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1. 发明申请

US20130198874A1 Model Animal for Pregnancy-induced Hypertension Syndrome, and Treatment Method Therefor 有权
公开(公告)号：US20130198874A1
公开(公告)日：2013-08-01
申请号：US13581510
申请日：2011-03-04
申请人： Masaru Okabe , Masahito Ikawa , Tadashi Kimura , Keiichi Kumasawa
发明人： Masaru Okabe , Masahito Ikawa , Tadashi Kimura , Keiichi Kumasawa
IPC分类号： A01K67/027 , A61D19/04
CPC分类号： A01K67/0278 , A01K67/0271 , A01K67/0275 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2217/072 , A01K2227/105 , A01K2267/0375 , A01K2267/0393 , A61D19/04 , C12N9/12 , C12N9/1205 , C12N15/8509 , C12N15/86 , C12N15/873 , C12N2015/8527 , C12N2740/15043 , C12N2740/16043 , C12N2799/027
摘要： A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum. Furthermore, when pravastatin was administered to this model animal, it was found that diseases such as pregnancy-induced hypertension syndrome were improved by the activation of placenta-derived growth factor (PIGF) which antagonizes sFLT1.

2. 发明授权

US09029627B2 Model animal for pregnancy-induced hypertension syndrome, and treatment method therefor 有权
标题翻译：妊娠高血压综合征模型动物及其治疗方法
公开(公告)号：US09029627B2
公开(公告)日：2015-05-12
申请号：US13581510
申请日：2011-03-04
申请人： Masaru Okabe , Masahito Ikawa , Tadashi Kimura , Keiichi Kumasawa
发明人： Masaru Okabe , Masahito Ikawa , Tadashi Kimura , Keiichi Kumasawa
IPC分类号： A01K67/027 , C12N15/85 , A61D19/04 , C12N9/12
CPC分类号： A01K67/0278 , A01K67/0271 , A01K67/0275 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2217/072 , A01K2227/105 , A01K2267/0375 , A01K2267/0393 , A61D19/04 , C12N9/12 , C12N9/1205 , C12N15/8509 , C12N15/86 , C12N15/873 , C12N2015/8527 , C12N2740/15043 , C12N2740/16043 , C12N2799/027
摘要： A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum. Furthermore, when pravastatin was administered to this model animal, it was found that diseases such as pregnancy-induced hypertension syndrome were improved by the activation of placenta-derived growth factor (PIGF) which antagonizes sFLT1.
摘要翻译：使用慢病毒载体产生在鼠胎盘中特异性表达人sFLT1的非人动物，以提供接近临床条件的诸如妊娠诱发的高血压综合征的模型动物，用于产生模型动物的方法，方法通过使用模型动物筛选候选化合物作为诸如妊娠诱发的高血压综合征的疾病的治疗剂，以及用于诸如妊娠诱发的高血压综合征的疾病的治疗剂。结果，发现模型动物表现出非常接近人类临床状况的症状，即高血压以及胎盘功能不全，子宫内生长迟缓，肾小球硬化和怀孕期间蛋白尿的表现，以及改善这些症状产后。此外，当对该模型动物施用普伐他汀时，发现通过激活拮抗sFLT1的胎盘衍生生长因子（PIGF）来改善诸如妊娠诱导的高血压综合征的疾病。

3. 发明授权

US09700024B2 Model animal for pregnancy-induced hypertension syndrome, and treatment method therefor 有权
公开(公告)号：US09700024B2
公开(公告)日：2017-07-11
申请号：US14686166
申请日：2015-04-14
申请人： FUSO PHARMACEUTICAL INDUSTRIES, LTD. , Masaru Okabe , Masahito Ikawa
发明人： Masaru Okabe , Masahito Ikawa , Tadashi Kimura , Keiichi Kumasawa
IPC分类号： A01K67/027 , C12N15/85 , A61D19/04 , C12N9/12 , C12N15/86 , C12N15/873
CPC分类号： A01K67/0278 , A01K67/0271 , A01K67/0275 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2217/072 , A01K2227/105 , A01K2267/0375 , A01K2267/0393 , A61D19/04 , C12N9/12 , C12N9/1205 , C12N15/8509 , C12N15/86 , C12N15/873 , C12N2015/8527 , C12N2740/15043 , C12N2740/16043 , C12N2799/027
摘要： A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum. Furthermore, when pravastatin was administered to this model animal, it was found that diseases such as pregnancy-induced hypertension syndrome were improved by the activation of placenta-derived growth factor (PIGF) which antagonizes sFLT1.

