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1. 发明授权

US5451659A Polypeptide, DNA fragment encoding the same, drug composition containing the same and process for producing the same 失效
标题翻译：多肽，编码相同的DNA片段，含有其的药物组合物及其制备方法
公开(公告)号：US5451659A
公开(公告)日：1995-09-19
申请号：US972387
申请日：1992-11-05
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： A61K38/00 , C07K14/81 , C12N15/15 , C12N1/20 , C12N9/48 , C12P21/06
CPC分类号： C07K14/811 , A61K38/00
摘要： This invention particularly provides a novel polypeptide having high protease-inhibiting activity, preferably FXa-inhibiting activity, which comprises, at least as a part of the polypeptide, an amino acid sequence resulting from substitution of an amino acid for at least one amino acid in the following amino acid sequence (1), wherein the amino acid substitution is at least one substitution selected from the following substitution means (i) to (iii). It also provides a process for the production of the polypeptide, a novel DNA fragment encoding the polypeptide and a drug composition containing the same.______________________________________ Amino acid sequence (1) ______________________________________ Cys Asn Leu Pro Ile Val Arg Gly Pro Cys Arg Ala Phe Ile Gln Leu Trp Ala Phe Asp Ala Val Lys Gly Lys Cys Val Leu Phe Pro Tyr Gly Gly Cys Gln Gly Asn Gly Asn Lys Phe Tyr Ser Glu Lys Glu Cys Arg Glu Tyr Cys ______________________________________ (i) Substitution of 15 position Gln counting from the N-terminus by an amino acid other than Gln.(ii) Substitution of 42 position Tyr counting from the N-terminus by an amino acid other than Tyr.(iii) Substitution of 7 position Arg counting from the N-terminus by an amino acid other than Arg.
摘要翻译：本发明特别提供了一种具有高蛋白酶抑制活性，优选为FXa抑制活性的新型多肽，其至少作为多肽的一部分，由氨基酸取代至少一个氨基酸而产生的氨基酸序列以下氨基酸序列（1），其中所述氨基酸取代为选自以下取代方案（i）至（iii）中的至少一种取代基。它还提供了制备多肽的方法，编码多肽的新型DNA片段和含有该多肽的药物组合物。 - 氨基酸序列（1） - Cys Asn Leu Pro Ile Val Arg Gly Pro Cys - Arg Ala Phe Ile Gln Leu Trp Ala Phe Asp - Ala Val Lys Gly Lys Cys Val Leu Phe Pro - Tyr Gly Gly Cys Gln Gly Asn Gly Asn Lys-Phe Tyr Ser Glu Lys Glu Cys Arg Glu Tyr - Cys - （i）通过除Gln之外的氨基酸从N末端取代15位Gln。（ii）用除Tyr之外的氨基酸从N末端取代42位Tyr计数。（iii）用除Arg以外的氨基酸从N末端取代7位Arg。

2. 发明授权

US5792629A Isolated DNA encoding novel protease inhibitory polypeptide 失效
标题翻译：分离DNA编码新型蛋白酶抑制性多肽
公开(公告)号：US5792629A
公开(公告)日：1998-08-11
申请号：US293150
申请日：1994-08-19
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： A61K38/55 , A61K38/00 , A61P1/00 , A61P1/16 , A61P7/02 , A61P9/08 , A61P9/10 , A61P11/16 , A61P13/02 , A61P15/00 , A61P29/00 , A61P37/08 , C07K14/81 , C12N1/21 , C12N9/99 , C12N15/09 , C12N15/15 , C12P21/02 , C12Q1/37 , C12R1/19 , C12N5/10 , C12N15/63
CPC分类号： C07K14/8114 , A61K38/005 , C12Q1/37
摘要： This invention provides a novel polypeptide which comprises an amino acid sequence that constitutes a portion of urinary trypsin inhibitor (UTI) and which has no antigenicity against human and high activity to inhibit various proteases, as well as other novel polypeptides having excellent activities to inhibit various proteases obtained by mutation of the former novel polypeptide. This invention also provides novel enzyme inhibition processes, drug compositions and treating methods making use of the novel polypeptide, DNA fragments containing nucleotide sequences which encode the novel polypeptides, vectors containing the DNA fragments and transformants transformed with the DNA fragments or the vectors, as well as processes for the production of the novel polypeptides.
摘要翻译：本发明提供了一种新型多肽，其包含构成尿胰蛋白酶抑制剂（UTI）的一部分的氨基酸序列，并且其对人体没有抗原性和抑制各种蛋白酶的高活性，以及具有优异的抑制各种蛋白酶活性的新型多肽通过前一种新型多肽突变获得的蛋白酶。本发明还提供新的酶抑制过程，药物组合物和利用新多肽的治疗方法，含有编码新多肽的核苷酸序列的DNA片段，含有DNA片段的载体和用DNA片段或载体转化的转化体作为生产新型多肽的方法。

