Other

Daiichi Sankyo Company, Limited

Mitsubishi-kagaku Foods Corporation

Takeshi Imanishi

Taisho Pharmaceutical Co., Ltd.

Nippon Suisan Kaisha, Ltd.

Osaka University

Riken Corporation

Sankyo Company, Limited

National Cerebral and Cardiovascular Center

Santaris Pharma A/s

Exiqon A/s

Protein Engineering Research Institute

Roche Innovation Center Copenhagen A/s

Tokyo University of Science Educational Foundation Administrative Organization

Satoshi Obika

Koji Morita

Masakatsu Kaneko

Masakazu Sato

Jun Goto

Yutaka Kawashima

Yoshiyuki Chiba

Mikio Satake

Chuzo Iwata

Atsushi Yamashita

Tatsuhiko Kodama

Masaaki Suzuki

Yasuyoshi Watanabe

Tsuyoshi Yamamoto

Tetsuji Yamaoka

Hisashi Doi

Toshiki Tanaka

Sachiro Kakinoki

Mariko Shiba

Haruki Nakamura

Takeshi Kuboyama

Takefumi Doi

Kazuyuki Miyashita

Kiyomi Sasaki

Yoichi Tachibana

Hidetaka Torigoe

Keisuke Narukawa

Tachibana Yoichi

An object of the present invention is to provide an oligonucleotide useful as a therapeutic agent for dyslipidemia that has excellent binding affinity to the PCSK9 gene as well as stability and safety. The oligonucleotide of the present invention contains a sugar-modified nucleoside, the sugar-modified nucleoside has a bridging structure between 4'-position and 2&#x2032;-position, and the oligonucleotide can bind to the human PCSK9 gene. Also, the present invention provides a therapeutic agent for dyslipidemia containing the oligonucleotide as an active ingredient, and the therapeutic agent preferably contains a bioabsorbable material as a carrier. The bioabsorbable material is preferably atelocollagen or peptide gel.

Oligonucleotide, and therapeutic agent for dyslipidemia containing oligonucleotide as active ingredient

A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.

Oligonucleotide analogues and methods utilizing the same

The present invention provides anF-labeled azide compound usable in the Huisgen reaction which enablesF-labeling although only a small quantity of alkyne compound is available as a counterpart substrate, more specifically theF-labeled azide compound enabling the PET to be applied to peptides or oligonucleotides and enabling theF-labeling of any sites of oligonucleotide other than the 5' end or 3&#x2032; end thereof, a reagent forF-labeling, and a method forF-labeling of an alkyne compound using the same.

[object Object]

An oligo- or polynucleotide analogue having one or more structures of the general formula

Bicyclonucleoside and oligonucleotide analogues

Oligonucleotide analogues which have anti-sense or anti-gene activity, as well as in vivo stability, or pharmaceutically acceptable salts thereof. The oligonucleotide analogues have one or more structural units represented by the following formula (1a): provided that when the oligonucleotide has two or more structural units of formula (1a), each B is the same or different, wherein B represents a purin-9-yl group or a 2-oxo-1,2-dihydropyrimidin-1-yl group.

Bicyclonucleoside analogues

A nucleotide analogue compound represented by formula (1) and salts thereof. In formula (1), A represents a direct bond, Calkylene, etc.; B represents an optionally substituted aromatic heterocyclic groups; and R, R, Rand Reach represents hydrogen, an amino-protecting group, a hydroxyl-protecting group, a phosphate group, or &#x2014;P(R)R, wherein Rand Reach represents hydroxyl, protected hydroxyl, mercapto, protected mercapto, etc. The compounds are useful as nucleotide analogues for producing oligonucleotide analogues useful in an antisense method and for producing intermediates thereof.

Nucleoside analogues and oligonucleotide derivative comprising nucleotide analogue thereof

An oligonucleotide analogue useful for the antisense method, etc., having excellent enzyme resistance, having potent selective binding affinity for single-stranded RNA, and further having an excellent triplex-forming capacity with double-stranded DNA, and a nucleoside analogue useful for its production are provided. Nucleoside analogues, which are compounds of the general formula (I) and salts thereof, and oligonucleotide analogues containing one or more of the nucleoside analogues: where Base is an aromatic heterocyclic group or the like optionally having a substituent; R, Rand Rare each a hydrogen atom, a protective group for an amino group, a protective group for a hydroxyl group, a phosphate group, or &#x2014;P(R)R[where Rand Rare each a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, etc.]; m=0 to 2; and n=1 to 3].

Artificial nucleic acids of n-o bond crosslinkage type

A compound of the formula (1): wherein Rand Rare the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or &#x2014;P(R)R, wherein Rand Rare the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent &#x3b1; selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

Nucleoside and oligonucleotide analogues

A probe for a gene or a primer for starting amplification comprising an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of the nucleoside units is a structure of the formula (2): wherein A represents a C-Calkylene group, and B is an unsubstituted purin-9-yl group, an unsubstituted 2-oxo-pyrimidin-1-yl-group, a substituted purin-9-yl-group or a substituted 2-oxo-pyrimidin-1-yl group. Also a method for preventing or treating a disease preventable or treatable by the antisense or antigene activity of an oligonucleotide by administering the oligonucleotide analogue.

Bicyclonucleoside analogues which exhibit anti-AIDS activity and intermediates to produce oligonucleotide analogues which have anti-sense or anti-gene activity as well as in vivo stability. Compounds of the following formula (1) or their pharmaceutically acceptable salts. wherein Rrepresents a hydrogen atom or a protecting group for a hydroxy group, Rrepresents an azido group or an optionally protected amino group or the like, B represents a purin-9-yl or a 2-oxo-1,2-dihydropyrimidin-1-yl group, which are optionally substituted with substituents selected from the group consisting of a halogen atom, an alkyl group having 1&#x2013;6 carbon atoms, a hydroxy group, a mercapto group and an amino group.

Nucleoside analogues expressed by the following general formula The oligonucleotide derivatives are triplex-forming oligonucleotide derivatives which bind specifically to target double-stranded DNA with high affinity in the antigene method to form triplexes, and can thereby control and inhibit the expression of relevant genes efficiently, and which show high resistance to nucleases.

Nucleoside analogs and oligonucleotide derivatives containing these analogs

Bicyclonucleoside and oligonucleotide analogue

Nucleotide analogues

Growing community of inventors

Nara, Japan

Takeshi Imanishi