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1. 发明申请

US20160159866A1 CLOSTRIDIAL NEUROTOXIN FUSION PROTEINS, PROPEPTIDE FUSIONS, THEIR EXPRESSION, AND USE 审中-公开
标题翻译：封闭神经毒素融合蛋白，丙型肝炎融合蛋白，其表达和用途
公开(公告)号：US20160159866A1
公开(公告)日：2016-06-09
申请号：US14964146
申请日：2015-12-09
申请人： Konstantin Ichtchenko , Edwin Vazquez-Cintron , Philip A. Band , Timothy J. Cardozo
发明人： Konstantin Ichtchenko , Edwin Vazquez-Cintron , Philip A. Band , Timothy J. Cardozo
IPC分类号： C07K14/33
CPC分类号： C07K14/33 , A61K2039/505 , C07K16/1282 , C07K2317/622 , C07K2319/00 , C07K2319/21 , C07K2319/22 , C07K2319/41 , C07K2319/50
摘要： The present invention is directed to a fusion protein comprising a light chain region of a Clostridial neurotoxin and a heavy chain region of a Clostridial neurotoxin, where the light and heavy chain regions are linked by a disulfide bond. The fusion protein also has a single chain antibody positioned upstream of the light chain region, where the single chain antibody possesses antigen-binding activity. Also disclosed are therapeutic agents, treatment methods, propeptide fusions, isolated nucleic acid molecules, expression systems, host cells, and methods of expressing fusion proteins.
摘要翻译：本发明涉及包含梭菌神经毒素的轻链区和梭菌神经毒素的重链区的融合蛋白，其中轻链和重链区通过二硫键连接。融合蛋白还具有位于轻链区域上游的单链抗体，其中单链抗体具有抗原结合活性。还公开了治疗剂，治疗方法，前肽融合物，分离的核酸分子，表达系统，宿主细胞和表达融合蛋白的方法。

2. 发明申请

US20120021002A1 GENETICALLY ENGINEERED CLOSTRIDIAL GENES, PROTEINS ENCODED BY THE ENGINEERED GENES, AND USES THEREOF 有权
标题翻译：遗传工程化遗传基因，工程基因编码的蛋白质及其用途
公开(公告)号：US20120021002A1
公开(公告)日：2012-01-26
申请号：US13252177
申请日：2011-10-03
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K39/08 , A61P37/04 , C07K14/33
CPC分类号： C12N9/52 , A61K39/00 , A61K39/08 , A61K2039/6037 , C07K14/33 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.
摘要翻译：本发明涉及具有轻链区域的轻链和重链区域通过二硫键连接的轻链区域和连接轻链区域和重链区域的中间区域的分离的梭菌神经毒素前肽。还公开了编码梭菌神经毒素前肽的分离的核酸分子。还公开了通过切割梭菌神经毒素前肽，疫苗或解毒剂产生的分离的，生理活性的梭菌神经毒素，以及针对或治疗梭菌神经毒素的毒性作用的方法。还公开了表达重组生理活性梭菌神经毒素的方法。还公开了具有梭菌神经毒素的重链区域和具有治疗功能的蛋白质的嵌合蛋白质。还公开了一种治疗方法。

3. 发明申请

US20100196421A1 GENETICALLY ENGINEERED CLOSTRIDIAL GENES, PROTEINS ENCODED BY THE ENGINEERED GENES, AND USES THEREOF 有权
标题翻译：遗传工程化遗传基因，工程基因编码的蛋白质及其用途
公开(公告)号：US20100196421A1
公开(公告)日：2010-08-05
申请号：US12762909
申请日：2010-04-19
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K39/08 , C12N15/31 , C12N15/63 , C12N5/04 , C12N5/07 , C12N1/21 , C07K2/00 , C07K14/33 , C12P21/00 , A61P37/04
CPC分类号： C12N9/52 , A61K39/00 , A61K39/08 , A61K2039/6037 , C07K14/33 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.
摘要翻译：本发明涉及具有轻链区域的轻链和重链区域通过二硫键连接的轻链区域和连接轻链区域和重链区域的中间区域的分离的梭菌神经毒素前肽。还公开了编码梭菌神经毒素前肽的分离的核酸分子。还公开了通过切割梭菌神经毒素前肽，疫苗或解毒剂产生的分离的，生理活性的梭菌神经毒素，以及针对或治疗梭菌神经毒素的毒性作用的方法。还公开了表达重组生理活性梭菌神经毒素的方法。还公开了具有梭菌神经毒素的重链区域和具有治疗功能的蛋白质的嵌合蛋白质。还公开了一种治疗方法。

