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1. 发明申请

US20110020932A1 IN VITRO DIFFERENTIATION/INDUCTION OF LYMPHOCYTE FROM STEM CELL HAVING GENOTYPE PROVIDED AFTER GENE RECONSTITUTION 审中-公开
标题翻译：在具有基因组重组后提供的基因组的干细胞中进行体外分化/诱导淋巴细胞
公开(公告)号：US20110020932A1
公开(公告)日：2011-01-27
申请号：US12442887
申请日：2007-09-21
申请人： Hiroshi Wakao , Shin-ichiro Fujii , Kanako Shimizu , Haruhiko Koseki , Masaru Taniguchi , Atsuo Ogura , Hiroshi Kawamoto
发明人： Hiroshi Wakao , Shin-ichiro Fujii , Kanako Shimizu , Haruhiko Koseki , Masaru Taniguchi , Atsuo Ogura , Hiroshi Kawamoto
IPC分类号： C12N5/10
CPC分类号： C12N5/0646 , C12N2501/23 , C12N2501/42 , C12N2502/1394 , C12N2502/99 , C12N2506/02 , C12N2517/04
摘要： The present invention provides a production method of a functional differentiated cell having a post-rearrangement genotype of a particular antigen receptor gene, which includes culturing a stem cell having the genotype in a medium to give the differentiated cell derived from the stem cell. As the stem cell having the genotype, a stem cell (e.g., ES cell) established by transplantation of the nucleus of a cell having the genotype is preferable. As the differentiated cell, NKT cell is preferable.
摘要翻译：本发明提供了具有特定抗原受体基因的重排后基因型的功能性分化细胞的制备方法，其包括在培养基中培养具有基因型的干细胞，得到源自干细胞的分化细胞。作为具有基因型的干细胞，优选通过移植具有基因型的细胞的细胞核建立的干细胞（例如ES细胞）。作为分化细胞，优选NKT细胞。

2. 发明申请

US20130295142A1 IMMUNOTHERAPY USING ALLO-NKT CELLS, CELLS FOR IMMUNOTHERAPY IN WHICH ALPHA CHAIN OF T-CELL RECEPTOR (TCR) GENE HAS BEEN REARRANGED TO UNIFORM V-ALPHA-J-ALPHA, AND BANKING OF NKT CELLS DERIVED FROM SAID CELLS 审中-公开
标题翻译：使用ALLO-NKT细胞的免疫疗法，其中T细胞受体（TCR）基因的免疫应答细胞已经被重新分化为V-ALPHA-J-ALPHA，以及从固体细胞衍生的NKT细胞的储存
公开(公告)号：US20130295142A1
公开(公告)日：2013-11-07
申请号：US13991059
申请日：2011-12-02
申请人： Masaru Taniguchi , Haruhiko Koseki , Hiroshi Watarai , Shin-ichiro Fujii
发明人： Masaru Taniguchi , Haruhiko Koseki , Hiroshi Watarai , Shin-ichiro Fujii
IPC分类号： A61K35/14 , C12N15/85 , A61K31/7028
摘要： The present invention provides an agent for an immunocyte therapy, comprising an NKT cell obtained by differentiating in vitro a cell having the α-chain region of the T cell receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, wherein an administration subject is an allogenic individual having MHC gene loci including at least one locus having a genotype different from that of the NKT cell. In addition, the present invention provides a bank of a human cell or an NKT cell derived from said cell, wherein the α-chain region of a T cell receptor (TCR) gene has been rearranged to uniform Vα-Jα. The agent and cell bank of the present invention are useful for the prophylaxis and/or treatment of cancer, infection, an allergic disease or an autoimmune disease.
摘要翻译：本发明提供了一种用于免疫细胞治疗的药剂，其包含NKT细胞，所述NKT细胞通过体外将具有T细胞受体基因的α链区域的细胞以NKT细胞受体特异性方式重排为均匀的Valpha-Jalpha获得，其中给药对象是具有MHC基因座的同种异体个体，其包含至少一个具有与NKT细胞基因型不同的基因座。此外，本发明提供了一种人源细胞或源自所述细胞的NKT细胞，其中T细胞受体（TCR）基因的α链区域被重新排列成均匀的Valpha-Jalpha。本发明的药剂和细胞库可用于预防和/或治疗癌症，感染，过敏性疾病或自身免疫性疾病。

