公开(公告)号：WO2016049174A1

公开(公告)日：2016-03-31

申请号：PCT/US2015/051705

申请日：2015-09-23

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： DIMARCHI, Richard D. ,  KOU, Binbin ,  ZHANG, Fa ,  MAYER, John P.

IPC: C07K14/62 ,  A61K38/28

CPC classification number: C07K14/62 ,  A61K38/00 ,  A61K38/28 ,  A61K47/00 ,  A61K47/48023 ,  A61K47/48046 ,  A61K47/48815

Abstract: Prodrug formulations of insulin and insulin analogs are provided wherein the insulin peptide has been modified by an amide bond linkage of a dipeptide prodrug element. The prodrugs disclosed herein have extended half-lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract translation: 提供了胰岛素和胰岛素类似物的前药制剂，其中胰岛素肽已经通过二肽前药成分的酰胺键键修饰。 本文公开的前体药物具有延长的半衰期并且通过由化学不稳定性驱动的非酶反应在生理条件下转化为活性形式。

公开(公告)号：WO2016049190A1

公开(公告)日：2016-03-31

申请号：PCT/US2015/051728

申请日：2015-09-23

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION ,  LIU, Fa

Inventor： LIU, Fa ,  DIMARCHI, Richard D. ,  MAYER, John P. ,  SMILEY, David L.

IPC: A61K38/28

CPC classification number: A61K38/22 ,  A61K9/0019 ,  A61K9/0024 ,  A61K38/00 ,  A61K38/28 ,  A61K47/02 ,  A61K47/48061 ,  A61K47/48246 ,  A61K47/64 ,  C07K2/00 ,  C07K14/575 ,  C07K14/605 ,  C07K14/62

Abstract: Disclosed herein are insulin agonist peptides conjugated to incretins wherein the incretin-insulin conjugate has agonist activity at the insulin receptor and the corresponding incretin receptor, and stimulates weight loss in an individual administered the compound.

Abstract translation: 本文公开了与肠降血糖素缀合的胰岛素激动剂肽，其中肠降血糖素 - 胰岛素缀合物在胰岛素受体和相应的肠降血糖素受体上具有激动剂活性，并且刺激施用化合物的个体的体重减轻。

公开(公告)号：WO2017210241A1

公开(公告)日：2017-12-07

申请号：PCT/US2017/035101

申请日：2017-05-31

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： DIMARCHI, Richard D. ,  MAYER, John P. ,  MROZ, Piotr

IPC: A61K38/00 ,  A61K38/16 ,  A61K38/26 ,  C07K14/605

Abstract: Modified glucagon peptides are disclosed having improved solubility and/or stability while retaining glucagon agonist activity. The glucagon peptides have been modified by the substitution of pyridyl-alanine for a native amino acid at one or more of positions 6, 10 or 13 and/or substitution with an amino acid in the D-conformation at position 20 or 21 compared to native glucagon.

Abstract translation: 公开了在保持胰高血糖素激动剂活性的同时具有改善的溶解度和/或稳定性的修饰的胰高血糖素肽。 胰高血糖素肽已经通过吡啶基丙氨酸取代6位，10位或13位的一个或多个天然氨基酸和/或用20位或21位的D构型中的氨基酸取代为天然氨基酸 胰高血糖素。

公开(公告)号：WO2017210168A1

公开(公告)日：2017-12-07

申请号：PCT/US2017/034961

申请日：2017-05-30

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： DIMARCHI, Richard D. ,  MAYER, John P. ,  MROZ, Piotr

IPC: A61K38/26 ,  C07K14/605

Abstract: Modified glucagon peptides are disclosed having improved solubility. The glucagon peptides have been modified by the replacement of one or more of the native amide bonds with ester bonds. The modifications enhance the solubility of the glucagon peptide wherein the native amide bonds are reconstituted in vivo upon administration to a patient.

Abstract translation: 公开了具有改善的溶解度的修饰的胰高血糖素肽。 胰高血糖素肽已经通过用酯键取代一个或多个天然酰胺键而被修饰。 这些修饰提高了胰高血糖素肽的溶解度，其中天然酰胺键在施用给患者后在体内重建。