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1. 发明申请

WO2015013169A9 BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES 审中-公开
标题翻译：合成APELIN多肽的生物活性
公开(公告)号：WO2015013169A9
公开(公告)日：2016-10-20
申请号：PCT/US2014047378
申请日：2014-07-21
申请人： NOVARTIS AG , CAPLAN SHARI L , GOLOSOV ANDREI , GROSCHE PHILIPP , GUIMARAES CARLA , KANTER AARON , LOU CHANGGANG , PARKER DAVID THOMAS , PETERS ERIC C , USERA AIMEE RICHARDSON , YASOSHIMA KAYO , YUAN JUN , ZECRI FREDERIC , ZHAO HONGJUAN
发明人： CAPLAN SHARI L , GOLOSOV ANDREI , GROSCHE PHILIPP , GUIMARAES CARLA , KANTER AARON , LOU CHANGGANG , PARKER DAVID THOMAS , PETERS ERIC C , USERA AIMEE RICHARDSON , YASOSHIMA KAYO , YUAN JUN , ZECRI FREDERIC , ZHAO HONGJUAN
IPC分类号： A61K47/48
CPC分类号： A61K38/10 , A61K38/00 , A61K45/06 , A61K47/542 , A61K47/643 , A61K47/68 , A61K47/6811 , C07K14/47 , C07K14/765 , C07K2319/30 , C07K2319/31
摘要： The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I': I' or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the 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.
摘要翻译：本发明提供了包含式I'的合成多肽：I'或其酰胺，其酯或其盐的生物缀合物，其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，X 9，X 10，X 11， X12和X13在本文中定义和半衰期延长部分，其中肽和半衰期延长部分任选地经由连接体共价连接或融合。多肽是APJ受体的激动剂。本发明还涉及本发明的生物缀合物的制备方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，布鲁加达综合征，室性心动过速，动脉粥样硬化，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（包括晒伤）和先兆子痫。本发明还提供药理活性剂和药物组合物的组合。

2. 发明申请

WO2015013168A1 CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE 审中-公开
标题翻译：治疗心力衰竭的循环多糖
公开(公告)号：WO2015013168A1
公开(公告)日：2015-01-29
申请号：PCT/US2014/047377
申请日：2014-07-21
申请人： NOVARTIS AG , BRUCE, Alexandra Marshall , GROSCHE, Philipp , GUIMARAES, Carla , KANTER, Aaron , LOU, Changgang , USERA, Aimee Richardson , YASOSHIMA, Kayo , YUAN, Jun , ZECRI, Frederic , ZHAO, Hongjuan
发明人： BRUCE, Alexandra Marshall , GROSCHE, Philipp , GUIMARAES, Carla , KANTER, Aaron , LOU, Changgang , USERA, Aimee Richardson , YASOSHIMA, Kayo , YUAN, Jun , ZECRI, Frederic , ZHAO, Hongjuan
IPC分类号： C07K14/47 , A61K38/17 , A61P9/04
CPC分类号： C07K14/47 , A61K38/12 , A61K38/1709 , A61K45/06 , A61K47/542 , A61K47/60 , A61K47/643 , A61K47/6811 , C07K7/64 , C07K14/765 , C07K16/461 , C07K2319/30 , C07K2319/31
摘要： The invention provides a cyclic polypeptide of Formula I': I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention or bioconjugates thereof, and their 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.
摘要翻译：本发明提供式I'的环状多肽：I或其酰胺，其酯或其盐或其生物缀合物，其中X1，X3，X4，X7，X8，X9，X10，X11，X12和X13被定义于此。多肽是APJ受体的激动剂。本发明还涉及制备本发明多肽或其生物缀合物的方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，Brugada综合征，心室心动过速，动脉粥样硬化，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（包括晒伤）和先兆子痫。本发明还提供药理活性剂和药物组合物的组合。

3. 发明申请

WO2016116842A9 SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE 审中-公开
公开(公告)号：WO2016116842A9
公开(公告)日：2016-07-28
申请号：PCT/IB2016/050206
申请日：2016-01-15
申请人： NOVARTIS AG , KANTER, Aaron , USERA, Aimee Richardson , ZECRI, Frederic
发明人： KANTER, Aaron , USERA, Aimee Richardson , ZECRI, Frederic
IPC分类号： A61K47/48 , A61K45/06 , A61P9/04
摘要： The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates 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.

