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1. 发明申请

US20110130305A1 Novel dyes and compositions, and processes for using same in analysis of protein aggregation and other applications 有权
标题翻译：新型染料和组合物，以及在蛋白质聚集和其他应用分析中使用相同的方法
公开(公告)号：US20110130305A1
公开(公告)日：2011-06-02
申请号：US12592639
申请日：2009-11-30
申请人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlum , Anatoliy Balanda
发明人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlum , Anatoliy Balanda
IPC分类号： C40B40/04 , C07D213/02 , C07D213/04 , C07D277/20 , C07D277/62 , C07D285/06 , C07D471/04 , C07D215/12 , C07D277/60 , C07D251/00 , C07K2/00 , C07K14/00 , C07H21/00 , C12N9/00 , C07K16/00 , C12N1/20 , G01N33/53 , G01N33/554 , G01N33/567 , C07K1/00
CPC分类号： C09B23/145 , C07D401/12 , C09B23/0008 , C09B23/0025 , C09B23/0058 , C09B23/0066 , C09B23/04 , C09B23/06 , C09B23/102 , C09B23/141 , G01N33/582 , G01N33/6845 , G01N2458/30 , G01N2800/2821 , G01N2800/2835
摘要： Provided are dyes and compositions which are useful in a number of applications, such as the detection and monitoring protein aggregation, kinetic studies of protein aggregation, neurofibrillary plaques analysis, evaluation of protein formulation stability, protein thermal stability shift assay and analysis of molecular chaperone activity. These dyes and compositions are also useful as probes in nucleic acid and protein detection.
摘要翻译：提供了可用于许多应用的染料和组合物，例如检测和监测蛋白质聚集，蛋白质聚集的动力学研究，神经原纤维斑块分析，蛋白质制剂稳定性的评估，蛋白质热稳定性转移测定和分子伴侣活性的分析。这些染料和组合物也可用作核酸和蛋白质检测中的探针。

2. 发明授权

US09200033B2 Enzyme-degradable polymer and application thereof 有权
标题翻译：酶可降解聚合物及其应用
公开(公告)号：US09200033B2
公开(公告)日：2015-12-01
申请号：US14119382
申请日：2011-05-24
申请人： Lijun Dai
发明人： Lijun Dai
IPC分类号： A61K31/4353 , A61K31/437 , A61K38/55 , A61K38/03 , A61K47/48 , C12Q1/37 , G01N33/50 , C07K2/00 , A61K9/51 , A61K47/42 , C12Q1/34
CPC分类号： C07K2/00 , A61K9/5146 , A61K47/42 , C12Q1/34
摘要： The present invention belongs to the biomedicine field and specifically concerns an enzyme-degradable polymer and the application thereof. To solve the problem of low sensitivity of the existing assay reagents, the present invention provides an enzyme-degradable polymer and the related application of the polymer. The present invention also provides hydrogels, nano-particles, fluorescent dye-labeled enzyme substrates and kits (packages) for detection or activity-analysis of biological enzymes based on the enzyme-degradable polymer. The formula of the enzyme-degradable polymer is P1-(aa)N-(AA)n-X X=[formula 1] wherein, (aa)N is a non-enzyme substrate domain, the N aa may be different (no correlation), and N is a non-negative integer; (AA)n is an enzyme substrate domain, the n AA may be different, and n is a non-negative integer; P1 is a protecting group of α-amino or functional group; P2 is a protecting group of α-amino; P3 is —NH2, a small molecule compound or a fragment of a polymer.
摘要翻译：本发明属于生物医药领域，具体涉及可降解酶的聚合物及其应用。为了解决现有测定试剂的低灵敏度问题，本发明提供了可降解酶的聚合物和聚合物的相关应用。本发明还提供用于基于酶可降解聚合物的生物酶的检测或活性分析的水凝胶，纳米颗粒，荧光染料标记的酶底物和试剂盒（包装）。酶可降解聚合物的配方为P1-（aa）N-（AA）nX X = [式1]其中（aa）N为非酶底物结构域，N aa可能不同（无相关），N为非负整数; （AA）n是酶底物结构域，n AA可以不同，n是非负整数; P1是α-氨基或官能团的保护基; P2是α-氨基的保护基; P3是-NH2，小分子化合物或聚合物的片段。

