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1. 发明授权

US06211356B1 Metallocene-phosphoramidite conjugates, process for their preparation and their use 失效
标题翻译：茂金属 - 亚磷酰胺共轭物，其制备方法及其用途
公开(公告)号：US06211356B1
公开(公告)日：2001-04-03
申请号：US09029954
申请日：1998-10-21
申请人： Manfred Wiessler , Dagmar Schütte
发明人： Manfred Wiessler , Dagmar Schütte
IPC分类号： C07H2300
CPC分类号： C07H19/10 , C07F17/00 , C07F17/02 , C07H21/00
摘要： The invention concerns metallocene-phosphoramidite conjugates comprising one or a plurality of metallocenes and one or a plurality of phosphoramidites. The invention further concerns a process for preparing the metallocene-phosphoramidite conjugates and their use.
摘要翻译：本发明涉及包含一种或多种金属茂和一种或多种亚磷酰胺的金属茂 - 亚磷酰胺缀合物。本发明还涉及一种制备茂金属 - 亚磷酰胺缀合物的方法及其应用。

2. 发明授权

US09234120B2 Method for applying a first metal onto a second metal, an isolator or semiconductor substrate, and the respective binding units 有权
标题翻译：用于将第一金属施加到第二金属，隔离器或半导体衬底上的方法以及各自的结合单元
公开(公告)号：US09234120B2
公开(公告)日：2016-01-12
申请号：US13813652
申请日：2011-08-12
申请人： Manfred Wiessler , Peter Lorenz , Heinz Fleischhacker , Karola Ursula Fleischhacker , Marlen Fleischhacker , Nadja Fleischhacker , Ranjita Ghosh-Moulick , Sandra Gilles , Dirk Mayer , Andreas Offenhaeusser
发明人： Manfred Wiessler , Peter Lorenz , Heinz Fleischhacker , Ranjita Ghosh-Moulick , Sandra Gilles , Dirk Mayer , Andreas Offenhaeusser
IPC分类号： C09J5/00 , C07D403/04 , C07D403/12 , C07F7/18 , H01L51/00
CPC分类号： C09J5/00 , C07B2200/11 , C07D403/04 , C07D403/12 , C07F7/1804 , H01L51/0022
摘要： The present invention concerns a method for applying a first metal onto a second metal, an isolator or semiconductor substrate by a Diels-Alder reaction, in particular a Diels-Alder reaction with inverse electron demand. The present invention further concerns the binding units L 1960 and F 160.
摘要翻译：本发明涉及通过Diels-Alder反应，特别是具有反电子需求的Diels-Alder反应将第一金属施加到第二金属，隔离器或半导体衬底上的方法。本发明还涉及绑定单元L 1960和F 160。

