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1. 发明授权

US5059538A Recombinant plasmid inserted with herpes simplex virus gene 失效
标题翻译：用HERPES SIMPLEX病毒基因插入的重组质粒
公开(公告)号：US5059538A
公开(公告)日：1991-10-22
申请号：US896923
申请日：1986-08-15
申请人： Chikateru Nozaki , Hiroshi Nakatake , Yoichiro Kino , Tatsuo Eto , Keiichi Makizumi , Nobuya Ohtomo
发明人： Chikateru Nozaki , Hiroshi Nakatake , Yoichiro Kino , Tatsuo Eto , Keiichi Makizumi , Nobuya Ohtomo
IPC分类号： C12N15/09 , A61K39/00 , C07H21/04 , C07K14/035 , C12N15/00 , C12N15/38 , C12N15/81 , C12P21/02 , C12R1/19 , C12R1/865
CPC分类号： C12N15/81 , C07K14/005 , A61K39/00 , C12N2710/16622 , Y10S435/942
摘要： A novel recombinant plasmid inserted with a herpes simplex virus gene, which comprises a plasmid vector containing a yeast DNA sequence and an Escherichia coli DNA sequence and carrying a promoter region and a herpes simplex virus gN gene (HSVgB) gene) recombined thereto under control of the promoter, said HSVgB gene lacking an N-terminal portion of the gene including a signal sequence-encoding region and optionally further lacking the region downstream therefrom, such as a gB gene lacking a DNA sequence encoding the N-terminal 30 amino acids, and a gB gene lacking a DNA sequence encoding the N-terminal 83 amino acids. The recombinant plasmid is useful for the production of transformed yeast, which is useful for the production of HSVgB proteins suitable for producing HSV vaccine and diagnostic reagents for herpes simplex virus infections.
摘要翻译：一种插入单纯疱疹病毒基因的新型重组质粒，其包含含有酵母DNA序列和大肠杆菌DNA序列并携带启动子区域和单纯疱疹病毒gN基因（HSVgB）基因）的质粒载体，启动子，所述HSVgB基因缺失包含信号序列编码区的基因的N末端部分，并且任选地进一步缺少其下游区域，例如缺乏编码N末端30个氨基酸的DNA序列的gB基因，以及缺乏编码N-末端83个氨基酸的DNA序列的gB基因。重组质粒可用于生产转化酵母，其可用于生产适用于生产HSV疫苗的HSVgB蛋白和用于单纯疱疹病毒感染的诊断试剂。

2. 发明授权

US06391542B1 Compositions and methods for treatment of Hepatitis C virus-associated diseases 失效
标题翻译：治疗丙型肝炎病毒相关疾病的组合物和方法
公开(公告)号：US06391542B1
公开(公告)日：2002-05-21
申请号：US08650093
申请日：1996-05-17
申请人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa , Shoji Furasako , Thomas W. Bruice , Walter F. Lima
发明人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa , Shoji Furasako , Thomas W. Bruice , Walter F. Lima
IPC分类号： C12Q168
CPC分类号： C12N15/1131 , C07H21/00 , C07K14/005 , C12N2310/315 , C12N2310/33 , C12N2310/3521 , C12N2310/3527 , C12N2770/24222 , C12Q1/707
摘要： Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.
摘要翻译：提供反义寡核苷酸，其与至少一部分HCV RNA互补并可与其相互杂交，并能够抑制HCV RNA的功能。可以施用这些寡核苷酸来体内或体外抑制丙型肝炎病毒的活性。这些化合物可以预防性地或治疗性地用于降低与丙型肝炎病毒相关的疾病的严重性，以及HCV和HCV相关疾病的诊断和检测。还公开了使用这些化合物的方法。

3. 发明授权

US06284458B1 Compositions and methods for treatment of hepatitis C virus-associated diseases 失效
公开(公告)号：US06284458B1
公开(公告)日：2001-09-04
申请号：US08397220
申请日：1995-03-09
申请人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa
发明人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa
IPC分类号： C12Q168
CPC分类号： C12N15/1131 , C07H21/00 , C07K14/005 , C12N2310/315 , C12N2310/33 , C12N2310/3521 , C12N2310/3527 , C12N2770/24222 , C12Q1/707
摘要： Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

