利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

100 条记录 (耗时 0.099 秒)

    Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
    65.
    发明授权
    Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase 有权
    包含与修饰或非天然核碱基连接的配体的寡核苷酸

    公开(公告)号：US07893224B2

    公开(公告)日：2011-02-22

    申请号：US12533710

    申请日：2009-07-31

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

    IPC分类号： C07G3/00 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/6561 ,  C07H21/02 ,  C12Q1/6883 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

    摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

    摘要翻译： 本发明的一个方面涉及包含至少一个与改变的或非天然核碱基连接的配体的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有与改变的或非天然核碱基连接的配体。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地包含与改变的或非天然核碱基连接的配体。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一个与改变的或非天然核碱基连接的配体的单链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

    Oligonucleotides comprising a modified or non-natural nucleobase
    67.
    发明授权
    Oligonucleotides comprising a modified or non-natural nucleobase 有权
    包含修饰或非天然核碱基的寡核苷酸

    公开(公告)号：US07772387B2

    公开(公告)日：2010-08-10

    申请号：US12495932

    申请日：2009-07-01

    申请人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

    发明人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/65515 ,  C07F9/65586 ,  C07F9/6561 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

    摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

    摘要翻译： 本发明的一个方面涉及包含至少一种非天然核碱基的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吲哚基，硝基吡咯基或硝基咪唑基。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有非天然核碱基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地含有非天然核碱基。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非天然核碱基的单链寡核苷酸。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

    MODIFIED iRNA AGENTS
    68.
    发明申请
    MODIFIED iRNA AGENTS 有权
    改性iRNA代理

    公开(公告)号：US20100179309A1

    公开(公告)日：2010-07-15

    申请号：US12619382

    申请日：2009-11-16

    申请人： Muthiah MANOHARAN ,  Kallanthottathil G. Rajeev

    发明人： Muthiah MANOHARAN ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H21/02

    CPC分类号： C12N15/111 ,  A61K47/554 ,  C12N2310/14 ,  C12N2310/323 ,  C12N2310/344 ,  C12N2310/3515 ,  C12N2320/51

    摘要： The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a carbohydrate; or a steroid, e.g., cholesterol, which is optionally substituted with at least one carbohydrate. is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.

    摘要翻译： 本发明涉及iRNA试剂，其优选包括其中核糖部分被除核糖以外的部分替代的单体。 包含这样的单体可以允许调节其引入其中的iRNA试剂的性质，例如通过使用非核糖部分作为配体或其他实体例如碳水化合物的点; 或类固醇，例如胆固醇，其任选被至少一种碳水化合物取代。 是直接或间接地束缚着。 本发明还涉及制备和使用这种修饰的iRNA试剂的方法。

    IRNA agents with biocleavable tethers
    69.
    发明授权
    IRNA agents with biocleavable tethers 有权
    具有生物可清除系绳的IRNA试剂

    公开(公告)号：US07723509B2

    公开(公告)日：2010-05-25

    申请号：US10985426

    申请日：2004-11-09

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H21/04 ,  A61K31/70

    CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/323 ,  C12N2310/3511 ,  C12N2320/51

    摘要： The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

    摘要翻译： 本发明涉及iRNA试剂，其优选包括其中核糖部分已被核糖替代的单体，其进一步包括具有一个或多个连接基团的系链，其中至少一个连接基团是可切割的 连接组。 系链又可以连接到所选择的部分，例如配体，例如靶向或递送部分，或改变物理性质的部分。 可切割连接基团是在细胞外部足够稳定的连接基团，使得其允许靶向治疗有益量的iRNA试剂（例如，单链或双链iRNA试剂），其通过可切割连接基团连接至 靶向细胞靶向细胞，但是在进入靶细胞时被切割以从靶向剂释放iRNA试剂。

    Targeting Lipids
    70.
    发明申请
    Targeting Lipids 审中-公开
    靶向脂质

    公开(公告)号：US20090247608A1

    公开(公告)日：2009-10-01

    申请号：US12328669

    申请日：2008-12-04

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Gayaprakash K. Narayananovair ,  Muthusamy Jayaraman

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Gayaprakash K. Narayananovair ,  Muthusamy Jayaraman

    IPC分类号： A61K31/713 ,  C07K14/00 ,  A61K47/42 ,  A61K31/7088 ,  C07K7/04 ,  C07K5/04 ,  A61K47/12

    摘要： The present invention provides targeting lipids of structure L100—linker—L101   (CI), where L100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L101 is a ligand or —CH2CH2(OCH2CH2)pO(CH2)qCH2-ligand, p is 1-1000, and q is 1-20. In addition, the invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo.

    摘要翻译： 本发明提供了结构<？in-line-formula description =“In-line Formulas”end =“lead”？> L100-linker-L101（CI），<？in-line-formula description =“In 其中L100是脂质，亲脂性，烷基，烯基或炔基，L101是配体或-CH2CH2（OCH2CH2）pO（CH2）qCH2-配体，p是1-1000，和 q是1-20。 此外，本发明提供了将治疗剂递送至细胞的组合物和方法。 特别地，这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒，并将包封的核酸有效地递送到细胞体内。