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1. 发明授权

US4076420A Apparatus for investigating fast chemical reactions by optical detection 失效
标题翻译：用于通过光学检测来调查快速化学反应的装置
公开(公告)号：US4076420A
公开(公告)日：1978-02-28
申请号：US498816
申请日：1974-08-19
申请人： Leo C. M. De Maeyer , Carl-Roland Rabl , Thomas M. Jovin , Detlev Riesner , Rudolf Rigler , Lutz Bodo Veil , Hans Lehrach
发明人： Leo C. M. De Maeyer , Carl-Roland Rabl , Thomas M. Jovin , Detlev Riesner , Rudolf Rigler , Lutz Bodo Veil , Hans Lehrach
IPC分类号： G01N21/25 , G01N21/27 , G01N21/00 , G01J3/30 , G01N1/10
CPC分类号： G01N21/272 , G01N21/253
摘要： A reaction kinetics measuring system which provides for the application of great variety of reaction initiating methods, as temperature or pressure or electrical field jump methods, mixing methods, flash photolysis method, and combinations of said methods, and for various optical detection methods, as absorption or fluorescence or scattered light or polarized light detection methods. The system features quickly and easily interchangeable optical elements in a number of optical paths, and a multitude of selectively usable measuring cells to adapt the system to the reaction initiating and detection methods used so that reliable and exactly reproducible results are obtained, which are comparable even if obtained under widely differing conditions.
摘要翻译：一种反应动力学测量系统，其提供了多种反应引发方法，如温度或压力或电场跃迁方法，混合方法，闪光光解法和所述方法的组合，并且用于各种光学检测方法，如吸收或荧光或散射光或偏振光检测方法。该系统在许多光路中具有快速且容易的可互换的光学元件，以及多个可选择使用的测量单元，以使系统适应于所使用的反应起始和检测方法，使得获得可靠且精确可重现的结果，甚至可比较如果在广泛不同的条件下获得。

2. 发明申请

US20090035823A1 Ligation-based synthesis of oligonucleotides with block structure 审中-公开
标题翻译：基于连接的具有嵌段结构的寡核苷酸合成
公开(公告)号：US20090035823A1
公开(公告)日：2009-02-05
申请号：US10553104
申请日：2004-04-14
申请人： Aleksey Soldatov , Tatiana Borodina , Hans Lehrach
发明人： Aleksey Soldatov , Tatiana Borodina , Hans Lehrach
IPC分类号： C12P19/34 , C07H21/00
CPC分类号： C12N15/66 , C12N15/10 , C12P19/34
摘要： The present invention relates to a method of producing single-stranded nucleic acid molecules from oligo- or polynucleotides wherein each of said oligo- or polynucleotides has a predefined 5′ or 3′ terminus, comprising the steps of (a) annealing an adaptor oligonucleotide simultaneously or step by step to (aa) a first oligo- or polynucleotide; and (ab) a second oligo- or polynucleotide wherein the 5′-terminus of said adaptor oligonucleotide is complementary in sequence to the 5′ terminus of said first oligo- or polynucleotide and the 3′terminus of said adaptor molecule is complementary in sequence to the 3′ terminus of said second oligo- or polynucleotide; and optionally (a′) simultaneously with or subsequently to step (a) annealing at least one further adaptor oligonucleotide to free termini of said first or second oligonucleotides and to free termini of further oligo- or polynucleotides; (b) optionally filling in gaps between the neighbouring ends of said oligo- or polynucleotides; (c) ligating said oligo- or polynucleotides; and (d) removing said at least one adaptor oligonucleotide. In a preferred embodiment of the method of the invention, said single-stranded nucleic acid molecules represent a collection of nucleic acid molecules wherein either said first or said second oligo- or polynucleotide is invariable in sequence between all members of said collection of nucleic acid molecules.
摘要翻译：本发明涉及从寡核苷酸或多核苷酸产生单链核酸分子的方法，其中所述寡核苷酸或多核苷酸中的每一个具有预定义的5'或3'末端，包括以下步骤：（a）同时对连接寡核苷酸进行退火或（aa）第一寡核苷酸或多核苷酸; 和（ab）第二寡核苷酸或其多核苷酸，其中所述衔接子寡核苷酸的5'-末端与所述第一寡核苷酸和多核苷酸的5'末端的序列互补，并且所述衔接子分子的3'末端是顺序互补的所述第二寡核苷酸或多核苷酸的3'末端; 和任选地（a'）与步骤（a）同时或之后步骤（a）将至少一个另外的接头寡核苷酸退火至所述第一或第二寡核苷酸的游离末端和另外的寡核苷酸或多核苷酸的游离末端; （b）任选地填充所述寡核苷酸或多核苷酸的相邻末端之间的间隙; （c）连接所述寡核苷酸或多核苷酸; 和（d）除去所述至少一种接头寡核苷酸。在本发明方法的优选实施方案中，所述单链核酸分子代表核酸分子的集合，其中所述第一或所述第二寡核苷酸或多核苷酸的序列在所述核酸分子集合的所有成员之间是不变的。

