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81. 发明授权

US07381700B2 Methods for treating pain associated with arthritis 失效
标题翻译：治疗与关节炎有关的疼痛的方法
公开(公告)号：US07381700B2
公开(公告)日：2008-06-03
申请号：US11159569
申请日：2005-06-22
申请人： Kei Roger Aoki , Micheal W. Grayston , Steven R. Carlson , Judith M. Leon
发明人： Kei Roger Aoki , Micheal W. Grayston , Steven R. Carlson , Judith M. Leon
IPC分类号： A61K39/08
CPC分类号： A61K38/4893 , A61K39/08 , Y02A50/469
摘要： A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.
摘要翻译：用于治疗患有疾病，病症或病症和相关疼痛的患者的方法和组合物包括向患者施用治疗有效量的神经毒素，所述神经毒素选自A，B，C，D型肉毒杆菌毒素， E，F和G.

82. 发明申请

US20080003240A1 Botulinum Toxin Screening Assays 失效
标题翻译：肉毒杆菌毒素筛选试验
公开(公告)号：US20080003240A1
公开(公告)日：2008-01-03
申请号：US10598073
申请日：2005-02-23
申请人： Ester Fernandez-Salas , Patton Garay , Kei Roger Aoki
发明人： Ester Fernandez-Salas , Patton Garay , Kei Roger Aoki
IPC分类号： A61K39/02 , A61P31/00 , C12Q1/02
CPC分类号： G01N33/56911 , G01N2333/50
摘要： Methods for detecting BoNT/A activity in a sample, methods for screening molecules able to compete with BoNT/A receptor binding, methods for reducing BoNT/A activity in a human and methods of marketing a neurotoxin capable of selectively binding to FGFR3 to a governmental or regional regulatory authority.
摘要翻译：用于检测样品中BoNT / A活性的方法，用于筛选能够与BoNT / A受体结合竞争的分子的方法，用于降低人类中的BoNT / A活性的方法和将能够选择性结合FGFR3的神经毒素销售给政府的方法或区域监管机构。

83. 发明授权

US07288260B2 Method for treating pain by peripheral administration of a neuroptoxin 有权
标题翻译：通过外周给药神经毒素治疗疼痛的方法
公开(公告)号：US07288260B2
公开(公告)日：2007-10-30
申请号：US10943133
申请日：2004-09-15
申请人： Kei Roger Aoki , Minglei Cui , Stephen W. Jenkins
发明人： Kei Roger Aoki , Minglei Cui , Stephen W. Jenkins
IPC分类号： A61K39/08 , A61K39/02
CPC分类号： A61K38/4893
摘要： Methods for treating a non-spasm caused pain by peripheral administration to a patient of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin.
摘要翻译：用于治疗非痉挛的方法通过外周给予患者治疗有效量的神经毒素如肉毒杆菌毒素而引起疼痛。

84. 发明授权

US07208285B2 Fret protease assays for botulinum serotype A/E toxins 有权
标题翻译：肉毒杆菌血清型A / E毒素的Fret蛋白酶检测
公开(公告)号：US07208285B2
公开(公告)日：2007-04-24
申请号：US09942024
申请日：2001-08-28
申请人： Lance E. Steward , Ester Fernandez-Salas , Kei Roger Aoki
发明人： Lance E. Steward , Ester Fernandez-Salas , Kei Roger Aoki
IPC分类号： C12Q1/37 , C07H21/04 , C12P21/06 , C12N15/74 , C07N14/435
CPC分类号： G01N33/582
摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
摘要翻译：本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。

85. 发明授权

US06776990B2 Methods and compositions for the treatment of pancreatitis 失效
公开(公告)号：US06776990B2
公开(公告)日：2004-08-17
申请号：US09288326
申请日：1999-04-08
申请人： George Sachs , Kei Roger Aoki
发明人： George Sachs , Kei Roger Aoki
IPC分类号： A61K3900
CPC分类号： C07K14/33 , A61K47/6415 , C07K2317/53 , C07K2319/00 , C07K2319/33
摘要： Methods and compositions for the treatment of acute pancreatitis in a mammal. Particular compositions comprise a binding element, a translocation element, and a therapeutic element able to prevent accumulation of digestive enzymes within the pancreas.

