公开(公告)号：US07253286B2

公开(公告)日：2007-08-07

申请号：US10420466

申请日：2003-04-18

申请人： Yasuhiro Funahashi ,  Akihiko Tsuruoka ,  Masayuki Matsukura ,  Toru Haneda ,  Yoshio Fukuda ,  Junichi Kamata ,  Keiko Takahashi ,  Tomohiro Matsushima ,  Kazuki Miyazaki ,  Ken-ichi Nomoto ,  Tatsuo Watanabe ,  Hiroshi Obaishi ,  Atsumi Yamaguchi ,  Sachi Suzuki ,  Katsuji Nakamura ,  Fusayo Mimura ,  Yuji Yamamoto ,  Junji Matsui ,  Kenji Matsui ,  Takako Yoshiba ,  Yasuyuki Suzuki ,  Itaru Arimoto

发明人： Yasuhiro Funahashi ,  Akihiko Tsuruoka ,  Masayuki Matsukura ,  Toru Haneda ,  Yoshio Fukuda ,  Junichi Kamata ,  Keiko Takahashi ,  Tomohiro Matsushima ,  Kazuki Miyazaki ,  Ken-ichi Nomoto ,  Tatsuo Watanabe ,  Hiroshi Obaishi ,  Atsumi Yamaguchi ,  Sachi Suzuki ,  Katsuji Nakamura ,  Fusayo Mimura ,  Yuji Yamamoto ,  Junji Matsui ,  Kenji Matsui ,  Takako Yoshiba ,  Yasuyuki Suzuki ,  Itaru Arimoto

IPC分类号： A61K31/47 ,  C07D215/16

CPC分类号： C07D213/73 ,  A61K31/4706 ,  A61K31/4745 ,  A61K31/517 ,  A61K31/519 ,  C07D207/34 ,  C07D213/26 ,  C07D213/68 ,  C07D213/74 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D215/18 ,  C07D215/233 ,  C07D215/36 ,  C07D215/38 ,  C07D215/48 ,  C07D239/34 ,  C07D239/42 ,  C07D239/47 ,  C07D239/88 ,  C07D249/04 ,  C07D261/14 ,  C07D277/48 ,  C07D307/68 ,  C07D319/06 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

摘要： Compounds represented by the following general formula: [wherein Ag is an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xg is —O—, —S—, etc.; Yg is an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tg1 is a group represented by the following general formula: (wherein Eg is a single bond or —N(Rg2)—, Rg1 and Rg2 each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, etc. and Zg represents a C1-8 alkyl group, a C3-8 alicyclic hydrocarbon group, a C6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.

摘要翻译： 由以下通式表示的化合物：其中A为任选取代的5至14元杂环基等; X-O是-O - ， - S-等; Y是任选取代的C 6-14芳基，任选取代的5至14元杂环基等; 并且T 1是由以下通式表示的基团：其中E是单键或-N（R 2）2 - R 1，G 1和R 2各自独立地表示氢原子，任选取代的C 1-6烷基等，Z

公开(公告)号：US20060030694A1

公开(公告)日：2006-02-09

申请号：US11114962

申请日：2005-04-26

申请人： Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

发明人： Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

IPC分类号： C07K14/705 ,  C07K16/46 ,  A61K38/17

CPC分类号： A61K48/00 ,  A61K9/0019 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/30 ,  C07K2319/32

摘要： This invention provides a method for treating a subject having a tumor and a method for inhibiting angiogenesis in a subject, both comprising administering to the subject an effective amount of a composition of matter comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety. This invention also provides a composition of matter comprising the extracellular domain of Notch4 receptor protein operably affixed to a half-life-increasing moiety. This invention further provides an article of manufacture. Finally, this invention provides a replicable vector which encodes a polypeptide comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety, a host vector system which comprises such replicable vector and a method of producing such polypeptide.