4. 发明授权

US06423489B1 Compositions and methods for treatment of Hepatitis C virus-associated diseases 失效
公开(公告)号：US06423489B1
公开(公告)日：2002-07-23
申请号：US08452841
申请日：1995-05-30
申请人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa , Shoji Furusako , Thomas W. Bruice , Walter F. Lima
发明人： Kevin P. Anderson , Ronnie C. Hanecak , Kazuya Hoshiko , Chikateru Nozaki , Tsukasa Nishihara , Hiroshi Nakatake , Fukusaburo Hamada , Tatsuo Eto , Shinichi Furukawa , Shoji Furusako , Thomas W. Bruice , Walter F. Lima
IPC分类号： C12Q168
CPC分类号： C12N15/1131 , C07H21/00 , C07K14/005 , C12N2310/315 , C12N2310/33 , C12N2310/3521 , C12N2310/3527 , C12N2770/24222 , C12Q1/707
摘要： Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

5. 发明授权

US4612283A Method for purification of HBs antigen 失效
标题翻译： HBs抗原纯化方法
公开(公告)号：US4612283A
公开(公告)日：1986-09-16
申请号：US656315
申请日：1984-10-01
申请人： Keishin Sugahara , Chikateru Nozaki , Fukusaburo Hamada , Fumio Miake , Nobuya Ohtomo
发明人： Keishin Sugahara , Chikateru Nozaki , Fukusaburo Hamada , Fumio Miake , Nobuya Ohtomo
IPC分类号： C12N15/09 , A61K39/00 , C07K1/22 , C07K14/005 , C07K14/02 , C07K14/10 , C07K14/18 , C07K14/195 , C12P21/00 , C12P21/02 , C12R1/19 , C12R1/865 , A61K39/29
CPC分类号： C07K14/005 , A61K39/00 , C12N2730/10122
摘要： A method for purification of HBs antigen, which comprises treating an HBs tigen-containing material with an acid, optionally subjecting to salting out with ammonium sulfate, and subjecting the material to a chromatography with hydroxyapatite, by which a highly purified HBs antigen suitable for the preparation of HBV vaccine or diagnostic agent can be obtained in an industrial scale. This method is particularly useful for the purification of HBs antigen-containing material produced by recombinants obtained by DNA recombination technique.
摘要翻译：一种用于纯化HBs抗原的方法，其包括用酸处理含HBs抗原的材料，任选地用硫酸铵进行盐析，并用羟基磷灰石进行色谱分离，通过该色谱法，适用于可以以工业规模获得HBV疫苗或诊断剂的制备。该方法对于通过DNA重组技术获得的重组体产生的含HBs抗原的材料的纯化特别有用。

6. 发明授权

US4997767A Yeast shuttle vector 失效
标题翻译：酵母穿梭载体
公开(公告)号：US4997767A
公开(公告)日：1991-03-05
申请号：US946329
申请日：1986-12-23
申请人： Chikateru Nozaki , Fukusaburo Hamada , Nobuya Ohtomo
发明人： Chikateru Nozaki , Fukusaburo Hamada , Nobuya Ohtomo
IPC分类号： C12N15/09 , A61K39/29 , C12N15/00 , C12N15/64 , C12N15/70 , C12N15/81 , C12R1/19 , C12R1/865
CPC分类号： C12N15/81 , C12N15/64 , C12N15/70 , Y10S435/911 , Y10S435/94 , Y10S435/942
摘要： Shuttle vectors including a DNA sequence of the yeast Saccharomyces cerevisiae including ars 1.2 micron ori and a marker gene for transformed yeast permitting synthesis of leucine by the transformant; adjacent to said ars 1 a DNA sequence of Escherichia coli which is either in EcoR1--PvuII or EcoR1--TthIII--I fragment of plasmid pBR322; and adjacent to the yeast marker gene the expression control region of the repressible acid phosphatase gene of yeast.
摘要翻译：穿梭载体包括酵母酿酒酵母的DNA序列，包括1.2微米的穗，以及转化酵母允许转化体合成亮氨酸的标记基因; 与所述ars1相邻的是质粒pBR322的EcoRⅠ-PvuII或EcoR1-TthIII-I片段中的大肠杆菌的DNA序列; 并与酵母标记基因相邻，是酵母抑制性酸性磷酸酶基因的表达控制区。

