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1. 发明授权

US08426131B2 Method for screening candidate compounds for antitumor drug 失效
标题翻译：筛选抗肿瘤药物候选化合物的方法
公开(公告)号：US08426131B2
公开(公告)日：2013-04-23
申请号：US12926346
申请日：2010-11-12
申请人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
发明人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
IPC分类号： C12Q1/68 , C12N5/10 , C12N5/078 , C12N15/85
CPC分类号： G01N33/57426 , G01N33/5011
摘要： Investigation on the frequency of FLT3/ITD found in various blood cancers has revealed that the frequency is high in acute myeloblastic leukemia in particular. Studies on the effects of FLT3/ITD in the blood cell lines revealed that the tyrosine residues in FLT3/ITD is constitutively phosphorylated in these cell lines and that blood cells into which FLT3/ITD is introduced show IL-3 independent proliferation. Moreover, the blood cells into which FLT3/ITD is introduced are found to be capable of forming tumors and inhibit cell differentiation. The inventors have found that it is possible to screen for pharmaceutical compounds against tumors by using inhibition of these FLT3/ITD functions as an index.
摘要翻译：对各种血液中FLT3 / ITD频率的调查显示，特别是急性成髓细胞白血病的频率高。关于FLT3 / ITD在血细胞系中的作用的研究表明，FLT3 / ITD中的酪氨酸残基在这些细胞系中被组成型磷酸化，并且引入了FLT3 / ITD的血细胞显示IL-3不依赖的增殖。此外，发现引入FLT3 / ITD的血细胞能够形成肿瘤并抑制细胞分化。本发明人已经发现，通过使用这些FLT3 / ITD功能的抑制作为指标，可以筛选针对肿瘤的药物化合物。

2. 发明申请

US20110257366A1 Method for screening candidate compounds for antitumor drug 失效
标题翻译：筛选抗肿瘤药物候选化合物的方法
公开(公告)号：US20110257366A1
公开(公告)日：2011-10-20
申请号：US12926346
申请日：2010-11-12
申请人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
发明人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
IPC分类号： C07K14/54 , C12Q1/48
CPC分类号： G01N33/57426 , G01N33/5011
摘要： Investigation on the frequency of FLT3/ITD found in various blood cancers has revealed that the frequency is high in acute myeloblastic leukemia in particular. Studies on the effects of FLT3/ITD in the blood cell lines revealed that the tyrosine residues in FLT3/ITD is constitutively phosphorylated in these cell lines and that blood cells into which FLT3/ITD is introduced show IL-3 independent proliferation. Moreover, the blood cells into which FLT3/ITD is introduced are found to be capable of forming tumors and inhibit cell differentiation. The inventors have found that it is possible to screen for pharmaceutical compounds against tumors by using inhibition of these FLT3/ITD functions as an index.
摘要翻译：对各种血液中FLT3 / ITD频率的调查显示，特别是急性成髓细胞白血病的频率高。关于FLT3 / ITD在血细胞系中的作用的研究表明，FLT3 / ITD中的酪氨酸残基在这些细胞系中被组成型磷酸化，并且引入了FLT3 / ITD的血细胞显示IL-3不依赖的增殖。此外，发现引入FLT3 / ITD的血细胞能够形成肿瘤并抑制细胞分化。本发明人已经发现，通过使用这些FLT3 / ITD功能的抑制作为指标，可以筛选针对肿瘤的药物化合物。

