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1. 发明申请

US20060210982A1 Cleavable assigned molecules and screening method using the same 审中-公开
标题翻译：可拆分的分子和筛选方法使用相同
公开(公告)号：US20060210982A1
公开(公告)日：2006-09-21
申请号：US10543682
申请日：2004-02-02
申请人： Hiroshi Yanagawa , Nobuhide Doi , Tetsuya Nagano , Hideaki Takashima
发明人： Hiroshi Yanagawa , Nobuhide Doi , Tetsuya Nagano , Hideaki Takashima
IPC分类号： C40B40/08
CPC分类号： C40B30/04 , C07K14/00 , C12N15/1075
摘要： A method for screening a nucleic acid library for a nucleic acid encoding a protein that interacts with a target substance, which comprises: the step of producing a library of assigning molecules each comprising a protein and a nucleic acid encoding the protein linked to each other via a linker cleavable under a condition that does not change a nucleotide sequence of the nucleic acid; the step of mixing the library of assigning molecules and the target substance; the step of separating an assigning molecule binding to the target substance; the step of cleaving a linker of the separated assigning molecule under a condition that does not change a nucleotide sequence of the nucleic acid to release the nucleic acid; and the step of collecting the released nucleic acid. By this method, screening for an assigning molecule that specifically binds to a target substance can be conducted with high efficiency.
摘要翻译：一种用于筛选编码与靶物质相互作用的蛋白质的核酸的核酸文库的方法，该方法包括：产生分配分子的文库的步骤，每个分子包含蛋白质和编码相互连接的蛋白质的核酸通过在不改变核酸的核苷酸序列的条件下可切割的接头; 分配分子的文库和目标物质的步骤; 分离与靶物质结合的分配分子的步骤; 在不改变核酸的核苷酸序列以释放核酸的条件下切割分离的分配分子的接头的步骤; 以及收集释放的核酸的步骤。通过该方法，可以高效率地进行与目标物质特异性结合的分配分子的筛选。

2. 发明授权

US07150978B2 Recombinant template used for producing a carboxy-terminal modified protien and a method of producing a carboxy-terminal modified protein 有权
标题翻译：用于制备羧基末端修饰的蛋白质的重组模板和产生羧基末端修饰蛋白质的方法
公开(公告)号：US07150978B2
公开(公告)日：2006-12-19
申请号：US10455453
申请日：2003-06-06
申请人： Hiroshi Yanagawa , Nobuhide Doi , Etsuko Miyamoto , Hideaki Takashima , Rieko Oyama
发明人： Hiroshi Yanagawa , Nobuhide Doi , Etsuko Miyamoto , Hideaki Takashima , Rieko Oyama
IPC分类号： C12P19/30
CPC分类号： C07K1/13 , C12P21/02
摘要： A translation template comprising an ORF region coding for a protein, a 5′ untranslated region comprising a transcription promoter and a translation enhancer and locating on the 5′ side of the ORF region, and a 3′ end region comprising a poly-A sequence and locating on the 3′ side of the ORF region, is expressed in a translation system in the presence of an agent for modifying a C-terminal of a protein, which comprises an acceptor portion having a group capable of binding to a protein through a transpeptidation reaction in a protein translation system and a modifying portion comprising a nonradioactive modifying substance linked to the acceptor portion via a nucleotide linker, to cause protein synthesis and the synthesized protein is purified. Thus, the yield of modified protein in a method of modifying C-terminal of protein is improved and detection of protein interaction based on various intermolecular interaction detection methods is realized at an improved level.
摘要翻译：翻译模板，其包含编码蛋白质的ORF区域，包含转录启动子的5'非翻译区和翻译增强子并且位于ORF区域的5'侧，以及包含poly-A序列的3'末端区域和位于ORF区域的3'侧的表达在翻译系统中，在存在用于修饰蛋白质C末端的试剂的情况下，其包含具有能够通过转肽酶结合蛋白质的基团的受体部分蛋白质翻译系统中的反应和包含通过核苷酸接头与受体部分连接的非放射性修饰物质的修饰部分进行蛋白质合成，合成的蛋白质被纯化。因此，改善蛋白质C-末端修饰方法中的修饰蛋白质的产率得到改善，基于各种分子间相互作用检测方法的蛋白质相互作用的检测得到提高。

