公开(公告)号：US11752211B2

公开(公告)日：2023-09-12

申请号：US16889201

申请日：2020-06-01

申请人： NOVARTIS AG

发明人： Alexandra Marshall Bruce ,  Aaron Kanter ,  Aimee Richardson Usera ,  Jun Yuan ,  Frederic Zecri

IPC分类号： A61K47/54 ,  A61K38/095 ,  A61K38/16 ,  A61K38/17 ,  A61K38/18 ,  A61K38/22 ,  A61K45/06 ,  C07C55/02 ,  C07C55/22 ,  C07C57/02 ,  C07C57/18 ,  C07C59/245 ,  C12N15/113

CPC分类号： A61K47/543 ,  A61K38/095 ,  A61K38/164 ,  A61K38/1709 ,  A61K38/1825 ,  A61K38/1841 ,  A61K38/2221 ,  A61K45/06 ,  A61K47/542 ,  C07C55/02 ,  C07C55/22 ,  C07C57/02 ,  C07C57/18 ,  C07C59/245 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/351

摘要： The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:






wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US09908919B2

公开(公告)日：2018-03-06

申请号：US14905333

申请日：2014-07-21

申请人： Novartis AG

发明人： Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan

IPC分类号： A61K38/10 ,  A61K38/04 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00 ,  C07K14/47 ,  A61K38/17 ,  A61K45/06 ,  A61K47/64 ,  A61K47/68

CPC分类号： C07K14/47 ,  A61K38/10 ,  A61K38/1709 ,  A61K45/06 ,  A61K47/643 ,  A61K47/6811

摘要： The invention provides a synthetic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-R-L-X6-X7-K-X9-P-X11-X12-X13  I or an amide, an ester, a salt thereof, or a bioconjugate thereof, wherein X1, X3, X6, X7, X9, X11, X12 and X13 are defined herein. The polypeptides and bioconjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides and bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US10786576B2

公开(公告)日：2020-09-29

申请号：US15985060

申请日：2018-05-21

申请人： NOVARTIS AG

发明人： Alexandra Marshall Bruce ,  Aaron Kanter ,  Changgang Lou ,  Aimee Richardson Usera ,  Jun Yuan ,  Frederic Zecri

IPC分类号： A61K47/54 ,  A61K38/095 ,  A61K38/08 ,  A61K38/16 ,  A61K38/17 ,  A61K38/18 ,  A61K38/22 ,  A61K45/06 ,  C07C55/02 ,  C07C55/22 ,  C07C57/02 ,  C07C57/18 ,  C07C59/245 ,  C12N15/113

摘要： The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US10676499B2

公开(公告)日：2020-06-09

申请号：US15536516

申请日：2015-12-16

申请人： NOVARTIS AG

发明人： David Barnes-Seeman ,  Scott Louis Cohen ,  John Louis Diener ,  Christian Gampe ,  James Roache ,  Amy White ,  Sarah Williams ,  Jun Yuan ,  Frederic Zecri

IPC分类号： C07H21/02 ,  C07F9/6561 ,  C07H19/167 ,  C07H19/207 ,  C07K14/575

摘要： The disclosure relates to nucleic acids that contain modifications at the 5′-end, 3′-end or 5′-end and 3′-ends, and compounds that can be used to make the modified nucleic acids are disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

公开(公告)号：US10588980B2

公开(公告)日：2020-03-17

申请号：US14738272

申请日：2015-06-12

申请人： Novartis AG

发明人： Alexandra Marshall Bruce ,  Aimee Richardson Usera ,  Frederic Zecri ,  Jun Yuan ,  Changgang Lou ,  Aaron Kanter

IPC分类号： A61K47/54 ,  A61K38/08 ,  A61K38/16 ,  A61K38/17 ,  A61K38/18 ,  A61K38/22 ,  A61K45/06 ,  C07C55/02 ,  C07C55/22 ,  C07C57/02 ,  C07C57/18 ,  C07C59/245 ,  C12N15/113

摘要： The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US20230183286A1

公开(公告)日：2023-06-15

申请号：US17820005

申请日：2022-08-16

申请人： NOVARTIS AG

发明人： David BARNES-SEEMAN ,  Scott Louis COHEN ,  John Louis DIENER ,  Christian GAMPE ,  James ROACHE ,  Amy White ,  Sarah Louise Williams ,  Jun Yuan ,  Frederic Zecri

IPC分类号： C07H21/02 ,  C07F9/6561 ,  C07H19/167 ,  C07H19/207 ,  C07K14/575

CPC分类号： C07H21/02 ,  C07F9/65616 ,  C07H19/167 ,  C07H19/207 ,  C07K14/5759

摘要： The disclosure relates to nucleic acids that contain modifications at the 5′-end, 3′-end or 5′-end and 3′-ends, and compounds that can be used to make the modified nucleic acids are disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

公开(公告)号：US11466048B2

公开(公告)日：2022-10-11

申请号：US16802014

申请日：2020-02-26

申请人： NOVARTIS AG

发明人： David Barnes-Seeman ,  Scott Louis Cohen ,  John Louis Diener ,  Christian Gampe ,  James Roache ,  Amy White ,  Sarah Louise Williams ,  Jun Yuan ,  Frederic Zecri

IPC分类号： C07H21/02 ,  C07F9/6561 ,  C07H19/167 ,  C07H19/207 ,  C07K14/575

摘要： The disclosure relates to nucleic acids that contain modifications at the 5′-end, 3′-end or 5′-end and 3′-ends, and compounds that can be used to make the modified nucleic acids are disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

公开(公告)号：US10005829B2

公开(公告)日：2018-06-26

申请号：US14440198

申请日：2013-11-19

申请人： Novartis AG

发明人： Frederic Zecri ,  Kayo Yasoshima ,  Philipp Grosche ,  Jun Yuan ,  Hongjuan Zhao

IPC分类号： A61K38/10 ,  C07K14/765 ,  C07K14/47 ,  A61K45/06 ,  A61K38/38

CPC分类号： C07K14/765 ,  A61K38/385 ,  A61K45/06 ,  C07K14/47 ,  A61K38/1709 ,  A61K2300/00

摘要： The invention relates to novel compositions comprising modified apelin-13 peptide sequences designed to treat cardiovascular disease in subjects to whom they are administered, and which exhibit greater resistance to degradation, and equivalent or greater bioactivity than their wild type counterparts. The invention also relates to methods of making said compositions and using said compositions as pharmaceutically active agents to treat cardiovascular disease.