3. 发明授权

US06503710B2 Mutation analysis using mass spectrometry 失效
标题翻译：使用质谱进行突变分析
公开(公告)号：US06503710B2
公开(公告)日：2003-01-07
申请号：US09321005
申请日：1999-05-27
申请人： Ivo Glynne Gut , Kurt Berlin , Doris Lechner , Hans Lehrach
发明人： Ivo Glynne Gut , Kurt Berlin , Doris Lechner , Hans Lehrach
IPC分类号： C07H2104
CPC分类号： C12Q1/6827 , Y10T436/24 , Y10T436/25125 , C12Q2563/167
摘要： The invention presents a method for examining genetic material (deoxyribonucleic acid, DNA) to detect the presence of pre-known mutations, especially single nucleotide polymorphisms (SNP), using mass spectrometry with ionization by matrix-assisted laser desorption (MALDI). The invention uses nucleoside triphosphates with modified sites for the method of primer extension in a duplicating, enzymatic reaction and at least partially removal of primers from the extension product, in combination with product neutralization by chemical treatment of the modified sites, so that the resulting DNA products can be, by using special matrix materials, preferredly ionized in an adduct-free form over other constituents in the reaction solution without any further cleaning. The method is particularly suitable for simultaneous identification of several mutations by multiplexing.
摘要翻译：本发明提出了一种使用通过基质辅助激光解吸（MALDI）电离质谱法检测遗传物质（脱氧核糖核酸，DNA）以检测已知突变，特别是单核苷酸多态性（SNP）的存在的方法。本发明使用具有修饰位点的核苷三磷酸作为引物延伸的方法，在复制，酶促反应中和至少部分地从延伸产物中除去引物，以及通过化学处理修饰位点的产物中和，从而得到的DNA 产品可以通过使用特殊的基质材料，优选以无加合物的形式与反应溶液中的其它组分电离，而无需任何进一步的清洁。该方法特别适用于通过复用同时鉴定几种突变。

4. 发明授权

US09175336B2 Method for differentiation of polynucleotide strands 有权
标题翻译：多核苷酸链分化方法
公开(公告)号：US09175336B2
公开(公告)日：2015-11-03
申请号：US13382673
申请日：2010-07-06
申请人： Aleksey Soldatov , Tatiana Borodina , Hans Lehrach
发明人： Aleksey Soldatov , Tatiana Borodina , Hans Lehrach
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6848 , C12Q1/6853 , C12Q1/6855 , C12Q1/6876 , C12Q2525/117
摘要： Objective of the present invention is to provide a method for keeping of directional information in double-stranded DNA. We suggest to convert polynucleotide into a hybrid double-stranded DNA. One particular strand of this hybrid double-stranded DNA should be synthesised using at least one modified nucleotide. Thus, this particular strand would contain modified nucleotides along the whole length. Density of directional markers would not depend on the length of polynucleotides. Any internal fragments of the hybrid double-stranded DNA would have directional information. When it is necessary the modified strand may be easily degraded or separated from the other strand. It was found that such hybrid double-stranded DNA may be easily generated in a number of molecular biology tasks and may be used for molecular cloning, library preparation and strand separation.
摘要翻译：本发明的目的是提供一种在双链DNA中保持定向信息的方法。我们建议将多核苷酸转化为杂交双链DNA。应该使用至少一个修饰的核苷酸合成该混合双链DNA的一个特定链。因此，该特定链将沿整个长度含有修饰的核苷酸。定向标记的密度不取决于多核苷酸的长度。混合双链DNA的任何内部片段都将具有方向性信息。当需要时，改性链可以容易地从另一条链中降解或分离。发现这样的杂合双链DNA可以容易地在多个分子生物学任务中产生，并且可以用于分子克隆，文库制备和链分离。

