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1. 发明授权

US07015017B2 Process and agent for instabilizing viral quasi-species-distributions avoiding resistance phenomena 失效
公开(公告)号：US07015017B2
公开(公告)日：2006-03-21
申请号：US10032897
申请日：2001-10-25
申请人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
发明人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12N15/11 , A61K48/00 , A61K2039/525 , C12N7/00 , C12N15/00 , C12N2740/16011 , C12N2795/18111 , Y10T436/143333
摘要： A process for instabilizing viral quasi-species-distributions under avoidance of resistance phenomena by replication of the nucleic acids of the viruses present in the quasi-species-distribution by of a defective replication system, a) whereby the defective replication system has a rate of misincorporation for nucleotides above the rate of misincorporation of the viral wild-type-replication system and, whereby the viruses are replicated by the replication system having the higher rate of misincorporation at least as effectively as it is done by the replication system of the wild-type virus, b) and/or negative influence of the replication of the consensus-sequence (nucleic acid sequence of the wild-type virus) in relation to other replicatable nucleic acids.

2. 发明授权

US06423516B1 Process and agent for instabilizing viral quasi-species-distributions avoiding resistance phenomena 失效
标题翻译：不稳定病毒准物种分布的过程和试剂，避免了阻力现象
公开(公告)号：US06423516B1
公开(公告)日：2002-07-23
申请号：US08362604
申请日：1996-03-22
申请人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
发明人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
IPC分类号： C12P1934
CPC分类号： C12N15/11 , A61K48/00 , A61K2039/525 , C12N7/00 , C12N15/00 , C12N2740/16011 , C12N2795/18111 , Y10T436/143333
摘要： A process for instabilizing viral quasi-species-distributions under avoidance of resistance phenomena by replication of the nucleic acids of the viruses present in the quasi-species-distribution by of a defective replication system, a) whereby the defective replication system has a rate of misincorporation for nucleotides above the rate of misincorporation of the viral wild-type-replication system and, whereby the viruses are replicated by the replication system having the higher rate of misincorporation at least as effectively as it is done by the replication system of the wild-type virus, b) and/or negative influence of the replication of the consensus-sequence (nucleic acid sequence of the wild-type virus) in relation to other replicatable nucleic acids.
摘要翻译：一种通过利用有缺陷的复制系统复制存在于准物种分布中的病毒的核酸来避免抗性现象来阻止病毒准物种分布的方法，其中缺陷复制系统的速率为对于高于病毒野生型复制系统错配的速率的核苷酸的错配，并且其中病毒由具有较高错配率的复制系统复制至少与野生型复制系统的复制系统一样有效地复制，类型病毒，b）和/或共有序列（野生型病毒的核酸序列）相对于其他可重复核酸的复制的负面影响。

3. 发明授权

US5871908A Process for the determination of in vitro amplified nucleic acids 失效
标题翻译：测定体外扩增核酸的方法
公开(公告)号：US5871908A
公开(公告)日：1999-02-16
申请号：US157195
申请日：1993-12-08
申请人： Karsten Henco , Manfred Eigen , Detlev Riesner
发明人： Karsten Henco , Manfred Eigen , Detlev Riesner
IPC分类号： B01L7/00 , C12Q1/68 , C12P19/34
CPC分类号： B01L7/52 , C12Q1/6825 , C12Q1/686
摘要： A process for the qualitative and quantitative determination of at least one in vitro amplified nucleic acid in a sealed reaction chamber,wherein during or subsequent to the amplification of the nucleic acid at least one substance (probe) is present which interacts with the nucleic acid to be detected;wherein spectroscopically measurable parameters of said substance (probe) are subject to variation, creating a measurable signal;wherein the sample to be measured is exposed to the action of a gradient capable of at least partially denaturing nucleic acids;with detection of the measurable parameter undergoing variation through the action of the gradient; andthe entire amplification reaction, including qualitative and quantitative determination, may be carried out in a sealed reaction chamber (measuring compartment) without intermittent opening,permitting to automatically operate the diagnostic method of DNA and RNA amplification in qualitative and quantitative fashion on large series of samples.
摘要翻译： PCT No.PCT / EP93 / 00254 Sec。 371日期：1993年12月8日 102（e）日期1993年12月8日PCT提交1993年2月4日PCT公布。公开号WO93 / 16194 日期1993年8月19日一种在密封反应室中定性和定量测定至少一种体外扩增的核酸的方法，其中在核酸扩增期间或之后存在至少一种物质（探针），其与与待检测的核酸; 其中所述物质（探针）的光谱可测量参数经历变化，产生可测量的信号; 其中要测量的样品暴露于能够至少部分变性核酸的梯度的作用; 通过梯度的作用检测可测量的参数变化; 并且包括定性和定量测定的整个扩增反应可以在密封的反应室（测量室）中进行，而不间断地打开，允许以定性和定量的方式自动操作DNA和RNA扩增的诊断方法样品。