3. 发明授权

US07919517B2 Indazole derivatives 失效
标题翻译：吲唑衍生物
公开(公告)号：US07919517B2
公开(公告)日：2011-04-05
申请号：US12275614
申请日：2008-11-21
申请人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
发明人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
IPC分类号： A61K31/416 , C07D231/56
CPC分类号： C07D231/56
摘要： The present invention provides a compound represented by Formula (I): [wherein R1 represents CONR1aR1b (wherein R1a and R1b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R1a and R1b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group) or the like, R2 represents a hydrogen atom, CONR2aR2b (wherein R2a and R2b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R2a and R2b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group), NR2cR2d (wherein R2c and R2d may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted aroyl, substituted or unsubstituted heteroaroyl, substituted or unsubstituted ararkyl, substituted or unsubstituted lower alkylsulfonyl or substituted or unsubstituted lower arylsulfonyl) or the like].
摘要翻译：本发明提供由式（I）表示的化合物：[其中R1表示CONR1aR1b（其中R1a和R1b可以相同或不同，各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳基或取代或未取代的杂环基，或者R1a和R1b与相邻的氮原子一起形成取代或未取代的杂环基）等，R2表示氢原子，CONR2aR2b（其中R2a和R2b可以是各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳基或取代或未取代的杂环基，或者R 2a和R 2b与相邻的氮原子一起形成取代基或未取代的杂环基），NR2cR2d（其中R2c和R2d可以相同或不同取代或未取代的杂芳酰基，取代或未取代的芳酰基，取代或未取代的低级烷基磺酰基或取代或未取代的低级芳基磺酰基）等，其中R 1表示氢原子，取代或未取代的低级烷基，取代或未取代的低级烷酰基，取代或未取代的芳酰基，。

4. 发明授权

US07125659B1 Method and screening candidate compounds for drug against tumor 失效
标题翻译：方法和筛选药物对肿瘤的候选化合物
公开(公告)号：US07125659B1
公开(公告)日：2006-10-24
申请号：US09763175
申请日：1999-08-19
申请人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
发明人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
IPC分类号： C12Q1/00 , G01N33/53 , G01N33/567 , A01N37/18 , A61K35/14
CPC分类号： G01N33/57426 , G01N33/5011
摘要： Investigation on the frequency of FLT3/ITD found in various blood cancers has revealed that the frequency is high in acute myeloblastic leukemia in particular. Studies on the effects of FLT3/ITD in the blood cell lines revealed that the tyrosine residues in FLT3/ITD is constitutively phosphorylated in these cell lines and that blood cells into which FLT3/ITD is introduced show IL-3 independent proliferation. Moreover, the blood cells into which FLT3/ITD is introduced are found to be capable of forming tumors and inhibit cell differentiation. The inventors have found that it is possible to screen for pharmaceutical compounds against tumors by using inhibition of these FLT3/ITD functions as an index.
摘要翻译：对各种血液中FLT3 / ITD频率的调查显示，特别是急性成髓细胞白血病的频率高。关于FLT3 / ITD在血细胞系中的作用的研究表明，FLT3 / ITD中的酪氨酸残基在这些细胞系中被组成型磷酸化，并且引入了FLT3 / ITD的血细胞显示IL-3不依赖的增殖。此外，发现引入FLT3 / ITD的血细胞能够形成肿瘤并抑制细胞分化。本发明人已经发现，通过使用这些FLT3 / ITD功能的抑制作为指标，可以筛选针对肿瘤的药物化合物。