4. 发明申请

WO2015200078A1 FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES 审中-公开
标题翻译：脂肪酸及其与生物分子结合的用途
公开(公告)号：WO2015200078A1
公开(公告)日：2015-12-30
申请号：PCT/US2015036328
申请日：2015-06-18
申请人： NOVARTIS AG , BARNES DAVID WENINGER , YAMADA KEN , IBEBUNJO CHIKWENDU , DUTTAROY ALOKESH , KIRMAN LOUISE CLARE , BRUCE ALEXANDRA MARSHALL , USERA AIMEE RICHARDSON , ZECRI FREDERIC , YUAN JUN , LOU CHANGGANG , KANTER AARON , BOSE AVIRUP
发明人： BARNES DAVID WENINGER , YAMADA KEN , IBEBUNJO CHIKWENDU , DUTTAROY ALOKESH , KIRMAN LOUISE CLARE , BRUCE ALEXANDRA MARSHALL , USERA AIMEE RICHARDSON , ZECRI FREDERIC , YUAN JUN , LOU CHANGGANG , KANTER AARON , BOSE AVIRUP
IPC分类号： A61K47/48 , A61P3/00 , C07K14/475
CPC分类号： A61K47/48038 , A61K38/08 , 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.
摘要翻译：本发明提供了一种缀合物，其包含通过接头与脂肪酸连接的生物分子，其中脂肪酸具有以下式A1，A2或A3：其中R1，R2，R3，R4，Ak，n，m和p如本文所定义。本发明还涉及制备本发明缀合物如GDF15缀合物的方法及其治疗用途，例如治疗或预防代谢紊乱或疾病，2型糖尿病，肥胖症，胰腺炎，血脂异常，酒精和非酒精性脂肪肝疾病/脂肪性肝炎和其他进行性肝病，胰岛素抵抗，高胰岛素血症，葡萄糖不耐受，高血糖症，代谢综合征，高血压，心血管疾病，动脉粥样硬化，外周动脉疾病，中风，心力衰竭，冠心病，糖尿病并发症（包括但不限于慢性肾脏病），神经病，胃轻瘫等代谢紊乱。本发明还提供药理活性剂和药物组合物的组合。

5. 发明申请

WO2007067333A3 TRIOXANE DIMERS HAVING HIGH ANTICANCER AND LONG-LASTING ANTIMALARIAL ACTIVITIES 审中-公开
标题翻译：具有高反应性和长寿命抗生素活性的三氧化二TIES
公开(公告)号：WO2007067333A3
公开(公告)日：2008-01-31
申请号：PCT/US2006044845
申请日：2006-11-17
申请人： UNIV JOHNS HOPKINS , US GOV HEALTH & HUMAN SERV , POSNER GARY H , PAIK IKHYEON , BORSTNIK KRISTINA , CHANG WONSUK , SINISHTAJ SANDRA , MAIO WILLIAM ANTHONY , D ANGELO JOHN GAETANO , WOODARD LAUREN ELAINE , KALINDA ALVIN SOLOMAN , USERA AIMEE R , HESS LINDSEY CATHERINE , ROSENTHAL ANDREW SCOTT , OH SEONGHO , BAEGE ASTRID C
发明人： POSNER GARY H , PAIK IKHYEON , BORSTNIK KRISTINA , CHANG WONSUK , SINISHTAJ SANDRA , MAIO WILLIAM ANTHONY , D ANGELO JOHN GAETANO , WOODARD LAUREN ELAINE , KALINDA ALVIN SOLOMAN , USERA AIMEE R , HESS LINDSEY CATHERINE , ROSENTHAL ANDREW SCOTT , OH SEONGHO , BAEGE ASTRID C
IPC分类号： A01N43/02 , A61K31/335
CPC分类号： C07D493/14 , A61K47/55 , C07D493/18 , C07D493/22
摘要： The invention provides novel trioxane dimers having formulae III, IV or V: methods for their preparation, pharmaceutical compositions containing these compounds, and methods for treating cancer and/or malaria using these compounds and compositions.
摘要翻译：本发明提供具有式III，IV或V的新型三恶烷二聚体：其制备方法，含有这些化合物的药物组合物，以及使用这些化合物和组合物治疗癌症和/或疟疾的方法。

