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1. 发明申请

US20090246170A1 Therapeutic Agent For Alzheimer's Disease 审中-公开
标题翻译：阿尔茨海默病治疗剂
公开(公告)号：US20090246170A1
公开(公告)日：2009-10-01
申请号：US12302927
申请日：2007-05-31
申请人： Makoto Inoue , Yumiko Tokusumi , Hitoshi Iwasaki , Hiroto Hara , Toshiaki Tabata , Mamoru Hasegawa
发明人： Makoto Inoue , Yumiko Tokusumi , Hitoshi Iwasaki , Hiroto Hara , Toshiaki Tabata , Mamoru Hasegawa
IPC分类号： A61K38/20 , A61K31/7088 , A61K38/19 , A61K38/02 , A61P25/28
CPC分类号： A61K35/76 , A61K38/2026 , A61K38/2066 , A61K38/2086 , A61K48/00 , C07K14/5428 , C12N15/86 , C12N2760/18843 , A61K2300/00
摘要： The present invention provides novel therapeutic methods and agents for treating Alzheimer's disease. Specifically, the present invention relates to anti-inflammatory cytokines, anti-inflammatory cytokine genes, negative-strand RNA viral vectors carrying an anti-inflammatory cytokine gene, which are used for treating Alzheimer's disease or developing therapeutic agents for Alzheimer's disease. The present invention also provides pharmaceutical compositions for treating or preventing Alzheimer's disease, which comprise the cytokines or vectors. The present invention further provides methods for treating Alzheimer's disease, which comprise the step of administering an anti-inflammatory cytokine, or a vector such as a negative-strand RNA viral vector carrying an anti-inflammatory cytokine gene. The present invention enables novel gene therapies for Alzheimer's disease.
摘要翻译：本发明提供治疗阿尔茨海默氏病的新型治疗方法和药剂。具体而言，本发明涉及抗炎细胞因子，抗炎细胞因子基因，携带抗炎细胞因子基因的负链RNA病毒载体，其用于治疗阿尔茨海默病或开发阿尔茨海默氏病的治疗剂。本发明还提供了用于治疗或预防阿尔茨海默病的药物组合物，其包含细胞因子或载体。本发明还提供了治疗阿尔茨海默病的方法，其包括施用抗炎细胞因子的步骤，或携带抗炎细胞因子基因的载体如负链RNA病毒载体。本发明使得能够进行阿尔茨海默病的新基因治疗。

2. 发明申请

US20120088819A1 METHOD FOR ENHANCING EXPRESSION OF RECOMBINANT PROTEIN 审中-公开
标题翻译：用于增强重组蛋白表达的方法
公开(公告)号：US20120088819A1
公开(公告)日：2012-04-12
申请号：US13126355
申请日：2009-10-30
申请人： Makoto Inoue , Koichi Saeki , Jun You , Toshiaki Tabata , Hitoshi Iwasaki , Tsugumine Shu , Mamoru Hasegawa
发明人： Makoto Inoue , Koichi Saeki , Jun You , Toshiaki Tabata , Hitoshi Iwasaki , Tsugumine Shu , Mamoru Hasegawa
IPC分类号： A61K31/7088 , C12N5/10 , C12P21/00 , C12N15/63
CPC分类号： C12N15/67 , A61K2039/53 , C07K2319/55 , C12N15/86 , C12N2760/18843
摘要： The present invention provides methods for enhancing protein expression from an RNA viral vector and RNA viral vectors with enhanced protein expression capacity. The present inventors successfully increased the level of protein expression significantly by expressing the proteins fused with an AB5B protein from RNA viral vectors. Effective gene therapy, gene vaccination, monoclonal antibody preparation, or such can be achieved by using a gene transfer RNA viral vector of the present invention.
摘要翻译：本发明提供了从具有增强的蛋白质表达能力的RNA病毒载体和RNA病毒载体增强蛋白质表达的方法。通过从RNA病毒载体表达与AB5B蛋白质融合的蛋白质，本发明人通过显着地成功地提高了蛋白质表达水平。有效的基因治疗，基因疫苗接种，单克隆抗体制备等可以通过使用本发明的基因转移RNA病毒载体来实现。

