公开(公告)号：US20160058881A1

公开(公告)日：2016-03-03

申请号：US14775985

申请日：2014-03-14

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： RICHARD D. DIMARCHI ,  Binbin KOU

IPC: A61K47/48 ,  A61K45/06 ,  A61K38/26

CPC classification number: A61K38/22 ,  A61K38/26 ,  A61K45/06 ,  A61K47/542 ,  C07K14/605 ,  A61K2300/00

Abstract: A prodrug derivative of a bioactive peptide (or polypeptide) is provided that exhibits prolonged half-life in serum and prolonged action in vivo, compared to the parent peptide or polypeptide. In some embodiments, the peptide is selected from the group consisting of glucagon, exendin-4, GLP-1, GLP-2, GIP, vasoactive intestinal peptide (VIP), Pituitary adenylate cyclase-activating polypeptide 27 (PACAP-27), peptide histidine methionine (PHM), oxyntomodulin, secretin, osteocalcin, growth hormone releasing hormone, as well as analogs, derivatives and conjugates.

Abstract translation: 与母体肽或多肽相比，提供生物活性肽（或多肽）的前药衍生物，其在血清中表现出延长的半衰期和体内延长的作用。 在一些实施方案中，肽选自胰高血糖素，毒蜥外泌肽-4，GLP-1，GLP-2，GIP，血管活性肠肽（VIP），垂体腺苷酸环化酶活化多肽27（PACAP-27），肽 组氨酸甲硫氨酸（PHM），胃泌酸调节素，促胰液素，骨钙素，生长激素释放激素，以及类似物，衍生物和缀合物。

公开(公告)号：US20160024169A1

公开(公告)日：2016-01-28

申请号：US14774357

申请日：2014-03-05

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： RICHARD D. DIMARCHI ,  TODD PARODY ,  JIE HAN ,  PENGYUN LI

IPC: C07K14/62 ,  C07K14/605

CPC classification number: C07K14/62 ,  C07K14/605 ,  C07K2319/00

Abstract: Disclosed herein are insulin agonist peptides conjugated to incretins wherein the insulin/incretin conjugate has agonist activity at both the insulin receptor and the corresponding incretin receptor. Insulin is a proven therapy for the treatment of juvenile-onset diabetes and later-stage adult-onset diabetes. The peptide is biosynthesized as a larger linear precursor of low potency (approximately 2% to 9% of native insulin), named proinsulin. Proinsulin is proteolytically converted to insulin by the selective removal of a 35-residue connecting peptide (C peptide).

Abstract translation: 本文公开了与肠降血糖素缀合的胰岛素激动剂肽，其中胰岛素/肠降血糖素缀合物在胰岛素受体和相应的肠降血糖素受体两者都具有激动剂活性。 胰岛素是用于治疗幼年型糖尿病和晚期成人发病的糖尿病的经证实的治疗方法。 肽被生物合成为较低效力的线性前体（约2％至9％的天然胰岛素），命名为胰岛素原。 通过选择性去除35个残基的连接肽（C肽）将胰岛素原蛋白水解转化为胰岛素。