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1. 发明申请

US20050158744A1 Surface-bound, unimolecular, double-stranded DNA 审中-公开
标题翻译：表面结合，单分子，双链DNA
公开(公告)号：US20050158744A1
公开(公告)日：2005-07-21
申请号：US10995043
申请日：2004-11-19
申请人： David Lockhart , Dirk Vetter , Martin Diggelmann
发明人： David Lockhart , Dirk Vetter , Martin Diggelmann
IPC分类号： B01J19/00 , C07B61/00 , C07H21/00 , C07K7/06 , C12N15/10 , C12Q1/68 , C12Q1/6811 , C12Q1/6837 , C40B40/06 , G01N33/53 , G01N33/551 , C07H21/02 , A61K48/00
CPC分类号： C12N15/1093 , B01J19/0046 , B01J2219/00529 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00619 , B01J2219/00626 , B01J2219/00635 , B01J2219/00637 , B01J2219/00659 , B01J2219/00722 , C07B2200/11 , C07H21/00 , C07K7/06 , C12Q1/6811 , C12Q1/6837 , C40B40/00 , C40B40/06 , G01N33/5308 , G01N33/551 , C12Q2565/525 , C12Q2525/205
摘要： Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.
摘要翻译：固体支持物上单分子双链寡核苷酸的文库。这些文库在药物发现中可用于筛选许多生物样品，用于双链寡核苷酸与肽，蛋白质，药物和RNA之间的特异性相互作用。在相关方面，本发明提供了在固体支持物上的构象限制探针的文库。使用双链寡核苷酸作为脚手架，探针的运动和灵活性受到限制。探针也可用于与药物发现和诊断相关的各种筛选程序。本发明还提供了制备和筛选上述文库的方法。

2. 发明申请

US20060292579A1 Methods of enzymatic discrimination enhancement and surface bound double-stranded DNA 审中-公开
标题翻译：酶鉴别增强方法和表面结合双链DNA
公开(公告)号：US20060292579A1
公开(公告)日：2006-12-28
申请号：US11176012
申请日：2005-07-05
申请人： David Lockhart , Mark Chee , Dirk Vetter , Martin Digglemann
发明人： David Lockhart , Mark Chee , Dirk Vetter , Martin Digglemann
IPC分类号： C12Q1/68
CPC分类号： C12N15/1093 , B01J19/0046 , B01J2219/00529 , B01J2219/00608 , B01J2219/00612 , B01J2219/00626 , B01J2219/0063 , B01J2219/00659 , B01J2219/00722 , C07B2200/11 , C07H21/00 , C12Q1/6827 , C12Q1/683 , C12Q1/6837 , C12Q1/6874 , C40B40/06 , C40B80/00 , G01N33/5308 , G01N33/551
摘要： Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.
摘要翻译：用于区分完全互补的杂交体与通过一个或多个碱基对不同的那些的方法和在固体支持物上的单分子双链寡核苷酸的文库。在一个实施方案中，本发明提供了使用核酸酶处理来提高高密度寡核苷酸阵列上杂交信号质量的方法。在另一个实施方案中，本发明提供了使用连接反应来提高高密度寡核苷酸阵列上杂交信号质量的方法。在另一个实施方案中，本发明提供了在固体支持物上的单分子或分子间双链寡核苷酸的文库。这些文库在药物发现中可用于筛选许多生物样品，用于双链寡核苷酸与肽，蛋白质，药物和RNA之间的特异性相互作用。在相关方面，本发明提供了在固体支持物上的构象限制探针的文库。使用双链寡核苷酸作为脚手架，探针的运动和灵活性受到限制。探针也可用于与药物发现和诊断相关的各种筛选程序。本发明还提供了制备和筛选上述文库的方法。

