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    Suppression of neuroendocrine diseases
    2.
    发明授权
    Suppression of neuroendocrine diseases 有权
    抑制神经内分泌疾病

    公开(公告)号：US08796216B2

    公开(公告)日：2014-08-05

    申请号：US12969810

    申请日：2010-12-16

    申请人： Stephen Johnstone ,  Philip Marks ,  Keith Foster

    发明人： Stephen Johnstone ,  Philip Marks ,  Keith Foster

    IPC分类号： A61K38/16 ,  C07K14/33 ,  C12P21/00

    CPC分类号： C12N9/52 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12P21/06

    摘要： The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumor cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalized and inhibits secretion from said tumor cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

    摘要翻译： 本发明涉及抑制神经内分泌疾病的方法。 该疗法使用非细胞毒性蛋白酶，其优选靶向神经内分泌肿瘤细胞，优选通过生长抑素或皮质抑素受体，GHRH受体，生长素释放肽受体，铃蟾肽受体，泌尿生素受体，黑色素浓缩激素受体1 ; KiSS-1受体或催乳素释放肽受体。 当这样传递时，蛋白酶被内化并且抑制来自所述肿瘤细胞的分泌。 本发明还涉及用于所述方法的多肽和核酸。

    FUSION PROTEINS
    3.
    发明申请
    FUSION PROTEINS 有权
    融合蛋白

    公开(公告)号：US20120064059A1

    公开(公告)日：2012-03-15

    申请号：US13239573

    申请日：2011-09-22

    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 ,  A61P25/04 ,  C12N15/63 ,  C12N9/50 ,  C12N15/57

    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; 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 acids 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; 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的易位结构域。 还描述了编码融合蛋白的核酸，其制备方法及其用途。

    Fusion proteins
    4.
    发明授权
    Fusion proteins 有权
    融合蛋白

    公开(公告)号：US08124405B2

    公开(公告)日：2012-02-28

    申请号：US11853517

    申请日：2007-09-11

    申请人： Keith Alan Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Lyndsey Durose

    发明人： Keith Alan Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Lyndsey Durose

    IPC分类号： C07K14/00 ,  C12N15/62 ,  C12N15/63

    CPC分类号： C12N9/50 ,  A61K38/00 ,  C07K14/33 ,  C07K2319/06 ,  C07K2319/50 ,  C12N15/62

    摘要： The invention provides 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 target cell; a Targeting Moiety that is capable of binding to a Binding Site on the target cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the target cell; 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 target cell.

    摘要翻译： 本发明提供了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靶细胞的胞外融合装置的蛋白质; 能够结合目标细胞上的结合位点的靶向物质，所述结合位点能够经历内吞作用以掺入靶细胞内的内体; 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; 以及能够将位于内体内的蛋白酶或蛋白酶片段穿过体内膜并进入靶细胞的胞质溶胶的易位结构域。

    Recombinant toxin fragments
    5.
    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。

    SUPPRESSION OF NEUROENDOCRINE DISEASES
    6.
    发明申请
    SUPPRESSION OF NEUROENDOCRINE DISEASES 有权
    抑制神经退行性疾病

    公开(公告)号：US20110160135A1

    公开(公告)日：2011-06-30

    申请号：US12969810

    申请日：2010-12-16

    申请人： Stephen JOHNSTONE ,  Philip MARKS ,  Keith FOSTER

    发明人： Stephen JOHNSTONE ,  Philip MARKS ,  Keith FOSTER

    IPC分类号： A61K38/16 ,  C07K14/00 ,  C12P21/00 ,  C07H21/04 ,  A61P5/00 ,  A61P19/00

    CPC分类号： C12N9/52 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12P21/06

    摘要： The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumour cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalised and inhibits secretion from said tumour cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

    摘要翻译： 本发明涉及抑制神经内分泌疾病的方法。 该疗法使用非细胞毒性蛋白酶，其优选靶向神经内分泌肿瘤细胞，优选通过生长抑素或皮质抑素受体，GHRH受体，生长素释放肽受体，铃蟾肽受体，泌尿生素受体，黑色素浓缩激素受体1 ; KiSS-1受体或催乳素释放肽受体。 当这样传递时，蛋白酶被内化并且抑制来自所述肿瘤细胞的分泌。 本发明还涉及用于所述方法的多肽和核酸。

    Curable and cured wood particle composites and method making same
    9.
    发明申请
    Curable and cured wood particle composites and method making same 有权
    可固化和固化的木颗粒复合材料和方法制作相同

    公开(公告)号：US20080287571A1

    公开(公告)日：2008-11-20

    申请号：US12150796

    申请日：2008-05-01

    申请人： Eric Gustave Lundquist ,  Allen Philip Marks

    发明人： Eric Gustave Lundquist ,  Allen Philip Marks

    IPC分类号： B27K3/00

    CPC分类号： C08L97/02 ,  Y10T428/2998 ,  C08L2666/04 ,  C08L2666/02

    摘要： Curable wood particle composites curable by the Michael addition reaction in the presence of weak base catalyst are disclosed, along with a method for making those curable wood particle composites. Cured wood particle composites are also disclosed, along with a method of making those cured wood particle composites.

    摘要翻译： 公开了在弱碱催化剂存在下通过迈克尔加成反应固化的可固化木颗粒复合材料，以及制备这些可固化木颗粒复合材料的方法。 还公开了固化木颗粒复合材料，以及制备这些固化木颗粒复合材料的方法。