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公开(公告)号：US10172907B2
公开(公告)日：2019-01-08
申请号：US13877955
申请日：2011-10-05
摘要： The invention concerns the contribution of elevated levels of circulating alsosterone to heart disease and other hyperaldosteronic conditions. Since activation of β-arrestin 1(βarr1) by the Angiotensin II (AngII) type 1 receptor (AT1R) mediates AngII-induced aldosterone production, β-arrestin 1(βarr1) is a therapeutic target for heart disease. The invention provides a βarr1 protein fragment comprising the C-terminus of βarr1 (βarr1ct; SEQ ID NO:3), compositions containing this protein fragment, and methods of using this protein fragment to reduce elevated levels of aldosterone in heart disease and other hyperaldosteronic conditions by inhibition of β-arrestin 1(βarr1). These compositions and methods are of therapeutic benefit in chronic heart failure and progression to heart failure after myocardial infarction (MI). Additionally, the invention provides an AngII peptide analog (SEQ ID NO:4), compositions containing this analog, and methods of using this analog for stimulation of βarr1 activity and aldosterone production.
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2.发明申请METHODS AND COMPOSITIONS FOR THERAPEUTIC MODULATION OF ALDOSTERONE LEVELS IN HEART DISEASE 审中-公开心脏疾病中阿尔托斯酮水平的治疗方法和组合物公开(公告)号：US20130274191A1
公开(公告)日：2013-10-17
申请号：US13877955
申请日：2011-10-05
IPC分类号： A61K38/08 , A61K31/41 , A61K31/4184
CPC分类号： A61K38/085 , A61K31/41 , A61K31/4184 , A61K38/1709 , A61P9/04 , C07K14/4703 , A61K2300/00
摘要： The disclosure describes the contribution of elevated levels of circulating alsosterone to heart disease and other hyperaldosteronic conditions. Since activation of beta-arrestin I (beta.arr-1) by the Angiotensin II (AngII) type 1 receptor (AT1R) mediates AngII-induced aldosterone production, beta-arrestin I (beta.arr-1) is a therapeutic target for heart disease. Specifically, the disclosure provides a beta.arr-1 protein fragment comprising the C-terminus of beta.arr-1 (beta.arr1ct; SEQ ID NO:3), compositions containing this protein fragment, and methods of using this protein fragment to reduce elevated levels of aldosterone in heart disease and other hyperaldosteronic conditions by inhibition of beta-arrestin (beta.arr-1). These compositions and methods are of therapeutic benefit in chronic heart failure and progression to heart failure after myocardial infarction (MI). Additionally, the invention provides an AngII peptide analog (SEQ ID NO:4), compositions containing this analog, and methods of using this analog for stimulation of beta.arr-1 activity and aldosterone production.
摘要翻译： 该公开内容描述了循环性强酮水平升高对心脏病和其它高醛状血糖状况的贡献。 由于血管紧张素II（AngII）1型受体（AT1R）的β-arrestin I（beta.arr-1）的激活介导AngII诱导的醛固酮生成，因此β抑制蛋白I（beta.arr-1）是治疗靶点 心脏病。 具体地，本公开提供了包含beta.arr-1（beta.arr1ct; SEQ ID NO：3）的C末端的beta.arr-1蛋白质片段，含有该蛋白质片段的组合物，以及使用该蛋白质片段 通过抑制β-抑制蛋白（beta.arr-1）降低心脏病和其他醛固酮增多症状中醛固酮的水平升高。 这些组合物和方法在心肌梗塞（MI）后在慢性心力衰竭和进展为心力衰竭中具有治疗益处。 此外，本发明提供AngII肽类似物（SEQ ID NO：4），含有该类似物的组合物，以及使用该类似物刺激beta.arr-1活性和醛固酮产生的方法。
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3.发明申请公开(公告)号：US20100048479A1
公开(公告)日：2010-02-25
申请号：US12513713
申请日：2007-11-09
IPC分类号： A61K38/16 , A61K31/711 , A61K31/7105 , A61P9/10
CPC分类号： A61K48/0075 , A61K48/0058 , C12N9/1205
摘要： The present invention relates to compositions and methods for the treatment of failing hearts. More specifically, the present invention provides for the inhibition of G-protein coupled receptor kinase 2 activity in the adrenal gland, which, for example, decreases catecholamine secretion and the sympathetic burden of the failing heart, thereby improving the cardiac adrenergic/inotropic reserve and overall contractile function.
摘要翻译： 本发明涉及治疗失败的心脏的组合物和方法。 更具体地，本发明提供对肾上腺中G蛋白偶联受体激酶2活性的抑制，其例如降低儿茶酚胺分泌和失败心脏的交感负担，从而改善心脏肾上腺素能/肌力储备和 整体收缩功能。
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公开(公告)号：US06683057B1
公开(公告)日：2004-01-27
申请号：US09400861
申请日：1999-09-21
IPC分类号： A01N4304
CPC分类号： C12N9/1205 , A61K31/70 , A61K38/45 , A61K48/00 , C12N2799/022
摘要： The present invention relates, in general, to vascular smooth muscle proliferation and, in particular, to a method of inhibiting arterial and venous smooth muscle proliferation resulting, for example, from arterial injury or vein grafting. The invention also relates to an expression construct encoding a G&bgr;&ggr; inhibitor suitable for use in such a method.
