Anti-EGFR antibody-drug conjugate with a cyclic dinucleotide derivative
[Problem] It is desired to develop an antibody-drug conjugate capable of being systemically administered and delivering a STING agonist specifically to a target cells or organ (for example, a tumor lesion), and a therapeutic agent and/or therapeutic method using the antibody-drug conjugate for diseases related to STING agonist activity, for example, diseases (for example, cancers) to which immunostimulation therapy can be applied. [Solution] The present invention provides a novel antibody-CDN derivative conjugate which can be systemically administered and exhibits an antitumor effect against an antigen-expressing tumor.
1 . An antibody-drug conjugate represented by the following formula (II):
wherein m 1 ranges from 1 to 10;
Ab represents an antibody or an antigen-binding fragment of the antibody, wherein the antibody optionally has a remodeled glycan,
wherein the antibody is an anti-EGFR antibody;
L represents a linker linking Ab and D, wherein
Ab is bound to L through the glycan or remodeled glycan of Ab, and
L is represented by -Lb-La-Lp-Lc-*
wherein the asterisk represents bonding to the drug D;
Lp is -GGFG- or -GGPI-:
La represents —C(═O)—CH 2 CH 2 —C(═O)—;
Lb represents the following formula:
wherein, in the structural formula of Lb shown above, the asterisk represents bonding to La, and the wavy line represents bonding to the glycan or remodeled glycan of Ab; and
Lc represents —NH—CH 2 —;
D represents a compound represented by the following formula (1):
wherein
L bonds to any —NH 2 or a hydroxy group included in L 1 ,
L 1 represents any one group of the formulas selected from the group consisting of:
wherein the wavy line represents a position of substitution,
Q and Q′ each independently represent a hydroxy group or a thiol group,
R 21 and R 22 each independently represent a hydroxy group or a fluorine atom, and
W represents —NH— or a sulfur atom.
2 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following two formulas:
wherein L 1 , Q, Q′, and W are as defined above.
3 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following four formulas:
wherein the asterisk represents bonding to L, and Q, Q′, and W are as defined above.
4 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following three formulas:
wherein the asterisk represents bonding to L, and W is as defined above.
5 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following three formulas:
wherein the asterisk represents bonding to L.
6 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following four formulas:
wherein the asterisk represents bonding to L.
7 . The antibody-drug conjugate according to claim 4 , wherein D is represented by the following formula:
wherein the asterisk represents bonding to L.
8 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following two formulas:
wherein the asterisk represents bonding to L, and W is as defined above.
9 . The antibody-drug conjugate according to claim 1 , wherein D is represented by any one of the following four formulas:
wherein the asterisk represents bonding to L.
10 . The antibody-drug conjugate according to claim 1 , wherein the average number of the conjugated drug molecules per antibody molecule in the antibody-drug conjugate ranges from 1 to 10.
11 . The antibody-drug conjugate according to claim 1 , wherein the antibody bonds via a glycan bonding to Asn297 of the antibody (N297 glycan) to L.
12 . The antibody-drug conjugate according to claim 11 , wherein the N297 glycan is N297-(Fuc)MSG1 or N297-(Fuc)SG having a structure represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on 1,2,3-triazole ring of Lb in the linker L, and
n 5 is an integer of 2 to 5;
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on 1,2,3-triazole ring of Lb in the linker L, and
n 5 is an integer of 2 to 5.
13 . The antibody-drug conjugate according to claim 11 , wherein the antibody-drug conjugate is represented by the following formula:
wherein m 2 represents an integer of 1 or 2,
L is a linker linking N297 glycan of Ab and D, as defined previously,
Ab represents an anti-EGFR antibody, or an antigen-binding fragment thereof,
N297 glycan of Ab is represented by N297-(Fuc)MSG1 or N297-(Fuc)SG having a structure represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on 1,2,3-triazole ring of Lb in the linker L, and
n 5 represents an integer of 2 to 5;
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on 1,2,3-triazole ring of Lb in the linker L, and
n 5 represents an integer of 2 to 5,
D is represented by any one of the following four formulas:
wherein the asterisk represents bonding to L.
14 . The antibody-drug conjugate according to claim 13 , wherein the antibody-drug conjugate is represented by the following formula selected from
wherein, in each the structural formula shown above, m 2 is an integer of 1 or 2,
N297 glycan of Ab is represented by any one of N297-(Fuc)MSG1 or N297-(Fuc)SG having a structure represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 represents an integer of 2 to 5; or
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 represents an integer of 2 to 5.
15 . The antibody-drug conjugate according to claim 13 , wherein the antibody-drug conjugate is represented by the following formula selected from
wherein, in each the structural formula shown above, m 2 is an integer of 1 or 2,
N297 glycan of Ab is represented by any one of N297-(Fuc)MSG1 or N297-(Fuc)SG having a structure represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 represents an integer of 2 to 5; or
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 represents an integer of 2 to 5.
16 . The antibody-drug conjugate according to claim 1 , wherein the antibody is an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 10 or an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 12.
17 . The antibody-drug conjugate according to claim 1 , wherein the antibody is an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 119 of SEQ ID NO: 10 or an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 116 of SEQ ID NO: 12.
18 . The antibody-drug conjugate according to claim 1 , wherein the antibody is an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 64 or
an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 70.
19 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 10, and
an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 12
wherein N297 glycan of Ab is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring,
n 5 is 3, and
m 2 is 2.
20 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a light chain variable region comprising of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 119 of SEQ ID NO: 10, and
an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 116 of SEQ ID NO: 12,
wherein N297 glycan of Ab is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring,
n 5 is 3, and
m 2 is 2.
