公开(公告)号：US20210188894A1

公开(公告)日：2021-06-24

申请号：US16077969

申请日：2017-02-17

Applicant: TOKYO INSTITUTE OF TECHNOLOGY ,  NISSAN CHEMICAL CORPORATION

Inventor： Kohji SEIO ,  Yoshiaki MASAKI ,  Keishi YAMAMOTO ,  Keita YOSHIDA ,  Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI

IPC: C07H21/02 ,  C07H19/067

Abstract: Provided is an artificial nucleoside or artificial nucleotide capable of composing an artificial oligonucleotide having superior nuclease resistance. The artificial nucleoside or artificial nucleotide is a compound represented by formula (I) or a salt thereof (wherein, Bx represents a pyrimidine base or purine base, R1, R2, R3 and R4 represent hydrogen atoms, C1-6 alkyl groups or the like, Y represents NR5R6 (wherein, R5 and R6, independently of each other, represent a hydrogen atom, C1-6 alkyl group or the like, or R5 and R6, together with a nitrogen atom bound thereto, form a 3- to 11-membered nitrogen-containing non-aromatic heterocyclic group) or an optionally substituted C2-9 aromatic heterocyclic group, Z1 and Z2 represent hydrogen atoms, hydroxyl group-protecting groups, phosphorous-containing groups or the like, and n represents an integer of 1 to 3).

公开(公告)号：US20200224196A1

公开(公告)日：2020-07-16

申请号：US16633532

申请日：2018-07-26

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI

IPC: C12N15/113 ,  A61K31/712 ,  C12N15/10

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula [Xz-Lx]m-X-Y-[Ly-Yz]n, wherein X is represented by Xa-Xb, Xa is coupled with Y, and Xb and Y hybridize. Xa is composed of 1 to 40 nucleotides and contains at least one modified-nucleotide. Xb is composed of 4 to 40 nucleotides and contains at least one modified-nucleotide. Y is composed of 4 to 40 nucleotides and contains at least one ribonucleotide. Xz and Yz are composed of 5 to 40 nucleotides and contain at least one modified-nucleotide. Nucleotide sequences X, Xz and Yz have an antisense sequence capable of hybridizing with a target RNA. Lx and Ly are composed of 0 to 20 nucleotides.

公开(公告)号：US20230203498A1

公开(公告)日：2023-06-29

申请号：US18054660

申请日：2022-11-11

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI

IPC: C12N15/113 ,  A61K48/00 ,  A61K31/7088 ,  C12P19/34

CPC classification number: C12N15/1137 ,  C12N15/113 ,  A61K48/00 ,  A61K31/7088 ,  C12P19/34 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2310/3515

Abstract: Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

公开(公告)号：US20230183702A1

公开(公告)日：2023-06-15

申请号：US18152504

申请日：2023-01-10

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI

IPC: C12N15/113 ,  C12N15/10 ,  A61K31/712

CPC classification number: C12N15/113 ,  A61K31/712 ,  C12N15/1024

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula [Xz — Lx]m — X — Y — [Ly — Yz]n, wherein X is represented by Xa-Xb, Xa is coupled with Y, and Xb and Y hybridize. Xa is composed of 1 to 40 nucleotides and contains at least one modified-nucleotide. Xb is composed of 4 to 40 nucleotides and contains at least one modified-nucleotide. Y is composed of 4 to 40 nucleotides and contains at least one ribonucleotide. Xz and Yz are composed of 5 to 40 nucleotides and contain at least one modified-nucleotide. Nucleotide sequences X, Xz and Yz have an antisense sequence capable of hybridizing with a target RNA. Lx and Ly are composed of 0 to 20 nucleotides.

公开(公告)号：US20190119683A1

公开(公告)日：2019-04-25

申请号：US16073114

申请日：2017-01-26

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI

IPC: C12N15/113

Abstract: Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

公开(公告)号：US20240084296A1

公开(公告)日：2024-03-14

申请号：US18162942

申请日：2023-02-01

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI ,  Masatoshi NIWA

IPC: C12N15/113 ,  A61K31/7088

CPC classification number: C12N15/113 ,  A61K31/7088 ,  C12N2310/141 ,  C12N2310/315 ,  C12N2310/3519 ,  C12N2310/531

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure.

公开(公告)号：US20230159925A1

公开(公告)日：2023-05-25

申请号：US17908849

申请日：2021-03-04

Applicant: NISSAN CHEMICAL CORPORATION ,  KYOTO UNIVERSITY

Inventor： Yusuke IRIYAMA ,  Yoshiki KONDO ,  Yuuki HIDAKA ,  Ryutarou ISHIKAWA ,  Hiroyuki TSUKADA ,  Takeru MAKIYAMA ,  Yuta YAMAMOTO

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/3231 ,  C12N2310/321 ,  C12N2310/315 ,  C12N2310/3341 ,  C12N2310/3515 ,  C12N2320/30

Abstract: The present invention provides a compound or a pharmaceutically acceptable salt thereof containing a modified oligonucleotide with a length of 8 to 80 consecutive nucleosides, in which the modified oligonucleotide has a nucleobase sequence containing at least 8 consecutive nucleobases contained in a nucleobase sequence of any one of SEQ ID NOs: 3 to 73. With the compound or a pharmaceutically acceptable salt thereof, it is possible to treat a disease or a condition against which inhibition of CALM2 gene expression by controlling of the CALM2 gene expression is effective (particularly, congenital long QT syndrome).

公开(公告)号：US20230127437A1

公开(公告)日：2023-04-27

申请号：US17795867

申请日：2021-01-29

Applicant: SANWA KAGAKU KENKYUSHO CO., LTD. ,  NISSAN CHEMICAL CORPORATION

Inventor： Shinji HASHIMOTO ,  Izumi GOTO ,  Yusuke IRIYAMA

IPC: C12N15/113 ,  A61P25/28

Abstract: The invention provides an antisense oligonucleotide capable of controlling ATN1 gene expression and treating dentatorubral-pallidoluysian atrophy. An inventive compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence including at least 8 contiguous nucleobases that are complementary to a transcript of ATN1, or a pharmacologically acceptable salt thereof.

公开(公告)号：US20210254055A1

公开(公告)日：2021-08-19

申请号：US16484064

申请日：2018-02-06

Applicant: NISSAN CHEMICAL CORPORATION

Inventor： Yusuke IRIYAMA ,  Hiroyuki NAKAJIMA ,  Tatsuro KANAKI ,  Masatoshi NIWA

IPC: C12N15/113 ,  A61K31/7088

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure.

公开(公告)号：US20210054377A1

公开(公告)日：2021-02-25

申请号：US16982448

申请日：2019-03-20

Applicant: TOKYO INSTITUTE OF TECHNOLOGY ,  NISSAN CHEMICAL CORPORATION

Inventor： Yoshiaki MASAKI ,  Kohji SEIO ,  Atsushi INOUE ,  Yusuke IRIYAMA ,  Tatsuro KANAKI ,  Hiroyuki NAKAJIMA

IPC: C12N15/113 ,  A61K31/7125

Abstract: The invention provides an antisense oligonucleotide reduced in toxicity. The antisense oligonucleotide has a central region, a 5′-side region and a 3′-side region, wherein the central region has a nucleotide (2′-3′ bridged nucleotide) in which the 2′-position and the 3′-position of a sugar moiety are bridged and/or a non-bridged nucleotide (3′-position-modified non-bridged nucleotide) having a substituent at the 3′-position.