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1. 发明申请

WO2008089485A2 CARBOXYETHYLPYRROLE COMPOUNDS AND METHODS OF THEIR PRODUCTION 审中-公开
标题翻译：羧甲基纤维素化合物及其生产方法
公开(公告)号：WO2008089485A2
公开(公告)日：2008-07-24
申请号：PCT/US2008/051685
申请日：2008-01-22
申请人： THE CLEVELAND CLINIC FOUNDATION , SALOMON, Robert, G. , CRABB, John, W. , LU, Liang , GU, Xiaorong , CHOI, Jaewoo
发明人： SALOMON, Robert, G. , CRABB, John, W. , LU, Liang , GU, Xiaorong , CHOI, Jaewoo
IPC分类号： G01N33/53
CPC分类号： G01N33/531 , C07C67/313 , C07C69/716 , C07C2603/18 , C07D207/337 , C07D495/04
摘要： Provided herein are a 9-fluorenylmethyl (Fm) ester of 4,7-dioxoheptanoic acid (DOHA) (DOHA-Fm) compound that is useful for the preparation of 2-(ω-carboxyethyl)pyrrole (CEP)-carrier derivatives, as well as methods of preparing same. Also provided are isolated CEP-protein derivatives, isolated phosphatidylethanolamine (PE)-CEP derivatives, isolated biotinylated CEP derivative, as well as methods of preparing same. Also included is a CEP- Fm modified lysine and a method of preparing a CEP-carrier derivatives using the CEP-Fm modified lysine.
摘要翻译：本文提供了可用于制备2-（α-羧乙基）吡咯（CEP） - 载体衍生物的4,7-二氧代庚酸（DOHA）（DOHA-Fm）化合物的9-芴基甲基（Fm）以及制备方法。还提供了分离的CEP-蛋白衍生物，分离的磷脂酰乙醇胺（PE）-CEP衍生物，分离的生物素化CEP衍生物，以及其制备方法。还包括CEP-Fm修饰的赖氨酸和使用CEP-Fm修饰的赖氨酸制备CEP-载体衍生物的方法。

2. 发明申请

WO2008013797A8 COMPOSITIONS AND METHODS FOR MACULAR DEGENERATION 审中-公开
标题翻译：麦芽糖变性的组合物和方法
公开(公告)号：WO2008013797A8
公开(公告)日：2008-05-02
申请号：PCT/US2007016619
申请日：2007-07-23
申请人： CLEVELAND CLINIC FOUNDATION , UNIV CASE WESTERN RESERVE , CRABB JOHN W , SALOMON ROBERT G , ANAND-APTE BELA , EBRAHEM QUTEBA , REGANATHAN KUTRALANATHAN
发明人： CRABB JOHN W , SALOMON ROBERT G , ANAND-APTE BELA , EBRAHEM QUTEBA , REGANATHAN KUTRALANATHAN
IPC分类号： A61K39/395
CPC分类号： C07K16/18 , A61K2039/505 , C07K16/44 , C07K2317/622 , C07K2317/76
摘要： The present invention pertains to methods of inhibiting angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits one or more CEP protein adducts wherein the angiogenesis is the result of oxidative peptide modification of polyunsaturated fatty acids (PUFA) in the individual, and administration of the agent inhibits angiogenesis in the individual. In one embodiment, the invention is directed to methods of inhibiting ocular angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the.agent inhibits ocular angiogenesis in the individual. In another embodiment, the invention is directed to methods of inhibiting choroidal neovascularization in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the agent inhibits choroidal neovascularization in the individual.
摘要翻译：本发明涉及在有需要的个体中抑制血管发生的方法，包括向个体施用抑制一种或多种CEP蛋白加合物的药剂，其中血管生成是个体中多不饱和脂肪酸（PUFA）的氧化肽修饰的结果，并且该药剂的给药抑制个体的血管发生。在一个实施方案中，本发明涉及在有需要的个体中抑制眼血管发生的方法，其包括向个体施用抑制一种或多种CEP蛋白加合物的血管生成活性的药剂，其中所述药物的给药在个人。在另一个实施方案中，本发明涉及在有需要的个体中抑制脉络膜新生血管形成的方法，包括向个体施用抑制一种或多种CEP蛋白加合物的血管生成活性的试剂，其中所述试剂的施用抑制个体中的脉络膜新生血管形成。