21 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 64, and
an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 70, wherein N297 glycan of Ab is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino groups at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal on each of 1-3 and 1-6 branched chains of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring,
n 5 is 3, and
m 2 is 2.
22 . A pharmaceutical composition comprising the antibody-drug conjugate according to claim 1 .
23 . The antibody-drug conjugate according to claim 1 , wherein the antibody or an antigen-binding fragment of the antibody is a protein produced in host cells by using a gene (a) which is modified by genetical engineering from a gene (b) of the antibody or an antigen-binding fragment of the antibody.
24 . The antibody-drug conjugate according to claim 10 , wherein the average number of the conjugated drug molecules per antibody molecule in the antibody-drug conjugate ranges from 1 to 5.
25 . The antibody-drug conjugate according to claim 24 , wherein the average number of the conjugated drug molecules per antibody molecule in the antibody-drug conjugate ranges from 3 to 5.
26 . The antibody-drug conjugate according to claim 11 , wherein the N297 glycan is a remodeled glycan.
27 . The antibody-drug conjugate according to claim 20 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 119 of SEQ ID NO: 10.
28 . The antibody-drug conjugate according to claim 20 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 116 of SEQ ID NO: 12.
29 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 10, and
an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 12,
wherein N297 glycan is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 is 3, and
m2 is 1.
30 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 119 of SEQ ID NO: 10, and
an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 116 of SEQ ID NO: 12,
wherein N297 glycan is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 is 3, and
m2 is 1.
31 . The antibody-drug conjugate according to claim 30 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 119 of SEQ ID NO: 10.
32 . The antibody-drug conjugate according to claim 30 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region comprising amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region comprising amino acid residues 1 to 116 of SEQ ID NO: 12.
33 . An antibody-drug conjugate represented by the following formula:
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 64, and
an antibody comprising a light chain comprising a CDRL1 comprising the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 comprising the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 comprising the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 comprising the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 comprising the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 comprising the amino acid sequence set forth in SEQ ID NO: 70,
wherein N297 glycan is represented by the following formula:
wherein the wavy line represents bonding to Asn297 of the antibody,
L(PEG) represents —(CH 2 —CH 2 —O)n 5 —CH 2 —CH 2 —NH—,
wherein the amino group at the right end of the L(PEG) is bound via an amide bond to a carboxyl group at the 2-position on a sialic acid at the non-reducing terminal of a 1-3 branched chain of β-Man in the N297 glycan,
the asterisk represents bonding to a nitrogen atom at 1- or 3-position on the 1,2,3-triazole ring, and
n 5 is 3, and
m2 is 1.
34 . The antibody-drug conjugate according to claim 1 , wherein one or two amino acids are deleted at a heavy chain carboxyl terminus.
35 . The pharmaceutical composition comprising according to claim 22 , wherein the average number of the conjugated drug molecules per antibody molecule in the antibody-drug conjugate ranges from 1 to 10.
36 . The pharmaceutical composition comprising according to claim 22 , wherein the average number of the conjugated drug molecules per antibody molecule in the antibody-drug conjugate ranges from 3 to 5.
37 . The antibody-drug conjugate according to claim 16 , wherein the antibody is an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 10 or an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 12.
38 . The antibody-drug conjugate according to claim 17 , wherein the antibody is an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 119 of SEQ ID NO: 10 or an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 116 of SEQ ID NO: 12.
39 . The antibody-drug conjugate according to claim 18 , wherein the antibody is an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 64; or an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 70.
40 . The antibody-drug conjugate according to claim 19 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 10, and
an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 12.
41 . The antibody-drug conjugate according to claim 20 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 119 of SEQ ID NO: 10, and
an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 116 of SEQ ID NO: 12.
42 . The antibody-drug conjugate according to claim 21 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 64; or
an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 70.
43 . The antibody-drug conjugate according to claim 41 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 119 of SEQ ID NO: 10.
44 . The antibody-drug conjugate according to claim 41 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 116 of SEQ ID NO: 12.
45 . The antibody-drug conjugate according to claim 29 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 10, and
an antibody comprising a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 12.
46 . The antibody-drug conjugate according to claim 30 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 119 of SEQ ID NO: 10, and
an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 116 of SEQ ID NO: 12.
47 . The antibody-drug conjugate according to claim 46 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 9 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 119 of SEQ ID NO: 10.
48 . The antibody-drug conjugate according to claim 46 , wherein Ab represents an antibody comprising a light chain comprising a light chain variable region consisting of amino acid residues 1 to 108 of SEQ ID NO: 11 and a heavy chain comprising a heavy chain variable region consisting of amino acid residues 1 to 116 of SEQ ID NO: 12.
49 . The antibody-drug conjugate according to claim 33 ,
wherein Ab represents any one selected from the group consisting of the following:
an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 59, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 60, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 61 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 62, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 63, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 64; or
an antibody comprising a light chain comprising a CDRL1 consisting of the amino acid sequence set forth in SEQ ID NO: 65, a CDRL2 consisting of the amino acid sequence set forth in SEQ ID NO: 66, and a CDRL3 consisting of the amino acid sequence set forth in SEQ ID NO: 67 and a heavy chain comprising a CDRH1 consisting of the amino acid sequence set forth in SEQ ID NO: 68, a CDRH2 consisting of the amino acid sequence set forth in SEQ ID NO: 69, and a CDRH3 consisting of the amino acid sequence set forth in SEQ ID NO: 70.