公开(公告)号：US06673787B2

公开(公告)日：2004-01-06

申请号：US10098420

申请日：2002-03-18

申请人： Toru Haneda ,  Akihiko Tsuruoka ,  Junichi Kamata ,  Tadashi Okabe ,  Keiko Takahashi ,  Kazumasa Nara ,  Shinichi Hamaoka ,  Norihiro Ueda ,  Takashi Owa ,  Toshiaki Wakabayashi ,  Yasuhiro Funahashi ,  Taro Semba ,  Naoko Hata ,  Yuji Yamamoto ,  Yoichi Ozawa ,  Noako Tsukahara

发明人： Toru Haneda ,  Akihiko Tsuruoka ,  Junichi Kamata ,  Tadashi Okabe ,  Keiko Takahashi ,  Kazumasa Nara ,  Shinichi Hamaoka ,  Norihiro Ueda ,  Takashi Owa ,  Toshiaki Wakabayashi ,  Yasuhiro Funahashi ,  Taro Semba ,  Naoko Hata ,  Yuji Yamamoto ,  Yoichi Ozawa ,  Noako Tsukahara

IPC分类号： A61K3133

CPC分类号： C07D401/12 ,  C07D209/04 ,  C07D209/30 ,  C07D209/42 ,  C07D403/12 ,  C07D409/12

摘要： The present invention creates a novel antiangiogenic agent and provides an antitumor agent which shows high safety as compared with conventional antitumor agents, has a sure effect and is able to be administered for a long period. That is, it provides an indole compound represented by the following formula (I), its pharmacologically acceptable salt or hydrates thereof. In the formula, R1 represents hydrogen atom, a halogen atom or cyano group; R2 and R3 are the same as or different from and each represents hydrogen atom, a C1-C4 lower alkyl group or a halogen atom; R4 represents hydrogen atom or a C1-C4 lower alkyl group; and the ring A represents cyanophenyl group, aminosulfonylphenyl group, aminopyridyl group, aminopyrimidyl group, a halopyridyl group or cyanothiophenyl group, provided that the case where all of R1, R2 and R3 are hydrogen atoms, where both R2 and R3 are hydrogen atoms or where the ring A is aminosulfonyl group and both R1 and R2 are halogen atoms is excluded. Further, when the ring A is cyanophenyl group, 2-amino-5-pyridyl group or a 2-halo-5-pyridyl group and R1 is cyano group or a halogen atom, at least one of R2 and R3 should not be a hydrogen atom.

摘要翻译： 本发明创造出一种新型抗血管生成剂，并提供与常规抗肿瘤剂相比显示出高安全性的抗肿瘤剂，具有确定的作用并且能够长时间施用。 也就是说，其提供由下式（I）表示的吲哚化合物，其药理学上可接受的盐或其水合物。在式中，R 1表示氢原子，卤素原子或氰基; R 2和R 3各自表示氢原子，C 1 -C 4低级烷基或卤素原子; R 4表示氢原子或C 1 -C 4低级烷基; 并且环A表示氰基苯基，氨基磺酰基苯基，氨基吡啶基，氨基嘧啶基，卤代吡啶基或氰基噻吩基，条件是所有R 1，R 2和R 3均为氢原子的情况，其中 R 2和R 3都是氢原子，或者其中环A是氨基磺酰基并且R 1和R 2都是卤素原子。 此外，当环A为氰基苯基，2-氨基-5-吡啶基或2-卤代-5-吡啶基，R 1为氰基或卤素原子时，R 2和 R 3不应该是氢原子。

公开(公告)号：US09945862B2

公开(公告)日：2018-04-17

申请号：US14122339

申请日：2012-05-31

申请人： Yasuhiro Funahashi ,  Tadashi Kadowaki ,  Junji Matsui ,  Jason S. Simon ,  Lucy Xu

发明人： Yasuhiro Funahashi ,  Tadashi Kadowaki ,  Junji Matsui ,  Jason S. Simon ,  Lucy Xu

IPC分类号： A61K31/47 ,  G01N33/574 ,  C12Q1/68

CPC分类号： G01N33/57407 ,  A61K31/47 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/57438

摘要： Biomarkers are provided that are predictive of a subject's responsiveness to a therapy comprising lenvatinib or a pharmaceutically acceptable salt thereof (e.g., lenvatinib mesylate). The biomarkers, compositions, and methods described herein are useful in selecting appropriate treatment modalities for a subject having cancer (e.g., thyroid cancer, kidney cancer), suspected of having cancer, or at risk of developing cancer.