3. 发明申请

WO2007095250A3 COMPOSITIONS AND METHODS FOR INHIBITING OPTIC NERVE DAMAGE 审中-公开
标题翻译：用于抑制视神经损伤的组合物和方法
公开(公告)号：WO2007095250A3
公开(公告)日：2007-12-27
申请号：PCT/US2007003834
申请日：2007-02-12
申请人： CLEVELAND CLINIC FOUNDATION , BHATTACHARYA SANJOY K , CRABB JOHN W
发明人： BHATTACHARYA SANJOY K , CRABB JOHN W
IPC分类号： A61K31/00 , A61K31/713 , A61P27/00 , C12N15/113
CPC分类号： C12N15/1137 , C12N2310/14
摘要： Provided herein is a method of inhibiting optic nerve damage in an individual in need thereof, comprising administering to the individual an agent that inhibits peptidyl arginine deiminase 2 (PAD2). In a particular embodiment, the present invention is directed to a method of inhibiting glaucomatous optic nerve damage in an individual in need thereof, comprising administering to the individual an agent that inhibits peptidyl arginine deiminase 2 (PAD2). The present invention is also directed to a method of treating glaucoma {e.g., primary open angle glaucoma) in an individual in need thereof, comprising administering to the individual an agent that inhibits (e.g., specifically inhibits) peptidyl arginine deiminase 2 (PAD2).
摘要翻译：本文提供了抑制有需要的个体的视神经损伤的方法，其包括向个体施用抑制肽基精氨酸脱亚氨酶2（PAD2）的药剂。在一个具体的实施方案中，本发明涉及抑制有需要的个体的青光眼性视神经损害的方法，其包括向个体施用抑制肽基精氨酸脱亚胺酶2（PAD2）的药剂。本发明还涉及在有需要的个体中治疗青光眼（例如原发性开角型青光眼）的方法，其包括向个体施用抑制（例如，特异性抑制）肽基精氨酸脱亚氨酶2（PAD2）的试剂。

4. 发明申请

WO2007095250A2 COMPOSITIONS AND METHODS FOR INHIBITING OPTIC NERVE DAMAGE 审中-公开
标题翻译：用于抑制眼神经损伤的组合物和方法
公开(公告)号：WO2007095250A2
公开(公告)日：2007-08-23
申请号：PCT/US2007/003834
申请日：2007-02-12
申请人： THE CLEVELAND CLINIC FOUNDATION , BHATTACHARYA, Sanjoy, K. , CRABB, John, W.
发明人： BHATTACHARYA, Sanjoy, K. , CRABB, John, W.
IPC分类号： C12N15/113
CPC分类号： C12N15/1137 , C12N2310/14
摘要： Provided herein is a method of inhibiting optic nerve damage in an individual in need thereof, comprising administering to the individual an agent that inhibits peptidyl arginine deiminase 2 (PAD2). In a particular embodiment, the present invention is directed to a method of inhibiting glaucomatous optic nerve damage in an individual in need thereof, comprising administering to the individual an agent that inhibits peptidyl arginine deiminase 2 (PAD2). The present invention is also directed to a method of treating glaucoma {e.g., primary open angle glaucoma) in an individual in need thereof, comprising administering to the individual an agent that inhibits (e.g., specifically inhibits) peptidyl arginine deiminase 2 (PAD2).
摘要翻译：本文提供了抑制有需要的个体的视神经损伤的方法，其包括向个体施用抑制肽基精氨酸脱亚氨酶2（PAD2）的药剂。在一个具体实施方案中，本发明涉及在有需要的个体中抑制青光眼性视神经损伤的方法，其包括向个体施用抑制肽基精氨酸脱亚氨酶2（PAD2）的药剂。本发明还涉及在有需要的个体中治疗青光眼（例如原发性开角型青光眼）的方法，其包括向个体施用抑制（例如，特异性抑制）肽基精氨酸脱亚氨酶2（PAD2）的药剂。

