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1. 发明申请

US20080233642A9 MAMMALIAN IMMORTALIZED LIVER CELL 审中-公开
标题翻译： MAMMALIAN IMMURALIZED LIVER CELL
公开(公告)号：US20080233642A9
公开(公告)日：2008-09-25
申请号：US10169084
申请日：2002-03-15
申请人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
发明人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
IPC分类号： C12N5/08
CPC分类号： C12N5/067 , A61K35/12 , C12N2503/00 , C12N2503/02 , C12N2510/04
摘要： The present invention provides a mammalian immortalized liver cell obtained by transferring a cell proliferation factor gene located between a pair of site-specific recombination sequences into a mammalian liver cell.
摘要翻译：本发明提供通过将位于一对位点特异性重组序列之间的细胞增殖因子基因转移到哺乳动物肝细胞中而获得的哺乳动物永生化肝细胞。

2. 发明授权

US07521234B2 Mammalian immortalized liver cell 失效
标题翻译：哺乳动物永生化肝细胞
公开(公告)号：US07521234B2
公开(公告)日：2009-04-21
申请号：US10169084
申请日：2002-03-15
申请人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
发明人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
IPC分类号： C12N5/08
CPC分类号： C12N5/067 , A61K35/12 , C12N2503/00 , C12N2503/02 , C12N2510/04
摘要： The present invention provides a mammalian immortalized liver cell obtained by transferring a cell proliferation factor gene located between a pair of site-specific recombination sequences into a mammalian liver cell.
摘要翻译：本发明提供通过将位于一对位点特异性重组序列之间的细胞增殖因子基因转移到哺乳动物肝细胞中而获得的哺乳动物永生化肝细胞。

3. 发明授权

US06645763B2 Immortalized bone marrow mesenchymal stem cell 失效
标题翻译：永生化骨髓间充质干细胞
公开(公告)号：US06645763B2
公开(公告)日：2003-11-11
申请号：US09975304
申请日：2001-10-12
申请人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara
发明人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara
IPC分类号： C12N508
CPC分类号： C12N9/1276 , C12N5/0663 , C12N2510/04 , C12N2799/027
摘要： The present invention provides a safe immortalized bone marrow mesenchymal stem cell obtained by transferring a cell proliferation factor gene inserted between a pair of site-specific recombination sequences to a bone marrow mesenchymal stem cell.
摘要翻译：本发明提供了通过将插入在一对位点特异性重组序列之间的细胞增殖因子基因转移到骨髓间充质干细胞而获得的安全永生化骨髓间充质干细胞。

4. 发明授权

US07033744B2 Method for proliferating a liver cell, a liver cell obtained thereby, and use thereof 失效
标题翻译：用于增殖肝细胞的方法，由此获得的肝细胞及其用途
公开(公告)号：US07033744B2
公开(公告)日：2006-04-25
申请号：US10169085
申请日：2002-03-15
申请人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
发明人： Naoya Kobayashi , Philippe Leboulch , Noriaki Tanaka , Toshiyoshi Fujiwara , Toshinori Totsugawa
IPC分类号： A01N1/00
CPC分类号： C12N5/067 , A61K35/12 , C12N2510/02 , C12N2510/04
摘要： The present invention provides a method comprising a step of transferring a cell proliferation factor gene into a mammalian liver cell to obtain an immortalized liver cell, a step of proliferating the immortalized liver cell, and a step of removing the cell proliferation factor gene from the immortalized liver cell; a large number of liver cells obtained thereby; and a treating agent and a artificial liver comprising obtained liver cell.
摘要翻译：本发明提供一种方法，其包括将细胞增殖因子基因转移到哺乳动物肝细胞中以获得永生化肝细胞，增殖永生化肝细胞的步骤和从永生化细胞中除去细胞增殖因子基因的步骤肝细胞; 由此获得大量肝细胞; 以及包含获得的肝细胞的处理剂和人造肝。