5. 发明授权

US08496927B2 CD20 negatively converted B-cell malignant lymphoma cell line and utilization thereof 失效
标题翻译： CD20阴性转化B细胞恶性淋巴瘤细胞系及其利用
公开(公告)号：US08496927B2
公开(公告)日：2013-07-30
申请号：US12311281
申请日：2007-09-21
申请人： Tomoki Naoe , Akihiro Tomita , Junji Hiraga
发明人： Tomoki Naoe , Akihiro Tomita , Junji Hiraga
IPC分类号： A01N63/00 , A01K67/00 , C12Q1/00 , A61K49/00
CPC分类号： G01N33/5052 , A01K67/0271 , A01K2207/12 , A01K2227/105 , A01K2267/0331 , C12N5/0694 , C12N2503/02 , G01N33/5011 , G01N2800/44
摘要： It is intended to provide a tool, a procedure and so on which are useful in developing a therapeutic strategy efficacious in inhibiting or overcoming the resistance against a CD20-directed molecular-targeted drug. Thus, a CD20-negatively converted B-cell malignant lymphocyte cell line is provided. Also, a model animal indicating the pathological conditions of CD20-negatively converted B-cell malignant lymphocyte is provided. Further, a method of screening a substance, which is efficacious against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B cell malignant lymphocyte, is provided. Furthermore, a drug against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B-cell malignant lymphocyte, which is characterized by being used together with a CD20-directed molecular-targeted drug, is provided. In one embodiment, a DNA methylase inhibitor or a histone deacetylase inhibitor is employed as the active ingredient.
摘要翻译：旨在提供可用于开发有效抑制或克服对CD20定向分子靶向药物的抗性的治疗策略的工具，程序等。因此，提供CD20阴性转化的B细胞恶性淋巴细胞细胞系。另外，提供了指示CD20-负转换的B细胞恶性淋巴细胞的病理状态的模型动物。此外，提供了筛选对CD20阳性B细胞恶性淋巴细胞或CD20-负向转化的B细胞恶性淋巴细胞有效的物质的方法。此外，提供了抗CD20阳性B细胞恶性淋巴细胞或CD20阴性转化的B细胞恶性淋巴细胞的药物，其特征在于与CD20定向的分子靶向药物一起使用。在一个实施方案中，使用DNA甲基化酶抑制剂或组蛋白脱乙酰酶抑制剂作为活性成分。

6. 发明申请

US20110318828A1 KIT FOR PREPARATION OF ANTIGEN-SPECIFIC CYTOTOXIC LYMPHOCYTES 审中-公开
标题翻译：用于制备抗原特异性细胞淋巴球蛋白的工具包
公开(公告)号：US20110318828A1
公开(公告)日：2011-12-29
申请号：US12998550
申请日：2009-10-29
申请人： Susumu Suzuki , Seiji Kojima , Tomoki Naoe
发明人： Susumu Suzuki , Seiji Kojima , Tomoki Naoe
IPC分类号： C12N5/0783 , C12M3/00
CPC分类号： C12N5/0638 , A61K2039/5158 , A61K2039/57 , C12M23/14 , C12M33/04 , C12N5/0636 , C12N2501/23
摘要： The invention is intended to further improve the operability, economic efficiency and safety in the preparation of antigen-specific CTLs. The invention provides a preparation kit used for a method for preparing antigen-specific cytotoxic T lymphocytes, the method comprising: a first step for inducing antigen-specific cytotoxic T lymphocytes, wherein the components of the first step include a culture medium contained in an injection vessel, a hermetically sealed culture vessel, and the like; a second step for preparing an activated T cell for antigen presentation, wherein the components of the second step include a culture medium contained in an injection vessel, a hermetically sealed culture vessel, and the like, and a third step for proliferating antigen-specific cytotoxic T lymphocytes, wherein the components of the third step include a culture medium contained in an injection vessel, a hermetically sealed separation vessel, a hermetically sealed culture vessel, and the like.
摘要翻译：本发明旨在进一步提高抗原特异性CTL的制备的可操作性，经济效率和安全性。本发明提供了一种用于制备抗原特异性细胞毒性T淋巴细胞的方法的制备试剂盒，该方法包括：诱导抗原特异性细胞毒性T淋巴细胞的第一步骤，其中第一步的成分包括注射剂中所含的培养基容器，气密密封培养容器等; 用于制备用于抗原呈递的活化T细胞的第二步骤，其中第二步的组分包括包含在注射容器中的培养基，密封的培养容器等，以及用于增殖抗原特异性细胞毒性的第三步骤 T淋巴细胞，其中第三步的组分包括包含在注射容器中的培养基，气密密封的分离容器，气密密封的培养容器等。

