of any one of claims 130 to 162, wherein

165. A １ and A ２ The conjugate of claim 163, wherein is a bond.

166. A １ and A ２ The conjugate of claim 163, wherein both are -OC(=O)-*.

167. A １ and A ２ One of the groups is OC(=O)-*, and A １ and A ２ The conjugate of claim 163, wherein the other is a bond.

168. A １ and A ２ is independently a bond, or 【Chemistry 411】 (In the formula, * represents D １ Or D ２ (Indicates the attachment point to The conjugate of claim 164,

169. A １ and A ２ On the other hand, 【Chemistry 412】 And A １ and A ２ The conjugate of claim 164, wherein the other is a bond.

170. A １ and A ２ Both 【Chemistry 413】 The conjugate of claim 164,

171. A １ and A ２ On the other hand, 【Chemistry 414】 And A １ and A ２ The conjugate of claim 164, wherein the other is OC(=O)-*.

172. i) A １ and A ２ is -OC(=O)-*; (ii) A １ and A ２ teeth, 【Chemistry 415】 or (iii) A １ is OC(=O)-*, and A ２ is a bond or (iv) A １ is OC(=O)-*, and A ２ teeth, 【Chemistry 416】 or (v) A １ is a bond, and A ２ teeth, 【Chemistry 417】 or (vi) A １ is a bond, and A ２ is OC(=O)-*, * is D １ Or D ２ The conjugate of claim 164, showing the point of attachment to

173. i) L ４ and L ５ are each independently 【Chemistry 418】 (In the formula, Z is -O-, -CH ２ --, --CH ２ O-, -CH ２ N (R Ｌ４５ )C(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NH-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)-, -C(=O)NR Ｌ４５ -, -C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)NR Ｌ４５ -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) ２ NH-, -NHS(O) ２ -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R Ｌ４５ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl) ； and X is a bond, triazolyl or -CH ２ -triazolyl-, X is R ２ Or R ３ (connected to or a spacer moiety having the structure (ii) L ４ and L ５ is, independently, 【Chemistry 419】 (In the formula, Z is -CH ２ --, --CH ２ O-, -CH ２ N (R Ｌ４５ )C(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)O-, -NHC(=O)C(R Ｌ４５ ) ２ NH-, -NHC(=O)C(R Ｌ４５ ) ２ NHC(=O)-, -C(=O)NR ｂ -, -C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH-, -CH ２ N.R. Ｌ４５ C(=O)NR Ｌ４５ -, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O) ２ NH-, -NHS(O) ２ -, -C(=O)-, -C(=O)O-, or -NH- (wherein each R Ｌ４５ are independently H, C １ ~C ６ Alkyl and C ３ ~C ８ cycloalkyl); and X is -CH ２ -Triazolyl-C １ ~C ４ Alkylene-OC(O)NHS(O) ２ NH-, -C ４ ~C ６ Cycloalkylene-OC(O)NHS(O) ２ NH-, -(CH ２ CH ２ O) ｎ -C(O)NHS(O) ２ NH-, -(CH ２ CH ２ O) ｎ -C(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ --, --CH ２ -Triazolyl-C １ ~C ４ Alkylene-OC(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ -, -C ４ ~C ６ Cycloalkylene-OC(O)NHS(O) ２ NH-(CH ２ CH ２ O) ｎ where each n is independently 1, 2, or 3; X is R ２ Or R ３ (connected to The conjugate of any one of claims 130 to 167, wherein the spacer moiety has the structure:

174. Z is -O-, -CH ２ N.R. Ｌ４５ C(=O)-, -CH ２ N.R. Ｌ４５ C(=O)NH- or -CH ２ X is a bond, triazolyl or -CH ２ -triazolyl-; and R Ｌ４５ is, at each occurrence, independently H or C １ ~C ３ The conjugate of claim 173, which is alkyl.

175. L ４ and L ５ are each independently 【Chemistry 420】 (In the formula, L ４ Or L ５ @ indicates the direct point of attachment to the phenyl group, and L ４ Or L ５ The @@ in is R ２ Or R ３ (Indicates the direct attachment point to The conjugate of any one of claims 130 to 174, wherein the spacer moiety is selected from the group consisting of:

176. R ２ and R ３ The hydrophilic groups represented by the formula (I) are each independently selected from polyethylene glycol, polyalkylene glycol, polyol, polysarcosine, sugar, oligosaccharide, polypeptide, 1 to 3 【Chemistry 421】 C substituted with ２ ~C ６ Alkyl or -OC(=O)NHS(O) ２ N.H.C.H. ２ CH ２ OCH ３ , -NHC(=O)C １ ~C ４ Alkylene-P(O)(OCH ２ CH ３ ) ２ and C substituted with 1 to 2 substituents independently selected from —COOH groups. ２ ~C ６ 176. The conjugate of any one of claims 130 to 175, comprising an alkyl.

