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1. 发明公开

CN105492074A 瘙痒的抑制无效
公开(公告)号：CN105492074A
公开(公告)日：2016-04-13
申请号：CN201480039346.0
申请日：2014-07-09
申请人：益普生生物创新有限公司
发明人： K·福斯特
IPC分类号： A61P25/00 , A61K38/48 , A61K39/08
CPC分类号： C12N9/52 , A61K38/00 , A61K38/48 , C07K7/08 , C07K2319/10 , C07K2319/55 , C12Y304/21072 , C12Y304/24013 , C12Y304/24069
摘要：本发明提供用于抑制或治疗瘙痒的多肽，其中该多肽包含：非细胞毒性蛋白酶，该蛋白酶能够裂解瘙痒-特异性DRG神经元或痒觉感受器(pruriceptor)中的SNARE蛋白；能够结合于瘙痒-特异性DRG神经元或痒觉感受器上的结合位点的靶向部分(TM)，所述结合位点能够经历胞吞作用而被并入至瘙痒-特异性DRG神经元或痒觉感受器内的内体，且其中所述瘙痒-特异性DRG神经元或痒觉感受器表达所述SNARE蛋白；和能够使来自内体内的蛋白酶易位、通过内体膜并且进入瘙痒-特异性DRG神经元或痒觉感受器的胞质溶胶的易位结构域；条件是该多肽不是梭菌神经毒素(全毒素)分子。

2. 发明公开

CN105102066A 抑制骨质疏松的治疗剂审中-实审
公开(公告)号：CN105102066A
公开(公告)日：2015-11-25
申请号：CN201480009280.0
申请日：2014-02-21
申请人： IPSEN生物创新有限公司
发明人：基思·福斯特
IPC分类号： A61P19/10 , A61K47/48
CPC分类号： C12N9/48 , A61K38/00 , A61K47/64 , A61K47/642 , C07K14/33 , C07K14/5437 , C07K2319/01 , C07K2319/06 , C07K2319/33 , C07K2319/74 , C12N9/52 , C12Y304/00 , C12Y304/24013
摘要：本发明提供用于抑制或治疗骨质疏松症的多肽，其中该多肽包含：非细胞毒性蛋白酶，该蛋白酶能够裂解肠嗜铬细胞中的SNARE蛋白；能够结合肠嗜铬细胞上的结合位点的靶向部分(TM)，所述结合位点能够进行胞吞作用以并入肠嗜铬细胞内的内体，且其中所述肠嗜铬细胞表达所述SNARE蛋白；和能够使所述蛋白酶从内体内易位、通过内体膜并且进入肠嗜铬细胞胞液的易位结构域；条件是所述多肽不是梭菌神经毒素(全毒素)分子。

3. 发明申请

US20150353908A1 THERAPEUTICS FOR SUPPRESSING OSTEOPOROSIS 审中-公开
标题翻译：抑制OSTEOPOSOSIS的治疗方法
公开(公告)号：US20150353908A1
公开(公告)日：2015-12-10
申请号：US14758435
申请日：2014-02-21
申请人： IPSEN BIOINNOVATION LIMITED
发明人： Keith FOSTER
IPC分类号： C12N9/48 , C07K14/33
CPC分类号： C12N9/48 , A61K38/00 , A61K47/64 , A61K47/642 , C07K14/33 , C07K14/5437 , C07K2319/01 , C07K2319/06 , C07K2319/33 , C07K2319/74 , C12N9/52 , C12Y304/00 , C12Y304/24013
摘要： The invention provides a polypeptide, for use in suppressing or treating osteoporosis, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an enterochromaffin cell; a Targeting Moiety (TM) that is capable of binding to a Binding Site on an enterochromaffin cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the enterochromaffin cell, and wherein said enterochromaffin cell expresses said SNARE protein; and a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the enterochromaffin cell; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.
摘要翻译：本发明提供了用于抑制或治疗骨质疏松症的多肽，其中所述多肽包含：非细胞毒性蛋白酶，所述蛋白酶能够切割肠嗜铬细胞中的SNARE蛋白; 能够结合到嗜铬细胞上的结合位点的靶向物（TM），所述结合位点能够经历内吞作用以掺入肠嗜铬细胞内的内体，并且其中所述肠嗜铬细胞表达所述SNARE蛋白; 以及能够将蛋白酶从内体内穿过内体膜并进入肠溶石蜡细胞的胞质溶胶的易位结构域; 条件是多肽不是梭菌神经毒素（全毒素）分子。