86. 发明授权

US5721215A Injectable therapy for control of muscle spasms and pain related to muscle spasms 失效
标题翻译：用于控制肌肉痉挛和与肌肉痉挛相关的疼痛的注射治疗
公开(公告)号：US5721215A
公开(公告)日：1998-02-24
申请号：US619780
申请日：1996-03-20
申请人： Kei Roger Aoki , Larry A. Wheeler , Michael E. Garst
发明人： Kei Roger Aoki , Larry A. Wheeler , Michael E. Garst
IPC分类号： A61K38/43 , A61K31/00 , A61K31/56 , A61K35/64 , A61K36/00 , A61K38/48 , A61K39/395 , A61K45/00 , A61K48/00 , A61P21/00 , A61P21/02 , A61P25/00 , A61K38/16 , A61M13/00
CPC分类号： G01N33/5088 , A61K38/1703 , A61K38/4893 , G01N2800/10
摘要： A method for administration of botulinum toxin, includes the steps of (a) selecting at least one neuromuscular blocking agent having a duration of activity shorter than neuromuscular blocking activity of botulinum toxin; (b) selecting at least one muscle of a muscle group; (c) intramuscularly injecting the selected agent into the selected muscle; (d) observing muscle relaxation in both the selected muscle and other nonselected muscles in the muscle group to determine spill-over, muscle tone and balance; (e) repeating steps (b)-(d) until a final muscle selection is found; and (f) intramuscularly injecting botulinum toxin into the final muscle selection.
摘要翻译：一种施用肉毒杆菌毒素的方法包括以下步骤：（a）选择至少一种具有短于肉毒杆菌毒素的神经肌肉阻滞活性的活性持续时间的神经肌肉阻滞剂; （b）选择肌群的至少一个肌肉; （c）将所选择的药剂肌内注射到所选择的肌肉中; （d）在所选择的肌肉和肌肉组中的其他非选择肌肉中观察肌肉松弛，以确定溢出，肌肉紧张度和平衡; （e）重复步骤（b） - （d），直到发现最终的肌肉选择; 和（f）肌肉注射肉毒毒素进入最终的肌肉选择。

87. 发明授权

US09139635B2 Non-cytotoxic protein conjugates 有权
标题翻译：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
申请人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： A61K38/48 , C07K14/575 , A61K31/711 , A61K47/48 , C07K14/33 , C12N9/64 , C12N15/62
CPC分类号： C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
摘要： 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.
摘要翻译：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。

88. 发明申请

US20140056870A1 FUSION PROTEINS 审中-公开
标题翻译：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
申请人： Peter James , Keith Foster , John Chaddock , Kei Roger Aoki , Lance Steward , Joseph Francis
发明人： Peter James , Keith Foster , John Chaddock , Kei Roger Aoki , Lance Steward , Joseph Francis
IPC分类号： C12N9/48 , A61P29/00 , A61K38/48 , C12N15/57 , C12N15/63
摘要： 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.
摘要翻译：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。

89. 发明授权

US08603779B2 Non-cytotoxic protein conjugates 有权
标题翻译：非细胞毒性蛋白偶联物
公开(公告)号：US08603779B2
公开(公告)日：2013-12-10
申请号：US13343892
申请日：2012-01-05
申请人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C07K14/00 , A61K38/16 , C12P21/04 , C12P21/06
CPC分类号： A61K38/4893 , A61K38/4886 , C07K14/575 , C07K2319/00 , C07K2319/01 , C12N9/52 , C12Y304/21072
摘要： 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.
摘要翻译：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。

90. 发明授权

US08399400B2 Fusion proteins 有权
公开(公告)号：US08399400B2
公开(公告)日：2013-03-19
申请号：US12862948
申请日：2010-08-25
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C07K14/00 , C07H21/02
CPC分类号： C12N9/96 , A61K38/00 , A61K47/64 , C07K2319/01 , C07K2319/33 , C07K2319/50 , C12N9/50
摘要： 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.

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