公开(公告)号：US11905308B2

公开(公告)日：2024-02-20

申请号：US17667988

申请日：2022-02-09

Applicant: Osaka University

Inventor： Satoshi Obika ,  Kosuke Ito ,  Takaki Habuchi ,  Masahiko Horiba

IPC: C07H21/02 ,  C07H19/10 ,  C12N15/113

CPC classification number: C07H19/10 ,  C07H21/02 ,  C12N15/113 ,  C12N2310/11

Abstract: The present invention aims to provide a nucleic acid compound that hardly forms non-Watson-Crick base pairs, and an oligonucleotide containing the nucleic acid compound and showing reduced non-specific binding with nucleic acids other than the target nucleic acid. The nucleic acid compound according to the present invention is characterized in that the 2-position carbonyl group of the pyrimidine base is functionally converted (X1 and X2 are each independently S or Se), and that the 2′-position and the 4′-position are bridged in a particular structure. The oligonucleotide according to the present invention is characterized in that at least one of thymidine and uridine is the nucleic acid compound.

公开(公告)号：US10190117B2

公开(公告)日：2019-01-29

申请号：US14898630

申请日：2014-06-16

Applicant: National University Corporation Tokyo Medical and Dental University ,  Osaka University

Inventor： Takanori Yokota ,  Kazutaka Nishina ,  Kotaro Yoshioka ,  Satoshi Obika ,  Takenori Shimo

IPC: C12N15/113 ,  A61K31/712 ,  A61K31/7125 ,  A61K31/713

Abstract: Disclosed are double-stranded antisense nucleic acid complexes that can efficiently alter the processing of RNA in a cell via an antisense effect, and methods for using the same. One method comprises contacting with the cell a double-stranded nucleic acid complex comprising: a first nucleic acid strand annealed to a second nucleic acid strand, wherein: the first nucleic acid strand comprises (i) nucleotides independently selected from natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs, (ii) no regions that have 4 or more consecutive natural DNA nucleotides, (iii) the total number of natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs in the first nucleic acid strand is from 8 to 100, and (iv) the first nucleic acid strand is capable of hybridizing to RNA inside of the cell; and the second nucleic acid strand comprises nucleotides independently selected from natural RNA nucleotides, modified RNA nucleotides, and nucleotide analogs.

公开(公告)号：US20240158790A1

公开(公告)日：2024-05-16

申请号：US18392869

申请日：2023-12-21

Applicant: National University Corporation Tokyo Medical and Dental University ,  Osaka University

Inventor： Takanori Yokota ,  Kazutaka Nishina ,  Satoshi Obika ,  Hidehiro Mizusawa

IPC: C12N15/113 ,  C12N15/11

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/15 ,  C12N2310/3181 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/52

Abstract: A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

公开(公告)号：US11234995B2

公开(公告)日：2022-02-01

申请号：US16068163

申请日：2017-01-05

Applicant: OSAKA UNIVERSITY ,  NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY ,  NATIONAL INSTITUTES OF BIOMEDICAL INNOVATION, HEALTH AND NUTRITION

Inventor： Masayuki Nakamori ,  Hideki Mochizuki ,  Satoshi Obika ,  Takanori Yokota ,  Tetuya Nagata ,  Yuya Kasahara

IPC: C12N15/11 ,  A61K31/712 ,  C07K14/47 ,  C12N15/113 ,  C07H21/02 ,  C12N15/09 ,  A61P25/28 ,  A61P25/16

Abstract: The present invention can provide a nucleic acid medicine which has a higher effect and a more prolonged effect of inhibiting the expression of α-synudein can be provided. Disclosed is the oligonucleotide or a pharmacologically acceptable salt thereof, the oligonucleotide containing at least one nucleoside structure represented by Formula (I): (where each of Base and A are defined substituent or structure), can bind to an α-synudein gene, has activity for inhibiting expression of the α-synudein gene, and is complementary to the α-synudein gene, and the oligonucleotide has a length of twelve to twenty bases.