5. 发明申请

US20070264243A1 REVERSIBLY IMMORTALIZED HEPATOCYTES AND METHODS OF USE 审中-公开
标题翻译：可逆性肝移植和使用方法
公开(公告)号：US20070264243A1
公开(公告)日：2007-11-15
申请号：US11738678
申请日：2007-04-23
申请人： Ira Fox , Philippe LeBoulch , Naoya Kobayashi
发明人： Ira Fox , Philippe LeBoulch , Naoya Kobayashi
IPC分类号： A61K48/00 , A61K39/00 , A61P1/16 , C12N5/08
CPC分类号： C12N5/067 , A61K35/12 , C12N9/00 , C12N9/1211 , C12N2510/04 , C12N2799/022 , C12N2799/027 , C12N2800/30
摘要： Hepatocyte cells that are reversibly immortalized and grown in culture, which are functional and safe for use in transplantation, are disclosed. Also disclosed are methods for immortalizing primary hepatocytes, expanding the population of immortalized hepatocytes in culture, then reversing the immortalization to produce hepatocytes that are functional and safe for use in transplantation.
摘要翻译：公开了可逆地永生化并在培养中生长的功能和安全用于移植的肝细胞细胞。还公开了用于永生化原代肝细胞的方法，扩大培养中永生化肝细胞的群体，然后逆转永生化以产生功能和安全用于移植的肝细胞。

6. 发明授权

US07629168B2 Insulin expressing human pancreatic islet cell line capable of reversibly proliferating and use thereof 失效
标题翻译：胰岛素表达人胰岛细胞系，其能够可逆地增殖并使用
公开(公告)号：US07629168B2
公开(公告)日：2009-12-08
申请号：US10578260
申请日：2003-11-10
申请人： Noriaki Tanaka , Naoya Kobayashi , Michiki Narushima , Yoshihito Tanaka
发明人： Noriaki Tanaka , Naoya Kobayashi , Michiki Narushima , Yoshihito Tanaka
IPC分类号： C12P5/06 , C12P21/06 , C12P21/04 , A61K48/00
CPC分类号： C12N5/0676 , A61K35/12 , C12N2510/04
摘要： A reversibly immortalized human pancreatic islet cell line containing an hTERT gene and an SV40T gene each interposed between a pair of LoxP sequences, characterized in that it is capable of producing insulin and enhancing expression of insulin after excising the hTERT gene and the SV40T gene, in particular, NAKT-13 (deposited with International Patent Organism Depository, National Institute of Advanced Industrial Science and Technology, address: AIST Tsukuba Central 6, 1-1, Higashi 1-Chome, Tsukuba-shi, Ibaraki-ken, 305-8566 Japan, deposited date: Sep. 4, 2003, accession number: FERM BP-08461) or a passage cell line thereof; a human pancreatic islet cell obtained by excising the hTERT gene and the SV40T gene from the reversibly immortalized human pancreatic islet cell line or passage cell line thereof; and use of these cells. By using the reversibly immortalized human pancreatic islet cell line of the invention insulin-producing cells can be easily and surely obtained in a number enough to meet the demand.
摘要翻译：一种含有hTERT基因和SV40T基因的可逆永生人胰岛细胞系，每个插入一对LoxP序列之间，其特征在于能够在切除hTERT基因和SV40T基因之后产生胰岛素并增强胰岛素的表达，特别是NAKT-13（保藏于国立先进工业科学与技术研究所国际专利生物保藏中心，地址：日本茨城市茨城市筑波市东1町1-1-1筑波中央6-1号日本305-8566 ，保藏日期：2003年9月4日，登录号：FERM BP-08461）或其传代细胞系; 通过从可逆永生化人胰岛细胞系或其传代细胞系中切除hTERT基因和SV40T基因获得的人胰岛细胞; 并使用这些细胞。通过使用本发明的可逆永生人胰岛细胞系，可以容易且可靠地获得足够数量的胰岛素产生细胞以满足需求。

