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11. 发明授权

US5780615A Glycosylation of lipids and lipid-containing particles and diagnostic and therapeutic methods and materials derived therefrom 失效
标题翻译：脂质和含脂质颗粒的糖基化及其衍生的诊断和治疗方法和材料
公开(公告)号：US5780615A
公开(公告)日：1998-07-14
申请号：US486605
申请日：1995-06-07
申请人： Richard J. Bucala , Helen Vlassara , Anthony Cerami
发明人： Richard J. Bucala , Helen Vlassara , Anthony Cerami
IPC分类号： G01N33/53 , A61K9/127 , A61K31/00 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/70 , A61K35/16 , A61K38/00 , A61K38/17 , A61K39/395 , A61K45/00 , A61P9/10 , A61P13/02 , A61P15/00 , A61P17/00 , A61P43/00 , G01N21/31 , G01N33/533 , G01N33/68 , G01N33/92 , C07H5/04
CPC分类号： G01N33/533 , A61K31/00 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/70 , A61K38/1709 , G01N33/6893 , G01N33/92 , G01N2800/042 , G01N2800/044 , G01N2800/323
摘要： The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as ME-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes and atherosclerosis. Diagnostic methods are contemplated, extending in utility from the detection of the onset and course of conditions in which variations in lipid oxidation, AGE-lipid levels, LDL levels, apolipoprotein levels, apolipoprotein receptor binding the like, may be measured, to drug discovery assays. Corresponding methods of treatment and pharmaceutical compositions are disclosed that are based on an active ingredient or ingredients that demonstrates the ability to modulate the levels of all of the foregoing markers of lipid oxidation.
摘要翻译：已经发现脂质和含脂质分子的体内氧化是通过这种脂质物质与还原糖如葡萄糖，高级糖基化终产物如ME-肽或形成晚期糖基化终产物的化合物的同时反应引发的，形成称为AGE-脂质的材料或颗粒。 AGE-脂质已经涉及老化过程，脂褐素异常形成和各种疾病状态如糖尿病和动脉粥样硬化。考虑到诊断方法，从检测可以测量脂质氧化，AGE-脂质水平，LDL水平，载脂蛋白水平，结合载脂蛋白受体等的药物发现测定。公开了相应的治疗方法和药物组合物，其基于表现出调节脂质氧化的所有前述标记物的水平的能力的活性成分或成分。

12. 发明授权

US5585344A Liver-derived receptors for advanced glycosylation endproducts and uses thereof 失效
标题翻译：用于晚期糖基化终产物的肝衍生受体及其用途
公开(公告)号：US5585344A
公开(公告)日：1996-12-17
申请号：US749438
申请日：1991-08-23
申请人： Helen Vlassara , Zhi Yang , Anthony Cerami
发明人： Helen Vlassara , Zhi Yang , Anthony Cerami
IPC分类号： A61K8/64 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/00 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K14/705 , C07K16/28 , G01N33/50 , G01N33/533 , G01N33/573 , G01N33/68 , A61K38/17
CPC分类号： G01N33/6893 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K39/0005 , A61K8/64 , A61Q19/08 , C07D405/14 , C07K14/705 , C07K16/28 , C07K16/2803 , G01N33/5091 , G01N33/533 , G01N33/573 , G01N33/68 , G01N33/6842 , G01N33/6887 , A61K2039/6081 , A61K38/00 , C07K2317/34 , C07K2317/77 , G01N2333/922
摘要： The present invention relates to receptors for advanced glycosylation endproducts derived from rat liver membranes, and that specifically comprise proteins determined to possess molecular masses of about 90 kD and 60 kD, respectively, as assessed by migration during SDS-PAGE. Partial N-terminal sequences have been determined and diagnostic and therapeutic agents, compositions and methods are proposed.
摘要翻译：本发明涉及来自大鼠肝膜的晚期糖基化终产物的受体，并且其特异性包括通过SDS-PAGE期间的迁移评估分别确定具有约90kD和60kD的分子量的蛋白质。已经确定了部分N-末端序列，并提出了诊断和治疗剂，组合物和方法。