6. 发明申请

WO2016116842A1 SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE 审中-公开
标题翻译：合成APELIN脂肪酸与改善的生命之间的联系
公开(公告)号：WO2016116842A1
公开(公告)日：2016-07-28
申请号：PCT/IB2016050206
申请日：2016-01-15
申请人： NOVARTIS AG , KANTER AARON , USERA AIMEE RICHARDSON , ZECRI FREDERIC
发明人： KANTER AARON , USERA AIMEE RICHARDSON , ZECRI FREDERIC
IPC分类号： A61K47/48 , A61K45/06 , A61P9/04
CPC分类号： A61K38/12 , A61K45/06 , A61K47/542 , A61K47/60 , A61K47/64 , A61K51/0402 , C07K7/64 , C07K14/47
摘要： The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates 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.
摘要翻译：本发明提供了包含式I的合成多肽：Q-R-P-R-L-C * -H-K-G-P-（Nle）-C * -F（I）或其酰胺或酯的缀合物或其药学上可接受的盐; 和选自以下的脂肪酸：其中所述脂肪酸通过其羧酸官能团之一，任选地经由聚乙二醇连接体共价连接到肽的N末端; 并且其中用“*”标记的两个半胱氨酸氨基酸在其侧链的硫醇官能团之间形成二硫键。缀合物是APJ受体的激动剂。本发明还涉及本发明的缀合物的制备方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，布鲁加达综合征，室性心动过速，动脉粥样硬化，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（包括晒伤）和先兆子痫。本发明还提供药理活性剂和药物组合物的组合。

7. 发明申请

WO2015200078A8 FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES 审中-公开
公开(公告)号：WO2015200078A8
公开(公告)日：2015-12-30
申请号：PCT/US2015/036328
申请日：2015-06-18
申请人： NOVARTIS AG , BARNES, David Weninger , YAMADA, Ken , IBEBUNJO, Chikwendu , DUTTAROY, Alokesh , KIRMAN, Louise Clare , BRUCE, Alexandra Marshall , USERA, Aimee Richardson , ZECRI, Frederic , YUAN, Jun , LOU, Changgang , KANTER, Aaron , BOSE, Avirup
发明人： BARNES, David Weninger , YAMADA, Ken , IBEBUNJO, Chikwendu , DUTTAROY, Alokesh , KIRMAN, Louise Clare , BRUCE, Alexandra Marshall , USERA, Aimee Richardson , ZECRI, Frederic , YUAN, Jun , LOU, Changgang , KANTER, Aaron , BOSE, Avirup
IPC分类号： A61K47/48 , A61P3/00 , C07K14/475
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 R 1 , R 2 , R 3 , R 4 , 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.

8. 发明申请

WO2015006728A3 LYSINE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS USING MICROBIAL TRANSGLUTAMINASE 审中-公开
标题翻译：使用微生物转氨酶的LYSINE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS
公开(公告)号：WO2015006728A3
公开(公告)日：2015-03-12
申请号：PCT/US2014046409
申请日：2014-07-11
申请人： USERA AIMEE , ROBINSON ZACHARY , COBB JENNIFER
发明人： USERA AIMEE , ROBINSON ZACHARY , COBB JENNIFER
IPC分类号： C07K1/13 , C07C13/45 , C07C237/06 , C07C247/04 , C07C317/24 , C07D209/42 , C07H13/00 , C07K5/062 , C07K5/072 , C07K5/083 , C07K7/02
CPC分类号： C07K5/101 , A61K38/00 , A61K38/05 , A61K38/06 , A61K38/07 , A61K47/6415 , A61K49/0002 , C07C271/22 , C07C317/28 , C07C2602/24 , C07D209/42 , C07D229/02 , C07D257/08 , C07K1/13 , C07K5/06043 , C07K5/06104 , C07K5/0808 , C07K7/02
摘要： The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.
摘要翻译：本发明涉及用于使用化学酶微生物转谷氨酰胺酶介导的反应对具有赖氨酸残基的蛋白质进行位点选择性修饰的功能化肽的方法和试剂。功能化蛋白质可用于研究或治疗用途。

