公开(公告)号：US20110160252A1

公开(公告)日：2011-06-30

申请号：US12999055

申请日：2009-06-18

申请人： Masashi Mizokami ,  Yasuhito Tanaka ,  Masaya Sugiyama ,  Masayuki Sudoh

发明人： Masashi Mizokami ,  Yasuhito Tanaka ,  Masaya Sugiyama ,  Masayuki Sudoh

IPC分类号： A61K31/44 ,  C07C229/34 ,  A61K31/195 ,  C07D213/55 ,  A61P31/12

CPC分类号： A61K31/13 ,  A61K31/165 ,  A61K31/201 ,  A61K31/381 ,  A61K31/405 ,  A61K31/4406 ,  A61K31/4418

摘要： First, the present inventors assessed the effect of the compound represented by formula (III) below on Huh-7 cells infected with HBV, and demonstrated that the compound alone had an anti-HBV effect in vitro.Formula (III) Then, the present inventors revealed that the HBV replication-suppressing effect of PEG-IFN is enhanced in chimeric mice having a human liver infected with genotype C or A HBV when PEG-IFN is used in combination with the compound represented by formula (III) above. The present inventors also revealed that the HBV replication-suppressing effect of Entecavir is enhanced in chimeric mice having a human liver infected with genotype C HBV (wild-type and Entecavir-resistant strains) when Entecavir is used in combination with the compound represented by formula (III) above. In addition, the present inventors revealed that the compound represented by formula (III) above exerts the anti-HBV effect not only against wild-type HBV strains but also against Entecavir- and/or Lamivudine-resistant HBV strains.

摘要翻译： 首先，本发明人评估了下述式（III）表示的化合物对HBV感染的Huh-7细胞的作用，并证明该化合物在体外具有抗HBV作用。 式（III）然后，本发明人揭示了当将PEG-IFN与由下列化合物组合使用时，将具有基因型C或A HBV感染的人肝的嵌合小鼠中的PEG-IFN的HBV复制抑制作用增强 上述式（III）。 本发明人还发现，当恩替卡韦与式（I）表示的化合物组合使用时，恩替卡韦的HBV复制抑制作用在具有感染基因型C HBV（野生型和恩替卡韦抗性菌株）的人肝脏的嵌合小鼠中得到增强 （三）。 此外，本发明人发现，上述式（III）表示的化合物不仅对抗野生型HBV株而且对依替卡韦和/或拉米夫定耐药的HBV株产生抗HBV作用。

公开(公告)号：US20140302082A1

公开(公告)日：2014-10-09

申请号：US14009049

申请日：2012-03-30

申请人： Takaji Wakita ,  Tomoko Date ,  Yasuhito Tanaka ,  Masashi Mizokami

发明人： Takaji Wakita ,  Tomoko Date ,  Yasuhito Tanaka ,  Masashi Mizokami

IPC分类号： C12N7/00 ,  C12Q1/70 ,  C07K16/08

CPC分类号： C12N7/00 ,  A61K39/00 ,  A61K39/12 ,  C07K14/005 ,  C07K16/082 ,  C07K16/109 ,  C12N15/86 ,  C12N2770/24221 ,  C12N2770/24222 ,  C12N2770/24231 ,  C12N2770/24234 ,  C12N2770/24243 ,  C12N2770/24251 ,  C12Q1/707 ,  C12Q2600/136 ,  C12Q2600/156

摘要： A subgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and a fullgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and infectious HCV particle-producing ability, each derived from a novel HCV of genotype 1b, are provided. Particularly, a subgenomic replicon RNA (nucleic acid) and a fullgenomic replicon RNA (nucleic acid), each derived from an HCV genome of the NC1 strain which is a novel HCV genotype 1b isolated from a patient with acute severe hepatitis C, are provided.

摘要翻译： 提供了具有优异的自主复制能力的亚基因组复制子RNA（核酸）和具有优异的自主复制能力和感染性HCV颗粒产生能力的全基因组复制子RNA（核酸），各自源自基因型1b的新型HCV。 特别地，提供了从NC1菌株的HCV基因组衍生的亚基因组复制子RNA（核酸）和全基因组复制子RNA（核酸），其是从急性重症丙型肝炎患者分离的新型HCV基因型1b。

