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    Conjugates of galactose-binding lectins and clostridial neurotoxins as analgesics
    2.
    发明授权
    Conjugates of galactose-binding lectins and clostridial neurotoxins as analgesics 失效
    与半乳糖结合的凝集素和梭菌神经毒素作为镇痛药的结合物

    公开(公告)号：US07052702B1

    公开(公告)日：2006-05-30

    申请号：US09529130

    申请日：1998-10-07

    申请人： Michael John Duggan ,  John Andrew Chaddock

    发明人： Michael John Duggan ,  John Andrew Chaddock

    IPC分类号： A61K39/68 ,  C07K14/00

    CPC分类号： A61K47/6415 ,  A61K38/00

    摘要： A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibers. They comprise a galactose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (L) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain, particularly chronic pain.

    摘要翻译： 提供了一类能够修改伤害感受传入功能的新型药剂。 这些试剂可以抑制神经递质从离散的神经元群中的释放，从而减少或优选地防止传入的疼痛信号从周围的中枢疼痛纤维的传播。 它们包含与梭菌神经毒素衍生物连接的半乳​​糖结合凝集素。 梭菌神经毒素的衍生物包括L链或其片段，其包括与具有膜易位活性的分子或结构域连接的轻链（L）链的活性蛋白水解酶结构域。 这些药剂可以用于或作为药物用于治疗疼痛，特别是慢性疼痛。

    Methods and compounds for the treatment of mucus hypersecretion
    4.
    发明授权
    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：US06632440B1

    公开(公告)日：2003-10-14

    申请号：US09763669

    申请日：2001-05-29

    申请人： Conrad Padraig Quinn ,  Keith Alan Foster ,  John Andrew Chaddock

    发明人： Conrad Padraig Quinn ,  Keith Alan Foster ,  John Andrew Chaddock

    IPC分类号： A61K3968

    CPC分类号： A61K47/62 ,  Y10S424/81

    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 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，其通过抑制粘液分泌细胞抑制粘液分泌，和/或抑制神经递质从控制或引导粘液分泌的神经细胞释放。

    MODIFIED NON-CYTOTOXIC PROTEASES
    6.
    发明申请
    MODIFIED NON-CYTOTOXIC PROTEASES 有权
    改良的非细胞毒素

    公开(公告)号：US20120128649A1

    公开(公告)日：2012-05-24

    申请号：US13202696

    申请日：2009-12-16

    申请人： John Andrew Chaddock ,  Keith Alan Foster

    发明人： John Andrew Chaddock ,  Keith Alan Foster

    IPC分类号： C12N9/96 ,  A61K8/66 ,  A61P21/00 ,  C07H21/04 ,  A61K38/48

    CPC分类号： A61K38/4893 ,  A61K38/00 ,  C07K2319/06 ,  C07K2319/33 ,  C07K2319/50 ,  C12N9/50 ,  C12N9/52 ,  C12Y304/24069

    摘要： The present invention relates to a modified polypeptide comprising a non-cytotoxic protease, a translocation domain, a destructive protease cleavage site and a Targeting Moiety that binds to a Binding Site on a nerve cell, wherein after cleavage of the destructive cleavage site the polypeptide has reduced potency. The destructive cleavage site is recognised and cleaved by a protease present at or in an off-site target cell, and, in one embodiment, the polypeptide is a modified clostridial neurotoxin. The present invention also relates to the use of said polypeptides for treating a range of conditions, and to nucleic acids encoding said polypeptides.

    摘要翻译： 本发明涉及包含非细胞毒性蛋白酶，易位结构域，破坏性蛋白酶切割位点和与神经细胞上的结合位点结合的靶向部位的修饰多肽，其中在所述破坏性切割位点切割后，所述多肽具有 功效降低 破坏性切割位点被存在于位点外靶点细胞上或位于外部靶细胞中的蛋白酶识别和切割，并且在一个实施方案中，多肽是经修饰的梭菌神经毒素。 本发明还涉及所述多肽用于治疗一系列病症的用途，以及编码所述多肽的核酸。

    Conjugates of galactose-binding lectins and clostridial neurotoxins as analgesics
    8.
    发明授权
    Conjugates of galactose-binding lectins and clostridial neurotoxins as analgesics 失效
    与半乳糖结合的凝集素和梭菌神经毒素作为镇痛药的结合物

    公开(公告)号：US07452543B2

    公开(公告)日：2008-11-18

    申请号：US11257500

    申请日：2005-10-25

    申请人： John Andrew Chaddock ,  Philip Marks ,  Michael John Duggan

    发明人： John Andrew Chaddock ,  Philip Marks ,  Michael John Duggan

    IPC分类号： A61K39/68 ,  C07K14/00

    CPC分类号： A61K47/6415 ,  A61K38/00

    摘要： A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibers. They comprise a galactose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (L) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain, particular chronic pain.

