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    PURIFICATION OF OLIGONUCLEOTIDES
    1.
    发明申请
    PURIFICATION OF OLIGONUCLEOTIDES 失效
    纯化寡核苷酸

    公开(公告)号：US20130066061A1

    公开(公告)日：2013-03-14

    申请号：US13421273

    申请日：2012-03-15

    申请人： Olaf Grössel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    发明人： Olaf Grössel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    IPC分类号： C07H1/06

    CPC分类号： C07H21/00

    摘要： A method for purifying a protected oligonucleotide comprising the steps of: a) providing a solution of the protected oligonucleotide in at least one solvent A having a boiling point below the boiling point of a solvent B, heating the solution at a temperature of at least 30° C. and below the boiling point of the at least solvent A, adding solvent B until precipitation of a material is visible in the solution, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant or b) providing solvent B, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, heating solvent B at a temperature above 30° C. and below the boiling point of solvent B, adding a solution of a protected oligonucleotide in at least one solvent A until precipitation of a material is visible in the solution, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant.

    摘要翻译： 一种用于纯化受保护的寡核苷酸的方法，包括以下步骤：a）在至少一种沸点低于溶剂B的沸点的溶剂A中提供被保护的寡核苷酸的溶液，在至少30℃的温度下加热该溶液 ℃，并且低于至少溶剂A的沸点，加入溶剂B直到溶液中可观察到材料沉淀，所述溶剂B是具有1至6个C原子的醇或具有2至6个碳原子的二醇 原子，使溶液在搅拌下冷却直至形成上清液和残余物，除去上清液或b）提供溶剂B，所述溶剂B是具有1至6个碳原子的醇或具有2至6个碳原子的二醇 C原子，加热溶剂B，温度高于30℃，低于溶剂B的沸点，在至少一种溶剂A中加入被保护的寡核苷酸的溶液，直到在溶液中析出材料，使得 解决方案冷却下来 在搅拌下直到形成上清液和残余物，除去上清液。

    SYNTHESIS OF OLIGONUCLEOTIDES
    2.
    发明申请
    SYNTHESIS OF OLIGONUCLEOTIDES 审中-公开
    合成寡核苷酸

    公开(公告)号：US20120322994A1

    公开(公告)日：2012-12-20

    申请号：US13421384

    申请日：2012-03-15

    申请人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    发明人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    IPC分类号： C07H1/00

    CPC分类号： C07H21/00

    摘要： A method for preparing an oligonucleotide comprising the steps of a) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有式（A）的含羟基化合物，b）在具有式（I）的活化剂（活化剂I）存在下使所述化合物与磷酸化剂反应， 制备磷酸化化合物; 和c）不分离的所述磷化物化合物与式（A）的第二种化合物反应，其中R 5，R 3，R 2，B独立选择，但与不同于活化剂I的活化剂II存在下，具有与上述相同的定义。

    PURIFICATION OF OLIGONUCLEOTIDES
    4.
    发明申请
    PURIFICATION OF OLIGONUCLEOTIDES 审中-公开
    纯化寡核苷酸

    公开(公告)号：US20100087635A1

    公开(公告)日：2010-04-08

    申请号：US12568229

    申请日：2009-09-28

    申请人： Olaf Grossel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    发明人： Olaf Grossel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    IPC分类号： C07H1/06

    CPC分类号： C07H21/00

    摘要： A method for purifying a protected oligonucleotide comprising the steps of: a) providing a solution of the protected oligonucleotide in at least one solvent A having a boiling point below the boiling point of a solvent B, heating the solution at a temperature of at least 30° C. and below the boiling point of the at least solvent A, adding solvent B until precipitation of a material is visible in the solution, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant or b) providing solvent B, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, heating solvent B at a temperature above 30° C. and below the boiling point of solvent B, adding a solution of a protected oligonucleotide in at least one solvent A until precipitation of a material is visible in the solution, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant.

    摘要翻译： 一种用于纯化受保护的寡核苷酸的方法，包括以下步骤：a）在至少一种沸点低于溶剂B的沸点的溶剂A中提供受保护的寡核苷酸的溶液，在至少30℃的温度下加热该溶液 ℃，并且低于至少溶剂A的沸点，加入溶剂B直到溶液中可观察到材料沉淀，所述溶剂B是具有1至6个C原子的醇或具有2至6个碳原子的二醇 原子，使溶液在搅拌下冷却直至形成上清液和残余物，除去上清液或b）提供溶剂B，所述溶剂B是具有1至6个碳原子的醇或具有2至6个碳原子的二醇 C原子，加热溶剂B，温度高于30℃，低于溶剂B的沸点，在至少一种溶剂A中加入被保护的寡核苷酸的溶液，直到在溶液中析出材料，使得 解决方案冷却下来 在搅拌下直到形成上清液和残余物，除去上清液。

    SYNTHESIS OF OLIGONUCLEOTIDES
    5.
    发明申请
    SYNTHESIS OF OLIGONUCLEOTIDES 审中-公开
    合成寡核苷酸

    公开(公告)号：US20110065909A1

    公开(公告)日：2011-03-17

    申请号：US12836062

    申请日：2010-07-14

    申请人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    发明人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    IPC分类号： C07H1/00

    CPC分类号： C07H21/00

    摘要： A method for preparing an oligonucleotide comprising the steps ofa) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有式（A）的含羟基化合物，b）在具有式（I）的活化剂（活化剂I）存在下使所述化合物与磷酸化剂反应， 制备磷酸化化合物; 和c）不分离的所述磷化物化合物与式（A）的第二种化合物反应，其中R 5，R 3，R 2，B独立选择，但与不同于活化剂I的活化剂II存在下，具有与上述相同的定义。