13. 发明授权

US5962245A Methods for detecting the presence of advanced glycosylation endproducts 失效
标题翻译：检测高级糖基化终产物存在的方法
公开(公告)号：US5962245A
公开(公告)日：1999-10-05
申请号：US475055
申请日：1995-06-07
申请人： Yong Ming Li , Helen Vlassara , Anthony Cerami
发明人： Yong Ming Li , Helen Vlassara , Anthony Cerami
IPC分类号： A61K8/64 , A61K38/00 , A61K38/03 , A61K38/16 , A61K38/47 , A61Q11/00 , C07K14/79 , C12N9/36 , C12Q1/00 , C12Q1/34 , G01N33/573 , G01N33/66 , G01N33/68 , G01N33/566
CPC分类号： A61Q11/00 , A61K8/64 , C07K14/79 , G01N33/573 , G01N33/66 , G01N33/68 , G01N33/6842 , A61K38/00 , G01N2333/79 , G01N2333/924 , G01N2333/936
摘要： The present invention is directed to methods for detecting the presence of advanced glycosylation endproducts using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to diagnostic methods for diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
摘要翻译：本发明涉及使用意想不到的发现来检测高级糖基化终产物的存在的方法，某些抗菌蛋白，特别是溶菌酶和乳铁蛋白与高亲和力的晚期糖基化终产物（AGE）结合，并且该结合活性基本上是非竞争性的具有细菌碳水化合物与抗菌蛋白质的结合。因此，本发明涉及与增加水平的AGE相关的疾病和病症的诊断方法，通过使用具有与其相关联的分子的组合物，所述组分具有亲水环结构域，该结构域与AGE结合活性相关，以及包含这种结构域的组合物。本发明还涉及用于将AGEs分离离开样品的组合物和装置。

14. 发明授权

US5811075A Method and agents for removing advanced glycosylation endproducts 失效
公开(公告)号：US5811075A
公开(公告)日：1998-09-22
申请号：US487398
申请日：1995-06-07
申请人： Helen Vlassara , Michael Brownlee , Anthony Cerami
发明人： Helen Vlassara , Michael Brownlee , Anthony Cerami
IPC分类号： A61K8/43 , A61K8/44 , A61K31/155 , A61K39/00 , A61K51/12 , A61Q11/00 , A61Q19/08 , C07K16/28 , G01N33/573 , A61K49/00 , C12Q1/00
CPC分类号： A61K8/44 , A61K31/155 , A61K39/0005 , A61K51/1203 , A61K8/43 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/6842 , A61K2039/6081 , C07K2317/77 , G01N2333/922 , G01N2800/042
摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

15. 再颁专利

USRE35465E Method and agents for removing advanced glycosylation endproducts 失效
标题翻译：去除高级糖基化终产物的方法和试剂
公开(公告)号：USRE35465E
公开(公告)日：1997-02-25
申请号：US437064
申请日：1995-05-09
申请人： Helen Vlassara , Michael Brownlee , Anthony Cerami
发明人： Helen Vlassara , Michael Brownlee , Anthony Cerami
IPC分类号： A61K8/43 , A61K31/155 , A61K31/4178 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/68 , A61K31/415
CPC分类号： A61K8/43 , A61K31/155 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K39/0005 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/68 , G01N33/6842 , G01N33/6893 , A61K2039/6081 , G01N2333/922
摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.
摘要翻译：本发明涉及通过刺激动物的体内增加其对晚期糖基化终产物的识别和亲和力来抑制和治疗动物中蛋白质老化的方法和相关药剂。具体地说，该方法考虑到某些药物的施用，例如晚期糖基化终产物，结合载体的终产物，刺激吞噬细胞增加其对晚期糖基化终产物的活性的单核因子，以及这些材料的混合物，单独或联合与其他共刺激剂。定义了许多诊断和治疗应用，并且也考虑了药物组合物。

16. 发明授权

US4900747A Method and agents for removing advanced glycosylation endproducts 失效
标题翻译：去除高级糖基化终产物的方法和试剂
公开(公告)号：US4900747A
公开(公告)日：1990-02-13
申请号：US91534
申请日：1987-09-03
申请人： Helen Vlassara , Michael Brownlee , Anthony Cerami
发明人： Helen Vlassara , Michael Brownlee , Anthony Cerami
IPC分类号： A61K8/43 , A61K8/64 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/00 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K14/705 , C07K16/28 , G01N33/50 , G01N33/533 , G01N33/573 , G01N33/58 , G01N33/68
CPC分类号： G01N33/6893 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/43 , A61K8/64 , A61Q19/08 , C07D405/14 , C07K14/705 , C07K16/28 , C07K16/2803 , G01N33/5091 , G01N33/533 , G01N33/573 , G01N33/582 , G01N33/68 , G01N33/6842 , A61K2039/6081 , C07K2317/77 , G01N2333/922 , G01N2800/042
摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.
摘要翻译：本发明涉及通过刺激动物的体内增加其对晚期糖基化终产物的识别和亲和力来抑制和治疗动物中蛋白质老化的方法和相关药剂。具体地说，该方法考虑到某些药物的施用，例如晚期糖基化终产物，结合载体的终产物，刺激吞噬细胞增加其对晚期糖基化终产物的活性的单核因子，以及这些材料的混合物，单独或联合与其他共刺激剂。定义了许多诊断和治疗应用，并且也考虑了药物组合物。