3. 发明申请

US20100196279A1 TREATMENT OF GAUCHER DISEASE WITH SPECIFIC PHARMACOLOGICAL CHAPERONES AND MONITORING TREATMENT USING SURROGATE MARKERS 失效
标题翻译：用特定的药物治疗方法治疗高血压病和使用现代标记物进行监测治疗
公开(公告)号：US20100196279A1
公开(公告)日：2010-08-05
申请号：US12595071
申请日：2008-04-11
申请人： David Lockhart
发明人： David Lockhart
IPC分类号： A61K49/00 , A61P43/00
CPC分类号： G01N33/92 , G01N2405/10 , G01N2800/52
摘要： Provided is a method of monitoring the treatment of Gaucher disease with specific pharmacological chaperones using systemic and/or cellular surrogate markers. Also provided is a new biomarker that may be used to monitor the progress of such treatment.
摘要翻译：提供了使用全身和/或细胞代谢标记物来监测具有特定药物伴侣的戈谢病治疗的方法。还提供了可用于监测这种治疗进展的新生物标志物。

4. 发明申请

US20050202500A1 Expression monitoring to high density oligonucleotide arrays 审中-公开
标题翻译：对高密度寡核苷酸阵列的表达监测
公开(公告)号：US20050202500A1
公开(公告)日：2005-09-15
申请号：US11118974
申请日：2005-04-28
申请人： David Lockhart , Eugene Brown , Gordon Wong , Mark Chee , Thomas Gingeras
发明人： David Lockhart , Eugene Brown , Gordon Wong , Mark Chee , Thomas Gingeras
IPC分类号： G01N33/53 , C12N15/09 , C12Q1/68 , G01N15/14 , G01N37/00 , C12P19/34 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6809 , C12Q1/6837 , G01N15/1475 , C12Q2565/507
摘要： This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on surface, where the array comprising more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface, the density of the different oligonucleotides is greater than about 60 different oligonucleotides per 1 cm2, and the olignucleotide probes are complementary to the RNA transcripts or nucleic acids derived from the RNA transcripts; and quantifying the hybridized nucleic acids in the array.
摘要翻译：本发明提供监测多种基因的表达水平的方法。所述方法包括将核酸样品与寡核苷酸探针的高密度阵列杂交，其中高密度阵列含有与核酸样品中靶核酸的子序列互补的寡核苷酸探针。在一个实施方案中，所述方法包括提供包含一个或多个靶基因的RNA转录物或衍生自RNA转录物的核酸的靶核酸库，将所述核酸库与固定在表面上的寡核苷酸探针阵列杂交，其中包含超过100种不同寡核苷酸的阵列和每种不同的寡核苷酸定位在表面的预定区域中，不同寡核苷酸的密度大于每1cm 2大约60个不同的寡核苷酸，并且寡核苷酸探针与衍生自RNA转录物的RNA转录物或核酸互补; 并量化阵列中的杂交核酸。

5. 发明授权

US06705754B2 Device and methods for mixing fluids 有权
标题翻译：混合流体的装置和方法
公开(公告)号：US06705754B2
公开(公告)日：2004-03-16
申请号：US10062431
申请日：2002-01-30
申请人： James L. Winkler , Mark Chee , David Lockhart
发明人： James L. Winkler , Mark Chee , David Lockhart
IPC分类号： B01F1100
CPC分类号： B01J19/28 , B01F9/0021 , B01J2219/00488 , B01J2219/00529 , B01J2219/00596 , B01J2219/00608 , B01J2219/00659 , B01J2219/00722 , C40B40/06 , C40B60/14 , Y10S435/809
摘要： The invention provides exemplary devices, systems and methods for mixing of fluids, such as biological fluids. One exemplary device comprises is particularly adapted for holding at least one cartridge having a chamber containing a biological fluid, with the chamber having a generally planar face. The device comprises a rotatable body having a rotational axis. The rotatable body includes at least one mounting element which is adapted to mount the rotatable body such that the face of the chamber is generally perpendicular to the rotational axis.
摘要翻译：本发明提供了用于混合流体例如生物流体的示例性装置，系统和方法。一个示例性装置包括特别适用于保持具有包含生物流体的腔室的至少一个筒，该腔室具有大致平坦的面。该装置包括具有旋转轴线的可转动体。可旋转主体包括至少一个安装元件，该安装元件适于安装可旋转主体，使得腔室的表面大致垂直于旋转轴线。

