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1. 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。

2. 发明申请

WO2006059113A2 FUSION PROTEINS 审中-公开
标题翻译：融合蛋白
公开(公告)号：WO2006059113A2
公开(公告)日：2006-06-08
申请号：PCT/GB2005/004606
申请日：2005-12-01
申请人： HEALTH PROTECTION AGENCY , FOSTER, Keith , CHADDOCK, John , MARKS, Philip , STANCOMBE, Patrick , DUROSE, Lyndsey
发明人： FOSTER, Keith , CHADDOCK, John , MARKS, Philip , STANCOMBE, Patrick , DUROSE, Lyndsey
IPC分类号： C07K14/33
CPC分类号： C12N9/50 , A61K38/00 , C07K14/33 , C07K2319/06 , C07K2319/50 , C12N15/62
摘要： The invention provides 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 target cell; a Targeting Moiety that is capable of binding to a Binding Site on the target cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the target cell; 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 target cell.
摘要翻译：本发明提供了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靶细胞的胞外融合装置的蛋白质; 能够结合目标细胞上的结合位点的靶向物质，所述结合位点能够经历内吞作用以掺入靶细胞内的内体; 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靶细胞的胞质溶胶中的易位结构域。

3. 发明申请

WO2004024909A2 RECOMBINANT TOXIN FRAGMENTS 审中-公开
标题翻译：重组毒素片段
公开(公告)号：WO2004024909A2
公开(公告)日：2004-03-25
申请号：PCT/GB2003/003824
申请日：2003-09-12
申请人： HEALTH PROTECTION AGENCY , SHONE, Clifford, Charles , FOSTER, Keith, Alan , CHADDOCK, John , MARKS, Philip , SUTTON, Mark, J. , STANCOMBE, Patrick , WAYNE, Jonathan
发明人： SHONE, Clifford, Charles , FOSTER, Keith, Alan , CHADDOCK, John , MARKS, Philip , SUTTON, Mark, J. , STANCOMBE, Patrick , WAYNE, Jonathan
IPC分类号： C12N9/52
CPC分类号： 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
摘要： 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.
摘要翻译：提供了包含第一和第二结构域的单个多肽。第一结构域使多肽能够切割一种或多种与胞吐作用相关的囊泡或质膜相关的蛋白质，而第二结构域使多肽易位于靶细胞或增加多肽或两者的溶解度。因此，该多肽结合梭菌毒素如肉毒杆菌或破伤风毒素的有用性质，而不与天然分子相关的毒性。多肽还可以含有将其靶向特定细胞的第三结构域，使得多肽可用于抑制靶细胞中的胞吐作用。还提供了包含多肽的融合蛋白，编码多肽的核酸和制备多肽的方法。多肽的受控活化是可能的，并且多肽可以并入疫苗和毒素测定中。

4. 发明申请

WO2012156743A1 THERAPEUTIC FUSION PROTEINS 审中-公开
标题翻译：治疗性融合蛋白
公开(公告)号：WO2012156743A1
公开(公告)日：2012-11-22
申请号：PCT/GB2012/051104
申请日：2012-05-16
申请人： SYNTAXIN LIMITED , CHADDOCK, John , HARPER, Elaine
发明人： CHADDOCK, John , HARPER, Elaine
IPC分类号： C12N15/62 , A61K47/48 , C07K7/23
CPC分类号： C12N9/96 , A61K38/00 , C07K7/18 , C07K7/23 , C07K14/575 , C07K14/57572 , C07K14/60 , C07K2319/00 , C07K2319/06 , C07K2319/21 , C07K2319/50 , C07K2319/74 , C12N9/50 , C12N9/52 , C12N15/62
摘要： The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.
摘要翻译：本发明涉及新型靶向分泌抑制剂（TSI）的构建，其包含非细胞毒性蛋白酶，易位肽和靶向部分肽，其中靶向部分肽具有游离N-末端结构域和游离N末端结构域 C末端结构域涉及其单链融合蛋白前体，以及激活所述单链融合蛋白前体的方法。

