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    CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE
    3.
    发明申请
    CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE 有权
    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

    Applicant: Frederic ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun Yuan ,  Aimee Richardson USERA ,  Changgang LOU ,  Aaron KANTER ,  Alexandra Marshall BRUCE ,  Carla Giumaraes

    Inventor： Frederic ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun Yuan ,  Aimee Richardson USERA ,  Changgang LOU ,  Aaron KANTER ,  Alexandra Marshall BRUCE ,  Carla Giumaraes

    IPC: C07K7/64 ,  A61K38/12 ,  A61K45/06 ,  C07K16/46

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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。

    SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE
    4.
    发明申请
    SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE 有权
    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

    Applicant: Aaron KANTER ,  Aimee Richardson USERA ,  Frederic ZECRI

    Inventor： Aaron KANTER ,  Aimee Richardson USERA ,  Frederic ZECRI

    IPC: A61K38/12 ,  A61K45/06 ,  A61K47/48

    CPC classification number: A61K38/12 ,  A61K45/06 ,  A61K47/542 ,  A61K47/60 ,  A61K47/64 ,  A61K51/0402 ,  C07K7/64 ,  C07K14/47

    Abstract: 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.

    Abstract translation: 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。

    Cyclic polypeptides for the treatment of heart failure
    6.
    发明授权
    Cyclic polypeptides for the treatment of heart failure 有权
    循环多肽用于治疗心力衰竭

    公开(公告)号：US09266925B2

    公开(公告)日：2016-02-23

    申请号：US14336262

    申请日：2014-07-21

    Applicant: Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan ,  Aimee Richardson Usera ,  Changgang Lou ,  Aaron Kanter ,  Alexandra Marshall Bruce ,  Carla Giumaraes

    Inventor： Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan ,  Aimee Richardson Usera ,  Changgang Lou ,  Aaron Kanter ,  Alexandra Marshall Bruce ,  Carla Giumaraes

    IPC: C07K7/64 ,  C07K16/46 ,  A61K38/12 ,  A61K45/06 ,  C07K14/47

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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。

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