公开(公告)号：US09707276B2

公开(公告)日：2017-07-18

申请号：US14648752

申请日：2013-11-22

Applicant: Merck Sharp & Dohme Corp. ,  Indiana University Research and Technology Corporation

Inventor： Michael Meehl ,  Richard D. DiMarchi ,  Pengyun Li

IPC: A61K38/28 ,  A61K38/22

CPC classification number: A61K38/28 ,  A61K38/22

Abstract: Compositions and formulations comprising insulin or insulin analogs comprising a carboxy terminal portion (CTP) peptide comprising amino acids 112-118 to 145 of the beta subunit of human chorionic gonadotropin (hCGβ) or a partial variant thereof that includes at least one O-glycosylation site of the CTP peptide, wherein the CTP peptide of the CTP peptide-based insulin or insulin analog is O-glycosylated are described. In particular embodiments, the O-glycosylated insulin analogs are produced in vivo and in further embodiments, the O-glycosylated CTP-based insulin analogs comprise predominantly mannotriose and mannotetrose O-glycans or predominantly mannose O-glycans.

公开(公告)号：US10696726B2

公开(公告)日：2020-06-30

申请号：US15846485

申请日：2017-12-19

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DiMarchi ,  Todd Parody ,  Jie Han ,  Pengyun Li

IPC: A61K38/28 ,  C07K14/62 ,  C07K14/605

Abstract: Disclosed herein are insulin agonist peptides conjugated to a glucagon analog wherein the insulin/glucagon conjugate is targeted to liver tissues upon administration to a patient.

公开(公告)号：US20150374795A1

公开(公告)日：2015-12-31

申请号：US14648752

申请日：2013-11-22

Applicant: MERCK SHARP & DOHME CORP. ,  INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DiMarchi ,  Pengyun Li ,  Michael Meehl

IPC: A61K38/28 ,  A61K38/22

CPC classification number: A61K38/28 ,  A61K38/22

Abstract: Compositions and formulations comprising insulin or insulin analogues comprising a carboxy terminal portion (CTP) peptide comprising amino acids 112-188 to 142 of the beta subunit of human chorionic gonadotropin (hCGβ) or a partial variant thereof that includes at least one O-glycosylation site of the CTP peptide, wherein the CTP peptide of the CTP peptide-based insulin or insulin analogue is O-glycosylated are described. In particular embodiments, the O-glycosylated insulin analogues are produced in vivo and in further embodiments, the O-glycosylated CTP-based insulin analogues comprise predominantly mannotriose and mannotetrose O-glycans or predominantly mannose O-glycans.

Abstract translation: 包含胰岛素或胰岛素类似物的组合物和制剂，其包含羧基末端部分（CTP）肽，其包含人绒毛膜促性腺激素（hCG / bgr）的β亚基的氨基酸112-188至142或其部分变体，其包含至少一个O-糖基化 描述了CTP肽的位点，其中基于CTP肽的胰岛素或胰岛素类似物的CTP肽是O-糖基化的。 在具体实施方案中，在体内产生O-糖基化的胰岛素类似物，并且在进一步的实施方案中，O-糖基化的基于CTP的胰岛素类似物主要包含甘露三糖和甘露聚糖O-聚糖或主要是甘露糖O-聚糖。

公开(公告)号：US11351268B2

公开(公告)日：2022-06-07

申请号：US16983726

申请日：2020-08-03

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DiMarchi ,  Alexei Kharitonenkov ,  Pengyun Li ,  Archita S. Agrawal

IPC: A61K47/66 ,  C07K14/50 ,  A61K47/65 ,  A61P3/04 ,  A61P3/10 ,  A61K38/03 ,  A61K38/17 ,  A61K38/26 ,  A61K38/28

Abstract: Disclosed herein are modified C-terminal fragments of FGF21 optimized for binding to Klotho β or antagonizing FGF21 activity. FGF21 peptides modified to comprise modifications to the C-terminal amino acid sequence are disclosed that have enhanced activity at the FGF21 receptor. Additionally, conjugates formed between the optimized FGF21 peptide fragments and insulin like peptides or nuclear hormone receptor ligands are provided.

公开(公告)号：US09573987B2

公开(公告)日：2017-02-21

申请号：US14366187

申请日：2012-12-19

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. Dimarchi ,  Pengyun Li

IPC: A61K38/28 ,  C07K14/62 ,  A61K47/48 ,  C07K14/00 ,  A61K38/00

CPC classification number: C07K14/62 ,  A61K38/00 ,  A61K38/28 ,  A61K47/60 ,  A61K47/64 ,  C07K14/00 ,  C07K2319/31 ,  C07K2319/91

Abstract: Insulin analogs comprising a non-native glycosylation site sequence are provided having high potency and specificity for the insulin receptor. In one embodiment a peptide sequence of greater than 18 amino acids is used as a linking moiety to link human insulin A and B chains, or analogs or derivatives thereof, to provide high potency single chain insulin analogs. In one embodiment the linking moiety comprises one or more glycosylation sites. Also disclosed are prodrug and conjugate derivatives of the insulin analogs.

Abstract translation: 提供包含非天然糖基化位点序列的胰岛素类似物具有对胰岛素受体的高效力和特异性。 在一个实施方案中，大于18个氨基酸的肽序列用作连接部分以连接人胰岛素A和B链或其类似物或衍生物，以提供高效单链胰岛素类似物。 在一个实施方案中，连接部分包含一个或多个糖基化位点。 还公开了胰岛素类似物的前药和缀合物衍生物。