公开(公告)号：US20190008886A1

公开(公告)日：2019-01-10

申请号：US16068163

申请日：2017-01-05

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

发明人： Masayuki NAKAMORI ,  Hideki MOCHIZUKI ,  Satoshi OBIKA ,  Takanori YOKOTA ,  Tetuya NAGATA ,  Yuya KASAHARA

IPC分类号： A61K31/712 ,  C12N15/113 ,  C07K14/47 ,  A61P25/28 ,  A61P25/16

摘要： 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：US20160130583A1

公开(公告)日：2016-05-12

申请号：US14898630

申请日：2014-06-16

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY ,  OSAKA UNIVERSITY

发明人： Takanori YOKOTA ,  Kazutaka NISHINA ,  Kotaro YOSHIOKA ,  Satoshi OBIKA ,  Takenori SHIMO

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  A61K31/713 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2310/533 ,  C12N2320/33 ,  C12N2310/321 ,  C12N2310/3521

摘要： 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.

摘要翻译： 公开了可以通过反义效应有效地改变细胞中RNA的加工的双链反义核酸复合物及其使用方法。 一种方法包括与细胞接触双链核酸复合物，其包含：退火至第二核酸链的第一核酸链，其中：所述第一核酸链包含（i）独立地选自天然DNA核苷酸，经修饰的DNA 核苷酸和核苷酸类似物，（ii）没有具有4个或更多个连续天然DNA核苷酸的区域，（iii）第一个核酸链中天然DNA核苷酸，修饰的DNA核苷酸和核苷酸类似物的总数为8至100个 ，和（iv）第一核酸链能够与细胞内的RNA杂交; 并且第二核酸链包含独立地选自天然RNA核苷酸，修饰的RNA核苷酸和核苷酸类似物的核苷酸。

公开(公告)号：US20220307019A1

公开(公告)日：2022-09-29

申请号：US17442663

申请日：2020-03-25

申请人： National University Corporation Tokyo Medical and Dental University ,  WAVE LIFE SCIENCES LTD.

发明人： Takanori YOKOTA ,  Takeshi WADA ,  Mamoru SHIMIZU

IPC分类号： C12N15/113

摘要： A double-stranded nucleic acid complex is a double-stranded nucleic acid complex including a first nucleic acid strand and a second nucleic acid strand bonded to each other, the second nucleic acid strand including a complementary region having a base sequence complementary to the first nucleic acid strand; the first nucleic acid strand including natural nucleosides and non-natural nucleosides; some of the nucleosides in at least one nucleic acid strand selected from the group consisting of the first nucleic acid strand and the second nucleic acid strand being bonded together by bonds including asymmetric phosphorus atoms; and absolute configurations of the asymmetric phosphorus atoms being regulated.

公开(公告)号：US20210010000A1

公开(公告)日：2021-01-14

申请号：US16982274

申请日：2019-03-19

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Tetsuya NAGATA ,  Kotaro YOSHIOKA

IPC分类号： C12N15/113 ,  A61K9/00 ,  A61P25/00

摘要： An object of the invention is to provide a low toxicity antisense nucleic acid medicine that can modulate expression of a target transcriptional product in the central nervous system and other sites of a subject. Provided is a low toxicity composition for modulating expression of a target transcriptional product in a site such as the central nervous system of a subject, having a nucleic acid complex formed by annealing together a first nucleic acid strand having an antisense oligonucleotide region with respect to the target transcriptional product, and a second nucleic acid strand having a complementary region that is complementary to at least part of the first nucleic acid strand.

公开(公告)号：US20160287714A1

公开(公告)日：2016-10-06

申请号：US15038374

申请日：2014-11-21

申请人： THE UNIVERSITY OF TOKYO ,  NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Kazunori KATAOKA ,  Yasutaka ANRAKU ,  Nobuhiro NISHIYAMA ,  Kanjiro MIYATA ,  Takehiko ISHII ,  Yu MATSUMOTO ,  Yu FUKUSATO ,  Akihiro MIZOGUCHI ,  Takanori YOKOTA ,  Hiroya KUWAHARA ,  Kazutaka NISHINA ,  Hidehiro MIZUSAWA

IPC分类号： A61K47/48 ,  A61K31/7088 ,  A61K39/44 ,  A61K9/00

CPC分类号： A61K47/60 ,  A61K9/0019 ,  A61K9/127 ,  A61K31/7088 ,  A61K39/44 ,  A61K47/543 ,  A61K47/549 ,  A61K47/554 ,  A61K47/645 ,  A61K47/6455 ,  A61K47/6905 ,  A61K47/6907 ,  A61K47/6911 ,  A61K2039/505 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/6093 ,  B01J13/02 ,  C07K16/00 ,  C07K2317/10 ,  C07K2317/94 ,  C08G69/10 ,  C08G69/40 ,  C08G81/00

摘要： The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.