公开(公告)号：US08993725B2

公开(公告)日：2015-03-31

申请号：US12657573

申请日：2010-01-21

申请人： Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

发明人： Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

IPC分类号： A61K38/00 ,  C07K14/00 ,  A61K48/00 ,  C07K14/705 ,  A61K9/00

CPC分类号： A61K48/00 ,  A61K9/0019 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/30 ,  C07K2319/32

摘要： This invention provides a method for treating a subject having a tumor and a method for inhibiting angiogenesis in a subject, both comprising administering to the subject an effective amount of a composition of matter comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety. This invention also provides a composition of matter comprising the extracellular domain of Notch4 receptor protein operably affixed to a half-life-increasing moiety. This invention further provides an article of manufacture. Finally, this invention provides a replicable vector which encodes a polypeptide comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety, a host vector system which comprises such replicable vector and a method of producing such polypeptide.

摘要翻译： 本发明提供了治疗患有肿瘤的受试者的方法和用于抑制受试者血管生成的方法，所述方法包括向受试者施用有效量的包含Notch受体蛋白的细胞外结构域的物质组合物， 生命增加部分。 本发明还提供了包含Notch4受体蛋白的细胞外结构域的物质组合物，其可操作地附着于半衰期增加的部分。 本发明还提供了一种制造品。 最后，本发明提供了可复制载体，其编码包含可操作地附着于半衰期增加部分的Notch受体蛋白的细胞外结构域的多肽，包含该可复制载体的宿主载体系统和产生该多肽的方法。

公开(公告)号：US08962650B2

公开(公告)日：2015-02-24

申请号：US14002018

申请日：2012-04-16

申请人： Yusuke Narita ,  Junji Matsui ,  Yasuhiro Funahashi

发明人： Yusuke Narita ,  Junji Matsui ,  Yasuhiro Funahashi

IPC分类号： A61K31/437 ,  A61K31/4353 ,  A61K31/47 ,  C07D215/48

CPC分类号： A61K31/47 ,  A61K31/437 ,  C07D215/48 ,  A61K2300/00

摘要： A therapeutic agent for tumor for combined use of a compound or pharmaceutically acceptable salt thereof represented by Formula (I) and a compound represented by Formula (II): wherein R1 is C1-6 alkyl or C3-8 cycloalkyl, R2 is a hydrogen atom or C1-6 alkoxy, and R3 is a hydrogen atom or a halogen atom, exhibits an excellent antitumor effect compared to cases where these are individually used.

摘要翻译： 用于组合使用由式（I）表示的化合物或其药学上可接受的盐和由式（II）表示的化合物的肿瘤治疗剂：其中R 1是C 1-6烷基或C 3-8环烷基，R 2是氢原子 或C 1-6烷氧基，并且R 3为氢原子或卤素原子，与单独使用它们的情况相比表现出优异的抗肿瘤效果。

公开(公告)号：US20130123274A1

公开(公告)日：2013-05-16

申请号：US13805826

申请日：2011-06-23

申请人： Takayuki Nakagawa ,  Tomohiro Matsushima ,  Yasuhiro Funahashi

发明人： Takayuki Nakagawa ,  Tomohiro Matsushima ,  Yasuhiro Funahashi

IPC分类号： A61K31/496 ,  A61K31/47

CPC分类号： A61K31/496 ,  A61K31/4427 ,  A61K31/4545 ,  A61K31/47 ,  A61K2300/00

摘要： An antitumor agent for combined use of a compound or pharmaceutically acceptable salt thereof represented by Formula (I) and a compound or pharmaceutically acceptable salt thereof represented by Formula (II) exhibits an excellent antitumor effect compared to cases where these are individually used, and exhibits antitumor effects against various cancer types: wherein R1 is azetidinyl and the like, R2 to R5 is a hydrogen atom or a halogen atom, R6 is C3-8 cycloalkyl and the like, R7 is a hydrogen atom and the like, and R8 is a halogen atom and the like.