9. 发明申请

WO2015200080A1 SITE SPECIFIC PROTEIN MODIFICATIONS 审中-公开
标题翻译：现场特定蛋白质修饰
公开(公告)号：WO2015200080A1
公开(公告)日：2015-12-30
申请号：PCT/US2015/036330
申请日：2015-06-18
申请人： NOVARTIS AG , USERA, Aimee Richardson , YUAN, Jun , LOU, Changgang
发明人： USERA, Aimee Richardson , YUAN, Jun , LOU, Changgang
IPC分类号： C07K1/107
CPC分类号： C07K1/13 , A61K47/48246 , A61K47/48369 , A61K47/542 , A61K47/60 , A61K47/64 , A61K47/68 , A61K51/088 , C07K1/1075 , C07K1/1077 , C07K14/475 , C07K14/705 , C07K16/00 , C07K2319/21 , C07K2319/30 , C07K2319/50
摘要： The present invention relates to method and reagents for use in site-selective modification of protein and peptide. The site selective modification is a selective derivation of the amino functionality at the N-terminus of the protein or the polypeptide using the presence of a neighboring histidine amino acid to increase the reactivity of the N-terminal amino functionality. The modified proteins or peptides obtained by method of the invention may be used for imaging study or therapeutic uses.
摘要翻译：本发明涉及用于蛋白质和肽的位点选择性修饰的方法和试剂。位点选择性修饰是使用相邻的组氨酸氨基酸的存在来增加N-末端氨基官能团的反应性来选择性地衍生蛋白质或多肽的N-末端的氨基官能团。通过本发明的方法获得的修饰的蛋白质或肽可用于成像研究或治疗用途。

10. 发明申请

WO2015013169A3 BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES 审中-公开
标题翻译：合成APELIN多肽的生物活性
公开(公告)号：WO2015013169A3
公开(公告)日：2015-03-19
申请号：PCT/US2014047378
申请日：2014-07-21
申请人： NOVARTIS AG , CAPLAN SHARI L , GOLOSOV ANDREI , GROSCHE PHILIPP , GUIMARAES CARLA , KANTER AARON , LOU CHANGGANG , PARKER DAVID THOMAS , PETERS ERIC C , USERA AIMEE RICHARDSON , YASOSHIMA KAYO , YUAN JUN , ZECRI FREDERIC , ZHAO HONGJUAN
发明人： CAPLAN SHARI L , GOLOSOV ANDREI , GROSCHE PHILIPP , GUIMARAES CARLA , KANTER AARON , LOU CHANGGANG , PARKER DAVID THOMAS , PETERS ERIC C , USERA AIMEE RICHARDSON , YASOSHIMA KAYO , YUAN JUN , ZECRI FREDERIC , ZHAO HONGJUAN
IPC分类号： A61K47/48
CPC分类号： A61K38/10 , A61K38/00 , A61K45/06 , A61K47/542 , A61K47/643 , A61K47/68 , A61K47/6811 , C07K14/47 , C07K14/765 , C07K2319/30 , C07K2319/31
摘要： The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I': I' or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the 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.
摘要翻译：本发明提供了包含式I'的合成多肽：I'或其酰胺，其酯或其盐的生物缀合物，其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，X 9，X 10，X 11， X12和X13在本文中定义和半衰期延长部分，其中肽和半衰期延长部分任选地经由连接体共价连接或融合。多肽是APJ受体的激动剂。本发明还涉及本发明的生物缀合物的制备方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，布鲁加达综合征，室性心动过速，动脉粥样硬化，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（包括晒伤）和先兆子痫。本发明还提供药理活性剂和药物组合物的组合。

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