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    ESTER-BASED INSULIN PRODRUGS
    11.
    发明申请
    ESTER-BASED INSULIN PRODRUGS 有权
    基于ESTER的胰岛素PRODRUGS

    公开(公告)号：US20140212419A1

    公开(公告)日：2014-07-31

    申请号：US14182706

    申请日：2014-02-18

    Applicant: Indiana University Research and Technology Corporation

    Inventor： Richard D. DiMARCHI ,  Arnab DE

    IPC: A61K38/28 ,  A61K39/395

    CPC classification number: A61K38/28 ,  A61K9/0019 ,  A61K38/26 ,  A61K39/395 ,  A61K47/48215 ,  A61K47/48246 ,  A61K47/60 ,  A61K47/64

    Abstract: Prodrug formulations of bioactive polypeptides are provided wherein the bioactive polypeptide has been modified by the linkage of a dipeptide to the bioactive polypeptide through an ester linkage. The prodrugs disclosed herein in some embodiments have extended half lives of at least 1.5 hours (e.g., at least 10 hours), and more typically greater than 20 hours and less than 70 hours, and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

    Abstract translation: 提供生物活性多肽的前药制剂，其中生物活性多肽已经通过二酯与生物活性多肽的连接通过酯键进行了修饰。 在一些实施方案中本文公开的前体药物具有至少1.5小时（例如，至少10小时），更通常大于20小时和小于70小时的半衰期延长，并且在生理条件下通过 由化学不稳定驱动的非酶反应。

    GLUCAGON ANTAGONIST-GIP AGONIST CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLIC DISORDERS AND OBESITY
    14.
    发明申请
    GLUCAGON ANTAGONIST-GIP AGONIST CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLIC DISORDERS AND OBESITY 审中-公开
    GLUCAGON ANTAGONIST-GIP激动剂联合用药和组合物治疗代谢障碍和肥胖

    公开(公告)号：US20140107021A1

    公开(公告)日：2014-04-17

    申请号：US14026671

    申请日：2013-09-13

    Applicant: Indiana University Research and Technology Corporation

    Inventor： Richard D. DiMARCHI ,  Tao MA

    IPC: C07K14/605 ,  A61K38/26

    CPC classification number: C07K14/605 ,  A61K38/26 ,  A61K2300/00

    Abstract: Provided herein are peptide combinations comprising a GIP agonist peptide and a glucagon antagonist peptide. In some embodiments, the peptide combination is provided as a composition, e.g., a pharmaceutical composition, while in other embodiments, the peptide combination is provided as a kit. In yet other embodiments, the peptide combination is provided as a conjugate, e.g., a fusion peptide, a heterodimer. In specific aspects, the GIP agonist peptide is an analog of native human glucagon. In specific aspects, the glucagon antagonist peptide is an analog of native human glucagon. In some embodiments, the GIP agonist peptide is covalently attached to the glucagon antagonist peptide via a linker. Method of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the peptide compositions described herein are further provided.

    Abstract translation: 本文提供了包含GIP激动剂肽和胰高血糖素拮抗肽的肽组合。 在一些实施方案中，肽组合作为组合物例如药物组合物提供，而在其它实施方案中，肽组合作为试剂盒提供。 在其它实施方案中，肽组合作为缀合物提供，例如融合肽，异二聚体。 在具体方面，GIP激动剂肽是天然人胰高血糖素的类似物。 在具体方面，胰高血糖素拮抗剂肽是天然人胰高血糖素的类似物。 在一些实施方案中，GIP激动剂肽通过接头共价连接到胰高血糖素拮抗剂肽。 进一步提供治疗疾病例如代谢紊乱（例如糖尿病和肥胖症）的方法，其包括施用本文所述的肽组合物。

    Glucagon Analogs Exhibiting GIP Receptor Activity
    19.
    发明申请
    Glucagon Analogs Exhibiting GIP Receptor Activity 审中-公开
    Glucagon类似物展示GIP受体活性

    公开(公告)号：US20150259393A1

    公开(公告)日：2015-09-17

    申请号：US14665508

    申请日：2015-03-23

    Applicant: Indiana University Research and Technology Corporation

    Inventor： Richard D. DiMARCHI ,  Brian P. WARD

    IPC: C07K14/605

    CPC classification number: C07K14/605 ,  A61K38/00

    Abstract: 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.

    Abstract translation: 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
    20.
    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：US20150148520A1

    公开(公告)日：2015-05-28

    申请号：US14563362

    申请日：2014-12-08

    Applicant: Indiana University Research and Technology Corporation

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

    IPC: C07K14/62 ,  A61K38/28 ,  A61K47/48

    CPC classification number: C07K14/62 ,  A61K38/00 ,  A61K38/18 ,  A61K38/28 ,  A61K47/60 ,  C07K14/475

    Abstract: 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.

    Abstract translation: 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。

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