7. 发明授权

US5024938A Recombinant DNA inserted with hepatitis B virus gene, mammalian cells transformed with cloned viral DNA, and production of hepatitis B virus proteins 失效
标题翻译：用乙型肝炎病毒基因插入的重组DNA，用克隆的病毒DNA转化的哺乳动物细胞，以及产生乙型肝炎病毒蛋白质
公开(公告)号：US5024938A
公开(公告)日：1991-06-18
申请号：US883138
申请日：1986-07-08
申请人： Chikateru Nozaki , Atsushi Miyanohara , Fukusaburo Hamada , Nobuya Ohtomo , Kenichi Matsubara
发明人： Chikateru Nozaki , Atsushi Miyanohara , Fukusaburo Hamada , Nobuya Ohtomo , Kenichi Matsubara
IPC分类号： C12N15/09 , A61K39/29 , C07H21/04 , C07K14/02 , C12N5/10 , C12P21/00 , C12P21/02
CPC分类号： C07K14/005 , C12N2730/10122
摘要： A recombinant DNA comprising 3 fragments of Hepatitis B virus DNA recombined with a vector consisting essentially of 0.31 Kb replication orgin of SV40 DNA inserted into EcoRI cleavage site of Escherichia coli plasmid which is deficient in the 1.426-2.521 Kb region of inhibiting replication in mammalian cells, wherein each HBV DNA fragment is a 3.2 Kb BamHI fragment consisting of 1.9 Kb HBc gene and 1.3 Kb HBs gene, and said HBV DNA fragments are arranged in a head-to-tail tandem relationship wherein the HBc gene positions at the head and the HBs gene positions at the tail, mammalian cells transformed with the recombinant DNA, and a method of production of Hepatitis B virus proteins, i.e. HBsAg and/or HBeAg. These HBV proteins have the same immunological properties as those of the natural HBV proteins originated from human blood plasma and can be used for the preparation of HBV vaccine and diagnostic reagents.
摘要翻译：将包含3个乙型肝炎病毒DNA片段的重组DNA与基本上由插入到在哺乳动物细胞中抑制复制的1.426-2.521Kb区域的缺失的大肠杆菌质粒的EcoRI切割位点的SV40DNA的0.31Kb复制形式的载体重组，其中每个HBV DNA片段是由1.9Kb HBc基因和1.3Kb HBs基因组成的3.2Kb BamHI片段，并且所述HBV DNA片段以头对尾串联关系排列，其中HBc基因位于头部和在尾部的HBs基因位置，用重组DNA转化的哺乳动物细胞，以及生产乙型肝炎病毒蛋白即HBsAg和/或HBeAg的方法。这些HBV蛋白质具有与源自人血浆的天然HBV蛋白质相同的免疫学特性，可用于制备HBV疫苗和诊断试剂。

8. 发明授权

US4778761A Recombinant plasmid inserted with hepatitis B virus gene, yeast transformed with said recombinant plasmid, and production of hepatitis B virus surface antigen 失效
标题翻译：插入乙型肝炎病毒基因的重组质粒，用所述重组质粒转化的酵母，并产生乙型肝炎病毒表面抗原
公开(公告)号：US4778761A
公开(公告)日：1988-10-18
申请号：US4424
申请日：1987-01-20
申请人： Atsushi Miyanohara , Chikateru Nozaki , Fukusaburo Hamada , Akio Toh-e , Nobuya Ohtomo , Kenichi Matsubara
发明人： Atsushi Miyanohara , Chikateru Nozaki , Fukusaburo Hamada , Akio Toh-e , Nobuya Ohtomo , Kenichi Matsubara
IPC分类号： C12N15/09 , A61K39/29 , C07H21/04 , C07K14/02 , C12N15/00 , C12N15/62 , C12N15/80 , C12N15/81 , C12P21/00 , C12P21/02 , C12R1/19 , C12R1/865 , C12N1/00
CPC分类号： C07K14/005 , C12N15/62 , C12N15/80 , C12N15/81 , C07K2319/00 , C07K2319/40 , C12N2730/10122
摘要： A recombinant plasmid inserted with Hepatitis B virus gene, which comprises a plasmid vector containing a yeast gene and an E. coli gene and carrying the expression control region of the repressible acid phosphatase gene of yeast and a Hepatitis B virus gene recombined thereto under control of the phosphatase promoter, a transformed yeast which is prepared by transforming a yeast with the recombinant plasmid, and a method of the production of Hepatitis B virus surface antigen in a large scale by culturing the transformed yeast in a medium. The Hepatitis B virus surface antigen prepared by the present invention has the same immunological properties as those of the natural antigen from human blood plasma and is useful for the preparation of Hepatitis B virus vaccine and diagnostic reagents.
摘要翻译：插入乙型肝炎病毒基因的重组质粒，其包含含有酵母基因和大肠杆菌基因的质粒载体，并携带酵母的可压制酸性磷酸酶基因的表达控制区和重组的乙型肝炎病毒基因的控制区磷酸酶启动子，通过用重组质粒转化酵母制备的转化酵母以及通过在培养基中培养转化的酵母大规模生产乙型肝炎病毒表面抗原的方法。本发明制备的乙型肝炎病毒表面抗原具有与人血浆天然抗原相同的免疫学特性，可用于制备乙型肝炎病毒疫苗和诊断试剂。