4. 发明申请

US20170327810A1 FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATING PAIN 审中-公开
公开(公告)号：US20170327810A1
公开(公告)日：2017-11-16
申请号：US15661433
申请日：2017-07-27
申请人： IPSEN BIOINNOVATION LIMITED , Allergan, Inc.
发明人： Peter JAMES , Keith FOSTER , John CHADDOCK , Roger Kei AOKI , Lance STEWARD , Joseph FRANCIS
IPC分类号： C12N9/52 , C07K14/575
CPC分类号： C12N9/52 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/575 , C07K2319/01 , C07K2319/50 , C07K2319/55 , C07K2319/74 , C12N15/625 , C12Y304/21072 , C12Y304/24013 , C12Y304/24068 , C12Y304/24069
摘要： A single chain polypeptide fusion protein, comprising: a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin targeting moiety; a protease cleavage site at which site the fusion protein is cleavable by a protease; a translocation domain capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; a first spacer located between the non-cytotoxic protease and the protease cleavage site; and a second spacer located between the galanin targeting moiety and the translocation domain.

5. 发明申请

US20160137999A1 SUPPRESSION OF ITCH 审中-公开
标题翻译：抑制ITCH
公开(公告)号：US20160137999A1
公开(公告)日：2016-05-19
申请号：US14900892
申请日：2014-07-09
申请人： IPSEN BIOINNOVATION LIMITED
发明人： Keith FOSTER
IPC分类号： C12N9/52 , C07K7/08
CPC分类号： C12N9/52 , A61K38/00 , A61K38/48 , C07K7/08 , C07K2319/10 , C07K2319/55 , C12Y304/21072 , C12Y304/24013 , C12Y304/24069
摘要： The invention provides a polypeptide, for use in suppressing or treating itch, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an itch-specific DRG neuron or a pruriceptor; a Targeting Moiety (TM) that is capable of binding to a Binding Site on the itch-specific DRG neuron or a pruriceptor, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the itch-specific DRG neuron or a pruriceptor, and wherein said itch-specific DRG neuron or a pruriceptor expresses said SNARE protein; and a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the itch-specific DRG neuron or a pruriceptor; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.
摘要翻译：本发明提供了用于抑制或治疗瘙痒的多肽，其中所述多肽包含：非细胞毒性蛋白酶，所述蛋白酶能够在瘙痒特异性DRG神经元或瘙痒感受物中切割SNARE蛋白; 能够结合瘙痒特异性DRG神经元上的结合位点的靶向物（TM），或者可以将结合位点能够进行内吞作用的瘙痒特异性DRG神经元或瘙痒剂，并且其中所述瘙痒特异性DRG神经元或pruriceptor表达所述SNARE蛋白; 以及易位区域，其能够将蛋白酶从内体内穿过内体膜并进入瘙痒特异性DRG神经元的细胞质溶液或精华中; 条件是多肽不是梭菌神经毒素（全毒素）分子。