3. 发明申请

US20110236362A1 NKT CELL-DERIVED iPS CELLS AND NKT CELLS DERIVED THEREFROM 有权
标题翻译： NKT细胞衍生的iPS细胞和NKT细胞衍生
公开(公告)号：US20110236362A1
公开(公告)日：2011-09-29
申请号：US13062453
申请日：2009-09-08
申请人： Hiroshi Watarai , Haruhiko Koseki , Masaru Taniguchi , Shin-ichiro Fujii
发明人： Hiroshi Watarai , Haruhiko Koseki , Masaru Taniguchi , Shin-ichiro Fujii
IPC分类号： A61K35/12 , C12N5/0783 , C12N15/85 , C12N5/071 , A61P35/00 , A61P31/00 , A61P37/08
CPC分类号： A61K31/7036 , A61K35/12 , C12N5/0646 , C12N5/0696 , C12N2501/23 , C12N2501/2302 , C12N2501/2307 , C12N2501/2315 , C12N2501/26 , C12N2501/42 , C12N2501/60 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/606 , C12N2506/11 , C12N2506/45
摘要： Provided are an iPS cell derived from a somatic cell such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, NKT cells differentiated from the iPS cell, a method of creating the same, and an immune cell therapy agent prepared using cells differentiated from the iPS cell. Also provided are an iPS cell having TCRα rearranged to NKT-TCR (NKT-iPS cell), obtained by contacting a somatic cell, such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, with nuclear reprogramming factors, isolated NKT cells obtained by differentiating the iPS cell ex vivo (iPS-NKT cell), a method of generating CD4/CD8-double positive NKT cells (DP-NKT cells) and mature NKT cells from NKT-iPS cells by altering the combination of feeder cells and/or cytokines, a method of expanding the iPS-NKT cells, and an NKT cell cytotherapy agent comprising NKT cells activated with α-galactosyl ceramide (α-GalCer), or iPS-NKT cells, and α-GalCer in combination.
摘要翻译：提供衍生自体细胞如NKT细胞的iPS细胞，其具有T细胞抗原受体基因的α链区域以NKT细胞受体特异性方式重排为均匀的Vα-Jα，从iPS分化的NKT细胞细胞，其制备方法以及使用从iPS细胞分化的细胞制备的免疫细胞治疗剂。还提供了将具有重排为T细胞抗原受体基因的α-链区域的体细胞例如NKT细胞与NKT-TCR（NKT-iPS细胞）重排的TCRα的iPS细胞重排为均匀的Vα -Jα以NKT细胞受体特异性方式，具有核重编程因子，通过离体iPS细胞（iPS-NKT细胞）分化获得的分离的NKT细胞，产生CD4 / CD8-双重阳性NKT细胞的方法（DP-NKT 细胞）和来自NKT-iPS细胞的成熟NKT细胞，通过改变饲养细胞和/或细胞因子的组合，扩增iPS-NKT细胞的方法和包含用α-半乳糖基神经酰胺（α）活化的NKT细胞的NKT细胞细胞治疗剂 -GalCer）或iPS-NKT细胞和α-GalCer组合。

4. 发明授权

US10813950B2 Immunotherapy using allo-NKT cells, cells for immunotherapy in which alpha chain of t-cell receptor (TCR) gene has been rearranged to uniform Vα-Jα, and banking of NKT cells derived from said cells 有权
公开(公告)号：US10813950B2
公开(公告)日：2020-10-27
申请号：US13991059
申请日：2011-12-02
申请人： Masaru Taniguchi , Haruhiko Koseki , Hiroshi Watarai , Shin-ichiro Fujii
发明人： Masaru Taniguchi , Haruhiko Koseki , Hiroshi Watarai , Shin-ichiro Fujii
IPC分类号： A61K35/17 , C12N5/0783 , C07K14/725 , A61K45/06 , A61K31/7028 , C12N15/85
摘要： The present invention provides an agent for an immunocyte therapy, comprising an NKT cell obtained by differentiating in vitro a cell having the α-chain region of the T cell receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, wherein an administration subject is an allogenic individual having MHC gene loci including at least one locus having a genotype different from that of the NKT cell. In addition, the present invention provides a bank of a human cell or an NKT cell derived from said cell, wherein the α-chain region of a T cell receptor (TCR) gene has been rearranged to uniform Vα-Jα. The agent and cell bank of the present invention are useful for the prophylaxis and/or treatment of cancer, infection, an allergic disease or an autoimmune disease.

