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    Recombinant toxin fragments
    1.
    发明授权
    Recombinant toxin fragments 有权
    重组毒素片段

    公开(公告)号：US08012479B2

    公开(公告)日：2011-09-06

    申请号：US12399542

    申请日：2009-03-06

    申请人： Clifford Charles Shone ,  Conrad Padraig Quinn ,  Keith Alan Foster ,  John Chaddock ,  Philip Marks ,  J. Mark Sutton ,  Patrick Stancombe ,  Jonathan Wayne

    发明人： Clifford Charles Shone ,  Conrad Padraig Quinn ,  Keith Alan Foster ,  John Chaddock ,  Philip Marks ,  J. Mark Sutton ,  Patrick Stancombe ,  Jonathan Wayne

    IPC分类号： A61K39/00 ,  A61K39/38 ,  A61K39/08

    CPC分类号： C12N15/62 ,  A61K38/00 ,  A61K39/00 ,  A61K39/08 ,  A61K47/6415 ,  A61K47/646 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/627 ,  C07K14/33 ,  C07K14/475 ,  C07K14/65 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/23 ,  C07K2319/50 ,  C07K2319/55 ,  C07K2319/705 ,  C07K2319/75 ,  C12N9/52 ,  Y02A50/469 ,  Y10S530/825

    摘要： Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain HN portion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell surface receptors to which native clostridial neurotoxin binds. Antibodies that bind to the polypeptides, and compositions comprising these antibodies, are also provided, as are DNA vaccines comprising polynucleotides that encode these polypeptides.The antigenic and antibody compositions, and the DNA vaccine compositions, can be used in methods of immunising against, or treating, clostridial neurotoxin poisoning in a subject by administering to that subject a therapeutically effective amount of the composition.

    摘要翻译： 提供抗原组合物，其包含包含第一和第二结构域的单链多肽，其中所述第一结构域是梭菌神经毒素轻链或其片段或变体，并且能够切割一种或多种与胞吐作用必需的相关蛋白或质膜相关蛋白; 并且所述第二结构域是梭菌神经毒素重链HN部分或其片段或变体，其中所述第二结构域能够（i）将多肽转位到细胞中，或（ii）与溶解度相比增加多肽的溶解度 或（iii）将多肽转移到细胞中并且与第一结构域本身的溶解度相比增加多肽的溶解度; 并且其中所述第二结构域缺少称为HC的梭菌神经毒素重链的功能性C-末端部分，从而使所述多肽不能结合作为天然梭菌神经毒素结合的天然细胞表面受体的细胞表面受体。 还提供了结合多肽的抗体和包含这些抗体的组合物，DNA疫苗也包括编码这些多肽的多核苷酸。 抗原和抗体组合物和DNA疫苗组合物可用于通过向该受试者施用治疗有效量的组合物来免疫或治疗受试者的梭菌神经毒素中毒的方法。

    Clostridial toxin derivatives able to modify peripheral sensory afferent functions
    4.
    发明申请
    Clostridial toxin derivatives able to modify peripheral sensory afferent functions 失效
    能够修饰周围感觉传入功能的梭菌毒素衍生物

    公开(公告)号：US20090131645A1

    公开(公告)日：2009-05-21

    申请号：US11819648

    申请日：2007-06-28

    申请人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    发明人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    IPC分类号： C07K19/00 ,  C12N9/54 ,  C07H21/00

    CPC分类号： C07K14/48 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/00 ,  Y10S424/832

    摘要： This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

    摘要翻译： 本发明描述了用于靶向控制哺乳动物细胞活性的新型试剂，特别是该试剂用于控制特定细胞类型与其外部环境的相互作用。 该试剂具有用作治疗各种疾病的药物的应用。 根据本发明的药剂包含以下列方式连接在一起的三个B，T和E域：域B结构域T域E，其中B区是绑定结构域，该结合域将该试剂结合到经历内吞作用的细胞上的结合位点 为了产生一个内体，结构域T是易位区域，它将试剂（有或者没有结合位点）从内体内穿过内体膜转移到细胞的细胞溶质中，E区是抑制 可循环膜囊将整体膜蛋白转运至细胞表面。

    Clostridial toxin derivatives able to modify peripheral sensory afferent functions
    5.
    发明申请
    Clostridial toxin derivatives able to modify peripheral sensory afferent functions 失效
    能够修饰周围感觉传入功能的梭菌毒素衍生物

    公开(公告)号：US20080319167A1

    公开(公告)日：2008-12-25

    申请号：US11819650

    申请日：2007-06-28

    申请人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    发明人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    IPC分类号： C07K14/33 ,  C07H21/00

    CPC分类号： C07K14/48 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/00 ,  Y10S424/832

    摘要： This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

    摘要翻译： 本发明描述了用于靶向控制哺乳动物细胞活性的新型试剂，特别是该试剂用于控制特定细胞类型与其外部环境的相互作用。 该试剂具有用作治疗各种疾病的药物的应用。 根据本发明的药剂包含以下列方式连接在一起的三个B，T和E域：域B结构域T域E，其中B区是绑定结构域，该结合域将该试剂结合到经历内吞作用的细胞上的结合位点 为了产生一个内体，结构域T是易位区域，它将试剂（有或者没有结合位点）从内体内穿过内体膜转移到细胞的细胞溶质中，E区是抑制 可循环膜囊将整体膜蛋白转运至细胞表面。

    CLOSTRIDIAL TOXIN DERIVATIVES ABLE TO MODIFY PERIPHERAL SENSORY AFFERENT FUNCTIONS
    9.
    发明申请
    CLOSTRIDIAL TOXIN DERIVATIVES ABLE TO MODIFY PERIPHERAL SENSORY AFFERENT FUNCTIONS 审中-公开
    外用毒素衍生物可修改外周感觉功能

    公开(公告)号：US20120141511A1

    公开(公告)日：2012-06-07

    申请号：US13270662

    申请日：2011-10-11

    申请人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    发明人： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    IPC分类号： A61K39/385 ,  C12P21/06 ,  A61K39/395 ,  A61P25/00 ,  C07K19/00 ,  C07K17/02

    CPC分类号： C07K14/48 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/00 ,  Y10S424/832

    摘要： A novel agent for the targeted control of a mammalian cell activity can be used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E, linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain, which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome; Domain T is the Translocation Domain, which translocates the agent from within the endosome across the endosomal membrane into the cytosol of the cell; and Domain E is the Effector Domain, which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

    摘要翻译： 用于靶向控制哺乳动物细胞活性的新型药剂可用于控制特定细胞类型与其外部环境的相互作用。 该试剂具有用作治疗各种疾病的药物的应用。 根据本发明的试剂包括以下列方式连接在一起的三个B区，T区和E区：域B域T域E，其中域B是结合域，其结合试剂到细胞上的结合位点 经历内吞以产生内体; 域T是易位结构域，其将来自内体的试剂从内体膜转移到细胞的胞质溶胶中; 并且E区是效应域，其抑制可循环膜囊泡将整合膜蛋白转运到细胞表面的能力。