3. 发明申请

US20120087940A1 VECTOR FOR TREATING ALZHEIMER'S DISEASE 审中-公开
标题翻译：用于治疗阿尔茨海默病的药物
公开(公告)号：US20120087940A1
公开(公告)日：2012-04-12
申请号：US13126293
申请日：2009-10-30
申请人： Makoto Inoue , Koichi Saeki , Jun You , Toshiaki Tabata , Hitoshi Iwasaki , Tsugumine Shu , Mamoru Hasegawa
发明人： Makoto Inoue , Koichi Saeki , Jun You , Toshiaki Tabata , Hitoshi Iwasaki , Tsugumine Shu , Mamoru Hasegawa
IPC分类号： A61K31/7105 , A61P25/28 , C12N15/86 , A61K39/00
CPC分类号： A61K39/0007 , A61K38/00 , A61K2039/53 , A61K2039/545 , C07K14/4711 , C07K2319/55 , C12N2760/18843 , C12N2799/021 , C12N2799/04
摘要： The present invention provides methods for efficiently inducing anti-Aβ antibody and methods for preventing and treating Alzheimer's disease. The present inventors successfully induced anti-Aβ antibody in a highly efficient manner by administering an RNA viral vector that expresses a fusion protein between an AB5 toxin B subunit and an Aβ antigen peptide. Administration of the vector resulted in a significant increase of anti-Aβ antibody in plasma, and decrease in the Aβ level in brain tissues and decrease in the anti-Aβ antibody-positive area. The present invention enables more efficient vaccine gene therapy for preventing and treating Alzheimer's disease.
摘要翻译：本发明提供了有效诱导抗Aβ的方法。抗体和预防和治疗阿尔茨海默病的方法。本发明人成功地诱导了抗A＆Bgr; 抗体，通过施用在AB5毒素B亚基和A＆bgr之间表达融合蛋白的RNA病毒载体以高效的方式; 抗原肽。载体的施用导致抗A和Bgr的显着增加; 血浆中的抗体，A和Bgr的减少; 脑组织中的水平和抗A和Bgr的降低; 抗体阳性区。本发明使得能够更有效地预防和治疗阿尔茨海默病的疫苗基因治疗。

4. 发明申请

US20090170798A1 Highly safe intranasally administrable gene vaccines for treating alzheimer's disease 审中-公开
标题翻译：用于治疗阿尔茨海默氏病的高度安全的鼻内给药基因疫苗
公开(公告)号：US20090170798A1
公开(公告)日：2009-07-02
申请号：US11918862
申请日：2006-04-20
申请人： Hideo Hara , Takeshi Tabira , Yoshikazu Yonemitsu , Makoto Inoue , Yumiko Tokusumi , Mamoru Hasegawa
发明人： Hideo Hara , Takeshi Tabira , Yoshikazu Yonemitsu , Makoto Inoue , Yumiko Tokusumi , Mamoru Hasegawa
IPC分类号： A61K31/7105 , C12N15/74 , A61P25/28
CPC分类号： C12N15/86 , A61K2039/5256 , A61K2039/543 , A61K2039/57 , C07K14/4711 , C12N2760/18843 , C12N2800/30
摘要： An objective of the present invention is to provide a safe and effective vaccine therapy for Alzheimer's disease. A minus strand RNA viral vector carrying amyloid gene was constructed, and administered intranasally to 24- to 25-months-old APP transgenic mice. The level of serum anti-A 42 antibody was determined and showed to be markedly higher than the control. The results of histological investigation showed that the administration of a vector of the present invention markedly reduced senile plaques in all of the frontal lobe, parietal lobe, and hippocampus. The brain A level was also markedly reduced. Furthermore, the administration of a vector of the present invention did not result in lymphocyte infiltration in the central nervous system.
摘要翻译：本发明的目的是为阿尔茨海默病提供安全有效的疫苗疗法。构建携带淀粉样蛋白基因的负链RNA病毒载体，鼻内给予24至25个月大的APP转基因小鼠。测定血清抗-A42抗体水平，显示明显高于对照组。组织学研究结果表明，施用本发明的载体显着降低了所有额叶，顶叶和海马中的老年斑。脑A水平也明显降低。此外，本发明的载体的施用不会导致中枢神经系统中的淋巴细胞浸润。

