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31. 发明授权

US06417195B1 Isoquinoline derivatives and isoquinoline combinatorial libraries 失效
标题翻译：异喹啉衍生物和异喹啉组合文库
公开(公告)号：US06417195B1
公开(公告)日：2002-07-09
申请号：US09506853
申请日：2000-02-17
申请人： Michal Lebl
发明人： Michal Lebl
IPC分类号： C07D21702
CPC分类号： C07D231/12 , C07B2200/11 , C07D217/26 , C07D233/56 , C07D249/08 , C07D401/12 , C07D401/14 , C07D471/14 , C40B40/00
摘要： The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinoline derivatives as well as novel libraries comprised of such compounds.
摘要翻译：本发明提供了基于异喹啉环的杂环化合物的合成。更具体地，本发明提供了新的异喹啉衍生物以及由这些化合物组成的新型文库。

32. 发明授权

US06127190A Method for producing combinatorial libraries having a predetermined frequency of each species of test compound 失效
标题翻译：制备具有每种试验化合物的预定频率的组合文库的方法
公开(公告)号：US06127190A
公开(公告)日：2000-10-03
申请号：US971775
申请日：1997-11-17
申请人： Michal Lebl
发明人： Michal Lebl
IPC分类号： B01J19/00 , C07B61/00 , C07K1/04 , C40B30/04 , C40B40/10 , C40B60/14 , C40B70/00 , G01N33/543 , G01N33/68 , G01N33/531
CPC分类号： C40B30/04 , B01J19/0046 , C07K1/047 , G01N33/54353 , G01N33/6845 , B01J2219/00315 , B01J2219/00515 , B01J2219/00527 , B01J2219/00545 , B01J2219/00554 , B01J2219/0059 , B01J2219/00592 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00644 , B01J2219/00657 , B01J2219/00659 , B01J2219/00725 , C07B2200/11 , C40B40/10 , C40B60/14 , C40B70/00
摘要： A technique is disclosed for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.
摘要翻译：公开了用于在固相载体上产生非随机组合文库的技术，其中一组预定种类的测试化合物中的每一个存在于预定数量的固相载体上，优选仅在一个固相载体上，并且每个固相载体仅具有一个试验化合物种。预定种类的测试化合物中的每一种都是绝对确定的，因为该技术不采用固相载体的随机分配。相反，该方法基于在其中加入多于一种类型的亚基的每个合成步骤之前逐步分割连续固相支持基质。固相载体的基质的非限制性实例包括聚丙烯膜，聚四氟丙烯膜和棉线。还公开了通过该技术制备的组合库。

33. 发明授权

US5635598A Selectively cleavabe linners based on iminodiacetic acid esters for solid phase peptide synthesis 失效
标题翻译：用于固相肽合成的基于亚氨基二乙酸酯的选择性切割的接头
公开(公告)号：US5635598A
公开(公告)日：1997-06-03
申请号：US263289
申请日：1994-06-21
申请人： Michal Lebl , Viktor Krchnak , Petr Kocis , Kit S. Lam
发明人： Michal Lebl , Viktor Krchnak , Petr Kocis , Kit S. Lam
IPC分类号： A61K38/00 , C07K5/00 , C07K1/04 , A61K38/02
CPC分类号： C07K1/042
摘要： The present invention is directed to linkers based on ester bond linkages, especially iminodiacetic acid ester bond linkages, for use in solid phase peptide synthesis. In particular, the invention is directed to cleavable linkers that can release peptide from the solid phase support under relatively mild conditions by formation of a diketopiperazine or other cyclic structure, such that the cyclic structure remains on the solid phase support, and, in a second cleavage, under more stringent conditions of high pH. The invention is further directed to solid phase supports prepared with multiple cleavable linkers, including a linker that is cleaved by formation of a cyclic product. One such second linker is an ester of hydroxymethylbenzoic acid, or esters formed by carboxy groups of aspartic or glutamic acid.
摘要翻译：本发明涉及用于固相肽合成的基于酯键连接的接头，特别是亚氨基二乙酸酯键键。特别地，本发明涉及可切割的接头，其可以通过形成二酮哌嗪或其它环状结构在相对温和的条件下从固相支持物释放肽，使得环状结构保留在固相载体上，并且在第二在更严格的高pH条件下开裂。本发明还涉及用多个可切割接头制备的固相载体，其包括通过形成环状产物而被切割的连接体。一个这样的第二接头是羟甲基苯甲酸的酯，或由天冬氨酸或谷氨酸的羧基形成的酯。