177. R ２ Or / and R ３ are each independently 【Chemistry 422】 (wherein n is an integer from 1 to 6). 【Chemistry 423】 The conjugate of any one of claims 130 to 175, selected from the group consisting of:

178. R ２ Or / and R ３ are each independently (i) the part: 【Chemistry 424】 (In the formula, f is an integer from 3 to 25; and R ２３ is H, -CH ３ or -CH ２ CH ２ C(=O)OH) Polysarcosine having the formula: (ii) Formula: 【Chemistry 425】 (wherein g and h are independently an integer from 2 to 30). or (iii) 【Chemistry 426】 The part represented by The conjugate of any one of claims 130 to 175, comprising:

179. R ２ Or R ３ The hydrophilic groups represented by (i) the part: 【Chemistry 427】 where f is an integer from 3 to 25; and R ２３ is H, -CH ３ or -CH ２ CH ２ C(=O)OH) or polysarcosine having the formula (ii) Formula: 【Chemistry 428】 (wherein g and h are independently an integer from 2 to 30). or (iii) 【Chemistry 429】 The part represented by The conjugate of any one of claims 130 to 175, comprising:

180. R ２ and R ３ are each independently 【Chemistry 430】 (wherein g and h are independently an integer from 20 to 30 (e.g., 23 or 24). The conjugate of any one of claims 130 to 175, selected from the group consisting of:

181. R ２ Or / and R ３ teeth, 【Chemistry 431】 The conjugate of claim 180, comprising:

182. R ２ and R ３ each independently represents the formula: 【Chemistry 432】 (wherein g and h are independently an integer from 2 to 30). The conjugate of claim 151, comprising a polyethylene glycol of

183. D １ and D. ２ The conjugate of any one of claims 103 to 182, wherein:

184. D １ and D. ２ The conjugate of any one of claims 103 to 182, wherein:

185. D １ and D. ２ The conjugate of any one of claims 103 to 184, wherein each of said agents is independently selected from a cytotoxic drug, a cytostatic drug, and an immunosuppressant.

186. D １ and D. ２ and R are each independently selected from an auristatin, a camptothecin, a duocarmycin, an etoposide, a maytansine, a maytansinoid, a taxane, a benzodiazepine or a benzodiazepine-containing drug (e.g., a pyrrolo[1,4]-benzodiazepine (PBD), an indolinobenzodiazepine, and an oxazolidinobenzodiazepine), and a vinca alkaloid.

