公开(公告)号：US20240269311A1

公开(公告)日：2024-08-15

申请号：US18619756

申请日：2024-03-28

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Tomohiro WATANABE ,  Noriko HATADA ,  Tomohiro FUJII

IPC: A61K47/68 ,  C07K5/08 ,  C07K16/46

CPC classification number: A61K47/6811 ,  C07K5/08 ,  C07K16/46

Abstract: A regioselective conjugate of an antibody and a functional substance comprising a structural unit represented by the following Formula (I):






wherein
Ig represents an immunoglobulin unit comprising two heavy chains and two light chains, and is regioselectively bonded to L1 adjacent to Ig via an amino group in side chains of lysine residues in the two heavy chains,
HG represents a hydrophilic group,
RA represents a side chain of a valine residue,
RB represents a side chain of a citrulline residue or the like,
ring A represents a divalent aromatic ring group optionally having a substituent,
R1 and R2 each independently represent a hydrogen atom or a monovalent group,
L1 and L2 each independently represent a divalent
D represents a functional substance, and
r is 1.5 to 2.5, or
a salt thereof, and
substances related thereto,

is excellent in desired properties while controlling a bonding ratio between the antibody and the functional substance within a specific range.

公开(公告)号：US20250101129A1

公开(公告)日：2025-03-27

申请号：US18966063

申请日：2024-12-02

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Tomohiro FUJII ,  Kenichiro ITO ,  Kazutoshi TAKAHASHI ,  Yoshihiko MATSUDA ,  Hiroki YAMAGUCHI ,  Naoko TSUYOSHI ,  Hayato NAGANO ,  Rika TAKASUGI

IPC: C07K16/32 ,  C07K16/28

Abstract: The present invention relates to a technology for easy chemical modification of only one heavy chain in the constituent unit of an antibody (immunoglobulin unit containing two heavy chains and optionally two light chains). More particularly, the present invention relates to a compound or a salt thereof, containing (A) an affinity substance containing first and second affinity moieties each having an affinity to the constant region in a heavy chain of an antibody; and (B) a reactive group for the antibody.

公开(公告)号：US20240000964A1

公开(公告)日：2024-01-04

申请号：US18354256

申请日：2023-07-18

Applicant: Ajinomoto Co., Inc.

Inventor： Tomohiro FUJII ,  Kei YAMADA ,  Yutaka MATSUDA ,  Ryusuke HIRAMA ,  Noriko HATADA

IPC: A61K47/68 ,  C07K16/32 ,  C07C247/16 ,  C07D271/113 ,  C07D213/71 ,  C07D225/08 ,  C07D403/12 ,  C07D401/12

CPC classification number: A61K47/6889 ,  C07K16/32 ,  A61K47/6855 ,  C07C247/16 ,  C07D271/113 ,  C07D213/71 ,  C07D225/08 ,  C07D403/12 ,  C07D401/12 ,  C07K2317/51 ,  C07K2317/52

Abstract: A desired antibody or antibody composition may be obtained by modifying a thiol group chemically introduced to an antibody to obtain an antibody composition comprising



(A) an antibody intermediate or a salt thereof having a bioorthogonal functional group which may be protected, which is represented by the following formula (A):






AbS-L-R]n  (A)





wherein
Ab is a certain antibody,
S is a sulfur atom,
L is a divalent group,
R is a bioorthogonal functional group which may be protected, and
n is an integer from 1 to 8, and


(B) a thiol group-introduced antibody or a salt thereof, which is represented by the following formula (B):






AbSH]n  (B)





wherein
Ab and n are the same as formulae (A), and
SH is a thiol group; and the like.

公开(公告)号：US20210139541A1

公开(公告)日：2021-05-13

申请号：US17119495

申请日：2020-12-11

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Noriko HATADA ,  Kei YAMADA ,  Natsuki SHIKIDA ,  Kazutaka SHIMBO ,  Tomohiro FUJII ,  Shigeo HIRASAWA

IPC: C07K14/00 ,  C07K16/00 ,  C07K1/06

Abstract: Compounds having an affinity substance to an antibody and a bioorthogonal functional group, represented by the following Formula (I): A-L-E-B  (I) wherein A is an affinity substance to an antibody, L is a divalent group comprising a leaving group, E is a divalent group comprising an electrophilic group (i) coupled with the leaving group and (ii) having ability to react with a nucleophilic group in the antibody, B is a bioorthogonal functional group, and the leaving group has ability to be cleaved and eliminated from E by a reaction between the nucleophilic group and the electrophilic group, or a salt thereof, and the like are useful for labelling antibodies.

公开(公告)号：US20240366783A1

公开(公告)日：2024-11-07

申请号：US18666145

申请日：2024-05-16

Applicant: AJINOMOTO CO., INC.

Inventor： Kei YAMADA ,  Yutaka MATSUDA ,  Tomohiro FUJII ,  Natsuki SHIKIDA ,  Reiko YUJI ,  Kazutaka SHIMBO ,  Yuji ITO

IPC: A61K47/68 ,  C07K16/00 ,  C07K19/00

Abstract: The present invention provides a technique enabling modification of a soluble protein and in particular regioselective modification of a soluble protein. More specifically, the present invention provides a compound having an affinity substance to a soluble protein, a cleavable portion, and a reactive group represented by the following Formula (I): A-L-B-R  (I) wherein A is an affinity substance to a soluble protein; L is a cleavable linker which is a divalent group comprising a cleavable portion; B is (a) a divalent group comprising a bioorthogonal functional group or (b) a divalent group comprising no bioorthogonal functional group; and R is a reactive group to the soluble protein; or a salt thereof.