5. 发明申请

WO2009083738A3 RNA DELIVERY VEHICLES 审中-公开
标题翻译： RNA交付车辆
公开(公告)号：WO2009083738A3
公开(公告)日：2009-08-27
申请号：PCT/GB2008051232
申请日：2008-12-31
申请人： SYNTAXIN LTD , CHADDOCK JOHN , BEARD MATTHEW
发明人： CHADDOCK JOHN , BEARD MATTHEW
IPC分类号： A61K47/48 , A61P1/06 , A61P11/00 , A61P25/14 , A61P35/00 , A61P37/08
CPC分类号： A61K47/6455 , A61K47/64 , A61K47/6415 , A61K47/6435
摘要： The present invention relates to double stranded nucleic acid (dsNA) delivery vehicles comprising a dsNA, and a clostridial endosomal translocation domain. Said delivery vehicle may further comprise a non-cytotoxic protease and/ or a Targeting Moiety (TM). The present invention also provides a method for delivering an RNA guide strand into a target cell, and to the use of a dsNA delivery vehicle for down-regulating mRNAactivity in a target cell. In one embodiment, the RNA guide strand binds to a SNARE mRNA target sequence, which leads to the suppression of SNARE protein expression in the target cell.
摘要翻译：本发明涉及包含dsNA和梭菌内体易位结构域的双链核酸（dsNA）递送载体。所述递送载体还可以包含非细胞毒性蛋白酶和/或Targeting Moiety TM。本发明还提供了将RNA引导链递送到靶细胞中的方法，以及用于下调靶细胞中的mRNA活性的dsNA递送载体的用途。在一个实施方案中，RNA指导链结合SNARE mRNA靶序列，其导致抑制靶细胞中的SNARE蛋白表达。

6. 发明申请

WO0010598B1 RECOMBINANT BOTULINIUM TOXIN FOR THE TREATMENT OF MUCUS HYPERSECRETION 审中-公开
标题翻译：用于治疗肌肉超声的重组苦素
公开(公告)号：WO0010598B1
公开(公告)日：2000-07-20
申请号：PCT/GB9902806
申请日：1999-08-25
申请人： MICROBIOLOGICAL RES AUTHORITY , QUINN CONRAD PADRAIG , FOSTER KEITH ALAN , CHADDOCK JOHN ANDREW
发明人： QUINN CONRAD PADRAIG , FOSTER KEITH ALAN , CHADDOCK JOHN ANDREW
IPC分类号： A61K9/12 , A61K35/74 , A61K38/00 , A61K45/00 , A61K47/48 , A61P11/00 , A61P11/06 , A61P11/12 , A61P43/00 , C07K14/195 , C07K14/33 , C07K19/00 , A61P11/02
CPC分类号： A61K47/62 , Y10S424/81
摘要： A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.
摘要翻译：一种治疗粘液分泌过多症的方法，慢性阻塞性肺疾病（COPD），哮喘和其他涉及COPD的临床病症的因素包括给予抑制或分泌粘液的粘液分泌细胞或神经元中的胞吐作用的化合物。还描述了一种用于治疗粘液分泌过高的化合物，其通过抑制由分泌分泌细菌的粘液分泌而抑制粘液分泌，和/或抑制神经递质从控制或引导粘液分泌的神经元细胞释放。

7. 发明申请

WO2006059093A3 FUSION PROTEINS 审中-公开
标题翻译：融合蛋白
公开(公告)号：WO2006059093A3
公开(公告)日：2006-08-17
申请号：PCT/GB2005004585
申请日：2005-12-01
申请人： HEALTH PROT AGENCY , ALLERGAN INC , FOSTER KEITH , CHADDOCK JOHN , MARKS PHILIP , STANCOMBE PATRICK , AOKI K ROGER , FRANCIS JOSEPH , STEWARD LANCE
发明人： FOSTER KEITH , CHADDOCK JOHN , MARKS PHILIP , STANCOMBE PATRICK , 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： C12N15/62 , A61K38/00 , C07K14/575 , C07K2319/00
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 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.
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。

