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    Methods and compounds for the treatment of mucus hypersecretion
    4.
    发明申请
    Methods and compounds for the treatment of mucus hypersecretion 失效
    用于治疗粘液分泌过多的方法和化合物

    公开(公告)号：US20070010447A1

    公开(公告)日：2007-01-11

    申请号：US11518213

    申请日：2006-09-11

    申请人： Conrad Quinn ,  Keith Foster ,  John Chaddock

    发明人： Conrad Quinn ,  Keith Foster ,  John Chaddock

    IPC分类号： A61K38/16

    CPC分类号： A61K38/4886 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/33

    摘要： A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

    摘要翻译： 一种治疗粘液分泌过多症的方法，慢性阻塞性肺疾病（COPD），哮喘和其它涉及COPD的临床病症的因素包括给予抑制或分泌粘液分泌细胞或神经元中的胞吐作用的化合物。 还描述了一种用于治疗粘液分泌过高的化合物，其通过抑制由分泌分泌细菌的粘液分泌而抑制粘液分泌，和/或抑制神经递质从控制或引导粘液分泌的神经元细胞释放。

    Inhibition of secretion from non-neuronal cells
    6.
    发明申请
    Inhibition of secretion from non-neuronal cells 审中-公开

    公开(公告)号：US20060216283A1

    公开(公告)日：2006-09-28

    申请号：US11327855

    申请日：2006-01-09

    申请人： Keith Foster ,  John Chaddock ,  Conrad Quinn ,  John Purkiss

    发明人： Keith Foster ,  John Chaddock ,  Conrad Quinn ,  John Purkiss

    IPC分类号： A61K48/00 ,  A61K39/35 ,  A61K39/00

    CPC分类号： A61K38/4886 ,  A61K47/64

    摘要： A method of treatment of disease by inhibition of cellular secretory processes is provided. The method has particular application in the treatment of diseases dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system, and bone cells. Agents and compositions therefor, as well as methods for manufacturing these agents and compositions, are provided. In a preferred embodiment a clostridial neurotoxin, substantially devoid of holotoxin binding affinity for neuronal cells of the presynaptic muscular junction, is associated with a targeting moiety. The targeting moiety is selected such that the clostridial toxin conjugate so formed may be directed to a non-neuronal target cell to which the conjugate may bind. Following binding, a neurotoxin component of the conjugate, which is capable of inhibition of cellular secretion, passes into the cytosol of the target cell by cellular internalisation mechanisms. Thereafter, inhibition of secretion from the target cell is effected.

    Recombinant toxin fragments
    7.
    发明申请
    Recombinant toxin fragments 失效
    重组毒素片段

    公开(公告)号：US20050244435A1

    公开(公告)日：2005-11-03

    申请号：US11077550

    申请日：2005-03-11

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

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

    IPC分类号： C12N15/09 ,  A61K20060101 ,  A61K38/00 ,  A61K38/16 ,  A61K39/00 ,  A61K39/08 ,  A61K47/48 ,  A61K48/00 ,  A61P31/04 ,  C07K14/33 ,  C07K14/65 ,  C07K19/00 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/52 ,  C12N15/31 ,  C12N15/62 ,  C12P21/02 ,  C12P21/04 ,  C12R1/145 ,  C12R1/19

    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H N N部分或其片段或变体，其中所述第二结构域能够（i）将所述多肽转位至细胞中，或（ii）增加 与第一结构域本身的溶解度相比，多肽的溶解度或（iii）两者都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HCC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的天然细胞表面受体的细胞表面受体 神经毒素结合。 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。

    Fusion proteins
    8.
    发明授权
    Fusion proteins 有权
    融合蛋白

    公开(公告)号：US09243301B2

    公开(公告)日：2016-01-26

    申请号：US13419381

    申请日：2012-03-13

    申请人： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

    发明人： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

    IPC分类号： A61K38/00 ,  C12N9/52 ,  C12N15/62 ,  C07K14/665

    CPC分类号： C12Y304/24069 ,  A61K38/00 ,  A61K38/1709 ,  A61K38/482 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/6415 ,  A61K47/65 ,  C07K14/665 ,  C07K2319/055 ,  C07K2319/06 ,  C07K2319/50 ,  C12N9/52 ,  C12N15/62

    摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the fusion proteins, methods of preparing same and uses thereof are also described.