6. 发明公开

EP2888359A1 FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATING PAIN 有权
标题翻译：融合蛋白的方法进行治疗，预防和减轻疼痛
公开(公告)号：EP2888359A1
公开(公告)日：2015-07-01
申请号：EP13759562.5
申请日：2013-08-27
申请人： Ipsen Bioinnovation Limited , ALLERGAN, INC.
发明人： JAMES, Peter , FOSTER, Keith , CHADDOCK, John , AOKI, Roger Kei , STEWARD, Lance , FRANCIS, Joseph
IPC分类号： C12N9/52 , C12N9/54 , C12N15/62 , A61K38/48 , A61K47/48
CPC分类号： C12N9/52 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/575 , C07K2319/01 , C07K2319/50 , C07K2319/55 , C07K2319/74 , C12N15/625 , C12Y304/21072 , C12Y304/24013 , C12Y304/24068 , C12Y304/24069
摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which protease is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent (eg clostridial neurotoxin L-chain or IgA protease); a galanin 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 (eg GALR1, GALR2, or GALR3 receptor); 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 and the galanin Targeting Moiety; a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent (eg HN domain of clostridial neurotoxin); a first spacer located between the non- cytotoxic protease and the protease cleavage site, wherein said first spacer comprises an amino acid sequence of from 4 to 25 amino acid residues; and a second spacer located between the galanin Targeting Moiety and the translocation domain, wherein said second spacer comprises an amino acid sequence of from 4 to 35 amino acid residues. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described (eg of treating, preventing or ameliorating pain).
摘要翻译：单链多肽的融合蛋白，其包含：非细胞毒性蛋白酶，其裂解伤害性疼痛感觉传入的细胞外融合器的蛋白质; 甘丙肽靶向部分，确实结合在伤害性感觉传入，其可以经历胞吞作用以被并入在核内体的结合位点; 蛋白酶裂解位点，其中所述融合蛋白是由位于非细胞毒性蛋白酶和甘丙肽靶向的部分之间的蛋白酶可切割的; 易位结构域的确从内易位所述蛋白酶到核内体，跨内体膜并进入所述伤害性感觉传入的胞质溶胶中; 从非细胞毒性蛋白酶和蛋白酶切割位点之间4至25个氨基酸的第一间隔物; 和第二间隔层从甘丙肽靶向部分，和易位结构域之间4至35个残基，包括编码该多肽的融合蛋白的核酸序列，它们的用途是如此描述和制备它们的方法。

7. 发明授权

EP3019241B1 SUPPRESSION OF ITCH 有权
公开(公告)号：EP3019241B1
公开(公告)日：2018-05-30
申请号：EP14739923.2
申请日：2014-07-09
申请人： Ipsen Bioinnovation Limited
发明人： FOSTER, Keith
IPC分类号： A61P25/00 , A61K38/48 , A61K39/08
CPC分类号： C12N9/52 , A61K38/00 , A61K38/48 , C07K7/08 , C07K2319/10 , C07K2319/55 , C12Y304/21072 , C12Y304/24013 , C12Y304/24069
摘要： The invention provides a polypeptide, for use in suppressing or treating itch, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an itch-specific DRG neuron or a pruriceptor; a Targeting Moiety (TM) that is capable of binding to a Binding Site on the itch-specific DRG neuron or a pruriceptor, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the itch-specific DRG neuron or a pruriceptor, and wherein said itch-specific DRG neuron or a pruriceptor expresses said SNARE protein; and a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the itch-specific DRG neuron or a pruriceptor; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.

8. 发明申请

WO2015004464A1 SUPPRESSION OF ITCH 审中-公开
标题翻译：抑制ITCH
公开(公告)号：WO2015004464A1
公开(公告)日：2015-01-15
申请号：PCT/GB2014/052101
申请日：2014-07-09
申请人： SYNTAXIN LIMITED
发明人： FOSTER, Keith
IPC分类号： A61P25/00 , A61K38/48 , A61K39/08
CPC分类号： C12N9/52 , A61K38/00 , A61K38/48 , C07K7/08 , C07K2319/10 , C07K2319/55 , C12Y304/21072 , C12Y304/24013 , C12Y304/24069
摘要： The invention provides a polypeptide, for use in suppressing or treating itch, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an itch-specific DRG neuron or a pruriceptor; a Targeting Moiety (TM) that is capable of binding to a Binding Site on the itch-specific DRG neuron or a pruriceptor, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the itch-specific DRG neuron or a pruriceptor, and wherein said itch- specific DRG neuron or a pruriceptor expresses said SNARE protein; and a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the itch-specific DRG neuron or a pruriceptor; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.
摘要翻译：本发明提供了用于抑制或治疗瘙痒的多肽，其中所述多肽包含：非细胞毒性蛋白酶，所述蛋白酶能够在瘙痒特异性DRG神经元或瘙痒感受物中切割SNARE蛋白; 能够结合瘙痒特异性DRG神经元上的结合位点的靶向物（TM），或者可以将结合位点能够进行内吞作用的朊病毒特异性DRG神经元或瘙痒剂并且其中所述瘙痒特异性DRG神经元或pruriceptor表达所述SNARE蛋白; 以及易位区域，其能够将蛋白酶从内体内穿过内体膜并进入瘙痒特异性DRG神经元的细胞质溶液或精华中; 条件是多肽不是梭菌神经毒素（全毒素）分子。