公开(公告)号：US20240218015A1

公开(公告)日：2024-07-04

申请号：US18598901

申请日：2024-03-07

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Yuichi NAKAHARA ,  Kei YAMADA ,  Keisuke KATO ,  Yuta ENDO ,  Brian Alan MENDELSOHN

IPC: C07K1/04 ,  C07K1/02

CPC classification number: C07K1/045 ,  C07K1/02

Abstract: A method for producing an intermediate antibody regioselectively modified, which comprises:



(1) mixing a solution comprising an antibody material and a solution comprising a reagent for regioselectively modifying an antibody in a micromixer to form a mixture comprising the antibody material and the reagent,
wherein the reagent comprises a compound comprising an affinity substance to an antibody and a reactive group to an antibody; and
(2) passing the mixture through a reaction channel to allow the antibody material and the reagent to react in the reaction channel to form a solution comprising an intermediate antibody regioselectively modified,
wherein the processes (1) and (2) are continuously performed in a flow microreactor,
is capable of rapidly producing a desired antibody derivative regioselectively having a functional substance or functional substances.

公开(公告)号：US20240165260A1

公开(公告)日：2024-05-23

申请号：US18523499

申请日：2023-11-29

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Tomohiro FUJII ,  Ryusuke HIRAMA ,  Thomas MARKOTAN ,  Allan PRIOR ,  Christopher WONG ,  Konstantinos PLAKAS ,  Tomohiro WATANABE

IPC: A61K47/68 ,  C07K5/062

CPC classification number: A61K47/6889 ,  A61K47/68031 ,  A61K47/6855 ,  C07K5/06052

Abstract: A conjugate of an antibody and a functional substance or a salt thereof, which comprises a structural unit represented by the following formula (I):






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 predetermined divalent 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, 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 are excellent in desired properties while controlling a binding ratio between the antibody and the functional substance within a desired range.

公开(公告)号：US20240285788A1

公开(公告)日：2024-08-29

申请号：US18619910

申请日：2024-03-28

Applicant: Ajinomoto Co., Inc.

Inventor： Yutaka MATSUDA ,  Tomohiro WATANABE ,  Noriko HATADA ,  Tomohiro FUJII

IPC: A61K47/68

CPC classification number: A61K47/6811

Abstract: A conjugate of an antibody and a functional substance, comprising a structural unit represented by the following Formula (1):






wherein
Ig represents an immunoglobulin unit comprising two heavy chains and two light chains, and is bonded to LA adjacent to Ig via a thiol group in side chains of a plurality of cysteine residues in the two heavy chains and the two light chains,
HG represents a hydrophilic group or a monovalent group comprising a hydrophilic group,
CS represents a divalent group comprising a cleavable site,
ring A represents a divalent aromatic ring group optionally having a substituent wherein the divalent aromatic ring group constitutes a π electron conjugated system with the cleavable site,
V represents an oxygen atom, a sulfur atom, or an amino group (NH),
LA and LB each independently represent a divalent group,
D represents a functional substance, and
an average number n of the bonds per the immunoglobulin unit is 1.5 or more, or
a salt thereof, and
a substance associated therewith,

is excellent in desired properties.

公开(公告)号：US20240115719A1

公开(公告)日：2024-04-11

申请号：US18463903

申请日：2023-09-08

Applicant: Ajinomoto Co., Inc.

Inventor： Tomohiro FUJII ,  Kei YAMADA ,  Yutaka MATSUDA ,  Ryusuke HIRAMA ,  Noriko HATADA ,  Naoko ARASHIDA

IPC: A61K47/68 ,  C07K16/28

CPC classification number: A61K47/68031 ,  C07K16/2803

Abstract: Compounds or salts thereof represented by formula (I):






wherein
X indicates a leaving group,
Y indicates an affinity peptide having a binding region in a CH2 domain in an immunoglobulin unit comprising two heavy chains and two light chains,
M indicates a trivalent group linking the carbon atom in C═O adjacent to M and the carbon atom in C═W via a main chain portion consisting of 3 to 5 carbon atoms,
O indicates an oxygen atom,
S indicates a sulfur atom,
W indicates an oxygen atom or a sulfur atom,
N3 indicates an azide group,
La indicates a bond or a divalent group, and
Lb indicates a bond or a divalent group; and antibodies or salts thereof which can be prepared using such a compound or salt thereof, are useful for controlling the bonding ratio of an antibody and a modifying group within a desired range.

公开(公告)号：US20240058473A1

公开(公告)日：2024-02-22

申请号：US18467134

申请日：2023-09-14

Applicant: Ajinomoto Co., Inc.

Inventor： Kei YAMADA ,  Yutaka MATSUDA ,  Ippei INOUE ,  Natsuki SHIKIDA ,  Kazutaka SHIMBO

IPC: A61K47/69 ,  A61K47/68

CPC classification number: A61K47/6949 ,  A61K47/6835 ,  A61K47/6889

Abstract: The present invention provides a highly controlled complex comprising an antibody and ferritin particles. More specifically, the present invention provides the inventions of a complex or salt thereof comprising (A) one IgG antibody and (B) two human ferritin particles comprising one or more human ferritin H chains linked thereto; and methods for producing the same.