5. 发明授权

US08945922B2 Generating a mature NKT cell from a reprogrammed somatic cell with a T-cell antigen receptor α-chain region rearranged to uniform Va-Ja in a NKT-cell specific way 有权
标题翻译：从具有T细胞抗原受体α链区域的重编程体细胞产生成熟的NKT细胞，以NKT细胞特异性方式重排为均匀的Va-Ja
公开(公告)号：US08945922B2
公开(公告)日：2015-02-03
申请号：US13062453
申请日：2009-09-08
申请人： Hiroshi Watarai , Haruhiko Koseki , Masaru Taniguchi , Shin-ichiro Fujii
发明人： Hiroshi Watarai , Haruhiko Koseki , Masaru Taniguchi , Shin-ichiro Fujii
IPC分类号： C12N5/02 , A61K31/7036 , C12N5/0783 , C12N5/074 , A61K35/12
CPC分类号： A61K31/7036 , A61K35/12 , C12N5/0646 , C12N5/0696 , C12N2501/23 , C12N2501/2302 , C12N2501/2307 , C12N2501/2315 , C12N2501/26 , C12N2501/42 , C12N2501/60 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/606 , C12N2506/11 , C12N2506/45
摘要： Provided are an iPS cell derived from a somatic cell such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, NKT cells differentiated from the iPS cell, a method of creating the same, and an immune cell therapy agent prepared using cells differentiated from the iPS cell. Also provided are an iPS cell having TCRα rearranged to NKT-TCR (NKT-iPS cell), obtained by contacting a somatic cell, such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, with nuclear reprogramming factors, isolated NKT cells obtained by differentiating the iPS cell ex vivo (iPS-NKT cell), a method of generating CD4/CD8-double positive NKT cells (DP-NKT cells) and mature NKT cells from NKT-iPS cells by altering the combination of feeder cells and/or cytokines, a method of expanding the iPS-NKT cells, and an NKT cell cytotherapy agent comprising NKT cells activated with α-galactosyl ceramide (α-GalCer), or iPS-NKT cells, and α-GalCer in combination.
摘要翻译：提供衍生自体细胞如NKT细胞的iPS细胞，其具有T细胞抗原受体基因的α链区域以NKT细胞受体特异性方式重排为均匀的Vα-Jα，从iPS分化的NKT细胞细胞，其制备方法以及使用从iPS细胞分化的细胞制备的免疫细胞治疗剂。还提供了将具有重排为T细胞抗原受体基因的α-链区域的体细胞例如NKT细胞与NKT-TCR（NKT-iPS细胞）重排的TCRα的iPS细胞重排为均匀的Vα -Jα以NKT细胞受体特异性方式，具有核重编程因子，通过离体iPS细胞（iPS-NKT细胞）分化获得的分离的NKT细胞，产生CD4 / CD8-双重阳性NKT细胞的方法（DP-NKT 细胞）和来自NKT-iPS细胞的成熟NKT细胞，通过改变饲养细胞和/或细胞因子的组合，扩增iPS-NKT细胞的方法和包含用α-半乳糖基神经酰胺（α）活化的NKT细胞的NKT细胞细胞治疗剂 -GalCer）或iPS-NKT细胞和α-GalCer组合。

6. 发明授权

US09783821B2 Cell for use in immunotherapy which contains modified nucleic acid construct encoding wilms tumor gene product or fragment thereof, method for producing said cell, and said nucleic acid construct 有权
公开(公告)号：US09783821B2
公开(公告)日：2017-10-10
申请号：US14235333
申请日：2012-07-30
申请人： Shin-ichiro Fujii , Kanako Shimizu , Jun Shinga
发明人： Shin-ichiro Fujii , Kanako Shimizu , Jun Shinga
IPC分类号： C12N15/85 , A61K39/00 , C07K14/47 , C07K14/82
CPC分类号： C12N15/85 , A61K39/0011 , A61K2039/5152 , A61K2039/5156 , C07K14/4748 , C07K14/82 , C07K2319/00 , C07K2319/50
摘要： A cell of the present invention contains a nucleic acid construct encoding a WT1 gene product or a fragment of the WT1 gene product. The nucleic acid construct contains (i) a region encoding a desired fragment of the WT1 gene product and (ii) only AUG as a functional start codon. The present invention can provide a cell into which the nucleic acid construct is introduced so that an expression level of a WT1 gene product or a fragment of the WT1 gene product is remarkably enhanced.

