Recombinant toxin fragments
    2.
    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

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

    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。

    Methods and compounds for the treatment of mucus hypersecretion
    8.
    发明申请
    Methods and compounds for the treatment of mucus hypersecretion 审中-公开
    用于治疗粘液分泌过多的方法和化合物

    公开(公告)号:US20090280066A1

    公开(公告)日:2009-11-12

    申请号:US11798610

    申请日:2007-05-15

    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。

    Methods and compounds for the treatment of mucus hypersecretion
    9.
    发明申请
    Methods and compounds for the treatment of mucus hypersecretion 审中-公开
    用于治疗粘液分泌过多的方法和化合物

    公开(公告)号:US20080152667A1

    公开(公告)日:2008-06-26

    申请号:US11808057

    申请日:2007-06-06

    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。