公开(公告)号：US20160310575A1

公开(公告)日：2016-10-27

申请号：US15102340

申请日：2014-12-19

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION ,  HOFFMANN-LA ROCHE INC.

Inventor： Sara BELLI ,  Konrad BLEICHER ,  Richard D. DIMARCHI ,  Eike HOFFMANN ,  Eric A. KITAS ,  Anish A. KONKAR

IPC: A61K38/26 ,  A61K45/06 ,  A61K47/48 ,  C07K14/605

CPC classification number: A61K38/26 ,  A61K38/00 ,  A61K45/06 ,  A61K47/543 ,  C07K14/605 ,  C07K2319/30

Abstract: Herein is reported a fusion polypeptide comprising i) one, two, three or four incretin receptor ligand polypeptides, and ii) one human immunoglobulin Fc-region, wherein at least one of the incretin receptor ligand polypeptides comprises an amino acid that is covalently conjugated to a lipid, and wherein each of the one, two, three or four incretin receptor ligand polypeptides is covalently conjugated by a peptide bond to a terminus of the human immunoglobulin Fc-region, whereby to each terminus of the human immunoglobulin Fc-region only a single incretin receptor ligand polypeptide is conjugated.

Abstract translation: 本文报道了融合多肽，其包含i）一个，两个，三个或四个肠降索内酯受体配体多肽，和ii）一个人免疫球蛋白Fc区，其中至少一个肠降血糖素受体配体多肽包含共价共轭 脂质，并且其中所述一个，两个，三个或四个肠降血糖素受体配体多肽中的每一个通过肽键共价结合到人免疫球蛋白Fc区的末端，由此到达人免疫球蛋白Fc区的每个末端只有 将单一肠降血糖素受体配体多肽缀合。

公开(公告)号：US20190218268A1

公开(公告)日：2019-07-18

申请号：US16098236

申请日：2017-05-31

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  John P. MAYER ,  Piotr MROZ

IPC: C07K14/605 ,  A61P3/10 ,  A61K38/26 ,  A61K38/28

Abstract: Modified glucagon peptides are disclosed having improved solubility and/or stability while retaining glucagon agonist activity. The glucagon peptides have been modified by the substitution of pyridyl-alanine for a native amino acid at one or more of positions 6, 10 or 13 and/or substitution with an amino acid in the D-conformation at position 20 or 21 compared to native glucagon.

公开(公告)号：US20230285578A1

公开(公告)日：2023-09-14

申请号：US17925477

申请日：2021-05-25

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Fa ZHANG

IPC: A61K47/64 ,  C07K14/635 ,  A61K9/20 ,  A61P5/18 ,  A61P19/10

CPC classification number: A61K47/64 ,  A61K9/20 ,  A61P5/18 ,  A61P19/10 ,  C07K14/635

Abstract: A novel derivative of parathyroid hormone is provided that has an extended time of action relative to known native parathyroid hormone agonist peptides, while minimizing excessive action shortly after administration. Compositions comprising the novel parathyroid hormone conjugates can be used to treat hypoparathyroidism and osteoporosis.

公开(公告)号：US20190290772A1

公开(公告)日：2019-09-26

申请号：US16302846

申请日：2017-05-26

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Brian FINAN ,  Bin YANG ,  Zhimeng ZHU

IPC: A61K47/55 ,  A61K47/54 ,  A61K47/65 ,  A61K47/64 ,  A61K31/197 ,  A61K38/26

Abstract: Provided herein are GLP-1 agonist peptides conjugated with thyroid hormone receptor ligands that are capable of acting at the thyroid 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, obesity, metabolic syndrome and chronic cardiovascular disease, comprising administering the conjugates of the invention.

公开(公告)号：US20170283479A1

公开(公告)日：2017-10-05

申请号：US15513762

申请日：2015-09-23

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Binbin KOU ,  Fa ZHANG ,  John P. MAYER

IPC: C07K14/62 ,  A61K38/28

CPC classification number: C07K14/62 ,  A61K38/00 ,  A61K38/28 ,  A61K47/00 ,  A61K47/54 ,  A61K47/543 ,  A61K47/6911

Abstract: Prodrug formulations of insulin and insulin analogs are provided wherein the insulin peptide has been modified by an amide bond linkage of a dipeptide prodrug element. The prodrugs disclosed herein have extended half-lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

公开(公告)号：US20170281788A1

公开(公告)日：2017-10-05

申请号：US15513748

申请日：2015-09-23

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  John P. MAYER ,  David L. SMILEY ,  Fa LIU

IPC: A61K47/48 ,  A61K38/28 ,  C07K19/00 ,  A61K38/22 ,  C07K14/575

CPC classification number: A61K38/22 ,  A61K9/0019 ,  A61K9/0024 ,  A61K38/00 ,  A61K38/28 ,  A61K47/02 ,  A61K47/545 ,  A61K47/64 ,  C07K2/00 ,  C07K14/575 ,  C07K14/605 ,  C07K14/62

Abstract: Disclosed herein are insulin agonist peptides conjugated to incretins wherein the incretin-insulin conjugate has agonist activity at the insulin receptor and the corresponding incretin receptor, and stimulates weight loss in an individual administered the compound.

公开(公告)号：US20240116998A1

公开(公告)日：2024-04-11

申请号：US18264157

申请日：2022-02-15

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Piotr Andrzej MROZ ,  Kishore THALLURI

IPC: C07K14/605 ,  A61P3/08

CPC classification number: C07K14/605 ,  A61P3/08 ,  A61K38/00

Abstract: Provided herein are GLP-1 receptor antagonists peptides and pharmaceutical compositions for the treatment of hypoglycemia. Further provided herein are methods of treating atypical hypoglycemia in patients that have become hyperinsulinemic, including those who become hyperinsulinemic after bariatric surgery.

公开(公告)号：US20230382966A1

公开(公告)日：2023-11-30

申请号：US18032479

申请日：2021-10-26

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Archita S. AGRAWAL

IPC: C07K14/50

CPC classification number: C07K14/50 ,  A61K38/00

Abstract: Compositions comprising novel peptides and dimers that exhibit antagonist activity against FGF23 binding to Klotho are disclosed. Such peptides can be used to treat hypoparathyroidism and osteoporosis.

公开(公告)号：US20190388510A1

公开(公告)日：2019-12-26

申请号：US16302795

申请日：2017-05-26

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Brian FINAN ,  Bin YANG ,  Zhimeng ZHU

IPC: A61K38/26 ,  A61K47/55 ,  A61P3/06 ,  A61P3/04 ,  A61P9/10 ,  A61K31/198

Abstract: Provided herein are glucagon agonist peptides conjugated with thyroid hormone receptor ligands that are capable of acting at the thyroid 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, obesity, metabolic syndrome and chronic cardiovascular disease, comprising administering the conjugates of the invention.

公开(公告)号：US20150299285A1

公开(公告)日：2015-10-22

申请号：US14366187

申请日：2012-12-19

Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

Inventor： Richard D. DIMARCHI ,  Pengyun LI

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

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。