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1. 发明申请

US20150030594A1 BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES 有权
标题翻译：合成APELIN多肽的生物活性
公开(公告)号：US20150030594A1
公开(公告)日：2015-01-29
申请号：US14336290
申请日：2014-07-21
申请人： Jun YUAN , Frederic ZECRI , Philipp GROSCHE , Hongjuan ZHAO , Andrei GOLOSOV , Kayo YASOSHIMA , David Thomas PARKER , Eric PETERS , Aimee Richardson USERA , Shari Lynn CAPLAN , Aaron KANTER , Changgang LOU , Carla Guimaraes
发明人： Jun YUAN , Frederic ZECRI , Philipp GROSCHE , Hongjuan ZHAO , Andrei GOLOSOV , Kayo YASOSHIMA , David Thomas PARKER , Eric PETERS , Aimee Richardson USERA , Shari Lynn CAPLAN , Aaron KANTER , Changgang LOU , Carla Guimaraes
IPC分类号： C07K7/08 , A61K45/06 , C07K14/47 , C07K16/00 , A61K39/395 , A61K47/48 , A61K38/10
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′ (SEQ ID NO: 1): 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：本发明提供包含式I'（SEQ ID NO：1）的合成多肽的生物缀合物或其酰胺，其酯或其盐，其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，X 9 ，X10，X11，X12和X13在本文中定义并且半衰期延长部分，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

US20160166634A1 BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES 审中-公开
公开(公告)号：US20160166634A1
公开(公告)日：2016-06-16
申请号：US15053316
申请日：2016-02-25
申请人： Shari Lynn CAPLAN , Andrei GOLOSOV , Philipp GROSCHE , Carla GUIMARAES , Aaron KANTER , Changgang LOU , David Thomas PARKER , Eric C. Peters , Aimee Richardson USERA , Kayo YASOSHIMA , Jun YUAN , Federic ZECRI , Hongjuan ZHAO
发明人： Shari Lynn CAPLAN , Andrei GOLOSOV , Philipp GROSCHE , Carla GUIMARAES , Aaron KANTER , Changgang LOU , David Thomas PARKER , Eric C. Peters , Aimee Richardson USERA , Kayo YASOSHIMA , Jun YUAN , Federic ZECRI , Hongjuan ZHAO
IPC分类号： A61K38/10 , A61K45/06 , C07K16/00 , C07K7/08 , C07K14/765 , 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′ (SEQ ID NO: 1): 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.

3. 发明申请

US20160108091A1 CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE 审中-公开
公开(公告)号：US20160108091A1
公开(公告)日：2016-04-21
申请号：US14963391
申请日：2015-12-09
申请人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun YUAN , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla GUIMARAES
发明人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun YUAN , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla GUIMARAES
IPC分类号： C07K7/64 , C07K14/765
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 (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13 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.

4. 发明申请

US20150031604A1 CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE 有权
标题翻译：治疗心力衰竭的循环多糖
公开(公告)号：US20150031604A1
公开(公告)日：2015-01-29
申请号：US14336262
申请日：2014-07-21
申请人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun Yuan , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla Giumaraes
发明人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun Yuan , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla Giumaraes
IPC分类号： C07K7/64 , A61K38/12 , A61K45/06 , C07K16/46
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 (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13 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（SEQ ID NO：1）的环状多肽：X1-R-X3-X4-LS-X7-X8-X9-X10-X11-X12-X13I或酰胺，酯或盐或其生物缀合物，其中X1，X3，X4，X7，X8，X9，X10，X11，X12和X13在本文中定义。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，潴留，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。

5. 发明申请

US20160030585A1 NOVEL FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES 审中-公开
标题翻译：新型脂肪酸及其与生物分子结合的用途
公开(公告)号：US20160030585A1
公开(公告)日：2016-02-04
申请号：US14738272
申请日：2015-06-12
申请人： David Weninger BARNES , Ken YAMADA , Chikwendu IBEBUNJO , Alokesh DUTTAROY , Louis Clare KIRMAN , Alexandra Marshall BRUCE , Aimee Richardson USERA , Frederic ZECRI , Jun YUAN , Changgang LOU , Aaron KANTER , Avirup BOSE
发明人： David Weninger BARNES , Ken YAMADA , Chikwendu IBEBUNJO , Alokesh DUTTAROY , Louis Clare KIRMAN , Alexandra Marshall BRUCE , Aimee Richardson USERA , Frederic ZECRI , Jun YUAN , Changgang LOU , Aaron KANTER , Avirup BOSE
IPC分类号： A61K47/48 , A61K45/06 , C07C55/22 , C07C59/245 , C07C57/02 , A61K38/22 , C07C55/02 , A61K38/17 , C12N15/113 , A61K38/16 , A61K38/08 , A61K38/18 , C07C57/18
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：本发明提供包含通过接头与脂肪酸连接的生物分子的缀合物，其中脂肪酸具有下列式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。

6. 发明申请

US20160213743A1 SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE 有权
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：US20160213743A1
公开(公告)日：2016-07-28
申请号：US14996418
申请日：2016-01-15
申请人： Aaron KANTER , Aimee Richardson USERA , Frederic ZECRI
发明人： Aaron KANTER , Aimee Richardson USERA , Frederic ZECRI
IPC分类号： A61K38/12 , A61K45/06 , A61K47/48
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。

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