3. 发明申请

US20150218203A1 MULTIPLE ORTHOGONAL LABELLING OF OLIGONUCLEOTIDES 有权
标题翻译：寡核苷酸的多重正交标记
公开(公告)号：US20150218203A1
公开(公告)日：2015-08-06
申请号：US14342021
申请日：2012-08-31
申请人： Juliane Becker , Andres Jäschke , Ayan Samanta , Manfred Wiessler
发明人： Juliane Becker , Andres Jäschke , Ayan Samanta , Manfred Wiessler
IPC分类号： C07H21/00
CPC分类号： C07H21/00
摘要： In summary, the present invention concerns a method for multiple orthogonal labelling of oligonucleotides, preferably RNA or DNA, by simultaneously performing the inverse Diels-Alder reaction (DAinv) and the copper-catalyzed click reaction (CuAAC), wherein the method is employed in a single step by just adding the different reaction components together and incubating the aqueous reaction mixture preferably for one hour at room temperature. In detail, the reaction components are one or more N3-modified labels, a copper compound, a stabilizing ligand, a reducing agent and one or more electron-deficient label-modified dienes that are added together with an at least double-modified oligonucleotide having one more nucleotides containing one or more N3-reactive groups and one or more electron-rich dienophiles, wherein a terminal alkyne moiety is preferably used as N3-reactive group(s) and a frans-cyclooctene moiety or norbornene is preferably used as electron-rich dienophile(s), more preferably frans-cyclooctene. Therefore, the present invention provides a one-pot method for post-synthetic multiple orthogonal labeling of oligonucleotides, which allows the site-specific introduction of more than one label, preferably of at least two labels into oligonucleotides after solid-phase synthesis, wherein the DAinv takes place on the dienophile modification only and the CuAAC selectively takes place on the N3-reactive group modification.
摘要翻译：总之，本发明涉及通过同时进行反狄尔斯 - 阿尔德反应（DAinv）和铜催化的咔嗒反应（CuAAC）来对寡核苷酸，优选RNA或DNA进行多重正交标记的方法，其中该方法用于通过仅将不同的反应组分加入一起并将该水性反应混合物在室温下温育1小时来进行单步骤。详细地，反应成分是与至少双修饰寡核苷酸一起加入的一种或多种N 3修饰标记，铜化合物，稳定配体，还原剂和一种或多种电子缺陷型标记修饰的二烯，另外还有一个含有一个或多个N 3 - 反应性基团和一个或多个富电子基性亲核体的核苷酸，其中末端炔部分优选用作N 3反应性基团，并且优选使用反式 - 环辛烯部分或降冰片烯作为电子 - 富含亲二烯体，更优选为反式环辛烯。因此，本发明提供了一种用于寡核苷酸的后合成多重正交标记的一锅法，其允许在固相合成之后将多于一个标记，优选至少两个标记的位点特异性引入寡核苷酸，其中 DAinv仅在亲双烯体修饰上发生，CuAAC选择性地发生在N 3反应性基团修饰上。

4. 发明授权

US08552183B2 Process for the covalent coupling of two molecules by means of a diels-alder reaction with inverse electron requirement 有权
标题翻译：通过具有反电子需求的狄尔斯 - 阿尔德反应共价偶联两个分子的方法
公开(公告)号：US08552183B2
公开(公告)日：2013-10-08
申请号：US12304982
申请日：2007-06-18
申请人： Manfred Wiessler , Eduard Müller , Peter Lorenz , Christian Kliem , Heinz Fleischhacker
发明人： Manfred Wiessler , Eduard Müller , Peter Lorenz , Christian Kliem , Heinz Fleischhacker
IPC分类号： C07D221/22 , C07D237/26 , C07D491/04 , C07D491/08
CPC分类号： C07D221/22 , C07D237/26 , C07D471/04 , C07D491/04 , C07D491/08
摘要： The present invention relates to a process for linking two molecules by means of a Diels Alder reaction with inverse electron requirement (DARinv), comprising the following steps: reaction of a (a) triazine or tetrazine with one or more electron-attracting substituents on the ring as a diene component, the electron-attracting substituents being selected from: COOR C(O)NR2 CX3 (X=halogen) halogen CN SO2—R or SO3—R PR2 wherein R═H, alkyl, aryl, heterocycle, which in turn may be substituted, where appropriate, with alkyl, OH, SH, halogen, aryl, heterocycle, nitro, carboxyamido or amine group. —heterocyclic rings having 1, 2 or 3 N, O or S atoms with a ring size of 5 or 6 ring members, which are substituted with at least one carboxyl, sulfonic acid or phosphone group with (b) an isolated double bond or triple bond in a (hetero)carbocyclic ring or an isolated olefinic double bond or triple bond in a linear or branched hydrocarbon chain which may also contain heteroatoms, where appropriate, as a dienophile component.
摘要翻译：本发明涉及通过Diels Alder反应与反电子需求（DARinv）连接两个分子的方法，包括以下步骤：（a）三嗪或四嗪与一种或多种吸电子取代基的反应环作为二烯成分，电子吸引取代基选自：COOR C（O）NR 2 CX 3（X =卤素）卤素CN SO 2 -R或SO 3 -R PR 2，其中R = H，烷基，芳基，杂环，其中在适当的情况下，可以用烷基，OH，SH，卤素，芳基，杂环，硝基，羧酰胺基或胺基取代。 - 杂环，其具有1,2或3个N，O或S原子，环的大小为5或6个环成员，其被至少一个羧基，磺酸或膦基取代，（b）分离的双键或三元组（杂）碳环或在线性或支链烃链中分离的烯属双键或三键键合，其中适当时也可含有杂原子作为亲双烯体组分。