7. 发明申请

US20090233323A1 METHOD FOR ANALYSIS OF NKT CELL FUNCTION 审中-公开
标题翻译： NKT细胞功能分析方法
公开(公告)号：US20090233323A1
公开(公告)日：2009-09-17
申请号：US11917817
申请日：2006-06-09
申请人： Shin-ichiro Fujii , Kanako Shimizu
发明人： Shin-ichiro Fujii , Kanako Shimizu
IPC分类号： C12Q1/02 , C12N5/06
CPC分类号： G01N33/56972 , C12N2510/00 , G01N33/5047 , G01N33/5091
摘要： The present invention provides a superior method of functional analysis of NKT cells, which enables function analysis of low frequency NKT cells, is independent of the function of autologous APCs, and can avoid an influence of secondary factors and the like. More specifically, the present invention provides a method of functional analysis of human NKT cells including (a) cocultivating a mononuclear cell derived from human peripheral blood with a CD1d-expressing antigen presenting cell derived from a heterologous animal, and (b) evaluating the functionality of NKT cells with the number of NKT cells and/or a substance specific to functional NKT cells as an index; a reagent for analysis of human NKT cells containing a CD1d-expressing antigen presenting cell derived from a heterologous animal; a kit containing (a) a CD1d-expressing antigen presenting cell derived from a heterologous animal, and (b) at least one reagent selected from the group consisting of a reagent for selection of human mononuclear cell, a reagent for measurement of the number of human NKT cells and a reagent for measurement of a substance specific to human functional NKT cells; and the like.
摘要翻译：本发明提供了NKT细胞功能分析的优异方法，能够对低频NKT细胞进行功能分析，与自体APC的功能无关，可以避免二次因子等的影响。更具体地说，本发明提供了一种人NKT细胞的功能分析方法，其包括（a）用源自异源动物的表达CD1d的抗原呈递细胞共培养源自人外周血的单核细胞，和（b）评估功能性具有NKT细胞数量和/或功能性NKT细胞特异性物质的NKT细胞作为指标; 用于分析含有衍生自异源动物的表达CD1d的抗原呈递细胞的人NKT细胞的试剂; 包含（a）来自异源动物的表达CD1d的抗原呈递细胞的试剂盒，和（b）至少一种选自人单核细胞的试剂，用于测定人单核细胞数的试剂人NKT细胞和用于测量人功能性NKT细胞特异性物质的试剂; 等等。

8. 发明申请

US20100233215A1 IMMUNOTHERAPY BY USING CELL CAPABLE OF CO-EXPRESSING TARGET ANTIGEN AND CD1d AND PULSED WITH CD1d LIGAND 审中-公开
标题翻译：通过使用能够共表达目标抗原和CD1d的细胞并用CD1d配体进行脉冲免疫
公开(公告)号：US20100233215A1
公开(公告)日：2010-09-16
申请号：US12280305
申请日：2007-02-21
申请人： Shin-ichiro Fujii , Kanako Shimizu
发明人： Shin-ichiro Fujii , Kanako Shimizu
IPC分类号： A61K39/00 , C12N5/10 , C12N5/02 , C12N7/00 , C12Q1/02 , C12N15/63
CPC分类号： C07K14/70539 , A61K39/0011 , G01N2333/70596
摘要： The present invention provides a novel immunity induction method, particularly, a method of simultaneously inducing activation of NKT cells and T-cell immune responses. To be more precise, the present invention provides a target antigen and CD1d co-expressing cell, and a preparation and identification method thereof; a target antigen and CD1d co-expressing cell capable of activating immunity to the target antigen, and a preparation method thereof; an immunoinducer to a target antigen or a pharmaceutical agent, which contains a target antigen and CD1d co-expressing cell capable of activating immunity to the target antigen; a target antigen and CD1d co-expressing vector; a kit containing an expression vector and/or a CD1d ligand; and the like.
摘要翻译：本发明提供了一种新的免疫诱导方法，特别是同时诱导NKT细胞活化和T细胞免疫应答的方法。更准确地说，本发明提供了靶抗原和CD1d共表达细胞及其制备和鉴定方法; 能够激活对靶抗原免疫的靶抗原和CD1d共表达细胞及其制备方法; 靶向抗原或药剂的免疫抑制剂，其含有能够激活对靶抗原免疫的靶抗原和CD1d共表达细胞; 靶抗原和CD1d共表达载体; 包含表达载体和/或CD1d配体的试剂盒; 等等。

