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1. 发明申请

US20050215468A1 Metal-binding compounds and uses therefor 失效
标题翻译：金属结合化合物及其用途
公开(公告)号：US20050215468A1
公开(公告)日：2005-09-29
申请号：US10894860
申请日：2004-07-19
申请人： David Bar-Or , C. Curtis , Edward Lau , Nagaraja Rao , James Winkler , Wannell Crook
发明人： David Bar-Or , C. Curtis , Edward Lau , Nagaraja Rao , James Winkler , Wannell Crook
IPC分类号： A61K38/06 , A61K38/08 , A61K38/10
CPC分类号： A61K38/06 , A61K8/64 , A61K38/08 , A61K38/10 , A61K2800/522 , A61Q19/00 , C07K5/0827 , C07K5/1027 , C07K14/47 , C07K14/4715
摘要： The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.
摘要翻译：本发明提供了减少动物中活性氧（ROS）所造成的损害的方法。本发明还提供了降低动物中金属浓度的方法。这些方法包括给予动物有效量的本申请中进一步描述的金属结合化合物。本发明进一步提供一种减少ROS对从动物中除去的细胞，组织或器官造成的损伤的方法。该方法包括使细胞，组织或器官与含有有效量的本发明金属结合化合物的溶液或培养基接触。本发明还提供新的金属结合化合物，包含金属结合化合物的药物组合物和包含容纳本发明的金属结合化合物的容器的试剂盒。

2. 发明申请

US20050142613A1 Test for the rapid evaluation of ischemic states and kits 审中-公开
标题翻译：测试缺血状态和试剂盒的快速评估
公开(公告)号：US20050142613A1
公开(公告)日：2005-06-30
申请号：US11033766
申请日：2005-01-12
申请人： David Bar-Or , Edward Lau , James Winkler , Gary Fagan , Hollie Wayment
发明人： David Bar-Or , Edward Lau , James Winkler , Gary Fagan , Hollie Wayment
IPC分类号： G01N33/68 , G01N33/53 , C07K14/765
CPC分类号： G01N33/6842 , G01N33/683
摘要： The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue.
摘要翻译：本发明涉及用于检测缺血状态的快速方法和用于这些方法的试剂盒。基于检测和定量缺血事件发生的血清蛋白白蛋白变化的存在的方法，提供了一种快速测试和定量缺血的方法; 用于检测和定量这种改变的方法包括评估和定量循环白蛋白的钴结合能力，分析和测量血清白蛋白结合外源钴的能力，检测和测量纯化白蛋白样品中内源性铜的存在，以及使用在缺血事件之后发生的血清白蛋白改变形式的特异性免疫测定。本发明还教导了通过测量缺血事件后出现的白蛋白N末端衍生物检测和测量缺血事件，包括缺乏一至四个N-末端氨基酸的截短的白蛋白物质或具有乙酰化N-末端的白蛋白 Asp残基。

