2. The conjugate or a salt thereof according to claim 1, wherein the immunoglobulin unit is a human immunoglobulin unit.

3. The conjugate or a salt thereof of claim 2, wherein the human immunoglobulin unit is a human IgG antibody.

4. The conjugate or a salt thereof according to claim 1, wherein the lysine residue is present at position 246/248, position 288/290, or position 317 in accordance with Eu numbering.

5. The conjugate or a salt thereof according to claim 1, wherein r is 1.9 to 2.1.

6. The conjugate or a salt thereof according to claim 1, wherein the hydrophilic group is one or more groups selected from the group consisting of a carboxylate group, a sulfonate group, a hydroxy group, a polyethylene glycol group, a polysarcosine group, and a sugar portion.

7. The conjugate or a salt thereof according to claim 1, wherein L1 represents a divalent group represented by the following formula (i): -L4-Y-L3- (i), wherein L3 and L4 each independently comprise a 150 divalent group selected from the group consisting of - (C(R)2)m-, -(O-C(R)2-C(R)2)m-, and -(C(R)2-C(R)2-O)m-, and a combination thereof, Rs each independently represent a hydrogen atom, a C1-6 alkyl, a C2-6 alkenyl, or a C2-6 alkynyl, m is an integer of 0 to 20, and Y represents a divalent group generated by a reaction of two bioorthogonal functional groups capable of reacting with each other.

8. The conjugate or a salt thereof according to claim 7, wherein L3 and L4 each independently comprise -(C(R)2)m-.

9. The conjugate or a salt thereof according to claim 7, wherein Y is a divalent group represented by any one of the following structural formulae: [Chemical formula 2] N O O S S N O O O S O S N N N N N N N wherein a white circle and a black circle each represent a bond, when the bond of the white circle is bonded to L3, the bond of the black circle is bonded to L4, and when the bond of the white circle is bonded to L4, the bond of the black circle is bonded to L3.

10. The conjugate or a salt thereof according to claim 1, 151 wherein the structural unit represented by formula (I) is a structural unit represented by the following formula (I-1), (I-2), (I-3), or (I-4): [Chemical formula 3] NH O RB O NH RA O L2 D (I-1) r N O R1 L1 O Ig wherein Ig, L1, L2, D, RA, RB, and r are the same as those in formula (I), and R1 represents a monovalent group comprising a hydrophilic group; [Chemical formula 4] NH O RB O NH RA O L2 D (I-2) r N O L1 O Ig R2 wherein Ig, L1, L2, D, RA, RB, and r are the same as those in formula (I), and R2 represents a monovalent group comprising a hydrophilic group; [Chemical formula 5] 152 NH O RB O NH RA O L2 D (I-3) N Ig R3 R4 O L1 O r wherein Ig, L1, L2, D, RA, RB, and r are the same as those in formula (I), R3 represents a hydrogen atom, a C1-6 alkyl, or a monovalent group comprising a hydrophilic group and R4 represents a monovalent group comprising a hydrophilic group; or [Chemical formula 6] NH O RB O NH RA O L2 D (I-4) N O L1 O Ig R1 r R6 wherein Ig, L1, L2, D, RA, RB, and r are the same as those in formula (I), R1 represents a hydrogen atom or a C1-6 alkyl, and R6 represents a monovalent group comprising a hydrophilic group.