5. 发明申请

WO2008089487A2 CARBOXYETHYLPYRROLE COMPOUNDS AND METHODS OF THEIR PRODUCTION 审中-公开
标题翻译：羧甲基纤维素化合物及其生产方法
公开(公告)号：WO2008089487A2
公开(公告)日：2008-07-24
申请号：PCT/US2008/051689
申请日：2008-01-22
申请人： THE CLEVELAND CLINIC FOUNDATION , SALOMON, Robert, G. , CRABB, John, W. , JAFFE, Keeve, Daryl , LU, Liang , GU, Xiaorong , CHOI, Jaewoo
发明人： SALOMON, Robert, G. , CRABB, John, W. , JAFFE, Keeve, Daryl , LU, Liang , GU, Xiaorong , CHOI, Jaewoo
IPC分类号： G01N33/53
CPC分类号： C07D495/04 , C07D207/337 , G01N33/531
摘要： The present invention involves methods of anchoring carboxyethylpyrrole (CEP) haptens to carriers via various linkers. Provided herein are 9-fluorenylmethyl (Fm) masked-CEP-linker acids and Fm masked-CEP-linker esters that are useful for the preparation of CEP-linker- carrier derivatives. Also provided are methods of preparing said Fm masked-CEP-linker acids, Fm masked-CEP-linker esters and CEP-linker-carrier derivatives.
摘要翻译：本发明涉及通过各种接头将羧乙基吡咯（CEP）半抗原锚定于载体的方法。本文提供了可用于制备CEP-接头 - 载体衍生物的9-芴基甲基（Fm）掩蔽的CEP-连接体酸和Fm掩蔽的CEP-接头酯。还提供了制备所述Fm掩蔽的CEP-连接体酸，Fm掩蔽的CEP-接头酯和CEP-接头 - 载体衍生物的方法。

6. 发明申请

WO2010132459A2 BIOMARKERS FOR ASSESSMENT OF AGE-RELATED MACULAR DEGENERATION 审中-公开
标题翻译：生物标志物评估与年龄有关的恶化程度
公开(公告)号：WO2010132459A2
公开(公告)日：2010-11-18
申请号：PCT/US2010034398
申请日：2010-05-11
申请人： CLEVELAND CLINIC FOUNDATION , UNIV CASE WESTERN RESERVE , CRABB JOHN W , NAGARAJ RAM H , GU JIAYIN , NI JIAQIAN , YUAN XIANGLIN
发明人： CRABB JOHN W , NAGARAJ RAM H , GU JIAYIN , NI JIAQIAN , YUAN XIANGLIN
IPC分类号： G01N33/68 , G01N33/15 , G01N33/53
CPC分类号： G01N33/6893 , G01N2500/00 , G01N2800/16 , G01N2800/164 , G01N2800/50
摘要： Biomarkers that can be used to assess the risk that a subject will develop age-related macular degeneration (AMD) and/or to assess the severity of AMD in the subject are described. The biomarkers are also useful in clinical trials to monitor the effect of a treatment and in pre-clinical trials to screen candidate therapies. The biomarkers can include carboxyethylpyrrole (CEP) adducts, carboxymethyllysine (CML), and pentosidine and be measured individually and in various combinations.
摘要翻译：描述了可用于评估受试者将发展年龄相关性黄斑变性（AMD）和/或评估受试者中AMD严重程度的风险的生物标志物。生物标志物也可用于临床试验，以监测治疗效果和临床前临床试验来筛选候选治疗。生物标志物可以包括羧乙基吡咯（CEP）加成物，羧甲基赖氨酸（CML）和戊糖氨酸，并且可以单独测量和以各种组合进行测量。