9. 发明申请

US20110280895A1 IMMUNOTHERAPEUTIC METHOD USING ALLO-CELLS WHICH CO-EXPRESS CD1d AND TARGET ANTIGEN 审中-公开
标题翻译：使用共表达CD1d和目标抗原的ALLO细胞的免疫疗法
公开(公告)号：US20110280895A1
公开(公告)日：2011-11-17
申请号：US13131299
申请日：2009-11-27
申请人： Shin-ichiro Fujii , Kanako Shimizu
发明人： Shin-ichiro Fujii , Kanako Shimizu
IPC分类号： A61K39/00 , A61K45/00 , A61P37/00 , C12N5/071
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2035/124 , A61K2039/5154 , A61K2039/5156
摘要： The present invention provides a means to be used for a new immunotherapy of cancer or infection utilizing activation of dendritic cell (DC) by innate immunity, namely, a method of preparing a cell co-expressing a target antigen and CD1d and having an ability to activate immunity against the target antigen, comprising the following steps (a) and (b):(a) a step of transfecting an mRNA encoding the target antigen into a CD1d-expressing cell to give a cell co-expressing the target antigen and CD1d; and (b) a step of treating the cell obtained in step (a) with a CD1d ligand in a culture medium.
摘要翻译：本发明提供了一种通过先天免疫使用树突状细胞（DC）活化的癌症或感染的新的免疫治疗方法，即，共同表达靶抗原和CD1d的细胞的制备方法，激活针对靶抗原的免疫，包括以下步骤（a）和（b）：（a）将编码靶抗原的mRNA转染到CD1d表达细胞中以产生共表达靶抗原和CD1d的细胞的步骤 ; 和（b）用培养基中的CD1d配体处理步骤（a）中获得的细胞的步骤。

10. 发明申请

US20140179004A1 CELL FOR USE IN IMMUNOTHERAPY WHICH CONTAINS MODIFIED NUCLEIC ACID CONSTRUCT ENCODING WILMS TUMOR GENE PRODUCT OR FRAGMENT THEREOF, METHOD FOR PRODUCING SAID CELL, AND SAID NUCLEIC ACID CONSTRUCT 有权
标题翻译：含有改性核酸结构的免疫球蛋白编码WUMUM肿瘤基因产物或其片段，用于生产细胞的方法和所述核酸结构
公开(公告)号：US20140179004A1
公开(公告)日：2014-06-26
申请号：US14235333
申请日：2012-07-30
申请人： Shin-ichiro Fujii , Kanako Shimizu , Jun Shinga
发明人： Shin-ichiro Fujii , Kanako Shimizu , Jun Shinga
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , A61K39/0011 , A61K2039/5152 , A61K2039/5156 , C07K14/4748 , C07K14/82 , C07K2319/00 , C07K2319/50
摘要： A cell of the present invention contains a nucleic acid construct encoding a WT1 gene product or a fragment of the WT1 gene product. The nucleic acid construct contains (i) a region encoding a desired fragment of the WT1 gene product and (ii) only AUG as a functional start codon. The present invention can provide a cell into which the nucleic acid construct is introduced so that an expression level of a WT1 gene product or a fragment of the WT1 gene product is remarkably enhanced.
摘要翻译：本发明的细胞含有编码WT1基因产物或WT1基因产物片段的核酸构建体。核酸构建体包含（i）编码WT1基因产物的期望片段的区域和（ii）仅AUG作为功能起始密码子。本发明可以提供引入核酸构建体的细胞，从而显着提高WT1基因产物或WT1基因产物的片段的表达水平。

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