    摘要翻译： 提供了一类能够修改伤害感受传入功能的新型药剂。 这些试剂可以抑制神经递质从离散的神经元群中的释放，从而减少或优选地防止传入的疼痛信号从周围的中枢疼痛纤维的传播。 它们包含与梭菌神经毒素衍生物连接的半乳​​糖结合凝集素。 梭菌神经毒素的衍生物包括L链或其片段，其包括与具有膜易位活性的分子或结构域连接的轻链（L）链的活性蛋白水解酶结构域。 这些药剂可以用于或作为药物用于治疗疼痛，特别是慢性疼痛。

    Use of a lectin or conjugates for modulation of c-fibre activity
    9.
    发明授权
    Use of a lectin or conjugates for modulation of c-fibre activity 失效
    使用凝集素或共轭物调节c-纤维活性

    公开(公告)号：US07208466B1

    公开(公告)日：2007-04-24

    申请号：US09937484

    申请日：2000-03-31

    申请人： Keith Alan Foster ,  John Andrew Chaddock ,  Conrad Padraig Quinn

    发明人： Keith Alan Foster ,  John Andrew Chaddock ,  Conrad Padraig Quinn

    IPC分类号： A61K38/00 ,  A61K51/00 ,  A61M36/14 ,  C07K16/00 ,  C07K17/00

    CPC分类号： C07K14/42 ,  A61K38/168 ,  A61K47/6415 ,  A61K48/00

    摘要： The present invention relates to the treatment of pain and to compounds that modulate C-fibre activity. In particular, the present invention relates to the use of a lectin in the manufacture of a medicament for modulation of C-fibre neuron activity, and to lectin conjugates. The lectin conjugates comprise a lectin coupled to a peptide or protein, wherein the peptide or protein is substantially free of Clostridial neurotoxin enzyme activity. The present invention also concerns methods for manufacturing conjugates. The compounds and compositions described have particular application in the treatment of diseases of which C-fibre activity is a component. Such diseases include pain, inflamation, psoriasis and other C-fibre related conditions.

    摘要翻译： 本发明涉及疼痛的治疗以及调节C-纤维活性的化合物。 特别地，本发明涉及凝集素在制备用于调节C-纤维神经元活性的药物和凝集素缀合物中的用途。 凝集素缀合物包含与肽或蛋白质偶联的凝集素，其中肽或蛋白质基本上不含梭菌神经毒素酶活性。 本发明还涉及制造缀合物的方法。 所述的化合物和组合物特别适用于治疗其C-纤维活性为组分的疾病。 这些疾病包括疼痛，炎症，牛皮癣和其他C纤维相关病症。

    Preparation of highly pure toxin fragments
    10.
    发明授权
    Preparation of highly pure toxin fragments 有权
    制备高纯度毒素片段

    公开(公告)号：US07193066B1

    公开(公告)日：2007-03-20

    申请号：US10070764

    申请日：2000-09-13

    申请人： John Andrew Chaddock ,  Frances Celine Gail Alexander ,  Keith Alan Foster

    发明人： John Andrew Chaddock ,  Frances Celine Gail Alexander ,  Keith Alan Foster

    IPC分类号： C07K1/00 ,  G01N33/537 ,  G01N33/549

    CPC分类号： C07K16/1282 ,  A61K38/164 ,  C07K14/33 ,  Y10S530/81 ,  Y10S530/811 ,  A61K2300/00

    摘要： Toxin derivatives are prepared by proteolytic treatment of holotoxin, and their toxicity is reduced by contacting the preparation with a ligand, which can be a metal or an antibody or another ligand. This ligand selectively binds to the toxin but not to the toxin derivative. Removing the ligand and toxin bound to the ligand further reduces toxicity. A second ligand is used to remove conjugates of the toxin and the first ligand. Compositions contain the purified derivative, optionally plus the toxin and the ligand.

    摘要翻译： 通过蛋白水解处理全毒素制备毒素衍生物，并且通过使制剂与可以是金属或抗体或另一种配体的配体接触来降低它们的毒性。 该配体选择性地结合毒素，但不与毒素衍生物结合。 去除与配体结合的配体和毒素进一步降低毒性。 第二配体用于去除毒素和第一配体的缀合物。 组合物含有纯化的衍生物，任选加上毒素和配体。