3. 发明申请

US20050010028A1 C-terminal modified protein and method for producing the same, modifying agent and translation template used for producing C-terminal modified protein, and method for detecting protein interaction with use of C-terminal modified protein 有权
标题翻译： C-末端修饰蛋白及其制备方法，用于生产C-末端修饰蛋白的修饰剂和翻译模板，以及使用C末端修饰蛋白检测蛋白质相互作用的方法
公开(公告)号：US20050010028A1
公开(公告)日：2005-01-13
申请号：US10455453
申请日：2003-06-06
申请人： Hiroshi Yanagawa , Nobuhide Doi , Etsuko Miyamoto , Hideaki Takashima , Rieko Oyama
发明人： Hiroshi Yanagawa , Nobuhide Doi , Etsuko Miyamoto , Hideaki Takashima , Rieko Oyama
IPC分类号： C07K1/13 , C12P21/02 , C07K9/00 , A61K38/14
CPC分类号： C07K1/13 , C12P21/02
摘要： A translation template comprising an ORF region coding for a protein, a 5′ untranslated region comprising a transcription promoter and a translation enhancer and locating on the 5′ side of the ORF region, and a 3′ end region comprising a poly-A sequence and locating on the 3′ side of the ORF region, is expressed in a translation system in the presence of an agent for modifying a C-terminal of a protein, which comprises an acceptor portion having a group capable of binding to a protein through a transpeptidation reaction in a protein translation system and a modifying portion comprising a nonradioactive modifying substance linked to the acceptor portion via a nucleotide linker, to cause protein synthesis and the synthesized protein is purified. Thus, the yield of modified protein in a method of modifying C-terminal of protein is improved and detection of protein interaction based on various intermolecular interaction detection methods is realized at an improved level.
摘要翻译：翻译模板，其包含编码蛋白质的ORF区域，包含转录启动子的5'非翻译区和翻译增强子并且位于ORF区域的5'侧，以及包含poly-A序列的3'末端区域和位于ORF区域的3'侧的表达在翻译系统中，在存在用于修饰蛋白质C末端的试剂的情况下，其包含具有能够通过转肽酶结合蛋白质的基团的受体部分蛋白质翻译系统中的反应和包含通过核苷酸接头与受体部分连接的非放射性修饰物质的修饰部分进行蛋白质合成，合成的蛋白质被纯化。因此，改善蛋白质C-末端修饰方法中的修饰蛋白质的产率得到改善，基于各种分子间相互作用检测方法的蛋白质相互作用的检测得到提高。

4. 发明授权

US08278427B2 Molecule for assigning genotype to phenotype and components thereof as well as method for constructing assigning molecule and method for utilizing assigning molecule 有权
标题翻译：用于将基因型分配给表型及其组分的分子以及用于构建分配分子的方法和用于分配分子的方法
公开(公告)号：US08278427B2
公开(公告)日：2012-10-02
申请号：US10460467
申请日：2003-06-13
申请人： Hiroshi Yanagawa , Etsuko Miyamoto , Hideaki Takashima
发明人： Hiroshi Yanagawa , Etsuko Miyamoto , Hideaki Takashima
IPC分类号： C07H21/04 , C12N15/00 , A61K31/70
CPC分类号： C12N15/1062
摘要： An assigning molecule obtained by ligating a genotype molecule to a phenotype molecule by transpeptidation, wherein the genotype molecule is constructed by bonding (a) a spacer molecule comprising a donor region which can be bonded to a 3′-terminal end of nucleic acid, a PEG region bonded to the donor region and a peptide acceptor region which is bonded to the PEG region, to (b) a 3′ end of a nucleic acid comprising a 5′ untranslated region comprising a transcription promoter and a translation enhancer; an ORF region which comprises a polyA sequence and which is bonded to the 3′-terminal side of the 5′ untranslated region; and a 3′-terminal region that is bonded to the 3′-terminal side of the ORF region.
摘要翻译：通过转基因将基因型分子连接到表型分子而获得的分配分子，其中所述基因型分子通过键合（a）包含可以键合到核酸的3'-末端的供体区的间隔分子，结合到供体区的PEG区和与PEG区结合的肽受体区，至（b）含有包含转录启动子和翻译增强子的5'非翻译区的核酸的3'末端; ORF区域，其包含polyA序列，并且其键合到5'非翻译区的3'末端侧; 和与ORF区域的3'末端侧键合的3'末端区域。