187. D １ and D. ２ is, independently, 【Chemistry 433】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

188. i) D １ teeth, 【Chemistry 434】 and D ２ teeth, 【Chemistry 435】 Is it; ii) D １ teeth, 【Chemistry 436】 and D ２ teeth, 【Chemistry 437】 Is it; iii) D １ teeth, 【Chemistry 438】 and D ２ teeth, 【Chemistry 439】 Is it; iv) D １ teeth, 【Chemistry 440】 and D ２ teeth, 【Chemistry 441】 Is it; v) D １ teeth, 【Chemical 442】 and D ２ teeth, 【Chemical 443】 Is it; (vi)D １ は、 【Chemical 444】 and D ２ teeth, 【Chemistry 445】 Is it; vii) D １ teeth, 【Chemical 446】 and D ２ teeth, 【Chemical 447】 Is it; viii) D １ teeth, 【Chemistry 448】 and D ２ teeth, 【Chemical 449】 Is it; ix) D １ teeth, 【Chemical 450】 and D ２ teeth, 【Chemistry 451】 Is it; x) D １ teeth, 【Chemistry 452】 and D ２ teeth, 【Chemistry 453】 Is it; xi) D １ teeth, 【Chemistry 454】 and D ２ teeth, 【Chemistry 455】 Is it; xii) D １ teeth, 【Chemistry 456】 and D ２ teeth, 【Chemistry 457】 Is it; xiii) D １ teeth, 【Chemistry 458】 and D ２ teeth, 【Chemistry 459】 Is it; xiv) D １ teeth, 【Chemistry 460】 and D ２ teeth, 【Chemistry 461】 Is it; xv) D １ teeth, 【Chemistry 462】 and D ２ teeth, 【Chemistry 463】 Is it; xvi) D １ teeth, 【Chemistry 464】 and D ２ teeth, 【Chemistry 465】 Is it; xvii) D １ teeth, 【Chemistry 466】 and D ２ teeth, 【Chemistry 467】 Is it; xviii)D １ は、 【Chemistry 468】 and D ２ teeth, 【Chemistry 469】 Is it; xix) D １ teeth, 【Chemistry 470】 and D ２ teeth, 【Chemistry 471】 Is it; xx)D １ teeth, 【Chemistry 472】 and D ２ teeth, 【Chemistry 473】 Is it; xxi) D １ teeth, 【Chemical 474】 and D ２ teeth, 【Chemistry 475】 Is it; xxii) D １ teeth, 【Chemistry 476】 and D ２ teeth, 【Chemistry 477】 Is it; xxiii) D １ teeth, 【Chemistry 478】 and D ２ teeth, 【Chemical 479】 Is it; xxiv) D １ teeth, 【Chemistry 480】 and D ２ teeth, 【Chemistry 481】 Is it; xxv) D １ teeth, 【Chemistry 482】 and D ２ teeth, 【Chemistry 483】 Is it; xxvi) D １ teeth, 【Chemistry 484】 and D ２ teeth, 【Chemistry 485】 Is it; xxvii) D １ teeth, 【Chemistry 486】 and D ２ teeth, 【Chemistry 487】 Is it; xxviii) D １ teeth, 【Chemistry 488】 and D ２ teeth, 【Chemistry 489】 Is it; xxix) D １ teeth, 【Chemistry 490】 and D ２ teeth, 【Chemistry 491】 Is it; xxx)D １ teeth, 【Chemistry 492】 and D ２ teeth, 【Chemistry 493】 Is it; xxxi)D １ teeth, 【Chemistry 494】 and D ２ teeth, 【Chemistry 495】 Is it; xxxii) D １ teeth, 【Chemistry 496】 and D ２ teeth, 【Chemistry 497】 Is it; xxxiii) D １ teeth, 【Chemistry 498】 and D ２ teeth, 【Chemistry 499】 Is it; xxxiv) D １ teeth, 【Chemical 500】 and D ２ teeth, 【Chemistry 501】 Is it; xxxv)D １ teeth, 【Chemistry 502】 and D ２ teeth, 【Chemistry 503】 Is it; xxxvi)D １ teeth, 【Chemistry 504】 and D ２ teeth, 【Chemistry 505】 Is it; xxxvii) D １ teeth, 【Chemistry 506】 and D ２ teeth, 【Chemistry 507】 Is it; xxxviii) D １ teeth, 【Chemistry 508】 and D ２ teeth, 【Chemistry 509】 Is it; xxxix)D １ teeth, 【Chemistry 510】 and D ２ teeth, 【Chemistry 511】 Is it; xl) D １ teeth, 【Chemistry 512】 and D ２ teeth, 【Chemistry 513】 Is it; xli) D １ teeth, 【Chemistry 514】 and D ２ teeth, 【Chemistry 515】 Is it; xlii) D １ teeth, 【Chemistry 516】 and D ２ teeth, 【Chemistry 517】 Is it; xliii) D １ teeth, 【Chemistry 518】 and D ２ teeth, 【Chemistry 519】 Is it; xliv) D １ teeth, 【Chemistry 520】 and D ２ teeth, 【Chemistry 521】 Is it; vl) D １ teeth, 【Chemistry 522】 and D ２ teeth, 【Chemistry 523】 Is it; xlviii) D １ teeth, 【Chemistry 524】 and D ２ teeth, 【Chemistry 525】 Is it; xlvii) D １ teeth, 【Chemistry 526】 and D ２ teeth, 【Chemistry 527】 Is it; xlviii) D １ teeth, 【Chemistry 528】 and D ２ teeth, 【Chemistry 529】 Is it; il)D １ は、 【Chemistry 530】 and D ２ teeth, 【Chemistry 531】 Is it; l) D １ teeth, 【Chemistry 532】 and D ２ teeth, 【Chemistry 533】 Is it; (li)D １ は、 【Chemical 534】 and D ２ teeth, 【Chemistry 535】 Is it; lii) D １ teeth, 【Chemistry 536】 and D ２ teeth, 【Chemistry 537】 Is it; liiii) D １ teeth, 【Chemistry 538】 and D ２ teeth, 【Chemistry 539】 Is it; liv)D １ teeth, 【Chemistry 540】 and D ２ teeth, 【Chemistry 541】 Is it; lv) D １ teeth, 【Chemical 542】 and D ２ teeth, 【Chemical 543】 Is it; lviii)D １ teeth, 【Chemical 544】 and D ２ teeth, 【Chemistry 545】 Is it; lvii) D １ teeth, 【Chemical 546】 and D ２ teeth, 【Chemical 547】 Is it; lviii) D １ teeth, 【Chemistry 548】 and D ２ teeth, 【Chemical 549】 Is it; lix)D １ teeth, 【Chemistry 550】 and D ２ teeth, 【Chemistry 551】 Is it; lx)D １ teeth, 【Chemistry 552】 and D ２ teeth, 【Chemistry 553】 Is it; lxi)D １ teeth, 【Chemical 554】 and D ２ teeth, 【Chemistry 555】 Is it; (lxii)D １ は、 【Chemistry 556】 and D ２ teeth, 【Chemistry 557】 Is it; lxiii) D １ teeth, 【Chemistry 558】 and D ２ teeth, 【Chemical 559】 or lxiv) D １ teeth, 【Chemistry 560】 and D ２ teeth, 【Chemistry 561】 and * indicates the point of attachment to the remainder of the molecule.

