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公开(公告)号：US20140348813A1
公开(公告)日：2014-11-27
申请号：US14166619
申请日：2014-01-28
申请人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
发明人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
CPC分类号： A61K38/465 , A61K9/0019 , A61K31/505 , A61K45/06 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/542 , A61K47/545 , A61K47/60 , C12N9/18 , C12Q1/44 , C12Y301/01084 , G01N2333/918 , A61K2300/00
摘要： Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.
摘要翻译： 提供了包含可卡因酯酶（CocE）和使CocE稳定化合物的组合物。 还提供了热稳定可卡因酯酶的方法。 另外提供了治疗经历可卡因诱导病症的哺乳动物的方法。 还提供了确定化合物是否是蛋白质的热稳定剂的方法。 另外提供了上述用于治疗可卡因诱导病症的组合物的用途。 另外提供了编码具有取代L169K和G173Q的CocE多肽和由该核酸编码的CocE多肽的分离的核酸及其药物组合物。 还提供了该组合物用于制备用于治疗可卡因诱导的病症和用于治疗可卡因诱导病症的药物的用途。
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公开(公告)号：US20110142816A1
公开(公告)日：2011-06-16
申请号：US12667895
申请日：2008-07-10
申请人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
发明人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
CPC分类号： A61K38/465 , A61K9/0019 , A61K31/505 , A61K45/06 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/542 , A61K47/545 , A61K47/60 , C12N9/18 , C12Q1/44 , C12Y301/01084 , G01N2333/918 , A61K2300/00
摘要： Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal under-going a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.
摘要翻译： 提供了包含可卡因酯酶（CocE）和使CocE稳定化合物的组合物。 还提供了热稳定可卡因酯酶的方法。 另外提供了治疗可卡因诱导病症的哺乳动物的方法。 还提供了确定化合物是否是蛋白质的热稳定剂的方法。 另外提供了上述用于治疗可卡因诱导病症的组合物的用途。 另外提供了编码具有取代L169K和G173Q的CocE多肽和由该核酸编码的CocE多肽的分离的核酸及其药物组合物。 还提供了该组合物用于制备用于治疗可卡因诱导的病症和用于治疗可卡因诱导病症的药物的用途。
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公开(公告)号：US08637009B2
公开(公告)日：2014-01-28
申请号：US12667895
申请日：2008-07-10
申请人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
发明人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovich , John J. Tesmer , Remy L. Brim
CPC分类号： A61K38/465 , A61K9/0019 , A61K31/505 , A61K45/06 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/542 , A61K47/545 , A61K47/60 , C12N9/18 , C12Q1/44 , C12Y301/01084 , G01N2333/918 , A61K2300/00
摘要： Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.
摘要翻译： 提供了包含可卡因酯酶（CocE）和使CocE稳定化合物的组合物。 还提供了热稳定可卡因酯酶的方法。 另外提供了治疗经历可卡因诱导病症的哺乳动物的方法。 还提供了确定化合物是否是蛋白质的热稳定剂的方法。 另外提供了上述用于治疗可卡因诱导病症的组合物的用途。 另外提供了编码具有取代L169K和G173Q的CocE多肽和由该核酸编码的CocE多肽的分离的核酸及其药物组合物。 还提供了该组合物用于制备用于治疗可卡因诱导的病症和用于治疗可卡因诱导病症的药物的用途。
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公开(公告)号：US09526786B2
公开(公告)日：2016-12-27
申请号：US14166619
申请日：2014-01-28
申请人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovic , John J. Tesmer , Remy L. Brim
发明人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovic , John J. Tesmer , Remy L. Brim
IPC分类号： A61K47/22 , C12N9/18 , C12N9/16 , A61K31/505 , A61K45/06 , A61K38/46 , A61K47/12 , A61K47/18 , C12Q1/44
CPC分类号： A61K38/465 , A61K9/0019 , A61K31/505 , A61K45/06 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/542 , A61K47/545 , A61K47/60 , C12N9/18 , C12Q1/44 , C12Y301/01084 , G01N2333/918 , A61K2300/00
摘要： Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.