7. 发明申请

WO2008089485A3 CARBOXYETHYLPYRROLE COMPOUNDS AND METHODS OF THEIR PRODUCTION 审中-公开
标题翻译：羧乙基吡咯化合物及其生产方法
公开(公告)号：WO2008089485A3
公开(公告)日：2008-09-04
申请号：PCT/US2008051685
申请日：2008-01-22
申请人： CLEVELAND CLINIC FOUNDATION , SALOMON ROBERT G , CRABB JOHN W , LU LIANG , GU XIAORONG , CHOI JAEWOO
发明人： SALOMON ROBERT G , CRABB JOHN W , LU LIANG , GU XIAORONG , CHOI JAEWOO
IPC分类号： G01N33/53 , C07D207/10 , C07D207/50
CPC分类号： G01N33/531 , C07C67/313 , C07C69/716 , C07C2603/18 , C07D207/337 , C07D495/04
摘要： Provided herein are a 9-fluorenylmethyl (Fm) ester of 4,7-dioxoheptanoic acid (DOHA) (DOHA-Fm) compound that is useful for the preparation of 2-(?-carboxyethyl)pyrrole (CEP)-carrier derivatives, as well as methods of preparing same. Also provided are isolated CEP-protein derivatives, isolated phosphatidylethanolamine (PE)-CEP derivatives, isolated biotinylated CEP derivative, as well as methods of preparing same. Also included is a CEP- Fm modified lysine and a method of preparing a CEP-carrier derivatives using the CEP-Fm modified lysine.
摘要翻译：本文提供可用于制备2-（α-羧乙基）吡咯（CEP） - 载体衍生物的4,7-二氧代庚酸（DOHA）（DOHA-Fm）化合物的9-芴基甲基（Fm）以及制备它的方法。还提供了分离的CEP-蛋白质衍生物，分离的磷脂酰乙醇胺（PE）-CEP衍生物，分离的生物素化的CEP衍生物，以及制备它们的方法。还包括CEP-Fm修饰的赖氨酸和使用CEP-Fm修饰的赖氨酸制备CEP-载体衍生物的方法。

8. 发明申请

WO2008013797A3 COMPOSITIONS AND METHODS FOR MACULAR DEGENERATION 审中-公开
标题翻译：黄斑变性的组合物和方法
公开(公告)号：WO2008013797A3
公开(公告)日：2008-03-13
申请号：PCT/US2007016619
申请日：2007-07-23
申请人： CLEVELAND CLINIC FOUNDATION , CRABB JOHN W , SALOMON ROBERT G , ANAND-APTE BELA , EBRAHEM QUTEBA , REGANATHAN KUTRALANATHAN
发明人： CRABB JOHN W , SALOMON ROBERT G , ANAND-APTE BELA , EBRAHEM QUTEBA , REGANATHAN KUTRALANATHAN
IPC分类号： A61K39/395
CPC分类号： C07K16/18 , A61K2039/505 , C07K16/44 , C07K2317/622 , C07K2317/76
摘要： The present invention pertains to methods of inhibiting angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits one or more CEP protein adducts wherein the angiogenesis is the result of oxidative peptide modification of polyunsaturated fatty acids (PUFA) in the individual, and administration of the agent inhibits angiogenesis in the individual. In one embodiment, the invention is directed to methods of inhibiting ocular angiogenesis in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the.agent inhibits ocular angiogenesis in the individual. In another embodiment, the invention is directed to methods of inhibiting choroidal neovascularization in an individual in need thereof comprising administering to the individual an agent that inhibits the angiogenic activity of one or more CEP protein adducts wherein administration of the agent inhibits choroidal neovascularization in the individual.
摘要翻译：本发明涉及抑制有需要的个体血管生成的方法，其包括向个体施用抑制一种或多种CEP蛋白加合物的试剂，其中血管生成是个体中多不饱和脂肪酸（PUFA）的氧化肽修饰的结果并且该药剂的施用抑制个体中的血管生成。在一个实施方案中，本发明涉及抑制有需要的个体的眼血管生成的方法，其包括向个体施用抑制一种或多种CEP蛋白加合物的血管生成活性的试剂，其中所述试剂的施用抑制个人。在另一个实施方案中，本发明涉及抑制有需要的个体的脉络膜新血管生成的方法，其包括向个体施用抑制一种或多种CEP蛋白加合物的血管生成活性的试剂，其中所述试剂的施用抑制个体中的脉络膜新血管生成。