189. i) A １ -D １ teeth, 【Chemistry 562】 and A ２ -D ２ teeth, 【Chemistry 563】 Is it; ii) A １ -D １ teeth, 【Chemistry 564】 and A ２ -D ２ teeth, 【Chemistry 565】 Is it; 2000 １ 10 １ は、 【Chemistry 566】 and A ２ -D ２ teeth, 【Chemistry 567】 Is it; iv) A １ -D １ teeth, 【Chemistry 568】 and A ２ -D ２ teeth, 【Chemical 569】 Is it; v) A １ -D １ teeth, 【Chemistry 570】 and A ２ -D ２ teeth, 【Chemistry 571】 Is it; (vi)A １ -D １ は、 【Chemistry 572】 and A ２ -D ２ teeth, 【Chemistry 573】 Is it; vii) A １ -D １ teeth, 【Chemical 574】 and A ２ -D ２ teeth, 【Chemistry 575】 Is it; viii)｡ １ -D １ は、 【Chemistry 576】 and A ２ -D ２ teeth, 【Chemistry 577】 Is it; ix)｡ １ -D １ は、 【Chemistry 578】 and A ２ -D ２ teeth, 【Chemical 579】 Is it; x) A １ -D １ teeth, 【Chemistry 580】 and A ２ -D ２ teeth, 【Chemistry 581】 Is it; xi) A １ -D １ teeth, 【Chemistry 582】 and A ２ -D ２ teeth, 【Chemistry 583】 Is it; x)))? １ . １ は、 【Chemistry 584】 and A ２ -D ２ teeth, 【Chemistry 585】 Is it; xiii)｡ １ -D １ は、 【Chemistry 586】 and A ２ -D ２ teeth, 【Chemistry 587】 Is it; 90) １ 10 １ は、 【Chemistry 588】 and A ２ -D ２ teeth, 【Chemistry 589】 Is it; xv) A １ -D １ teeth, 【Chemistry 590】 and A ２ -D ２ teeth, 【Chemistry 591】 Is it; xvi) A １ -D １ teeth, 【Chemistry 592】 and A ２ -D ２ teeth, 【Chemistry 593】 Is it; xvii)｡ １ -D １ は、 【Chemistry 594】 and A ２ -D ２ teeth, 【Chemistry 595】 Is it; xviii)｡ １ -D １ は、 【Chemistry 596】 and A ２ -D ２ teeth, 【Chemistry 597】 Is it; xix) A １ -D １ teeth, 【Chemistry 598】 and A ２ -D ２ teeth, 【Chemistry 599】 Is it; xx) A １ -D １ teeth, 【Chemical 600】 and A ２ -D ２ teeth, 【Chemistry 601】 Is it; xx))? １ . １ は、 【Chemistry 602】 and A ２ -D ２ teeth, 【Chemistry 603】 Is it; xx))? １ . １ は、 【Chemistry 604】 and A ２ -D ２ teeth, 【Chemistry 605】 Is it; 10.00 １ 10 １ は、 【Chemistry 606】 and A ２ -D ２ teeth, 【Chemistry 607】 Is it; 2000) １ 10 １ は、 【Chemistry 608】 and A ２ -D ２ teeth, 【Chemistry 609】 Is it; xxv) A １ -D １ teeth, 【Chemistry 610】 and A ２ -D ２ teeth, 【Chemistry 611】 Is it; xxvi)A １ -D １ は、 【Chemistry 612】 and A ２ -D ２ teeth, 【Chemistry 613】 Is it; xxv))? １ . １ は、 【Chemistry 614】 and A ２ -D ２ teeth, 【Chemistry 615】 Is it; xx)) １ . １ は、 【Chemistry 616】 and A ２ -D ２ teeth, 【Chemistry 617】 Is it; xxix) A １ -D １ teeth, 【Chemistry 618】 and A ２ -D ２ teeth, 【Chemistry 619】 Is it; xxx)A １ -D １ teeth, 【Chemistry 620】 and A ２ -D ２ teeth, 【Chemistry 621】 Is it; xxxi)A １ -D １ は、 【Chemical Formula 622】 and A ２ -D ２ teeth, 【Chemical Formula 623】 Is it; xx)))? １ . １ は、 【Chemical Formula 624】 and A ２ -D ２ teeth, 【Chemistry 625】 Is it; xxxiii)! １ -D １ は、 【Chemical 626】 and A ２ -D ２ teeth, 【Chemical Formula 627】 Is it; xxxiv) A １ -D １ teeth, 