# US 9,872,924 B2 · Antibody-drug conjugate produced by binding through linker having hydrophilic structure

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- Number: US 9,872,924 B2
- Document ID: US9872924B2
- Status: Granted
- Kind: B2
- Application number: 14/436,458
- Filed: 2013-10-17
- Published: 2015-12-10
- Granted: 2018-01-23
- Earliest claimed: 2012-10-19
- Assignees: Daiichi Sankyo Company, Limited
- Applicants: Daiichi Sankyo Company, Limited
- Inventors: Hiroyuki Naito; Takashi Nakada; Masao Yoshida; Shinji Ashida; Takeshi Masuda; Hideki Miyazaki; Yuji Kasuya; Yuki Abe; Yusuke Ogitani
- Web page: https://patentgrep.com/patent/US9872924B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61K 47/68037: {the drug being a camptothecin [CPT] or derivatives}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/00: Drugs for dermatological disorders
- A61P 35/00: Antineoplastic agents
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/30: from tumour cells
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula (I) is conjugated to an antibody via a linker having a structure represented by the following formula: -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- or -L1-L2-LP- wherein the antibody is connected to the terminal of L1, the antitumor compound is connected to the terminal of Lc or LP, and any one or two or more of linkers of L1, L2, and LP has a hydrophilic structure.

## Claims

### Claim 1

An antibody-drug conjugate comprising an antitumor compound represented by the following formula:
wherein the antitumor compound is conjugated to an antibody via a linker having a structure represented by the following formula:
-L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- or -L1-L2-LP-
wherein the antibody is connected to the terminal of L1, the antitumor compound is connected to the terminal of Lc or LP,
wherein
n1 represents an integer of 0 to 6,
L1 represents -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, -(Succinimid-3-yl-N)—CH[—(CH2)n3-COOH]—C(═O)—, —CH2—C(═O)—NH—(CH2)n4-C(═O)—,
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-, or —C(═O)—(CH2)n5-C(═O)—,
wherein n2 represents an integer of 2 to 8, n3 represents an integer of 1 to 8, n4 represents an integer of 1 to 8, n5 represents an integer of 1 to 8,
L2 represents —NH—(CH2—CH2—O)n6-CH2—CH2—C(═O)—, —N[—(CH2CH2—O)n7-CH2CH2—OH]—CH2—C(═O)—, —S—(CH2)n8-C(═O)—, or a single bond,
wherein n6 represents an integer of 0 to 6, n7 represents an integer of 1 to 4, n8 represents an integer of 1 to 6,
LP represents: (i) a peptide residue consisting of 3 to 8 amino acids wherein the peptide residue has a hydrophilic amino acid other than glycine at the N terminal, or (ii) a peptide residue comprising GGFGG (SEQ ID NO: 40) or GGFGGG (SEQ ID NO: 41),
La represents —C(═O)—NH—, —NR1—(CH2)n9-, —O—, or a single bond,
wherein n9 represents an integer of 1 to 6, R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)na-COOH, or —(CH2)nb-OH, na represents an integer of 1 to 4, nb represents an integer of 1 to 6,
Lb represents —CR2(—R3)—, —O—, —NR4—, or a single bond,
wherein R2 and R3 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)nc-NH2, —(CH2)nd-COOH, or —(CH2)ne-OH, R4 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, nc represents an integer of 0 to 6, nd represents an integer of 1 to 4, ne represents an integer of 1 to 4, provided that when nc is 0, R2 and R3 are not the same as each other,
Lc represents —CH2— or —C(═O)—,
-(Succinimid-3-yl-N)— has a structure represented by the following formula:
which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
—(N-ly-3-Succinimid)- has a structure represented by the following formula:
which is connected to L2 at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
cyc.Hex(1,4) represents a 1,4-cyclohexylene group,
when L2 is —S—(CH2)n8-C(═O)—, L1 is —C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-.

### Claim 2 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein
L1 is -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, -(Succinimid-3-yl-N)—CH[—(CH2)n3-COOH]—C(═O)—, or —CH2—C(═O)—NH—(CH2)n4-C(═O)—,
wherein n2 represents an integer of 2 to 8, n3 represents an integer of 1 to 8, n4 represents an integer of 1 to 8,
L2 is —NH—(CH2—CH2—O)n6-CH2—CH2—C(═O)—, —N[—(CH2CH2—O)n7-CH2CH2—OH]—CH2—C(═O)—, or a single bond,
wherein n6 represents an integer of 0 to 6, n7 represents an integer of 1 to 4,
LP is (i) a peptide residue consisting of 3 to 8 amino acids wherein the peptide residue has a hydrophilic amino acid other than glycine at the N terminal, or (ii) a peptide residue comprising GGFGG (SEQ ID NO: 40) or GGFGGG (SEQ ID NO: 41),
each of La and Lb is a single bond, and
Lc is —C(═O)—.

