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    TREATMENT OF PAIN
    11.
    发明申请
    TREATMENT OF PAIN 有权
    治疗疼痛

    公开(公告)号：US20120189610A1

    公开(公告)日：2012-07-26

    申请号：US13360565

    申请日：2012-01-27

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

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

    IPC: A61K38/48 ,  A61P25/04 ,  A61P29/00

    CPC classification number: 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

    Abstract: Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is 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, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translation 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.

    Abstract translation: 用于治疗特定疼痛病症的治疗分子的用途，其中所述治疗分子是单链多肽融合蛋白，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蛋白质或蛋白酶片段的蛋白质 伤害性感觉传入的胞外融合装置; 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，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的翻译结构域。

    NON-CYTOTOXIC FUSION PROTEINS COMPRISING EGF MUTEINS
    12.
    发明申请
    NON-CYTOTOXIC FUSION PROTEINS COMPRISING EGF MUTEINS 有权
    包含EGF的蛋白质的非细胞毒素融合蛋白

    公开(公告)号：US20110177056A1

    公开(公告)日：2011-07-21

    申请号：US13059695

    申请日：2009-08-19

    Applicant: Aimee Cossins ,  Ian Birch-Machin ,  Patrick Stancombe

    Inventor： Aimee Cossins ,  Ian Birch-Machin ,  Patrick Stancombe

    IPC: A61K38/48 ,  C12N9/50 ,  C07H21/00 ,  C12N9/52 ,  A61P29/00 ,  A61P43/00 ,  A61P35/00 ,  A61P5/00 ,  A61P11/00

    CPC classification number: C07K14/485 ,  A61K38/00 ,  C07K2319/01 ,  C07K2319/50

    Abstract: The present invention relates to fusion proteins comprising a non-cytotoxic protease and a EGF mutein ligand. The EGF mutein provides improved EGF receptor activation for the claimed fusion proteins. Also provided is the use of said polypeptides as therapeutics for suppressing mucus hypersecretion, inflammation, endocrine neoplasia and/or neuroendocrine disorders, neuroendocrine tumours, for suppressing cancers such as colorectal cancer, prostate cancer, breast cancer, and lung cancer.

    Abstract translation: 本发明涉及包含非细胞毒性蛋白酶和EGF突变蛋白配体的融合蛋白。 EGF突变蛋白为所要求的融合蛋白提供改善的EGF受体活化。 还提供了所述多肽作为抑制粘液分泌过多，炎症，内分泌瘤形成和/或神经内分泌障碍，神经内分泌肿瘤，用于抑制癌症如结肠直肠癌，前列腺癌，乳腺癌和肺癌的治疗剂的用途。

    FUSION PROTEINS
    13.
    发明申请
    FUSION PROTEINS 审中-公开
    融合蛋白

    公开(公告)号：US20110091437A1

    公开(公告)日：2011-04-21

    申请号：US12868510

    申请日：2010-08-25

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

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

    IPC: A61K38/48 ,  C12N9/96 ,  C12N15/57 ,  C12N15/63 ,  C12P21/02 ,  A61P29/00

    CPC classification number: 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

    Abstract: 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 dynorphin 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 dynorphin 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.

    Abstract translation: 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强啡肽靶向部位，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; 蛋白酶切割位点位于融合蛋白可被蛋白酶切割的蛋白酶切割位点，其中蛋白酶切割位点位于非细胞毒性蛋白酶或其片段与强啡肽靶向部位之间; 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。

    TREATMENT OF PAIN
    14.
    发明申请
    TREATMENT OF PAIN 审中-公开
    治疗疼痛

    公开(公告)号：US20100034802A1

    公开(公告)日：2010-02-11

    申请号：US12303078

    申请日：2007-06-01

    Applicant: Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  K. Roger Aoki ,  Joseph Francis ,  Lance Steward

    Inventor： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  K. Roger Aoki ,  Joseph Francis ,  Lance Steward

    IPC: A61K38/48 ,  C12N9/48 ,  A61P25/00

    CPC classification number: 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

    Abstract: Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is 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.

    Abstract translation: 用于治疗特定疼痛病症的治疗分子的用途，其中所述治疗分子是单链多肽融合蛋白，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器的蛋白质; 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。

    Fusion Proteins
    15.
    发明申请
    Fusion Proteins 有权
    融合蛋白

    公开(公告)号：US20090004174A1

    公开(公告)日：2009-01-01

    申请号：US11792076

    申请日：2005-12-01

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

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

    IPC: C12N9/50 ,  C07K14/00 ,  C12N15/11 ,  C12N15/62 ,  C12P21/02 ,  A61K38/48 ,  A61P37/00 ,  A61P19/00 ,  A61P9/00 ,  A61P1/00

    CPC classification number: C12N9/50 ,  A61K38/00 ,  C07K14/33 ,  C07K2319/06 ,  C07K2319/50 ,  C12N15/62

    Abstract: 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 endocome within the target cell; a protease cleaving site at which site the fusion protein is cleavable by the protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and the 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.

    Abstract translation: 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; 能够结合靶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皮细胞; 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
    19.
    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

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

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

    IPC: 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 classification number: 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

    Abstract: 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.

    Abstract translation: 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。

    Non-cytotoxic fusion proteins comprising EGF muteins
    20.
    发明授权
    Non-cytotoxic fusion proteins comprising EGF muteins 有权
    包含EGF突变蛋白的非细胞毒性融合蛋白

    公开(公告)号：US08614069B2

    公开(公告)日：2013-12-24

    申请号：US13059695

    申请日：2009-08-19

    Applicant: Aimee Cossins ,  Ian Birch-Machin ,  Patrick Stancombe

    Inventor： Aimee Cossins ,  Ian Birch-Machin ,  Patrick Stancombe

    IPC: C12P21/04

    CPC classification number: C07K14/485 ,  A61K38/00 ,  C07K2319/01 ,  C07K2319/50

    Abstract: The present invention relates to fusion proteins comprising a non-cytotoxic protease and a EGF mutein ligand. The EGF mutein provides improved EGF receptor activation for the claimed fusion proteins. Also provided is the use of said polypeptides as therapeutics for suppressing mucus hypersecretion, inflammation, endocrine neoplasia and/or neuroendocrine disorders, neuroendocrine tumors, for suppressing cancers such as colorectal cancer, prostate cancer, breast cancer, and lung cancer.

    Abstract translation: 本发明涉及包含非细胞毒性蛋白酶和EGF突变蛋白配体的融合蛋白。 EGF突变蛋白为所要求的融合蛋白提供改善的EGF受体活化。 还提供了所述多肽作为抑制粘液分泌过多，炎症，内分泌瘤形成和/或神经内分泌障碍，神经内分泌肿瘤，用于抑制癌症如结肠直肠癌，前列腺癌，乳腺癌和肺癌的治疗剂的用途。

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