公开(公告)号：US20130177551A1

公开(公告)日：2013-07-11

申请号：US13683527

申请日：2012-11-21

申请人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

发明人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

IPC分类号： G01N33/92

CPC分类号： G01N33/561 ,  C07K16/18 ,  G01N33/6893 ,  G01N33/92 ,  G01N2333/775 ,  G01N2800/32

摘要： Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotien A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

摘要翻译： 本文提供用于确定受试者，特别是人类受试者是否处于发展，具有或经历心血管疾病并发症的风险的方法，以及治疗由目前的心血管疾病风险的方法鉴定的受试者的方法。 在一个实施方案中，该方法包括确定来自受试者的身体样品中一种或多种氧化的载脂蛋白A-I相关生物分子的水平。 此外，提供了用于本方法的试剂盒和试剂。 还提供了用于监测受试者心血管疾病状态或治疗剂对心血管疾病受试者的影响的方法。 这种方法包括测定在受试者随时间或治疗之前或之后取自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关分子的水平。

公开(公告)号：US08722344B2

公开(公告)日：2014-05-13

申请号：US13683527

申请日：2012-11-21

申请人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

发明人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

IPC分类号： G01N33/53

CPC分类号： G01N33/561 ,  C07K16/18 ,  G01N33/6893 ,  G01N33/92 ,  G01N2333/775 ,  G01N2800/32

摘要： Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotien A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

摘要翻译： 本文提供用于确定受试者，特别是人类受试者是否处于发展，具有或经历心血管疾病并发症的风险的方法，以及治疗由目前的心血管疾病风险的方法鉴定的受试者的方法。 在一个实施方案中，该方法包括确定来自受试者的身体样品中一种或多种氧化的载脂蛋白A-I相关生物分子的水平。 此外，提供了用于本方法的试剂盒和试剂。 还提供了用于监测受试者心血管疾病状态或治疗剂对心血管疾病受试者的影响的方法。 这种方法包括测定在受试者随时间或治疗之前或之后取自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关分子的水平。

公开(公告)号：US08338110B2

公开(公告)日：2012-12-25

申请号：US12730137

申请日：2010-03-23

申请人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

发明人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

IPC分类号： G01N33/53

CPC分类号： G01N33/561 ,  C07K16/18 ,  G01N33/6893 ,  G01N33/92 ,  G01N2333/775 ,  G01N2800/32

摘要： Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotein A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

摘要翻译： 本文提供用于确定受试者，特别是人类受试者是否处于发展，具有或经历心血管疾病并发症的风险的方法，以及治疗由目前的心血管疾病风险的方法鉴定的受试者的方法。 在一个实施方案中，该方法包括确定来自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关生物分子的水平。 此外，提供了用于本方法的试剂盒和试剂。 还提供了用于监测受试者心血管疾病状态或治疗剂对心血管疾病受试者的影响的方法。 这种方法包括测定在受试者随时间或治疗之前或之后取自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关分子的水平。

公开(公告)号：US07781219B2

公开(公告)日：2010-08-24

申请号：US11005563

申请日：2004-12-06

申请人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

发明人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

IPC分类号： G01N33/53

CPC分类号： G01N33/561 ,  C07K16/18 ,  G01N33/6893 ,  G01N33/92 ,  G01N2333/775 ,  G01N2800/32

摘要： Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotien A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

摘要翻译： 本文提供用于确定受试者，特别是人类受试者是否处于发展，具有或经历心血管疾病并发症的风险的方法，以及治疗由目前的心血管疾病风险的方法鉴定的受试者的方法。 在一个实施方案中，该方法包括确定来自受试者的身体样品中一种或多种氧化的载脂蛋白A-I相关生物分子的水平。 此外，提供了用于本方法的试剂盒和试剂。 还提供了用于监测受试者心血管疾病状态或治疗剂对心血管疾病受试者的影响的方法。 这种方法包括测定在受试者随时间或治疗之前或之后取自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关分子的水平。

