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。

公开(公告)号：US20100203027A1

公开(公告)日：2010-08-12

申请号：US12597567

申请日：2008-04-25

申请人： Kenzaburo Tani ,  Hiroyuki Inoue ,  Makoto Inoue ,  Hiroaki Kinoh ,  Mamoru Hasegawa

发明人： Kenzaburo Tani ,  Hiroyuki Inoue ,  Makoto Inoue ,  Hiroaki Kinoh ,  Mamoru Hasegawa

IPC分类号： A61K35/12 ,  C12N15/74 ,  A61K31/7088 ,  A61P43/00

CPC分类号： A61K38/195 ,  A61K38/193 ,  A61K48/00 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2760/18843

摘要： An objective of the present invention is to provide safe viral vectors for gene therapy that can be introduced by a simple technique and sufficiently express genes of interest in vivo. The present inventors demonstrated that anti-tumor effect can be produced when a heparin-binding cytokine such as granulocyte macrophage colony stimulating factor (GM-CSF) and a chemokine such as TARC or RANTES are expressed in vivo using a viral vector based on a negative-strand RNA virus. The present inventors also demonstrated that the protective effect of the vector is superior to that of conventional adenovirus vectors. Thus, the present invention relates to negative-strand RNA viral vectors comprising a cytokine gene and a chemokine gene. The viral vectors are suitable for treatment of cancers, in particular, metastatic cancers. The present invention also provides compositions comprising such viral vectors, and gene therapy methods using them.

摘要翻译： 本发明的目的是提供用于基因治疗的安全病毒载体，其可以通过简单的技术引入并充分表达感兴趣的基因。 本发明人证明，当使用基于阴性的病毒载体在体内表达肝素结合细胞因子如粒细胞巨噬细胞集落刺激因子（GM-CSF）和趋化因子如TARC或RANTES时可产生抗肿瘤效应 品牌RNA病毒。 本发明人还证明，载体的保护作用优于常规腺病毒载体。 因此，本发明涉及包含细胞因子基因和趋化因子基因的负链RNA病毒载体。 病毒载体适合于治疗癌症，特别是转移性癌症。 本发明还提供包含这种病毒载体的组合物，以及使用它们的基因治疗方法。

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。

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。

公开(公告)号：US20100209974A1

公开(公告)日：2010-08-19

申请号：US12373684

申请日：2007-07-03

申请人： Jun You ,  Makoto Inoue ,  Mamoru Hasegawa

发明人： Jun You ,  Makoto Inoue ,  Mamoru Hasegawa

IPC分类号： C12N15/86 ,  C12N15/33 ,  C12N15/64

CPC分类号： C12N15/86 ,  C12N2760/18843 ,  C12N2760/18871 ,  C12N2820/00

摘要： The present inventors succeeded in producing non-replicating SeV vectors whose genomic RNAs lack all genes for the NP, P, and L proteins, which are RNP-constituting proteins. The present inventors confirmed that the NP/P/L-deficient SeV vectors carrying a marker gene such as GFP provide high productivity, and high transfer and expression efficiencies of foreign genes (high MOI infection is essential for achieving high expression levels). By lacking the L gene or two or more of the NP, P, and L genes, the vectors of the present invention enable lowering the level of virus-derived proteins expressed in host cells, thereby reducing the immunogenicity upon in vivo administration.

摘要翻译： 本发明人成功地生产了非复制型SeV载体，其基因组RNA缺乏作为构成RNP的蛋白质的NP，P和L蛋白的所有基因。 本发明人确认携带GFP等标记基因的NP / P / L-缺陷型SeV载体提供高生产率，外源基因的高转移和表达效率（高MOI感染对于获得高表达水平至关重要）。 通过缺乏L基因或两个以上的NP，P和L基因，本发明的载体能够降低在宿主细胞中表达的病毒衍生的蛋白质的水平，从而降低体内给药时的免疫原性。