    摘要翻译： 一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段可以切割伤害性感觉传入的胞外融合装置的蛋白质; 可以结合伤害性感觉传入物上的结合位点的靶向物质，其结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 蛋白酶切割位点，位于融合蛋白可被位于非细胞毒性蛋白酶和靶向部位之间的蛋白酶切割; 以及易位区域，其可以将位于内体内的蛋白酶或蛋白酶片段穿过内体膜并转移到伤害性感觉传入物的胞质溶胶中; 其中靶向部分是BAM，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。 还描述了编码融合蛋白的核酸序列，其制备方法及其用途。

    Fusion Proteins
    9.
    发明申请
    Fusion Proteins 有权
    融合蛋白

    公开(公告)号：US20100247509A1

    公开(公告)日：2010-09-30

    申请号：US11792210

    申请日：2005-12-01

    申请人： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

    发明人： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

    IPC分类号： A61K38/48 ,  C07H21/04 ,  A61P29/00 ,  C12N9/48 ,  C12N15/74 ,  C12P21/00 ,  C12P21/02

    CPC分类号： C07K14/575 ,  A61K31/711 ,  A61K38/4893 ,  A61K47/64 ,  A61K47/6415 ,  C07K14/33 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/33 ,  C12N9/6489 ,  C12N15/62 ,  C12Y304/24069

    摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

    摘要翻译： 一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入的胞外融合装置的蛋白质; 能够结合伤害性感觉传入的结合位点的靶向部位，该结合位点能够经历内吞作用以掺入伤害性感觉传入内的内体; 蛋白酶切割位点，其中融合蛋白可被蛋白酶切割，其中蛋白酶切割位点位于非细胞毒性蛋白酶或其片段与靶向部位之间; 以及易位区域，其能够将位于内体内的蛋白酶或蛋白酶片段穿过内体膜并转移到伤害性感觉传入物的胞质溶胶中。 还描述了编码多肽融合蛋白的核酸序列，其制备方法及其用途。

    Re-targeted toxin conjugates
    10.
    发明申请
    Re-targeted toxin conjugates 审中-公开
    再靶向毒素共轭物

    公开(公告)号：US20070184048A1

    公开(公告)日：2007-08-09

    申请号：US10571515

    申请日：2004-09-13

    申请人： Keith Foster ,  John Chaddock ,  Charles Penn

    发明人： Keith Foster ,  John Chaddock ,  Charles Penn

    IPC分类号： A61K39/00 ,  G01N33/567 ,  A61K39/395

    CPC分类号： C12N9/52 ,  A61K47/64 ,  A61K47/642

    摘要： The present invention provides a method for designing a re-targeted toxin conjugate for use in treating a medical condition or disease. Also provided, is the use of said conjugates in the manufacture of a medicament for treating medical conditions or diseases. The conjugates include a Targeting Moiety, which directs the conjugate to a desired target cell, and are characterised by a Targeting Moiety that increases exocytic fusion in the target cell. The present invention also provides methods for identifying agonists suitable for use as Targeting Moieties, and methods for preparing conjugates comprising said Targeting Moieties, to re-target a toxin to a cell of therapeutic interest. In particular, the present invention describes a method for designing a toxin conjugate, and describes therapeutic applications of said conjugates to inhibit or reduce cellular processes. Even more particularly, the present invention describes a method for designing toxin conjugates based upon non-cytotoxic toxins able to inhibit exocytosis, such as clostridial neurotoxins, and describes therapeutic applications of said conjugates to inhibit or reduce exocytosis (for example secretion, or the delivery of proteins such as receptors, transporters, and membrane channels to the plasma membrane of a cell).

    摘要翻译： 本发明提供了一种用于设计用于治疗医学病症或疾病的再靶向毒素缀合物的方法。 还提供了所述缀合物在制备用于治疗医学病症或疾病的药物中的用途。 缀合物包括将缀合物引导至期望的靶细胞的靶向部位，其特征在于靶细胞增加靶细胞中的胞外融合。 本发明还提供了用于鉴定适合用作靶向部分的激动剂的方法，以及用于制备包含所述靶向部分的缀合物的方法，以将毒素重新靶向治疗感兴趣的细胞。 特别地，本发明描述了一种用于设计毒素缀合物的方法，并且描述了所述缀合物抑制或减少细胞过程的治疗应用。 甚至更具体地，本发明描述了一种基于能够抑制胞吐作用的非细胞毒素毒素（例如梭菌神经毒素）设计毒素缀合物的方法，并且描述了所述缀合物抑制或减少胞吐作用（例如分泌或递送）的治疗应用 的蛋白质，如受体，转运蛋白和膜通道的细胞质膜）。