### Claim 3 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein LP is a peptide residue having a hydrophilic amino acid other than glycine at the N terminal.

### Claim 4 (depends on 3)

The antibody-drug conjugate according to claim 3, wherein the hydrophilic amino acid other than glycine is aspartic acid, glutamic acid, lysine, serine, threonine, glutamine, asparagine, histidine, tyrosine, or arginine.

### Claim 5 (depends on 3)

The antibody-drug conjugate according to claim 3, wherein the N-terminal hydrophilic amino acid other than glycine in LP is glutamic acid, aspartic acid, or lysine.

### Claim 6 (depends on 4)

The antibody-drug conjugate according to claim 4, wherein the peptide residue following the N-terminal hydrophilic amino acid in LP is an amino acid residue comprising an amino acid selected from phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, and aspartic acid.

### Claim 7 (depends on 6)

The antibody-drug conjugate according to claim 6, wherein a peptide residue following the N-terminal hydrophilic amino acid in LP is a peptide residue consisting of 3 or 4 amino acids.

### Claim 8 (depends on 7)

The antibody-drug conjugate according to claim 7, wherein the peptide residue following the N-terminal hydrophilic amino acid in LP is GGF or GGFG (SEQ ID NO. 33).

### Claim 9 (depends on 8)

The antibody-drug conjugate according to claim 8, wherein LP is DGGF (SEQ ID NO. 34), KGGF (SEQ ID NO. 35), EGGF (SEQ ID NO. 36), DGGFG (SEQ ID NO. 37), KGGFG (SEQ ID NO. 38), or EGGFG (SEQ ID NO. 39).

### Claim 10 (depends on 8)

The antibody-drug conjugate according to claim 8, wherein LP is DGGFG (SEQ ID NO. 37), KGGFG (SEQ ID NO. 38), or EGGFG (SEQ ID NO. 39).

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The antibody-drug conjugate according to any one of claims 1 to 10, wherein the linker is a linker having a structure represented by -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc.

### Claim 12 (depends on 11)

The antibody-drug conjugate according to claim 11, wherein Lc is —C(═O)—.

### Claim 13 (depends on 12)

The antibody-drug conjugate according to claim 12, wherein L1 is -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, n2 is an integer of 2 to 5, and L2 is a single bond.

### Claim 14 (depends on 13)

The antibody-drug conjugate according to claim 13, wherein n2 is 5.

### Claim 15 (depends on 14)

The antibody-drug conjugate according to claim 14, wherein n1 is 1 to 3.

### Claim 16 (depends on 15)

The antibody-drug conjugate according to claim 15, wherein the structure of the —NH—(CH2)n1-La-Lb-Lc- moiety in the linker is
—NH—CH2—C(═O)—,
—NH—(CH2)2—C(═O)—,
—NH—(CH2)3—C(═O)—,
—NH—CH2—O—CH2—C(═O)—, or
—NH—(CH2)2—O—CH2—C(═O)—.

### Claim 17 (depends on 15)

The antibody-drug conjugate according to claim 15, wherein
the structure of the —NH—(CH2)n1-La-Lb-Lc- moiety in the linker is
—NH—CH2—C(═O)—,
—NH—(CH2)2—C(═O)—, or
—NH—(CH2)3—C(═O)—.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The antibody-drug conjugate according to any one of claims 1 to 10, wherein the linker is a linker having a structure represented by -L1-L2-Lc-.

### Claim 19 (depends on 18)

The antibody-drug conjugate according to claim 18, wherein L1 is -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, n2 is an integer of 2 to 5, and L2 is a single bond.

### Claim 20 (depends on 19)

The antibody-drug conjugate according to claim 19, wherein n2 is 5.

### Claim 21 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein the peptide residue consists of 4 to 8 amino acids in the linker.

### Claim 22 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein LP is GGFGG (SEQ ID NO: 40) or GGFGGG (SEQ ID NO: 40).

### Claim 23 (depends on 22)

The antibody-drug conjugate according to claim 22, wherein L1 is -(Succinimid-3-yl-N)—(CH2)n2-C(═O)— and n2 is an integer of 2 to 5.

### Claim 24 (depends on 23)

The antibody-drug conjugate according to claim 23, wherein n2 is 5.

### Claim 25 (depends on 22)

The antibody-drug conjugate according to claim 22, wherein L1 is -(Succinimid-3-yl-N)—CH[—(CH2)n3-COOH]—C(═O)—.

### Claim 26 (depends on 25)

The antibody-drug conjugate according to claim 25, wherein n3 is 2 or 3.

### Claim 27 (depends on 22)

The antibody-drug conjugate according to claim 22, wherein L2 is —N[—(CH2CH2—O)n7-CH2CH2—OH]—CH2—C(═O)—.

