公开(公告)号：US08614093B2

公开(公告)日：2013-12-24

申请号：US12934394

申请日：2009-03-24

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura

IPC分类号： C12N5/00 ,  C12N5/02 ,  C12N5/071

CPC分类号： A61K38/18 ,  A61K38/00 ,  C07K14/4703 ,  C07K14/4747 ,  C12N5/0639 ,  C12N2501/22 ,  C12N2501/2304 ,  C12N2501/415

摘要： According to the present invention, a composition for inducing or activating dendritic cell-like cells so as to treat or prevent cancer by immunotherapy is provided.Specifically, the following is provided: an agent for activating cancer immunity, which comprises, as an active ingredient, the following REIC protein: (a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2; or (b) a protein consisting of an amino acid sequence derived from the amino acid sequence shown in SEQ ID NO: 2 by substitution, deletion, or addition of one or more amino acid(s) and having the activity of inducing differentiation from monocytes into dendritic cell-like cells.

摘要翻译： 根据本发明，提供了用于诱导或激活树突状细胞样细胞以通过免疫治疗来治疗或预防癌症的组合物。 具体而言，提供以下功能：用于激活癌症免疫的药剂，其包含作为活性成分的以下REIC蛋白质：（a）由SEQ ID NO：2所示的氨基酸序列组成的蛋白质; 或（b）通过取代，缺失或添加一个或多个氨基酸并且具有诱导从单核细胞分化的活性的由源自SEQ ID NO：2所示氨基酸序列的氨基酸序列组成的蛋白质 进入树突状细胞样细胞。

公开(公告)号：US08658612B2

公开(公告)日：2014-02-25

申请号：US13056443

申请日：2009-07-30

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Yuji Kashiwakura ,  Masami Watanabe ,  Nam-ho Huh ,  Masakiyo Sakaguchi

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Yuji Kashiwakura ,  Masami Watanabe ,  Nam-ho Huh ,  Masakiyo Sakaguchi

IPC分类号： A01N43/04 ,  C12N15/00 ,  C12N15/63 ,  C07H21/04

CPC分类号： C07K14/47 ,  A61K35/13 ,  A61K38/00 ,  C12N2799/022

摘要： A method for potentiating the antitumor immunity in an animal by administering REIC/Dkk-3, or a therapeutic agent for malignant mesothelioma containing REIC/Dkk-3, or a vector containing the DNA as an active ingredient; wherein the DNA consists of the nucleotide sequence shown in SEQ ID NO: 1; or (b) a DNA hybridizing under stringent conditions to the DNA consisting of a nucleotide sequence complementary to the nucleotide sequence shown in SEQ ID NO: 1 and encoding a protein having apoptosis-inducing activity and interleukin (IL-7) production-accelerating activity in cells.

摘要翻译： 通过施用REIC / Dkk-3或含有REIC / Dkk-3的恶性间皮瘤的治疗剂或含有该DNA作为活性成分的载体来增强动物的抗肿瘤免疫力的方法。 其中DNA由SEQ ID NO：1所示的核苷酸序列组成; 或（b）在严格条件下与由与SEQ ID NO：1所示核苷酸序列互补的核苷酸序列组成的DNA杂交并编码具有凋亡诱导活性和白细胞介素（IL-7）产生加速活性的蛋白质的DNA 在细胞中。

公开(公告)号：US20120034251A1

公开(公告)日：2012-02-09

申请号：US12934394

申请日：2009-03-24

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura

IPC分类号： A61K38/17 ,  A61K31/711 ,  A61P37/04 ,  C12N15/861 ,  C12N5/0784 ,  A61P35/00 ,  C12N5/0786 ,  C12N15/85

CPC分类号： A61K38/18 ,  A61K38/00 ,  C07K14/4703 ,  C07K14/4747 ,  C12N5/0639 ,  C12N2501/22 ,  C12N2501/2304 ,  C12N2501/415

摘要： According to the present invention, a composition for inducing or activating dendritic cell-like cells so as to treat or prevent cancer by immunotherapy is provided.Specifically, the following is provided: an agent for activating cancer immunity, which comprises, as an active ingredient, the following REIC protein: (a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2; or (b) a protein consisting of an amino acid sequence derived from the amino acid sequence shown in SEQ ID NO: 2 by substitution, deletion, or addition of one or more amino acid(s) and having the activity of inducing differentiation from monocytes into dendritic cell-like cells.