4. 发明授权

US5849545A Substrate material for simultaneously binding genotypic and phenotypic substances 失效
标题翻译：用于同时结合基因型和表型物质的底物材料
公开(公告)号：US5849545A
公开(公告)日：1998-12-15
申请号：US834834
申请日：1997-04-10
申请人： Karsten Henco , Manfred Eigen
发明人： Karsten Henco , Manfred Eigen
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6834
摘要： Described is a support material that can simultaneously bind both genotypic and phenotypic substances. The respective areas, which can have surface-modifying matter such as anionic exchangers and/or affinity ligands, simultaneously bind, for example, nucleic acids and proteins or peptides. The support materials described can be used in processes for evolutive optimization of biopolymers, wherein genotype and phenotype can be bound at the same time so as to furnish them for further analysis.
摘要翻译：描述了可同时结合基因型和表型物质的支持材料。可以具有表面改性物质如阴离子交换剂和/或亲和配体的各个区域同时结合例如核酸和蛋白质或肽。所描述的载体材料可用于生物聚合物的进化优化的方法，其中基因型和表型可以同时结合，以便进一步分析。

5. 发明授权

US5582665A Process for sealing at least one well out of a number of wells provided in a plate for receiving chemical and/or biochemical and/or microbiological substances, and installation for carrying out the process 失效
标题翻译：从用于接收化学和/或生物化学和/或微生物物质的板中提供的多个孔中的至少一个孔密封的方法，以及用于进行该过程的装置
公开(公告)号：US5582665A
公开(公告)日：1996-12-10
申请号：US378925
申请日：1995-01-25
申请人： Manfred Eigen , Wolfgang Simm
发明人： Manfred Eigen , Wolfgang Simm
IPC分类号： B29C65/00 , B29C65/18 , B65B7/16 , B65B9/04
CPC分类号： B29C65/18 , B29C65/305 , B29C65/7808 , B29C66/112 , B29C66/131 , B29C66/24221 , B29C66/53461 , B29C66/81433 , B29C66/8181 , B29C66/81831 , B29C66/8223 , B29C66/8322 , B29C66/91231 , B29C66/91421 , B29C66/91431 , B29C66/91641 , B65B9/042 , B29C66/71 , B29C66/73113 , B29C66/73365 , B29C66/954 , B29C66/961 , B65B7/165
摘要： A plate having wells therein for receiving chemical substances is provided with a coverplate covering said filled wells. The process for sealing the wells by providing a joining seam running around the wells provides the joining seam such that it has a profiled cross-section in order to increase the contact surface between the plate and the coverplate. To this end a welding die has a front surface provided with projecting profiled regions and being heated to a temperature in the region of the melting point of the coverplate. The welding die is placed on the coverplate means and remains there for a fixed first period. Then the welding die is pressed down through a fixed path and remains in this position for a fixed second period. Removing the welding die from the coverplate is the last step in the process.
摘要翻译：在其中具有用于接收化学物质的孔的板上设置有覆盖所述填充的孔的盖板。通过提供在井周围延伸的连接缝来密封井的过程提供了接合缝，使得其具有成型横截面以增加板和盖板之间的接触表面。为此，焊接模具具有设置有突出型面区域的正面，并被加热到覆盖层熔点区域内的温度。将焊接模具放置在盖板装置上并保持在固定的第一周期。然后，焊接模具通过固定路径被压下，并保持在该位置固定的第二周期。从盖板上取下焊接模具是此过程的最后一步。