5. 发明授权

US07595199B1 Method of detecting amyloid-like fibrils or protein aggregates 失效
标题翻译：检测淀粉样样原纤维或蛋白质聚集体的方法
公开(公告)号：US07595199B1
公开(公告)日：2009-09-29
申请号：US09485005
申请日：1998-07-31
申请人： Erich Wanker , Hans Lehrach , Eberhard Scherzinger , Gillian Bates
发明人： Erich Wanker , Hans Lehrach , Eberhard Scherzinger , Gillian Bates
IPC分类号： G01N1/18
CPC分类号： G01N33/6896 , G01N2333/4709 , Y10T436/105831 , Y10T436/107497 , Y10T436/25125 , Y10T436/25375 , Y10T436/255
摘要： The present invention relates to methods of detecting the presence of detergent- or urea-insoluble amyloid-like fibrils or protein aggregates on filters. Preferably, said fibrils or aggregates are indicative of a disease, preferably of a neurodegenerative disease such as Alzheimer's disease or Huntington's disease. In addition, the present invention relates to inhibitors identified by the method of the invention, to pharmaceutical compositions comprising said inhibitors and to diagnostic compositions useful for the investigation of said amyloid-like fibrils or aggregates.
摘要翻译：本发明涉及在过滤器上检测洗涤剂或尿素不溶性淀粉样样原纤维或蛋白质聚集体的存在的方法。优选地，所述原纤维或聚集体指示疾病，优选神经变性疾病，例如阿尔茨海默病或亨廷顿病。此外，本发明涉及通过本发明的方法鉴定的抑制剂，包含所述抑制剂的药物组合物和用于研究所述淀粉状样原纤维或聚集体的诊断组合物。

6. 发明申请

US20060073564A1 Nucleic acid molecule encoding a (poly)peptide co-segregating in mutated form with Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) 审中-公开
公开(公告)号：US20060073564A1
公开(公告)日：2006-04-06
申请号：US11244302
申请日：2005-10-04
申请人： Leena Peltonen , Johanna Aaltonen , Petra Bjorses , Jaakko Perheentupa , Aarno Palotie , Nina Horelli-Kuitunen , Marie-Laure Yaspo , Hans Lehrach
发明人： Leena Peltonen , Johanna Aaltonen , Petra Bjorses , Jaakko Perheentupa , Aarno Palotie , Nina Horelli-Kuitunen , Marie-Laure Yaspo , Hans Lehrach
IPC分类号： C12P21/06 , C07H21/04 , C07K14/47
CPC分类号： C07K14/4713 , A61K38/00 , A61K48/00
摘要： The present invention relates to a nucleic acid molecule encoding a (poly)peptide co-segregating in mutated form with Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). In addition, the invention relates to a mammalian, preferably murine, homologue of the above nucleic acid molecule. The present invention further relates to a nucleic acid molecule deviating by at least one mutation from the nucleic acid molecule described above wherein said mutation co-segregates with APECED and is an insertion, a deletion, a substitution and/or an inversion, and wherein said mutation further results in a loss or a gain of function of the (poly)peptide encoded by said mutated nucleic acid molecule. Furthermore, the present invention relates to a vector comprising the nucleic acid molecules described above and to a host transformed with said vector. In addition, the present invention relates to a process of recombinantly producing a (poly)peptide encoded by the nucleic acid molecules described above comprising culturing or raising said host and isolating said (poly)peptide from said culture or said host. The present invention further relates to the (poly)peptide encoded by said nucleic acid molecules or produced by the process described above. Additionally, the present invention relates to an antibody that specifically recognizes said (poly)peptides. Moreover, the present invention relates to a method for testing for a carriership for APECED or for a corresponding disease state comprising testing a sample obtained from a prospective patient or from a person suspected of carrying a predisposition for a mutation in the wild-type nucleic acid molecule described above or a mutated form of the (poly)peptide encoded by said mutated nucleic acid molecule in an immuno-assay using the antibody described above.