公开(公告)号：US07521043B2

公开(公告)日：2009-04-21

申请号：US10585884

申请日：2005-01-12

申请人： Yasuo Iwadate ,  Akira Yamaura ,  Makoto Inoue ,  Mamoru Hasegawa

发明人： Yasuo Iwadate ,  Akira Yamaura ,  Makoto Inoue ,  Mamoru Hasegawa

IPC分类号： A01N63/00 ,  A01N43/04

CPC分类号： C07K14/55 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/53 ,  A61K2039/55533 ,  C07K14/4748 ,  C12N2760/18832 ,  C12N2760/18843

摘要： The present invention provides methods for treating tumors, which comprise the step of administering into tumor sites a minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides compositions for treating tumors, which comprise as an active ingredient the minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides kits for treating tumors, which comprise the minus-strand RNA viral vector encoding an immunostimulatory cytokine, and a tumor antigen or a vector expressing the antigen.

摘要翻译： 本发明提供了治疗肿瘤的方法，其包括向肿瘤位点施用编码免疫刺激性细胞因子的负链RNA病毒载体或用该载体引入的细胞的步骤。 本发明还提供了用于治疗肿瘤的组合物，其包含编码免疫刺激性细胞因子的负链RNA病毒载体或与载体一起引入的细胞作为活性成分。 本发明还提供了用于治疗肿瘤的试剂盒，其包含编码免疫刺激性细胞因子的负链RNA病毒载体和表达该抗原的肿瘤抗原或载体。

公开(公告)号：US20080038234A1

公开(公告)日：2008-02-14

申请号：US10599176

申请日：2005-03-22

申请人： Shuji Hayashi ,  Makoto Inoue ,  Mamoru Hasegawa

发明人： Shuji Hayashi ,  Makoto Inoue ,  Mamoru Hasegawa

IPC分类号： A61K35/28 ,  A61P1/16 ,  A61P35/00 ,  C12N15/63 ,  C12N5/10

CPC分类号： A61K48/0008 ,  A61K35/28 ,  A61K38/1825 ,  A61K38/1833 ,  A61K38/21 ,  C12N2710/10343 ,  C12N2760/18843

摘要： The present invention provides transformed bone marrow-related cells that are associated with tissue maintenance and/or repair. Further, the invention provides methods for diagnosing and treating diseased tissues using the transformed bone marrow-related cells. The transformed bone marrow-related cells of the present invention are transformed bone marrow-related cells that are introduced with gene-carrying vectors and that are associated with tissue maintenance and/or repair. Moreover, the methods for preparing the transformed bone marrow-related cells of the present invention comprise the step of using gene-carrying vectors to introduce genes to bone marrow-related cells taken from mammals.

摘要翻译： 本发明提供与组织维持和/或修复相关的转化的骨髓相关细胞。 此外，本发明提供了使用转化的骨髓相关细胞诊断和治疗患病组织的方法。 本发明的转化的骨髓相关细胞是与基因携带载体一起引入并与组织维持和/或修复相关联的转化骨髓相关细胞。 此外，本发明的转化骨髓相关细胞的制备方法包括使用基因携带载体将基因引入到从哺乳动物取得的骨髓相关细胞的步骤。

公开(公告)号：US20070248627A1

公开(公告)日：2007-10-25

申请号：US10585884

申请日：2005-01-12

申请人： Yasuo Iwadate ,  Akira Yamaura ,  Makoto Inoue ,  Mamoru Hasegawa

发明人： Yasuo Iwadate ,  Akira Yamaura ,  Makoto Inoue ,  Mamoru Hasegawa

IPC分类号： A61K39/00 ,  A61K31/7052 ,  A61P35/00

CPC分类号： C07K14/55 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/53 ,  A61K2039/55533 ,  C07K14/4748 ,  C12N2760/18832 ,  C12N2760/18843

摘要： The present invention provides methods for treating tumors, which comprise the step of administering into tumor sites a minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides compositions for treating tumors, which comprise as an active ingredient the minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides kits for treating tumors, which comprise the minus-strand RNA viral vector encoding an immunostimulatory cytokine, and a tumor antigen or a vector expressing the antigen.

