公开(公告)号：US09783592B2

公开(公告)日：2017-10-10

申请号：US14808668

申请日：2015-07-24

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  Bin Yang ,  Brian Finan

IPC: C07K14/605 ,  A61K38/26 ,  C07K14/72 ,  A61K47/48

CPC classification number: C07K14/721 ,  A61K38/26 ,  A61K47/55 ,  A61K47/554 ,  A61K47/64 ,  C07K14/605 ,  C07K14/72

Abstract: Provided herein are glucagon superfamily peptides conjugated with NHR ligands that are capable of acting at a nuclear hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein are methods of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the conjugates of the invention.

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：US10174093B2

公开(公告)日：2019-01-08

申请号：US15670200

申请日：2017-08-07

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  David L. Smiley

IPC: A61K38/26 ,  C07K14/605 ,  G01N33/74 ,  A61K39/395 ,  C07K16/28 ,  A61K47/60 ,  A61K49/00 ,  A61K38/00

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

公开(公告)号：US09790263B2

公开(公告)日：2017-10-17

申请号：US14840580

申请日：2015-08-31

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  Tao Ma

IPC: A61K38/26 ,  C07K14/605 ,  C07K7/00 ,  A61K38/00

CPC classification number: C07K14/605 ,  A61K38/00 ,  A61K38/26

Abstract: Glucagon peptides with increased GIP activity are provided, optionally with GLP-1 and/or glucagon activity. In some embodiments, C-terminally extended glucagon peptides comprising an amino acid sequence substantially similar to native glucagon are provided herein.

公开(公告)号：US09340600B2

公开(公告)日：2016-05-17

申请号：US13920188

申请日：2013-06-18

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi

IPC: C07K14/605 ,  A61K38/26 ,  A61K38/16 ,  A61K38/17

CPC classification number: C07K14/605 ,  A61K38/16 ,  A61K38/17 ,  A61K38/26

Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

公开(公告)号：US09249206B2

公开(公告)日：2016-02-02

申请号：US13728110

申请日：2012-12-27

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  Brian P. Ward

IPC: A61K38/26 ,  A61P3/10 ,  C07K14/605 ,  A61K38/00

CPC classification number: C07K14/605 ,  A61K38/00

Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

公开(公告)号：US09089539B2

公开(公告)日：2015-07-28

申请号：US14182706

申请日：2014-02-18

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  Arnab De

IPC: A61K38/00 ,  C07K14/62 ,  A61K38/28 ,  A61K9/00 ,  A61K38/26 ,  A61K47/48 ,  A61K39/395

CPC classification number: A61K38/28 ,  A61K9/0019 ,  A61K38/26 ,  A61K39/395 ,  A61K47/48215 ,  A61K47/48246 ,  A61K47/60 ,  A61K47/64

Abstract: Prodrug formulations of bioactive polypeptides are provided wherein the bioactive polypeptide has been modified by the linkage of a dipeptide to the bioactive polypeptide through an ester linkage. The prodrugs disclosed herein in some embodiments have extended half lives of at least 1.5 hours (e.g., at least 10 hours), and more typically greater than 20 hours and less than 70 hours, and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract translation: 提供生物活性多肽的前药制剂，其中生物活性多肽已经通过二酯与生物活性多肽的连接通过酯键进行了修饰。 在一些实施方案中本文公开的前体药物具有至少1.5小时（例如，至少10小时），更通常大于20小时和小于70小时的半衰期延长，并且在生理条件下通过 由化学不稳定驱动的非酶反应。