7. 发明授权

US07005008B2 Reaction vessel 失效
标题翻译：反应容器
公开(公告)号：US07005008B2
公开(公告)日：2006-02-28
申请号：US09883435
申请日：2001-06-18
申请人： Günther Knebel , Lajos Nyársik , Holger Friedrich Heinrich Eickhoff , Hans Lehrach
发明人： Günther Knebel , Lajos Nyársik , Holger Friedrich Heinrich Eickhoff , Hans Lehrach
IPC分类号： C30B35/00 , B01D9/02
CPC分类号： C30B7/00 , B01J19/0046 , B01L3/06 , B01L3/5085 , B01L3/5088 , B01L2300/0829 , C30B29/58 , Y10T117/10 , Y10T117/1016 , Y10T117/1024
摘要： The invention relates to a reaction vessel (1) for producing a sample, in particular a crystal, from a substance in solution or in liquid form, having several reaction chambers (6) each forming a separate gas chamber, consisting of at least one housing part, and each reaction chamber (6) has a reservoir (7) and several reaction areas (8) co-operating therewith, connected to one another and to the reservoir (7) in order to exchange gas. The reservoirs and the reaction areas co-operating with them are disposed immediately adjacent to one another in rows, distributed in a predeterminable, identical manner, these rows running parallel with one another. Each row of reservoirs (7) therefore co-operates with at least one row of reaction areas (8).
摘要翻译：本发明涉及一种用于从溶液或液体形式的物质中生产样品，特别是晶体的反应容器（1），其具有几个反应室（6），每个反应室形成分离的气室，所述反应室由至少一个壳体部分，并且每个反应室（6）具有储存器（7）和与其配合的几个反应区域（8），彼此连接并连接到储存器（7）以便交换气体。储存器和与它们配合的反应区域以彼此相邻的方式彼此直接相邻布置，以可预定的相同方式分布，这些排彼此平行地延伸。因此，每排储存器（7）与至少一排反应区域（8）共同操作。

8. 发明授权

US09335329B2 Diagnostic prediction of rheumatoid arthritis and systemic lupus erythematosus 有权
标题翻译：类风湿关节炎和系统性红斑狼疮的诊断预测
公开(公告)号：US09335329B2
公开(公告)日：2016-05-10
申请号：US13141916
申请日：2009-12-18
申请人： Zoltán Konthur , Hans Lehrach , Karl Skriner
发明人： Zoltán Konthur , Hans Lehrach , Karl Skriner
IPC分类号： G01N33/564 , G01N33/68 , C07K16/44
CPC分类号： G01N33/6875 , C07K16/44 , C07K2317/34 , C07K2317/41 , G01N33/564 , G01N2440/18 , G01N2800/102 , G01N2800/104
摘要： The present invention pertains to a diagnostic assay for the diagnosis of an autoimmune disease. The present invention provides an improved diagnostic assay for the diagnosis of an autoimmune disease, particularly rheumatoid arthritis (RA) and Systemic Lupus Erythematosus (SLE). In particular the invention pertains to a method of determining in a sample of a subject the presence of two or more antibodies comprising the step of determining whether an antibody is present in a sample that specifically recognizes a hnRNP-DL polypeptide or a fragment thereof or a splice variant thereof and the further step of determining whether at least one further antibody is present in the sample that specifically recognizes a at least one other hnRNP polypeptide which is not sequence homologue to said hnRNP-DL polypeptide or fragments thereof or splice variants thereof, and/or said CCP peptide and/or a polypeptide comprising at least the Fc-part of IgG, respectively. The invention also relates to polypeptides, protein sets and antibodies that may be used in such methods and assays and for therapeutic use in RA and SLE patients.
摘要翻译：本发明涉及诊断自身免疫性疾病的诊断方法。本发明提供了用于诊断自身免疫性疾病，特别是类风湿性关节炎（RA）和系统性红斑狼疮（SLE））的改进的诊断测定法。具体地，本发明涉及在受试者样品中测定两种或更多种抗体的存在的方法，其包括确定抗体是否存在于特异性识别hnRNP-DL多肽或其片段的样品中或其剪接变体以及确定样品中是否存在至少一种另外的抗体的步骤，所述另外的抗体特异性识别与所述hnRNP-DL多肽或其片段或其剪接变体不是序列同源物的至少一种其它hnRNP多肽，以及 /或所述CCP肽和/或分别至少包含IgG的Fc-部分的多肽。本发明还涉及可用于这些方法和测定中并用于RA和SLE患者中的治疗用途的多肽，蛋白质组和抗体。