5. 发明授权

US6037335A Phosphonate-nucleotide ester derivatives 失效
标题翻译：膦酸酯 - 核苷酸酯衍生物
公开(公告)号：US6037335A
公开(公告)日：2000-03-14
申请号：US942490
申请日：1997-10-02
申请人： Hideaki Takashima , Naoko Inoue , Masaru Ubasawa , Kouichi Sekiya , Shingo Yabuuchi
发明人： Hideaki Takashima , Naoko Inoue , Masaru Ubasawa , Kouichi Sekiya , Shingo Yabuuchi
IPC分类号： C07F9/6561 , A61K31/675 , C07F9/6512
CPC分类号： C07F9/6561 , C07F9/65616
摘要： Phosphonate-nucleotide ester compounds of the formula (I) have excellent antiviral activity and antineoplastic activity. Further, they can be orally administered. ##STR1## wherein ring A represents ##STR2## wherein R.sup.1 and R.sup.2 independently represent hydrogen, halogen, hydroxyl, mercapto, C.sub.6 -C.sub.10 arylthio or amino; R.sup.3 represents C.sub.1 -C.sub.4 alkyl or ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; R.sup.4 represents ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; X, Y and Z independently represent methyne or nitrogen atom; or a pharmaceutically acceptable salt thereof.
摘要翻译：式（I）的膦酸酯 - 核苷酸酯化合物具有优异的抗病毒活性和抗肿瘤活性。此外，它们可以口服给药。其中环A表示其中R1和R2独立地表示氢，卤素，羟基，巯基，C6-C10芳硫基或氨基; R 3表示具有一个或多个选自氟，C 1 -C 4烷氧基，苯氧基，C 7 -C 10苯基烷氧基和C 2 -C 5酰氧基的取代基的C 1 -C 4烷基或乙基; R4表示具有一个或多个选自氟，C 1 -C 4烷氧基，苯氧基，C 7 -C 10苯基烷氧基和C 2 -C 5酰氧基的取代基的乙基; X，Y和Z独立地表示甲炔或氮原子; 或其药学上可接受的盐。

6. 发明授权

US5840716A Phosphonate nucleotide compounds 失效
标题翻译：磷酸核苷酸化合物
公开(公告)号：US5840716A
公开(公告)日：1998-11-24
申请号：US785606
申请日：1997-01-17
申请人： Masaru Ubasawa , Kouichi Sekiya , Hideaki Takashima , Naoko Ueda , Satoshi Yuasa , Naohiro Kamiya
发明人： Masaru Ubasawa , Kouichi Sekiya , Hideaki Takashima , Naoko Ueda , Satoshi Yuasa , Naohiro Kamiya
IPC分类号： C07F9/6561 , A01N57/00 , C07F9/02
CPC分类号： C07F9/6561 , C07F9/65616
摘要： A phosphonate nucleotide compound having antiviral activity and is useful for an orally available and highly safe antiviral agent, which is represented by the following formula (I): ##STR1## wherein R.sup.1 represents hydrogen, a C.sub.1 -C.sub.6 alkoxy, a halogen-substituted C.sub.1 -C.sub.4 alkoxy, halogen, amino, or nitro; R.sup.2 and R.sup.3 independently represent hydrogen, a C.sub.1 -C.sub.22 alkyl, an acyloxymethy, an acylthioethyl, or a halogen-substituted ethyl; R.sup.4 represents hydrogen, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 hydroxyalkyl, or a halogen-substituted C.sub.1 -C.sub.4 alkyl; and X represents carbon or nitrogen.
摘要翻译：具有抗病毒活性的膦酸酯核苷酸化合物，可用于口服可用和高度安全的抗病毒剂，其由下式（I）表示：其中R 1表示氢，C 1 -C 6烷氧基，卤素取代的C 1 -C 4烷氧基，卤素，氨基或硝基; R2和R3独立地表示氢，C1-C22烷基，酰氧基甲基，酰基硫代乙基或卤素取代的乙基; R4表示氢，C1-C4烷基，C1-C4羟基烷基或卤素取代的C1-C4烷基; X表示碳或氮。

7. 发明授权

US4078111A Process of extrusion-coating the central core with an insulator of high pressure-processed polyethylene 失效
标题翻译：用高压加工聚乙烯绝缘体挤压中心芯的方法
公开(公告)号：US4078111A
公开(公告)日：1978-03-07
申请号：US688264
申请日：1976-05-20
申请人： Koji Yamaguchi , Hideaki Takashima , Iwao Tsurutani , Toshio Nagasawa
发明人： Koji Yamaguchi , Hideaki Takashima , Iwao Tsurutani , Toshio Nagasawa
IPC分类号： B29C47/88 , H01B13/016 , H01B13/14 , H01B3/30
CPC分类号： B29C47/8815 , B29C47/0016 , B29C47/8895 , H01B13/14
摘要： Provided hereinbelow is a process of extrusion-coating the central core, said core being used in a submarine coaxial cable, with an insulator of high pressure-processed polyethylene having a density of from 0.925 to 0.940 g/cm.sup.3 and a melt index of from 0.01 to 0.3 g/10 min with advantages in that said coaxial cable is allowed to be placed on a sea bottom of not less than 500 meters in depth and to effectively transmit alternating current signals with a maximum frequency of not less than 30 MHZ, while attenuation of said signals is reduced, and thus, said coaxial cable has a transmission capacity of not less than 3000 circuits or channels with a frequency band of from 3 to 6 KHz per each circuit or channels, wherein the insulator-covered-core is continuously extruded from an extruder and then is gradually cooled in cooling water troughs to room temperature so that the water content of said insulator, without formation of voids between said central core and said insulator, is reduced by as much as possible.
摘要翻译：在下文中提供了一种挤压涂覆中心芯的方法，所述芯用在海底同轴电缆中，其中具有密度为0.925-0.940g / cm 3和熔体指数为0.01的高压加工聚乙烯绝缘体至0.3g / 10min，其特征在于允许将所述同轴电缆放置在深度不小于500米的海底上，并有效地传输最大频率不小于30MHz的交流信号，同时衰减的所述信号被减少，因此，所述同轴电缆具有每个电路或通道具有不小于3000个电路或具有3至6KHz频带的通道的传输容量，其中绝缘体覆盖芯被连续挤出然后在冷却水槽中逐渐冷却至室温，使得所述绝缘体的水含量在所述中心芯和所述绝缘体之间不形成空隙，由此减少越多越好。