6. 发明授权

US06203989B1 Methods and compositions for amplifying detectable signals in specific binding assays 有权
公开(公告)号：US06203989B1
公开(公告)日：2001-03-20
申请号：US09276774
申请日：1999-03-25
申请人： Martin J. Goldberg , Govinda Rao S. Yelagalawadi , Eugene Yuji Tanimoto , Huu Minh Tran , Helin Dong , David Lockhart , Thomas B. Ryder , Janet A. Warrington , Jody Beecher
发明人： Martin J. Goldberg , Govinda Rao S. Yelagalawadi , Eugene Yuji Tanimoto , Huu Minh Tran , Helin Dong , David Lockhart , Thomas B. Ryder , Janet A. Warrington , Jody Beecher
IPC分类号： C12Q168
CPC分类号： C12Q1/682 , C12Q1/6804 , Y10S436/807 , C12Q2565/501 , C12Q2563/131 , C12Q2527/125 , C12Q2563/107 , C12Q2563/125 , C12Q2563/143 , C12Q2537/125
摘要： Methods and compounds are provided for detecting target molecules in a sample using specific binding assays. In particular, methods are provided for detecting a nucleic acid target in a sample. In one embodiment, the method comprises hybridizing a nucleic acid target, comprising a target nucleic acid sequence, to a nucleic acid probe, comprising a probe nucleic acid sequence, wherein the target comprises a binding ligand. The hydridized target is contacted with a receptor comprising multiple sites capable of binding the binding ligand to complex the receptor to the binding ligand, and the receptor is contacted with an amplification reagent, comprising a plurality of the binding ligands, to complex the amplification reagent to the receptor. The presence of the complexed amplification reagent then is detected, for example, by detecting the presence of a detectable label, such as a fluorescent label, for example, on the receptor or the amplification reagent. Optionally, the amplification reagent, comprising a plurality of the binding ligands, is contacted with labeled receptor molecules thereby to complex a plurality of labeled receptor molecules to the amplification reagent, and the labeled receptor molecules complexed to the amplification reagent are detected. This permits the detectable signal to be enhanced and amplified. In one embodiment, the binding ligand is biotin, the receptor is streptavidin, and the amplification reagent is an antibody or a DNA matrix. In another embodiment, an array of different nucleic acid probes immobilized on a surface, each having a defined sequence and location on the surface, may be used in the assays, thus permitting screening and detection of binding of a large number of nucleic acids.

7. 发明授权

US09336382B2 Systems, methods, and apparatus for securing user documents 有权
公开(公告)号：US09336382B2
公开(公告)日：2016-05-10
申请号：US13156045
申请日：2011-06-08
申请人： Brian John Cepuran , Daryl McMillan , David Lockhart , Dariusz Grabka
发明人： Brian John Cepuran , Daryl McMillan , David Lockhart , Dariusz Grabka
IPC分类号： H04L29/06 , G06F21/51
摘要： The invention is directed to systems, methods and apparatus for securing documents. The system comprises a server having a processor and a data storage device for storing documents, at least one document provider connected to the server, the at least one document provider operable to provide user documents to the server for storage in the data storage device, the user documents containing at least one object of security concern, and at least one document consumer connected to the server, the at least one document consumer operable to receive the user documents containing the at least one object of security concern from the server. The processor in the server is operable to determine whether to provide the at least one object of security concern to the at least one document consumer based on at least one security setting, and based on the decision either provide the documents with the at least one object of security concern or provide a replacement documents without the security of concern and an indication on each replacement document that that the at least one object of security concern has been excluded.

