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公开(公告)号：US20090162341A1
公开(公告)日：2009-06-25
申请号：US11791979
申请日：2005-12-01
Applicant: Keith Foster , John Chaddock , Charles Penn , Roger K. Aoki , Joseph Francis , Lance Steward
Inventor： Keith Foster , John Chaddock , Charles Penn , Roger K. Aoki , Joseph Francis , Lance Steward
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 non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said 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 said 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: 一种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，其包含：（i）靶向物质（TM），其中所述TM是存在于所述伤害性感觉传入细胞上的受体的激动剂，以及 其中所述受体经历内吞作用以掺入伤害性感觉传入细胞内的内体中; （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所述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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公开(公告)号：US20080187960A1
公开(公告)日：2008-08-07
申请号：US11829118
申请日：2007-07-27
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
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 non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said 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 said 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: 一种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，其包含：（i）靶向物质（TM），其中所述TM是存在于所述伤害性感觉传入细胞上的受体的激动剂，以及 其中所述受体经历内吞作用以掺入伤害性感觉传入细胞内的内体中; （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所述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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公开(公告)号：US07356878B2
公开(公告)日：2008-04-15
申请号：US11137681
申请日：2005-05-25
Applicant: Keith Foster
Inventor： Keith Foster
IPC: E05F1/00
CPC classification number: E05F3/108 , E05F3/12 , E05Y2201/20 , E05Y2201/254 , E05Y2800/21 , E05Y2900/132 , Y10T16/276 , Y10T16/2771 , Y10T16/2777 , Y10T16/2793 , Y10T16/2799 , Y10T16/283 , Y10T16/56 , Y10T16/593
Abstract: A door closer includes an anchor assembly for mounting on a door frame, an actuator assembly for mounting within the thickness of a door which is hinged for movement between open and closed positions, an operating member coupled by a linkage to the anchor assembly and mounted for a range of movements between a retracted position and an extended position, a resilient driving apparatus arranged to exert a driving force on the operating member, a damper mechanism operatively connected to the operating member so as to damp movement of the operating member at least in a direction towards the retracted position, and a resilient thrust device arranged to exert an increased driving force on the operating member over a defined part of its range of movement as the operating member approaches the retracted position.
Abstract translation: 门关闭器包括用于安装在门框上的锚固组件，用于安装在门的厚度内的致动器组件，门的厚度被铰接以在打开和关闭位置之间运动;操作构件通过联动装置联接到锚固组件， 在缩回位置和延伸位置之间的一系列运动;弹性驱动装置，其布置成在所述操作构件上施加驱动力;阻尼机构，其可操作地连接到所述操作构件，以便阻止所述操作构件的运动至少在 朝向缩回位置的方向，以及弹性推力装置，其布置成当操作构件接近缩回位置时，在其移动范围的限定部分上对操作构件施加增加的驱动力。
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Patent Agency Ranking
公开(公告)号：US20070248626A1
公开(公告)日：2007-10-25
申请号：US11644010
申请日：2006-12-22
Applicant: Clifford Shone , Conrad Quinn , Keith Foster , John Chaddock , Philip Marks , J. Sutton , Patrick Stancombe , Jonathan Wayne
Inventor： Clifford Shone , Conrad Quinn , Keith Foster , John Chaddock , Philip Marks , J. Sutton , Patrick Stancombe , Jonathan Wayne
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: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
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公开(公告)号：US20060216283A1
公开(公告)日：2006-09-28
申请号：US11327855
申请日：2006-01-09
Applicant: Keith Foster , John Chaddock , Conrad Quinn , John Purkiss
Inventor： Keith Foster , John Chaddock , Conrad Quinn , John Purkiss
CPC classification number: A61K38/4886 , A61K47/64
Abstract: A method of treatment of disease by inhibition of cellular secretory processes is provided. The method has particular application in the treatment of diseases dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system, and bone cells. Agents and compositions therefor, as well as methods for manufacturing these agents and compositions, are provided. In a preferred embodiment a clostridial neurotoxin, substantially devoid of holotoxin binding affinity for neuronal cells of the presynaptic muscular junction, is associated with a targeting moiety. The targeting moiety is selected such that the clostridial toxin conjugate so formed may be directed to a non-neuronal target cell to which the conjugate may bind. Following binding, a neurotoxin component of the conjugate, which is capable of inhibition of cellular secretion, passes into the cytosol of the target cell by cellular internalisation mechanisms. Thereafter, inhibition of secretion from the target cell is effected.
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公开(公告)号：US20060116852A1
公开(公告)日：2006-06-01
申请号：US11000631
申请日：2004-12-01
Applicant: Donald Yuhas , James Voth , Patrick Schneider , Keith Foster
Inventor： Donald Yuhas , James Voth , Patrick Schneider , Keith Foster
IPC: G01B11/02
CPC classification number: B60R16/0207 , G01B15/00
Abstract: The present invention is a method for determining the center to center spacing of conductors in an insulated, multi-conductor, flat cable. The method comprising applying an X-ray field to the cable, detecting the X-ray field intensity that passes through the cable, obtaining a digitized output waveform of the X-ray field intensity as a function of cable position, and determining a trough location of the waveform by averaging calculated position values for the center of the conductor at several longitudinal positions along a cross section of the conductor.
Abstract translation: 本发明是用于确定绝缘多导体扁平电缆中的导体的中心到中心间隔的方法。 该方法包括对电缆施加X射线场，检测通过电缆的X射线场强度，获得作为电缆位置的函数的X射线场强度的数字化输出波形，以及确定槽位置 通过在沿着导体的横截面的几个纵向位置处对导体的中心的计算的位置值求平均来计算波形。
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公开(公告)号：US20060110410A1
公开(公告)日：2006-05-25
申请号：US10527411
申请日：2003-09-12
Applicant: Clifford Shone , Keith Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
Inventor： Clifford Shone , Keith Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC classification number: A61K39/08 , A61K38/00 , A61K39/00 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , C12N15/62 , Y10S530/825
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide, is possible and the polypeptide can be incorporated into vaccines and toxin assays.
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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。
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