7. 发明申请

US20090148424A1 Reversibly immortalized mammalian liver cells and use thereof 审中-公开
标题翻译：可逆永生化的哺乳动物肝细胞及其用途
公开(公告)号：US20090148424A1
公开(公告)日：2009-06-11
申请号：US10594544
申请日：2004-03-31
申请人： Naoya Kobayashi , Noriaki Tanaka , Michinori Kohara
发明人： Naoya Kobayashi , Noriaki Tanaka , Michinori Kohara
IPC分类号： A61K35/12 , C12N5/06 , C12N5/08 , A01N1/02 , C12N15/00
CPC分类号： C12N5/067 , A01K2207/15 , A01K2227/106 , A01K2267/035 , A61K35/12 , A61M1/3689 , C12N2510/04 , C12N2800/30
摘要： The present invention provides a reversibly immortalized mammalian liver cell line, especially CYNK-1 (deposited with International Patent Organism Depository, National Institute of Advanced Industrial Science and Technology, address: AIST Tsukuba Central 6, 1-1, Higashi 1-Chome, Tsukuba-shi, Ibaraki-ken, 305-8566 Japan, deposited date: Mar. 10, 2004, accession number: FERM BP-08657) comprising an immortalizing gene interposed between a pair of site-specific recombination sequences and a suicide gene in the outside of the pair of site-specific recombination sequences, characterized in that the suicide gene can exhibit its function after excision of the pair of site-specific recombination sequences, or passage cell line thereof; a mammalian liver cell obtained by excising the immortalizing gene from the reversibly immortalized mammalian liver cell line or passage cell line thereof; and use of these cells. By utilizing the reversibly immortalized mammalian liver cell line of the present invention enables the obtainment of the number of the liver cells and utilization as materials for artificial liver reactors and cell preparations.
摘要翻译：本发明提供了可逆地永生化的哺乳动物肝细胞系，特别是CYNK-1（保藏在国际专利生物保藏中心，国立先进工业科学和技术研究所，地址：筑波中心6-1-1，Higashi 1-Chome，Tsukuba -shi，Ibaraki-ken，305-8566日本，保藏日期：2004年3月10日，登录号：FERM BP-08657），其包含插入一对位点特异性重组序列之间的永生化基因和外部的自杀基因的特异性重组序列，其特征在于，自杀基因可以在切除一对位点特异性重组序列或其通过细胞系后显示其功能; 通过从可逆永生化的哺乳动物肝细胞系或其通过细胞系切除永生化基因获得的哺乳动物肝细胞; 并使用这些细胞。通过利用本发明的可逆永生化的哺乳动物肝细胞系，可以获得肝细胞的数量和用作人造肝反应器和细胞制剂的材料。

8. 发明授权

US07919080B2 Immortalized hepatocyte cell line secreting modified insulin with glucose sensitivity 失效
标题翻译：具有葡萄糖敏感性的永生化肝细胞细胞系分泌修饰胰岛素
公开(公告)号：US07919080B2
公开(公告)日：2011-04-05
申请号：US11984006
申请日：2007-11-13
申请人： Naoya Kobayashi , Noriaki Tanaka , Teru Okitsu , Ji-Won Yoon , Hee-Sook Jun , Seungjin Shin
发明人： Naoya Kobayashi , Noriaki Tanaka , Teru Okitsu , Ji-Won Yoon , Hee-Sook Jun , Seungjin Shin
IPC分类号： A01N63/00 , A01N65/00 , A61K48/00
CPC分类号： C12N15/907 , A61K35/12 , A61K48/00 , C07K14/62 , C12N5/067 , C12N15/63 , C12N2501/70 , C12N2510/00 , C12N2510/04
摘要： The present invention provides a cell line which can be substituted for β cells in human mature pancreatic islets and express insulin in a glucose-concentration dependent manner, and enables the easy obtainment of the number of cells which meets the demand. The present invention also provides a therapeutical cell preparation for treating diabetes. The cell lines of the present invention can be obtained by integrating both a nucleotide sequence encoding tamoxifen-induced Cre recombinase and a nucleotide sequence encoding insulin regulated by glucose-sensitive promoter into the chromosome in a human immortalized hepatic cell line FERM BP-7498 containing the TERT gene inserted in between a pair of LoxP sequences.
摘要翻译：本发明提供可以代替“bgr”的细胞系。人成熟胰岛中的细胞并以葡萄糖浓度依赖的方式表达胰岛素，并且能够容易地获得满足需求的细胞数量。本发明还提供了治疗糖尿病的治疗细胞制剂。本发明的细胞系可以通过将编码他莫昔芬诱导的Cre重组酶的核苷酸序列与编码由葡萄糖敏感性启动子调节的胰岛素的核苷酸序列整合到人永生化肝细胞系FERM BP-7498中而获得，所述人类永生化肝细胞系FERM BP-7498含有 TERT基因插入一对LoxP序列之间。