公开(公告)号：US20120190576A1

公开(公告)日：2012-07-26

申请号：US13384031

申请日：2010-07-12

申请人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

发明人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

IPC分类号： C40B30/04 ,  C07K14/00

CPC分类号： C07K9/00 ,  C07K14/47 ,  G01N33/57438 ,  G01N33/57469 ,  G01N2400/02 ,  G01N2800/085

摘要： The present invention is directed to developing a glycan markers capable of detecting a hepatic disease, and more specifically to developing a glycan marker indicating a hepatic disease-state. Furthermore, the present invention is also directed to developing a glycan marker capable of distinguishing hepatic disease-states with the progress of hepatocarcinoma. The present inventors identified, among the serum glycoproteins, glycopeptides and glycoproteins in which a glycan structure specifically changes due to a hepatic diseases including hepatocarcinoma and provide these as novel glycan markers (glycopeptide and glycoprotein) specific to hepatic disease-states.

摘要翻译： 本发明涉及开发能够检测肝脏疾病的聚糖标记物，更具体地说，涉及发展表达肝病状态的聚糖标记物。 此外，本发明还涉及开发能够区分肝脏疾病状态与肝癌进展的聚糖标记。 本发明人鉴定了血清糖蛋白中由于包括肝癌在内的肝脏疾病而特异性地改变聚糖结构的糖肽和糖蛋白，并将其提供为肝脏疾病状态特异性的新型聚糖标记（糖肽和糖蛋白）。

公开(公告)号：US20120172247A1

公开(公告)日：2012-07-05

申请号：US13374807

申请日：2012-01-13

申请人： Hisashi Narimatsu ,  Yuzuru Ikehara ,  Atsushi Kuno ,  Maki Sogabe ,  Yasuhito Tanaka ,  Masashi Mizokami ,  Kiyoaki Ito ,  Shunsuke Matsubara ,  Chikayuki Tsuruno ,  Youichi Takahama ,  Takashi Kagawa ,  Shinya Nagai

发明人： Hisashi Narimatsu ,  Yuzuru Ikehara ,  Atsushi Kuno ,  Maki Sogabe ,  Yasuhito Tanaka ,  Masashi Mizokami ,  Kiyoaki Ito ,  Shunsuke Matsubara ,  Chikayuki Tsuruno ,  Youichi Takahama ,  Takashi Kagawa ,  Shinya Nagai

IPC分类号： C40B30/04 ,  G01N33/82 ,  C07K14/47 ,  G01N33/566

CPC分类号： G01N33/68 ,  C07K14/4726 ,  C07K14/473 ,  G01N33/5308 ,  G01N33/57438 ,  G01N33/6893 ,  G01N2333/4724 ,  G01N2333/4728 ,  G01N2400/00 ,  G01N2400/02 ,  G01N2800/085 ,  Y10T436/143333

摘要： An object of the present invention is to provide a method for measuring a glycan-marker glycoprotein, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a method for examining liver disease, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Disclosed is a method for measuring at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP) contained in a sample collected from a subject, comprising: measuring AGP binding to a first lectin selected from AOL and MAL, when the glycoprotein is AGP; and measuring M2BP binding to a second lectin selected from WFA, BPL, AAL, RCA120, and TJAII, when the glycoprotein is M2BP.

摘要翻译： 本发明的目的是提供一种测定聚糖标记糖蛋白的方法，通过该方法可以以比常规方法更高的精度检测肝脏疾病。 另外，本发明的目的在于提供一种检查肝脏疾病的方法，通过该方法能够以比常规方法更高的精度检测肝脏疾病。 公开了一种测量从受试者收集的样品中含有的至少一种选自α-1-酸糖蛋白（AGP）和Mac-2结合蛋白（M2BP）的糖蛋白的方法，包括：测量与所选第一凝集素的AGP结合 来自AOL和MAL，当糖蛋白是AGP时; 并且当糖蛋白是M2BP时，测量M2BP与选自WFA，BPL，AAL，RCA120和TJAII的第二凝集素的结合。

公开(公告)号：US09796761B2

公开(公告)日：2017-10-24

申请号：US13384031

申请日：2010-07-12

申请人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

发明人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

IPC分类号： C40B30/04 ,  C07K14/00 ,  C07K9/00 ,  C07K14/47 ,  G01N33/574

CPC分类号： C07K9/00 ,  C07K14/47 ,  G01N33/57438 ,  G01N33/57469 ,  G01N2400/02 ,  G01N2800/085

摘要： The present invention is directed to developing a glycan markers capable of detecting a hepatic disease, and more specifically to developing a glycan marker indicating a hepatic disease-state. Furthermore, the present invention is also directed to developing a glycan marker capable of distinguishing hepatic disease-states with the progress of hepatocarcinoma. The present inventors identified, among the serum glycoproteins, glycopeptides and glycoproteins in which a glycan structure specifically changes due to a hepatic diseases including hepatocarcinoma and provide these as novel glycan markers (glycopeptide and glycoprotein) specific to hepatic disease-states.

