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    Plant and Plant Storage Organ Having Glp-1 Derivative Accumulated Therein and Method of Producing the Same
    1.
    发明申请
    Plant and Plant Storage Organ Having Glp-1 Derivative Accumulated Therein and Method of Producing the Same 失效
    含有Glp-1衍生物的植物和植物储存器官及其生产方法

    公开(公告)号：US20080292732A1

    公开(公告)日：2008-11-27

    申请号：US11662650

    申请日：2004-09-14

    申请人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Fumio Takaiwa ,  Hiroshi Yasuda ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita

    发明人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Fumio Takaiwa ,  Hiroshi Yasuda ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita

    IPC分类号： A61K36/00 ,  C12N15/82 ,  A01H5/00 ,  A61P31/10

    CPC分类号： A61K38/26 ,  A23L33/105 ,  C12N15/8257

    摘要： The present invention is to provide a plant and a plant storage organ thereof in which GLP-1 derivatives are accumulated, and a method of producing them in order to develop a method for ingesting orally GLP-1 derivatives at a low cost and to make use of it in diabetic treatment. A transgenic plant or a plant storage organ thereof in which GLP-1 derivatives are accumulated cleavable with a digestive enzyme is produced by a method comprising: integrating into a vector a linked GLP-1s-DNA which comprises tandem repeated “n” DNAs (“n” being an integer of 3 or more) encoding a GLP-1 derivative consisting of GLP-1 (7-36) or of an amino acid sequence of GLP-1 (7-36) in which one or a few amino acids are deleted, substituted and/or added, and C-terminal consists of Arg or Lys, and having GLP-1 activity; introducing the vector into a plant cell; and redifferentiating the obtained transformant. The transgenic plant and the plant storage organ are useful as a pharmaceutical composition or a food or drink for treating or preventing diabetes.

    摘要翻译： 本发明提供一种其中积聚有GLP-1衍生物的植物和植物贮藏器官及其生产方法，以便开发低成本摄取口服GLP-1衍生物的方法并使用 的糖尿病治疗。 GLP-1衍生物可以用消化酶积聚可切割的转基因植物或植物贮藏器官是通过以下方法产生的：将连接的GLP-1s-DNA整合到载体中，所述连接的GLP-1s-DNA包含串联重复的“n”DNA（“ 编号由GLP-1（7-36）或GLP-1（7-36）的氨基酸序列组成的GLP-1衍生物的n“为3以上的整数，其中一个或几个氨基酸为 缺失，取代和/或添加，C-末端由Arg或Lys组成，具有GLP-1活性; 将载体导入植物细胞; 并对所得转化体进行重新分化。 转基因植物和植物贮藏器官可用作药物组合物或用于治疗或预防糖尿病的食物或饮料。

    GLP-1 derivative
    2.
    发明授权
    GLP-1 derivative 失效
    GLP-1衍生物

    公开(公告)号：US07847063B2

    公开(公告)日：2010-12-07

    申请号：US10550624

    申请日：2004-03-26

    申请人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Fumio Takaiwa ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita ,  Yukari Kobara

    发明人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Fumio Takaiwa ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita ,  Yukari Kobara

    IPC分类号： A61K38/00 ,  C07K14/00

    CPC分类号： C12N15/8257 ,  C07K14/605 ,  C12N15/8216

    摘要： The present invention provides a method for highly producing a recombinant protein in a plant storage organ and a GLP-1 derivative. The plant storage organ in which the recombinant protein is highly produced is obtained by transformation with the use of a vector which comprises a recombinant protein gene, a cytokinin-related gene, a drug-resistant gene and a removable DNA element, in which the cytokinin-related gene and the drug-resistant gene exist in the positions so that they can behave together with the DNA element, while the recombinant protein to be expressed in the plant storage organ exists in the position so that it would not behave together with the DNA element. The GLP-1 is produced by using the method, and a derivative having been stabilized against enzymatic digestion is further provided.

    摘要翻译： 本发明提供了在植物贮藏器官和GLP-1衍生物中高度产生重组蛋白的方法。 通过使用包含重组蛋白基因，细胞分裂素相关基因，耐药性基因和可移除DNA元件的载体转化获得重组蛋白质高度产生的植物贮藏器官，其中细胞分裂素 相关基因和耐药基因存在于可以与DNA元件一起表现的位置，而在植物储存器官中表达的重组蛋白存在于与DNA不一致的位置 元件。 通过使用该方法制备GLP-1，进一步提供了稳定的酶促消化的衍生物。

    Plant and plant storage organ having GLP-1 derivative accumulated therein and method of producing the same
    3.
    发明授权
    Plant and plant storage organ having GLP-1 derivative accumulated therein and method of producing the same 失效
    蓄积有GLP-1衍生物的植物贮藏器具及其制造方法

    公开(公告)号：US07947876B2

    公开(公告)日：2011-05-24

    申请号：US11662650

    申请日：2004-09-14

    申请人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Humio Takaiwa ,  Hiroshi Yasuda ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita

    发明人： Koichi Sugita ,  Saori Kasahara ,  Hiroyasu Ebinuma ,  Humio Takaiwa ,  Hiroshi Yasuda ,  Takahito Jomori ,  Yuji Hayashi ,  Akira Tashita

    IPC分类号： A01H5/00 ,  C12N15/82

    CPC分类号： A61K38/26 ,  A23L33/105 ,  C12N15/8257

    摘要： The present invention is regarding plants and plant storage organs thereof in which GLP-1 derivatives are accumulated, and methods of producing them. The transgenic plants and plant storage organs thereof accumulate tandem repeated GLP-1 derivatives cleavable with intestinal digestive enzyme to monomeric molecules and are produced by methods comprising: integrating into vectors linked DNAs which comprise tandem repeated DNAs encoding the GLP-1 derivative with trypsin resistance in which the amino acid in the 26th position is Gln, the amino acid in the 34th position is Asn or Asp, and C-terminal consists of Arg or Lys to produce monomeric molecules; introducing the vectors into plant cells; and redifferentiating the obtained transformants. The edible transgenic plants and plant storage organs are useful for treating diabetes and can be ingested by diabetic patients.