34. 发明授权

US4483794A Analogs of neurohypophysial hormones 失效
标题翻译：神经体外激素类似物
公开(公告)号：US4483794A
公开(公告)日：1984-11-20
申请号：US493370
申请日：1983-05-10
申请人： Tomislav Barth , Karel Jost , Michal Lebl , Alena Machova , Linda Servitova , Jirina Slaninova
发明人： Tomislav Barth , Karel Jost , Michal Lebl , Alena Machova , Linda Servitova , Jirina Slaninova
IPC分类号： A61K38/00 , C07K7/16 , C07C103/52
CPC分类号： C07K7/16 , A61K38/00 , Y10S514/935 , Y10S930/15 , Y10S930/27
摘要： Analogs of neurohypophysial hormones with inhibition properties are described. The hormones are of the formula ##STR1## wherein in all chiral amino acids are of the L-series and the aromatic amino acid in the position 2, indicated with an asterisk, is of the D-series, and where R.sup.1 and R.sup.2 are hydrogen or a methyl group, R.sup.3 is hydrogen, an amino group, or a triglycylamine grouping, R.sup.4 is hydrogen, a methyl, ethyl or ethoxy group, R.sup.5 is S--CH.sub.2 or S--S group, X.sup.1 is a residue of isoleucine or phenylalanine, X.sup.2 is a residue of leucine or lysine, and X.sup.3 is a glycinamide residue or a hydroxyl group.These compounds exhibit inhibition effects towards the uterotonic and pressor activity of natural hormones. The common structural feature of all these analogues is the presence of an aromatic hydrophobic D-amino acid in the position 2.
摘要翻译：描述了具有抑制性质的神经嗜酸性激素的类似物。激素具有式（IMAGE），其中所有手性氨基酸均为L系列，位置2为芳族氨基酸，以星号表示，为D系列，其中R1和R2为氢或甲基，R 3是氢，氨基或三甘氨酰胺基，R 4是氢，甲基，乙基或乙氧基，R 5是S-CH 2或SS基，X 1是异亮氨酸或苯丙氨酸的残基，X 2是亮氨酸或赖氨酸的残基，X3是甘氨酰胺残基或羟基。这些化合物对天然激素的子宫肌力和加压活性表现出抑制作用。所有这些类似物的常见结构特征是在位置2存在芳族疏水性D-氨基酸。

35. 发明授权

US08394923B2 Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses 有权
标题翻译：用于分离不同密度的液相和氟相有机合成的装置和方法
公开(公告)号：US08394923B2
公开(公告)日：2013-03-12
申请号：US13470130
申请日：2012-05-11
申请人： Michal Lebl
发明人： Michal Lebl
IPC分类号： A61K33/00
CPC分类号： C07K1/045 , B01D17/0202 , B01D17/0217 , B01J19/0046 , B01J2219/00315 , B01J2219/00326 , B01J2219/00351 , B01J2219/00421 , B01J2219/00466 , B01J2219/0049 , B01J2219/005 , B01J2219/00511 , B01J2219/00585 , B01J2219/00596 , B01J2219/00599 , B01J2219/00605 , B01J2219/00621 , B01J2219/00626 , B01J2219/00659 , B01J2219/00689 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B04B5/0407 , B04B5/0421 , C07K1/04 , C40B40/06 , C40B40/10 , C40B50/08 , C40B60/14 , G01N35/028 , G01N2035/00495
摘要： A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.
摘要翻译：公开了一种简单有效的装置和方法，用于分离用于高通量组合有机合成或平行提取大型文库或有机化合物的大量阵列的方法中的不混溶或部分混溶液体层。该装置和方法无论作为组合有机合成或纯化（提取）的自动机器人或手动系统的一部分是有用的。在优选实施例中，公开了用于分离与微量滴定板型阵列的反应容器相容的不混溶或部分可混溶液体的层的装置和方法。发现基于离心的液体去除的另一种应用是在生物测定中进行洗涤或在改性底物上进行合成。

