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1. 发明专利

JP2007228962A Method for producing human hepatocyte chimera rat 审中-公开
标题翻译：生产人肝细胞癌的方法
公开(公告)号：JP2007228962A
公开(公告)日：2007-09-13
申请号：JP2007022116
申请日：2007-01-31
申请人： Bio Integurensu:Kk , Hiroshima Industrial Promotion Organization , Hiroshima Univ , Phoenix Bio:Kk , 国立大学法人広島大学 , 株式会社バイオインテグレンス , 株式会社フェニックスバイオ , 財団法人ひろしま産業振興機構
发明人： YOSHIZATO KATSUTOSHI , MUKOYA TOMOYO , IGARASHI TOMOKA , TACHIBANA ARI , ASAHARA TOSHIMASA , ODAN HIDEKI
IPC分类号： A01K67/027 , A61L27/00 , C12N5/07 , C12N5/077 , C12N5/078
摘要： PROBLEM TO BE SOLVED: To provide a method for transplanting human hepatocytes separated from a human hepatocyte chimera mouse into a rat. SOLUTION: This method for transplanting human hepatocytes into a bone marrow cell-replaced rat obtained by replacing ≥95% of rat bone marrow cells by the bone marrow cells of an immunity-deficient mouse. The human hepatocytes are obtained by separating and purifying the human hepatocytes recovered from a human hepatocyte chimera mouse from mouse hepatocytes with an antibody specifically recognizing the human hepatocytes. Also, the bone marrow cell-replaced rate obtained by transplanting the marrow of an immunity-deficient mouse into a young rat irradiated with X-rays. COPYRIGHT: (C)2007,JPO&INPIT
摘要翻译：待解决的问题：提供将人肝细胞嵌合体小鼠分离的人肝细胞移植到大鼠中的方法。解决方案：将人肝细胞移植到通过免疫缺陷小鼠的骨髓细胞代替大于95％的大鼠骨髓细胞获得的骨髓细胞替代大鼠中的方法。通过用特异性识别人肝细胞的抗体从小鼠肝细胞中分离和纯化从人肝细胞嵌合体小鼠中回收的人肝细胞获得人肝细胞。此外，通过将免疫缺陷小鼠的骨髓移植到用X射线照射的幼鼠中获得的骨髓细胞替代率。版权所有（C）2007，JPO＆INPIT

2. 发明专利

JP2008044898A Hemophilia b curative agent and method for producing the same 有权
标题翻译：乙酰肝素B治疗剂及其生产方法
公开(公告)号：JP2008044898A
公开(公告)日：2008-02-28
申请号：JP2006222787
申请日：2006-08-17
申请人： Hiroshima Industrial Promotion Organization , Hiroshima Univ , 国立大学法人広島大学 , 財団法人ひろしま産業振興機構
发明人： MUKOYA TOMOYO , YOSHIZATO KATSUTOSHI , OHASHI KAZUO , YOSHIOKA AKIRA
IPC分类号： A61K35/407 , A01K67/027 , A61K38/36 , A61P7/04 , C12N5/07 , C12N5/077 , C12N5/078 , C12N15/09 , C12P21/02
摘要： PROBLEM TO BE SOLVED: To provide a safe hemophilia B curative agent enabling itself to be supplied in large quantities, and to provide a method for producing the same.
SOLUTION: The hemophilia B curative agent contains human hepatocytes proliferated in the body of an immunodeficient nonhuman animal with hepatopathy. The method for producing the hemophilia B curative agent in large quantities comprises the step of creating a chimeric nonhuman animal by transplanting human hepatocytes into an immunodeficient nonhuman animal with hepatopathy and the step of retrieving human hepatocytes proliferated in the body of the chimeric nonhuman animal. The human hepatocytes thus retrieved has the hemostatic function for coagulation factor IX-deleted human plasma.
COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：要解决的问题：提供一种能够大量供应自身的安全的血友病B治疗剂，并提供其生产方法。解决方案：血友病B治疗剂含有人类肝细胞在具有肝病的免疫缺陷型非人动物体内增殖。大量生产血友病B治疗剂的方法包括通过将人肝细胞移植到具有肝病的免疫缺陷型非人动物中并产生在嵌合非人动物体内增殖的人肝细胞的步骤来产生嵌合非人动物的步骤。如此回收的人肝细胞具有凝血因子IX缺失的人血浆的止血功能。版权所有（C）2008，JPO＆INPIT