9. 发明申请

WO2010132459A3 BIOMARKERS FOR ASSESSMENT OF AGE-RELATED MACULAR DEGENERATION 审中-公开
公开(公告)号：WO2010132459A3
公开(公告)日：2010-11-18
申请号：PCT/US2010/034398
申请日：2010-05-11
申请人： CLEVELAND CLINIC FOUNDATION , CASE WESTERN RESERVE UNIVERSITY , CRABB, John W. , NAGARAJ, Ram H. , GU, Jiayin , NI, Jiaqian , YUAN, Xianglin
发明人： CRABB, John W. , NAGARAJ, Ram H. , GU, Jiayin , NI, Jiaqian , YUAN, Xianglin
IPC分类号： G01N33/68 , G01N33/53 , G01N33/15
摘要： Biomarkers that can be used to assess the risk that a subject will develop age-related macular degeneration (AMD) and/or to assess the severity of AMD in the subject are described. The biomarkers are also useful in clinical trials to monitor the effect of a treatment and in pre-clinical trials to screen candidate therapies. The biomarkers can include carboxyethylpyrrole (CEP) adducts, carboxymethyllysine (CML), and pentosidine and be measured individually and in various combinations.

10. 发明申请

WO2008089487A3 CARBOXYETHYLPYRROLE COMPOUNDS AND METHODS OF THEIR PRODUCTION 审中-公开
标题翻译：羧乙基吡咯化合物及其生产方法
公开(公告)号：WO2008089487A3
公开(公告)日：2008-09-18
申请号：PCT/US2008051689
申请日：2008-01-22
申请人： CLEVELAND CLINIC FOUNDATION , SALOMON ROBERT G , CRABB JOHN W , JAFFE KEEVE DARYL , LU LIANG , GU XIAORONG , CHOI JAEWOO
发明人： SALOMON ROBERT G , CRABB JOHN W , JAFFE KEEVE DARYL , LU LIANG , GU XIAORONG , CHOI JAEWOO
IPC分类号： G01N33/53 , C07D207/10 , C07D207/50
CPC分类号： C07D495/04 , C07D207/337 , G01N33/531
摘要： The present invention involves methods of anchoring carboxyethylpyrrole (CEP) haptens to carriers via various linkers. Provided herein are 9-fluorenylmethyl (Fm) masked-CEP-linker acids and Fm masked-CEP-linker esters that are useful for the preparation of CEP-linker- carrier derivatives. Also provided are methods of preparing said Fm masked-CEP-linker acids, Fm masked-CEP-linker esters and CEP-linker-carrier derivatives.
摘要翻译：本发明涉及通过各种连接子将羧乙基吡咯（CEP）半抗原锚定到载体上的方法。本文提供了可用于制备CEP-连接体 - 载体衍生物的9-芴基甲基（Fm）掩蔽CEP-连接体酸和Fm掩蔽CEP连接体酯。还提供了制备所述Fm掩蔽的CEP连接子酸，Fm掩蔽的CEP连接子酯和CEP连接子载体衍生物的方法。

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