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108 条记录 (耗时 0.023 秒)

    Method of down-regulating gene expression
    3.
    发明授权
    Method of down-regulating gene expression 失效
    降低基因表达的方法

    公开(公告)号：US06936593B1

    公开(公告)日：2005-08-30

    申请号：US09777526

    申请日：2001-02-06

    申请人： Sudhir Agrawal ,  Robert B. Diasio ,  Ruiwen Zhang

    发明人： Sudhir Agrawal ,  Robert B. Diasio ,  Ruiwen Zhang

    IPC分类号： A01N43/04 ,  A61K31/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/85 ,  C12P19/34 ,  C12Q1/68

    CPC分类号： A61K31/7125 ,  Y02A50/387 ,  Y02A50/402 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/414 ,  Y02A50/423

    摘要： Disclosed is a method of down-regulating the expression of a gene in an animal, wherein a pharmacological formulation comprising a chimeric oligonucleotide complementary to the gene is orally administered to an animal. The oligonucleotide administered has at least one phosphorothioate internucleotide linkage and at least one alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, phosphoramidite, phosphate ester, carbamate, carbonate, phosphate triester, acetamidate, or carboxymethyl ester internucleotide linkage.

    摘要翻译： 公开了一种下调动物基因表达的方法，其中将包含与该基因互补的嵌合寡核苷酸的药理学制剂口服给予动物。 所施用的寡核苷酸具有至少一个硫代磷酸酯核苷酸间键和至少一种烷基膦酸盐，二硫代磷酸盐，烷基磷硫酸盐，氨基磷酸盐，亚磷酰胺，磷酸酯，氨基甲酸盐，碳酸盐，磷酸三酯，乙酰胺盐或羧甲基酯核苷酸间键。

    Short immunomodulatory oligonucleotides
    5.
    发明申请
    Short immunomodulatory oligonucleotides 失效
    短免疫调节寡核苷酸

    公开(公告)号：US20040156825A1

    公开(公告)日：2004-08-12

    申请号：US10361111

    申请日：2003-02-07

    申请人： Hybridon, Inc.

    发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

    IPC分类号： A61K048/00 ,  C07H021/02

    CPC分类号： C07H21/02 ,  A61K2039/55561

    摘要： The invention relates to modulation of the immune system. More particularly, the invention relates to modulating the immune system through the use of oligonucleotide-derived compounds. The invention provides immunostimulatory agents that are less expensive to make than existing immunostimulatory oligonucleotides. The immunostimulatory agents according to the invention can, in preferred embodiments, cause immune stimulation across species lines.

    摘要翻译： 本发明涉及免疫系统的调节。 更具体地，本发明涉及通过使用寡核苷酸衍生的化合物调节免疫系统。 本发明提供免疫刺激剂，其比现有免疫刺激性寡核苷酸便宜。 在优选实施方案中，根据本发明的免疫刺激剂可以跨物种系引起免疫刺激。

    Inhibition of infectious agents by exogenous oligonucleotides
    6.
    发明申请
    Inhibition of infectious agents by exogenous oligonucleotides 审中-公开
    通过外源寡核苷酸抑制感染因子

    公开(公告)号：US20030186911A1

    公开(公告)日：2003-10-02

    申请号：US10292148

    申请日：2002-11-12

    申请人： Hybridon, Inc.

    发明人： John Goodchild ,  Paul C. Zamecnik ,  Sudhir Agrawal

    IPC分类号： A61K048/00 ,  C07H021/04

    CPC分类号： A61K31/70 ,  C07H21/00 ,  C12N15/1131 ,  C12N15/1132 ,  C12N2310/315 ,  C12Q1/701 ,  Y02A50/387 ,  Y02A50/409

    摘要： Inhibition of replication of an infectious agent, gene expression of an infectious agent, or both, by administration of an oligonucleotide complementary to highly conserved regions of the infectious agent is described. Inhibition of replication of a virus, gene expression of a virus, or both, by administration of an oligonucleotide complementary to highly conserved regions of the virus is also described.