4. 发明申请

US20090013418A1 Trophectodermal Cell-Specific Gene Transfer Methods 有权
标题翻译： Trophectodermal细胞特异性基因转移方法
公开(公告)号：US20090013418A1
公开(公告)日：2009-01-08
申请号：US12063576
申请日：2006-07-31
申请人： Masaru Okabe , Masahito Ikawa
发明人： Masaru Okabe , Masahito Ikawa
IPC分类号： A61K49/00 , C12N15/09 , C12N5/00 , A01K67/027
CPC分类号： C12N15/86 , A01K2217/05 , A01K2227/10 , A01K2267/03 , A01K2267/0393 , C12N5/0605 , C12N2510/00 , C12N2799/027
摘要： The present inventors discovered that genes could be introduced specifically into trophectodermal cells with high efficiency, by infecting blastocysts with viral vectors carrying an arbitrary polynucleotide, or by using a nucleic acid transfection reagent in blastocysts, from which zona pellucida (extracellular matrix covering preimplantation early embryos to protect them from infection of viruses and the like) is removed. This method has no risk of infecting cells of the inner cell mass, which develops into a fetus in the future, with the introduced polynucleotide because the trophectoderm serves as a barrier. The present invention provides methods for introducing foreign genes into only placenta but not fetus, which enables rescue of genetically mutant animals from embryonic lethality due to placental abnormality and allows their birth. Furthermore, it is possible to analyze expression and effect of genes that regulate placental formation or placental function by using these methods.
摘要翻译：本发明人发现，通过用携带任意多核苷酸的病毒载体感染囊胚，或者通过使用囊胚中的核酸转染试剂，将透明带（细胞外基质覆盖植入前的早期胚胎），将基因以高效率特异性地引入培养胚胎细胞中以防止它们免受病毒感染等）被去除。这种方法没有感染未来发育成胎儿的内细胞团的细胞与引入的多核苷酸的风险，因为滋养外胚层作为屏障。本发明提供了将外源基因引入胎盘而不是胎儿的方法，其能够由于胎盘异常而从胚胎致死性中拯救遗传突变的动物，并允许其诞生。此外，可以通过使用这些方法来分析调节胎盘形成或胎盘功能的基因的表达和效果。

5. 发明授权

US08815598B2 Trophectodermal cell-specific gene transfer methods 有权
标题翻译：滋养细胞特异性基因转移方法
公开(公告)号：US08815598B2
公开(公告)日：2014-08-26
申请号：US12063576
申请日：2006-07-31
申请人： Masaru Okabe , Masahito Ikawa
发明人： Masaru Okabe , Masahito Ikawa
IPC分类号： C12N15/00 , C12N15/86 , C12N5/00 , C12N5/02 , C12N5/073
CPC分类号： C12N15/86 , A01K2217/05 , A01K2227/10 , A01K2267/03 , A01K2267/0393 , C12N5/0605 , C12N2510/00 , C12N2799/027
摘要： The present inventors discovered that genes could be introduced specifically into trophectodermal cells with high efficiency, by infecting blastocysts with viral vectors carrying an arbitrary polynucleotide, or by using a nucleic acid transfection reagent in blastocysts, from which zona pellucida (extracellular matrix covering preimplantation early embryos to protect them from infection of viruses and the like) is removed. This method has no risk of infecting cells of the inner cell mass, which develops into a fetus in the future, with the introduced polynucleotide because the trophectoderm serves as a barrier. The present invention provides methods for introducing foreign genes into only placenta but not fetus, which enables rescue of genetically mutant animals from embryonic lethality due to placental abnormality and allows their birth. Furthermore, it is possible to analyze expression and effect of genes that regulate placental formation or placental function by using these methods.
摘要翻译：本发明人发现，通过用携带任意多核苷酸的病毒载体感染囊胚，或者通过使用囊胚中的核酸转染试剂，将透明带（细胞外基质覆盖植入前的早期胚胎），将基因以高效率特异性地引入培养胚胎细胞中以防止它们免受病毒感染等）被去除。这种方法没有感染未来发育成胎儿的内细胞团的细胞与引入的多核苷酸的风险，因为滋养外胚层作为屏障。本发明提供了将外源基因引入胎盘而不是胎儿的方法，其能够由于胎盘异常而从胚胎致死性中拯救遗传突变的动物，并允许其诞生。此外，可以通过使用这些方法来分析调节胎盘形成或胎盘功能的基因的表达和效果。

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