5. 发明申请

US20100016545A1 PROCESS FOR THE COVALENT COUPLING OF TWO MOLECULES BY MEANS OF A DIELS-ALDER REACTION WITH INVERSE ELECTRON REQUIREMENT 有权
标题翻译：通过具有反向电子要求的直接反应的两种分子的共价偶联方法
公开(公告)号：US20100016545A1
公开(公告)日：2010-01-21
申请号：US12304982
申请日：2007-06-18
申请人： Manfred Wiessler , Eduard Müller , Peter Lorenz , Christian Kliem , Heinz Fleischhacker
发明人： Manfred Wiessler , Eduard Müller , Peter Lorenz , Christian Kliem , Heinz Fleischhacker
IPC分类号： C07D257/08 , C07D253/07 , C07D487/04 , C07D491/048 , C07D237/26 , C07K2/00 , C07H21/00 , A61K47/48
CPC分类号： C07D221/22 , C07D237/26 , C07D471/04 , C07D491/04 , C07D491/08
摘要： The present invention relates to a process for linking two molecules by means of a Diels Alder reaction with inverse electron requirement (DARinv), comprising the following steps: reaction of a (a) triazine or tetrazine with one or more electron-attracting substituents on the ring as a diene component, the electron-attracting substituents being selected from: COOR C(O)NR2 CX3 (X=halogen) halogen CN SO2—R or SO3—R PR2 wherein R═H, alkyl, aryl, heterocycle, which in turn may be substituted, where appropriate, with alkyl, OH, SH, halogen, aryl, heterocycle, nitro, carboxyamido or amine group. —heterocyclic rings having 1, 2 or 3 N, O or S atoms with a ring size of 5 or 6 ring members, which are substituted with at least one carboxyl, sulfonic acid or phosphone group with (b) an isolated double bond or triple bond in a (hetero)carbocyclic ring or an isolated olefinic double bond or triple bond in a linear or branched hydrocarbon chain which may also contain heteroatoms, where appropriate, as a dienophile component.
摘要翻译：本发明涉及通过Diels Alder反应与反电子需求（DARinv）连接两个分子的方法，包括以下步骤：（a）三嗪或四嗪与一种或多种吸电子取代基的反应环作为二烯成分，电子吸引取代基选自：COOR C（O）NR 2 CX 3（X =卤素）卤素CN SO 2 -R或SO 3 -R PR 2其中RH，烷基，芳基，杂环，其又可以在适当的情况下，被烷基，OH，SH，卤素，芳基，杂环，硝基，羧酰胺基或胺基取代。 - 杂环，其具有1,2或3个N，O或S原子，环的大小为5或6个环成员，其被至少一个羧基，磺酸或膦基取代，（b）分离的双键或三元组（杂）碳环或在线性或支链烃链中分离的烯属双键或三键键合，其中适当时也可含有杂原子作为亲双烯体组分。

6. 发明授权

US06743584B1 Molecular-biological marker for analytical electron microscopy 失效
标题翻译：分子电子显微镜的分子生物学标记
公开(公告)号：US06743584B1
公开(公告)日：2004-06-01
申请号：US09914397
申请日：2002-03-01
申请人： Sabine Bub , Helmut Troester , Karsten Richter , Ansgar Haking , Stefan Raddatz , Manfred Wiessler , Eberhard Spiess , Michael Trendelenburg
发明人： Sabine Bub , Helmut Troester , Karsten Richter , Ansgar Haking , Stefan Raddatz , Manfred Wiessler , Eberhard Spiess , Michael Trendelenburg
IPC分类号： C12Q168
CPC分类号： C12N15/70
摘要： The invention relates to plasmids derived from pBluescript KS(+), which contains more than 1, preferably 2, 7, 14, 21 and 27, respective SK primer elements, and their use in analytical electron microscopy.
摘要翻译：本发明涉及衍生自pBluescript KS（+）的质粒，其含有多于1种，优选2种，7种，14种，21种和27种各自的SK引物元件，以及它们在分析电子显微镜中的应用。