【Chemical Formula 628】 and A ２ -D ２ teeth, 【Chemical Formula 629】 Is it; xxxv) A １ -D １ teeth, 【Chemistry 630】 and A ２ -D ２ teeth, 【Chemistry 631】 Is it; 1000) １ 10 １ は、 【Chemistry 632】 and A ２ -D ２ teeth, 【Chemistry 633】 Is it; xxxvii) A １ -D １ teeth, 【Chemical Formula 634】 and A ２ -D ２ teeth, 【Chemistry 635】 Is it; xxxv))))? １ . １ は、 【Chemistry 636】 and A ２ -D ２ teeth, 【Chemical 637】 Is it; xxxix) A １ -D １ teeth, 【Chemical 638】 and A ２ -D ２ teeth, 【Chemical Formula 639】 Is it; xl) A １ -D １ teeth, 【Chemistry 640】 and A ２ -D ２ teeth, 【Chemistry 641】 Is it; xli) A １ -D １ teeth, 【Chemical Formula 642】 and A ２ -D ２ teeth, 【Chemical 643】 Is it; 2000 １ 10 １ は、 【Chemical Formula 644】 and A ２ -D ２ teeth, 【Chemistry 645】 Is it; xliii)｡ １ -D １ は、 【Chemical 646】 and A ２ -D ２ teeth, 【Chemical 647】 Is it; xliv)｡ １ --D １ は、 【Chemical 648】 and A ２ -D ２ teeth, 【Chemical Formula 649】 Is it; xlv) A １ -D １ teeth, 【Chemistry 650】 and A ２ -D ２ teeth, 【Chemistry 651】 Is it; 10.00 １ 10 １ は、 【Chemistry 652】 and A ２ -D ２ teeth, 【Chemistry 653】 Is it; xlvii) A １ -D １ teeth, 【Chemistry 654】 and A ２ -D ２ teeth, 【Chemistry 655】 Is it; xlviii) A １ -D １ teeth, 【Chemistry 656】 and A ２ -D ２ teeth, 【Chemistry 657】 Is it; 90 １ 10 １ は、 【Chemistry 658】 and A ２ -D ２ teeth, 【Chemical 659】 Is it; l) A １ -D １ teeth, 【Chemistry 660】 and A ２ -D ２ teeth, 【Chemistry 661】 Is it; (li)A １ -D １ は、 【Chemical Formula 662】 and A ２ -D ２ teeth, 【Chemical Formula 663】 Is it; lii) A １ -D １ teeth, 【Chemical Formula 664】 and A ２ -D ２ teeth, 【Chemical Formula 665】 Is it; 2000 １ 10 １ は、 【Chemical Formula 666】 and A ２ -D ２ teeth, 【Chemical 667】 Is it; liv) A １ -D １ teeth, 【Chemical 668】 and A ２ -D ２ teeth, 【Chemical Formula 669】 Is it; lv) A １ -D １ teeth, 【Chemistry 670】 and A ２ -D ２ teeth, 【Chemistry 671】 Is it; lvi)A １ -D １ は、 【Chemical 672】 and A ２ -D ２ teeth, 【Chemical Formula 673】 Is it; lvii) A １ -D １ teeth, 【Chemical Formula 674】 and A ２ -D ２ teeth, 【Chemistry 675】 Is it; lviii) A １ -D １ teeth, 【Chemical Formula 676】 and A ２ -D ２ teeth, 【Chemical Formula 677】 Is it; 00) １ 10 １ は、 【Chemical Formula 678】 and A ２ -D ２ teeth, 【Chemical Formula 679】 Is it; lx) A １ -D １ teeth, 【Chemistry 680】 and A ２ -D ２ teeth, 【Chemistry 681】 Is it; lxi)A １ -D １ teeth, 【Chemistry 682】 and A ２ -D ２ teeth, 【Chemistry 683】 Is it; (lxii)A １ -D １ は、 【Chemistry 684】 and A ２ -D ２ teeth, 【Chemistry 685】 Is it; lxiii)A １ -D １ は、 【Chemistry 686】 and A ２ -D ２ teeth, 【Chemistry 687】 or lxiv) A １ -D １ teeth, 【Chemistry 688】 and A ２ -D ２ teeth, 【Chemistry 689】 and * indicates the point of attachment to the remainder of the molecule.

