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    Fusion proteins
    21.
    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。

    Methods and compounds for the treatment of mucus hypersecretion
    25.
    发明申请
    Methods and compounds for the treatment of mucus hypersecretion 审中-公开
    用于治疗粘液分泌过多的方法和化合物

    公开(公告)号：US20090280066A1

    公开(公告)日：2009-11-12

    申请号：US11798610

    申请日：2007-05-15

    Applicant: Conrad Padraig Quinn ,  Keith Alan Foster ,  John Chaddock

    Inventor： Conrad Padraig Quinn ,  Keith Alan Foster ,  John Chaddock

    IPC: A61K9/12 ,  C12N9/50 ,  C07H21/04 ,  A61K38/48 ,  C12P21/06

    CPC classification number: A61K38/4886 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/33

    Abstract: 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 secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

    Abstract translation: 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，其通过抑制由分泌分泌细菌的粘液分泌而抑制粘液分泌，和/或抑制神经递质从控制或引导粘液分泌的神经元细胞释放。

    TREATMENT OF MUCUS HYPERSECRETION
    26.
    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
    27.
    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。

    Non-cytotoxic protein conjugates
    29.
    发明授权
    Non-cytotoxic protein conjugates 有权
    非细胞毒性蛋白偶联物

    公开(公告)号：US09139635B2

    公开(公告)日：2015-09-22

    申请号：US13072865

    申请日：2011-03-28

    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 ,  C07K14/575 ,  A61K31/711 ,  A61K47/48 ,  C07K14/33 ,  C12N9/64 ,  C12N15/62

    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: 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 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含：（i）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细胞内的内体 ; （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。

    FUSION PROTEINS
    30.
    发明申请
    FUSION PROTEINS 审中-公开
    融合蛋白

    公开(公告)号：US20140056870A1

    公开(公告)日：2014-02-27

    申请号：US13595927

    申请日：2012-08-27

    Applicant: Peter James ,  Keith Foster ,  John Chaddock ,  Kei Roger Aoki ,  Lance Steward ,  Joseph Francis

    Inventor： Peter James ,  Keith Foster ,  John Chaddock ,  Kei Roger Aoki ,  Lance Steward ,  Joseph Francis

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

    Abstract: A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which cleaves a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin Targeting Moiety that binds a Binding Site on the nociceptive sensory afferent, which can undergo endocytosis to be incorporated into an endosome; a protease cleavage site where the fusion protein is cleavable by a protease located between the non-cytotoxic protease and the galanin Targeting Moiety; a translocation domain that translocates the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; a first spacer from 4 to 25 amino acids between the non-cytotoxic protease and protease cleavage site; and a second spacer comprising from 4 to 35 residues between the galanin Targeting Moiety and translocation domain. 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，其切割伤害性感觉传入的胞外融合装置的蛋白质; 将甘露聚糖靶向部位结合到伤害性感觉传入物上的结合位点，其可能经历内吞作用以掺入内体; 蛋白酶切割位点，其中融合蛋白可被位于非细胞毒性蛋白酶和甘丙肽靶向部位之间的蛋白酶切割; 一个易位结构域，其从内体内转移蛋白酶，穿过内体膜并进入伤害性感觉传入体的细胞溶质; 非细胞毒性蛋白酶和蛋白酶切割位点之间的4至25个氨基酸的第一个间隔区; 以及在甘露糖靶向部位和易位结构域之间包含4至35个残基的第二间隔物。 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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