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公开(公告)号：US08206723B2
公开(公告)日：2012-06-26
申请号：US12416470
申请日：2009-04-01
IPC分类号： C07K14/33
CPC分类号： C07K14/33 , A61K38/00 , Y10S530/825
摘要： Modified neurotoxin comprising neurotoxin including structural modification, wherein the structural modification alters the biological persistence, such as the biological half-life and/or a biological activity of the modified neurotoxin relative to an identical neurotoxin without the structural modification. In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In another embodiment, methods of using the modified neurotoxin to treat conditions include treating various disorders, neuromuscular aliments and pain.
摘要翻译： 包含神经毒素的改性神经毒素包括结构修饰，其中所述结构修饰改变了相对于相同的神经毒素而没有结构修饰的生物学持久性，例如修饰的神经毒素的生物半衰期和/或生物活性。 在一个实施方案中，制备修饰的神经毒素的方法包括使用重组技术。 在另一个实施方案中，使用经修饰的神经毒素治疗病症的方法包括治疗各种疾病，神经肌肉营养和疼痛。
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公开(公告)号：US08053208B2
公开(公告)日：2011-11-08
申请号：US12620400
申请日：2009-11-17
IPC分类号： A61K38/00 , C07K7/00 , C07K14/00 , C07K16/00 , C07K17/00 , C07K5/00 , C12Q1/37 , C12N1/20 , G01N33/533
CPC分类号： C12Q1/37 , C07K14/001 , C07K14/435 , G01N33/56911 , G01N2333/33
摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
摘要翻译： 本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。 本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。
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43.发明授权Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity 有权梭菌毒素活性的发光共振能量转移（LRET）测定公开(公告)号：US08022172B2
公开(公告)日：2011-09-20
申请号：US11752596
申请日：2007-05-23
申请人： Dudley J. Williams , Marcella A. Gilmore , Lance E. Steward , Marc Verhagen , Kei Roger Aoki , Ester Fernandez-Salas
发明人： Dudley J. Williams , Marcella A. Gilmore , Lance E. Steward , Marc Verhagen , Kei Roger Aoki , Ester Fernandez-Salas
IPC分类号： A61K38/00 , C07K7/00 , C07K17/00 , C07K14/00 , C07K16/00 , C07K5/00 , C12N1/20 , C12N11/00 , G01N33/533 , G01N33/554 , G01N33/569
CPC分类号： C12Q1/37 , C07K14/001 , C07K14/435 , G01N33/542 , G01N33/56911 , G01N2333/33
摘要： Clostridial toxin substrates comprising a lanthanide donor complex, an acceptor, and a Clostridial toxin recognition sequence including a cleavage site; methods for determining the activity of a Clostridial toxin from a test sample using such Clostridial toxin substrates; cell compositions comprising such Clostridial toxin substrates and a Clostridial toxin receptor; and methods for determining the activity of a Clostridial toxin from a test sample using such cell compositions.
摘要翻译： 包含镧系元素供体复合物，受体和包含切割位点的梭菌毒素识别序列的梭菌毒素底物; 使用这种梭菌毒素底物从测试样品测定梭菌毒素的活性的方法; 包含这种梭菌毒素底物和梭菌毒素受体的细胞组合物; 以及使用这种细胞组合物从测试样品测定梭菌毒素的活性的方法。
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公开(公告)号：US07811584B2
公开(公告)日：2010-10-12
申请号：US12210770
申请日：2008-09-15
申请人： Lance E. Steward , Ester Fernandez-Salas , Joseph Francis , Shengwen Li , Marcella A. Gilmore , Kei Roger Aoki
发明人： Lance E. Steward , Ester Fernandez-Salas , Joseph Francis , Shengwen Li , Marcella A. Gilmore , Kei Roger Aoki
CPC分类号： A61K38/4886 , C07K14/33 , C07K2319/00 , C07K2319/035 , C07K2319/06
摘要： The present invention is directed to multivalent Clostridial toxin comprising more than one binding domain directed to a cell surface molecule of a target cell. Such modified toxins are useful as therapeutic compositions to prevent exocytosis and secretion by the target cell. Conditions in which such compositions man be useful include, without limitation, disorders of the sensory or motor nervous system, acute or chronic pain, cancer, pancreatitis, hyperhydrosis, glandular disorders, viral infections, cystic fibrosis and the like. The invention is also directed to methods of using and administering such a composition, and methods of treating a given condition using such a composition.