3. 发明授权

US5589360A Polypeptide, DNA fragment encoding the same, drug composition containing the same and process for producing the same 失效
标题翻译：多肽，编码相同的DNA片段，含有其的药物组合物及其制备方法
公开(公告)号：US5589360A
公开(公告)日：1996-12-31
申请号：US431412
申请日：1995-04-28
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： A61K38/00 , C07K14/81 , C12N15/15 , C12P21/06 , C07H19/00 , C07H21/00 , C12N1/20
CPC分类号： C07K14/811 , A61K38/00
摘要： This invention particularly provides a novel polypeptide having high protease-inhibiting activity, preferably FXa-inhibiting activity, which comprises, an lease as a part of the polypeptide, an amino acid sequence resulting from substitution of an amino acid for at least one amino acid in the following amino acid sequence (1), wherein the amino acid substitution is at least one substitution selected from the following substitution means (i) to (iii). It also provides a process for the production of the polypeptide, a novel DNA fragment encoding the polypeptide and a drug composition containing the same.______________________________________ Amino acid sequence (1) ______________________________________ Cys Asn Leu Pro Ile Val Arg Gly Pro Cys Arg Ala Phe Ile Gln Leu Trp Ala Phe Asp Ala Val Lys Gly Lys Cys Val Leu Phe Pro Tyr Gly Gly Cys Gln Gly Asn Gly Asn Lys Phe Tyr Ser Glu Lys Glu Cys Arg Glu Tyr Cys ______________________________________ (i) Substitution of 15 position Gln counting from the N-terminus by an amino acid other than Gln.(ii) Substitution of 42 position Tyr counting from the N-terminus by an amino acid other than Tyr.(iii) Substitution of 7 position Arg counting from the N-terminus by an amino acid other than Arg.
摘要翻译：本发明特别提供了具有高蛋白酶抑制活性，优选FXa抑制活性的新型多肽，其包括作为多肽的一部分的租赁，由氨基酸取代至少一个氨基酸得到的氨基酸序列以下氨基酸序列（1），其中所述氨基酸取代为选自以下取代方案（i）至（iii）中的至少一种取代基。它还提供了制备多肽的方法，编码多肽的新型DNA片段和含有该多肽的药物组合物。 - 氨基酸序列（1） - Cys Asn Leu Pro Ile Val Arg Gly Pro Cys - Arg Ala Phe Ile Gln Leu Trp Ala Phe Asp - Ala Val Lys Gly Lys Cys Val Leu Phe Pro - Tyr Gly Gly Cys Gln Gly Asn Gly Asn Lys-Phe Tyr Ser Glu Lys Glu Cys Arg Glu Tyr - Cys - （i）通过除Gln之外的氨基酸从N末端取代15位Gln。（ii）用除Tyr之外的氨基酸从N末端取代42位Tyr计数。（iii）用除Arg以外的氨基酸从N末端取代7位Arg。