3. 发明授权

US07473558B2 Marker useful for detection and measurement of free radical damage and method 失效
标题翻译：标记用于检测和测量自由基损伤和方法
公开(公告)号：US07473558B2
公开(公告)日：2009-01-06
申请号：US10232341
申请日：2002-08-30
申请人： David Bar-Or , Edward Lau
发明人： David Bar-Or , Edward Lau
IPC分类号： G01N33/20
CPC分类号： C07K14/765 , G01N33/68 , G01N2800/52 , Y10S436/903 , Y10S436/904
摘要： The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations affect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R (SEQ ID NO:1), wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring albumin (including no additional chemical group), for detection and quantification of the marker. Methods of the present invention also include use of the marker as a “biochemical tag,” thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics which result in the generation of free radicals, such as Photofrin® (porfimer sodium), or which act to limit free-radical damage. The marker also acts as a “biological tag” of a process implicated in a wide array of diseases and sequelae and, accordingly, may be used to test for the occurrence or non-occurrence of such diseases and sequelae. One such disease is ischemia.
摘要翻译：本发明教导了一种可用于检测和测量自由基损伤的标记物。具体地说，本发明利用在存在自由基的情况下白蛋白分子的N末端，人血液中的循环蛋白发生的改变。这些改变影响白蛋白分子的N末端结合金属的能力。用于检测和定量这种改变的方法包括评估和定量含白蛋白的样品的钴结合能力，分析和测量白蛋白结合外源钴的能力，检测和测量纯化的白蛋白样品中铜的存在以及使用对自由基损伤发生的血清白蛋白改变形式特异的免疫学检测。本发明还教导了化合物Asp-Ala-His-Lys-R（SEQ ID NO：1）的用途，其中R是当与能够结合N的任何化合物结合时能够检测到的任何化学基团 - 天然存在的白蛋白（包括没有其他化学基团），用于检测和定量标记物。本发明的方法还包括使用标记物作为“生物化学标签”，从而允许灵敏检测和测量导致产生自由基的临床药物和治疗剂的功效，例如Photofrin（porfimer 钠），或其作用是限制自由基损伤。该标记还用作涉及广泛疾病和后遗症的过程的“生物标签”，因此可用于测试这种疾病和后遗症的发生或不发生。一种这样的疾病是缺血。

4. 发明授权

US07449338B2 Tests for the rapid evaluation of ischemic states and kits 有权
标题翻译：检测缺血状态和试剂盒的快速评估
公开(公告)号：US07449338B2
公开(公告)日：2008-11-11
申请号：US10319263
申请日：2002-12-13
申请人： David Bar-Or , Edward Lau , James V. Winkler , Gary Fagan , Hollie Wayment
发明人： David Bar-Or , Edward Lau , James V. Winkler , Gary Fagan , Hollie Wayment
IPC分类号： G01N33/48
CPC分类号： G01N33/6842 , C07K14/765 , G01N33/68
摘要： The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue.
摘要翻译：本发明涉及用于检测缺血状态的快速方法和用于这些方法的试剂盒。基于检测和定量缺血事件发生的血清蛋白白蛋白变化的存在的方法，提供了一种快速测试和定量缺血的方法; 用于检测和定量这种改变的方法包括评估和定量循环白蛋白的钴结合能力，分析和测量血清白蛋白结合外源钴的能力，检测和测量纯化白蛋白样品中内源性铜的存在，以及使用在缺血事件之后发生的血清白蛋白改变形式的特异性免疫测定。本发明还教导了通过测量缺血事件后出现的白蛋白N末端衍生物检测和测量缺血事件，包括缺乏一至四个N-末端氨基酸的截短的白蛋白物质或具有乙酰化N-末端的白蛋白 Asp残基。

5. 发明申请

US20100144644A1 METAL-BINDING COMPOUNDS AND USES THEREFOR 有权
公开(公告)号：US20100144644A1
公开(公告)日：2010-06-10
申请号：US12610508
申请日：2009-11-02
申请人： David Bar-Or , C. Gerald Curtis , Edward Lau , Nagaraja K.R. Rao , James V. Winkler , Wannell M. Crook
发明人： David Bar-Or , C. Gerald Curtis , Edward Lau , Nagaraja K.R. Rao , James V. Winkler , Wannell M. Crook
IPC分类号： A61K38/08 , A61P9/00 , A61P9/10
CPC分类号： A61K38/06 , A61K8/64 , A61K38/08 , A61K38/10 , A61K2800/522 , A61Q19/00 , C07K5/0827 , C07K5/1027 , C07K14/47 , C07K14/4715
摘要： The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