17. 发明授权

US5766856A Diagnostic method for evaluating advanced glycosylation endproducts using MAC-2 receptor 失效
标题翻译：用MAC-2受体评估晚期糖基化终产物的诊断方法
公开(公告)号：US5766856A
公开(公告)日：1998-06-16
申请号：US234817
申请日：1994-04-28
申请人： Farhad Imani , Helen Vlassara , Anthony Cerami
发明人： Farhad Imani , Helen Vlassara , Anthony Cerami
IPC分类号： A61K31/155 , A61K38/00 , A61Q11/00 , C07K14/47 , C07K16/28 , G01N33/566 , G01N33/573 , G01N33/53 , G01N33/68
CPC分类号： A61K31/155 , C07K14/4726 , C07K16/28 , G01N33/566 , G01N33/573 , A61K38/00 , G01N2333/922 , G01N2800/042 , Y10S436/811
摘要： Soluble and membrane associated forms of Mac-2 (also termed Carbohydrate Binding Protein �CBP!-35 and L-34) recognizes and binds to Advanced Glycosylation Endproducts (AGEs) with higher affinity than it binds carbohydrates, such as its "natural" ligand, galactose. The level of soluble Mac-2 in plasma or serum provides a prognostic indicator of the susceptibility of an individual to AGE complications. Thus, the present invention includes various therapeutic and diagnostic utilities predicated on the identification and activities of Mac-2 for binding AGEs. Pharmaceutical compositions of the invention comprise an effective amount of Mac-2 admixed with a pharmaceutically acceptable carrier. Diagnostic utilities include assays such as immunoassays for the presence and amount of Mac-2 in a biological sample, e.g., serum or plasma. Such assays can be performed with labeled receptors, antibodies, ligands and other binding partners of Mac-2. The invention further provides screening assays to evaluate new drugs by their ability to promote or inhibit Mac-2 production or activity, as desired. The above assays can be used to detect the presence or activity of invasive stimuli, pathology or injury, the presence or absence of which may affect the structure or function of specific organs. In a specific embodiment, the level of soluble Mac-2 varies between different populations of diabetics, and between diabetics and normals.
摘要翻译： Mac-2（也称为碳水化合物结合蛋白[CBP] -35和L-34）的可溶性和膜相关形式识别和结合具有比其结合碳水化合物更高亲和力的高级糖基化终产物（AGE），例如其“天然”配体，半乳糖。血浆或血清中可溶性Mac-2的水平提供个体对AGE并发症易感性的预后指标。因此，本发明包括各种用于结合AGEs的Mac-2的鉴定和活性的治疗和诊断实用性。本发明的药物组合物包含与药学上可接受的载体混合的有效量的Mac-2。诊断实用程序包括测定，例如生物样品中例如血清或血浆中Mac-2的存在和量的免疫测定。可用标记的受体，抗体，配体和Mac-2的其他结合配偶体进行此类测定。本发明进一步提供了筛选测定法，以根据需要通过其促进或抑制Mac-2生产或活性的能力评价新药物。上述测定可用于检测侵袭性刺激，病理或损伤的存在或活性，其存在或不存在可能影响特定器官的结构或功能。在一个具体实施方案中，可溶性Mac-2的水平在不同糖尿病患者之间以及糖尿病患者和正常人之间变化。