9. 发明申请

US20110311999A1 DIAGNOSTIC PREDICTION OF RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS 有权
标题翻译：湿疹性红斑狼疮和系统性红斑狼疮的诊断预测
公开(公告)号：US20110311999A1
公开(公告)日：2011-12-22
申请号：US13141916
申请日：2009-12-18
申请人： Zoltán Konthur , Hans Lehrach , Karl Skriner
发明人： Zoltán Konthur , Hans Lehrach , Karl Skriner
IPC分类号： G01N33/566 , C07K16/18 , C07K14/435
CPC分类号： G01N33/6875 , C07K16/44 , C07K2317/34 , C07K2317/41 , G01N33/564 , G01N2440/18 , G01N2800/102 , G01N2800/104
摘要： The present invention pertains to a diagnostic assay for the diagnosis of an autoimmune disease. The present invention provides an improved diagnostic assay for the diagnosis of an autoimmune disease, particularly rheumatoid arthritis (RA) and Systemic Lupus Erythematosus (SLE). In particular the invention pertains to a method of determining in a sample of a subject the presence of two or more antibodies comprising the step of determining whether an antibody is present in a sample that specifically recognizes a hnRNP-DL polypeptide or a fragment thereof or a splice variant thereof and the further step of determining whether at least one further antibody is present in the sample that specifically recognizes a at least one other hnRNP polypeptide which is not sequence homologue to said hnRNP-DL polypeptide or fragments thereof or splice variants thereof, and/or said CCP peptide and/or a polypeptide comprising at least the Fc-part of IgG, respectively. The invention also relates to polypeptides, protein sets and antibodies that may be used in such methods and assays and for therapeutic use in RA and SLE patients.
摘要翻译：本发明涉及诊断自身免疫性疾病的诊断方法。本发明提供了用于诊断自身免疫性疾病，特别是类风湿性关节炎（RA）和系统性红斑狼疮（SLE））的改进的诊断测定法。具体地，本发明涉及在受试者样品中测定两种或更多种抗体的存在的方法，其包括确定抗体是否存在于特异性识别hnRNP-DL多肽或其片段的样品中或其剪接变体以及确定样品中是否存在至少一种另外的抗体的步骤，所述另外的抗体特异性识别与所述hnRNP-DL多肽或其片段或其剪接变体不是序列同源物的至少一种其它hnRNP多肽，以及 /或所述CCP肽和/或分别至少包含IgG的Fc-部分的多肽。本发明还涉及可用于这些方法和测定中并用于RA和SLE患者中的治疗用途的多肽，蛋白质组和抗体。

10. 发明申请

US20110191087A1 COMPUTER IMPLEMENTED MODEL OF BIOLOGICAL NETWORKS 审中-公开
标题翻译：计算机实现生物网络的实现模型
公开(公告)号：US20110191087A1
公开(公告)日：2011-08-04
申请号：US13061975
申请日：2009-09-03
申请人： Hans Lehrach , Ralf Herwig , Christoph Wierling
发明人： Hans Lehrach , Ralf Herwig , Christoph Wierling
IPC分类号： G06G7/48
CPC分类号： G16B5/00 , G06F17/10
摘要： The present invention relates to a computer-implemented method of producing a kinetic model of a biological network, the method comprising (a) choosing a network topology, wherein the nodes of said topology represent biological entities and the edges of said topology represent interactions between said entities; (b) assigning kinetic laws and kinetic constants to said interactions; and (c) assigning starting concentrations to said biological entities, wherein (i) one part of said kinetic constants and independently one part of said starting concentrations are experimental data; and (ii) the remaining part of said kinetic constants and independently the remaining part of said starting concentrations are chosen randomly.
摘要翻译：本发明涉及一种生成生物网络的动力学模型的计算机实现的方法，所述方法包括：（a）选择网络拓扑，其中所述拓扑的节点表示生物实体，并且所述拓扑的边缘表示所述实体; （b）为所述相互作用分配动力学规律和动力学常数; 和（c）将起始浓度分配给所述生物实体，其中（i）所述动力学常数的一部分和所述起始浓度的独立一部分是实验数据; 和（ii）所述动力学常数的剩余部分，并且独立地选择所述起始浓度的剩余部分是随机选择的。

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