4. 发明申请

US20160296608A1 TREATMENT METHODS USING ATOXIC NEUROTOXIN DERIVATIVES 审中-公开
标题翻译：使用过氧化神经毒素衍生物的治疗方法
公开(公告)号：US20160296608A1
公开(公告)日：2016-10-13
申请号：US15130100
申请日：2016-04-15
申请人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
发明人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K38/48 , A61K9/00
CPC分类号： C07K14/001 , A61K9/0019 , A61K38/4893 , C07K14/33 , C07K2319/50 , C12N9/52 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to a treatment method. This method involves contacting a subject with an isolated, physiologically active, atoxic derivative of a Clostridial neurotoxin. Contacting is carried out to treat the subject. The derivative of a Clostridial neurotoxin does not possess a cargo attachment peptide sequence at its N-terminus.
摘要翻译：本发明涉及治疗方法。该方法包括使受试者与梭菌神经毒素的分离的，生理活性的无毒衍生物接触。进行接触治疗对象。梭菌神经毒素的衍生物在其N-末端不具有载体附着肽序列。

5. 发明授权

US08865186B2 Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof 有权
标题翻译：基因工程梭菌基因，由工程基因编码的蛋白质及其用途
公开(公告)号：US08865186B2
公开(公告)日：2014-10-21
申请号：US13252177
申请日：2011-10-03
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K38/00 , C12N9/52 , C07K14/33 , A61K39/08 , A61K39/00
CPC分类号： C12N9/52 , A61K39/00 , A61K39/08 , A61K2039/6037 , C07K14/33 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.
摘要翻译：本发明涉及具有轻链区域的轻链和重链区域通过二硫键连接的轻链区域和连接轻链区域和重链区域的中间区域的分离的梭菌神经毒素前肽。还公开了编码梭菌神经毒素前肽的分离的核酸分子。还公开了通过切割梭菌神经毒素前肽，疫苗或解毒剂产生的分离的，生理活性的梭菌神经毒素，以及针对或治疗梭菌神经毒素的毒性作用的方法。还公开了表达重组生理活性梭菌神经毒素的方法。还公开了具有梭菌神经毒素的重链区域和具有治疗功能的蛋白质的嵌合蛋白质。还公开了一种治疗方法。

6. 发明申请

US20140212456A1 TREATMENT METHODS USING ATOXIC NEUROTOXIN DERIVATIVES 有权
标题翻译：使用过氧化神经毒素衍生物的治疗方法
公开(公告)号：US20140212456A1
公开(公告)日：2014-07-31
申请号：US14166434
申请日：2014-01-28
申请人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
发明人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
IPC分类号： C12N9/52 , C07K14/00
CPC分类号： A61K38/4893 , A61K9/0019 , C07K14/001 , C07K14/33 , C07K2319/50 , C12N9/52 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to a treatment method. This method involves contacting a subject with an isolated, physiologically active, atoxic derivative of a Clostridial neurotoxin. Contacting is carried out to treat the subject. The derivative of a Clostridial neurotoxin does not possess a cargo attachment peptide sequence at its N-terminus.
摘要翻译：本发明涉及治疗方法。该方法包括使受试者与梭菌神经毒素的分离的，生理活性的无毒衍生物接触。进行接触治疗对象。梭菌神经毒素的衍生物在其N-末端不具有载体附着肽序列。

7. 发明授权

US07785606B2 Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof 有权
标题翻译：基因工程梭菌基因，由工程基因编码的蛋白质及其用途
公开(公告)号：US07785606B2
公开(公告)日：2010-08-31
申请号：US11284930
申请日：2005-11-22
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K39/08 , C07K14/33
CPC分类号： C12N9/52 , A61K39/00 , A61K39/08 , A61K2039/6037 , C07K14/33 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.
摘要翻译：本发明涉及具有轻链区域的轻链和重链区域通过二硫键连接的轻链区域和连接轻链区域和重链区域的中间区域的分离的梭菌神经毒素前肽。还公开了编码梭菌神经毒素前肽的分离的核酸分子。还公开了通过切割梭菌神经毒素前肽，疫苗或解毒剂产生的分离的，生理活性的梭菌神经毒素，以及针对或治疗梭菌神经毒素的毒性作用的方法。还公开了表达重组生理活性的梭菌神经毒素的方法。还公开了具有梭菌神经毒素的重链区域和具有治疗功能的蛋白质的嵌合蛋白质。还公开了一种治疗方法。