    摘要翻译： 本发明涉及其中积累GLP-1衍生物的植物和植物贮藏器官及其生产方法。 其转基因植物和植物储存器官将可与肠消化酶切割的串联重复的GLP-1衍生物积聚到单体分子中，并通过以下方法产生：包括：将包含编码GLP-1衍生物的串联重复DNA与胰蛋白酶抗性的连锁DNA连接 其中第26位的氨基酸是Gln，第34位的氨基酸是Asn或Asp，C末端由Arg或Lys组成以产生单体分子; 将载体导入植物细胞; 并重新分化获得的转化体。 可食用的转基因植物和植物贮藏器官可用于治疗糖尿病并可被糖尿病患者摄入。

    Agent for preventing/ameliorating obesity comprising methylidene hydrizide compound as active ingredient
    7.
    发明授权
    Agent for preventing/ameliorating obesity comprising methylidene hydrizide compound as active ingredient 失效
    包含亚甲基氢化物化合物作为活性成分的用于预防/改善肥胖症的药剂

    公开(公告)号：US07081473B2

    公开(公告)日：2006-07-25

    申请号：US10514027

    申请日：2003-05-20

    申请人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

    发明人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

    IPC分类号： A61K31/166 ,  A61K31/4045 ,  A61P3/04 ,  C07C243/18 ,  C07D209/08 ,  C07D409/06

    CPC分类号： C07C243/38 ,  A61K31/166 ,  A61K31/4045 ,  C07D209/08 ,  C07D209/14 ,  C07D409/06

    摘要： The present invention provides a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity based on inhibition of GIP functions, which comprises, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, halogen, a nitro group or a cyano group, R2 and R3 each represent hydrogen or halogen, hydrogen or a methoxy group, or both R2 and R3 may form an optionally substituted benzene or pyrrole ring, and A represents nitrogen or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene or pyrrole ring, R7, R8 and R9 each represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group or the like, and R1 represents an optionally substituted morpholyl group or the like) or a pharmaceutically acceptable salt thereof.

    摘要翻译： 本发明提供了GIP功能的低分子抑制剂，另外，作为活性成分，由以下通式（I）表示的化合物作为活性成分，可以抑制GIP功能的抑制/改善， （其中R 1表示氢，卤素，硝基或氰基，R 2和R 3各自表示氢或卤素，氢， 或甲氧基，或者R 2和R 3都可以形成任选取代的苯或吡咯环，A表示氮或CR 4， 其中R 4表示氢，任选取代的C 1 -C 6烷基，-OR 7，-NR 8 R 9， 或者可以与R 3，R 3，R 3，R 11， 形成任选取代的苯或吡咯环，R 7，R 8和R 9各自表示氢或任选取代的C 1至C 6 Al 烷基，R 10表示C1〜C6烷基等，R 1表示任选取代的吗啉基等）或其药学上可接受的盐。

    Agents for preventing or ameliorating insulin resistance and /or obesity
    8.
    发明申请
    Agents for preventing or ameliorating insulin resistance and /or obesity 失效
    用于预防或改善胰岛素抵抗和/或肥胖的药剂

    公开(公告)号：US20050159415A1

    公开(公告)日：2005-07-21

    申请号：US10514027

    申请日：2003-05-20

    申请人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

    发明人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

    IPC分类号： A61K31/166 ,  A61K31/4045 ,  A61P3/04 ,  A61P43/00 ,  C07C243/38 ,  C07D209/08 ,  C07D209/14 ,  C07D409/06 ,  A61K31/537 ,  A61K31/165 ,  A61K31/40 ,  A61K31/405 ,  A61K31/445

    CPC分类号： C07C243/38 ,  A61K31/166 ,  A61K31/4045 ,  C07D209/08 ,  C07D209/14 ,  C07D409/06

    摘要： The present invention provides a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity based on inhibition of GIP functions, which comprises, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, halogen, a nitro group or a cyano group, R2 and R3 each represent hydrogen or halogen, hydrogen or a methoxy group, or both R2 and R3 may form an optionally substituted benzene or pyrrole ring, and A represents nitrogen or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R1 or —SO2—R or may, together with R3, form an optionally substituted benzene or pyrrole ring, R7, R8 and R9 each represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group or the like, and R1 represents an optionally substituted morpholyl group or the like) or a pharmaceutically acceptable salt thereof.

    摘要翻译： 本发明提供了GIP功能的低分子抑制剂，另外，作为活性成分，由以下通式（I）表示的化合物作为活性成分，可以抑制GIP功能的抑制/改善， （其中R 1表示氢，卤素，硝基或氰基，R 2和R 3各自表示氢或卤素，氢， 或甲氧基，或者R 2和R 3都可以形成任选取代的苯或吡咯环，A表示氮或CR 4， 其中R 4表示氢，任选取代的C 1 -C 6烷基，-OR 7，-NR 8 R 9， 或者可以与R 3一起形成任选取代的苯或吡咯，其中R 1，R 2，R 3， R 7，R 8和R 9各自表示氢或任选取代的C 1至C 6烷基，R S 或其药学上可接受的盐，其中R 1表示C1至C6烷基等，R 1表示任选取代的吗啉基等）或其药学上可接受的盐。