摘要翻译： 提供了包含可卡因酯酶（CocE）和使CocE稳定化合物的组合物。 还提供了热稳定可卡因酯酶的方法。 另外提供了治疗经历可卡因诱导病症的哺乳动物的方法。 还提供了确定化合物是否是蛋白质的热稳定剂的方法。 另外提供了上述用于治疗可卡因诱导病症的组合物的用途。 另外提供了编码具有取代L169K和G173Q的CocE多肽和由该核酸编码的CocE多肽的分离的核酸及其药物组合物。 还提供了该组合物用于制备用于治疗可卡因诱导的病症和用于治疗可卡因诱导病症的药物的用途。
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公开(公告)号：US20170106056A1
公开(公告)日：2017-04-20
申请号：US15390514
申请日：2016-12-25
申请人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovic , John J. Tesmer , Remy L. Brim
发明人： Donald W. Landry , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Joanne MacDonald , Milan N. Stojanovic , John J. Tesmer , Remy L. Brim
CPC分类号： A61K38/465 , A61K9/0019 , A61K31/505 , A61K45/06 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/542 , A61K47/545 , A61K47/60 , C12N9/18 , C12Q1/44 , C12Y301/01084 , G01N2333/918 , A61K2300/00
摘要： Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.
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公开(公告)号：US08318156B2
公开(公告)日：2012-11-27
申请号：US12373510
申请日：2007-07-10
申请人： Donald W Landry , Joanne MacDonald , Shi-Xian Deng , Chang-Guo Zhan , Daquan Gao , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Victor Yang , Mei-Chuan Holden Ko , John J. Tesmer , Tien-Yi Lee , Young Min Kwon
发明人： Donald W Landry , Joanne MacDonald , Shi-Xian Deng , Chang-Guo Zhan , Daquan Gao , James H. Woods , Roger K. Sunahara , Diwahar L. Narasimhan , Victor Yang , Mei-Chuan Holden Ko , John J. Tesmer , Tien-Yi Lee , Young Min Kwon
CPC分类号： C12N9/18 , A61K38/00 , A61K38/465 , C12Y301/01084
摘要： Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.
摘要翻译： 本文公开的本发明的实施方案通常涉及抗可卡因治疗剂。 具体地，本发明的一些实施方案涉及可以防止可卡因在受试者中的有毒和增强作用的高效，耐热和持久的可卡因酯酶（CocE）突变体。 本文提供显示耐热酯酶活性的突变型CocE多肽。 还提供了通过施用突变体CocE处理需要的受试者中可卡因诱导的病症的方法以及候选酯酶多肽的高通量筛选方法。
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公开(公告)号：US08501692B2
公开(公告)日：2013-08-06
申请号：US13515511
申请日：2010-12-14
申请人： Roger K. Sunahara , John J. G. Tesmer , Diwahar Narasimhan , James H. Woods , Mark R. Nance , Elin Edwald
发明人： Roger K. Sunahara , John J. G. Tesmer , Diwahar Narasimhan , James H. Woods , Mark R. Nance , Elin Edwald
CPC分类号： A61K38/465 , C12N9/18 , C12Y301/01084
摘要： The present invention relates to compositions and methods for treating and preventing cocaine addiction. In particular, the present invention provides mutated cocaine esterase proteins for use in treating and preventing cocaine addiction.
摘要翻译： 本发明涉及治疗和预防可卡因成瘾的组合物和方法。 特别地，本发明提供用于治疗和预防可卡因成瘾的突变可卡因酯酶蛋白。
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公开(公告)号：US20130039900A1
公开(公告)日：2013-02-14
申请号：US13515511
申请日：2010-12-14
申请人： Roger K. Sunahara , John J.G. Tesmer , Diwahar Narasimhan , James H. Woods , Mark R. Nance , Elin Edwald
发明人： Roger K. Sunahara , John J.G. Tesmer , Diwahar Narasimhan , James H. Woods , Mark R. Nance , Elin Edwald
CPC分类号： A61K38/465 , C12N9/18 , C12Y301/01084
摘要： The present invention relates to compositions and methods for treating and preventing cocaine addiction. In particular, the present invention provides mutated cocaine esterase proteins for use in treating and preventing cocaine addiction.
摘要翻译： 本发明涉及治疗和预防可卡因成瘾的组合物和方法。 特别地，本发明提供用于治疗和预防可卡因成瘾的突变可卡因酯酶蛋白。
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公开(公告)号：US09695227B2
公开(公告)日：2017-07-04
申请号：US14129100
申请日：2012-06-21
申请人： Jan Steyaert , Els Pardon , Toon Laeremans , Brian Kobilka , Søren Rasmussen , Sebastian Granier , Roger K. Sunahara
发明人： Jan Steyaert , Els Pardon , Toon Laeremans , Brian Kobilka , Søren Rasmussen , Sebastian Granier , Roger K. Sunahara
IPC分类号： C07K16/28 , C07K14/705 , C07K14/47 , C07K14/435 , G01N33/74
CPC分类号： C07K14/705 , C07K14/435 , C07K14/4722 , C07K14/70571 , C07K16/28 , C07K2317/22 , C07K2317/569 , C12N2799/026 , G01N33/74 , G01N2333/726 , G01N2500/02
摘要： The present invention relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present invention relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present invention can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.
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