公开(公告)号：US20100183607A1

公开(公告)日：2010-07-22

申请号：US12730137

申请日：2010-03-23

申请人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

发明人： Stanley L. Hazen ,  Michael Kinter ,  Marc S. Penn ,  Jonathan Smith ,  Lemin Zheng

IPC分类号： A61K39/395 ,  C07K16/18 ,  C07K14/775 ,  A61K31/573 ,  A61K38/47 ,  A61K38/16 ,  A61K38/48 ,  A61K31/58 ,  A61K31/542 ,  A61K38/44 ,  A61K31/737 ,  A61K31/60 ,  A61K38/49 ,  A61K31/554 ,  A61P9/00 ,  C12Q1/00 ,  G01N33/00 ,  C12Q1/28 ,  G01N33/566 ,  G01N33/53

CPC分类号： G01N33/561 ,  C07K16/18 ,  G01N33/6893 ,  G01N33/92 ,  G01N2333/775 ,  G01N2800/32

摘要： Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotein A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

摘要翻译： 本文提供用于确定受试者，特别是人类受试者是否处于发展，具有或经历心血管疾病并发症的风险的方法，以及治疗由目前的心血管疾病风险的方法鉴定的受试者的方法。 在一个实施方案中，该方法包括确定来自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关生物分子的水平。 此外，提供了用于本方法的试剂盒和试剂。 还提供了用于监测受试者心血管疾病状态或治疗剂对心血管疾病受试者的影响的方法。 这种方法包括测定在受试者随时间或治疗之前或之后取自受试者的身体样品中一种或多种氧化的载脂蛋白A-1相关分子的水平。

公开(公告)号：US07459286B1

公开(公告)日：2008-12-02

申请号：US10972058

申请日：2004-10-22

申请人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

发明人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

IPC分类号： C12Q1/28 ,  G01N33/48

CPC分类号： G01N33/573 ,  C12Q1/28 ,  G01N33/6893 ,  G01N2333/908 ,  G01N2800/32 ,  G01N2800/50 ,  G01N2800/56

摘要： Methods for characterizing the near term risk of experiencing a major adverse cardiac event in a patient presenting with chest pain are provided. In one embodiment the method comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of MPO mass in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the patient. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, chlorotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation product. Levels of MPO activity, MPO mass, or the select MPO-generated oxidation product in bodily samples from the test subject are then compared to a control value that is derived from measurements of MPO activity, MPO mass, or the select MPO-generated oxidation product in comparable bodily samples obtained from control population. Such comparison can also be used to determine treatment of the patient immediately at presentation in the emergency room.

摘要翻译： 提供了表征患有胸痛的患者的主要不良心脏事件的近期风险的方法。 在一个实施方案中，该方法包括确定从患者获得的身体样品中髓过氧化物酶（MPO）活性的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的MPO质量的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的一种或多种选择的MPO产生的氧化产物的水平。 选择的MPO生成的氧化产物是二酪氨酸，硝基酪氨酸，氯酪氨酸，甲硫氨酸亚砜或MPO产生的脂质过氧化产物。 然后将来自测试受试者的身体样品中的MPO活性，MPO质量或选择的MPO生成的氧化产物的水平与从MPO活性，MPO质量或选择的MPO产生的氧化产物的测量结果相关的对照值进行比较 在从对照群体获得的可比较的身体样品中。 这种比较也可用于在急诊室中呈现时立即确定患者的治疗。

公开(公告)号：US08349581B2

公开(公告)日：2013-01-08

申请号：US12265081

申请日：2008-11-05

申请人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

发明人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

IPC分类号： C12Q1/28 ,  G01N33/48

CPC分类号： G01N33/573 ,  C12Q1/28 ,  G01N33/6893 ,  G01N2333/908 ,  G01N2800/32 ,  G01N2800/50 ,  G01N2800/56

摘要： Methods for characterizing the near term risk of experiencing a major adverse cardiac event in a patient presenting with chest pain are provided. In one embodiment the method comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of MPO mass in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the patient. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, chlorotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation product.