5. 发明申请

US20050130123A1 Methods of examining (-) strand rna virus vectors having lowered ability to form grains and method of constructing the same 审中-公开
标题翻译：检查具有降低形成颗粒能力的（ - ）链rna病毒载体的方法及其构建方法
公开(公告)号：US20050130123A1
公开(公告)日：2005-06-16
申请号：US10489384
申请日：2002-09-18
申请人： Makoto Inoue , Yumiko Tokusumi , Akihiro Iida , Mamoru Hasegawa
发明人： Makoto Inoue , Yumiko Tokusumi , Akihiro Iida , Mamoru Hasegawa
IPC分类号： A61K48/00 , C12N7/01 , C12N7/04 , C12N15/45 , C12N15/86 , C12Q1/70 , C12N15/867 , C12Q1/68
CPC分类号： C12N7/00 , A61K48/00 , C12N15/86 , C12N2760/18843 , C12N2760/18861 , C12N2800/30
摘要： The present invention provides methods for testing and producing (−) strand RNA virus vectors with reduced or eliminated particle formation ability or cytotoxicity. It was revealed that a deficiency in M protein localization in cells introduced with such a (−) strand RNA virus vector could result in the suppression of virus-like particle (VLP) formation in the cells. The present invention provides methods for testing and screening for a (−) strand RNA virus vector in which particle formation ability has been reduced or eliminated, and methods for producing a recombinant (−) strand RNA virus vector in which particle formation ability has been reduced or eliminated. Such a vector, in which VLP formation has been reduced or eliminated, is extremely useful as a vector for gene therapy, since it neither induces cytotoxicity nor immune response due to the secondary release of viruses from cells in which it has been introduced.
摘要翻译：本发明提供了测试和生产（ - ）链RNA病毒载体的方法，其具有降低或消除的颗粒形成能力或细胞毒性。显示出用这种（ - ）链RNA病毒载体引入的细胞中M蛋白定位的缺陷可导致细胞中病毒样颗粒（VLP）形成的抑制。本发明提供了用于测定和筛选其中减少或消除了颗粒形成能力的（ - ）链RNA病毒载体的方法，以及用于生产其中颗粒形成能力已经降低的重组（ - ）链RNA病毒载体的方法或消除。已经减少或消除VLP形成的这种载体作为用于基因治疗的载体是非常有用的，因为它既不引起细胞毒性也不诱导免疫应答，这是由于病毒从其引入细胞的二次释放引起的。

6. 发明授权

US07226786B2 Envelope gene-deficient Paramyxovirus vector 有权
标题翻译：包膜基因缺陷型副粘病毒载体
公开(公告)号：US07226786B2
公开(公告)日：2007-06-05
申请号：US10316535
申请日：2002-12-10
申请人： Kaio Kitazato , Tsugumine Shu , Hidekazu Kuma , Yasuji Ueda , Makoto Asakawa , Mamoru Hasegawa , Akihiro Iida , Fumino Tokito , Takahiro Hirata , Tsuyoshi Tokusumi , Makoto Inoue , Yumiko Tokusumi
发明人： Kaio Kitazato , Tsugumine Shu , Hidekazu Kuma , Yasuji Ueda , Makoto Asakawa , Mamoru Hasegawa , Akihiro Iida , Fumino Tokito , Takahiro Hirata , Tsuyoshi Tokusumi , Makoto Inoue , Yumiko Tokusumi
IPC分类号： C12N15/00 , C12N15/86
CPC分类号： C12N15/86 , A61K48/00 , A61K2039/5254 , A61K2039/5256 , C12N7/00 , C12N2760/18823 , C12N2760/18843 , C12N2760/18845 , C12N2760/18861 , C12N2800/30 , C12N2810/6081
摘要： F gene-deficient virus virions are successfully recovered by using an F gene-deficient Sendai virus genomic cDNA. Further, F gene-deficient infectious viral particles are successfully constructed by using F-expressing cells as helper cells. Also, F gene and HN gene-deficient virus virions are successfully recovered by using a virus genomic cDNA deficient in both F gene and HN gene. Further, F gene and HN gene-deficient infectious viral particles are successfully produced by using F- and HN-expressing cells as helper cells. A virus deficient in F gene and HN gene and having F protein is constructed by using F-expressing cells as helper cells. In addition, M gene-deficient infectious virus particles were produced using helper cells expressing M protein. From cells infected with M gene-deficient viruses, release of virus-like particles was inhibited. Further, a VSV-G pseudo type virus is successfully constructed by using VSV-G-expressing cells. Techniques for constructing these deficient viruses contribute to the development of vectors of Paramyxoviridae usable in gene therapy.
摘要翻译：通过使用F基因缺陷的仙台病毒基因组cDNA成功地回收了F基因缺陷型病毒粒子。此外，通过使用F表达细胞作为辅助细胞，成功构建了F基因缺陷型感染性病毒颗粒。此外，通过使用F基因和HN基因缺陷的病毒基因组cDNA，成功地回收了F基因和HN基因缺陷型病毒粒子。此外，通过使用F-和HN表达细胞作为辅助细胞，F基因和HN基因缺陷型感染性病毒颗粒成功产生。通过使用F表达细胞作为辅助细胞构建F基因和HN基因并具有F蛋白的病毒。此外，使用表达M蛋白的辅助细胞产生M基因缺陷型感染性病毒颗粒。从感染M基因缺陷病毒的细胞中，病毒样颗粒的释放被抑制。此外，通过使用表达VSV-G的细胞成功地构建了VSV-G伪型病毒。用于构建这些缺陷病毒的技术有助于可用于基因治疗的副粘病毒科的载体的发育。