8. 发明授权

US06197775B1 Phosphonate nucleotide derivatives 失效
标题翻译：磷酸核苷酸衍生物
公开(公告)号：US06197775B1
公开(公告)日：2001-03-06
申请号：US08973762
申请日：1997-12-11
申请人： Masaru Ubasawa , Hideaki Takashima , Kouichi Sekiya , Naoko Inoue , Satoshi Yuasa , Naohiro Kamiya
发明人： Masaru Ubasawa , Hideaki Takashima , Kouichi Sekiya , Naoko Inoue , Satoshi Yuasa , Naohiro Kamiya
IPC分类号： A01N4390
CPC分类号： C07F9/6561 , C07F9/65616
摘要： A compound represented by the following general formula (I) which has an antiviral activity: wherein R1 represents hydrogen atom, C1-C6 alkyl group, or C7-C10 aralkyl group; R2 represents C1-C6 alkyl group, C7-C10 aralkyl group, or phenyl group; R3 and R4 independently represent hydrogen atom, C1-C6 alkyl group, acyloxymethyl group, acylthioethyl group, or ethyl gorup substituted with at least one halogen atom; R5 represents hydrogen atom, C1-C4 alkyl gorup, C1-C4 hydroxyalkyl group, C1-C4 alkyl group substituted with at least one halogen atom; and X represents carbon atom or nitrogen atom.
摘要翻译：由具有抗病毒活性的以下通式（I）表示的化合物：其中R1表示氢原子，C1-C6烷基或C7-C10芳烷基; R2表示C1-C6烷基，C7-C10芳烷基或苯基; R3和R4独立地表示氢原子，C1-C6烷基，酰氧基甲基，酰基硫代乙基或被至少一个卤素原子取代的乙基; R5代表氢原子，C1-C4烷基羰基，C1-C4羟基烷基，被至少一个卤素原子取代的C1-C4烷基; X表示碳原子或氮原子。

9. 发明授权

US06194398B1 Phosphonate nucleotide compound 失效
标题翻译：磷酸核苷酸化合物
公开(公告)号：US06194398B1
公开(公告)日：2001-02-27
申请号：US09242111
申请日：1999-06-17
申请人： Masaru Ubasawa , Kouichi Sekiya , Hideaki Takashima , Naoko Ueda , Satoshi Yuasa , Naohiro Kamiya
发明人： Masaru Ubasawa , Kouichi Sekiya , Hideaki Takashima , Naoko Ueda , Satoshi Yuasa , Naohiro Kamiya
IPC分类号： C07D47324
CPC分类号： C07F9/6561 , C07F9/65616
摘要： A phosphonate nucleotide compound represented by formula (I): (wherein R1 is a C1-C6 alkyl group or the like, R2 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms or the like, R3 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms or the like, R4 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms and X is a carbon atom or a nitrogen atom), a salt thereof, a hydrate thereof or a solvate thereof, as well as a medicament containing the same. It is useful as an antiviral agent for human immunodeficiency virus, herpes simplex virus, hepatitis B virus or the like and as an antitumor agent.
摘要翻译：由式（I）表示的膦酸酯核苷酸化合物:(其中R1是C1-C6烷基等，R2是氢原子，被一个或多个卤素原子取代的C1-C4烷基等，R3是氢原子，被一个或多个卤素原子等取代的C 1 -C 4烷基，R 4是氢原子，被一个或多个卤素原子取代的C 1 -C 4烷基，X是碳原子或氮原子），其盐，其水合物或其溶剂合物，以及含有它们的药物。作为人体免疫缺陷病毒，单纯疱疹病毒，乙型肝炎病毒等的抗病毒剂，作为抗肿瘤剂是有用的。

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