公开(公告)号：US09234184B2

公开(公告)日：2016-01-12

申请号：US14009049

申请日：2012-03-30

申请人： Takaji Wakita ,  Tomoko Date ,  Yasuhito Tanaka ,  Masashi Mizokami

发明人： Takaji Wakita ,  Tomoko Date ,  Yasuhito Tanaka ,  Masashi Mizokami

IPC分类号： C12N7/08 ,  C12N7/00 ,  C12N7/04 ,  C12N15/86 ,  C07K16/10 ,  C12Q1/70 ,  C07K16/08 ,  C07K14/005 ,  A61K39/12 ,  A61K39/00

CPC分类号： C12N7/00 ,  A61K39/00 ,  A61K39/12 ,  C07K14/005 ,  C07K16/082 ,  C07K16/109 ,  C12N15/86 ,  C12N2770/24221 ,  C12N2770/24222 ,  C12N2770/24231 ,  C12N2770/24234 ,  C12N2770/24243 ,  C12N2770/24251 ,  C12Q1/707 ,  C12Q2600/136 ,  C12Q2600/156

摘要： A subgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and a fullgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and infectious HCV particle-producing ability, each derived from a novel HCV of genotype 1b, are provided. Particularly, a subgenomic replicon RNA (nucleic acid) and a fullgenomic replicon RNA (nucleic acid), each derived from an HCV genome of the NC1 strain which is a novel HCV genotype 1b isolated from a patient with acute severe hepatitis C, are provided.

摘要翻译： 提供了具有优异的自主复制能力的亚基因组复制子RNA（核酸）和具有优异的自主复制能力和感染性HCV颗粒产生能力的全基因组复制子RNA（核酸），各自源自基因型1b的新型HCV。 特别地，提供了从NC1菌株的HCV基因组衍生的亚基因组复制子RNA（核酸）和全基因组复制子RNA（核酸），其是从急性重症丙型肝炎患者分离的新型HCV基因型1b。

公开(公告)号：US08623608B2

公开(公告)日：2014-01-07

申请号：US13374807

申请日：2012-01-13

申请人： Hisashi Narimatsu ,  Yuzuru Ikehara ,  Atsushi Kuno ,  Maki Sogabe ,  Yasuhito Tanaka ,  Masashi Mizokami ,  Kiyoaki Ito ,  Shunsuke Matsubara ,  Chikayuki Tsuruno ,  Youichi Takahama ,  Takashi Kagawa ,  Shinya Nagai

发明人： Hisashi Narimatsu ,  Yuzuru Ikehara ,  Atsushi Kuno ,  Maki Sogabe ,  Yasuhito Tanaka ,  Masashi Mizokami ,  Kiyoaki Ito ,  Shunsuke Matsubara ,  Chikayuki Tsuruno ,  Youichi Takahama ,  Takashi Kagawa ,  Shinya Nagai

IPC分类号： G01N33/53 ,  G01N33/543

CPC分类号： G01N33/68 ,  C07K14/4726 ,  C07K14/473 ,  G01N33/5308 ,  G01N33/57438 ,  G01N33/6893 ,  G01N2333/4724 ,  G01N2333/4728 ,  G01N2400/00 ,  G01N2400/02 ,  G01N2800/085 ,  Y10T436/143333

摘要： An object of the present invention is to provide a method for measuring a glycan-marker glycoprotein, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a method for examining liver disease, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Disclosed is a method for measuring at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP) contained in a sample collected from a subject, comprising: measuring AGP binding to a first lectin selected from AOL and MAL, when the glycoprotein is AGP; and measuring M2BP binding to a second lectin selected from WFA, BPL, AAL, RCA120, and TJAII, when the glycoprotein is M2BP.

