公开(公告)号：US20170313755A1

公开(公告)日：2017-11-02

申请号：US15487768

申请日：2017-04-14

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DiMARCHI ,  Sarah J. BRANDT ,  Alexander ZAYKOV ,  Yan ZHAO

IPC: C07K14/62 ,  C07K14/00 ,  A61K38/00

CPC classification number: C07K14/62 ,  A61K38/00

Abstract: Disclosed herein are insulin analog conjugates comprising an insulin agonist covalently linked to an insulin antagonist peptide. The conjugates are high potency insulin agonists but with decreased maximal activity relative to the maximal activity of native insulin.

公开(公告)号：US20160340400A1

公开(公告)日：2016-11-24

申请号：US15229942

申请日：2016-08-05

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

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

IPC: C07K14/62 ,  A61K38/18 ,  A61K38/28 ,  C07K14/475 ,  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。

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。