9. 发明公开

EP3246405A1 FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATING PAIN 审中-公开
标题翻译：融合蛋白和治疗，预防或改善疼痛的方法
公开(公告)号：EP3246405A1
公开(公告)日：2017-11-22
申请号：EP17165621.8
申请日：2013-08-27
申请人： Ipsen Bioinnovation Limited , ALLERGAN, INC.
发明人： JAMES, Peter , FOSTER, Keith , CHADDOCK, John , AOKI, Roger Kei , STEWARD, Lance , FRANCIS, Joseph
IPC分类号： C12N9/52 , C12N9/54 , C12N15/62 , A61K38/48
CPC分类号： C12N9/52 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/575 , C07K2319/01 , C07K2319/50 , C07K2319/55 , C07K2319/74 , C12N15/625 , C12Y304/21072 , C12Y304/24013 , C12Y304/24068 , C12Y304/24069
摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which protease is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent (eg clostridial neurotoxin L-chain or IgA protease); a galanin 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 (eg GALR1, GALR2, or GALR3 receptor); 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 and the galanin Targeting Moiety; a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent (eg HN domain of clostridial neurotoxin); a first spacer located between the non- cytotoxic protease and the protease cleavage site, wherein said first spacer comprises an amino acid sequence of from 4 to 25 amino acid residues; and a second spacer located between the galanin Targeting Moiety and the translocation domain, wherein said second spacer comprises an amino acid sequence of from 4 to 35 amino acid residues. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described (eg of treating, preventing or ameliorating pain).
摘要翻译：单链多肽融合蛋白，其包含：非细胞毒性蛋白酶，所述蛋白酶能够切割伤害性感觉传入的胞吐融合装置（例如梭菌神经毒素L链或IgA蛋白酶）的蛋白质; 甘丙肽靶向部分，其能够结合伤害性感觉传入的结合位点，该结合位点能够经历内吞作用以并入感受伤害性感觉传入（例如GALR1，GALR2或GALR3受体）内的内体; 蛋白酶切割位点，在该位点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和甘丙肽靶向部分之间; 能够将蛋白酶从内体内转移穿过内体膜并进入伤害感觉传入细胞的胞质溶胶（例如梭菌神经毒素的HN结构域）的转位结构域; 位于非细胞毒性蛋白酶和蛋白酶切割位点之间的第一间隔区，其中所述第一间隔区包含4至25个氨基酸残基的氨基酸序列; 和位于甘丙肽靶向部分和易位结构域之间的第二间隔区，其中所述第二间隔区包含4至35个氨基酸残基的氨基酸序列。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（例如治疗，预防或改善疼痛）。

10. 发明公开

EP2958629A1 THERAPEUTICS FOR SUPPRESSING OSTEOPOROSIS 审中-公开
标题翻译： THERAPEUTIKA ZUR OSTEOPOROSE-UNTERDRÜCKUNG
公开(公告)号：EP2958629A1
公开(公告)日：2015-12-30
申请号：EP14706942.1
申请日：2014-02-21
申请人： Ipsen Bioinnovation Limited
发明人： FOSTER, Keith
IPC分类号： A61P19/10 , A61K47/48
CPC分类号： C12N9/48 , A61K38/00 , A61K47/64 , A61K47/642 , C07K14/33 , C07K14/5437 , C07K2319/01 , C07K2319/06 , C07K2319/33 , C07K2319/74 , C12N9/52 , C12Y304/00 , C12Y304/24013
摘要： The invention provides a polypeptide, for use in suppressing or treating osteoporosis, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an enterochromaffin cell; a Targeting Moiety (TM) that is capable of binding to a Binding Site on an enterochromaffin cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the enterochromaffin cell, and wherein said enterochromaffin cell expresses said SNARE protein; anda translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the enterochromaffin cell;with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.
摘要翻译：本发明提供了用于抑制或治疗骨质疏松症的多肽，其中所述多肽包含：非细胞毒性蛋白酶，所述蛋白酶能够切割肠嗜铬细胞中的SNARE蛋白; 能够结合到嗜铬细胞上的结合位点的靶向物（TM），所述结合位点能够经历内吞作用以掺入肠嗜铬细胞内的内体，并且其中所述肠嗜铬细胞表达所述SNARE蛋白; 以及能够将蛋白酶从内体内穿过内体膜并进入肠嗜铬细胞的胞质溶胶的易位结构域; 条件是多肽不是梭菌神经毒素（全毒素）分子。

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