摘要翻译： 本发明涉及包含针对靶细胞的细胞表面分子的多于一个结合结构域的多价梭菌毒素。 这样的修饰毒素可用作治疗组合物，以防止靶细胞的胞吐作用和分泌。 这种组合物可用的条件包括但不限于感觉或运动神经系统的疾病，急性或慢性疼痛，癌症，胰腺炎，超氧化，腺体疾病，病毒感染，囊性纤维变性等。 本发明还涉及使用和施用这种组合物的方法，以及使用这种组合物治疗给定病症的方法。
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45.发明授权Cell compositions useful for cell-based FRET assays for clostridial toxins 有权用于梭菌毒素的基于细胞的FRET测定的细胞组合物公开(公告)号：US07749759B2
公开(公告)日：2010-07-06
申请号：US12192925
申请日：2008-08-15
IPC分类号： C12N5/00
CPC分类号： C07K14/005 , C07K14/33 , C07K14/4702 , C07K14/4725 , C12N2710/16622 , C12N2740/16122 , C12Q1/37
摘要： The present invention provides a method of determining clostridial toxin activity by (a) contacting with a sample a cell containing a clostridial toxin substrate that includes a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the donor fluorophore and the acceptor, where resonance energy transfer is exhibited between the donor fluorophore and the acceptor under the appropriate conditions; (b) exciting the donor fluorophore; and (c) determining resonance energy transfer of the contacted cell relative to a control cell, where a difference in resonance energy transfer of the contacted cell as compared to the control cell is indicative of clostridial toxin activity.
摘要翻译： 本发明提供了一种通过（a）使样品与包含供体荧光团的梭菌毒素底物的细胞接触来测定梭菌毒素活性的方法; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 以及包含介入供体荧光团和受体之间的切割位点的梭菌毒素识别序列，其中在适当条件下在供体荧光团和受体之间显示共振能量转移; （b）激发供体荧光团; 和（c）确定接触细胞相对于对照细胞的共振能量转移，其中与对照细胞相比，所接触的细胞的共振能量转移的差异指示梭菌毒素活性。
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公开(公告)号：US07718766B2
公开(公告)日：2010-05-18
申请号：US12042458
申请日：2008-10-31
CPC分类号： G01N33/582
摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
摘要翻译： 本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。 本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。
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公开(公告)号：US07645570B2
公开(公告)日：2010-01-12
申请号：US12047441
申请日：2008-03-13
CPC分类号： G01N33/56911 , G01N2333/50
摘要： Methods for detecting BoNT/A activity in a sample, methods for screening molecules able to compete with BoNT/A receptor binding, methods for reducing BoNT/A activity in a human and methods of marketing a neurotoxin capable of selectively binding to FGFR3 to a governmental or regional regulatory authority.
摘要翻译： 用于检测样品中BoNT / A活性的方法，用于筛选能够与BoNT / A受体结合竞争的分子的方法，用于降低人类中的BoNT / A活性的方法和将能够选择性结合FGFR3的神经毒素销售给政府的方法 或区域监管机构。
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公开(公告)号：US20090317839A1
公开(公告)日：2009-12-24
申请号：US12545647
申请日：2009-08-21
IPC分类号： G01N33/569
CPC分类号： G01N33/56911 , G01N2333/50
摘要： Methods for detecting BoNT/A activity in a sample, methods for screening molecules able to compete with BoNT/A receptor binding, methods for reducing BoNT/A activity in a human and methods of marketing a neurotoxin capable of selectively binding to FGFR3 to a governmental or regional regulatory authority.
摘要翻译： 用于检测样品中BoNT / A活性的方法，用于筛选能够与BoNT / A受体结合竞争的分子的方法，用于降低人类中的BoNT / A活性的方法和将能够选择性结合FGFR3的神经毒素销售给政府的方法 或区域监管机构。
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公开(公告)号：US20090018081A1
公开(公告)日：2009-01-15
申请号：US12192854
申请日：2008-08-15
申请人： Lance E. Steward , Joseph Francis , Ester Fernandez-Salas , Marcella A. Gilmore , Shengwen Li , J. Oliver Dolly , Kei Roger Aoki
发明人： Lance E. Steward , Joseph Francis , Ester Fernandez-Salas , Marcella A. Gilmore , Shengwen Li , J. Oliver Dolly , Kei Roger Aoki
IPC分类号： A61K38/16 , C07K14/00 , C07K14/655 , C07K16/00 , A61P37/02 , C12N15/64 , C07H21/00 , C12P21/00
CPC分类号： C12N9/52 , C07K14/33 , C07K14/575 , C07K14/57509 , C07K14/635 , C07K14/655 , C07K2319/035 , C07K2319/50 , C07K2319/55
摘要： Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.
摘要翻译： 包含可活化的重组神经毒素和由其衍生的多肽的组合物。 本发明还包括编码这种多肽的核酸，以及制备这种多肽和核酸的方法。
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50.发明申请FRET PROTEASE ASSAYS FOR BOTULINUM SEROTYPE A/E TOXINS 失效用于BOTULINUM SEROTYPE A / E毒素的FRET PROTEASE测定公开(公告)号：US20080146786A1
公开(公告)日：2008-06-19
申请号：US11609189
申请日：2006-12-11
IPC分类号： C07K14/195
CPC分类号： G01N33/582
摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
摘要翻译： 本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。 本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。
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