摘要翻译： 根据本发明，提供了用于诱导或激活树突状细胞样细胞以通过免疫治疗来治疗或预防癌症的组合物。 具体而言，提供以下功能：用于激活癌症免疫的药剂，其包含作为活性成分的以下REIC蛋白质：（a）由SEQ ID NO：2所示的氨基酸序列组成的蛋白质; 或（b）通过取代，缺失或添加一个或多个氨基酸并且具有诱导从单核细胞分化的活性的由源自SEQ ID NO：2所示氨基酸序列的氨基酸序列组成的蛋白质 进入树突状细胞样细胞。

公开(公告)号：US08946173B2

公开(公告)日：2015-02-03

申请号：US12734488

申请日：2008-11-05

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura ,  Kensuke Kawasaki

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura ,  Kensuke Kawasaki

IPC分类号： A61K48/00 ,  C12N15/00 ,  C12N15/86 ,  A61K31/713

CPC分类号： A61K31/713 ,  A61K48/00 ,  C12N2710/10043

摘要： The present invention provides a drug capable of causing cancer cells to restore anticancer drug sensitivity in cases in which cancer has acquired resistance to an anticancer drug and inducing cell death in cancer cells. The present invention specifically provides a cancer cell death inducing agent comprising REIC/Dkk-3 DNA as an active ingredient and having effects of potentiating an anticancer drug for cancer cells having anticancer drug resistance.

摘要翻译： 本发明提供了能够使癌细胞恢复抗癌药敏感性的药物，其中癌症已获得抗癌药物的抗性并诱导癌细胞中的细胞死亡。 本发明具体提供了包含REIC / Dkk-3 DNA作为活性成分的癌细胞死亡诱导剂，并具有增强抗癌药抗癌药物抗性的癌细胞的作用。

公开(公告)号：US20110269824A1

公开(公告)日：2011-11-03

申请号：US12734488

申请日：2008-11-05

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura ,  Kensuke Kawasaki

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Masami Watanabe ,  Yuji Kashiwakura ,  Kensuke Kawasaki

IPC分类号： A61K31/7088 ,  C12N15/861 ,  A61P35/00 ,  C12N15/85

CPC分类号： A61K31/713 ,  A61K48/00 ,  C12N2710/10043

摘要： The present invention provides a drug capable of causing cancer cells to restore anticancer drug sensitivity in cases in which cancer has acquired resistance to an anticancer drug and inducing cell death in cancer cells. The present invention specifically provides a cancer cell death inducing agent comprising REIC/Dkk-3 DNA as an active ingredient and having effects of potentiating an anticancer drug for cancer cells having anticancer drug resistance.

摘要翻译： 本发明提供了能够使癌细胞恢复抗癌药敏感性的药物，其中癌症已获得抗癌药物的抗性并诱导癌细胞中的细胞死亡。 本发明具体提供了包含REIC / Dkk-3 DNA作为活性成分的癌细胞死亡诱导剂，并具有增强抗癌药抗癌药物抗性的癌细胞的作用。

公开(公告)号：US20110189237A1

公开(公告)日：2011-08-04

申请号：US13056443

申请日：2009-07-30

申请人： Hiromi Kumon ,  Yasutomo Nasu ,  Yuji Kashiwakura ,  Masami Watanabe ,  Nam-ho Huh ,  Masakiyo Sakaguchi

发明人： Hiromi Kumon ,  Yasutomo Nasu ,  Yuji Kashiwakura ,  Masami Watanabe ,  Nam-ho Huh ,  Masakiyo Sakaguchi

IPC分类号： A61K31/7088 ,  A61P35/00 ,  A61P37/04

CPC分类号： C07K14/47 ,  A61K35/13 ,  A61K38/00 ,  C12N2799/022

摘要： According to the present invention, a method for treating malignant mesothelioma using REIC/Dkk-3 and a therapeutic agent for malignant mesothelioma comprising REIC/Dkk-3 are provided. A mesothelioma therapeutic agent is provided, comprising the following REIC/Dkk-3 DNA or a vector comprising the DNA as an active ingredient: (a) a DNA consisting of the nucleotide sequence shown in SEQ ID NO: 1; or (b) a DNA hybridizing under stringent conditions to a DNA consisting of a nucleotide sequence complementary to the nucleotide sequence shown in SEQ ID NO: 1 and encoding a protein having apoptosis-inducing activity and IL-7 production-accelerating activity in cells.

摘要翻译： 根据本发明，提供了使用REIC / Dkk-3治疗恶性间皮瘤的方法和包含REIC / Dkk-3的恶性间皮瘤治疗剂。 提供间皮瘤治疗剂，其包含以下REIC / Dkk-3 DNA或包含该DNA作为活性成分的载体：（a）由SEQ ID NO：1所示核苷酸序列组成的DNA; 或（b）在严格条件下与由与SEQ ID NO：1所示核苷酸序列互补的核苷酸序列组成的DNA杂交并编码细胞中具有凋亡诱导活性和IL-7生产加速活性的蛋白质的DNA。

公开(公告)号：US20140147917A1

公开(公告)日：2014-05-29

申请号：US14119772

申请日：2012-05-25

申请人： Hiromi Kumon ,  Namho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

发明人： Hiromi Kumon ,  Namho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

IPC分类号： C12N15/86

CPC分类号： C12N15/86 ,  A61K35/761 ,  A61K38/1709 ,  A61K48/0066 ,  C07K14/4702 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2830/15 ,  C12N2830/30

摘要： An objective of the present invention is to provide an adenovirus vector expressing a REIC/Dkk-3 protein at a high level and containing a DNA construct for expression of REIC/Dkk-3 DNA, wherein the DNA construct is prepared by ligating, from the 5′ terminal side, (i) a CMV promoter, (ii) REIC/Dkk-3 DNA, (iii) a polyA addition sequence, and (iv) enhancers prepared by linking an hTERT (Telomerase Reverse Transcriptase) enhancer, an SV40 enhancer, and a CMV enhancer in this order.

