公开(公告)号：US09447162B2

公开(公告)日：2016-09-20

申请号：US14535853

申请日：2014-11-07

Applicant: Indiana University Research and Technology Corporation

Inventor： Jonathan Day ,  James Patterson ,  Joseph Chabenne ,  Maria DiMarchi ,  David L. Smiley ,  Richard D. DiMarchi

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

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

Abstract: 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).

Abstract translation: 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）。

公开(公告)号：US08900593B2

公开(公告)日：2014-12-02

申请号：US13737232

申请日：2013-01-09

Applicant: Indiana University Research and Technology Corporation

Inventor： Jonathan Day ,  James Patterson ,  Joseph Chabenne ,  Maria DiMarchi ,  David L. Smiley ,  Richard D. DiMarchi

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

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

Abstract: 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).

Abstract translation: 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）。