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公开(公告)号：US09243301B2
公开(公告)日：2016-01-26
申请号：US13419381
申请日：2012-03-13
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: A61K38/00 , C12N9/52 , C12N15/62 , C07K14/665
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 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, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation 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; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the 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可以切割伤害性感觉传入的胞外融合装置的蛋白质; 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，位于融合蛋白可被位于非细胞毒性蛋白酶和靶向部位之间的蛋白酶切割; 以及易位区域，其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; 其中靶向部分是BAM，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。 还描述了编码融合蛋白的核酸序列，其制备方法及其用途。
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公开(公告)号：US20110171191A1
公开(公告)日：2011-07-14
申请号：US12996643
申请日：2009-06-11
Applicant: Stephen Johnstone , Philip Marks , Keith Foster
Inventor： Stephen Johnstone , Philip Marks , Keith Foster
IPC: A61K38/48 , C12N9/96 , C07H21/00 , A61K31/7088 , A61P35/00 , A61P35/04 , A61P3/00 , A61P9/12 , A61P1/12 , A61P1/00
CPC classification number: C12N9/6489 , A61K38/4893 , A61K47/6415 , C07K2319/035 , C07K2319/06
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 receptora 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 tumourcell. 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，泌尿生长因受体α黑素浓缩激素受体1靶向神经内分泌肿瘤细胞; 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分泌 - 从所述的肿瘤。 本发明还涉及用于所述方法的多肽和核酸。
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公开(公告)号：US20100247509A1
公开(公告)日：2010-09-30
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
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。
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公开(公告)号：US20080070278A1
公开(公告)日：2008-03-20
申请号：US11819647
申请日：2007-06-28
Applicant: John North , Keith Foster , Conrad Quinn , Clifford Shone
Inventor： John North , Keith Foster , Conrad Quinn , Clifford Shone
CPC classification number: C12N15/62 , A61K38/00 , A61K47/62 , A61K47/6415 , C07K14/33 , C07K2319/00 , Y02A50/469
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 Translation 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 为了产生内体，结构域T是翻译区，其将试剂（含或不含结合位点）从内体内穿过内体膜转移到细胞的胞质溶胶中，域E是抑制 可循环膜囊将整体膜蛋白转运至细胞表面。
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公开(公告)号：US20070184048A1
公开(公告)日：2007-08-09
申请号：US10571515
申请日：2004-09-13
Applicant: Keith Foster , John Chaddock , Charles Penn
Inventor： Keith Foster , John Chaddock , Charles Penn
IPC: A61K39/00 , G01N33/567 , A61K39/395
CPC classification number: C12N9/52 , A61K47/64 , A61K47/642
Abstract: The present invention provides a method for designing a re-targeted toxin conjugate for use in treating a medical condition or disease. Also provided, is the use of said conjugates in the manufacture of a medicament for treating medical conditions or diseases. The conjugates include a Targeting Moiety, which directs the conjugate to a desired target cell, and are characterised by a Targeting Moiety that increases exocytic fusion in the target cell. The present invention also provides methods for identifying agonists suitable for use as Targeting Moieties, and methods for preparing conjugates comprising said Targeting Moieties, to re-target a toxin to a cell of therapeutic interest. In particular, the present invention describes a method for designing a toxin conjugate, and describes therapeutic applications of said conjugates to inhibit or reduce cellular processes. Even more particularly, the present invention describes a method for designing toxin conjugates based upon non-cytotoxic toxins able to inhibit exocytosis, such as clostridial neurotoxins, and describes therapeutic applications of said conjugates to inhibit or reduce exocytosis (for example secretion, or the delivery of proteins such as receptors, transporters, and membrane channels to the plasma membrane of a cell).