3. 发明专利

JP2007037542A Method for treating mouse having human hepatocyte 有权
标题翻译：用于治疗人类肝细胞的小鼠的方法
公开(公告)号：JP2007037542A
公开(公告)日：2007-02-15
申请号：JP2006181621
申请日：2006-06-30
申请人： Bio Integurensu:Kk , Hiroshima Industrial Promotion Organization , 株式会社バイオインテグレンス , 財団法人ひろしま産業振興機構
发明人： MUKOYA TOMOYO , YOSHIZATO KATSUTOSHI , MASUMOTO NORIO , KATAOKA YOSHIO , TSUNODA TATSUHIKO , MIYA FUYUKI
IPC分类号： A01K67/027 , A61K35/407 , A61K38/27 , A61P1/00 , A61P1/16 , A61P5/02 , A61P43/00
摘要： PROBLEM TO BE SOLVED: To provide a method for obtaining a mouse individual of which the mouse hepatocytes are substituted by human hepatocytes grown from human adult hepatocytes in a high ratio, and to provide a method for improving fatty liver of a mouse to which human young hepatocytes are transplanted and which suffers from immunodeficiency hepatopathy.
SOLUTION: In this method for obtaining the mouse individual, the human adult hepatocytes are transplanted to a mouse suffering from the immunodeficiency hepatopathy and then a human growth hormone is administered to the mouse, so that the substitution ratio of the human adult hepatocytes is increased twice or more. Further, the fatty liver is improved by continuously administering the human growth hormone for a fixed period to the mouse to which the human young hepatocytes are transplanted and which suffers from the immunodeficiency hepatopathy.
COPYRIGHT: (C)2007,JPO&INPIT
摘要翻译：待解决的问题：提供一种获得小鼠肝细胞由人成人肝细胞以高比例生长的人肝细胞代替的小鼠个体的方法，并提供一种改善小鼠脂肪肝的方法哪些人类年轻肝细胞被移植并且患有免疫缺陷性肝病。解决方案：在获得小鼠个体的方法中，将人成年肝细胞移植到患有免疫缺陷型肝病的小鼠中，然后向小鼠施用人生长激素，使得人成人肝细胞的取代比例增加两倍以上。此外，通过将人生长激素持续施用于移植人类年轻肝细胞并且患有免疫缺陷型肝病的小鼠，来改善脂肪肝。版权所有（C）2007，JPO＆INPIT

4. 发明专利

JP2013085485A Chimeric non-human animal carrying human hepatocyte 有权
标题翻译：动物非人类动物携带人类肝脏
公开(公告)号：JP2013085485A
公开(公告)日：2013-05-13
申请号：JP2011226233
申请日：2011-10-13
申请人： Phoenix Bio:Kk , 株式会社フェニックスバイオ , Tottori Univ , 国立大学法人鳥取大学
发明人： OSHIMURA MITSUO , KATSUKI YASUHIRO , MUKOYA TOMOYO , SHIMADA TAKU , KAKUNI MASAKAZU , HAMAMURA RIKO , KAMIMURA HIDETAKA , KAWAMURA AKIO , NAKATA NAOYUKI , OBUCHI MASATO , KATO KOTA
IPC分类号： A01K67/027 , G01N33/15 , G01N33/50
CPC分类号： A01K67/0271 , A01K2207/12 , A01K2217/075 , A01K2227/105 , A01K2267/03 , C12N9/0042 , G01N33/5067 , G01N33/5088
摘要： PROBLEM TO BE SOLVED: To provide a chimeric non-human animal having a human hepatocyte population in the body thereof, wherein the influence of the metabolism of a drug by cells of the non-human animal is suppressed or deleted.SOLUTION: The method for producing the chimeric non-human animal in which a drug metabolism system is deleted or suppressed and which has a drug metabolism system to be driven by a human hepatocyte comprises transplanting a human hepatocyte into a non-human animal that is characterized in that (i) the non-human animal is immunocompromised, (ii) the non-human animal is suffered from a hepatic disorder and (iii) the function of endogenous Cyp3a gene is deleted in the non-human animal.
摘要翻译：待解决的问题：提供其体内具有人肝细胞群体的嵌合非人动物，其中抑制或缺失了非人动物细胞对药物代谢的影响。解决方案：制备其中药物代谢系统被缺失或抑制并且具有由人肝细胞驱动的药物代谢系统的嵌合非人动物的方法包括将人肝细胞移植到非人动物中其特征在于（i）非人类动物是免疫受损的，（ii）非人类动物患有肝脏疾病，和（iii）在非人类动物中内源性Cyp3a基因的功能被缺失。版权所有（C）2013，JPO＆INPIT