### Claim 28 (depends on 27)

The antibody-drug conjugate according to claim 27, wherein n7 is 2 to 4.

### Claim 29 (depends on 25, 26, 27, 28)

The antibody-drug conjugate according to any one of claims 25 to 28, wherein the linker is a linker having a structure represented by -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc.

### Claim 30 (depends on 29)

The antibody-drug conjugate according to claim 29, wherein Lc is —C(═O)—.

### Claim 31 (depends on 30)

The antibody-drug conjugate according to claim 30, wherein n1 is 1 to 3.

### Claim 32 (depends on 1, 2)

The antibody-drug conjugate according to claim 1 or 2, wherein the drug-linker structure moiety in the antibody-drug conjugate has one structure selected from the following drug-linker structure group:
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2-O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2-O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH—O—CH—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CHCHH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)—CH2CHCHH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CHCHH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CHCHH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)—CH2CHCHH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2—O—CH2—C(═O)—(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-NH—CH2CH2—O—CH2—C(═O)—(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGF (SEQ ID NO. 34)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-KGGF (SEQ ID NO. 35)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-DGGFG (SEQ ID NO. 37)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-KGGFG (SEQ ID NO. 38)-(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFGG (SEQ ID NO. 40)-(NH-DX),
-(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFGGG (SEQ ID NO. 41)-(NH-DX),
—CH2—C(═O)—NH—CH2CHz-C(═O)-GGFGG (SEQ ID NO. 40)-(NH-DX),
—CH2—C(═O)—NH—CH2CH2—C(═O)-GGFGGG (SEQ ID NO. 41)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-GGFGG (SEQ ID NO. 40)-(NH-DX),
—C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-S—CH2CH2—C(═O)-GGFGGG (SEQ ID NO. 41)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-GGFGG (SEQ ID NO. 40)-(NH-DX),
—C(═O)—CH2CH2CH2CH2CH2CH2—C(═O)-GGFGGG (SEQ ID NO. 41)-(NH-DX)
wherein -(Succinimid-3-yl-N)— has a structure represented by the following formula:
which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
cyc.Hex(1,4) represents a 1,4-cyclohexylene group, —(N-ly-3-Succinimid)- has a structure represented by the following formula:
which is connected to L2 at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, and
—(NH-DX) is a group represented by the following formula:
wherein the nitrogen atom of the amino group at position 1 is the connecting position.

### Claim 33 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein an average number of conjugated antitumor compounds per antibody is in a range of from 1 to 10.

### Claim 34 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein an average number of conjugated antitumor compounds per antibody is in a range of from 1 to 8.

### Claim 35 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein an average number of conjugated antitumor compounds per antibody is in a range of from 3 to 8.

### Claim 36 (depends on 1)

The antibody-drug conjugate according to claim 1, wherein the antibody is an antibody having one or more of a property of recognizing a target cell, a property of binding to a target cell, a property of internalizing in a target cell, and a property of damaging a target cell.

### Claim 37 (depends on 36)

The antibody-drug conjugate according to claim 36, wherein the target cell is a tumor cell.

### Claim 38 (depends on 36)

The antibody-drug conjugate according to claim 36, wherein the antibody is an anti-A33 antibody, an anti-B7-H3 antibody, an anti-CanAg antibody, an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CEA antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-G250 antibody, an anti-MUC1 antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-PSMA antibody, an anti-tenascin-C antibody, an anti-SLC44A4 antibody, or an anti-mesothelin antibody.

### Claim 39 (depends on 36)

The antibody-drug conjugate according to claim 36, wherein the antibody is an anti-B7-H3 antibody, an anti-CD30 antibody, an anti-CD33 antibody, or an anti-CD70 antibody.

### Claim 40 (depends on 36)

The antibody-drug conjugate according to claim 36, wherein the antibody is an anti-B7-H3 antibody.

### Claim 41 (depends on 1)

A drug containing the antibody-drug conjugate according to claim 1 or a salt thereof.

### Claim 42 (depends on 1)

An antitumor drug and/or anticancer drug containing the antibody-drug conjugate according to claim 1 or a salt thereof.

### Claim 43 (depends on 42)

The antitumor drug and/or anticancer drug according to claim 42, which is applied to lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, or esophageal cancer.

### Claim 44 (depends on 1)

A pharmaceutical composition containing the antibody-drug conjugate according to claim 1, a salt thereof or a hydrate thereof as an active component, and a pharmaceutically acceptable formulation component.

### Claim 45 (depends on 44)

The pharmaceutical composition according to claim 44, which is applied to lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, or esophageal cancer.

### Claim 46 (depends on 1)

A method for treating tumor and/or cancer comprising administering the antibody-drug conjugate according to claim 1, a salt thereof or a hydrate thereof.

### Claim 47 (depends on 46)

The treatment method according to claim 46, which is applied to lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, or esophageal cancer.