3. 发明申请

US20150031046A1 Bioanalytical Reagent used in Heterogeneous Phase and Usage Method Thereof 审中-公开
标题翻译：生物分析试剂用于异相及其使用方法
公开(公告)号：US20150031046A1
公开(公告)日：2015-01-29
申请号：US14119527
申请日：2011-05-24
申请人： Lijun Dai
发明人： Lijun Dai
IPC分类号： G01N33/543 , G01N33/58
CPC分类号： G01N33/54346 , C12Q1/37 , G01N33/5306 , G01N33/542 , G01N33/54306 , G01N33/54353 , G01N33/582
摘要： A bioanalytical reagent used in a heterogeneous phase and a usage method thereof are provided to increase the signal intensity from the bioanalytical reagent. The bioanalytical reagent includes a target detector and a signal generator. The signal generator is represented by the following formula: (p1) y-(a trigger)z-(LS) N-a degradable polymer coupled with a contrast agent in latent state via covalent bonds-p2, wherein p1 is a protecting group for the end group of the trigger, LS is a self-immolative linker or spacer, p2 is a protecting group for the end group of the degradable polymer, y is 0 or 1, and Z, N are non-negative integer. The signal generator is in a latent state during wash and separation procedures, until an inducing matter or a condition, which excites the contrast agent from a latent state to an active state, is added or applied into the analysis system after the separation procedure so as to degrade directly the polymer or to stimulate the triggers in sequence before degrading the polymer. As a result, the detection signal is excited or its intensity is remarkably increased. The bioanalytical reagent used in a heterogeneous phase has high sensitivity and good stability. The bioanalytical reagent used in a heterogeneous phase is employed simply and exactly.
摘要翻译：提供用于异相的生物分析试剂及其使用方法以增加生物分析试剂的信号强度。生物分析试剂包括目标检测器和信号发生器。信号发生器由以下公式表示：（p1）y-（a触发）z-（LS）可降解聚合物通过共价键-P2与潜在状态的对比剂偶联，其中p1是末端的保护基一组触发剂，LS为自褪色接头或间隔基，p2为可降解聚合物端基的保护基，y为0或1，Z，N为非负整数。在洗涤和分离过程中，信号发生器处于潜伏状态，直到在分离过程之后，将激发造影剂从潜在状态到活性状态的诱导物质或条件加入或应用于分析系统中，以便在降解聚合物之前直接降解聚合物或刺激触发剂。结果，检测信号被激发或其强度显着增加。在异相中使用的生物分析试剂具有高灵敏度和良好的稳定性。简单而准确地使用在异相中使用的生物分析试剂。

4. 发明申请

US20130137112A1 DYES FOR ANALYSIS OF PROTEIN AGGREGATION 审中-公开
标题翻译：用于分析蛋白质聚集的染料
公开(公告)号：US20130137112A1
公开(公告)日：2013-05-30
申请号：US13510976
申请日：2010-11-30
申请人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlam , Anatoliy Balanda , Dee Shen
发明人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlam , Anatoliy Balanda , Dee Shen
IPC分类号： C07D401/12
摘要： Provided are dyes and compositions which are useful in a number of applications, such as the detection and monitoring protein aggregation, kinetic studies of protein aggregation, neurofibrillary plaques analysis, evaluation of protein formulation stability, and analysis of molecular chaperone activity.
摘要翻译：提供可用于许多应用的染料和组合物，例如检测和监测蛋白质聚集，蛋白质聚集的动力学研究，神经原纤维斑块分析，蛋白质制剂稳定性的评估和分子伴侣活性的分析。

5. 发明申请

US20090098057A1 SILICA-CORED CARRIER PARTICLE 审中-公开
公开(公告)号：US20090098057A1
公开(公告)日：2009-04-16
申请号：US11872866
申请日：2007-10-16
申请人： Shiying Zheng , Lijun Dai , Ruizheng Wang , Tiecheng A. Qiao , Wenyi Che , William J. Harrison
发明人： Shiying Zheng , Lijun Dai , Ruizheng Wang , Tiecheng A. Qiao , Wenyi Che , William J. Harrison
IPC分类号： A61K49/00 , A61B5/00
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0093
摘要： A nanoparticulate imaging probe with an oxide core, a biocompatible polymeric shell covalently attached to the oxide core, a dye, and a cleavable spacer that covalently binds the dye to the probe. When the spacer is cleaved, the dye is liberated from the probe. The emissions of the dye are quenched when the dye is bound to the probe and not quenched when the dye is liberated from the probe. The spacer can be, for example, a peptide. The oxide core can be, for example, a silicon oxide core.