摘要翻译： 本发明提供了治疗肿瘤的方法，其包括向肿瘤位点施用编码免疫刺激性细胞因子的负链RNA病毒载体或用该载体引入的细胞的步骤。 本发明还提供了用于治疗肿瘤的组合物，其包含编码免疫刺激性细胞因子的负链RNA病毒载体或与载体一起引入的细胞作为活性成分。 本发明还提供了用于治疗肿瘤的试剂盒，其包含编码免疫刺激性细胞因子的负链RNA病毒载体和表达该抗原的肿瘤抗原或载体。

公开(公告)号：US20050191617A1

公开(公告)日：2005-09-01

申请号：US10516429

申请日：2003-06-03

申请人： Makoto Inoue ,  Mamoru Hasegawa ,  Takashi Hironaka

发明人： Makoto Inoue ,  Mamoru Hasegawa ,  Takashi Hironaka

IPC分类号： A61K48/00 ,  A61P19/08 ,  A61P25/00 ,  A61P37/06 ,  A61P43/00 ,  C07K16/00 ,  C07K16/22 ,  C07K16/28 ,  C12N15/86 ,  C12Q1/70 ,  C07K16/08 ,  C12N5/06 ,  C12N7/00

CPC分类号： C07K16/00 ,  A61K48/00 ,  A61K48/005 ,  C07K16/22 ,  C07K16/2818 ,  C07K2317/55 ,  C07K2317/76 ,  C12N15/86 ,  C12N2760/18843 ,  C12N2760/18871 ,  C12N2800/30

摘要： The present invention provides paramyxoviral vectors expressing polypeptides that comprise antibody variable regions. A vector of this invention, encoding antibody variable regions of the H and L chains, succeeded in simultaneously expressing these antibody chains to form a Fab, and further succeeded in expressing a single chain antibody at a high level. The vectors of this invention are suitable as vectors for gene therapy, to be administered in vivo or ex vivo to living bodies. In particular, vectors expressing antibody fragments against neurite outgrowth inhibitors are useful in gene therapies for nerve lesions. Further, vectors of this invention that express antibodies which inhibit immune activation signal transduction enable the long-term expression of genes from the vectors.

摘要翻译： 本发明提供了表达包含抗体可变区的多肽的副粘病毒载体。 编码H和L链的抗体可变区的本发明的载体成功地同时表达这些抗体链以形成Fab，并且进一步以高水平表达单链抗体。 本发明的载体适合作为用于基因治疗的载体，在体内或离体给予生物体。 特别地，表达针对神经突增生抑制剂的抗体片段的载体可用于神经损伤的基因治疗。 此外，本发明的表达抑制免疫激活信号转导的抗体的载体能够从载体中长期表达基因。

公开(公告)号：US08283163B2

公开(公告)日：2012-10-09

申请号：US12600103

申请日：2008-05-12

申请人： Makoto Inoue ,  Mamoru Hasegawa ,  Yoshikazu Yonemitsu ,  Yui Harada

发明人： Makoto Inoue ,  Mamoru Hasegawa ,  Yoshikazu Yonemitsu ,  Yui Harada

IPC分类号： C12N5/071 ,  C12N5/02

CPC分类号： C12N5/0639 ,  C12N2501/125 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26

摘要： The present invention provides methods for producing DCs, which comprise the step of culturing DC precursor cells in the presence of multiple cytokines, dendritic cells produced thereby, and uses thereof. The methods of the present invention enable production of large quantities of DC precursors with a high ability to differentiate into DCs. The present invention enables one to obtain large quantities of DCs from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immunotherapy, treatment of infection, and such. Thus, an enhancement is expected for the effect of DC vaccines.

摘要翻译： 本发明提供了生产DC的方法，其包括在多种细胞因子存在下培养DC前体细胞的步骤，由此产生的树突状细胞及其用途。 本发明的方法能够生产具有高分化成DC的能力的大量DC前体。 本发明能够从少量的DC前体细胞获得大量的DC，因此能够更容易地增加DC-基抗肿瘤免疫治疗中的DC给药次数，感染治疗等。 因此，预期DC疫苗的效果将得到改善。