摘要翻译： 本发明提供囊泡，缀合物，包含用于向大脑递送药物的囊泡或缀合物的组合物及其施用方法。 本发明的组合物是用于根据给药方案向受试者施用的组合物，其包含用于药物递送的载体，其中所述给药方案包括将所述组合物施用于已经禁食或引起低血糖并诱导 增加受试者的血糖水平，并且载体在其外表面用GLUT1配体修饰。

公开(公告)号：US20220175817A1

公开(公告)日：2022-06-09

申请号：US17602035

申请日：2020-04-08

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Tetsuya NAGATA

IPC分类号： A61K31/713 ,  C12N15/113 ,  C12N9/12 ,  A61K47/56

摘要： A nucleic acid complex that exhibits an excellent antisense effect in the skeletal muscle and/or heart muscle, and a composition for treating or preventing a muscle disease that develops in the skeletal muscle, heart muscle, and the like having the nucleic acid complex as an active ingredient is disclosed. Also provided is a double-stranded nucleic acid complex in which a first nucleic acid strand that hybridizes to the transcription product of a target gene and has an antisense effect on the transcription product is annealed with a second nucleic acid strand that has a base sequence complementary to the first nucleic acid strand and is bound to cholesterol or analog thereof.

公开(公告)号：US20210130825A1

公开(公告)日：2021-05-06

申请号：US16975441

申请日：2019-02-27

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Satoru ISHIBASHI

IPC分类号： C12N15/113 ,  A61K47/54 ,  A61K9/00 ,  A61P9/10

摘要： The present invention provides an antisense nucleic acid medicine that can modulate expression of a target transcriptional product in an ischemic site of a subject. The present invention also provides a composition for modulating expression of a target transcriptional product in an ischemic site of a subject, having a nucleic acid complex formed by annealing together a first nucleic acid strand having an antisense oligonucleotide region with respect to the target transcriptional product, and a lipid-conjugated second nucleic acid strand having a complementary region that is complementary to at least part of the first nucleic acid strand.

公开(公告)号：US20220135972A1

公开(公告)日：2022-05-05

申请号：US17432858

申请日：2020-02-20

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Rintaro HARA ,  Tetsuya NAGATA ,  Hideki KIZAWA ,  Koh TAKAGI

IPC分类号： C12N15/113

摘要： An object of the present invention is to provide a double-stranded nucleic acid complex having a reduced number of PS modifications in an antisense strand and maintaining an antisense effect. An optimal PS modification pattern for double-stranded nucleic acid complexes is disclosed. Such a nucleic acid complex comprising an antisense strand having an optimal PS modification pattern has a characteristic of having low toxicity and high bioavailability. The double-stranded nucleic acid complex comprising an antisense strand having an optimal PS modification pattern according to the present invention is useful when used as a nucleic acid drug that utilizes inhibition of expression of a specific gene (knockdown), activity that changes the function of coating or non-coding RNA for a specific gene, or activity that changes the function of RNA by inducing exon skipping during processing of pre-mRNA for a specific gene.

公开(公告)号：US20210317455A1

公开(公告)日：2021-10-14

申请号：US17264451

申请日：2019-08-02

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Fumika SAKAUE

IPC分类号： C12N15/115 ,  A61P25/28

摘要： This invention provides a nucleic acid that can attenuate toxicity caused by abnormal accumulation of RNA-binding proteins in cells and can be used for prevention or treatment of neurodegenerative diseases and an agent for prevention or treatment of neurodegenerative diseases containing such nucleic acid. Such nucleic acid comprises a repeat RNA consisting of nucleotides represented by the formula: (U(Me)GX1X2X3 . . . Xm)n, wherein U(Me) is 2′-O-Me-modified; X1, X2, X3, . . . Xm may or may not be present, each independently represent A, C, G, or U in the presence thereof, and may be the same or different; m is 1 to 10; G, X1, X2, X3, . . . Xm may or may not be each independently 2′-O-Me-modified; and n is 4 to 15. The agent for prevention or treatment of neurodegenerative diseases induced by abnormal accumulation of TDP-43 in cells comprises such nucleic acid as an active ingredient.

公开(公告)号：US20210163934A1

公开(公告)日：2021-06-03

申请号：US16982758

申请日：2019-03-22

申请人： NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY

发明人： Takanori YOKOTA ,  Tetsuya NAGATA ,  Hideki FURUKAWA ,  Yasuo NAKAGAWA ,  Takatoshi YOGO ,  Ryosuke TOKUNOH ,  Shigekazu SASAKI ,  Kosuke HIDAKA ,  Tomohiro SEKI ,  Kenichi MIYATA ,  Yusuke ADACHI ,  Naoto ARIMURA

IPC分类号： C12N15/113 ,  A61P25/28 ,  A61K31/713

摘要： The object of the present invention is to provide a nucleic acid agent that can be efficiently delivered to the nervous system, particularly the central nervous system to which the BBB mechanism prevents drug delivery, and can produce an antisense effect on a target transcriptional product at the delivered site, and a composition comprising the same.
Provided is a double-stranded nucleic acid complex formed by annealing a first nucleic acid strand capable of hybridizing to part of a target transcriptional product, and has an antisense effect on the target transcriptional product, to a second nucleic acid strand comprising a base sequence complementary to the first nucleic acid strand, and is bound to tocopherol or an analog thereof, cholesterol or an analog thereof, or a substituted or unsubstituted C1-30 alkyl group, a substituted or unsubstituted C2-30 alkenyl group, or a substituted or unsubstituted C1-30 alkoxy group.