摘要翻译： 本发明的目的是提供高水平表达REIC / Dkk-3蛋白的腺病毒载体，并含有用于表达REIC / Dkk-3 DNA的DNA构建体，其中所述DNA构建体通过从 5'末端，（i）CMV启动子，（ii）REIC / Dkk-3 DNA，（iii）polyA加成序列，和（iv）通过连接hTERT（端粒酶逆转录酶）增强子，SV40增强子 ，和CMV增强子。

公开(公告)号：US09493776B2

公开(公告)日：2016-11-15

申请号：US13510719

申请日：2010-11-19

申请人： Hiromi Kumon ,  Nam-Ho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

发明人： Hiromi Kumon ,  Nam-Ho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

IPC分类号： C12N15/86 ,  A61K48/00 ,  A61K38/00 ,  C12N15/67 ,  C12N15/85 ,  A61K38/17 ,  C12P21/02

CPC分类号： C12N15/67 ,  A61K38/1761 ,  C12N15/85 ,  C12N2799/025 ,  C12N2830/00 ,  C12N2830/50 ,  C12P21/02

摘要： An object of the present invention is to provide a method for increasing the expression of foreign genes, in particular, using a promoter, an enhancer, and the like, and an expression cassette containing a promoter, an enhancer, and the like, by which gene expression can be increased. The purpose is achieved with the use of the gene expression cassette comprising a DNA construct containing a gene to be expressed and a poly A addition sequence that are located downstream of a 1st promoter, and further comprising an enhancer or a 2nd promoter ligated downstream of the DNA construct.

摘要翻译： 本发明的目的是提供一种增加外源基因表达的方法，特别是使用启动子，增强子等，以及含有启动子，增强子等的表达盒，通过该方法， 可以增加基因表达。 该目的是通过使用包含含有待表达基因的DNA构建体和位于第一启动子下游的多聚A加成序列的基因表达盒来实现的，并且还包含连接在第一启动子下游的增强子或第二启动子 DNA构建体。

公开(公告)号：US20130267025A1

公开(公告)日：2013-10-10

申请号：US13807747

申请日：2011-07-01

申请人： Hiromi Kumon ,  Masami Watanabe ,  Junichiro Futami ,  Yasuyuki Fujii ,  Hideo Ueki ,  Kazuhiko Ochiai

发明人： Hiromi Kumon ,  Masami Watanabe ,  Junichiro Futami ,  Yasuyuki Fujii ,  Hideo Ueki ,  Kazuhiko Ochiai

IPC分类号： C07K14/47

CPC分类号： C07K14/4747 ,  A61K38/00 ,  A61K48/00 ,  C07K14/47 ,  C07K14/4703

摘要： A polypeptide capable of strongly inducing and activating dendritic-cell-like cells for treating or prevent cancer by immunotherapy, and DNA encoding the polypeptide. The polypeptide is a polypeptide (a) or (b) consisting of a partial region of the REIC/Dkk-3 protein.

摘要翻译： 能够强烈诱导和激活用于通过免疫治疗治疗或预防癌症的树突状细胞样细胞的多肽和编码该多肽的DNA。 多肽是由REIC / Dkk-3蛋白的部分区域组成的多肽（a）或（b）。

公开(公告)号：US20120309050A1

公开(公告)日：2012-12-06

申请号：US13510719

申请日：2010-11-19

申请人： Hiromi Kumon ,  Nam-Ho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

发明人： Hiromi Kumon ,  Nam-Ho Huh ,  Masakiyo Sakaguchi ,  Masami Watanabe

IPC分类号： C12N15/63 ,  C12N1/19 ,  C12N1/15 ,  C12N1/21 ,  C12P21/00 ,  C12N5/10

CPC分类号： C12N15/67 ,  A61K38/1761 ,  C12N15/85 ,  C12N2799/025 ,  C12N2830/00 ,  C12N2830/50 ,  C12P21/02

摘要： An object of the present invention is to provide a method for increasing the expression of foreign genes, in particular, using a promoter, an enhancer, and the like, and an expression cassette containing a promoter, an enhancer, and the like, by which gene expression can be increased. The purpose is achieved with the use of the gene expression cassette comprising a DNA construct containing a gene to be expressed and a poly A addition sequence that are located downstream of a 1st promoter, and further comprising an enhancer or a 2nd promoter ligated downstream of the DNA construct.

摘要翻译： 本发明的目的是提供一种增加外源基因表达的方法，特别是使用启动子，增强子等，以及含有启动子，增强子等的表达盒，通过该方法， 可以增加基因表达。 该目的是通过使用包含含有待表达基因的DNA构建体和位于第一启动子下游的多聚A加成序列的基因表达盒来实现的，并且还包含连接在第一启动子下游的增强子或第二启动子 DNA构建体。