Abstract translation: 本发明提供了一种用于设计用于治疗医学病症或疾病的再靶向毒素缀合物的方法。 还提供了所述缀合物在制备用于治疗医学病症或疾病的药物中的用途。 缀合物包括将缀合物引导至期望的靶细胞的靶向部位，其特征在于靶细胞增加靶细胞中的胞外融合。 本发明还提供了用于鉴定适合用作靶向部分的激动剂的方法，以及用于制备包含所述靶向部分的缀合物的方法，以将毒素重新靶向治疗感兴趣的细胞。 特别地，本发明描述了一种用于设计毒素缀合物的方法，并且描述了所述缀合物抑制或减少细胞过程的治疗应用。 甚至更具体地，本发明描述了一种基于能够抑制胞吐作用的非细胞毒素毒素（例如梭菌神经毒素）设计毒素缀合物的方法，并且描述了所述缀合物抑制或减少胞吐作用（例如分泌或递送）的治疗应用 的蛋白质，如受体，转运蛋白和膜通道的细胞质膜）。
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Patent Agency Ranking
公开(公告)号：US3971217A
公开(公告)日：1976-07-27
申请号：US511523
申请日：1974-10-03
Applicant: Donald Firth , Keith Foster , Christopher John Hooke
Inventor： Donald Firth , Keith Foster , Christopher John Hooke
IPC: B25D9/12 , E02F3/40 , E02F9/22 , E21B4/14 , E21B7/26 , F16J3/02 , F16J15/52 , F15B13/09 , F15B15/04
CPC classification number: B25D9/12 , E02F3/405 , E02F9/221 , E21B4/14 , E21B7/26 , F16J15/52 , F16J3/02
Abstract: A fluid operated reciprocatable device has an outer, usually fixed, membernd an inner relatively movable member joined by a resilient member e.g., of rubber. The outer member is closed at one end so as to form an enclosure into which fluid under pressure can be admitted so as to displace the inner member in a given axial direction relative to the outer member. When a pulsating pressure is applied to the fluid the inner member vibrates axially in accordance with the pulses. The resilient member is proportioned so that its dimension in the axial direction is large in comparison with the thickness between the outer and inner members, e.g. 4 times larger. The properties of the resilient member are chosen so that it acts not only as a seal between the outer and inner members to contain fluid, but as a return spring whereby the inner member is returned, between fluid pulses, from an axially displaced position.
Abstract translation: 流体操作的可往复运动的装置具有外部通常固定的构件和通过弹性构件（例如橡胶）连接的内部相对可动构件。 外部构件在一端封闭，以便形成一个外壳，可以承受压力下的流体，从而相对于外部构件在给定的轴向方向上移动内部构件。 当对流体施加脉动压力时，内部构件根据脉冲轴向振动。 弹性构件成比例，使得其在轴向方向上的尺寸与外构件和内构件之间的厚度相比是大的。 4倍大。 弹性构件的性质被选择成使得其不仅作为外部构件和内部构件之间的密封件以容纳流体，而且作为复位弹簧，由此内部构件在流体脉冲之间从轴向移位的位置返回。
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公开(公告)号：US10240138B2
公开(公告)日：2019-03-26
申请号：US12996641
申请日：2009-06-11
Applicant: Frederic Madec , Phil Lecane , Philip Marks , Keith Foster
Inventor： Frederic Madec , Phil Lecane , Philip Marks , Keith Foster
IPC: C12N9/50 , C12N9/64 , C07K7/08 , C07K14/33 , C07K14/48 , C07K14/575 , C07K14/60 , C07K14/65 , C07K14/82 , A61K38/00
Abstract: The present invention relates to a method for suppressing or treating cancer, in particular to a method for suppressing or treating one or more of colorectal cancer, breast cancer, prostate cancer and/or lung cancer. The therapy employs use of a non-cytotoxic protease, which is targeted to a growth hormone-secreting cell such as to a pituitary cell. When so delivered, the protease is internalized and inhibits secretion/transmission of growth hormone from said cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.
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公开(公告)号：US08796216B2
公开(公告)日：2014-08-05
申请号：US12969810
申请日：2010-12-16
Applicant: Stephen Johnstone , Philip Marks , Keith Foster
Inventor： Stephen Johnstone , Philip Marks , Keith Foster
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 tumor 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 internalized and inhibits secretion from said tumor 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。
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公开(公告)号：US08778634B2
公开(公告)日：2014-07-15
申请号：US13418453
申请日：2012-03-13
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: C12N9/6432 , A61K38/00 , A61K38/22 , A61K38/48 , A61K47/48246 , A61K47/48338 , A61K47/48361 , A61K47/64 , A61K47/65 , A61K47/67 , C07K14/665 , C07K2319/00 , C07K2319/01 , C07K2319/21 , C07K2319/55 , C12N9/96 , C12N15/62 , C12Y304/00 , C12Y304/21006
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 wherein the Targeting Moiety is selected from the group consisting of BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.
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，其中易位域将内体内的蛋白酶或蛋白酶片段转移穿过内体膜，并转移到伤害性感觉传入细胞的胞质溶胶中，其中靶向部分选自BAM ，内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。
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公开(公告)号：US08187834B2
公开(公告)日：2012-05-29
申请号：US11791979
申请日：2005-12-01
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: 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。
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