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    SUPPRESSION OF NEUROENDOCRINE DISEASES
    11.
    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

    Applicant: Stephen JOHNSTONE ,  Philip MARKS ,  Keith FOSTER

    Inventor： Stephen JOHNSTONE ,  Philip MARKS ,  Keith FOSTER

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

    CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12P21/06

    Abstract: 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.

    Abstract translation: 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。

    Treatment of pain
    14.
    发明授权
    Treatment of pain 有权
    治疗疼痛

    公开(公告)号：US09072736B2

    公开(公告)日：2015-07-07

    申请号：US13360565

    申请日：2012-01-27

    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 ,  A61K47/48 ,  C12N9/52

    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。

    Fusion proteins
    15.
    发明授权
    Fusion proteins 有权
    融合蛋白

    公开(公告)号：US08956847B2

    公开(公告)日：2015-02-17

    申请号：US13738235

    申请日：2013-01-10

    Applicant: Syntaxin, Limited

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

    IPC: C12N9/50 ,  C07K14/33 ,  C12N15/62 ,  A61K38/00

    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。

    TREATMENT OF PAIN
    17.
    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
    19.
    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
    20.
    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。

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