6. 发明申请

US20100249016A1 METAL-BINDING COMPOUNDS AND USES THEREFOR 有权
标题翻译：金属结合化合物及其用途
公开(公告)号：US20100249016A1
公开(公告)日：2010-09-30
申请号：US12562136
申请日：2009-09-18
申请人： David Bar-Or , C. Gerald Curtis , Edward Lau , Nagaraja K. R. Rao , James V. Winkler , Wannell M. Crook
发明人： David Bar-Or , C. Gerald Curtis , Edward Lau , Nagaraja K. R. Rao , James V. Winkler , Wannell M. Crook
IPC分类号： A61K38/04 , A61K38/08 , A61K38/07 , A61P31/04 , A61P9/10 , A61P25/00 , A61P29/00
CPC分类号： C07K5/0827 , A61K38/00 , C07K5/1027 , C07K14/47 , C07K14/4715
摘要： The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.
摘要翻译：本发明提供了减少动物中活性氧（ROS）所造成的损害的方法。本发明还提供了降低动物中金属浓度的方法。这些方法包括给予动物有效量的本申请中进一步描述的金属结合化合物。本发明进一步提供一种减少ROS对从动物中除去的细胞，组织或器官造成的损伤的方法。该方法包括使细胞，组织或器官与含有有效量的本发明金属结合化合物的溶液或培养基接触。本发明还提供新的金属结合化合物，包含金属结合化合物的药物组合物和包含容纳本发明的金属结合化合物的容器的试剂盒。

7. 发明授权

US07070937B1 Marker useful for detection and measurement of free radical damage and method 失效
标题翻译：标记用于检测和测量自由基损伤和方法
公开(公告)号：US07070937B1
公开(公告)日：2006-07-04
申请号：US09820416
申请日：2001-03-29
申请人： David Bar-Or , Edward Lau
发明人： David Bar-Or , Edward Lau
IPC分类号： G01N33/53 , G01N33/537 , G01N33/543 , C12Q1/50
CPC分类号： G01N33/6893 , G01N2800/52
摘要： The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin-containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the peptide Asp Ala His Lys and the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of producing a detectable signal when a metal ion capable of binding to the N-terminus of naturally-occurring albumin is bound to the compound, for detection and quantitation of the marker. Methods of the present invention also include use of the marker as a “biochemical tag,” thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics which result in the generation of free radicals or which act to limit free radical damage. The marker also acts as a “biological tag” of a process implicated in a wide array of diseases and conditions and, accordingly, may be used to monitor and assess such diseases and conditions. Finally, the invention provides antibodies, immunoassays, and kits for use in detecting or quantitating the marker.
摘要翻译：本发明教导了一种可用于检测和测量自由基损伤的标记物。具体地说，本发明利用在存在自由基的情况下白蛋白分子的N末端，人血液中的循环蛋白发生的改变。这些改变影响白蛋白分子的N-末端结合金属的能力。用于检测和定量这种改变的方法包括评估和定量含白蛋白的样品的钴结合能力，分析和测量白蛋白结合外源钴的能力，检测和测量纯化白蛋白样品中铜的存在和使用对自由基损伤发生的血清白蛋白改变形式特异的免疫学检测。本发明还教导了肽Asp Ala His Lys和化合物Asp-Ala-His-Lys-R的用途，其中R是能够产生可检测信号的任何化学基团，当金属离子能够结合到天然存在的白蛋白的N末端与化合物结合，用于检测和定量标记物。本发明的方法还包括使用标记物作为“生物化学标签”，从而允许灵敏检测和测量导致产生自由基或用于限制自由基损伤的临床药物和治疗剂的功效。该标记还充当涉及广泛疾病和病症的过程的“生物标签”，因此可用于监测和评估这些疾病和病症。最后，本发明提供用于检测或定量标记物的抗体，免疫测定和试剂盒。