36. 发明申请

US20120129704A1 GENERATION OF UNIFORM FRAGMENTS OF NUCLEIC ACIDS USING PATTERNED SUBSTRATES 有权
标题翻译：使用图案基质生成含有核酸的均质片段
公开(公告)号：US20120129704A1
公开(公告)日：2012-05-24
申请号：US13260205
申请日：2010-04-02
申请人： Kevin Gunderson , Michal Lebl , David L. Heiner
发明人： Kevin Gunderson , Michal Lebl , David L. Heiner
IPC分类号： C12Q1/68 , B01J19/08 , G01N33/50 , C40B20/00 , C07H21/00 , C12P19/34
CPC分类号： C12N15/10 , C12N15/101 , Y10T436/143333
摘要： Methods of generating nucleic acid fragments of substantially uniform length from sample nucleic acids comprising linearly stretching the sample nucleic acids over a substrate having a plurality of cleavage regions separated by relatively consistent distances, cleaving the linearly stretched sample nucleic acids at the cleavage regions, and collecting the resulting nucleic acid fragments. The method may further include collecting and concentrating the resultant nucleic acid fragments of substantially uniform length.
摘要翻译：从样品核酸产生具有基本上均匀长度的核酸片段的方法，包括在具有通过相对一致距离分离的多个切割区域的底物上线性拉伸样品核酸，在切割区域切割线性拉伸的样品核酸，并收集得到的核酸片段。该方法还可以包括收集和浓缩所得到的基本上均匀长度的核酸片段。

37. 发明授权

US07977456B2 Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses 有权
标题翻译：用于分离不同密度的液相和氟相有机合成的装置和方法
公开(公告)号：US07977456B2
公开(公告)日：2011-07-12
申请号：US10838582
申请日：2004-05-03
申请人： Michal Lebl
发明人： Michal Lebl
IPC分类号： A61K38/00
CPC分类号： C07K1/045 , B01D17/0202 , B01D17/0217 , B01J19/0046 , B01J2219/00315 , B01J2219/00326 , B01J2219/00351 , B01J2219/00421 , B01J2219/00466 , B01J2219/0049 , B01J2219/005 , B01J2219/00511 , B01J2219/00585 , B01J2219/00596 , B01J2219/00599 , B01J2219/00605 , B01J2219/00621 , B01J2219/00626 , B01J2219/00659 , B01J2219/00689 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B04B5/0407 , B04B5/0421 , C07K1/04 , C40B40/06 , C40B40/10 , C40B50/08 , C40B60/14 , G01N35/028 , G01N2035/00495
摘要： A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.
摘要翻译：公开了一种简单有效的装置和方法，用于分离用于高通量组合有机合成或平行提取大型文库或有机化合物的大量阵列的方法中的不混溶或部分混溶液体层。该装置和方法无论作为组合有机合成或纯化（提取）的自动机器人或手动系统的一部分是有用的。在优选实施例中，公开了用于分离与微量滴定板型阵列的反应容器相容的不混溶或部分可混溶液体的层的装置和方法。发现基于离心的液体去除的另一种应用是在生物测定中进行洗涤或在改性底物上进行合成。

38. 发明申请

US20110136696A1 CONTINUOUS POLYMER SYNTHESIZER 有权
标题翻译：连续聚合物合成
公开(公告)号：US20110136696A1
公开(公告)日：2011-06-09
申请号：US13029071
申请日：2011-02-16
申请人： David L. Heiner , Aaron C. Jones , Steven P. Fambro , Mark J. Nibbe , Steve R. Burgett , Brett M. Ellman , Michal Lebl
发明人： David L. Heiner , Aaron C. Jones , Steven P. Fambro , Mark J. Nibbe , Steve R. Burgett , Brett M. Ellman , Michal Lebl
IPC分类号： C40B50/00
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/00283 , B01J2219/00315 , B01J2219/00326 , B01J2219/0036 , B01J2219/00423 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00612 , B01J2219/00659 , B01J2219/00675 , B01J2219/00693 , B01J2219/00722 , B01J2219/00725 , C40B60/14 , Y10T436/115831 , Y10T436/12
摘要： Described is a system and method for synthesizing polymeric molecules such as oligonucleotides and polypeptides. The system is capable of continuously synthesizing molecules by providing an array of reaction sites and an array of stations for carrying out synthetic manipulations. The reaction sites in the former array can be placed in a fixed order and at fixed intervals relative to each other. Similarly, the stations can be placed in a fixed order and at fixed intervals relative to each other. The two arrays can be moved relative to each other such that the stations carry out desired steps of a reaction scheme at each reaction site. The relative locations of the stations and the schedule for the relative movement can correlate with the order and duration of reaction steps in the reaction scheme such that once a reaction site has completed a cycle of interacting with the full array of stations then the reaction scheme is complete.
摘要翻译：描述了用于合成聚合物分子如寡核苷酸和多肽的系统和方法。该系统能够通过提供反应位点阵列和用于进行合成操作的站阵列来连续合成分子。前一阵列中的反应位点可以相对于彼此以固定的顺序和固定的间隔放置。类似地，站可以以固定的顺序相对于彼此以固定的间隔放置。两个阵列可以相对于彼此移动，使得站在每个反应位置进行反应方案的期望步骤。站的相对位置和相对运动的时间表可以与反应方案中的反应步骤的顺序和持续时间相关联，使得一旦反应位点完成了与整个站阵列相互作用的循环，则反应方案为完成。