8. 发明授权

US07851143B2 Assays for diagnosing and evaluating treatment options for Fabry disease 有权
标题翻译：用于诊断和评估法布里病治疗选择的方法
公开(公告)号：US07851143B2
公开(公告)日：2010-12-14
申请号：US11749512
申请日：2007-05-16
申请人： Christine Kaneski , Sang-Hoon Shin , Gary Murray , Karin Ludwig , David Lockhart , Jeff Castelli
发明人： Christine Kaneski , Sang-Hoon Shin , Gary Murray , Karin Ludwig , David Lockhart , Jeff Castelli
IPC分类号： C12Q1/00 , C12Q1/02 , C12Q1/34
CPC分类号： A61K31/445 , A61K9/0053 , A61K9/48 , A61K31/45 , A61K45/06 , C07D211/46 , G01N33/5094 , G01N2333/924 , G01N2333/94 , G01N2800/04 , G01N2800/52 , A61K2300/00
摘要： Provided are in vitro and in vivo methods for determining whether a patient with Fabry disease will respond to treatment with a specific pharmacological chaperone.
摘要翻译：提供了用于确定法布里病患者是否将以特定药物伴侣的治疗反应的体外和体内方法。

9. 发明申请

US20100266571A1 DOSING REGIMENS FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES USING PHARMACOLOGICAL CHAPERONES 有权
标题翻译：使用药理学治疗治疗体液储存疾病的剂量方案
公开(公告)号：US20100266571A1
公开(公告)日：2010-10-21
申请号：US12597238
申请日：2008-04-28
申请人： David Lockhart , Brandon Wustman
发明人： David Lockhart , Brandon Wustman
IPC分类号： A61K38/47 , A61K31/445 , A61K31/70 , A61K31/713 , A61P25/16 , A61P25/28 , A61P7/06
CPC分类号： A61K31/445 , A61K31/45
摘要： The present invention provides dosing regimens for administering pharmacological chaperones to a subject in need thereof. The dosing regimens can be used to treat disorders caused by improper protein misfolding, such as lysosomal storage disorders.
摘要翻译：本发明提供了用于向有需要的受试者施用药理学伴侣的给药方案。给药方案可用于治疗由不适当的蛋白质错误折叠引起的疾病，例如溶酶体贮积障碍。

10. 发明申请

US20070105093A1 Uncoupling of DNA insert propagation and expression of protein for phage display 有权
标题翻译： DNA插入片段的解偶联和蛋白质的表达用于噬菌体展示
公开(公告)号：US20070105093A1
公开(公告)日：2007-05-10
申请号：US11534527
申请日：2006-09-22
申请人： Pietro Ciceri , Patrick Zarrinkar , Daniel Treiber , David Lockhart
发明人： Pietro Ciceri , Patrick Zarrinkar , Daniel Treiber , David Lockhart
IPC分类号： C40B30/06 , C40B50/06 , C40B40/08 , C40B40/10
CPC分类号： C07H21/04 , C12N15/1037 , C40B40/02
摘要： The present invention provides an advance in phage display technology by permitting the uncoupling of the propagation of phages containing inserted sequences encoding heterologous polypeptides from the expression of said polypeptides. The invention provides phage constructs and methods for their use to permit phage coat protein expression, and thus phage propagation, in the absence of display of heterologous polypeptides, which may be expressed as a fusion with said coat protein in a regulated manner.
摘要翻译：本发明通过允许从所述多肽的表达中分离含有编码异源多肽的插入序列的噬菌体的繁殖来提供噬菌体展示技术的进步。本发明提供了噬菌体构建体和方法，用于在不显示异源多肽的情况下允许噬菌体外壳蛋白表达，从而允许噬菌体扩增，从而可以以调节的方式表达为与所述外壳蛋白的融合。

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