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    Fusion proteins
    11.
    发明授权
    Fusion proteins 有权
    融合蛋白

    公开(公告)号：US08067200B2

    公开(公告)日：2011-11-29

    申请号：US11792210

    申请日：2005-12-01

    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: C12P21/06 ,  C17H17/00 ,  C07K14/00

    CPC classification number: C07K14/575 ,  A61K31/711 ,  A61K38/4893 ,  A61K47/64 ,  A61K47/6415 ,  C07K14/33 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/33 ,  C12N9/6489 ,  C12N15/62 ,  C12Y304/24069

    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 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. 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。 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。

    Clostridial toxin derivatives able to modify peripheral sensory afferent functions
    14.
    发明授权
    Clostridial toxin derivatives able to modify peripheral sensory afferent functions 失效
    能够修饰周围感觉传入功能的梭菌毒素衍生物

    公开(公告)号：US07892560B2

    公开(公告)日：2011-02-22

    申请号：US11819648

    申请日：2007-06-28

    Applicant: Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    Inventor： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

    IPC: A61K38/16 ,  A61K38/18 ,  C07K14/33 ,  C07K14/485

    CPC classification number: C07K14/48 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/00 ,  Y10S424/832

    Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

    Abstract translation: 本发明描述了用于靶向控制哺乳动物细胞活性的新型试剂，特别是该试剂用于控制特定细胞类型与其外部环境的相互作用。 该试剂具有用作治疗各种疾病的药物的应用。 根据本发明的药剂包含以下列方式连接在一起的三个B，T和E域：域B结构域T域E，其中B区是绑定结构域，该结合域将该试剂结合到经历内吞作用的细胞上的结合位点 为了产生一个内体，结构域T是易位区域，它将试剂（有或者没有结合位点）从内体内穿过内体膜转移到细胞的细胞溶质中，E区是抑制 可循环膜囊将整体膜蛋白转运至细胞表面。

    TREATMENT OF MUCUS HYPERSECRETION
    15.
    发明申请
    TREATMENT OF MUCUS HYPERSECRETION 审中-公开
    治疗妊娠高血压

    公开(公告)号：US20080249019A1

    公开(公告)日：2008-10-09

    申请号：US12101749

    申请日：2008-04-11

    Applicant: Keith Alan Foster ,  John Chaddock

    Inventor： Keith Alan Foster ,  John Chaddock

    IPC: A61K38/02 ,  A61P11/06 ,  A61P11/16

    CPC classification number: C07K14/33 ,  A61K38/00 ,  C07K2319/33 ,  Y02A50/471 ,  Y02A50/473

    Abstract: A polypeptide and a nucleic acid encoding the polypeptide are described. The polypeptide includes a cytotoxic toxin, a targeting domain that selectively binds to a target cell that is a mucus-secreting cell and a translocating domain that translocates the cytotoxic toxin into the target cell. A nucleic acid encoding the polypeptide is also described. Also described is a pharmaceutical composition for topical administration to a patient suffering from mucus hypersecretion which includes the polypeptide and a formulation component selected from the group consisting of an excipient, an adjuvant and a propellant. Methods of treating hypersecretion of mucus, chronic obstructive pulmonary disease (COPD) or asthma are also described. These methods include administering to a patient in need thereof a therapeutically effective amount of the polypeptide.

    Abstract translation: 描述了编码多肽的多肽和核酸。 该多肽包括细胞毒素毒素，靶向结构域，其选择性地结合靶分泌细胞，其是分泌粘液的细胞，以及将细胞毒性毒素转移到靶细胞中的易位结构域。 还描述了编码该多肽的核酸。 还描述了一种用于局部给予患有粘液分泌过高的患者的药物组合物，其包括多肽和选自赋形剂，佐剂和推进剂的制剂成分。 还描述了治疗粘液分泌过多，慢性阻塞性肺疾病（COPD）或哮喘的方法。 这些方法包括向有需要的患者施用治疗有效量的多肽。

    FUSION PROTEINS
    16.
    发明申请
    FUSION PROTEINS 有权
    融合蛋白

    公开(公告)号：US20080064092A1

    公开(公告)日：2008-03-13

    申请号：US11853517

    申请日：2007-09-11

    Applicant: Keith FOSTER ,  John CHADDOCK ,  Philip MARKS ,  Patrick STANCOMBE ,  Lyndsey DUROSE

    Inventor： Keith FOSTER ,  John CHADDOCK ,  Philip MARKS ,  Patrick STANCOMBE ,  Lyndsey DUROSE

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

    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 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.