190. D １ And / or D ２ The conjugate of any one of claims 103 to 184, wherein is an auristatin.

191. D １ and D. ２ The conjugate of claim 190, wherein both of are auristatins.

192. D １ And / or D ２ The conjugate of any one of claims 116 to 184, wherein said compound is a topoisomerase 1 inhibitor.

193. D １ and D. ２ The conjugate of claim 192, wherein both of are topoisomerase 1 inhibitors.

194. D １ and D. ２ is an auristatin, and D １ and D. ２ The conjugate according to any one of claims 116 to 184, wherein the other is a topoisomerase 1 inhibitor.

195. D １ is an auristatin, and D ２ The conjugate of claim 194, wherein said compound is a topoisomerase 1 inhibitor.

196. D １ is a topoisomerase 1 inhibitor, and D ２ The conjugate of claim 194, wherein is an auristatin.

197. D １ and D. ２ is, independently, 【Chemistry 690】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to The conjugate of claim 190, selected from the group consisting of:

198. D １ and D. ２ is, independently, 【Chemistry 691】 The conjugate of claim 197, selected from the group consisting of:

199. D １ and D. ２ is, independently, 【Chemical Formula 692】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

200. D １ and D. ２ is, independently, 【Chemistry 693】 (In the formula, * represents A １ Or A ２ (Indicates the attachment point to or a pharma- ceutically acceptable salt thereof.

201. D １ and D. ２ is independently selected from an antitubulin agent, a tubulin inhibitor, a DNA minor groove binder, a DNA replication inhibitor, an alkylating agent, an antibiotic, an antifolate, an antimetabolite, a chemotherapeutic sensitizer, a topoisomerase inhibitor, and / or a vinca alkaloid.

202. D １ and D. ２ are each independently selected from an Eg5 inhibitor, a V-ATPase inhibitor, an HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, MetAP (methionine aminopeptidase), an inhibitor of the nuclear export of protein CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reaction in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, a HDAC inhibitor, a DNA damaging agent, a DNA alkylating agent, a DNA interfering agent, a DNA minor groove binder, an RNA polymerase inhibitor, an amanitin, a spliceosome inhibitor, a topoisomerase inhibitor, a DHFR inhibitor, or a proapoptotic agent; １ Also D ２ A conjugate according to any one of claims 103 to 184, provided that said conjugate is not a BH3 mimetic.

203. A conjugate comprising an antibody or antigen-binding fragment bound to one or more (eg, 1-16, such as 1-4) compounds independently selected from claims 94 or 96.

204. The conjugate of any one of claims 103 to 203, wherein the antibody or antigen-binding fragment binds to a target antigen on a cancer cell.

205. (i) the target antigen is selected from BCMA, CD33, HER2, CD38, CD48, CD79b, PCAD, CD74, CD138, SLAMF7, CD123, CLL1, FLT3, CD7, CKIT, CD56, DLL3, DLK1, B7-H3, EGFR, CD71, EphA2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, TROP2, LIV1, CD46, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; (ii) the target antigen is selected from EGFR, CD7, HER2, EPCAM, FOLR1, ENPP3, MET, AXL, SLC34A2, Nectin4, MSLN, F3, MUC16, SLC39A6, TFRC, TACSTD2, and GPNMB; or (iii) The conjugate of claim 204, wherein the target antigen is PCAD, CD48, CD74, EphA2, HER2, TROP2, B7-H3 or 5T4.

206. 206. The conjugate of claim 204 or 205, wherein the antibody or antigen-binding fragment thereof is selected from Table D1.

207. The conjugate of claim 204, wherein said antibody or antigen-binding fragment having CDR sequences is selected from those in Tables D3 and D8, or said antibody or antigen-binding fragment having variable regions is selected from those in Tables D2 and D8, or said antibody or antigen-binding fragment having full length is selected from those in Tables D4, D5 and D7.

208. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 268, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 269, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 172, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 256, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 257, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 263, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 265; 6) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 258, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; 7) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 259, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 260, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 261; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 215, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 264, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174; and 8) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 169, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 170, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 171; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 266, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 173, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 174 The conjugate of claim 204, which is an anti-CD74 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

209. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-CD74 antibody comprising (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 262, or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

267.

210. The antibody or antigen-binding fragment comprises: (a) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 237, or a sequence at least 95% identical to SEQ ID NO: 237; (b) a heavy chain amino acid sequence of SEQ ID NO:236, or a sequence at least 95% identical to SEQ ID NO:236, and a light chain amino acid sequence of SEQ ID NO:237, or a sequence at least 95% identical to SEQ ID NO:237; or (c) a heavy chain amino acid sequence of SEQ ID NO: 118, or a sequence at least 95% identical to SEQ ID NO: 118, and a light chain amino acid sequence of SEQ ID NO: 239, or a sequence at least 95% identical to SEQ ID NO:

239. The conjugate of claim 204, which is an anti-CD74 antibody comprising:

211. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 271, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 272, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 281, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 283; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 274, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 285, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 276, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 287, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 282, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 279, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 275, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 273; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 284, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 288, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 286; and 5) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 51, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 52, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 53; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 54, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 55, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 56 The conjugate of claim 204, which is an anti-CD48 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

212. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 270 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 280; or (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

14.

213. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-CD48 antibody comprising: (a) a heavy chain amino acid sequence of SEQ ID NO:240, or a sequence that is at least 95% identical to SEQ ID NO:240, and a light chain amino acid sequence of SEQ ID NO:243, or a sequence that is at least 95% identical to SEQ ID NO:243; or (b) a heavy chain amino acid sequence of SEQ ID NO:242, or a sequence that is at least 95% identical to SEQ ID NO:242, and a light chain amino acid sequence of SEQ ID NO:243, or a sequence that is at least 95% identical to SEQ ID NO:243; c) a heavy chain amino acid sequence of SEQ ID NO:240, or a sequence that is at least 95% identical to SEQ ID NO:240, and a light chain amino acid sequence of SEQ ID NO:69, or a sequence that is at least 95% identical to SEQ ID NO:

70.

214. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 289, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 290, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 297, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 299; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 292, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 293, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 294, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 295; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 302, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 298, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 39, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 40, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 291; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 300, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 301, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 44 The conjugate of claim 204, which is an anti-Her2 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

215. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:9 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

296.

216. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-Her2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO:245, or a sequence that is at least 95% identical to SEQ ID NO:245, and a light chain amino acid sequence of SEQ ID NO:66, or a sequence that is at least 95% identical to SEQ ID NO:

66.

217. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 304, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 305, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 312, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 314; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 307, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 309, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 277, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 278; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 317, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 313, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 310, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 308, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 306; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 315, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 25, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 316 The conjugate of claim 204, which is an anti-PCAD antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

218. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 303 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

311.

219. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-PCAD antibody comprising a heavy chain amino acid sequence of SEQ ID NO:248 or a sequence that is at least 95% identical to SEQ ID NO:248 and a light chain amino acid sequence of SEQ ID NO:250 or a sequence that is at least 95% identical to SEQ ID NO:

250.

220. The antibody or antigen-binding fragment comprises: 1) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 319, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 320, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 330, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 332; 2) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 322, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 324; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; 3) a heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 325, a heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 326, a heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 327; a light chain CDR1 (LCDR1) consisting of SEQ ID NO: 336, a light chain CDR2 (LCDR2) consisting of SEQ ID NO: 331, and a light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335; and 4) heavy chain CDR1 (HCDR1) consisting of SEQ ID NO: 328, heavy chain CDR2 (HCDR2) consisting of SEQ ID NO: 323, heavy chain CDR3 (HCDR3) consisting of SEQ ID NO: 321; light chain CDR1 (LCDR1) consisting of SEQ ID NO: 333, light chain CDR2 (LCDR2) consisting of SEQ ID NO: 334, and light chain CDR3 (LCDR3) consisting of SEQ ID NO: 335 The conjugate of claim 204, which is an anti-EphA2 antibody comprising three heavy chain CDRs and three light chain CDRs selected from the group consisting of:

221. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:318 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

329.

222. The conjugate of claim 204, wherein the antibody or antigen-binding fragment is an anti-EphA2 antibody comprising a heavy chain amino acid sequence of SEQ ID NO:252 or a sequence that is at least 95% identical to SEQ ID NO:252 and a light chain amino acid sequence of SEQ ID NO:254 or a sequence that is at least 95% identical to SEQ ID NO:

254.

223. The conjugate according to any one of claims 208 to 222, wherein the antibody or antigen-binding fragment thereof comprises one or more cysteine ​​substitutions selected from E152C, S375C or both E152C and S375C in the heavy chain of the antibody or antigen-binding fragment thereof, positions numbered according to the EU system.

224. The conjugate of any one of claims 208 to 222, wherein the antibody or antigen-binding fragment thereof comprises one or more Fc-silencing mutations.

225. 225. A composition comprising multiple copies of the antibody drug conjugate of any one of claims 103 to 224, wherein the average a of said antibody drug conjugate in said composition is from about 1 to about 8, such as from about 1 to about 6, from about 1 to about 4 or from about 1 to about 2.

226. The formula: 【Chemical Formula 694】 【Chemistry 695】 【Chemistry 696】 【Chemical Formula 697】 (In the formula, A １ and A ２ are each independently a bond, 【Chemistry 698】 and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ indicating the point of attachment to g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 2 to 5); and n is an integer from 1 to 12 (e.g., 2 to 5).

88. The compound according to any one of claims 1 to 87, represented by any one of:

227. A １ and A ２ each independently represents a bond and O-C(=O)-* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ or a pharma- ceutically acceptable salt thereof.

228. The formula: 【Chemistry 699】 【Chemical 700】 【Chemistry 701】 【Chemistry 702】 (In the formula, A １ and A ２ are each independently a bond, 【Chemistry 703】 and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ indicating the point of attachment to g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., from 2 to 5); n is an integer from 1 to 12 (e.g., from 2 to 5); and ** indicates the binding point to Ab) The conjugate of any one of claims 116 to 224, represented by any one of:

229. A １ and A ２ each independently represents a bond and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ The conjugate of claim 228, wherein:

230. Formula (D5a-1): 【Chemistry 704】 (In the formula, A １ and A ２ are each independently a bond, 【Chemistry 705】 and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ indicating the point of attachment to g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); and n is an integer from 1 to 12 (e.g., 5 to 10).

88. The compound according to any one of claims 1 to 87, or a pharma- ceutically acceptable salt thereof.

231. A １ and A ２ each independently represents a bond and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ or a pharma- ceutically acceptable salt thereof.