9. 发明申请

US20050164365A1 Genetically modified ecarin and process for producing the same 审中-公开
标题翻译：转基因茄子及其生产方法
公开(公告)号：US20050164365A1
公开(公告)日：2005-07-28
申请号：US10482925
申请日：2002-07-04
申请人： Hiroshi Yonemura , Takayuki Imamura , Hiroshi Nakatake , Kenji Soejima , Chikateru Nozaki
发明人： Hiroshi Yonemura , Takayuki Imamura , Hiroshi Nakatake , Kenji Soejima , Chikateru Nozaki
IPC分类号： C12N9/64 , C12N15/12 , C07H21/04 , C12N1/21 , C12N5/06 , C12N15/74
CPC分类号： C12N9/6418
摘要： A recombinant ecarin protein that specifically activates prothrombin, said protein being efficiently prepared by the genetic engineering technique comprising the steps: (1) culturing a transformant microorganism or animal cell transformed with an expression vector in which a gene encoding ecarin is incorporated to the downstream of a promoter so as to produce and accumulate ecarin in culture supernatant or within said transformant and recovering the produced ecarin; and (2) purifying a solution containing the recovered ecarin to obtain purified ecarin. The present invention allows for production of recombinant ecarin on an industrial scale.
摘要翻译：一种特异性激活凝血酶原的重组ecarin蛋白，所述蛋白通过遗传工程技术有效地制备，包括以下步骤：（1）培养用表达载体转化的转化体微生物或动物细胞，其中将编码ecarin的基因并入到促进剂，以在培养上清液或所述转化体内产生和积累ecarin并回收所产生的ecarin; 和（2）纯化含有回收的ecarin的溶液以获得纯化的ecarin。本发明允许以工业规模生产重组ecarin。

10. 发明授权

US07635577B2 Process for producing human thrombin by gene modification technique 失效
标题翻译：通过基因修饰技术生产人凝血酶的方法
公开(公告)号：US07635577B2
公开(公告)日：2009-12-22
申请号：US10482926
申请日：2002-07-04
申请人： Hiroshi Yonemura , Tajayuki Imamura , Hiroshi Nakatake , Kenji Soejima , Chikateru Nozaki
发明人： Hiroshi Yonemura , Tajayuki Imamura , Hiroshi Nakatake , Kenji Soejima , Chikateru Nozaki
IPC分类号： C12P21/04
CPC分类号： C12N9/6424 , C12Y304/21005
摘要： A genetic recombinant human thrombin is provided. Human thrombin is efficiently prepared by the genetic engineering technique comprising the steps: (1) culturing a transfectant animal cell transfected with an expression vector in which a gene encoding human prethrombin is incorporated to the downstream of a promoter so as to produce and accumulate prethrombin in culture supernatant and recovering the produced human prethrombin; (2) treating a solution containing human prethrombin recovered in step (1) with ecarin so as to convert human prethrombin into human thrombin; and (3) purifying the solution obtained after the above activation process to obtain purified human thrombin. The present invention allows for provision of human thrombin in a large scale in a safe and economical manner due to exclusion of blood-derived components.
摘要翻译：提供了基因重组人凝血酶。通过基因工程技术有效制备人凝血酶，所述方法包括以下步骤：（1）培养用表达载体转染的转染细胞动物细胞，其中将编码人凝血酶原的基因并入启动子的下游，以产生并累积凝血酶原培养上清液并回收生产的人凝血酶原; （2）用ecarin处理步骤（1）中回收的含有人凝血酶原的溶液，以将人凝血酶原转化为人凝血酶; （3）纯化上述活化处理后得到的溶液，得到纯化人凝血酶。本发明允许以安全和经济的方式大规模提供人类凝血酶，因为排除了血液衍生的成分。

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