5. 发明专利

JP2009273408A Method for detecting murine pneumocystis carinii 有权
标题翻译：检测毛细血管球蛋白CARINII的方法
公开(公告)号：JP2009273408A
公开(公告)日：2009-11-26
申请号：JP2008127762
申请日：2008-05-14
申请人： Phoenix Bio:Kk , 株式会社フェニックスバイオ
发明人： MUKOYA TOMOYO , YANAGI AIMI , TACHIBANA ARI
IPC分类号： C12N15/09 , C12Q1/68
摘要： PROBLEM TO BE SOLVED: To provide a primer and probe for PCR which can detect murine carinii in high sensitivity without false detection or detection omission: and to provide a method for detecting murine Pneumocystis carinii which can detect murine carinii in high sensitivity without false detection or detection omission.
SOLUTION: Disclosed is a method for detecting murine Pneumocystis carinii including a process of performing PCR using DNA extracted from murine lung as a template and using a set of a primer comprising DNA consisting of 40 bases at a maximum which is included in the 3' end of base sequence comprising a specific sequence and another different primer comprising DNA consisting of 40 bases at a maximum which is included in the 3' end of base sequence comprising a specific sequence in the presence of Taqman probe providing DNA containing 50 bases at a maximum including a base sequence of base number 25 to 50 in a base sequence comprising a specific sequence; and a process of detecting DNA amplification by detecting fluorescent light.
COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：要解决的问题：提供PCR的引物和探针，其可以高灵敏度地检测鼠卡氏杆菌，而没有错误检测或检测省略：提供一种检测鼠卡氏肺囊虫的方法，其可以高灵敏度检测卡氏肺杆菌，而没有错误检测或检测省略。解决方案：公开了一种用于检测鼠卡氏肺囊虫的方法，包括使用从小鼠肺提取的DNA作为模板进行PCR的方法，并使用一组包含由最多40个碱基组成的DNA的引物，其包含在 3'末端的碱基序列，另外一个不同的引物包含由最多含有40个碱基的DNA组成的碱基序列的3'末端，其包含特异性序列，在Taqman探针的存在下，提供含有50个碱基的DNA 在包含特定序列的碱基序列中包含碱基序列25至50的最大值; 以及通过检测荧光来检测DNA扩增的过程。版权所有（C）2010，JPO＆INPIT

6. 发明专利

JP2015002723A ＨＢＶ特異的人工ＤＮＡヌクレアーゼ审中-公开
标题翻译： HBV特异性人工DNA核酸
公开(公告)号：JP2015002723A
公开(公告)日：2015-01-08
申请号：JP2013130908
申请日：2013-06-21
申请人：公益財団法人東京都医学総合研究所 , Tokyo Metropolitan Institute Of Medical Science , 株式会社フェニックスバイオ , Phoenix Bio:Kk
发明人： OBARA MICHINORI , ISHIDA YUJI , MUKOYA TOMOYO , SHIMADA TAKU
IPC分类号： C12N15/09 , A61K31/711 , A61K35/76 , A61K38/46 , A61K48/00 , A61P31/20 , C12N9/22
CPC分类号： A61K31/711 , A61K38/00 , C07K14/195 , C07K2319/00 , C07K2319/01 , C12N9/22
摘要：【課題】HBV感染の根治を目的とする新たな治療手段を提供することを目的とする。【解決手段】HBV DNAと特異的に結合するように改変されたXanthomonas属細菌由来のTALEと、配列非依存性のエンドヌクレアーゼとを含んでなる、HBV特異的人工DNAヌクレアーゼ。【選択図】なし
摘要翻译：要解决的问题：提供完全治愈HBV感染的新型治疗手段。解决方案：HBV特异性人造DNA核酸酶包含：修饰为特异性结合HBV DNA的黄单胞菌属细菌衍生的TALE（转录激活子样效应物）和序列无关内切核酸酶。

