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公开(公告)号：US09683019B2
公开(公告)日：2017-06-20
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
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.
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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
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。
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公开(公告)号：US09266925B2
公开(公告)日：2016-02-23
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
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。
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公开(公告)号：US09683018B2
公开(公告)日：2017-06-20
申请号：US14905338
申请日：2014-07-21
申请人： Frederic Zecri , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Jun Yuan
发明人： Frederic Zecri , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Jun Yuan
IPC分类号： A61K38/12 , C07K7/50 , A61K38/10 , C07K7/04 , C07K7/08 , C07K14/47 , A61K38/08 , A61K45/06 , C07K7/06
摘要： The invention provides a synthetic polypeptide of Formula I′: X1-R-P-R-X5-X6-X7-K-X9-P-X11-X12-X13 or an amide, an ester, a salt or a bioconjugate thereof, wherein X1, X5, X6, X7, X9 and X11 to 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 or 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.
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公开(公告)号：US09340582B2
公开(公告)日：2016-05-17
申请号：US14336290
申请日：2014-07-21
申请人： Jun Yuan , Frederic Zecri , Philipp Grosche , Hongjuan Zhao , Eric Peters , Shari Lynn Caplan , Changgang Lou
发明人： Jun Yuan , Frederic Zecri , Philipp Grosche , Hongjuan Zhao , Eric Peters , Shari Lynn Caplan , Changgang Lou
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。
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6.发明授权公开(公告)号：US08921307B2
公开(公告)日：2014-12-30
申请号：US14082771
申请日：2013-11-18
申请人： Frédéric Zecri , Kayo Yasoshima , Philipp Grosche , Jun Yuan , Hongjuan Zhao
发明人： Frédéric Zecri , Kayo Yasoshima , Philipp Grosche , Jun Yuan , Hongjuan Zhao
摘要： The invention provides a synthetic polypeptide of Formula I′ (SEQ ID NO: 1): X1-X2-X3-R—X5-X6-X7-X8-X9-X10-X11-X12-X13 I or an amide, an ester or a salt thereof, wherein X1, X2, X3, X5, X6, 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, 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： 本发明提供式I'（SEQ ID NO：1）的合成多肽：X1-X2-X3-R-X5-X6-X7-X8-X9-X10-X11-X12-X13I或酰胺，酯 或其盐，其中X 1，X 2，X 3，X 5，X 6，X 7，X 8，X 9，X 10，X 11，X 12和X 13如本文所定义。 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，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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7.发明申请公开(公告)号：US20150284446A1
公开(公告)日：2015-10-08
申请号：US14440198
申请日：2013-11-19
申请人： Frédéric ZECRI , Kayo YASOSHIMA , Philipp GROSCHE , Jun YUAN , Hongjuan ZHAO
发明人： Frederic Zecri , Kayo Yasoshima , Philipp Grosche , Jun Yuan , Hongjuan Zhao
IPC分类号： C07K14/765 , 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.
摘要翻译： 本发明涉及包含修饰的apelin-13肽序列的新型组合物，其设计用于治疗其给药对象的心血管疾病，并且其表现出比其野生型对应物更大的降解抗性和等同或更大的生物活性。 本发明还涉及制备所述组合物并使用所述组合物作为药物活性剂治疗心血管疾病的方法。
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8.发明申请公开(公告)号：US20140155315A1
公开(公告)日：2014-06-05
申请号：US14082771
申请日：2013-11-18
申请人： Frédéric Zecri , Kayo Yasoshima , Philipp Grosche , Jun Yuan , Hongjuan Zhao
发明人： Frédéric Zecri , Kayo Yasoshima , Philipp Grosche , Jun Yuan , Hongjuan Zhao
摘要： The invention provides a synthetic polypeptide of Formula I′ (SEQ ID NO: 1): X1-X2-X3-R—X5-X6-X7-X8-X9-X10-X11-X12-X13 I or an amide, an ester or a salt thereof, wherein X1, X2, X3, X5, X6, 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, 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： 本发明提供式I'（SEQ ID NO：1）的合成多肽：X1-X2-X3-R-X5-X6-X7-X8-X9-X10-X11-X12-X13I或酰胺，酯 或其盐，其中X 1，X 2，X 3，X 5，X 6，X 7，X 8，X 9，X 10，X 11，X 12和X 13如本文所定义。 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，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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9.发明授权Method and system for providing an uplink structure and improved channelization scheme in a wireless communication network 有权在无线通信网络中提供上行链路结构和改进的信道化方案的方法和系统公开(公告)号：US09036570B2
公开(公告)日：2015-05-19
申请号：US13264936
申请日：2010-04-16
申请人： Sophie Vrzic , Mo-Han Fong , DongSheng Yu , Robert Novak , Jun Yuan
发明人： Sophie Vrzic , Mo-Han Fong , DongSheng Yu , Robert Novak , Jun Yuan
CPC分类号： H04W36/385 , H04J13/16 , H04L5/0007 , H04L5/0037 , H04L5/0092 , H04W72/042 , H04W72/0453
摘要： A method and system are provided to perform channelization in a wireless communication network, wherein the wireless communication network including at least one base station that is communicatively coupled to at least one mobile terminal. A bandwidth of the wireless communication network is divided into a plurality of zones at the base station. Resource blocks are provided at the base station to receive data symbols transmitted in the wireless communication network. A plurality of resource blocks are combined at the base station to form a physical basic channel unit which are allocated to one of the plurality of zones at the base station. A permutation is performed on the physical basic channel unit to form a logical basic channel unit. A channel is provided to communicatively couple the base station and the mobile terminal so that the mobile terminal may send an access grant message and a user identification to the base station to transmit data in the logical basic channel unit.
摘要翻译： 提供了一种在无线通信网络中执行信道化的方法和系统，其中所述无线通信网络包括通信地耦合到至少一个移动终端的至少一个基站。 无线通信网络的带宽在基站被分成多个区域。 在基站处提供资源块以接收在无线通信网络中发送的数据符号。 在基站处组合多个资源块，以形成分配给基站的多个区域之一的物理基本信道单元。 在物理基本信道单元上执行置换以形成逻辑基本信道单元。 提供了一种通信来通信地耦合基站和移动终端，使得移动终端可以向基站发送接入许可消息和用户标识以在逻辑基本信道单元中发送数据。
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公开(公告)号：US08671395B1
公开(公告)日：2014-03-11
申请号：US12879458
申请日：2010-09-10
申请人： Jun Yuan , Akok Jain , Manpreet Singh Reehal , Vinaya Kumar Singh
发明人： Jun Yuan , Akok Jain , Manpreet Singh Reehal , Vinaya Kumar Singh
CPC分类号： G06F17/5009 , G06F2217/06
摘要： The present disclosure relates to a method for avoiding deadends in a constrained simulation. The method may include analyzing a first deadend during a simulation and a first constraint of the simulation. The method may further include determining if the first constraint causes the first deadend. If the first constraint causes the first deadend, the method may also include defining a first lookahead constraint corresponding to the first constraint. The method may additionally include rerunning a first previous cycle in the simulation while adding the first lookahead constraint to the simulation.
摘要翻译： 本公开涉及一种用于在受限模拟中避免死角的方法。 该方法可以包括在模拟期间分析第一死区和模拟的第一约束。 所述方法还可以包括确定所述第一约束是否引起所述第一死锁。 如果第一约束导致第一个停止，则该方法还可以包括定义与第一约束相对应的第一前瞻约束。 该方法可以另外包括在模拟中重新运行第一先前循环，同时将第一前视约束添加到模拟中。
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