9. 发明申请

US20090209033A1 Immortalized hepatocyte cell line secreting modified insulin with glucose sensitivity 失效
标题翻译：具有葡萄糖敏感性的永生化肝细胞细胞系分泌修饰胰岛素
公开(公告)号：US20090209033A1
公开(公告)日：2009-08-20
申请号：US11984006
申请日：2007-11-13
申请人： Naoya Kobayashi , Noriaki Tanaka , Teru Okitsu , Ji-Won Yoon , Hee-Sook Jun , Seungjin Shin
发明人： Naoya Kobayashi , Noriaki Tanaka , Teru Okitsu , Ji-Won Yoon , Hee-Sook Jun , Seungjin Shin
IPC分类号： C12N5/08 , C12N5/06
CPC分类号： C12N15/907 , A61K35/12 , A61K48/00 , C07K14/62 , C12N5/067 , C12N15/63 , C12N2501/70 , C12N2510/00 , C12N2510/04
摘要： The present invention provides a cell line which can be substituted for β cells in human mature pancreatic islets and express insulin in a glucose-concentration dependent manner, and enables the easy obtainment of the number of cells which meets the demand. The present invention also provides a therapeutical cell preparation for treating diabetes. The cell lines of the present invention can be obtained by integrating both a nucleotide sequence encoding tamoxifen-induced Cre recombinase and a nucleotide sequence encoding insulin regulated by glucose-sensitive promoter into the chromosome in a human immortalized hepatic cell line FERM BP-7498 containing the TERT gene inserted in between a pair of LoxP sequences.
摘要翻译：本发明提供了可以在人成熟胰岛中代替β细胞并以葡萄糖浓度依赖性方式表达胰岛素的细胞系，并且能够容易地获得满足需求的细胞数量。本发明还提供了治疗糖尿病的治疗细胞制剂。本发明的细胞系可以通过将编码他莫昔芬诱导的Cre重组酶的核苷酸序列与编码由葡萄糖敏感性启动子调节的胰岛素的核苷酸序列整合到人永生化肝细胞系FERM BP-7498中而获得，所述人类永生化肝细胞系FERM BP-7498含有 TERT基因插入一对LoxP序列之间。

10. 发明授权

US08697438B2 Cell cultivation method and cell culture 有权
公开(公告)号：US08697438B2
公开(公告)日：2014-04-15
申请号：US13336347
申请日：2011-12-23
申请人： Naoya Kobayashi , Noriaki Tanaka
发明人： Naoya Kobayashi , Noriaki Tanaka
IPC分类号： C12N5/00 , C12N5/02 , C12N5/071 , A01N63/00 , A01N65/00
CPC分类号： C12N5/0671 , C12N5/067 , C12N5/0676 , C12N2533/50 , C12N2533/52 , C12N2533/54
摘要： Provided is a cell cultivation method in which the cell is cultured using a peptide hydrogel as a scaffold, for carrying out high-dimensional culture of a cell such as porcine hepatocyte, human hepatocyte, porcine pancreatic islet or human pancreatic islet for a long period under conditions where cell survival, cell morphology and cell functions are maintained. Also provided are a cell culture including a cell and a peptide hydrogel obtained by the above-described cultivation method, a bioreactor including the cell culture, and a cell preparation including the cell culture.

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