39. 发明申请

US20110072914A1 Flow Cells And Manifolds Having An Electroosmotic Pump 有权
标题翻译：具有电渗泵的流动池和歧管
公开(公告)号：US20110072914A1
公开(公告)日：2011-03-31
申请号：US12031054
申请日：2008-02-14
申请人： Michal Lebl , Dale Buermann , Mark T. Reed , David L. Heiner , Alexander Triener
发明人： Michal Lebl , Dale Buermann , Mark T. Reed , David L. Heiner , Alexander Triener
IPC分类号： G01N1/14 , F04B37/10 , B01L3/02
CPC分类号： F04B19/006 , B01L3/502715 , B01L3/50273 , B01L7/00 , B01L2300/0816 , B01L2300/0877 , B01L2400/0418 , G01N35/00613 , G01N35/1095 , Y10T436/2575
摘要： A flows cell for use in a microfluidic detection system is provided. The flow cell includes a flows cell body having a channel that is configured to convey a solution through the flows cell body. The flow cell also includes a bottom surface and a top surface. The bottom surface is configured to be removably held by the detection system and the top surface is transparent and permits light to pass therethrough. The flow cell body also includes fluidic inlet and outlet ports that are in fluid communication with the channel. A pump cavity is also provided in the flow cell body. The pump cavity fluidly communicates with, and is interposed between, an end of the channel and one of the fluidic inlet and outlet ports. An electroosmotic (EO) pump is held in the pump cavity. The EO pump induces flow of the solution through the EO pump and channel between the fluidic inlet and outlet ports.
摘要翻译：提供了一种用于微流体检测系统的流通池。流动池包括具有通道的流动池主体，该通道被配置为将溶液输送通过流动池主体。流动池还包括底面和顶面。底表面被构造成由检测系统可移除地保持，并且顶表面是透明的并且允许光通过。流动池体还包括与通道流体连通的流体入口和出口。在流动池主体中还设有泵腔。泵腔与通道的端部和流体入口和出口之一流体连通并且介于其间。电渗（EO）泵保持在泵腔中。 EO泵通过EO泵和流体入口和出口之间的通道引起溶液的流动。

40. 发明授权

US06846460B1 Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses 有权
标题翻译：用于分离不同密度的液相和氟相有机合成的装置和方法
公开(公告)号：US06846460B1
公开(公告)日：2005-01-25
申请号：US09493741
申请日：2000-01-28
申请人： Michal Lebl
发明人： Michal Lebl
IPC分类号： B01D17/02 , B01J19/00 , B04B5/04 , C07K1/04 , C40B40/06 , C40B40/10 , C40B50/08 , C40B60/14 , G01N35/00 , G01N35/02 , B01L11/00
CPC分类号： C07K1/045 , B01D17/0202 , B01D17/0217 , B01J19/0046 , B01J2219/00315 , B01J2219/00326 , B01J2219/00351 , B01J2219/00421 , B01J2219/00466 , B01J2219/0049 , B01J2219/005 , B01J2219/00511 , B01J2219/00585 , B01J2219/00596 , B01J2219/00599 , B01J2219/00605 , B01J2219/00621 , B01J2219/00626 , B01J2219/00659 , B01J2219/00689 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B04B5/0407 , B04B5/0421 , C07K1/04 , C40B40/06 , C40B40/10 , C40B50/08 , C40B60/14 , G01N35/028 , G01N2035/00495
摘要： A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.
摘要翻译：公开了一种简单有效的装置和方法，用于分离用于高通量组合有机合成或平行提取大型文库或有机化合物的大量阵列的方法中的不混溶或部分混溶液体层。该装置和方法无论作为组合有机合成或纯化（提取）的自动机器人或手动系统的一部分是有用的。在优选实施例中，公开了用于分离与微量滴定板型阵列的反应容器相容的不混溶或部分可混溶液体的层的装置和方法。发现基于离心的液体去除的另一种应用是在生物测定中进行洗涤或在改性底物上进行合成。

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