    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。

    FUSION PROTEINS
    18.
    发明申请
    FUSION PROTEINS 有权
    融合蛋白

    公开(公告)号：US20130189238A1

    公开(公告)日：2013-07-25

    申请号：US13774587

    申请日：2013-02-22

    Applicant: Syntaxin Ltd. ,  Allergan Inc.

    Inventor： Keith FOSTER ,  John CHADDOCK ,  Philip MARKS ,  Patrick STANCOMBE ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

    IPC: C12N9/96

    CPC classification number: C12N9/96 ,  A61K38/00 ,  A61K47/64 ,  C07K2319/01 ,  C07K2319/33 ,  C07K2319/50 ,  C12N9/50

    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。

    NON-CYTOTOXIC PROTEIN CONJUGATES
    19.
    发明申请
    NON-CYTOTOXIC PROTEIN CONJUGATES 有权
    非细胞毒素蛋白结合

    公开(公告)号：US20120156186A1

    公开(公告)日：2012-06-21

    申请号：US13343892

    申请日：2012-01-05

    Applicant: Keith FOSTER ,  John CHADDOCK ,  Charles PENN ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

    Inventor： Keith FOSTER ,  John CHADDOCK ,  Charles PENN ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

    IPC: A61K38/48 ,  A61P21/00 ,  C12P21/00 ,  C12N9/96 ,  C12N15/57

    CPC classification number: A61K38/4893 ,  A61K38/4886 ,  C07K14/575 ,  C07K2319/00 ,  C07K2319/01 ,  C12N9/52 ,  C12Y304/21072

    Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a galanin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are is also described.

    Abstract translation: 本发明涉及用于抑制或减少伤害性感觉传入细胞中的胞外融合的非细胞毒性蛋白质缀合物。 所述蛋白质缀合物包括：（i）甘丙肽靶向部分（TM），其中所述TM是存在于伤害性感觉传入细胞上的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入物内的内体 细胞; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域（Translocation Domain），其中易位域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细胞的胞质溶胶中。 还描述了编码蛋白质缀合物的核酸序列，其制备方法及其用途。

    NON-CYTOTOXIC PROTEIN CONJUGATES
    20.
    发明申请
    NON-CYTOTOXIC PROTEIN CONJUGATES 有权
    非细胞毒素蛋白结合

    公开(公告)号：US20120058098A1

    公开(公告)日：2012-03-08

    申请号：US13212868

    申请日：2011-08-18

    Applicant: Keith FOSTER ,  John CHADDOCK ,  Charles PENN ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

    Inventor： Keith FOSTER ,  John CHADDOCK ,  Charles PENN ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

    IPC: A61K38/48 ,  C12N9/96 ,  A61P25/00 ,  C07H21/04 ,  A61P29/00

    CPC classification number: C12N9/96 ,  A61K38/482 ,  A61K38/4893 ,  A61K47/48246 ,  A61K47/64 ,  C07K14/665 ,  C07K2319/00

    Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

    Abstract translation: 本发明涉及用于抑制或减少伤害性感觉传入细胞中胞外融合的非细胞毒性蛋白质缀合物。 所述蛋白质缀合物包含：（i）强啡肽靶向剂量（TM），其中所述TM是感受伤害感觉传入细胞上存在的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入物内的内体 细胞; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域（Translocation Domain），其中易位域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细胞的胞质溶胶中。 还描述了编码蛋白质缀合物的核酸序列，其制备方法及其用途。

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