6. 发明授权

US07241569B2 Method and a device for the evaluation of biopolymer fitness 有权
标题翻译：用于评估生物聚合物适应性的方法和装置
公开(公告)号：US07241569B2
公开(公告)日：2007-07-10
申请号：US10435674
申请日：2003-05-12
申请人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
发明人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
IPC分类号： G01N33/543
CPC分类号： G01N21/6452 , C12Q1/04 , C12Q1/6827 , G01N21/64 , G01N21/6402 , G01N21/6408 , G01N21/6428 , G01N21/6458 , G02B21/24 , Y10S435/808 , Y10S436/805 , Y10T436/11 , C12Q2565/107 , C12Q2561/113 , C12Q2535/131
摘要： A Method for identifying one or a small number of molecules, especially in a dilution of ≦1 μM, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined.The device which can be preferably used for performing the method according to the invention is a per se known system of microscope optics for laser focusing for fluorescence excitation in a small measuring compartment of a very diluted solution and for imaging the emitted light in the subsequent measurement through confocal imaging wherein at least one system of optics with high numerical aperture of preferably ≧1.2 N.A. is employed, the light quantity is limited by a confocally arranged pinhole aperture in the object plane behind the microscope objective, and the measuring compartment is positioned at a distance of between 0 and 1000 μm from the observation objective.
摘要翻译：使用测量时间<= 500ms的激光激发FCS和要分析的分子的短扩散路径来识别一个或少数分子，特别是稀释度为<=1μM的分子的方法，其中测量在通过确定通过待检测分子的发光测量确定的材料特异性参数，优选<= 10 -14 / 1的小体积单位。可以优选用于执行根据本发明的方法的装置是本身已知的用于在非常稀释的溶液的小测量室中进行荧光激发的激光聚焦的显微镜光学系统，并且用于在后续测量中对发射的光进行成像通过共焦成像，其中使用具有优选> = 1.2NA的高数值孔径的至少一个光学系统，光量受到在显微镜物镜后面的物平面中的共同排列的针孔的限制，并且测量室位于与观察目标之间的距离为0至1000μm。

7. 发明授权

US06849461B2 Method and device for the selective withdrawal of components from complex mixtures 失效
标题翻译：从复杂混合物中选择性取出组分的方法和装置
公开(公告)号：US06849461B2
公开(公告)日：2005-02-01
申请号：US08750715
申请日：1995-06-16
申请人： Manfred Eigen , Rudolf Rigler , Karsten Henco
发明人： Manfred Eigen , Rudolf Rigler , Karsten Henco
IPC分类号： B01L3/02 , B67D7/70 , C12M1/26 , G01N15/10 , G01N21/84 , G01N1/14 , G01N21/64 , G01N21/75 , G01N33/15
CPC分类号： B01L3/0268 , C12M33/07 , G01N15/10 , Y10T436/2575
摘要： The method according to the invention permits a selected withdrawal of one or a few molecularly disperse or cellular components of a system, such as molecules, molecular complexes, vesicles, micelles, cells, optionally together with an associated volume element V having a size of 10−9 l≧V≧10−18 l from a larger sample volume. The selected transfer of the sought component to another environment is effected by defining the space and time of withdrawal by means of a signal correlating with the small component to be withdrawn. The method is particularly useful for the withdrawal of non-abundant components the existence of which can be detected in a preceding step by a scanning process. The method is also useful for the withdrawal of per se unidentified components.
摘要翻译：根据本发明的方法允许选择性地撤出系统的一种或几种分子分散或细胞组分，例如分子，分子复合物，囊泡，胶束，细胞，任选地与尺寸为10的相关体积元素V一起 <9> l> = V> = 10 l。所寻求的组件选择的转移到另一环境是通过借助与要撤回的小组件相关联的信号定义撤回的空间和时间来实现的。该方法对于通过扫描过程在前一步骤中可以检测到其存在的非丰富成分是特别有用的。该方法对于本身不确定的组分的撤回也是有用的。

8. 发明授权

US5807677A Method for direct identification of few nucleic acid strands 失效
标题翻译：用于直接鉴定少量核酸链的方法
公开(公告)号：US5807677A
公开(公告)日：1998-09-15
申请号：US574916
申请日：1995-12-19
申请人： Manfred Eigen , Rudolf Rigler
发明人： Manfred Eigen , Rudolf Rigler
IPC分类号： C12N15/09 , C07H21/04 , C12Q1/68 , C07H19/00 , C07H21/02 , C12P19/34
CPC分类号： C12Q1/6816
摘要： A method for the direct identification of few, preferably single nucleic acid strands of a specific target sequence (10) in a test solution comprising the following steps: a) Preparation of a reference solution with a mixture (11) of different, short primers (12, 13, 14) each with a so-called antisense-sequence (a', b', c') complementary to a section (a, b, c) of the target sequence (10), and marked with one or more dye molecules, b) mixture of the reference solution with the test solution and incubation of this mixture (15) under conditions allowing hybridization of the primers (12, 1, 14) with the nucleic acid strands to be identified, and then c) identification of the target sequence (10) in the incubated solution (15) by discriminating few, preferably one of the nucleic acid strands to be identified to which one or more primers (12, 13, 14) have hybridized against the background of the non-hybridized primers (12, 13, 14).
摘要翻译：一种用于直接鉴定测试溶液中特定靶序列（10）的少数优选单个核酸链的方法，包括以下步骤：a）用不同的短引物（11）的混合物（11）制备参考溶液 12，13,14），每个具有与靶序列（10）的部分（a，b，c）互补的所谓的反义序列（a'，b'，c'），并用一个或多个染料分子，b）参考溶液与测试溶液的混合物，并在允许引物（12,1,14）与要鉴定的核酸链杂交的条件下温育该混合物（15），然后c）鉴定通过区分待鉴定的至少一个或多个引物（12,13,14）与非天然存在的背景杂交的一些或多个引物（12,13,14）杂交的核酸链中的一个，优选地是待孵育溶液（15）中的靶序列（10）杂交引物（12,13,14）。