1. A conjugate of an antibody and a functional substance
or a salt thereof, which comprises a structural unit
represented by the following formula (I):
[Chemical formula 1]
NH
O
RB
O
NH
RA
O
L2 D (I) X
N
O
L1
O
Ig R1
n
r
wherein
Ig represents an immunoglobulin unit comprising two
heavy chains and two light chains, and regioselectively
forms an amide bond with a carbonyl group adjacent to Ig
via an amino group in side chains of lysine residues in the
two heavy chains,
L1 and L2 each represent a divalent group,
R1 represents a monovalent group optionally comprising
a hydrophilic group,
X represents a divalent group optionally having a
substituent, wherein the divalent group has 1 to 3 carbon
atoms constituting a main chain portion linking two atoms
present on both sides of X, and the substituent is a
monovalent group optionally comprising a hydrophilic group,
D represents a functional substance,
RA represents a side chain of a valine residue,
RB represents a side chain of a citrulline residue or
an alanine residue,
n is 0 or 1, wherein when n is 1, the substituent in X
together with R1 may form a ring optionally comprising a
WE CLAIM:
149
hydrophilic group, and
an average ratio r of the amide bonds per two heavy
chains is 1.5 to 2.5, and
wherein at least one hydrophilic group is present in
the structural unit.
2. The conjugate or a salt thereof according to claim 1,
wherein the immunoglobulin unit is a human immunoglobulin
unit.
3. The conjugate or a salt thereof of claim 2, wherein
the human immunoglobulin unit is a human IgG antibody.
4. The conjugate or a salt thereof according to claim 1,
wherein the lysine residue is present at position 246/248,
position 288/290, or position 317 in accordance with Eu
numbering.
5. The conjugate or a salt thereof according to claim 1,
wherein r is 1.9 to 2.1.
6. The conjugate or a salt thereof according to claim 1,
wherein the hydrophilic group is one or more groups
selected from the group consisting of a carboxylate group,
a sulfonate group, a hydroxy group, a polyethylene glycol
group, a polysarcosine group, and a sugar portion.
7. The conjugate or a salt thereof according to claim 1,
wherein L1 represents a divalent group represented by the
following formula (i):
-L4-Y-L3- (i),
wherein L3 and L4 each independently comprise a
150
divalent group selected from the group consisting of -
(C(R)2)m-, -(O-C(R)2-C(R)2)m-, and -(C(R)2-C(R)2-O)m-, and a
combination thereof,
Rs each independently represent a hydrogen atom, a C1-6
alkyl, a C2-6 alkenyl, or a C2-6 alkynyl,
m is an integer of 0 to 20, and
Y represents a divalent group generated by a reaction
of two bioorthogonal functional groups capable of reacting
with each other.
8. The conjugate or a salt thereof according to claim 7,
wherein L3 and L4 each independently comprise -(C(R)2)m-.
9. The conjugate or a salt thereof according to claim 7,
wherein Y is a divalent group represented by any one of the
following structural formulae:
[Chemical formula 2]
N
O
O
S
S
N
O
O
O S
O
S N
N
N
N
N
N
N
wherein a white circle and a black circle each
represent a bond,
when the bond of the white circle is bonded to L3, the
bond of the black circle is bonded to L4, and
when the bond of the white circle is bonded to L4, the
bond of the black circle is bonded to L3.
10. The conjugate or a salt thereof according to claim 1,
151
wherein the structural unit represented by formula (I) is a
structural unit represented by the following formula (I-1),
(I-2), (I-3), or (I-4):
[Chemical formula 3]
NH
O
RB
O
NH
RA
O
L2 D (I-1)
r
N
O
R1
L1
O
Ig
wherein
Ig, L1, L2, D, RA, RB, and r are the same as those in
formula (I), and
R1 represents a monovalent group comprising a
hydrophilic group;
[Chemical formula 4]
NH
O
RB
O
NH
RA
O
L2 D (I-2)
r
N
O
L1
O
Ig
R2
wherein
Ig, L1, L2, D, RA, RB, and r are the same as those in
formula (I), and
R2 represents a monovalent group comprising a
hydrophilic group;
[Chemical formula 5]
152
NH
O
RB
O
NH
RA
O
L2 D (I-3)
N
Ig
R3 R4
O
L1
O
r
wherein
Ig, L1, L2, D, RA, RB, and r are the same as those in
formula (I),
R3 represents a hydrogen atom, a C1-6 alkyl, or a
monovalent group comprising a hydrophilic group and
R4 represents a monovalent group comprising a
hydrophilic group; or
[Chemical formula 6]
NH
O
RB
O
NH
RA
O
L2 D (I-4)
N
O
L1
O
Ig R1
r
R6
wherein
Ig, L1, L2, D, RA, RB, and r are the same as those in
formula (I),
R1 represents a hydrogen atom or a C1-6 alkyl, and
R6 represents a monovalent group comprising a
hydrophilic group.