4. 发明授权

US5409895A Protease inhibitory polypeptides derived from urinary trypsin inhibitor and compositions thereof 失效
标题翻译：衍生自尿胰蛋白酶抑制剂的蛋白酶抑制多肽及其组合物
公开(公告)号：US5409895A
公开(公告)日：1995-04-25
申请号：US791213
申请日：1991-11-13
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： A61K38/55 , A61K38/00 , A61P1/00 , A61P1/16 , A61P7/02 , A61P9/08 , A61P9/10 , A61P11/16 , A61P13/02 , A61P15/00 , A61P29/00 , A61P37/08 , C07K14/81 , C12N1/21 , C12N9/99 , C12N15/09 , C12N15/15 , C12P21/02 , C12Q1/37 , C12R1/19 , A61K37/64 , C07K7/10
CPC分类号： C07K14/8114 , A61K38/005 , C12Q1/37
摘要： This invention provides a novel polypeptide which comprises an amino acid sequence that constitutes a portion of urinary trypsin inhibitor (UTI) and which has no antigenicity against human and high activity to inhibit various proteases, as well as other novel polypeptides having excellent activities to inhibit various proteases obtained by mutation of the former novel polypeptide. This invention also provides novel enzyme inhibition processes, drug compositions and treating methods making use of the novel polypeptide, DNA fragments containing nucleotide sequences which encode the novel polypeptides, vectors containing the DNA fragments and transformants transformed with the DNA fragments or the vectors, as well as processes for the production of the novel polypeptides.
摘要翻译：本发明提供了一种新型多肽，其包含构成尿胰蛋白酶抑制剂（UTI）的一部分的氨基酸序列，并且其对人体没有抗原性和抑制各种蛋白酶的高活性，以及具有优异的抑制各种蛋白酶活性的新型多肽通过前一种新型多肽突变获得的蛋白酶。本发明还提供新的酶抑制过程，药物组合物和利用新多肽的治疗方法，含有编码新多肽的核苷酸序列的DNA片段，含有DNA片段的载体和用DNA片段或载体转化的转化体作为生产新型多肽的方法。

5. 发明授权

US5840518A DNA fragment, vector containing the DNA fragment, transformant transformed with the vector and process for producing protein using the vector 失效
标题翻译： DNA片段，含有DNA片段的载体，用载体转化的转化体和使用载体产生蛋白质的方法
公开(公告)号：US5840518A
公开(公告)日：1998-11-24
申请号：US235515
申请日：1994-04-29
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： C07K19/00 , C07K14/00 , C07K14/81 , C12N1/19 , C12N1/21 , C12N15/09 , C12N15/62 , C12N15/67 , C12P21/02 , C12R1/19 , C12N15/00 , C12N15/11 , C12N15/70
CPC分类号： C12N15/625 , C07K14/8135 , C12N15/67 , C07K2319/036
摘要： DNA fragments having a nucleotide sequence represented by x and vectors containing the DNA fragment, wherein the nucleotide sequence x encodes an amino acid sequence represented by any one of the following formulae 1 to 8: formula 1 AVLPQEEEGSG, formula 2 AVLPQEEEGSGGGQLVTEVTKKEDSG, formula 3 AVLDQEEEGSG, formula 4 AVLPQEEEGDG, formula 5 AVLPQEEEGSGD, formula 6 AVLPQEEEGSGDD, formula 7 AVLPQEEEGSGDDD, and formula 8 ADDPQEEEGSG. Expression of a protein of interest and its secretion from host cells into the extracellular milieu can be increased by expressing or secreting the protein of interest in the form of a fusion protein with a specified polypeptide encoded by the DNA fragment of the present invention using the vector of the present invention, by means of recombinant DNA techniques in which the inventive DNA fragment is used.
摘要翻译：具有由x表示的核苷酸序列的DNA片段和含有该DNA片段的载体，其中该核苷酸序列x编码由下式1至8中任一项表示的氨基酸序列：式1 AVLPQEEEGSG，式2 AVLPQEEEGSGGGQLVTEVTKKEDSG，式3 AVLDQEEEGSG，式4 AVLPQEEEGDG，式5 AVLPQEEEGSGD，式6 AVLPQEEEGSGDD，式7 AVLPQEEEGSGDDD和式8 ADDPQEEEGSG。目的蛋白质及其从宿主细胞分泌到细胞外环境中的表达可以通过使用本发明的DNA片段编码的具有特定多肽的融合蛋白的形式来表达或分泌感兴趣的蛋白质，通过使用本发明的DNA片段的重组DNA技术进行。