6. 发明申请

US20070237821A1 Nanogel-based contrast agents for optical molecular imaging 审中-公开
标题翻译：基于Nanogel的光学分子成像造影剂
公开(公告)号：US20070237821A1
公开(公告)日：2007-10-11
申请号：US11401343
申请日：2006-04-10
申请人： Jeffrey Leon , James Bennett , Tiecheng Qiao , John Harder , Thomas Mourey , Gary Slater , Lijun Dai
发明人： Jeffrey Leon , James Bennett , Tiecheng Qiao , John Harder , Thomas Mourey , Gary Slater , Lijun Dai
IPC分类号： A61K9/14
CPC分类号： A61K49/0093 , A61K47/6903 , A61K47/6933 , A61K49/0032 , A61K49/0073 , B82Y5/00
摘要： The present invention relates to a nanogel comprising a polymer network of repetitive, crosslinked, ethylenically unsaturated monomers of Formula I: (X)m-(Y)n-(Z)o Formula I wherein X is a water-soluble monomer containing ionic or hydrogen bonding moieties; Y is a water-soluble macromonomer containing repetitive hydrophilic units bound to a polymerizeable ethylenically unsaturated group; Z is a multifunctional crosslinking monomer; m ranges from 50-90 mol %; n ranges from 2-30 mol %; and o range from 1-15 mol % and a method for preparing a nanogel comprising preparing a header composition of a mixture of monomers X, Y, and Z, and a first portion of initiators in water; preparing a reactor composition of a second portion initiators, surfactant, and water; bringing the reactor composition to the polymerization temperature; holding the reactor composition at the polymerization temperature, and adding the header composition to the reactor composition to form a nanogel of Formula I.
摘要翻译：本发明涉及纳米凝胶，其包含式I的重复，交联，烯键式不饱和单体的聚合物网络：<？在线公式描述=“在线式”末端=“铅”→（X）m- （Y）n-（Z）o式I <？in-line-formula description =“In-line Formulas”end =“tail”？>其中X是含有离子或氢键结构部分的水溶性单体; Y是含有与可聚合烯属不饱和基团结合的重复亲水单元的水溶性大分子单体; Z是多功能交联单体; m范围为50-90摩尔％; n范围为2-30mol％; 其范围为1-15mol％，制备纳米凝胶的方法包括制备单体X，Y和Z的混合物的头部组合物和在水中的第一部分引发剂; 制备第二部分引发剂，表面活性剂和水的反应器组合物; 使反应器组成达到聚合温度; 将反应器组合物保持在聚合温度，并将集管组合物加入到反应器组合物中以形成式I的纳米凝胶。

7. 发明申请

US20090169482A1 SILICA-CORED CARRIER PARTICLE 审中-公开
标题翻译：二氧化硅载体颗粒
公开(公告)号：US20090169482A1
公开(公告)日：2009-07-02
申请号：US11930417
申请日：2007-10-31
申请人： Shiying Zheng , Lijun Dai , Ruizheng Wang , Tiecheng A. Qiao , Wenyi Che , William J. Harrison
发明人： Shiying Zheng , Lijun Dai , Ruizheng Wang , Tiecheng A. Qiao , Wenyi Che , William J. Harrison
IPC分类号： A61K49/00
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0093
摘要： A nanoparticulate imaging probe with an oxide core, a biocompatible polymeric shell covalently attached to the oxide core, a dye, and a cleavable spacer that covalently binds the dye to the probe. When the spacer is cleaved, the dye is liberated from the probe. The emissions of the dye are quenched when the dye is bound to the probe and not quenched when the dye is liberated from the probe. The spacer can be, for example, a peptide. The oxide core can be, for example, a silicon oxide core.
摘要翻译：具有氧化物核心，共价连接到氧化物核心的生物相容性聚合物外壳的纳米颗粒成像探针，染料和将染料共价结合到探针上的可切割间隔物。当间隔物被切割时，染料从探针中释放出来。当染料与探针结合时，染料的排放物被淬灭，当染料从探针中释放出来时，染料的发射不被淬灭。间隔物可以是例如肽。氧化物核可以是例如氧化硅芯。