18. 发明授权

US5891341A Compositions and devices for partitioning advanced glycosylation endproducts, and methods of their use 失效
标题翻译：用于分配高级糖基化终产物的组合物和装置及其使用方法
公开(公告)号：US5891341A
公开(公告)日：1999-04-06
申请号：US628380
申请日：1996-04-05
申请人： Yong Ming Li , Helen Vlassara , Anthony Cerami
发明人： Yong Ming Li , Helen Vlassara , Anthony Cerami
IPC分类号： G01N33/566 , A61K8/00 , A61K8/64 , A61K9/06 , A61K9/22 , A61K38/00 , A61K38/16 , A61K38/40 , A61K38/46 , A61K49/00 , A61P13/02 , A61P15/00 , A61P31/04 , A61Q11/00 , A61Q17/04 , B01D11/04 , C07K7/08 , C07K14/79 , C12N9/36 , G01N33/68 , G01N35/00 , A01N1/02
CPC分类号： A61Q11/00 , A61K8/64 , C07K14/79 , C12N9/2462 , G01N33/68 , G01N33/6842 , A61K38/00 , B01L2400/0406 , G01N2333/79 , G01N2333/924 , G01N2333/936 , G01N35/00069 , Y10S530/811 , Y10S530/812 , Y10S530/815
摘要： The present invention is directed to compositions and devices based upon the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions and devices having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
摘要翻译：本发明涉及基于意想不到的发现的某些抗菌蛋白质，特别是溶菌酶和乳铁蛋白与高亲和力的晚期糖基化终产物（AGE）结合的组合物和装置，并且该结合活性与细菌碳水化合物的结合基本上是非竞争性的对抗菌蛋白质。因此，本发明涉及通过使用与其相关联的具有亲水环结构域的分子的组合物和装置来治疗与增加的AGE水平相关的疾病和病症的方法，该结构域与AGE结合活性相关，以及包含这种域。本发明还涉及用于将AGEs分离离开样品的组合物和装置。

19. 发明授权

US4371374A Monitoring metabolic control in diabetic patients by measuring glycosylated amino acids and peptides in urine 失效
标题翻译：通过测量尿中的糖基化氨基酸和肽来监测糖尿病患者的代谢控制
公开(公告)号：US4371374A
公开(公告)日：1983-02-01
申请号：US207471
申请日：1980-11-17
申请人： Anthony Cerami , Michael Brownlee , Helen Vlassara
发明人： Anthony Cerami , Michael Brownlee , Helen Vlassara
IPC分类号： G01N33/66 , G01N33/68 , G01N33/50
CPC分类号： G01N33/6842 , G01N33/66 , G01N33/68
摘要： A method of monitoring metabolic control in a diabetes patient comprising measuring the amount of non-enzymatic glycosylated amino acids and peptides in urine of the patient; a method of measurement and a test kit for the measurement are disclosed.
摘要翻译：一种监测糖尿病患者代谢控制的方法，包括测量患者尿液中非酶糖基化氨基酸和肽的量; 公开了一种用于测量的测量方法和测试套件。

20. 发明授权

US5861238A Methods for partitioning advanced glycosylation endproducts 失效
标题翻译：分配高级糖基化终产物的方法
公开(公告)号：US5861238A
公开(公告)日：1999-01-19
申请号：US487058
申请日：1995-06-07
申请人： Yong Ming Li , Helen Vlassara , Anthony Cerami
发明人： Yong Ming Li , Helen Vlassara , Anthony Cerami
IPC分类号： A61K8/64 , A61K38/00 , A61K38/03 , A61K38/16 , A61K38/47 , A61Q11/00 , C07K14/79 , C12N9/36 , C12Q1/00 , C12Q1/34 , G01N33/573 , G01N33/66 , G01N33/68 , A01N1/02
CPC分类号： A61Q11/00 , A61K8/64 , C07K14/79 , G01N33/573 , G01N33/66 , G01N33/68 , G01N33/6842 , A61K38/00 , G01N2333/79 , G01N2333/924 , G01N2333/936
摘要： The present invention is directed to methods for partitioning advanced glycosylation endproducts out of a biological sample using the unexpected discovery that certain antibacterial proteins, in particular lysozyme and particular fragments thereof, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to therapeutic methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain to remove AGEs from biological material. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
摘要翻译：本发明涉及使用意想不到的发现，即某些抗菌蛋白，特别是溶菌酶及其特定片段以高亲和力结合晚期糖基化终产物（AGE）而将生物样品中的高级糖基化终产物分配的方法，并且该结合活性与细菌碳水化合物与抗菌蛋白的结合基本上是非竞争性的。因此，本发明涉及用于治疗与增加水平的AGE相关的疾病和病症的治疗方法，通过使用具有与其相关联的具有亲水环结构域的分子的组合物，该结构域与AGE结合活性相关，以及包含这种结构域的组合物从生物材料中去除AGEs。本发明还涉及用于将AGEs分离离开样品的组合物和装置。

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