7. 发明授权

US06521604B1 Compounds containing boron for energy-filtering transmission electron microscopy and for boron neutron-capture therapy 失效
标题翻译：含硼的化合物用于能量过滤透射电子显微镜和硼中子捕获治疗
公开(公告)号：US06521604B1
公开(公告)日：2003-02-18
申请号：US09601373
申请日：2000-12-15
申请人： Manfred Wiessler , Helmut Tröster , Stefan Raddatz , Eberhard Spiess , Michael Trendelenburg
发明人： Manfred Wiessler , Helmut Tröster , Stefan Raddatz , Eberhard Spiess , Michael Trendelenburg
IPC分类号： A61K3169
CPC分类号： C07F5/027 , A61K41/0095 , A61K49/0002
摘要： The invention relates to a compound which contains boron and which comprises the following general formula (1) in which Cb represents carborane, R2 and R3, independent of one another, represent a hydrogen atom or an organic radical, and R and R1, independent of one another, represent a hydrogen atom or an organic group, or R and R1 form a carbonyl group with the carbon atom to which they are bound. The invention also relates to a method of producing a compound containing boron and to the application of the same.
摘要翻译：本发明涉及一种含有硼的化合物，它包括下列通式（1），其中Cb代表碳硼烷，R2和R3彼此独立地表示氢原子或有机基团，R和R1彼此独立地表示氢原子或有机基团，或者R 1和R 1与它们所结合的碳原子形成羰基。本发明还涉及含硼化合物的制备方法及其应用。

8. 发明授权

US06489302B1 Saccharide conjugates 失效
标题翻译：糖共轭物
公开(公告)号：US06489302B1
公开(公告)日：2002-12-03
申请号：US08981672
申请日：1998-04-20
申请人： Manfred Wiessler , Konrad Beyreuther
发明人： Manfred Wiessler , Konrad Beyreuther
IPC分类号： A61K3170
CPC分类号： A61K51/0491 , A61K47/54 , A61K47/549 , C07H11/04 , C07H15/18 , Y10S514/885 , Y10S514/904
摘要： This invention relates to a conjugate, comprising a saccharide and one or more therapeutic or diagnostic agents, as well as the use of the conjugate. The conjugate of the present invention may be used for diagnosing cancer or viral diseases. The conjugate of the present invention may also be used to prevent and/or treat neurological diseases.
摘要翻译：本发明涉及包含糖和一种或多种治疗或诊断剂的缀合物，以及缀合物的用途。本发明的缀合物可用于诊断癌症或病毒性疾病。本发明的缀合物也可用于预防和/或治疗神经疾病。