7. 发明授权

US07956060B2 Pyrimidine derivative compound 失效
标题翻译：嘧啶衍生物化合物
公开(公告)号：US07956060B2
公开(公告)日：2011-06-07
申请号：US10594369
申请日：2005-03-30
申请人： Hitoshi Arai , Tsutomu Matsumura , Syoichi Isami , Hiroshi Ishida , Koji Hagihara , Hiroshi Umehara , Yoshinori Yamashita , Nana Oiwa , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi
发明人： Hitoshi Arai , Tsutomu Matsumura , Syoichi Isami , Hiroshi Ishida , Koji Hagihara , Hiroshi Umehara , Yoshinori Yamashita , Nana Oiwa , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi
IPC分类号： C07D471/04 , C07D471/22 , C07D487/04 , C07D239/70 , C07D471/00 , C07D487/00 , C07D401/00 , C07D403/00 , C07D405/00 , C07D409/00 , C07D411/00 , C07D413/00 , C07D417/00 , C07D419/00 , A61K31/505 , A01N43/56
CPC分类号： C07D413/04 , C07D413/14
摘要： The present invention provides an antitumor agent and the like, which comprises as an active ingredient, a pyrimidine derivative represented by Formula (I): [wherein —X—Y—Z— represents —O—CR3═N— (wherein R3 represents a hydrogen atom, a substituted or unsubstituted aromatic heterocyclic group and the like) and the like, R1 represents —NR10R11 (wherein R10 and R11 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl and the like) and the like, R2 represents —NR13R14 (wherein R13 and R14 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl and the like)] or a pharmaceutically acceptable salt thereof.
摘要翻译：本发明提供了包含作为活性成分的式（I）所示的嘧啶衍生物的抗肿瘤剂等：[其中-X-Y-Z-表示-O-CR 3 = N-（其中R 3表示氢原子，取代或未取代的芳族杂环基等）等，R 1表示-NR 10 R 11（其中R 10和R 11可以相同或不同，各自表示氢原子，取代或未取代的低级烷基等）等等，R 2表示-NR 13 R 14（其中R 13和R 14可以相同或不同，各自表示氢原子，取代或未取代的低级烷基等）]或其药学上可接受的盐。

8. 发明授权

US07858333B2 Method for screening candidate compounds for antitumor drug 失效
标题翻译：筛选抗肿瘤药物候选化合物的方法
公开(公告)号：US07858333B2
公开(公告)日：2010-12-28
申请号：US11521372
申请日：2006-09-15
申请人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
发明人： Hitoshi Kiyoi , Tomoki Naoe , Masayuki Towatari , Toshio Kitamura
IPC分类号： C12Q1/50
CPC分类号： G01N33/57426 , G01N33/5011
摘要： Investigation on the frequency of FLT3/ITD found in various blood cancers has revealed that the frequency is high in acute myeloblastic leukemia in particular. Studies on the effects of FLT3/ITD in the blood cell lines revealed that the tyrosine residues in FLT3/ITD is constitutively phosphorylated in these cell lines and that blood cells into which FLT3/ITD is introduced show IL-3 independent proliferation. Moreover, the blood cells into which FLT3/ITD is introduced are found to be capable of forming tumors and inhibit cell differentiation. The inventors have found that it is possible to screen for pharmaceutical compounds against tumors by using inhibition of these FLT3/ITD functions as an index.
摘要翻译：对各种血液中FLT3 / ITD频率的调查显示，特别是急性成髓细胞白血病的频率高。关于FLT3 / ITD在血细胞系中的作用的研究表明，FLT3 / ITD中的酪氨酸残基在这些细胞系中被组成型磷酸化，并且引入了FLT3 / ITD的血细胞显示IL-3不依赖的增殖。此外，发现引入FLT3 / ITD的血细胞能够形成肿瘤并抑制细胞分化。本发明人已经发现，通过使用这些FLT3 / ITD功能的抑制作为指标，可以筛选针对肿瘤的药物化合物。