8. 发明授权

US06492179B1 Test for rapid evaluation of ischemic states and kit 有权
标题翻译：测试快速评估缺血状态和试剂盒
公开(公告)号：US06492179B1
公开(公告)日：2002-12-10
申请号：US09165581
申请日：1998-10-02
申请人： David Bar-Or , Edward Lau , James V. Winkler
发明人： David Bar-Or , Edward Lau , James V. Winkler
IPC分类号： G01N3320
CPC分类号： G01N33/6842 , G01N33/683 , Y10S436/903 , Y10S436/904
摘要： The present invention relates to a rapid method for the detection of ischemic states and to a kit for use in such a method. Provided for is a rapid method of testing for the existence of and quantifying ischemia based upon method of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating blood, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay sepcific to the alterated form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring human albumin (including no additional chemical group), for detection and quantification of an ischemic event.
摘要翻译：本发明涉及用于检测缺血状态的快速方法和用于这种方法的试剂盒。提供了一种基于检测和定量缺血事件发生的血清蛋白白蛋白改变的存在的方法来测试缺血的存在和定量的快速方法; 用于检测和定量这种改变的方法包括评估和定量循环血液的钴结合能力，分析和测量血清白蛋白结合外源钴的能力，检测和测量纯化白蛋白样品中铜的存在，以及使用免疫学测定与缺血事件发生的血清白蛋白的改变形式分离。本发明还教导了化合物Asp-Ala-His-Lys-R的用途，其中R是当与能够结合天然存在的人白蛋白N末端的任何化合物结合时能够检测到的任何化学基团（包括没有其他化学组），用于检测和定量缺血事件。

9. 发明授权

US07282369B2 Tests for the rapid evaluation of ischemic states and kits 有权
标题翻译：检测缺血状态和试剂盒的快速评估
公开(公告)号：US07282369B2
公开(公告)日：2007-10-16
申请号：US10414469
申请日：2003-04-15
申请人： David Bar-Or , Edward Lau , James V Winkler
发明人： David Bar-Or , Edward Lau , James V Winkler
IPC分类号： G01N33/20 , G01N33/48 , G01N31/00
CPC分类号： G01N33/6842 , G01N33/683 , Y10T436/107497
摘要： The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue.
摘要翻译：本发明涉及用于检测缺血状态的快速方法和用于这些方法的试剂盒。基于检测和定量缺血事件发生的血清蛋白白蛋白变化的存在的方法，提供了一种快速测试和定量缺血的方法; 用于检测和定量这种改变的方法包括评估和定量循环白蛋白的钴结合能力，分析和测量血清白蛋白结合外源钴的能力，检测和测量纯化白蛋白样品中内源性铜的存在，以及使用在缺血事件之后发生的血清白蛋白改变形式的特异性免疫测定。本发明还教导了通过测量缺血事件后出现的白蛋白N末端衍生物检测和测量缺血事件，包括缺乏一至四个N-末端氨基酸的截短的白蛋白物质或具有乙酰化N-末端的白蛋白 Asp残基。

10. 发明授权

US06475743B1 Marker useful for detection and measurement of free radical damage and method 失效
标题翻译：标记用于检测和测量自由基损伤和方法
公开(公告)号：US06475743B1
公开(公告)日：2002-11-05
申请号：US09165961
申请日：1998-10-02
申请人： David Bar-Or , Edward Lau
发明人： David Bar-Or , Edward Lau
IPC分类号： G01N3353
CPC分类号： C07K14/765 , G01N33/68 , G01N2800/52 , Y10S436/903 , Y10S436/904
摘要： The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R [SEQ ID NO:1], wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring albumin, for detection and quantification of the marker. Methods of the present invention also include use of the marker as a “biochemical tag,” thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics.
摘要翻译：本发明教导了一种可用于检测和测量自由基损伤的标记物。具体地说，本发明利用在存在自由基的情况下白蛋白分子的N末端，人血液中的循环蛋白发生的改变。这些改变影响白蛋白分子的N-末端结合金属的能力。用于检测和定量这种改变的方法包括评估和定量含白蛋白的样品的钴结合能力，分析和测量白蛋白结合外源钴的能力，检测和测量纯化的白蛋白样品中铜的存在以及使用对自由基损伤发生的血清白蛋白改变形式特异的免疫学检测。本发明还教导了化合物Asp-Ala-His-Lys-R [SEQ ID NO：1]的用途，其中R是当与能够结合N的任何化合物结合时能够检测到的任何化学基团 - 天然存在的白蛋白，用于检测和定量标记物。本发明的方法还包括使用标记物作为“生化标签”，从而允许灵敏检测和测量临床药物和治疗剂的功效。

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