    Method for preparing oligonucleotides
    6.
    发明申请
    Method for preparing oligonucleotides 失效
    寡核苷酸的制备方法

    公开(公告)号：US20110224424A1

    公开(公告)日：2011-09-15

    申请号：US13115845

    申请日：2011-05-25

    申请人： Ilaria ADAMO ,  Cécile DUEYMES ,  Andreas SCHÖNBERGER ,  Jean-Louis IMBACH ,  Albert MEYER ,  Francois MORVAN ,  Francoise DEBART ,  Jean-Jacques VASSEUR ,  Meinolf LANGE ,  Fritz LINK

    发明人： Ilaria ADAMO ,  Cécile DUEYMES ,  Andreas SCHÖNBERGER ,  Jean-Louis IMBACH ,  Albert MEYER ,  Francois MORVAN ,  Francoise DEBART ,  Jean-Jacques VASSEUR ,  Meinolf LANGE ,  Fritz LINK

    IPC分类号： C07H1/00 ,  C07H11/04

    CPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55 ,  Y02P20/582

    摘要： A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large- scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3′-protected compound of formula: with a nucleotide derivative having a 5′-protection group, or reacting a 5′-protected compound of formula with a nucleotide derivative having a 3′-protection group.

    摘要翻译： 一种制备寡核苷酸的溶液相合成方法，其中至少一些试剂是固体负载的。 适用于大规模合成的方法包括在保持固体的活化剂存在下将受保护化合物与具有保护基团的核苷酸衍生物偶联，得到具有P（III） - 核苷酸键的细长寡核苷酸; 任选地通过与固体支持的封端剂反应进行加帽和/或通过寡核苷酸与固体支持的氧化或硫化试剂的反应进行氧化或硫化来加工细长的寡核苷酸; 并移除保护组。 偶联可以包括使下式的3'-保护的化合物与具有5'-保护基团的核苷酸衍生物反应，或使5受保护的式的化合物与具有3'-保护基团的核苷酸衍生物反应。

    Synthesis of oligonucleotides
    7.
    发明申请
    Synthesis of oligonucleotides 审中-公开
    寡核苷酸的合成

    公开(公告)号：US20110201799A1

    公开(公告)日：2011-08-18

    申请号：US12839078

    申请日：2010-07-19

    申请人： Meinolf LANGE ,  Andreas HOHLFELD ,  Andreas SCHÖNBERGER ,  Christina KIRCHHOFF ,  Olaf GRÖSSEL

    发明人： Meinolf LANGE ,  Andreas HOHLFELD ,  Andreas SCHÖNBERGER ,  Christina KIRCHHOFF ,  Olaf GRÖSSEL

    IPC分类号： C07H21/00

    CPC分类号： C07H21/00

    摘要： A method for preparing an oligonucleotide comprising the steps of a) providing a hydroxyl containing compound having formula (1), wherein B is a heterocyclic base, and radicals R2, R3 and R5 are as defined in the description; b) reacting said compound with a phosphitylating agent in the presence of an activator I having formula (I), wherein R=alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl; R1, R2=either H or form a 5- to 6-membered ring together; X1, X2=independently either N or CH; Y=H or Si(R4)3, with R4=alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl; B=deprotonated acid; to prepare a phosphitylated compound; c) reacting said phosphitylated compound without isolation with a second compound having the formula (1), wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II selected from the group of imidazole, imidazolium salts, and mixtures thereof.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有式（1）的含羟基化合物，其中B为杂环碱基，R2，R3和R5基团如说明书中所定义; b）在具有式（I）的活化剂I的存在下使所述化合物与磷酸化剂反应，其中R =烷基，环烷基，芳基，芳烷基，杂烷基，杂芳基; R1，R2 = H或一起形成5-至6-元环; X1，X2 =独立地为N或CH; Y = H或Si（R4）3，其中R4 =烷基，环烷基，芳基，芳烷基，杂烷基，杂芳基; B =去质子酸 以制备磷酸化化合物; c）使所述磷化物化合物与不具有式（1）的第二化合物反应，其中独立地选择R 5，R 3，R 2，B，但在活化剂II的存在下具有与上述相同的定义，所述活化剂II选自 咪唑，咪唑鎓盐及其混合物。

    Method for preparing oligonucleotides
    10.
    发明申请
    Method for preparing oligonucleotides 审中-公开
    寡核苷酸的制备方法

    公开(公告)号：US20100069623A1

    公开(公告)日：2010-03-18

    申请号：US12417750

    申请日：2009-04-03

    申请人： Ilaria Adamo ,  Cècile Dueymes ,  Andreas Schönberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    发明人： Ilaria Adamo ,  Cècile Dueymes ,  Andreas Schönberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    IPC分类号： C07H21/04

    CPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55 ,  Y02P20/582

    摘要： A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3′-protected compound of formula: with a nucleotide derivative having a 5′-protection group, or reacting a 5′-protected compound of formula with a nucleotide derivative having a 3′-protection group.

    摘要翻译： 一种制备寡核苷酸的溶液相合成方法，其中至少一些试剂是固体负载的。 适用于大规模合成的方法包括在保持固体的活化剂存在下将受保护的化合物与具有保护基团的核苷酸衍生物偶联，得到具有P（III） - 核苷酸键的细长寡核苷酸; 任选地通过与固体支持的封端剂反应进行加帽和/或通过寡核苷酸与固体支持的氧化或硫化试剂的反应进行氧化或硫化来加工细长的寡核苷酸; 并移除保护组。 偶联可以包括使下式的3'-保护的化合物与具有5'-保护基团的核苷酸衍生物反应，或使5受保护的式的化合物与具有3'-保护基团的核苷酸衍生物反应。