摘要翻译： 由式（I）表示的化合物或其药学上可接受的盐及其由式（II）表示的化合物或其药学上可接受的盐组合使用的抗肿瘤剂与单独使用它们的情况相比显示出优异的抗肿瘤效果， 针对各种癌症类型的抗肿瘤效果：其中R1为氮杂环丁烷基等，R2至R5为氢原子或卤素原子，R6为C3-8环烷基等，R7为氢原子等，R8为 卤素原子等。

公开(公告)号：US20060247259A1

公开(公告)日：2006-11-02

申请号：US11293785

申请日：2005-12-02

申请人： Yasuhiro Funahashi ,  Akihiko Tsuruoka ,  Masayuki Matsukura ,  Toru Haneda ,  Yoshio Fukuda ,  Junichi Kamata ,  Keiko Takahashi ,  Tomohiro Matsushima ,  Kazuki Miyazaki ,  Ken-ichi Nomoto ,  Tatsuo Watanabe ,  Hiroshi Obaishi ,  Atsumi Yamaguchi ,  Sachi Suzuki ,  Katsuji Nakamura ,  Fusayo Mimura ,  Yuji Yamamoto ,  Junji Matsui ,  Kenji Matsui ,  Takako Yoshiba ,  Yasuyuki Suzuki ,  Itaru Arimoto

发明人： Yasuhiro Funahashi ,  Akihiko Tsuruoka ,  Masayuki Matsukura ,  Toru Haneda ,  Yoshio Fukuda ,  Junichi Kamata ,  Keiko Takahashi ,  Tomohiro Matsushima ,  Kazuki Miyazaki ,  Ken-ichi Nomoto ,  Tatsuo Watanabe ,  Hiroshi Obaishi ,  Atsumi Yamaguchi ,  Sachi Suzuki ,  Katsuji Nakamura ,  Fusayo Mimura ,  Yuji Yamamoto ,  Junji Matsui ,  Kenji Matsui ,  Takako Yoshiba ,  Yasuyuki Suzuki ,  Itaru Arimoto

IPC分类号： A61K31/519 ,  A61K31/517 ,  A61K31/4745 ,  A61K31/4706 ,  C07D487/02 ,  C07D471/02

CPC分类号： C07D213/73 ,  A61K31/4706 ,  A61K31/4745 ,  A61K31/517 ,  A61K31/519 ,  C07D207/34 ,  C07D213/26 ,  C07D213/68 ,  C07D213/74 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D215/18 ,  C07D215/233 ,  C07D215/36 ,  C07D215/38 ,  C07D215/48 ,  C07D239/34 ,  C07D239/42 ,  C07D239/47 ,  C07D239/88 ,  C07D249/04 ,  C07D261/14 ,  C07D277/48 ,  C07D307/68 ,  C07D319/06 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

摘要： Compounds represented by the following general formula: [wherein Ag is an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xg is —O—, —S—, etc.; Yg is an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tg1 is a group represented by the following general formula: (wherein Eg is a single bond or —N(Rg2)—, Rg1 and Rg2 each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, etc. and Zg represents a C1-8 alkyl group, a C3-8 alicyclic hydrocarbon group, a C6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.

公开(公告)号：US06638964B2

公开(公告)日：2003-10-28

申请号：US10098421

申请日：2002-03-18

申请人： Toru Haneda ,  Akihiko Tsuruoka ,  Junichi Kamata ,  Tadashi Okabe ,  Keiko Takahashi ,  Kazumasa Nara ,  Shinichi Hamaoka ,  Norihiro Ueda ,  Takashi Owa ,  Toshiaki Wakabayashi ,  Yasuhiro Funahashi ,  Taro Semba ,  Naoko Hata ,  Yuji Yamamoto ,  Yoichi Ozawa ,  Noako Tsukahara

发明人： Toru Haneda ,  Akihiko Tsuruoka ,  Junichi Kamata ,  Tadashi Okabe ,  Keiko Takahashi ,  Kazumasa Nara ,  Shinichi Hamaoka ,  Norihiro Ueda ,  Takashi Owa ,  Toshiaki Wakabayashi ,  Yasuhiro Funahashi ,  Taro Semba ,  Naoko Hata ,  Yuji Yamamoto ,  Yoichi Ozawa ,  Noako Tsukahara