8. 发明申请

WO2005023309A2 RE-TARGETED TOXIN CONJUGATES 审中-公开
标题翻译：重新定位的毒素结合物
公开(公告)号：WO2005023309A2
公开(公告)日：2005-03-17
申请号：PCT/GB2004/003904
申请日：2004-09-13
申请人： HEALTH PROTECTION 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.
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，以及制备包含所述靶向部分的缀合物的方法。

9. 发明申请

WO2004024909A3 RECOMBINANT COLSTRIDIUM NEUROTOXIN FRAGMENTS 审中-公开
标题翻译：重组菌神经毒素片段
公开(公告)号：WO2004024909A3
公开(公告)日：2004-07-08
申请号：PCT/GB0303824
申请日：2003-09-12
申请人： HEALTH PROT AGENCY , SHONE CLIFFORD CHARLES , FOSTER KEITH ALAN , CHADDOCK JOHN , MARKS PHILIP , SUTTON MARK J , STANCOMBE PATRICK , WAYNE JONATHAN
发明人： SHONE CLIFFORD CHARLES , FOSTER KEITH ALAN , CHADDOCK JOHN , MARKS PHILIP , SUTTON MARK J , STANCOMBE PATRICK , WAYNE JONATHAN
IPC分类号： 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分类号： 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
摘要： 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.
摘要翻译：提供了包含第一和第二结构域的单个多肽。第一结构域使多肽能够切割一种或多种与胞吐作用相关的囊泡或质膜相关的蛋白质，而第二结构域使多肽易位于靶细胞或增加多肽或两者的溶解度。因此，该多肽结合梭菌毒素如肉毒杆菌或破伤风毒素的有用性质，而不与天然分子相关的毒性。多肽还可以含有将其靶向特定细胞的第三结构域，使得多肽可用于抑制靶细胞中的胞吐作用。还提供了包含多肽的融合蛋白，编码多肽的核酸和制备多肽的方法。多肽的受控活化是可能的，并且多肽可以并入疫苗和毒素测定中。

10. 发明申请

WO2009083738A2 RNA DELIVERY VEHICLES 审中-公开
标题翻译： RNA交付车辆
公开(公告)号：WO2009083738A2
公开(公告)日：2009-07-09
申请号：PCT/GB2008/051232
申请日：2008-12-31
申请人： SYNTAXIN LIMITED , CHADDOCK, John , BEARD, Matthew
发明人： CHADDOCK, John , BEARD, Matthew
IPC分类号： A61K47/48 , A61P1/06 , A61P37/08 , A61P11/00 , A61P35/00 , A61P25/14
CPC分类号： A61K47/6455 , A61K47/64 , A61K47/6415 , A61K47/6435
摘要： The present invention relates to double stranded nucleic acid (dsNA) delivery vehicles comprising a dsNA, and a clostridial endosomal translocation domain. Said delivery vehicle may further comprise a non-cytotoxic protease and/ or a Targeting Moiety (TM). The present invention also provides a method for delivering an RNA guide strand into a target cell, and to the use of a dsNA delivery vehicle for down-regulating mRNAactivity in a target cell. In one embodiment, the RNA guide strand binds to a SNARE mRNA target sequence, which leads to the suppression of SNARE protein expression in the target cell.
摘要翻译：本发明涉及包含dsNA和梭菌内体移位结构域的双链核酸（dsNA）递送运载体。所述递送载体可以进一步包含非细胞毒性蛋白酶和/或靶向部分TM。本发明还提供了将RNA引导链递送到靶细胞中的方法，以及dsNA递送载体用于下调靶细胞中的mRNA活性的用途。在一个实施方案中，RNA指导链结合SNARE mRNA靶序列，其导致靶细胞中SNARE蛋白表达的抑制。

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