摘要翻译： 提供了表征患有胸痛的患者的主要不良心脏事件的近期风险的方法。 在一个实施方案中，该方法包括确定从患者获得的身体样品中髓过氧化物酶（MPO）活性的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的MPO质量的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的一种或多种选择的MPO产生的氧化产物的水平。 选择的MPO生成的氧化产物是二酪氨酸，硝基酪氨酸，氯酪氨酸，甲硫氨酸亚砜或MPO产生的脂质过氧化产物。

公开(公告)号：US07378396B2

公开(公告)日：2008-05-27

申请号：US11198005

申请日：2005-08-05

申请人： Stanley L. Hazen ,  Marc S. Penn

发明人： Stanley L. Hazen ,  Marc S. Penn

IPC分类号： A61K38/07 ,  A61K38/08 ,  A61K38/10 ,  A61K38/16

CPC分类号： C07K16/18 ,  A61K38/1709 ,  C07K14/775 ,  C07K16/40 ,  C07K16/44 ,  G01N2333/775 ,  G01N2333/902 ,  G01N2500/02 ,  G01N2800/32

摘要： The present invention provides methods and agents for treating subjects who have or are at risk of developing or having cardiovascular disease. Such agents inhibit binding of myeloperoxidase (MPO) to a molecule comprising the MPO binding site of apolipoprotein A-1 (apoA-1) and include a peptide fragment of apoA-1 comprising at least 4 contiguous amino acids in SEQ ID. NO: 2, a modified form of the apo-1 fragment comprising one or more D amino acids, a retro-inverso form of the apoA-1 peptide fragment, an organo-mimetic of the apoA-1 peptide fragment, a peptide-mimetic of the apoA1 peptide fragment, or a nucleic acid encoding the apo A-1 peptide fragment. The present invention also provides methods of identifying or screening test agents for treating subjects having or at risk of having or developing CVD. The method comprises incubating one or more test agents and MPO with a molecule comprising the MPO binding site of apoA-1 under conditions which permit binding of MPO to the MPO binding site and determining whether one or more of the agents inhibit such binding.

摘要翻译： 本发明提供用于治疗患有或有发展中心或患有心血管疾病的风险的受试者的方法和试剂。 这样的试剂抑制髓过氧化物酶（MPO）与包含载脂蛋白A-1（apoA-1）的MPO结合位点的分子的结合，并且包括在SEQ ID NO：1中包含至少4个连续氨基酸的载脂蛋白-1的肽片段。 NO：2，包含一个或多个D氨基酸的载脂蛋白-1片段的修饰形式，载脂蛋白-A-1肽片段的逆反式形式，载脂蛋白-A-1肽片段的有机模拟物，肽模拟物 的apoA1肽片段，或编码载脂蛋白A-1肽片段的核酸。 本发明还提供鉴定或筛选用于治疗患有或有发生CVD的风险的受试者的方法。 该方法包括在允许MPO与MPO结合位点结合并确定一种或多种药物是否抑制这种结合的条件下，将一种或多种测试剂和MPO与包含apoA-1的MPO结合位点的分子一起孵育。

公开(公告)号：US07776563B2

公开(公告)日：2010-08-17

申请号：US12126109

申请日：2008-05-23

申请人： Stanley L. Hazen ,  Marc S. Penn

发明人： Stanley L. Hazen ,  Marc S. Penn

IPC分类号： C12Q1/28

CPC分类号： C07K16/18 ,  A61K38/1709 ,  C07K14/775 ,  C07K16/40 ,  C07K16/44 ,  G01N2333/775 ,  G01N2333/902 ,  G01N2500/02 ,  G01N2800/32

