公开(公告)号：US07846722B2

公开(公告)日：2010-12-07

申请号：US11754046

申请日：2007-05-25

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： C12N5/00 ,  C12N5/02 ,  C12N5/071

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。

公开(公告)号：US20080220456A1

公开(公告)日：2008-09-11

申请号：US11754046

申请日：2007-05-25

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： G01N33/569 ,  C07K14/33 ,  C12N15/31 ,  C12N15/63 ,  C12N5/06 ,  G01N33/554

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。

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。

公开(公告)号：US07998749B2

公开(公告)日：2011-08-16

申请号：US11548411

申请日：2006-10-11

申请人： Marcella A. Gilmore ,  Dudley J. Williams ,  Lance E. Steward ,  Kei Roger Aoki

发明人： Marcella A. Gilmore ,  Dudley J. Williams ,  Lance E. Steward ,  Kei Roger Aoki

IPC分类号： G01N27/76 ,  G01N33/00 ,  C12Q1/68 ,  C12Q1/26 ,  C07H21/04

CPC分类号： G01N33/542

摘要： The present invention provides a method of determining the proximity, or changes in the proximity of two or more molecular features labeled with fluorophores able to undergo DARET. In preferred embodiments the change in proximity of molecular features in a sample is correlated with changes in the fluorescence polarization of the sample, and may be monitored in real time.

摘要翻译： 本发明提供了一种确定两个或多个分子特征的邻近性的变化或方法，所述分子特征用能够进行DARET的荧光团标记。 在优选实施例中，样品中分子特征的接近度的变化与样品的荧光偏振的变化相关，并且可以实时监测。

公开(公告)号：US20100081156A1

公开(公告)日：2010-04-01

申请号：US12604138

申请日：2009-10-22

申请人： Dudley J. Williams ,  Marcella A. Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella A. Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.

摘要翻译： 本发明提供一种通过（a）在适合于梭菌毒素蛋白酶活性的条件下用样品处理包括荧光团的梭菌毒素底物来确定梭菌毒素的存在或活性的方法; 一个胖胖的小组 和含有插入在荧光团和膨化基团之间的切割位点的梭菌毒素识别序列; （b）用平面偏振光激发荧光团; 和（c）确定经处理的底物相对于对照底物的荧光偏振，其中与对照底物的荧光偏振相比，经处理的底物的荧光偏振的变化指示梭菌毒素的存在或活性。

公开(公告)号：US20100081155A1

公开(公告)日：2010-04-01

申请号：US12604059

申请日：2009-10-22

申请人： Dudley J. Williams ,  Marcella A. Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella A. Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.

公开(公告)号：US07632655B2

公开(公告)日：2009-12-15

申请号：US12125723

申请日：2008-05-22

申请人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37 ,  C12N11/16

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.

公开(公告)号：US07635574B2

公开(公告)日：2009-12-22

申请号：US12125235

申请日：2008-05-22

申请人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37 ,  C12N11/16

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.

公开(公告)号：US07399607B2

公开(公告)日：2008-07-15

申请号：US10948097

申请日：2004-09-22

申请人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37 ,  C12N11/16

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.

摘要翻译： 本发明提供一种通过（a）在适合于梭菌毒素蛋白酶活性的条件下用样品处理包括荧光团的梭菌毒素底物来确定梭菌毒素的存在或活性的方法; 一个胖胖的小组 和含有插入在荧光团和膨化基团之间的切割位点的梭菌毒素识别序列; （b）用平面偏振光激发荧光团; 和（c）确定经处理的底物相对于对照底物的荧光偏振，其中与对照底物的荧光偏振相比，经处理的底物的荧光偏振的变化指示梭菌毒素的存在或活性。

公开(公告)号：US20080305510A1

公开(公告)日：2008-12-11

申请号：US12125723

申请日：2008-05-22

申请人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

发明人： Dudley J. Williams ,  Marcella Gilmore ,  Lance Steward ,  Marc Verhagen ,  Kei Roger Aoki

IPC分类号： C12Q1/37

CPC分类号： G01N33/542 ,  C12N9/52 ,  C12Q1/37 ,  G01N2333/33

摘要： The present invention provides a method of determining the presence or activity of a clostridial toxin by (a) treating with a sample, under conditions suitable for clostridial toxin protease activity, a clostridial toxin substrate which includes a fluorophore; a bulking group; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the fluorophore and the bulking group; (b) exciting the fluorophore with plane polarized light; and (c) determining fluorescence polarization of the treated substrate relative to a control substrate, where a change in fluorescence polarization of the treated substrate as compared to fluorescence polarization of the control substrate is indicative of the presence or activity of the clostridial toxin.