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11. 发明申请

WO2006059105A3 NON-CYTOTOXIC PROTEIN CONJUGATES 审中-公开
标题翻译：非细胞毒素蛋白结合
公开(公告)号：WO2006059105A3
公开(公告)日：2006-08-31
申请号：PCT/GB2005004598
申请日：2005-12-01
申请人： HEALTH PROT AGENCY , ALLERGAN INC , FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES , AOKI K ROGER , FRANCIS JOSEPH , STEWARD LANCE
发明人： FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES , AOKI K ROGER , FRANCIS JOSEPH , STEWARD LANCE
IPC分类号： A61K38/16 , C07K14/00 , C07K14/435 , C07K19/00 , C12N15/62
CPC分类号： C07K14/33 , A61K38/00 , C07K2319/00
摘要： 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.
摘要翻译：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。

12. 发明申请

WO03102169B1 ANAEROBE TARGETED ENZYME-MEDIATED PRODRUG THERAPY 审中-公开
标题翻译： ANAEROBE目标ENZYME介导的PRODRUG治疗
公开(公告)号：WO03102169B1
公开(公告)日：2004-05-27
申请号：PCT/US0317291
申请日：2003-05-30
申请人： UNIV LELAND STANFORD JUNIOR , HEALTH PROT AGENCY
发明人： BROWN JOHN M , LIU SHIE-CHAU , GIACCIA AMATO J , MINTON NIGEL P
IPC分类号： A61K35/74 , A61K48/00 , C12N1/20 , C12N1/21 , C12N9/02 , C12N15/74
CPC分类号： A61K48/0058 , A61K35/742 , A61K38/50 , C12N1/20 , C12N9/0004 , C12N15/74 , C12R1/145
摘要： Recombinant anaerobic bacterial compositions that under anaerobic conditions present in a solid tumor and produce an enzyme capable of catalyzing the conversion of a prodrug to its cytotoxic product in situ are described. Methods of treating tumors using the composition are also described.
摘要翻译：描述了在固体肿瘤中存在于厌氧条件下产生能够催化前体药物转化为其细胞毒性产物的酶的酶的重组厌氧细菌组合物。还描述了使用该组合物治疗肿瘤的方法。

13. 发明申请

WO2006059105A8 NON-CYTOTOXIC PROTEIN CONJUGATES 审中-公开
标题翻译：非细胞毒素蛋白结合
公开(公告)号：WO2006059105A8
公开(公告)日：2007-11-08
申请号：PCT/GB2005004598
申请日：2005-12-01
申请人： HEALTH PROT AGENCY , ALLERGAN INC , FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES , AOKI K ROGER , FRANCIS JOSEPH , STEWARD LANCE
发明人： FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES , AOKI K ROGER , FRANCIS JOSEPH , STEWARD LANCE
IPC分类号： A61K38/16 , C07K14/00 , C07K14/435 , C07K19/00 , C12N15/62
CPC分类号： C07K14/33 , A61K38/00 , C07K2319/00
摘要： 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.
摘要翻译：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。

14. 发明申请

WO2005023309A3 DESIGN OF RE-TARGETED TOXIN CONJUGATES 审中-公开
标题翻译：重定向毒素结合物的设计
公开(公告)号：WO2005023309A3
公开(公告)日：2005-09-15
申请号：PCT/GB2004003904
申请日：2004-09-13
申请人： HEALTH PROT AGENCY , FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES
发明人： FOSTER KEITH , CHADDOCK JOHN , PENN CHARLES
IPC分类号： A61K47/48
CPC分类号： C12N9/52 , A61K47/64 , A61K47/642
摘要： 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).
摘要翻译：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。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（如梭菌神经毒素）设计毒素结合物的方法，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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