8. 发明授权

US09133343B2 Dyes and compositions, and processes for using same in analysis of protein aggregation and other applications 有权
标题翻译：染料和组合物，以及在蛋白质聚集和其他应用的分析中使用它们的方法
公开(公告)号：US09133343B2
公开(公告)日：2015-09-15
申请号：US12592639
申请日：2009-11-30
申请人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlam , Anatoliy Balanda
发明人： Wayne Forrest Patton , Sergiy M. Yarmoluk , Praveen Pande , Vladyslava Kovalska , Lijun Dai , Kateryna Volkova , Jack Coleman , Mykhaylo Losytskyy , Anthony Ludlam , Anatoliy Balanda
IPC分类号： C07D251/00 , C07D471/00 , C07D213/00 , B01L3/00 , G03C5/00 , C09B23/14 , C07H19/04
CPC分类号： C09B23/145 , C07D401/12 , C09B23/0008 , C09B23/0025 , C09B23/0058 , C09B23/0066 , C09B23/04 , C09B23/06 , C09B23/102 , C09B23/141 , G01N33/582 , G01N33/6845 , G01N2458/30 , G01N2800/2821 , G01N2800/2835
摘要： Provided are dyes and compositions which are useful in a number of applications, such as the detection and monitoring protein aggregation, kinetic studies of protein aggregation, neurofibrillary plaques analysis, evaluation of protein formulation stability, protein thermal stability shift assay and analysis of molecular chaperone activity. These dyes and compositions are also useful as probes in nucleic acid and protein detection.
摘要翻译：提供了可用于许多应用的染料和组合物，例如检测和监测蛋白质聚集，蛋白质聚集的动力学研究，神经原纤维斑块分析，蛋白质制剂稳定性的评估，蛋白质热稳定性转移测定和分子伴侣活性的分析。这些染料和组合物也可用作核酸和蛋白质检测中的探针。

9. 发明申请

US20140243429A1 Enzyme-Degradable Polymer and Application Thereof 有权
标题翻译：酶降解聚合物及其应用
公开(公告)号：US20140243429A1
公开(公告)日：2014-08-28
申请号：US14119382
申请日：2011-05-24
申请人： Lijun Dai
发明人： Lijun Dai
IPC分类号： C07K2/00 , C12Q1/34 , A61K47/42
CPC分类号： C07K2/00 , A61K9/5146 , A61K47/42 , C12Q1/34
摘要： The present invention belongs to the biomedicine field and specifically concerns an enzyme-degradable polymer and the application thereof. To solve the problem of low sensitivity of the existing assay reagents, the present invention provides an enzyme-degradable polymer and the related application of the polymer. The present invention also provides hydrogels, nano-particles, fluorescent dye-labeled enzyme substrates and kits (packages) for detection or activity-analysis of biological enzymes based on the enzyme-degradable polymer. The formula of the enzyme-degradable polymer is P1-(aa)N-(AA)n-X X=[formula 1] wherein, (aa)N is a non-enzyme substrate domain, the N aa may be different (no correlation), and N is a non-negative integer; (AA)n is an enzyme substrate domain, the n AA may be different, and n is a non-negative integer; P1 is a protecting group of α-amino or functional group; P2 is a protecting group of α-amino; P3 is —NH2, a small molecule compound or a fragment of a polymer.
摘要翻译：本发明属于生物医药领域，具体涉及可降解酶的聚合物及其应用。为了解决现有测定试剂的低灵敏度问题，本发明提供了可降解酶的聚合物和聚合物的相关应用。本发明还提供用于基于酶可降解聚合物的生物酶的检测或活性分析的水凝胶，纳米颗粒，荧光染料标记的酶底物和试剂盒（包装）。酶可降解聚合物的配方为P1-（aa）N-（AA）nX X = [式1]其中（aa）N为非酶底物结构域，N aa可能不同（无相关），N为非负整数; （AA）n是酶底物结构域，n AA可以不同，n是非负整数; P1是α-氨基或官能团的保护基; P2是α-氨基的保护基; P3是-NH2，小分子化合物或聚合物的片段。

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