232. Formula (D5a-2): 【Chemistry 706】 (In the formula, A １ and A ２ are each independently a bond, 【Chemistry 707】 and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ indicating the point of attachment to g for each occurrence is independently an integer from 20 to 30 (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30); o for each occurrence is independently an integer from 1 to 9 (e.g., 1 to 3); n is an integer from 1 to 12 (e.g., 5 to 10); and ** indicates the binding point to Ab) The conjugate according to any one of claims 116 to 224.

233. A １ and A ２ each independently represents a bond and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ The conjugate of claim 232, wherein:

234. The formula: 【Chemistry 708】 【Chemistry 709】 【Chemistry 710】 【Chemistry 711】 【Chemistry 712】 【Chemistry 713】 【Chemical Formula 714】 【Chemistry 715】 【Chemical 716】 【Chemistry 717】 【Chemistry 718】 【Chemical 719】 (In the formula, A １ Or A ２ are each independently a bond, 【Chemistry 720】 and -OC(=O)-* (wherein * represents D １ Or D ２ indicates the point of attachment to Ab; **--- indicates the point of attachment to Ab; and 【Chemistry 721】 D １ Or D ２ (Indicating the direct attachment point to The conjugate of any one of claims 116 to 224, represented by:

235. A １ and A ２ each independently represents a bond and —O—C(═O)—* (wherein A １ and A ２ The * in the figure indicates D. １ Or D ２ The conjugate of claim 234, wherein:

236. 235. A pharmaceutical composition comprising the conjugate of any one of claims 103 to 224 or 234 and a pharma- ceutically acceptable carrier.

237. 236. A method of treating a subject having or suspected of having cancer, comprising administering to the subject a therapeutically effective amount of a conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 236.

238. The method of claim 237, wherein the cancer expresses a target antigen.

239. The method of claim 237 or 238, wherein the cancer is a tumor or blood cancer, and optionally the cancer is breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, gastric cancer, colon cancer, or head and neck cancer.

240. 236. A method of reducing or inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 236.

241. The method of claim 240, wherein the tumor expresses a target antigen.

242. The method of claim 240 or 241, wherein the tumor is breast cancer, gastric cancer, bladder cancer, brain cancer, cervical cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, melanoma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, stomach cancer, colon cancer or head and neck cancer.

243. 236. A method of reducing or inhibiting a hematological cancer in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 236.

244. 244. The method of claim 243, wherein the hematological cancer expresses a target antigen.

245. The method of claim 243 or 244, wherein the hematological cancer is chronic lymphocytic leukemia (CLL), follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), acute monocytic leukemia (AMoL), Hodgkin's lymphoma, non-Hodgkin's lymphoma, or myelodysplastic syndrome (MDS).

246. 246. The method of any one of claims 240-245, wherein administration of the conjugate or pharmaceutical composition reduces or inhibits the growth of the tumor or hematological cancer by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99%.

247. 236. A method of reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 236.

248. The method of claim 247, wherein the cancer cell population expresses a target antigen.

249. 249. The method of claim 247 or 248, wherein the cancer cell population is derived from a tumor or blood cancer, and optionally the cancer cell population is derived from breast cancer, multiple myeloma, plasma cell myeloma, leukemia, lymphoma, sarcoma, gastric cancer, acute myeloid leukemia, bladder cancer, brain cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia including acute lymphoblastic leukemia, follicular lymphoma, lymphoid neoplasms of T-cell or B-cell origin, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, splenic cancer, pancreatic cancer, gastric cancer, colon cancer, or head and neck cancer.

250. 250. The method of any one of claims 247-249, wherein administration of the conjugate or pharmaceutical composition reduces the cancer cell population or slows the expansion of the cancer cell population by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99%.

251. The method of any one of claims 237-250, wherein the antibody drug conjugate is administered as a monotherapy.

252. The method of any one of claims 237-250, wherein the antibody drug conjugate is administered concomitantly with another therapeutic agent or radiation therapy.

253. The method of claim 252, wherein the antibody drug conjugate is administered in an amount effective to sensitize the tumor cells to one or more additional therapeutic agents and / or radiation therapy.

254. 251. The method of any one of claims 237-250, further comprising administering to said subject in need thereof at least one additional therapeutic agent.

255. The method of claim 254, wherein the one additional therapeutic agent is a taxane, a vinca alkaloid, a MEK inhibitor, an ERK inhibitor, a topoisomerase inhibitor, or a RAF inhibitor.

256. Use of a conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 198 for the manufacture of a medicament for (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumor in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

257. A conjugate according to any one of claims 103 to 235 or a pharmaceutical composition according to claim 198 for use in (i) treating a subject having or suspected of having cancer, (ii) reducing or inhibiting the growth of a tumour in a subject, (iii) reducing or inhibiting a hematological cancer in a subject, or (iv) reducing or slowing the expansion of a cancer cell population in a subject.

Images