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    Immunostimulatory oligoribonucleotides
    1.
    发明申请
    Immunostimulatory oligoribonucleotides 有权
    免疫刺激寡核糖核苷酸

    公开(公告)号：US20070142315A1

    公开(公告)日：2007-06-21

    申请号：US11603978

    申请日：2006-11-22

    申请人： Alexandra Forsbach ,  Jorg Vollmer ,  Grayson Lipford

    发明人： Alexandra Forsbach ,  Jorg Vollmer ,  Grayson Lipford

    IPC分类号： A61K48/00 ,  A61K9/14 ,  C07H21/02

    CPC分类号： A61K39/39 ,  A61K31/7105 ,  A61K2039/55561 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/315

    摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).

    摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。

    Immunostimulatory viral RNA oligonucleotides
    4.
    发明申请
    Immunostimulatory viral RNA oligonucleotides 审中-公开
    免疫刺激性病毒RNA寡核苷酸

    公开(公告)号：US20050256073A1

    公开(公告)日：2005-11-17

    申请号：US11061140

    申请日：2005-02-18

    申请人： Grayson Lipford ,  Alexandra Forsbach

    发明人： Grayson Lipford ,  Alexandra Forsbach

    IPC分类号： A61K31/7088 ,  A61K31/7105 ,  A61K31/7125 ,  A61K39/39 ,  A61K48/00 ,  C12N15/11 ,  C12Q1/68

    CPC分类号： A61K39/39 ,  A61K2039/55561

    摘要： Immunostimulatory sequence-specific RNA oligonucleotides corresponding to 3′ terminal sequences of single-stranded minus-sense RNA genomic RNAs are provided. Also provided are compositions and methods relating to an immunostimulatory 4-mer RNA motif provided as 5′-C/U-U-G/U-U-3′. Incorporation of this short RNA motif is sufficient to confer new and altered immunostimulatory properties in new and existing oligonucleotides, including CpG oligodeoxynucleotides. Also provided are methods for use of the immunostimulatory RNA oligonucleotides and DNA:RNA chimeric oligonucleotides of the invention to induce an immune response in vitro and in vivo, as well as to treat allergy, asthma, infection, and cancer in a subject. Single-stranded oligoribonucleotides of the invention are believed to signal through a Toll-like receptor (TLR) chosen from TLR9, TLR8, TLR7, and TLR3. The oligoribonucleotides can also be used in a method to screen for TLR antagonists.

    摘要翻译： 提供了对应于单链负义RNA基因组RNA的3'末端序列的免疫刺激序列特异性RNA寡核苷酸。 还提供了与作为5'-C / U-U-G-U-U-3'提供的免疫刺激性4聚体RNA基序相关的组合物和方法。 引入这种短RNA基序足以在新的和现有的寡核苷酸（包括CpG寡脱氧核苷酸）中赋予新的和改变的免疫刺激性质。 还提供了使用本发明的免疫刺激性RNA寡核苷酸和DNA：RNA嵌合寡核苷酸在体外和体内诱导免疫应答以及治疗受试者中的过敏，哮喘，感染和癌症的方法。 据信本发明的单链寡核糖核苷酸通过选自TLR9，TLR8，TLR7和TLR3的Toll样受体（TLR）发出信号。 寡核糖核苷酸也可用于筛选TLR拮抗剂的方法中。

    Pharmaceutical compositions comprising a polynucleotide and optionally an antigen especially for vaccination
    7.
    发明申请
    Pharmaceutical compositions comprising a polynucleotide and optionally an antigen especially for vaccination 审中-公开
    包含多核苷酸和任选的抗原的药物组合物，尤其用于疫苗接种

    公开(公告)号：US20090060927A1

    公开(公告)日：2009-03-05

    申请号：US10811226

    申请日：2004-03-26

    申请人： Hermann Wagner ,  Grayson Lipford ,  Klaus Heeg

    发明人： Hermann Wagner ,  Grayson Lipford ,  Klaus Heeg

    IPC分类号： A61K39/00

    CPC分类号： A61K39/39 ,  A61K2039/55561 ,  Y02A50/41

    摘要： The present invention relates to pharmaceutical compositions comprising at least one fragment of a polynucleotide, preferably at least one antigen, and optionally a pharmaceutically acceptable carrier and/or diluent. In accordance with the present invention was found that the introduction of the pharmaceutical composition into vertebrates will achieve regulation of growth, induction of cellular transcription and translation, protein synthesis, protein expression or protein secretion. The pharmaceutical compositions are useful in vaccination protocols but also in any other therapeutic situation in which immunomodulation is of benefit, such as sub-optimal immune responses, reaction to pathogens, tolerance or autoimmunity.