9. 发明授权

US06369109B1 Betulinic acid and derivatives thereof useful for the treatment of neuroectodermal tumor 有权
标题翻译：桦木酸及其衍生物可用于治疗神经外胚层肿瘤
公开(公告)号：US06369109B1
公开(公告)日：2002-04-09
申请号：US09182588
申请日：1998-10-28
申请人： Klaus Michael Debatin , Simone Fulda , Manfred Wiessler , Marek Los , Walter Mier
发明人： Klaus Michael Debatin , Simone Fulda , Manfred Wiessler , Marek Los , Walter Mier
IPC分类号： A61K3120
CPC分类号： A61K31/045 , C07J63/008
摘要： The present invention is, generally, directed to the use of betulinic acid and derivatives thereof for the treatment of neuroectodermal tumors. The present invention is based on the discovery that betulinic acid and its derivatives are potent anti-neuroectodermal agents. As disclosed herein, betulinic acid and its derivatives are useful for the treatment of neuroectodermal tumors, including, due to its distinct mechanism of action, neuroectodermal tumors that are resistant to conventional chemotherapeutical agents. In addition to the new use of known compounds, the invention discloses novel compounds and pharmaceutical compositions for the treatment of neuroectodermal tumors.
摘要翻译：本发明一般涉及桦木酸及其衍生物用于治疗神经外胚层肿瘤的用途。本发明基于桦木酸及其衍生物是有效的抗神经外胚层药物的发现。如本文所公开的，桦木酸及其衍生物可用于治疗神经外胚层肿瘤，包括由于其独特的作用机制，对常规化学治疗剂具有抗性的神经外胚层肿瘤。除了已知化合物的新用途外，本发明还公开了用于治疗神经外胚层肿瘤的新型化合物和药物组合物。

10. 发明授权

US09315537B2 Multiple orthogonal labelling of oligonucleotides 有权
标题翻译：寡核苷酸的多重正交标记
公开(公告)号：US09315537B2
公开(公告)日：2016-04-19
申请号：US14342021
申请日：2012-08-31
申请人： Juliane Becker , Andres Jäschke , Ayan Samanta , Manfred Wiessler
发明人： Juliane Becker , Andres Jäschke , Ayan Samanta , Manfred Wiessler
IPC分类号： C07H19/04 , C07H21/00
CPC分类号： C07H21/00
摘要： In summary, the present invention concerns a method for multiple orthogonal labelling of oligonucleotides, preferably RNA or DNA, by simultaneously performing the inverse Diels-Alder reaction (DAinv) and the copper-catalyzed click reaction (CuAAC), wherein the method is employed in a single step by just adding the different reaction components together and incubating the aqueous reaction mixture preferably for one hour at room temperature. In detail, the reaction components are one or more N3-modified labels, a copper compound, a stabilizing ligand, a reducing agent and one or more electron-deficient label-modified dienes that are added together with an at least double-modified oligonucleotide having one more nucleotides containing one or more N3-reactive groups and one or more electron-rich dienophiles, wherein a terminal alkyne moiety is preferably used as N3-reactive group(s) and a frans-cyclooctene moiety or norbornene is preferably used as electron-rich dienophile(s), more preferably frans-cyclooctene. Therefore, the present invention provides a one-pot method for post-synthetic multiple orthogonal labeling of oligonucleotides, which allows the site-specific introduction of more than one label, preferably of at least two labels into oligonucleotides after solid-phase synthesis, wherein the DAinv takes place on the dienophile modification only and the CuAAC selectively takes place on the N3-reactive group modification.
摘要翻译：总之，本发明涉及通过同时进行反狄尔斯 - 阿尔德反应（DAinv）和铜催化的咔嗒反应（CuAAC）来对寡核苷酸（优选RNA或DNA）进行多重正交标记的方法，其中该方法用于通过仅将不同的反应组分加入一起并将该水性反应混合物在室温下温育1小时来进行单步骤。详细地，反应成分是与至少双修饰寡核苷酸一起加入的一种或多种N 3修饰标记，铜化合物，稳定配体，还原剂和一种或多种电子缺陷型标记修饰的二烯，另外还有一个含有一个或多个N 3 - 反应性基团和一个或多个富电子基性亲核体的核苷酸，其中末端炔部分优选用作N 3反应性基团，并且优选使用反式 - 环辛烯部分或降冰片烯作为电子 - 富含亲二烯体，更优选为反式环辛烯。因此，本发明提供了一种用于寡核苷酸的后合成多重正交标记的一锅法，其允许在固相合成之后将多于一个标记，优选至少两个标记的位点特异性引入寡核苷酸，其中 DAinv仅在亲双烯体修饰上发生，CuAAC选择性地发生在N 3反应性基团修饰上。

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