9. 发明申请

US20090082348A1 INDAZOLE DERIVATIVES 失效
标题翻译：吲哚衍生物
公开(公告)号：US20090082348A1
公开(公告)日：2009-03-26
申请号：US12275614
申请日：2008-11-21
申请人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
发明人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
IPC分类号： A61K31/5377 , A61K31/416 , A61K31/496 , A61K31/454 , A61K31/506 , A61K31/4439 , A61P35/00
CPC分类号： C07D231/56
摘要： The present invention provides a compound represented by Formula (I): [wherein R1 represents CONR1aR1b (wherein R1a and R1b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R1a and R1b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group) or the like, R2 represents a hydrogen atom, CONR2aR2b (wherein R2a and R2b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R2a and R2b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group), NR2cR2d (wherein R2c and R2d may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted aroyl, substituted or unsubstituted heteroaroyl, substituted or unsubstituted ararkyl, substituted or unsubstituted lower alkylsulfonyl or substituted or unsubstituted lower arylsulfonyl) or the like].
摘要翻译：本发明提供由式（I）表示的化合物：[其中R1表示CONR1aR1b（其中R1a和R1b可以相同或不同，各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳基或取代或未取代的杂环基，或者R1a和R1b与相邻的氮原子一起形成取代或未取代的杂环基）等，R2表示氢原子，CONR2aR2b（其中R2a和R2b可以是各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳基或取代或未取代的杂环基，或者R 2a和R 2b与相邻的氮原子一起形成取代基或未取代的杂环基），NR2cR2d（其中R2c和R2d可以相同或不同取代或未取代的芳酰基，取代或未取代的芳酰基，取代或未取代的低级烷基磺酰基或取代或未取代的低级芳基磺酰基）等。。

10. 发明授权

US07470717B2 Indazole derivatives 失效
标题翻译：吲唑衍生物
公开(公告)号：US07470717B2
公开(公告)日：2008-12-30
申请号：US10548475
申请日：2004-07-30
申请人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
发明人： Yoshihisa Ohta , Fumihiko Kanai , Shinji Nara , Yutaka Kanda , Hiroshi Umehara , Yukimasa Shiotsu , Tomoki Naoe , Hitoshi Kiyoi , Keiko Kawashima , Hiromi Ando , Motoki Miyama
IPC分类号： A61K31/416 , C07D231/56
CPC分类号： C07D231/56
摘要： The present invention provides a compound represented by Formula (I): [wherein R1 represents CONR1aR1b (wherein R1a and R1b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R1a and R1b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group) or the like, R2 represents a hydrogen atom, CONR2aR2b (wherein R2a and R2b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted ararkyl or a substituted or unsubstituted heterocyclic group, or R2a and R2b are combined together with the adjacent nitrogen atom thereto to form a substituted or unsubstituted heterocyclic group), NR2cR2d (wherein R2c and R2d may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted aroyl, substituted or unsubstituted heteroaroyl, substituted or unsubstituted ararkyl, substituted or unsubstituted lower alkylsulfonyl or substituted or unsubstituted lower arylsulfonyl) or the like].
摘要翻译：本发明提供由式（I）表示的化合物：[其中R1表示CONR1aR1b（其中R1a和R1b可以相同或不同，各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳烷基或取代或未取代的杂环基，或者R1a和R1b与相邻的氮原子一起形成取代或未取代的杂环基）等，R2表示氢原子，CONR2aR2b（其中R2a和R2b可以是各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳基，取代或未取代的芳烷基或取代或未取代的杂环基，或R 2a和R 2b与相邻的氮原子一起形成取代基或未取代的杂环基），NR2cR2d（其中R2c和R2d可以相同或不同取代或未取代的杂芳酰基，取代或未取代的芳烷基，取代或未取代的低级烷基磺酰基或取代或未取代的低级芳基磺酰基）等，其中R 1代表氢原子，取代或未取代的低级烷基，取代或未取代的低级烷酰基，取代或未取代的芳酰基，。

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