    摘要翻译： 本发明涉及包含多核苷酸的至少一个片段，优选至少一种抗原和任选的药学上可接受的载体和/或稀释剂的药物组合物。 发现根据本发明，将药物组合物引入脊椎动物将实现生长调节，诱导细胞转录和翻译，蛋白质合成，蛋白质表达或蛋白质分泌。 药物组合物可用于疫苗接种方案，但也可用于免疫调节有益的任何其它治疗情况，例如亚最佳免疫应答，对病原体的反应，耐受性或自身免疫性。

    Nucleic acids for high throughput screening of CpG-based immuno-agonist/antagonist
    9.
    发明授权
    Nucleic acids for high throughput screening of CpG-based immuno-agonist/antagonist 失效
    用于高通量筛选基于CpG的免疫激动剂/拮抗剂的核酸

    公开(公告)号：US06943240B2

    公开(公告)日：2005-09-13

    申请号：US09954987

    申请日：2001-09-17

    申请人： Stefan Bauer ,  Grayson Lipford ,  Hermann Wagner

    发明人： Stefan Bauer ,  Grayson Lipford ,  Hermann Wagner

    IPC分类号： G01N33/50 ,  A61K45/00 ,  A61K48/00 ,  A61P37/00 ,  C07K14/705 ,  C07K16/28 ,  C07K19/00 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12Q1/02 ,  C12Q1/68 ,  G01N27/447 ,  G01N33/15 ,  G01N33/53 ,  G01N33/566 ,  C07H21/00

    CPC分类号： C07K14/705

    摘要： The invention pertains to murine TLR9 and related TLR9s which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR9. The invention further relates to methods of using such murine and non-murine TLR9 nucleic acids and polypeptides, especially in methods for screening for agonists and antagonists of immunostimulatory CpG nucleic acids. Also included are murine TLR9 inhibitors which inhibit murine TLR9 activity by inhibiting the expression or function of murine TLR9. In a further aspect the present invention pertains to murine TLR7 and murine TLR8, as well as related TLR7 and TLR8 molecules which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR7 and TLR8. Methods are included for screening for ligands of TLR7 and TLR8, as well as for inhibitors and agonists and antagonists of signaling mediated by TLR7 and TLR8.

    摘要翻译： 本发明涉及鼠TLR9和相关TLR9，其包括鼠特异性氨基酸，以及编码这些多肽的核酸。 本发明还包括鼠TLR9的片段和生物学功能变体。 本发明还涉及使用这种鼠和非鼠TLR9核酸和多肽的方法，特别是用于筛选免疫刺激性CpG核酸的激动剂和拮抗剂的方法。 还包括通过抑制鼠TLR9的表达或功能来抑制鼠TLR9活性的鼠TLR9抑制剂。 在另一方面，本发明涉及鼠TLR7和鼠TLR8，以及包括鼠特异性氨基酸的相关TLR7和TLR8分子，以及编码那些多肽的核酸。 本发明还包括鼠TLR7和TLR8的片段和生物功能变体。 包括用于筛选TLR7和TLR8配体的方法，以及由TLR7和TLR8介导的抑制剂和激动剂和信号通路拮抗剂。

    Process for high throughput screening of CpG-based immuno-agonist/antagonist
    10.
    发明申请
    Process for high throughput screening of CpG-based immuno-agonist/antagonist 失效
    基于CpG的免疫激动剂/拮抗剂的高通量筛选方法

    公开(公告)号：US20050181422A1

    公开(公告)日：2005-08-18

    申请号：US11084777

    申请日：2005-03-18

    申请人： Stefan Bauer ,  Grayson Lipford ,  Hermann Wagner

    发明人： Stefan Bauer ,  Grayson Lipford ,  Hermann Wagner

    IPC分类号： G01N33/50 ,  A61K45/00 ,  A61K48/00 ,  A61P37/00 ,  C07K14/705 ,  C07K16/28 ,  C07K19/00 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12Q1/02 ,  C12Q1/68 ,  G01N27/447 ,  G01N33/15 ,  G01N33/53 ,  G01N33/566

    CPC分类号： C07K14/705

    摘要： The invention pertains to murine TLR9 and related TLR9s which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR9. The invention further relates to methods of using such murine and non-murine TLR9 nucleic acids and polypeptides, especially in methods for screening for agonists and antagonists of immunostimulatory CpG nucleic acids. Also included are murine TLR9 inhibitors which inhibit murine TLR9 activity by inhibiting the expression or function of murine TLR9. In a further aspect the present invention pertains to murine TLR7 and murine TLR8, as well as related TLR7 and TLR8 molecules which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR7 and TLR8. Methods are included for screening for ligands of TLR7 and TLR8, as well as for inhibitors and agonists and antagonists of signaling mediated by TLR7 and TLR8.

    摘要翻译： 本发明涉及鼠TLR9和相关TLR9，其包括鼠特异性氨基酸，以及编码这些多肽的核酸。 本发明还包括鼠TLR9的片段和生物学功能变体。 本发明还涉及使用这种鼠和非鼠TLR9核酸和多肽的方法，特别是用于筛选免疫刺激性CpG核酸的激动剂和拮抗剂的方法。 还包括通过抑制鼠TLR9的表达或功能来抑制鼠TLR9活性的鼠TLR9抑制剂。 在另一方面，本发明涉及鼠TLR7和鼠TLR8，以及包括鼠特异性氨基酸的相关TLR7和TLR8分子，以及编码那些多肽的核酸。 本发明还包括鼠TLR7和TLR8的片段和生物功能变体。 包括用于筛选TLR7和TLR8配体的方法，以及由TLR7和TLR8介导的抑制剂和激动剂和信号通路拮抗剂。