7. 发明申请

US20070009949A1 Paramyxovirus-derived RNP 审中-公开
标题翻译：副粘病毒衍生的RNP
公开(公告)号：US20070009949A1
公开(公告)日：2007-01-11
申请号：US11515341
申请日：2006-09-01
申请人： Kaio Kitazato , Tsugumine Shu , Hidekazu Kuma , Yasuji Ueda , Makoto Asakawa , Mamoru Hasegawa , Akihiro Iida , Takahiro Hirata , Makoto Inoue , Yumiko Tokusumi
发明人： Kaio Kitazato , Tsugumine Shu , Hidekazu Kuma , Yasuji Ueda , Makoto Asakawa , Mamoru Hasegawa , Akihiro Iida , Takahiro Hirata , Makoto Inoue , Yumiko Tokusumi
IPC分类号： C12Q1/68 , C12N7/00 , C12N5/00 , C12N7/01 , C12N5/02
CPC分类号： C07K14/005 , A61K48/00 , A61K2039/5254 , A61K2039/5256 , C12N7/00 , C12N15/86 , C12N2710/24143 , C12N2760/18811 , C12N2760/18822 , C12N2760/18823 , C12N2760/18843 , C12N2760/18845 , C12N2760/18861 , C12N2760/20222 , C12N2800/30 , C12N2810/6081
摘要： A functional RNP containing negative-strand single-stranded RNA derived from Sendai virus, which has been modified so as not to express at least one envelope protein, has been successfully prepared. An RNP comprising a foreign gene is prepared and inserted into a cell with the use of a cationic liposome, thereby successfully expressing the foreign gene.
摘要翻译：已经成功地制备了已经被修饰以便不表达至少一种包膜蛋白的来源于仙台病毒的负链单链RNA的功能性RNP。制备包含外来基因的RNP，并使用阳离子脂质体将其插入细胞中，从而成功地表达外源基因。

8. 发明申请

US20100167341A1 NOVEL PROTEIN EXPRESSION SYSTEM 审中-公开
标题翻译：新型蛋白质表达系统
公开(公告)号：US20100167341A1
公开(公告)日：2010-07-01
申请号：US12160573
申请日：2007-01-17
申请人： Jun You , Toshiaki Tabata , Makoto Inoue , Tsugumine Shu , Mamoru Hasegawa
发明人： Jun You , Toshiaki Tabata , Makoto Inoue , Tsugumine Shu , Mamoru Hasegawa
IPC分类号： C12P21/06 , C12N15/86 , C07H21/02
CPC分类号： C12N15/86 , C12N7/00 , C12N2760/18823 , C12N2760/18843 , C12P21/02
摘要： The present inventors devised a protein expression system with coexisting MiniSeV and SeV particles, and assessed the system for the ability to transfer a gene(s) of interest into target cells, and to express the gene(s) in the target cells. It was shown that the expression system of the present invention had a high ability to transfer a gene(s) of interest into target cells, and a high ability to express the gene(s) in the target cells.
摘要翻译：本发明人设计了具有共存的MiniSeV和SeV颗粒的蛋白质表达系统，并评估了该系统将目的基因转移到靶细胞中的能力，并表达靶细胞中的基因。结果表明，本发明的表达系统具有将目标基因转移到靶细胞中的高能力，以及在靶细胞中表达基因的高能力。