摘要翻译： 本发明的目的是提供一种测定聚糖标记糖蛋白的方法，通过该方法可以以比常规方法更高的精度检测肝脏疾病。 另外，本发明的目的在于提供一种检查肝脏疾病的方法，通过该方法能够以比常规方法更高的精度检测肝脏疾病。 公开了一种测量从受试者收集的样品中含有的至少一种选自α-1-酸糖蛋白（AGP）和Mac-2结合蛋白（M2BP）的糖蛋白的方法，包括：测量与所选第一凝集素的AGP结合 来自AOL和MAL，当糖蛋白是AGP时; 并且当糖蛋白是M2BP时，测量M2BP与选自WFA，BPL，AAL，RCA120和TJAII的第二凝集素的结合。

公开(公告)号：US20100028973A1

公开(公告)日：2010-02-04

申请号：US12442695

申请日：2007-09-26

申请人： Tatsuya Yamaguchi ,  Masaya Segawa ,  Masashi Mizokami ,  Yasuhito Tanaka ,  Kunitada Shimotohno ,  Makoto Hijikata

发明人： Tatsuya Yamaguchi ,  Masaya Segawa ,  Masashi Mizokami ,  Yasuhito Tanaka ,  Kunitada Shimotohno ,  Makoto Hijikata

IPC分类号： C12N7/00

CPC分类号： C12Q1/045 ,  C12N7/00 ,  C12N2730/10151 ,  C12N2730/10152 ,  C12N2770/24251 ,  C12N2770/24252 ,  C12Q1/025

摘要： The present invention provides (i) a method for proliferating a hepatitis virus, the method including the steps of: infecting, with the hepatitis virus, cells packed into a lumen of a hollow fiber made of a permeabilized membrane; and culturing the cells or (ii) a method for proliferating a hepatitis virus, the method including the steps of: infecting cells with the hepatitis virus; packing the cells into a lumen of a hollow fiber made of a permeabilized membrane; and culturing the cells. This provides an experimental system for infecting in vitro culture cells with a hepatitis virus such as HBV or HCV and then proliferating the hepatitis virus.

摘要翻译： 本发明提供（i）一种增加肝炎病毒的方法，其特征在于，包括以下步骤：用肝炎病毒感染填充在由透化膜构成的中空纤维的内腔中的细胞; 和（ii）增殖型肝炎病毒的方法，所述方法包括以下步骤：用所述肝炎病毒感染细胞; 将细胞包装到由透化膜制成的中空纤维的内腔中; 并培养细胞。 这提供了用肝炎病毒如HBV或HCV感染体外培养细胞，然后增殖肝炎病毒的实验系统。

公开(公告)号：US5831037A

公开(公告)日：1998-11-03

申请号：US501761

申请日：1995-07-12

申请人： Hiroyuki Ohsuga ,  Hiroaki Nakagawa ,  Chizu Ishida ,  Masahiro Fujimori ,  Yoshinori Tsukamoto ,  Noriko Takahashi ,  Yoshiya Kawamura ,  Masashi Mizokami ,  Koichi Sato ,  Kazuo Yoshioka ,  Tetsuya Kibe

发明人： Hiroyuki Ohsuga ,  Hiroaki Nakagawa ,  Chizu Ishida ,  Masahiro Fujimori ,  Yoshinori Tsukamoto ,  Noriko Takahashi ,  Yoshiya Kawamura ,  Masashi Mizokami ,  Koichi Sato ,  Kazuo Yoshioka ,  Tetsuya Kibe

IPC分类号： G01N33/50 ,  G01N30/88 ,  G01N33/66 ,  G01N33/68 ,  G01N33/48

CPC分类号： G01N33/6854 ,  Y10S436/824 ,  Y10T436/143333 ,  Y10T436/25375

摘要： The present invention relates to a novel clinical examination method which comprises analyzing the alteration in the amount of a specific component in oligosaccharides of immunogloblin G. Human diseases such as liver diseases, malignant hypertension, immunogloblin A-nephropathy, pediatric disorders, etc., are examined in terms of the alteration in bisecting N-acetylglucosamine-containing oligosaccharides in immunogloblin G from collected humor. The present invention provides highly accurate information in a manner applicable to practical operation for examination of liver diseases, allergic diseases, malignant hypertension, immunogloblin A nephropathy, pediatric disorders, as well as aging-dependent variations and the therapeutic effect of interferon.

摘要翻译： 本发明涉及一种新的临床检查方法，其包括分析免疫球蛋白G的寡糖中特异性成分的量的变化。人类疾病如肝脏疾病，恶性高血压，免疫球蛋白A肾病，儿科疾病等 根据收集的幽默在免疫球蛋白G中平均分解含N-乙酰葡糖胺的寡糖的变化进行检查。 本发明以适用于肝脏疾病，过敏性疾病，恶性高血压，免疫球蛋白A肾病，儿科疾病以及老化依赖性变异和干扰素治疗效果的实际操作的方式提供高度准确的信息。