6. 发明授权

US5679770A Polypeptide, DNA fragment encoding the same, drug composition containing the same and process for producing the same 失效
标题翻译：多肽，编码相同的DNA片段，含有其的药物组合物及其制备方法
公开(公告)号：US5679770A
公开(公告)日：1997-10-21
申请号：US57971
申请日：1993-05-06
申请人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
发明人： Hideaki Morishita , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： A61K38/00 , C07K14/81 , A61K38/16 , A61K38/55 , C07K14/00
CPC分类号： C07K14/811 , A61K38/00
摘要： This invention particularly provides a novel polypeptide having high protease-inhibiting activity, preferably FXa-inhibiting activity, which comprises, at least as a part of the polypeptide, an amino acid sequence resulting from substitution of an amino acid for at least one amino acid in the following amino acid sequence (1), wherein the amino acid substitution is at least one substitution selected from the following substitution means (i) to (iii). It also provides a process for the production of the polypeptide, a novel DNA fragment encoding the polypeptide and a drug composition containing the same. Amino acid sequence (1) ##STR1## (i) Substitution of 15 position Gln counting from the N-terminus by an amino acid other than Gln. (ii) Substitution of 42 position Tyr counting from the N-terminus by an amino acid other than Tyr. (iii) Substitution of 7 position Arg counting from the N-terminus by an amino acid other than Arg.
摘要翻译：本发明特别提供了一种具有高蛋白酶抑制活性，优选为FXa抑制活性的新型多肽，其至少作为多肽的一部分，由氨基酸取代至少一个氨基酸而产生的氨基酸序列以下氨基酸序列（1），其中所述氨基酸取代为选自以下取代方案（i）至（iii）中的至少一种取代基。它还提供了制备多肽的方法，编码多肽的新型DNA片段和含有该多肽的药物组合物。氨基酸序列（1）CysAsnLeuProIleValArgGlyProCys ArgAlaPheIleGlnLeuTrpAlaPheAsp AlaValLysGlyLysCysValLeuPhePro TyrGlyGlyCysGlnGlyAsnGlyAsnLys PheTyrSerGluLysGluCysArgGluTyr Cys（i）用除Gln之外的氨基酸从N末端取代15位Gln。（ii）用除Tyr之外的氨基酸从N末端取代42位Tyr计数。（iii）用除Arg以外的氨基酸从N末端取代7位Arg。

7. 发明授权

US06218134B1 Process for specific binding assay for measuring the amount of analyte in a liquid test sample 失效
标题翻译：用于测量液体测试样品中分析物的量的特异性结合测定法
公开(公告)号：US06218134B1
公开(公告)日：2001-04-17
申请号：US08637905
申请日：1996-04-26
申请人： Tadakazu Yamauchi , Toshinori Kanamori , Masahiro Nobuhara
发明人： Tadakazu Yamauchi , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： G01N3353
CPC分类号： G01N33/5438 , G01N33/54386 , G01N33/558 , Y10S435/81 , Y10S435/962 , Y10S435/97 , Y10S436/807
摘要： A specific binding assay process which is useful for quick qualitative or quantitative measurement and which can be used for various purposes, and a specific binding assay device suitable for the practice of the process, in which a substance to be assayed in a liquid test sample is determined qualitatively or quantitatively by developing the substance in a liquid test sample in a matrix, which comprises the steps of, for example: allowing the substance to be assayed to reach with a specific binding substance which has specific affinity for the substance to be assayed; allowing a signal substance generator (a substance which competes with the substance to be assayed for the specific binding substance and which generates a signal) to change its distribution in the matrix in response to the reaction of the above step, and; detecting the resulting distributional changes at a detection means as changes of signals which are rate-limited by the mass transfer of a signal substance generated from the signal substance generator.
摘要翻译：可用于快速定性或定量测量并可用于各种目的的特异性结合测定方法，以及适于实施该方法的特异性结合测定装置，其中待测物质在液体测试样品中为通过在基质中液体测试样品中开发物质定性或定量地测定，其包括以下步骤：允许用特异性结合物质测定物质以对待测物质具有特异性亲和力; 允许响应于上述步骤的反应使信号物质发生器（与物质竞争的物质与特定结合物质进行测定并产生信号）改变其在基质中的分布，并且检测所得到的分布在由t产生的信号物质的传质速率限制的信号变化时，在检测装置处的变化他信号物质发生器。