9. 发明申请

US20090162320A1 GENE TRANSFER INTO AIRWAY EPITHELIAL STEM CELL BY USING LENTIVIRAL VECTOR PSEUDOTYPED WITH RNA VIRUS OR DNA VIRUS SPIKE PROTEIN 审中-公开
标题翻译：通过使用用RNA病毒或DNA病毒SPIKE蛋白质刺激的宿主细胞将基因转移到空中上皮细胞中
公开(公告)号：US20090162320A1
公开(公告)日：2009-06-25
申请号：US12091646
申请日：2006-10-27
申请人： Katsuyuki Mitomo , Makoto Inoue , Hitoshi Iwasaki , Mamoru Hasegawa
发明人： Katsuyuki Mitomo , Makoto Inoue , Hitoshi Iwasaki , Mamoru Hasegawa
IPC分类号： C12N15/86 , C12N5/10 , A61K48/00 , A61P11/00
CPC分类号： C12N15/86 , A61K9/0043 , A61K38/162 , A61K38/1709 , A61K38/177 , A61K48/00 , C07K14/4712 , C12N5/0688 , C12N7/00 , C12N2510/00 , C12N2740/15033 , C12N2740/15043 , C12N2740/15045 , C12N2810/6072 , C12N2810/609
摘要： The present inventors successfully introduced genes into stem cells of airway epithelial tissues using simian immunodeficiency virus vectors pseudotyped with F and HN, which are envelope glycoproteins of Sendai virus. Gene transfer into airway epithelial tissue stem cells using a vector of the present invention is useful for gene therapy of genetic respiratory diseases such as cystic fibrosis. Furthermore, it is possible to select respiratory organs such as the lungs as production tissues for providing proteins that are deficient due to genetic diseases.
摘要翻译：本发明人成功地将基因引入气道上皮组织的干细胞，其中使用以F和HN为假型的猿免疫缺陷病毒载体，其是仙台病毒的包膜糖蛋白。使用本发明的载体将基因转移到气道上皮组织干细胞中可用于遗传呼吸系统疾病如囊性纤维化的基因治疗。此外，可以选择诸如肺的呼吸器官作为用于提供由于遗传疾病而缺陷的蛋白质的生产组织。

10. 发明申请

US20110162093A1 METHODS FOR PRODUCING ANTIBODIES 审中-公开
标题翻译：生产抗体的方法
公开(公告)号：US20110162093A1
公开(公告)日：2011-06-30
申请号：US11922278
申请日：2006-06-13
申请人： Yasuji Ueda , Hiroto Hara , Tsugumine Shu , Mamoru Hasegawa
发明人： Yasuji Ueda , Hiroto Hara , Tsugumine Shu , Mamoru Hasegawa
IPC分类号： C12P21/00 , C12N5/07
CPC分类号： C12N15/86 , A61K2039/5256 , A61K2039/53 , C07K16/00 , C07K16/1063 , C12N2760/18843
摘要： [Problems to be Solved] The present invention provides methods for producing antibodies and antibody-producing cells.[Means for Solving the Problems] The present invention provides methods for producing antibodies or antibody-producing cells, such methods including the steps of inoculating non-human animals with minus-strand RNA viral vectors carrying nucleic acids which encode foreign polypeptides to be used as antigens, nucleic acids producing the viral vectors, cells into which the vectors or the nucleic acids producing the vectors have been introduced, or lysates of the cells; and collecting the antibodies or antibody-producing cells from the animals. The antibody production can be induced efficiently by the immune activating effect of the minus-strand RNA viral vectors and a high expression of the antigen polypeptides. The antibodies produced by the methods of the present invention can be used in research and development and in the clinical field.
摘要翻译： [待解决的问题]本发明提供了产生抗体和产生抗体的细胞的方法。解决问题的手段本发明提供了产生抗体或抗体产生细胞的方法，包括以下步骤：将携带编码外源多肽的核酸的负链RNA病毒载体接种在非人动物中，以用作为产生病毒载体的核酸，产生载体的载体或核酸的细胞或细胞的裂解物; 并从动物中收集抗体或产生抗体的细胞。可以通过负链RNA病毒载体的免疫激活作用和抗原多肽的高表达来有效诱导抗体产生。通过本发明的方法产生的抗体可用于研究和开发以及临床领域。

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