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    Therapeutic Agent For Alzheimer's Disease
    4.
    发明申请
    Therapeutic Agent For Alzheimer's Disease 审中-公开
    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。

    Envelope gene-deficient Paramyxovirus vector
    5.
    发明授权
    Envelope gene-deficient Paramyxovirus vector 有权
    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。

    NON-REPLICATING PARAMYXOVIRIDAE VIRUS VECTOR
    8.
    发明申请
    NON-REPLICATING PARAMYXOVIRIDAE VIRUS VECTOR 审中-公开
    非替代寄生虫病毒载体

    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。

    Paramyxoviruses comprising modified transcription start sequence
    9.
    发明授权
    Paramyxoviruses comprising modified transcription start sequence 失效
    副粘病毒包括修饰的转录起始序列

    公开(公告)号：US07144579B2

    公开(公告)日：2006-12-05

    申请号：US09979908

    申请日：2001-11-28

    申请人： Yoshiyuki Nagai ,  Atsushi Kato ,  Mamoru Hasegawa ,  Makoto Inoue

    发明人： Yoshiyuki Nagai ,  Atsushi Kato ,  Mamoru Hasegawa ,  Makoto Inoue

    IPC分类号： C07H19/00 ,  C12N15/63 ,  C12N15/66 ,  A61K39/12 ,  A61K39/155

    CPC分类号： C07K14/005 ,  A61K48/00 ,  C12N15/86 ,  C12N2760/18822 ,  C12N2760/18843

    摘要： The present invention provides virus vectors of the family Paramyxoviridae in which the transcription start (S) sequence has been modified so as to modify the expression of genes located downstream thereof, a method for producing the vectors, and uses thereof. By measuring the transcription initiation efficiency of the S sequence of each gene carried by Sendai viruses (SeV), it was clarified that the S sequence of F gene has a significantly lower ability to promote transcription than the other three S sequences. When the S sequence of the F gene of wild type Sendai virus was substituted by the S sequence of the P/M/HN gene-type showing a high transcription initiation efficiency, the F gene of the resultant Sendai virus mutant and genes located downstream thereof show elevated expression levels. It was also revealed that this mutant proliferates more quickly than the wild type. The vectors of this invention are useful in elevating the expression of foreign genes and producing pharmaceutical compositions and vaccines. Furthermore, by lowering virus gene expression from virus vectors, it is possible to suppress transcription and/or replication and reduce cytotoxicity of the vector genome.

    摘要翻译： 本发明提供了副粘病毒科的病毒载体，其中已经修饰了转录起始（S）序列，以便修饰其下游的基因的表达，生成载体的方法及其用途。 通过测量仙台病毒（SeV）携带的每个基因的S序列的转录起始效率，阐明了F基因的S序列比其他三个S序列具有显着较低的促进转录能力。 当野生型仙台病毒的F基因的S序列被显示高转录起始效率的P / M / HN基因型的S序列取代时，得到的仙台病毒突变体的F基因和位于其下游的基因 显示升高的表达水平。 还显示，该突变体比野生型增殖更快。 本发明的载体可用于提高外源基因的表达并产生药物组合物和疫苗。 此外，通过降低来自病毒载体的病毒基因表达，可以抑制转录和/或复制并降低载体基因组的细胞毒性。