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1.发明申请Leucine-based motifs and enhanced biological persistence of clostridial neurotoxins 有权基于亮氨酸的图案和增强的梭菌神经毒素的生物持续性公开(公告)号：US20050260230A1
公开(公告)日：2005-11-24
申请号：US10753537
申请日：2004-01-08
IPC分类号： C12N15/09 , A61K38/00 , A61P1/00 , A61P5/00 , A61P21/00 , A61P25/00 , A61P25/04 , A61P27/02 , A61P29/02 , A61P37/00 , C07K14/33 , A61K39/08
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：US20060039929A1
公开(公告)日：2006-02-23
申请号：US11036532
申请日：2005-01-14
申请人： Ester Fernandez-Salas , Lance Steward , Todd Herrington , K. Aoki
发明人： Ester Fernandez-Salas , Lance Steward , Todd Herrington , K. Aoki
CPC分类号： C07K14/33 , A61K38/00 , C07K2319/01 , Y02A50/469 , Y10S530/825
摘要： The present invention relates to a toxin comprising a modified light chain of a botulinum toxin type E, wherein the modified light chain comprises amino acid sequence PFVNKQFN (SEQ ID NO: 144) at the N-terminus, and amino acid sequence xExxxLL (SEQ ID NO: 112) at the C-terminus, wherein x is any amino acid.
摘要翻译： 本发明涉及包含E型肉毒杆菌毒素的修饰轻链的毒素，其中所述修饰的轻链在N-末端包含氨基酸序列PFVNKQFN（SEQ ID NO：144）和氨基酸序列xExxxLL（SEQ ID NO： NO：112），其中x是任何氨基酸。
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公开(公告)号：US20060024331A1
公开(公告)日：2006-02-02
申请号：US10909769
申请日：2004-08-02
申请人： Ester Fernandez-Salas , Lance Steward , Wei-Jen Lin , Kei Aoki , George Sachs
发明人： Ester Fernandez-Salas , Lance Steward , Wei-Jen Lin , Kei Aoki , George Sachs
CPC分类号： C07K14/33 , A61K38/00 , A61K47/64 , C07K2319/03 , C07K2319/10 , C07K2319/50 , C07K2319/55
摘要： The present invention relates to a compound comprising a toxin linked to a translocator. Non-limiting examples of toxins of the present invention are botulimum toxin, butyricum toxin, tetani toxins and the light chains thereof. In some embodiments, the translocator of the present invention comprises a protein transduction domain.
摘要翻译： 本发明涉及包含与易位素连接的毒素的化合物。 本发明的毒素的非限制性实例是肉毒杆菌毒素，丁酸毒素，破伤风毒素及其轻链。 在一些实施方案中，本发明的易位点包含蛋白质转导结构域。
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公开(公告)号：US20080038756A1
公开(公告)日：2008-02-14
申请号：US11780925
申请日：2007-07-20
申请人： Lance Steward , Ester Fernandez-Salas , Kei Aoki
发明人： Lance Steward , Ester Fernandez-Salas , Kei Aoki
IPC分类号： G01N33/569 , C07K14/33 , C12Q1/04
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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5.发明申请LUMINESCENCE RESONANCE ENERGY TRANSFER (LRET) ASSAYS FOR CLOSTRIDIAL TOXIN ACTIVITY 有权光合能力转移（LRET）用于离子毒素活性的测定公开(公告)号：US20070243565A1
公开(公告)日：2007-10-18
申请号：US11752596
申请日：2007-05-23
申请人： Dudley Williams , Marcella Gilmore , Lance Steward , Marc Verhagen , Kei Aoki , Ester Fernandez-Salas
发明人： Dudley Williams , Marcella Gilmore , Lance Steward , Marc Verhagen , Kei Aoki , Ester Fernandez-Salas
IPC分类号： G01N33/554 , C07H19/00 , C12N1/20 , C12N15/00
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：US20080057575A1
公开(公告)日：2008-03-06
申请号：US11570706
申请日：2005-08-03
申请人： Ester Fernandez-Salas , Lance Steward , Ronald Miller , Kei Aoki , Marcella Gilmore , Shengwen Li
发明人： Ester Fernandez-Salas , Lance Steward , Ronald Miller , Kei Aoki , Marcella Gilmore , Shengwen Li
CPC分类号： C07K14/33
摘要： Nucleic acid molecules that comprise modified open reading frames providing increased expression of the encoded active BoNT/A in a heterologous cell, expression constructs and cells comprising such nucleic acid molecules and methods useful for expressing the encoding active BoNT/A from such nucleic acid molecules, expression constructs and cells.
摘要翻译： 包含修饰的开放阅读框的核酸分子提供编码的活性BoNT / A在异源细胞中的表达增加，表达构建体和包含此类核酸分子的细胞以及用于从该核酸分子表达编码活性BoNT / A的方法， 表达构建体和细胞。
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公开(公告)号：US20080032931A1
公开(公告)日：2008-02-07
申请号：US11834068
申请日：2007-08-06
申请人： Lance Steward , Joseph Francis , Ester Fernandez-Salas , Marcella Gilmore , Shengwen Li , J. Dolly , Kei Aoki
发明人： Lance Steward , Joseph Francis , Ester Fernandez-Salas , Marcella Gilmore , Shengwen Li , J. Dolly , Kei Aoki
IPC分类号： A61K38/22 , A61P43/00 , C07H21/00 , C07K14/575 , C12P21/02
CPC分类号： C12N9/52 , C07K1/22 , C07K14/33 , C07K14/68 , C07K14/695 , C07K2319/03 , C07K2319/035 , C07K2319/50
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.
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公开(公告)号：US20080032318A1
公开(公告)日：2008-02-07
申请号：US11780872
申请日：2007-07-20
申请人： Lance Steward , Ester Fernandez-Salas , Kei Aoki
发明人： Lance Steward , Ester Fernandez-Salas , Kei Aoki
IPC分类号： G01N33/569 , C07K14/33 , C12Q1/04
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.
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公开(公告)号：US20080032930A1
公开(公告)日：2008-02-07
申请号：US11832173
申请日：2007-08-01
申请人： Lance Steward , Joseph Francis , Ester Fernandez-Salas , Marcella Gilmore , Shengwen Li , J. Dolly , Kei Aoki
发明人： Lance Steward , Joseph Francis , Ester Fernandez-Salas , Marcella Gilmore , Shengwen Li , J. Dolly , Kei Aoki
CPC分类号： C07K1/22 , C07K14/33 , C07K14/68 , C07K14/695 , C12N9/52
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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10.发明申请CELL-BASED FLUORESCENCE RESONANCE ENERGY TRANSFER (FRET) ASSAYS FOR CLOSTRIDIAL TOXINS 审中-公开基于细胞的荧光共振能量转移（FRET）用于封闭毒素的测定公开(公告)号：US20070122858A1
公开(公告)日：2007-05-31
申请号：US11621212
申请日：2007-01-09
申请人： Ester Fernandez-Salas , Lance Steward , Kei Aoki
发明人： Ester Fernandez-Salas , Lance Steward , Kei Aoki
IPC分类号： G01N33/554 , C12N1/21 , C07K14/705
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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