8. 发明授权

US09315549B2 Treatment methods using atoxic neurotoxin derivatives 有权
标题翻译：使用毒性神经毒素衍生物的治疗方法
公开(公告)号：US09315549B2
公开(公告)日：2016-04-19
申请号：US14166434
申请日：2014-01-28
申请人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
发明人： Edwin J. Vazquez-Cintron , Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61K38/48 , C07K14/00 , C07K14/33 , C12N9/52
CPC分类号： A61K38/4893 , A61K9/0019 , C07K14/001 , C07K14/33 , C07K2319/50 , C12N9/52 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to a treatment method. This method involves contacting a subject with an isolated, physiologically active, atoxic derivative of a Clostridial neurotoxin. Contacting is carried out to treat the subject. The derivative of a Clostridial neurotoxin does not possess a cargo attachment peptide sequence at its N-terminus.
摘要翻译：本发明涉及治疗方法。该方法包括使受试者与梭菌神经毒素的分离的，生理活性的无毒衍生物接触。进行接触治疗对象。梭菌神经毒素的衍生物在其N-末端不具有载体附着肽序列。

9. 发明授权

US08980284B2 Recombinant derivatives of botulinum neurotoxins engineered for trafficking studies and neuronal delivery 有权
标题翻译：用于贩运研究和神经元递送的肉毒杆菌神经毒素的重组衍生物
公开(公告)号：US08980284B2
公开(公告)日：2015-03-17
申请号：US13013518
申请日：2011-01-25
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： C07K1/00 , C07K14/00 , C07K17/00 , A61K39/08 , A61K39/02 , C12N9/52 , C07K14/33 , G01N33/50 , A61K38/00
CPC分类号： C12N9/52 , A61K38/00 , C07K14/33 , C07K2319/02 , C07K2319/036 , C07K2319/50 , G01N33/5058 , G01N2333/33 , Y02A50/469
摘要： This invention relates to isolated Clostridium botulinum propeptides and neurotoxins, isolated nucleic acid molecules encoding Clostridium botulinum propeptides and neurotoxins, methods of expression, treatment methods, and methods of detecting neurotoxin trafficking. The isolated Clostridium botulinum propeptides have a light chain region; a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond; an intermediate region connecting the light and heavy chain regions and comprising a highly specific protease cleavage site; and an S6 peptide sequence according to SEQ ID NO:2 positioned upstream from, but not attached directly to, the N-terminus of the neurotoxin propeptide at the light chain region to enable site specific attachment of cargo.
摘要翻译：本发明涉及分离的肉毒杆菌前肽和神经毒素，编码肉毒杆菌前列腺和神经毒素的分离的核酸分子，表达方法，治疗方法和检测神经毒素运输的方法。分离的肉毒杆菌前肽具有轻链区域; 重链区，其中轻链和重链区通过二硫键连接; 连接轻链区和重链区并包含高度特异性蛋白酶切割位点的中间区; 以及位于轻链区域的位于神经毒素前肽的N-末端上游但不直接附着的SEQ ID NO：2的S6肽序列，以使得能够特异性地附着货物。

10. 发明授权

US08044188B2 Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof 有权
标题翻译：基因工程梭菌基因，由工程基因编码的蛋白质及其用途
公开(公告)号：US08044188B2
公开(公告)日：2011-10-25
申请号：US12762909
申请日：2010-04-19
申请人： Konstantin Ichtchenko , Philip A. Band
发明人： Konstantin Ichtchenko , Philip A. Band
IPC分类号： A61P37/04 , C12N15/31
CPC分类号： C12N9/52 , A61K39/00 , A61K39/08 , A61K2039/6037 , C07K14/33 , C12Y304/24069 , Y02A50/469
摘要： The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.
摘要翻译：本发明涉及具有轻链区域的轻链和重链区域通过二硫键连接的轻链区域和连接轻链区域和重链区域的中间区域的分离的梭菌神经毒素前肽。还公开了编码梭菌神经毒素前肽的分离的核酸分子。还公开了通过切割梭菌神经毒素前肽，疫苗或解毒剂产生的分离的，生理活性的梭菌神经毒素，以及针对或治疗梭菌神经毒素的毒性作用的方法。还公开了表达重组生理活性梭菌神经毒素的方法。还公开了具有梭菌神经毒素的重链区域和具有治疗功能的蛋白质的嵌合蛋白质。还公开了一种治疗方法。

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