EA202090282A1 - COMPOSITIONS OF OLIGONUCLEOTIDES AND METHODS FOR PRODUCING THEM - Google Patents

COMPOSITIONS OF OLIGONUCLEOTIDES AND METHODS FOR PRODUCING THEM

Info

Publication number
EA202090282A1
EA202090282A1 EA202090282A EA202090282A EA202090282A1 EA 202090282 A1 EA202090282 A1 EA 202090282A1 EA 202090282 A EA202090282 A EA 202090282A EA 202090282 A EA202090282 A EA 202090282A EA 202090282 A1 EA202090282 A1 EA 202090282A1
Authority
EA
Eurasian Patent Office
Prior art keywords
free
amino group
oligonucleotides
compositions
protected
Prior art date
Application number
EA202090282A
Other languages
Russian (ru)
Inventor
Премчандран Х. Рамия
Original Assignee
Джерон Корпорейшн
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Джерон Корпорейшн filed Critical Джерон Корпорейшн
Publication of EA202090282A1 publication Critical patent/EA202090282A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers

Abstract

В настоящем описании представлен твердофазный способ получения олигонуклеотидов посредством последовательных циклов связывания, включающих по меньшей мере одно связывание динуклеотидной димерной субъединицы со свободной 3'-концевой группой растущей цепи. Олигонуклеотиды содержат по меньшей мере две нуклеозидные субъединицы, связанные N3'P5' фосфорамидатной связью. Указанный способ может включать стадии (a) снятия защиты с защищенной 3'-аминогруппы концевого нуклеозида, присоединенного к твердофазной подложке, причем указанное снятие защиты приводит к образованию свободной 3'-аминогруппы; (b) приведения в контакт свободной 3'-аминогруппы с димером 3'-защищенный аминодинуклеотид-5'-фосфорамидит в присутствии нуклеофильного катализатора с получением межнуклеозидной N3'P5' фосфорамидитной связи; и (c) окисления (например, сульфирования) указанной связи. Композиции, полученные рассматриваемыми способами, могут содержать сниженное количество одного или более (N-x) олигонуклеотидных продуктов. Представлены также фармацевтические композиции, содержащие рассматриваемые олигонуклеотидные композиции.In the present description, a solid-phase method for producing oligonucleotides by successive binding cycles comprising at least one binding of a dinucleotide dimeric subunit to the free 3'-terminal group of the growing chain is presented. Oligonucleotides contain at least two nucleoside subunits linked by an N3'P5 'phosphoramidate linkage. Said method may include the steps of (a) deprotecting a protected 3'-amino group of a terminal nucleoside attached to a solid phase support, said deprotection leading to the formation of a free 3'-amino group; (b) contacting the free 3'-amino group with a dimer, a 3'-protected aminodinucleotide-5'-phosphoramidite in the presence of a nucleophilic catalyst to give an internucleoside N3'P5 'phosphoramidite bond; and (c) oxidizing (e.g., sulfonating) said bond. Compositions obtained by the considered methods may contain a reduced amount of one or more (N-x) oligonucleotide products. Also provided are pharmaceutical compositions containing the subject oligonucleotide compositions.

EA202090282A 2015-04-23 2015-04-29 COMPOSITIONS OF OLIGONUCLEOTIDES AND METHODS FOR PRODUCING THEM EA202090282A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201562151909P 2015-04-23 2015-04-23

Publications (1)

Publication Number Publication Date
EA202090282A1 true EA202090282A1 (en) 2020-05-20

Family

ID=70847680

Family Applications (1)

Application Number Title Priority Date Filing Date
EA202090282A EA202090282A1 (en) 2015-04-23 2015-04-29 COMPOSITIONS OF OLIGONUCLEOTIDES AND METHODS FOR PRODUCING THEM

Country Status (1)

Country Link
EA (1) EA202090282A1 (en)

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