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66 条记录 (耗时 0.036 秒)

    Vectors and methods for immunization or therapeutic protocols
    31.
    发明授权
    Vectors and methods for immunization or therapeutic protocols 失效
    载体和免疫方法或治疗方案

    公开(公告)号：US06821957B2

    公开(公告)日：2004-11-23

    申请号：US09965101

    申请日：2001-09-26

    申请人： Arthur M. Krieg ,  Heather L. Davis ,  Tong Wu ,  Schorr Joachim

    发明人： Arthur M. Krieg ,  Heather L. Davis ,  Tong Wu ,  Schorr Joachim

    IPC分类号： A61K4800

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/292 ,  A61K39/39 ,  A61K48/00 ,  A61K2039/53 ,  A61K2039/55561 ,  A61K2039/57 ,  C12N2710/10343 ,  C12N2730/10134

    摘要： The present invention shows that DNA vaccine vectors can be improved by removal of CpG-N motifs and optional addition of CpG-S motifs. In addition, for high and long-lasting levels of expression, the optimized vector should include a promoter/enhancer that is not down-regulated by the cytokines induced by the immunostimulatory CpG motifs. Vectors and methods of use for immununostimulation are provided herein. The invention also provides improved gene therapy vectors by determining the CpG-N and CpG-S motifs present in the construct, removing stimulatory CpG (CpG-S) motifs and/or inserting neutralizing CpG (CpG-N) motifs, thereby producing a nucleic acid construct providing enhanced expression of the therapeutic polypeptide. Methods of use for such vectors are also included herein.

    摘要翻译： 本发明显示可以通过除去CpG-N基序和任选添加CpG-S基序来改善DNA疫苗载体。 此外，对于高和长期的表达水平，优化的载体应包括不被免疫刺激性CpG基序诱导的细胞因子下调的启动子/增强子。 本文提供了用于免疫刺激的载体和方法。 本发明还通过确定构建体中存在的CpG-N和CpG-S基序，除去刺激性CpG（CpG-S）基序和/或插入中和CpG（CpG-N）基序，从而产生核酸 提供治疗性多肽的增强的表达。 这些载体的使用方法也包括在本文中。

    Use of nucleic acids containing unmethylated CPC dinucleotide in the treatment of LPS-associated disorders
    34.
    发明授权
    Use of nucleic acids containing unmethylated CPC dinucleotide in the treatment of LPS-associated disorders 失效
    含有非甲基化CPG二核苷酸的核酸在治疗LPS相关疾病中的应用

    公开(公告)号：US06214806B1

    公开(公告)日：2001-04-10

    申请号：US09030701

    申请日：1998-02-25

    申请人： Arthur M. Krieg ,  David A. Schwartz

    发明人： Arthur M. Krieg ,  David A. Schwartz

    IPC分类号： A61K3170

    CPC分类号： C07H21/00

    摘要： The present invention is based on the finding that nucleic acids containing at least one unmethylated cytosine-guanine (CpG) dinucleotide affect immune responses in a subject. These nucleic acids containing at least one unmethylated cytosine-guanine (CpG) dinucleotide can be used to treat pulmonary disorders having an immunologic component, such as a response to inhaled lipopolysaccharide. The invention provides methods of treating subjects who have or are at risk of having these pulmonary disorders, and methods of altering the immunological components of the pulmonary disorders. The invention also provides pharmaceutical compositions for treating pulmonary disorders that have an immunologic component.

    摘要翻译： 本发明基于以下发现：含有至少一种非甲基化胞嘧啶 - 鸟嘌呤（CpG）二核苷酸的核酸影响受试者的免疫应答。 含有至少一个非甲基化胞嘧啶 - 鸟嘌呤（CpG）二核苷酸的这些核酸可用于治疗具有免疫组分的肺部疾病，例如对吸入的脂多糖的反应。 本发明提供了治疗患有或有风险患有这些肺部疾病的受试者的方法，以及改变肺部疾病的免疫组分的方法。 本发明还提供了用于治疗具有免疫组分的肺部疾病的药物组合物。

    Combination motif immune stimulatory oligonucleotides with improved activity
    36.
    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。

    Immunomodulatory oligonucleotides
    39.
    发明授权
    Immunomodulatory oligonucleotides 有权

    公开(公告)号：US08148340B2

    公开(公告)日：2012-04-03

    申请号：US10888089

    申请日：2004-07-09

    申请人： Arthur M. Krieg ,  Dennis Klinman ,  Alfred D. Steinberg

    发明人： Arthur M. Krieg ,  Dennis Klinman ,  Alfred D. Steinberg

    IPC分类号： C12N15/11 ,  C07H21/02

    CPC分类号： A61K31/4706 ,  A61K39/39 ,  A61K2039/55561 ,  C07H21/00 ,  C12Q1/68

    摘要： Oligonucleotides containing unthylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response in a subject are disclosed. Also disclosed are therapies for treating diseases associated with immune system activation that are initiated by unthylated CpG dinucleotides in a subject comprising administering to the subject oligonucleotides that do not contain unmethylated CpG sequences (i.e. methylated CpG sequences or no CpG sequence) to outcompete unmethylated CpG nucleic acids for binding. Further disclosed are methylated CpG containing dinucleotides for use antisense therapies or as in vivo hybridization probes, and immunoinhibitory oligonucleotides for use as antiviral therapeutics.