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    Sequence requirements for inhibitory oligonucleotides
    6.
    发明申请
    Sequence requirements for inhibitory oligonucleotides 审中-公开
    抑制性寡核苷酸的序列要求

    公开(公告)号：US20050239733A1

    公开(公告)日：2005-10-27

    申请号：US10977560

    申请日：2004-10-29

    申请人： Marion Jurk ,  Jorg Vollmer ,  Arthur Krieg ,  Eugen Uhlmann

    发明人： Marion Jurk ,  Jorg Vollmer ,  Arthur Krieg ,  Eugen Uhlmann

    IPC分类号： A61K48/00 ,  C07H21/04 ,  C12N15/117

    CPC分类号： C12N15/117 ,  C12N2310/17 ,  C12N2310/321 ,  C12N2310/334 ,  C12N2310/3341 ,  C12N2310/336 ,  C12N2310/3521

    摘要： Novel oligonucleotides having immune inhibitory effects, and methods for their use, are provided. The inhibitory oligonucleotides include those that specifically inhibit certain Toll-like receptors, including TLR7, TLR8, and TLR9. Certain of the immunoinhibitory oligonucleotides inhibit a combination of TLRs selected from TLR7, TLR8, and TLR9. Inhibitors of TLR9 are characterized by a 5′ CC dinucleotide appropriately spaced upstream of a G-rich oligomer. Inhibitors of TLR8 include specific simple dinucleotides and oligonucleotides ending at their 3′ termini with the specific dinucleotides. TLR7 inhibitors include oligonucleotides having a phosphorothioate backbone. Also provided are combinations and conjugates involving the inhibitory oligonucleotides of the invention and other agents, where the other agents include TLR agonists and antigens. Compositions of the invention can be used to shape an immune response, reduce unwanted specific TLR-mediated immunostimulation, and to treat conditions including allergy, asthma, infection, and cancer.

    摘要翻译： 提供了具有免疫抑制作用的新型寡核苷酸及其使用方法。 抑制性寡核苷酸包括特异性抑制某些Toll样受体的那些，包括TLR7，TLR8和TLR9。 某些免疫抑制性寡核苷酸抑制了选自TLR7，TLR8和TLR9的TLR的组合。 TLR9的抑制剂的特征在于在富G寡聚体上游适当间隔5'CC二核苷酸。 TLR8的抑制剂包括特异性简单二核苷酸和寡核苷酸终止于其3'末端与特异性二核苷酸。 TLR7抑制剂包括具有硫代磷酸酯骨架的寡核苷酸。 还提供了涉及本发明的抑制性寡核苷酸和其它试剂的组合和缀合物，其中其它试剂包括TLR激动剂和抗原。 可以使用本发明的组合物来形成免疫应答，减少不需要的特异性TLR介导的免疫刺激，并且治疗包括变态反应，哮喘，感染和癌症的病症。

    Combination motif immune stimulatory oligonucleotides with improved activity
    8.
    发明授权
    Combination motif immune stimulatory oligonucleotides with improved activity 失效
    具有改善活性的组合基序免疫刺激性寡核苷酸

    公开(公告)号：US08198251B2

    公开(公告)日：2012-06-12

    申请号：US12190402

    申请日：2008-08-12

    申请人： Jorg Vollmer ,  Eugen Uhlmann ,  Arthur M. Krieg ,  Douglas C. Hanson ,  Ulrike Samulowitz

    发明人： Jorg Vollmer ,  Eugen Uhlmann ,  Arthur M. Krieg ,  Douglas C. Hanson ,  Ulrike Samulowitz

    IPC分类号： A61K48/00

    CPC分类号： A61K31/7088 ,  A61K39/39 ,  A61K2039/55561 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/31 ,  C12N2310/315

    摘要： Immunostimulatory oligonucleotides, which contain a CpG immunostimulatory motif and a second motif that is capable of forming secondary structure, including duplex and higher order structures in vitro and in vivo, are disclosed. They include nucleic acids, or pharmaceutically acceptable salts thereof, having base sequences that include 5′ TCGTCGTTTTCGGCGCGCGCCGT 3′ (SEQ ID NO: 1), in which each C is unmethylated and 3′ refers to the 3′ end of the nucleic acid. The oligonucleotides activate B cells and NK cells and induce expression of type I interferon and interferon-γ. The oligonucleotides are useful for treating a variety of disorders and conditions, including allergy, asthma, infection, and cancer. In addition to their use as single agents and as combination therapies, the disclosed oligonucleotides are useful as adjuvants in vaccines.

    摘要翻译： 公开了含有CpG免疫刺激基序和能够形成二级结构的第二基序的免疫刺激性寡核苷酸，包括体外和体内的双链体和高级结构。 它们包括具有碱基序列的核酸或其药学上可接受的盐，其包含5'TCGTCGTTTTCGGCGCGCGCCGT 3'（SEQ ID NO：1），其中每个C是未甲基化的，3'是指核酸的3'末端。 寡核苷酸激活B细胞和NK细胞并诱导I型干扰素和干扰素-γ的表达。 寡核苷酸可用于治疗各种疾病和病症，包括过敏，哮喘，感染和癌症。 除了它们作为单一药剂和联合疗法的用途之外，所公开的寡核苷酸可用作疫苗中的佐剂。