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    MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY
    2.
    发明申请
    MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY 审中-公开
    改良的寡核苷酸类似物与增强的免疫活性

    公开(公告)号：US20110244025A1

    公开(公告)日：2011-10-06

    申请号：US12946379

    申请日：2010-11-15

    申请人： Eugen Uhlmann ,  Arthur M. Krieg ,  Grayson B. Lipford

    发明人： Eugen Uhlmann ,  Arthur M. Krieg ,  Grayson B. Lipford

    IPC分类号： A61K9/127 ,  C07H21/02 ,  A61K39/00 ,  A61P11/00 ,  A61P31/14 ,  A61P35/00 ,  A61P37/08 ,  A61P37/04 ,  A61P11/06 ,  C12N5/02 ,  B82Y5/00

    CPC分类号： C07H21/00 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/3183 ,  C12N2310/321 ,  C12N2310/3515 ,  C12N2310/3529

    摘要： The invention provides immunostimulatory compositions and methods for their use. In particular, the immunostimulatory compositions of the invention include RNA-like polymers that incorporate an immunostimulatory sequence motif and at least one chemical modification to confer improved stability against nuclease degradation and improved activity. Specific modifications involving phosphate linkages, nucleotide analogs, and combinations thereof are provided. Compositions of the invention optionally include an antigen and can be used to stimulate an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an to allergic condition, or asthma. Modified oligoribonucleotide analogs of the invention are believed to stimulate Toll-like receptors TLR7 and TLR8.

    摘要翻译： 本发明提供免疫刺激组合物及其使用方法。 特别地，本发明的免疫刺激组合物包括纳入免疫刺激序列基序的RNA样聚合物和至少一种化学修饰，以提供改善的对核酸酶降解的稳定性和改善的活性。 提供了涉及磷酸键，核苷酸类似物及其组合的具体修饰。 本发明的组合物任选地包括抗原并且可以用于刺激免疫应答。 还提供了可用于治疗感染，癌症，过敏性疾病或哮喘的受试者的组合物和方法。 据信本发明的修饰的寡核糖核苷酸类似物刺激Toll样受体TLR7和TLR8。

    Polyamide nucleic acid derivatives and agents, and processes for preparing them
    6.
    发明授权
    Polyamide nucleic acid derivatives and agents, and processes for preparing them 失效
    聚酰胺核酸衍生物和试剂，及其制备方法

    公开(公告)号：US07550582B2

    公开(公告)日：2009-06-23

    申请号：US11855443

    申请日：2007-09-14

    申请人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    发明人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    IPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C07K14/003 ,  A61K38/00 ,  Y10T436/143333

    摘要： The present invention relates to PNA derivatives which carry, at the C terminus, or at both the C and N termini of the PNA backbone, one or more phosphoryl radicals. The phosphoryl radicals carry, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the above-mentioned PNA derivatives and to their use as pharmaceuticals or diagnostic agents.

    摘要翻译： 本发明涉及在C末端或在PNA主链的C和N末端携带一个或多个磷酰基的PNA衍生物。 磷酰基在适当的情况下携带一个或多个标记基团，用于交联的基团，促进细胞内摄取的基团，或增加PNA衍生物对核酸的结合亲和力的基团。 本发明还涉及制备上述PNA衍生物的方法及其作为药物或诊断剂的用途。

    Polyamide-oligonucleotide derivatives, their preparation and use
    7.
    发明授权
    Polyamide-oligonucleotide derivatives, their preparation and use 失效
    聚酰胺 - 寡核苷酸衍生物，其制备和用途

    公开(公告)号：US07485421B2

    公开(公告)日：2009-02-03

    申请号：US10939214

    申请日：2004-09-10

    申请人： Eugen Uhlmann ,  Gerhard Breipohl

    发明人： Eugen Uhlmann ,  Gerhard Breipohl

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： C07H21/00 ,  A61K47/59 ,  A61K47/595 ,  A61K47/60 ,  A61K47/605 ,  C07K14/003

    摘要： Polyamide-oligonucleotide derivatives of the formula F[(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF′ wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t≧2; x is 1 to 20; DNA is a nucleic acid such as DNA or RNA or a known derivative thereof; Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S; PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F′ are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof, a process for their preparation and their use as pharmaceutical, as gene probe and as primer, are described.

    摘要翻译： F [（DNA-Li）q（PNA-Li）r（DNA-Li）s（（N-1）） 其中q，r，s，t彼此独立地为0或1，其中总共为 两个或更多个相邻的q，r，s和t> = 2; x为1〜20; DNA是核酸如DNA或RNA或其已知衍生物; Li是DNA与PNA之间的共价连接，其中共价连接包含与C，N，O或S组成的系列中至少一个原子的键或有机基团; PNA是含有与胸腺嘧啶不同的至少一个核苷酸碱基的聚酰胺结构; 并且F和F'是端基和/或通过共价键连接在一起，并且描述了其生理学上耐受的盐，它们的制备方法及其作为药物的用途，作为基因探针和引物。

    Polyamide nucleic acid derivatives, and agents, and processes for preparing them
    8.
    发明授权
    Polyamide nucleic acid derivatives, and agents, and processes for preparing them 有权
    聚酰胺核酸衍生物和试剂，及其制备方法

    公开(公告)号：US07241882B2

    公开(公告)日：2007-07-10

    申请号：US10863999

    申请日：2004-06-09

    申请人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    发明人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    IPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C07H21/00

    摘要： The present invention relates to PNA derivatives which carry, at the N terminus of the PNA backbone, a phosphoryl radical. The phosphoryl radical can be, for example, a phosphate radical, or a substituted phosphoryl radical, with substituted phosphoryl derivatives carrying, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the abovementioned PNA derivatives and to their use as pharmaceuticals and diagnostic agents.

    摘要翻译： 本发明涉及在PNA主链的N末端携带磷酰基的PNA衍生物。 磷酰基可以是例如磷酸根或取代的磷酰基，其中取代的磷酰基衍生物在适当的情况下携带一个或多个标记基团，交联基团，促进细胞内摄取的基团或增加结合的基团 PNA衍生物对核酸的亲和力。 本发明还涉及制备上述PNA衍生物的方法及其作为药物和诊断剂的用途。

    Sequence requirements for inhibitory oligonucleotides
    10.
    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。