公开(公告)号：US20190270996A1

公开(公告)日：2019-09-05

申请号：US16410803

申请日：2019-05-13

Applicant: National University Corporation Tokyo Medical and Dental University ,  Osaka University

Inventor： TAKANORI YOKOTA ,  Kazutaka Nishina ,  Satoshi Obika ,  Hidehiro Mizusawa

IPC: C12N15/113 ,  C12N15/11

Abstract: A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

公开(公告)号：US10329567B2

公开(公告)日：2019-06-25

申请号：US16021165

申请日：2018-06-28

Applicant: National University Corporation Tokyo Medical and Dental University ,  Osaka University

Inventor： Takanori Yokota ,  Kazutaka Nishina ,  Satoshi Obika ,  Hidehiro Mizusawa

IPC: C12N15/09 ,  C12N15/113 ,  C12N15/11

Abstract: A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

公开(公告)号：US12104154B2

公开(公告)日：2024-10-01

申请号：US17666341

申请日：2022-02-07

Applicant: Osaka University

Inventor： Satoshi Obika ,  Reiko Waki ,  Takao Inoue ,  Tokuyuki Yoshida ,  Kunihiko Morihiro ,  Yuya Kasahara ,  Atsushi Mikami

IPC: C12N15/113 ,  A61K31/7115 ,  A61K31/712

CPC classification number: C12N15/113 ,  A61K31/7115 ,  A61K31/712

Abstract: The present invention aims to provide an antisense oligonucleic acid with reduced hepatotoxicity. The antisense oligonucleic acid according to the present invention is characterized in that it has a base length of not less than 7 nt and not more than 30 nt, wherein nucleic acid residues of not less than 1 nt and not more than 5 nt respectively from the both terminals are 2′,4′-bridged nucleic acids, 2′,4′-non-bridged nucleic acid residue(s) is(are) present between the above-mentioned both terminals, and one or more bases in the nucleic acid residue(s) of the above-mentioned 2′,4′-non-bridged nucleic acid residue(s) is/are modified.

公开(公告)号：US11261440B2

公开(公告)日：2022-03-01

申请号：US16487762

申请日：2018-02-20

Applicant: Osaka University

Inventor： Satoshi Obika ,  Reiko Waki ,  Takao Inoue ,  Tokuyuki Yoshida ,  Kunihiko Morihiro ,  Yuya Kasahara ,  Atsushi Mikami

IPC: C12N15/113 ,  A61K31/7115 ,  A61K31/712

Abstract: The present invention aims to provide an antisense oligonucleic acid with reduced hepatotoxicity. The antisense oligonucleic acid according to the present invention is characterized in that it has a base length of not less than 7 nt and not more than 30 nt, wherein nucleic acid residues of not less than 1 nt and not more than 5 nt respectively from the both terminals are 2′,4′-bridged nucleic acids, 2′,4′-non-bridged nucleic acid residue(s) is(are) present between the above-mentioned both terminals, and one or more bases in the nucleic acid residue(s) of the above-mentioned 2′,4′-non-bridged nucleic acid residue(s) is/are modified.

公开(公告)号：US10961269B2

公开(公告)日：2021-03-30

申请号：US15760513

申请日：2016-09-20

Applicant: MITSUBISHI TANABE PHARMA CORPORATION ,  OSAKA UNIVERSITY

Inventor： Satoshi Obika ,  Eiji Kawanishi ,  Hiroaki Sawamoto ,  Shuhei Yamakoshi ,  Yuuki Aral ,  Shinji Kumagai

IPC: C07H19/06 ,  C07H9/06 ,  C07H21/00 ,  C07H19/16 ,  C07H1/00 ,  C07C279/16 ,  C07D498/04 ,  C07D498/08

Abstract: A method for preparing a compound represented by general formula I: or a salt thereof includes a step of reacting a compound represented by formula II: with a reducing agent to cleave an oxazolidine ring fused to a cycle A′. The reducing agent includes at least one of phosphines, metal hydrides, or transition metal catalysts in the presence of hydrogen gas.

公开(公告)号：US20180320181A1

公开(公告)日：2018-11-08

申请号：US16021165

申请日：2018-06-28

Applicant: National University Corporation Tokyo Medical and Dental University ,  Osaka University

Inventor： Takanori Yokota ,  Kazutaka Nishina ,  Satoshi Obika ,  Hidehiro Mizusawa

IPC: C12N15/113 ,  C12N15/11

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/15 ,  C12N2310/3181 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/52

Abstract: A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.