IPC分类号： A61K31405

CPC分类号： C07D401/12 ,  C07D209/04 ,  C07D209/30 ,  C07D209/42 ,  C07D403/12 ,  C07D409/12

摘要： The present invention creates a novel antiangiogenic agent and provides an antitumor agent which shows high safety as compared with conventional antitumor agents, has a sure effect and is able to be administered for a long period. That is, it provides an indole compound represented by the following formula (I), its pharmacologically acceptable salt or hydrates thereof: In the formula, R1 represents hydrogen atom, a halogen atom or cyano group; R2 and R3 are the same as or different from and each represents hydrogen atom, a C1˜C4 lower alkyl group or a halogen atom; R4 represents hydrogen atom or a C1˜C4 lower alkyl group; and the ring A represents cyanophenyl group, aminosulfonylphenyl group, aminopyridyl group, aminopyrimidyl group, a halopyridyl group or cyanothiophenyl group, provided that the case where all of R1, R2 and R3 are hydrogen atoms, where both R2 and R3 are hydrogen atoms or where the ring A is aminosulfonyl group and both R1 and R2 are halogen atoms is excluded. Further, when the ring A is cyanophenyl group, 2-amino-5-pyridyl group or a 2-halo-5-pyridyl group and R1 is cyano group or a halogen atom, at least one of R2 and R3 should not be a hydrogen atom.

摘要翻译： 本发明创造出一种新型抗血管生成剂，并提供与常规抗肿瘤剂相比显示出高安全性的抗肿瘤剂，具有确定的作用并且能够长时间施用。 也就是说，其提供由下式（I）表示的吲哚化合物，其药理学上可接受的盐或水合物：在式中，R 1表示氢原子，卤素原子或氰基; R 2和R 3各自代表氢原子，C 1 -C 4低级烷基或卤素原子; R 4表示氢原子或C 1 -C 4低级烷基; 并且环A表示氰基苯基，氨基磺酰基苯基，氨基吡啶基，氨基嘧啶基，卤代吡啶基或氰基噻吩基，条件是所有R 1，R 2和R 3均为氢原子的情况，其中 R 2和R 3都是氢原子，或者其中环A是氨基磺酰基并且R 1和R 2都是卤素原子。 此外，当环A为氰基苯基，2-氨基-5-吡啶基或2-卤代-5-吡啶基，R 1为氰基或卤素原子时，R 2和 R 3不应该是氢原子。

公开(公告)号：US5691915A

公开(公告)日：1997-11-25

申请号：US402377

申请日：1995-03-13

申请人： Yasuhiro Funahashi ,  Kazunori Ikami ,  Yukie Hasegawa

发明人： Yasuhiro Funahashi ,  Kazunori Ikami ,  Yukie Hasegawa

IPC分类号： G10K15/04 ,  H04N7/173 ,  H04N21/472 ,  H04N21/6437 ,  H04Q1/00

CPC分类号： H04N7/17336 ,  G06Q20/10 ,  G06Q20/204 ,  H04N7/17318

摘要： When the terminal 5 requests a partial access of a desired karaoke song to the center 3 in S380, only the climactic passage data of the karaoke song is transmitted from the center 3 to the terminal 5. The terminal 5 reproduces the climactic passage in S400. Then, the terminal 5 determines whether or not the user will pay for the karaoke song in S410. When the payment is confirmed, the terminal 5 requests total access to the center 3 in S340, receives the entire data of the karaoke song in S350, and reproduces the data in S360. It is possible to prevent the user from erroneously requesting a total access of a karaoke song which the user does not want to sing. It is ensured that the user can obtain karaoke songs which he/she really wants to sing, within a short period of time.

摘要翻译： 当终端5在S380中请求对中心3的期望的卡拉OK歌曲的部分访问时，只有卡拉OK歌曲的高潮通过数据从中心3发送到终端5.终端5在S400中再现高潮通道。 然后，终端5确定在S410中用户是否将支付卡拉OK歌曲。 当确认支付时，终端5在S340请求对中心3的全部访问，在S350中接收卡拉OK歌曲的全部数据，并在S360中再现数据。 可以防止用户错误地请求用户不想唱歌的卡拉OK歌曲的全部访问。 确保用户可以在短时间内获得他/她真正想唱的卡拉OK歌曲。