9. 发明授权

US5224536A Thermostatting device 失效
标题翻译：恒温装置
公开(公告)号：US5224536A
公开(公告)日：1993-07-06
申请号：US688491
申请日：1991-05-17
申请人： Manfred Eigen , Hajo Otten , Gunter Bauer
发明人： Manfred Eigen , Hajo Otten , Gunter Bauer
IPC分类号： B01L7/04 , B01L7/00 , G01N35/00 , G05D23/00 , G05D23/19
CPC分类号： B01L7/5255 , B01L7/52 , B01L7/54 , G05D23/192
摘要： Thermostatting device for adjusting the temperature of a sample to any vas within a predetermined temperature range, comprising a main body (12) of good heat-conducting properties which has its first end thermally connected to a first thermostat (14) and its second end thermally connected to a second thermostat (16) that can be set to a temperature different from that of the first thermostat, the main body (12) being sized in such a way that a temperature gradient develops along the main body (12) between these ends, and comprising a sample holder body (22) arranged on the main body (12) for being thermally coupled with the latter at any point between the ends of the main body.
摘要翻译： PCT No.PCT / EP89 / 01387第 371日期1991年5月17日 102（e）日期1991年5月17日PCT提交1989年11月17日PCT公布。出版物WO90 / 05947 日期：1990年5月31日。用于将样品的温度调节到预定温度范围内的任何值的恒温装置，包括具有良好导热性质的主体（12），该主体具有热连接到第一恒温器），其第二端热连接到第二恒温器（16），该第二恒温器可被设定为与第一恒温器的温度不同的温度，主体（12）的尺寸设定成沿着主体形成温度梯度（12），并且包括布置在主体（12）上的样品保持器主体（22），用于在主体的端部之间的任何点处与后者热耦合。

10. 发明授权

US4043559A Educational game 失效
标题翻译：教育游戏
公开(公告)号：US4043559A
公开(公告)日：1977-08-23
申请号：US630793
申请日：1975-11-11
申请人： Manfred Eigen , Winkler, Ruthild
发明人： Manfred Eigen , Winkler, Ruthild
IPC分类号： A63F3/00 , A63F3/02 , A63F3/04 , G09B23/02
CPC分类号： G09B23/02 , A63F3/0457 , A63F2003/00343 , A63F2003/00719 , A63F2003/00744
摘要： An educational game arrangement in which a systematic set of games may be played on a plurality of interrelated templates or game boards. The games played on the boards are aimed at teaching statistical principles, for example, as applied to situations in chemistry, biology, physics and economy, for example. The boards are superimposed on each other within a holding arrangement, and may be easily selected for playing a particular game. The boards or templates are held in predetermined registered position with respect to each other in the holding unit, and a transparent covering plate is positioned over the stack of the game boards. The latter is provided with coordinate markings along their rims, and the selected game board is visible through the transparent cover. The cover has openings or recesses which are arranged to correspond to a coordinate grid formed by the coordinate markings on the templates or game boards. Marking elements in the form of balls, for example, are insertable in the recesses or openings in accordance with predetermined rules dependent on numbers resulting from a toss of dice.
摘要翻译：一种教育游戏装置，其中可以在多个相关联的模板或游戏板上播放系统的游戏。例如，在化学，生物学，物理学和经济学等方面，统计学原理如何应用于教学中的游戏。这些板在保持装置内彼此叠置，并且可以容易地选择用于玩特定游戏。板或模板在保持单元中相对于彼此保持在预定的注册位置，并且透明覆盖板位于游戏板的堆叠之上。后者具有沿其边缘的坐标标记，所选择的游戏板通过透明盖可见。盖具有开口或凹部，其被设置为对应于由模板或游戏板上的坐标标记形成的坐标网格。例如，球的形式的标记元件可根据预先确定的规则被插入到凹槽或开口中，这取决于由骰子折腾而产生的数字。

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