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    GIP RECEPTOR-ACTIVE GLUCAGON COMPOUNDS
    1.
    发明申请
    GIP RECEPTOR-ACTIVE GLUCAGON COMPOUNDS 有权
    GIP受体活性GLUCAGON化合物

    公开(公告)号：US20160052989A1

    公开(公告)日：2016-02-25

    申请号：US14840580

    申请日：2015-08-31

    申请人： Indiana University Research and Technology Corporation

    发明人： Richard D. DiMARCHI ,  Tao MA

    IPC分类号： C07K14/605

    CPC分类号： C07K14/605 ,  A61K38/00 ,  A61K38/26

    摘要： Glucagon peptides with increased GIP activity are provided, optionally with GLP-1 and/or glucagon activity. In some embodiments, C-terminally extended glucagon peptides comprising an amino acid sequence substantially similar to native glucagon are provided herein.

    摘要翻译： 提供具有增加的GIP活性的胰高血糖素肽，任选地具有GLP-1和/或胰高血糖素活性。 在一些实施方案中，本文提供了包含与天然胰高血糖素基本相似的氨基酸序列的C末端扩增的胰高血糖素肽。

    GLUCAGON/GLP-1 RECEPTOR CO-AGONISTS
    2.
    发明申请
    GLUCAGON/GLP-1 RECEPTOR CO-AGONISTS 审中-公开
    GLUCAGON / GLP-1受体协同作用

    公开(公告)号：US20150126440A1

    公开(公告)日：2015-05-07

    申请号：US14535853

    申请日：2014-11-07

    申请人： INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

    发明人： Jonathan DAY ,  James PATTERSON ,  Joseph CHABENNE ,  Maria DiMARCHI ,  David L. SMILEY ,  Richard D. DiMARCHI

    IPC分类号： C07K14/605 ,  C07K16/00 ,  A61K38/26 ,  A61K47/48

    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 (KRNRNNIA) 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（KRNRNNIA）和SEQ ID NO：28（KRNR）。

    GLUCAGON ANALOGS EXHIBITING GIP RECEPTOR ACTIVITY
    7.
    发明申请
    GLUCAGON ANALOGS EXHIBITING GIP RECEPTOR ACTIVITY 有权
    GLUCAGON ANALOGS展示GIP受体活性

    公开(公告)号：US20140011738A1

    公开(公告)日：2014-01-09

    申请号：US13920188

    申请日：2013-06-18

    申请人： INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

    发明人： Richard D. DiMARCHI

    IPC分类号： C07K14/605

    CPC分类号： C07K14/605 ,  A61K38/16 ,  A61K38/17 ,  A61K38/26

    摘要： Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

    摘要翻译： 本文提供了在GIP受体上表现出有效活性的胰高血糖素类似物，并且因此被预期用于治疗糖尿病和肥胖症。 在示例性实施方案中，本公开的胰高血糖素类似物在GIP受体下显示EC50，其在纳摩尔或皮摩尔范围内。

    SINGLE CHAIN INSULIN AGONISTS EXHIBITING HIGH ACTIVITY AT THE INSULIN RECEPTOR
    10.
    发明申请
    SINGLE CHAIN INSULIN AGONISTS EXHIBITING HIGH ACTIVITY AT THE INSULIN RECEPTOR 审中-公开
    单链胰岛素激素在胰岛素受体中展示高活性

    公开(公告)号：US20160340400A1

    公开(公告)日：2016-11-24

    申请号：US15229942

    申请日：2016-08-05

    申请人： INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

    发明人： Richard D. DiMARCHI ,  Yulia AZRIEL ,  Zachary KAUR ,  Jonathan MEYERS ,  Todd PARODY ,  Yan ZHAO

    IPC分类号： C07K14/62 ,  A61K38/18 ,  A61K38/28 ,  C07K14/475 ,  A61K47/48

    CPC分类号： C07K14/62 ,  A61K38/00 ,  A61K38/18 ,  A61K38/28 ,  A61K47/60 ,  C07K14/475

    摘要： Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.

    摘要翻译： 提供具有对胰岛素受体具有高效力和特异性的单链胰岛素类似物。 如本文所公开的，优选尺寸的连接部分可用于连接人胰岛素A和B链或其类似物或衍生物，其中B链的B25氨基酸的羧基末端连接到A1氨基酸的氨基末端 A链通过中间连接部分。 在实施方案中，连接部分包含6-16个单体单元的聚乙二醇，并且在替代实施方案中，连接部分包含衍生自IGF-1 C-肽的非天然氨基酸序列，并且包含至少8个氨基酸且不包含 长度超过12个氨基酸。 还公开了单链胰岛素类似物的前药和缀合物衍生物。