7. 发明专利

JP2013230093A Urokinase-type plasminogen activator transgenic mouse 有权
标题翻译：尿激酶型PLASMINOGEN ACTIVATOR TRANSGENIC MOUSE
公开(公告)号：JP2013230093A
公开(公告)日：2013-11-14
申请号：JP2012102814
申请日：2012-04-27
申请人： Tokyo Metropolitan Institute Of Medical Science , 公益財団法人東京都医学総合研究所 , Chugai Pharmaceut Co Ltd , 中外製薬株式会社 , Phoenix Bio:Kk , 株式会社フェニックスバイオ
发明人： OBARA MICHINORI , TERAKOSOSHITA KOICHI , KAWASE YOSUKE , MUKOYA TOMOYO , OSHITA HIROKI , HAMAMURA RIKO
IPC分类号： A01K67/027 , C12N15/09 , G01N33/15 , G01N33/50
CPC分类号： A01K67/0275 , A01K67/0271 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2217/15 , A01K2217/206 , A01K2227/105 , A01K2267/0337 , A01K2267/035 , C12N9/6462 , C12N15/8509 , C12N15/8775 , C12N2015/8581 , G01N33/5067 , G01N33/5088 , Y10T436/146666
摘要： PROBLEM TO BE SOLVED: To provide a hepatopathy mouse with a high degree of disorder to original hepatocytes of the mouse while having a uPA gene in a heterozygous form, and a method for efficiently producing the mouse.SOLUTION: A method for producing a hepatopathy mouse with a uPA gene in a heterozygous form, includes the steps of: (i) transforming a mouse ES cell with a DNA fragment that contains a liver-specific promoter/enhancer and urokinase-type plasminogen activator-encoding cDNA that is operably linked under the control of the liver-specific promoter/enhancer; (ii) injecting the transformed mouse ES cell obtained in the step (i) into a host embryo; (iii) transplanting the host embryo obtained in the step (ii) and injected with the ES cell, into the uterus of a surrogate mother mouse to obtain a chimeric mouse; and (iv) mating the chimeric mouse obtained in the step (iii) to obtain a transgenic mouse in which the DNA fragment is introduced in the heterozygous form.
摘要翻译：要解决的问题：提供具有高度紊乱的肝病小鼠，同时具有杂合形式的uPA基因，以及有效地产生小鼠的方法。解决方案：一种肝病小鼠的制备方法具有杂合形式的uPA基因包括以下步骤：（i）用包含肝特异性启动子/增强子和编码尿激酶型纤溶酶原激活物编码cDNA的DNA片段转化小鼠ES细胞，所述cDNA可操作地连接在控制肝脏特异性启动子/增强子; （ii）将步骤（i）中获得的转化的小鼠ES细胞注入宿主胚胎; （iii）将步骤（ii）中获得的宿主胚胎移植并注射到ES细胞进入代孕母鼠的子宫中以获得嵌合小鼠; 和（iv）将步骤（iii）中获得的嵌合小鼠交配以获得其中DNA片段以杂合形式引入的转基因小鼠。

8. 发明专利

JP2012039888A Hepatitis b virus-infected model human hepatocyte 有权
标题翻译：乙型肝炎病毒感染模型人类肝脏
公开(公告)号：JP2012039888A
公开(公告)日：2012-03-01
申请号：JP2010181121
申请日：2010-08-12
申请人： Phoenix Bio:Kk , 株式会社フェニックスバイオ
发明人： ISHIDA YUJI , MUKOYA TOMOYO
IPC分类号： C12N5/071 , A01K67/027 , C12Q1/06
摘要： PROBLEM TO BE SOLVED: To provide a stably suppliable hepatitis B virus-infected model human hepatocyte reproducing HBV infection in a human living body.SOLUTION: The hepatitis B virus-infected model cell is obtained by a method including: a first step of producing a chimera non-human animal by transplanting human hepatocytes to a non-human animal with an immunodeficient hepatopathy; a second step of separating human hepatocytes grown in the body of the chimera non-human animal; and a third step of infecting the separated human hepatocytes with the HBV. Further, a method for preventing the hepatitis B or screening of a therapeutic agent, including a third step of selecting a test article to reduce the amount of hepatitis B viruses in the culture supernatant or in cells to 50% or less by supplying the test article is also provided.
摘要翻译：要解决的问题：提供一种稳定可供应的乙型肝炎病毒感染模型人类肝细胞在人体内再现HBV感染。乙型肝炎病毒感染的模型细胞通过以下方法获得：包括：通过用免疫缺陷性肝病将人肝细胞移植到非人动物来产生嵌合体非人动物的第一步骤; 分离生长在嵌合体非人动物体内的人肝细胞的第二步骤; 以及用HBV感染分离的人肝细胞的第三步。另外，本发明提供一种预防乙型肝炎或治疗剂的筛选的方法，其特征在于，包括：第3步骤，通过供给上述试验物，选择试验物品，将培养上清液或细胞中的乙型肝炎病毒量减少到50％以下也提供。版权所有（C）2012，JPO＆INPIT

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