    摘要翻译： 描述了通过施用与感染因子的高度保守区域互补的寡核苷酸来抑制感染因子的复制，感染因子或两者的基因表达。 还描述了通过施用与病毒的高度保守区域互补的寡核苷酸对病毒的复制，病毒的基因表达或两者的抑制。

    Method of modulating gene expression with reduced immunostimulatory response
    8.
    发明授权
    Method of modulating gene expression with reduced immunostimulatory response 失效
    用免疫刺激反应降低调节基因表达的方法

    公开(公告)号：US5968909A

    公开(公告)日：1999-10-19

    申请号：US511536

    申请日：1995-08-04

    申请人： Sudhir Agrawal ,  Jamal Temsamani ,  Qiuyan Zhao

    发明人： Sudhir Agrawal ,  Jamal Temsamani ,  Qiuyan Zhao

    IPC分类号： C12N15/09 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7088 ,  A61K31/7125 ,  A61K48/00 ,  A61P31/00 ,  A61P35/00 ,  C07H21/00 ,  C07H21/04

    CPC分类号： A61K31/7125 ,  C07H21/00

    摘要： The present invention provides a method of reducing the immunostimulatory effects of certain phosphorothioate oligonucleotides used to treat pathogen-mediated disease states and other medical conditions. Immunostimulatory effects of phosphorothioate oligonucleotides are reduced in accordance with the method of the invention by modifying at least one chemical structure within the phosphorothioate oligonucleotide to produce an immunostimulatory response-reducing phosphorothioate oligonucleotide, which is then administered to a mammal afflicted with the disease or condition being treated. The immune response of the mammal is also monitored in the method of the invention.

    摘要翻译： 本发明提供降低用于治疗病原体介导的疾病状态和其他医学病症的某些硫代磷酸酯寡核苷酸的免疫刺激作用的方法。 通过改变硫代磷酸酯寡核苷酸内的至少一种化学结构以产生免疫刺激性应答还原型硫代磷酸酯寡核苷酸，然后将其施用于患有疾病或病症的哺乳动物，根据本发明的方法减少硫代磷酸酯寡核苷酸的免疫刺激作用 治疗。 还在本发明的方法中监测哺乳动物的免疫应答。

    Procedure for the solid phase synthesis of .sup.35 S-labeled oligonucleotides with 3H-1,2-benzodithiol-3-one-1,1-dioxide
    9.
    发明授权
    Procedure for the solid phase synthesis of .sup.35 S-labeled oligonucleotides with 3H-1,2-benzodithiol-3-one-1,1-dioxide 失效
    用3H-1,2-苯并二硫醇-3-酮-1,1-二氧化物固相合成35S标记寡核苷酸的方法

    公开(公告)号：US5833944A

    公开(公告)日：1998-11-10

    申请号：US335100

    申请日：1994-11-07

    申请人： Radhakrishnan P. Iyer ,  Sudhir Agrawal ,  Weitian Tan

    发明人： Radhakrishnan P. Iyer ,  Sudhir Agrawal ,  Weitian Tan

    IPC分类号： C07B59/00 ,  C07H21/00 ,  A61K51/00 ,  A61M36/14

    CPC分类号： C07H21/00 ,  C07B59/002

    摘要： This invention provides a novel compound for .sup.35 S-labelling oligonucleotides. The compound is .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1) ##STR1## wherein the asterisk indicates the position of the .sup.35 S. Also provided is a method of synthesizing this compound, comprising first contacting .sup.35 S-thiobenzoic acid (4) with thiosalicylic acid (5) in acid medium to yield the condensation product, .sup.35 S-3 H 1,2-benzodithiol-3-one (2). .sup.35 S-3 H 1,2-benzodithiol-3-one (2) is then oxidized with a suitable oxidating agent such as trifuoroacetic acid and hydrogen perioxide to yield the desired product, .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1). Any oligonucleotide susceptible to oxidative sulfurized by 3H-1,2-benzodithiol-3-one-1,1 dioxide can be labeled by .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1). Accordingly, this invention also provides novel methods for .sup.35 S-labelling oligonucleotides. The compound and methods are useful for tracing biodistribution and degradation of antisense oligonucleotides in pharmacokinetic studies.

    摘要翻译： 本发明提供了一种用于35S标记寡核苷酸的新型化合物。 化合物是35S-3H-1,2-苯并二硫醇-3-酮二氧化物（1），其中星号表示35S的位置。 还提供了一种合成该化合物的方法，包括首先在酸性介质中将35S-硫代苯甲酸（4）与硫代水杨酸（5）接触以产生缩合产物，35S-3 H 1,2-苯并二硫酚-3-酮（2 ）。 然后用合适的氧化剂如三氟乙酸和二氧化碳氧化35S-3 H 1,2-苯并二硫醇-3-酮（2），得到所需产物，35S-3H-1,2-苯并二硫醇-3-酮 -1二氧化物（1）。 任何对3H-1,2-苯并二硫酚-3-酮二氧化物进行氧化硫化的寡核苷酸可用35S-3H-1,2-苯并二硫酚-3-酮二氧化物（1）进行标记。 因此，本发明还提供了35S标记寡核苷酸的新方法。 该化合物和方法可用于在药代动力学研究中追踪反义寡核苷酸的生物分布和降解。