摘要： The present invention provides methods and agents for treating subjects who have or are at risk of developing or having cardiovascular disease. Such agents inhibit binding of myeloperoxidase (MPO) to a molecule comprising the MPO binding site of apolipoprotein A-1 (apoA-1) and include a peptide fragment of apoA-1 comprising at least 4 contiguous amino acids in SEQ ID. NO: 2, a modified form of the apo-1 fragment comprising one or more D amino acids, a retro-inverso form of the apoA-1 peptide fragment, an organo-mimetic of the apoA-1 peptide fragment, a peptide-mimetic of the apoA1 peptide fragment, or a nucleic acid encoding the apo A-1 peptide fragment. The present invention also provides methods of identifying or screening test agents for treating subjects having or at risk of having or developing CVD. The method comprises incubating one or more test agents and MPO with a molecule comprising the MPO binding site of apoA-1 under conditions which permit binding of MPO to the MPO binding site and determining whether one or more of the agents inhibit such binding.

摘要翻译： 本发明提供用于治疗患有或有发展中心或患有心血管疾病的风险的受试者的方法和试剂。 这样的试剂抑制髓过氧化物酶（MPO）与包含载脂蛋白A-1（apoA-1）的MPO结合位点的分子的结合，并且包括在SEQ ID NO：1中包含至少4个连续氨基酸的载脂蛋白-1的肽片段。 NO：2，包含一个或多个D氨基酸的载脂蛋白-1片段的修饰形式，载脂蛋白-A-1肽片段的逆反式形式，载脂蛋白-A-1肽片段的有机模拟物，肽模拟物 的apoA1肽片段，或编码载脂蛋白A-1肽片段的核酸。 本发明还提供鉴定或筛选用于治疗患有或有发生CVD的风险的受试者的方法。 该方法包括在允许MPO与MPO结合位点结合并确定一种或多种药物是否抑制这种结合的条件下，将一种或多种测试剂和MPO与包含apoA-1的MPO结合位点的分子一起孵育。

公开(公告)号：US20090061472A1

公开(公告)日：2009-03-05

申请号：US12265081

申请日：2008-11-05

申请人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

发明人： Stanley L. Hazen ,  Marc S. Penn ,  Renliang Zhang

IPC分类号： C12Q1/28 ,  G01N33/92 ,  G01N33/68

CPC分类号： G01N33/573 ,  C12Q1/28 ,  G01N33/6893 ,  G01N2333/908 ,  G01N2800/32 ,  G01N2800/50 ,  G01N2800/56

摘要： Methods for characterizing the near term risk of experiencing a major adverse cardiac event in a patient presenting with chest pain are provided. In one embodiment the method comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of MPO mass in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the patient. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, chlorotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation product. Levels of MPO activity, MPO mass, or the select MPO-generated oxidation product in bodily samples from the test subject are then compared to a control value that is derived from measurements of MPO activity, MPO mass, or the select MPO-generated oxidation product in comparable bodily samples obtained from control population. Such comparison can also be used to determine the near term treatment of the patient.

摘要翻译： 提供了表征患有胸痛的患者的主要不良心脏事件的近期风险的方法。 在一个实施方案中，该方法包括确定从患者获得的身体样品中髓过氧化物酶（MPO）活性的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的MPO质量的水平。 在另一个实施方案中，该方法包括确定从患者获得的身体样品中的一种或多种选择的MPO产生的氧化产物的水平。 选择的MPO生成的氧化产物是二酪氨酸，硝基酪氨酸，氯酪氨酸，甲硫氨酸亚砜或MPO产生的脂质过氧化产物。 然后将来自测试受试者的身体样品中的MPO活性，MPO质量或选择的MPO生成的氧化产物的水平与从MPO活性，MPO质量或选择的MPO产生的氧化产物的测量结果相关的对照值进行比较 在从对照群体获得的可比较的身体样品中。 这种比较也可用于确定患者的近期治疗。