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    Recombinant toxin fragments
    3.
    发明授权
    Recombinant toxin fragments 失效
    重组毒素片段

    公开(公告)号：US07674470B2

    公开(公告)日：2010-03-09

    申请号：US11077550

    申请日：2005-03-11

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

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

    IPC分类号： A61K39/08 ,  A61K39/085 ,  A61K39/40 ,  A61K39/02 ,  A61K38/00 ,  A61K39/38 ,  C07K14/00 ,  C07K17/00 ,  C07K2/00 ,  C07K4/00 ,  C07K1/00

    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。

    Recombinant Toxin Fragments
    4.
    发明申请
    Recombinant Toxin Fragments 有权
    重组毒素片段

    公开(公告)号：US20090274708A1

    公开(公告)日：2009-11-05

    申请号：US12399542

    申请日：2009-03-06

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

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

    IPC分类号： A61K39/395 ,  C07K16/00 ,  C07K16/12

    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相关的蛋白质或质膜相关蛋白; 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指定为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。

    Assay with reduced background
    7.
    发明申请
    Assay with reduced background 审中-公开
    测定减少背景

    公开(公告)号：US20090186368A1

    公开(公告)日：2009-07-23

    申请号：US12285766

    申请日：2008-10-14

    申请人： Neil David Hammond Raven ,  Matthew Patrick Wictome ,  J. Mark Sutton ,  Susan O'Brien ,  Heather Murdoch

    发明人： Neil David Hammond Raven ,  Matthew Patrick Wictome ,  J. Mark Sutton ,  Susan O'Brien ,  Heather Murdoch

    IPC分类号： G01N33/53

    CPC分类号： G01N33/581 ,  C12Q1/485 ,  C12Q1/66 ,  Y10T436/25125

    摘要： In an assay, an analyte in a sample is contacted with a thermostable reporter adenylate kinase coupled to a binding agent specific for the analyte, wherein a complex is formed. ADP is added, and then formation of ATP is monitored. Prior to the addition of ADP, endogenous kinase and uncomplexed thermostable reporter adenylate kinase is substantially removed by washing and residual endogenous kinase is inactivated by heating. Prior to contacting the analyte with the thermostable reporter adenylate kinase, the sample has a background activity of at least 300,000 Relative Light Units per mg protein per ml sample when measured in the presence of luciferin/luciferase by a luminometer.

    摘要翻译： 在测定中，将样品中的分析物与偶联到分析物特异性结合剂的热稳定报告基因腺苷酸激酶接触，其中形成复合物。 添加ADP，然后监测ATP的形成。 在添加ADP之前，通过洗涤基本上除去内源性激酶和未复合的热稳定报告基因腺苷酸激酶，并且通过加热使残留的内源性激酶失活。 在将分析物与热稳定报告基因腺苷酸激酶接触之前，当在荧光素/荧光素酶存在下通过发光计测量时，样品的背景活性为每毫升样品中每mg蛋白质至少300,000个相对光单位。

    Biological indicator
    8.
    发明授权
    Biological indicator 有权
    生物指标

    公开(公告)号：US09102976B2

    公开(公告)日：2015-08-11

    申请号：US13776316

    申请日：2013-02-25

    申请人： J. Mark Sutton ,  Neil David Hammond Raven

    发明人： J. Mark Sutton ,  Neil David Hammond Raven

    IPC分类号： C12Q1/70 ,  C12Q1/48 ,  C12Q1/22

    CPC分类号： C12Q1/485 ,  C12Q1/22

    摘要： A kinase is used in a biological indicator for validation of treatment processes designed to reduce the amount or activity of a biological agent in a sample. The indication can be used for validation of sterilization treatment. The formation of ATP from a substrate comprising ADP is measured via the liciferin/luciferate system in a luminameter. Thermostable adenylate kinase from sulfolobus acidocaldarius is especially suitable for the validation of procedures to inactivate transmissable spongiform encephalopathy agents.

    摘要翻译： 激酶用于生物学指标，用于验证设计用于减少样品中生物试剂的量或活性的处理过程。 该指示可用于灭菌处理的验证。 在含有ADP的底物中形成ATP通过发光体中的无花果素/萤光素体系进行测定。 来自硫酸杆菌的热稳定腺苷酸激酶特别适用于灭活可透过性海绵状脑病的药物。