摘要翻译： 本发明一般涉及血管平滑肌增生，特别涉及抑制动脉和静脉平滑肌增生的方法，其导致例如动脉损伤或静脉移植。 本发明还涉及编码适用于这种方法的Gbetagamma抑制剂的表达构建体。
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公开(公告)号：US08383601B2
公开(公告)日：2013-02-26
申请号：US12447558
申请日：2007-10-30
CPC分类号： C12N15/86 , C07K14/4728 , C12N2750/14143 , C12N2830/008
摘要： The invention provides nucleic acid segments, compositions and methods for the treatment of heart failure, vascular dysfunction, endothelial dysfunction, diabetes, [Ca2+]i regulation and NO synthase dysfunction. Adeno-associated and adenovirus are used as gene delivery vectors for the nucleic acid segments to product long term over-expression of S100A1, a small calcium sensing protein associated with the disclosed ailments and dysfunctions.
摘要翻译： 本发明提供用于治疗心力衰竭，血管功能障碍，内皮功能障碍，糖尿病，[Ca 2+] i调节和NO合成酶功能障碍的核酸区段，组合物和方法。 腺相关腺病毒和腺病毒用作核酸片段的基因递送载体以产生S100A1的长期过表达，S100A1是与所公开的疾病和功能障碍相关的小的钙感觉蛋白。
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公开(公告)号：US20100190840A1
公开(公告)日：2010-07-29
申请号：US12447558
申请日：2007-10-30
IPC分类号： A61K31/711 , C07H21/04 , A61P9/04 , C12N15/63
CPC分类号： C12N15/86 , C07K14/4728 , C12N2750/14143 , C12N2830/008
摘要： The invention provides nucleic acid segments, compositions and methods for the treatment of heart failure, vascular dysfunction, endothelial dysfunction, diabetes, [Ca2+]i regulation and NO synthase dysfunction. Adeno-associated and adenovirus are used as gene delivery vectors for the nucleic acid segments to product long term over-expression of S100A1, a small calcium sensing protein associated with the disclosed ailments and dysfunctions.
摘要翻译： 本发明提供用于治疗心力衰竭，血管功能障碍，内皮功能障碍，糖尿病，[Ca 2+] i调节和NO合成酶功能障碍的核酸区段，组合物和方法。 腺相关腺病毒和腺病毒用作核酸片段的基因递送载体以产生S100A1的长期过表达，S100A1是与所公开的疾病和功能障碍相关的小的钙感觉蛋白。
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7.发明授权Use of exogenous &bgr;-adrenergic receptor and &bgr;-adrenergic receptor kinase gene constructs to enhance myocardial function 有权使用外源β-肾上腺素能受体和β-肾上腺素能受体激酶基因构建体来增强心肌功能公开(公告)号：US06436908B1
公开(公告)日：2002-08-20
申请号：US09285677
申请日：1999-04-05
IPC分类号： A61K3170
CPC分类号： C12N9/1205 , A61K31/70 , A61K38/1787 , A61K48/00
摘要： The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&bgr;-AR). &bgr;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &bgr;-AR transgene, a &bgr;-ARK transgene, or a &bgr;-ARK inhibitor transgene.
摘要翻译： 本发明涉及用于治疗慢性心力衰竭和伴随心肌β-肾上腺素能受体（β-AR）减少的数量或功能的其它心脏疾病状态的基因治疗。 β-AR受体功能在转基因动物中通过递送和表达β-2-肾上腺素能受体基因或编码β肾上腺素能受体激酶抑制剂的基因而增加，导致体内左心室功能增加。 本发明包括重组质粒载体，替代β-肾上腺素能受体基因递送策略，以及携带β-AR转基因，β-ARK转基因或β-ARK抑制剂转基因的转基因小鼠。
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公开(公告)号：US06627602B2
公开(公告)日：2003-09-30
申请号：US10280085
申请日：2002-10-25
申请人： Jonathan S. Stamler , Robert J. Lefkowitz , Erin J. Whalen , Walter J. Koch , Claude A. Piantadosi
发明人： Jonathan S. Stamler , Robert J. Lefkowitz , Erin J. Whalen , Walter J. Koch , Claude A. Piantadosi
IPC分类号： A61K3800
CPC分类号： A61K31/21 , A61K31/19 , A61K31/223 , A61K31/5377 , A61K38/063
摘要： Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.
摘要翻译： 通过抑制G蛋白受体激酶来防止控制疾病的受体的脱敏。 这具有适用性，例如对于患有心力衰竭的患者或手术后左心室心脏装置或心脏泵，或即将进行手术并且心脏事件或鸦片剂或阿片剂或成瘾患有高胆固醇或囊性纤维化的患者，或 类风湿关节炎。
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公开(公告)号：US20090053696A1
公开(公告)日：2009-02-26
申请号：US11667013
申请日：2005-11-04
申请人： Walter J. Koch , Guido Iaccarino
发明人： Walter J. Koch , Guido Iaccarino
CPC分类号： C12Q1/6883 , C12Q1/485 , C12Q2600/158 , G01N33/5091 , G01N33/573
摘要： The present invention relates, in general, to heart failure, and, in particular, to a method of evaluating heart failure patients by monitoring β-adrenergic receptor kinase (βARK1) levels in lymphocytes from such patients.
摘要翻译： 本发明一般涉及心力衰竭，特别涉及通过监测来自这些患者的淋巴细胞中的β-肾上腺素能受体激酶（βARK1）水平来评价心力衰竭患者的方法。
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公开(公告)号：US07060871B2
公开(公告)日：2006-06-13
申请号：US10183344
申请日：2002-06-28
IPC分类号： A01K67/033 , A01K67/027 , G01N33/00 , C12N15/63 , C12N15/00
CPC分类号： C12N9/1205 , A61K31/70 , A61K38/1787 , A61K48/00
摘要： The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (β-AR). β-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a β-AR transgene, a β-ARK transgene, or a β-ARK inhibitor transgene.
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