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    GLUCAGON ANALOGS EXHIBITING ENHANCED SOLUBILITY AND STABILITY IN PHYSIOLOGICAL pH BUFFERS
    1.
    发明申请
    GLUCAGON ANALOGS EXHIBITING ENHANCED SOLUBILITY AND STABILITY IN PHYSIOLOGICAL pH BUFFERS 有权
    GLUCAGON ANALOGS展示增强的生理pH缓冲液中的溶解性和稳定性

    公开(公告)号：US20110190200A1

    公开(公告)日：2011-08-04

    申请号：US12999284

    申请日：2009-06-16

    申请人： Richard D. DiMarchi ,  David L. Smiley ,  Maria Dimarchi ,  Joseph Chabenne ,  Jonathan Day

    发明人： Richard D. DiMarchi ,  David L. Smiley ,  Maria Dimarchi ,  Joseph Chabenne ,  Jonathan Day

    IPC分类号： A61K38/26 ,  C07K14/605 ,  A61P3/08

    CPC分类号： C07K14/605 ,  A61K38/00

    摘要： Modified glucagon peptides are disclosed having improved solubility and/or half-life while retaining glucagon agonist activity. The glycogen peptides have been modified by substitution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further enhance the solubility of the glucagon agonist analogs.

    摘要翻译： 公开了具有改善的溶解度和/或半衰期同时保留胰高血糖素激动剂活性的改良的胰高血糖素肽。 糖原肽已经通过用带氨基酸的氨基酸取代天然氨基酸和/或添加到肽的羧基末端而被修饰。 修饰的胰高血糖素激动剂可以通过聚乙二醇化，或加入选自SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23或两者的羧基末端肽进一步修饰，以进一步增强溶解度 的胰高血糖素激动剂类似物。

    Glucagon/GLP-1 receptor co-agonists
    3.
    发明授权
    Glucagon/GLP-1 receptor co-agonists 有权
    胰高血糖素/ GLP-1受体共激动剂

    公开(公告)号：US08454971B2

    公开(公告)日：2013-06-04

    申请号：US12527140

    申请日：2008-02-13

    申请人： Jonathan Day ,  James Patterson ,  Joseph Chabenne ,  Maria Dimarchi ,  David L. Smiley ,  Richard D. Dimarchi

    发明人： Jonathan Day ,  James Patterson ,  Joseph Chabenne ,  Maria Dimarchi ,  David L. Smiley ,  Richard D. Dimarchi

    IPC分类号： A61K38/26 ,  C07K14/605

    CPC分类号： C07K14/605 ,  A61K38/00 ,  A61K38/26 ,  A61K47/60 ,  C07K16/00 ,  C07K2317/52 ,  C07K2319/30

    摘要： Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming lactam bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (K-RNRNNIA) and SEQ ID NO: 28 (KRNR).

    摘要翻译： 公开了相对于天然胰高血糖素在胰高血糖素受体上具有增强的效力的改良的胰高血糖素肽。 通过形成内酰胺桥或用酰胺基取代末端羧酸对胰高血糖素肽进一步修饰产生显示胰高血糖素/ GLP-1受体共激动剂活性的肽。 这些高效胰高血糖素类似物的溶解度和稳定性可以通过聚乙二醇化，多肽羧基末端氨基酸的取代或加入选自SEQ ID NO：26（GPSSGAPPPS ），SEQ ID NO：27（K-RNRNNIA）和SEQ ID NO：28（KRNR）。

    Glucagon analogs exhibiting enhanced solubility and stability in physiological pH buffers
    5.
    发明授权
    Glucagon analogs exhibiting enhanced solubility and stability in physiological pH buffers 有权
    在生理pH缓冲液中表现出增强的溶解度和稳定性的胰高血糖素类似物

    公开(公告)号：US08450270B2

    公开(公告)日：2013-05-28

    申请号：US12999284

    申请日：2009-06-16

    申请人： Richard D. Dimarchi ,  David L. Smiley ,  Maria Dimarchi ,  Joseph Chabenne ,  Jonathan Day

    发明人： Richard D. Dimarchi ,  David L. Smiley ,  Maria Dimarchi ,  Joseph Chabenne ,  Jonathan Day

    IPC分类号： A61K35/00

    CPC分类号： C07K14/605 ,  A61K38/00

    摘要： Modified glucagon peptides are disclosed having improved solubility and/or half-life while retaining glucagon agonist activity. The glycogen peptides have been modified by substitution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further enhance the solubility of the glucagon agonist analogs.

    摘要翻译： 公开了具有改善的溶解度和/或半衰期同时保留胰高血糖素激动剂活性的改良的胰高血糖素肽。 糖原肽已经通过用带氨基酸的氨基酸取代天然氨基酸和/或添加到肽的羧基末端而被修饰。 修饰的胰高血糖素激动剂可以通过聚乙二醇化，或加入选自SEQ ID NO：20，SEQ ID NO：21，SEQ ID NO：23或两者的羧基末端肽进一步修饰，以进一步增强溶解度 的胰高血糖素激动剂类似物。