8. 发明授权

US5516644A Electrochemical immunochromatographic assay 失效
标题翻译：电化学免疫层析法
公开(公告)号：US5516644A
公开(公告)日：1996-05-14
申请号：US243095
申请日：1994-05-16
申请人： Tadakazu Yamauchi , Toshinori Kanamori , Masahiro Nobuhara
发明人： Tadakazu Yamauchi , Toshinori Kanamori , Masahiro Nobuhara
IPC分类号： G01N33/542 , G01N33/543 , G01N33/557 , G01N33/558 , G01N33/535 , G01N33/544 , G01N33/551 , G01N33/561
CPC分类号： G01N33/5438 , G01N33/54386 , G01N33/558 , Y10S435/81 , Y10S435/962 , Y10S435/97 , Y10S436/807
摘要： A specific binding assay process which is useful for quick qualitative or quantitative measurement and which can be used for various purposes, and a specific binding assay device suitable for the practice of the process,in which a substance to be assayed in a liquid test sample is determined qualitatively or quantitatively by developing the substance in a liquid test sample in a matrix, which comprises the steps of, for example:allowing the substance to be assayed to react with a specific binding substance which has specific affinity for the substance to be assayed;allowing a signal substance generator (a substance which competes with the substance to be assayed for the specific binding substance and which generates a signal) to chance its distribution in the matrix in response to the reaction of the above step, and;detecting the resulting distributional changes at a detection means as changes of signals which are rate-limited by the mass transfer of a signal substance generated from the signal substance generator.
摘要翻译：可用于快速定性或定量测量并可用于各种目的的特异性结合测定方法，以及适于实施该方法的特异性结合测定装置，其中待测物质在液体测试样品中为通过在基质中液体测试样品中开发物质进行定性或定量测定，其包括以下步骤：使待测物质与对待测物质具有特异性亲和力的特异性结合物质反应; 允许响应于上述步骤的反应使信号物质发生器（与物质竞争的物质被测定为特异性结合物质并产生信号）偶然地分布在基质中; 在检测装置处检测所得到的分布变化，作为通过由信号物质发生器产生的信号物质的质量传递而受速率限制的信号的变化。

9. 发明授权

US4680261A Process for producing interferon 失效
标题翻译：生产干扰素的方法
公开(公告)号：US4680261A
公开(公告)日：1987-07-14
申请号：US645761
申请日：1984-08-30
申请人： Masahiro Nobuhara , Toshinori Kanamori , Kiyoshi Yamaguchi , Ei Mochida
发明人： Masahiro Nobuhara , Toshinori Kanamori , Kiyoshi Yamaguchi , Ei Mochida
IPC分类号： C12P21/00 , A61K38/21 , C07K14/555 , C12N5/08 , C12R1/91 , A61K45/02
CPC分类号： C07K14/555 , Y10S435/811
摘要： A process for producing interferon comprises culturing interferon-producing mammalian cells in a cell culture medium containing at least one compound selected from the group consisting of ascorbic acid, an ascorbic acid derivative and a vanadium compound. According to the process of the present invention, interferon can be produced in large amounts.
摘要翻译：制备干扰素的方法包括在含有至少一种选自抗坏血酸，抗坏血酸衍生物和钒化合物的化合物的细胞培养基中培养产生干扰素的哺乳动物细胞。根据本发明的方法，可以大量生产干扰素。

10. 发明授权

US5262526A Fluorescent compound, complex, reagent, and specific binding assay employing said reagent 失效
标题翻译：使用所述试剂的荧光化合物，复合物，试剂和特异性结合测定
公开(公告)号：US5262526A
公开(公告)日：1993-11-16
申请号：US811533
申请日：1991-12-20
申请人： Kazumi Sasamoto , Daikichi Horiguchi , Masahiro Nobuhara , Hiroshi Mochizuki
发明人： Kazumi Sasamoto , Daikichi Horiguchi , Masahiro Nobuhara , Hiroshi Mochizuki
IPC分类号： C07D471/22 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/576 , G01N33/76 , G01N33/78 , C07D257/10 , C07H19/073 , C09D29/036
CPC分类号： C07D471/22 , G01N33/533 , G01N33/5764 , G01N33/76 , G01N33/78
摘要： A fluorescent compound, which is readily capable of forming a stable complex with a rare-earth metal ion having fluorescence with satisfactory intensity even in an aqueous system and long fluorescence lifetime when formed a complex with the rare-earth metal ion, a complex of the fluorescent compound and the rare-earth metal ion, and a labelled reagent made therefrom, together with a specific binding assay using said labelling agent.A fluorescent compound expressed by the following formula A, typically exemplified by 2,15-diaza[3,3](2,9)-1,10-phenanthrolinophane-N.sup.2,N.sup.15 -diacetic acid. ##STR1##

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