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1. 发明公开

US20240165131A1 TREATING AND PREVENTING DISEASE WITH TMA AND TMAO LOWERING AGENTS 审中-公开
公开(公告)号：US20240165131A1
公开(公告)日：2024-05-23
申请号：US18426704
申请日：2024-01-30
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen
IPC分类号： A61K31/616 , A61K31/00 , A61K31/13 , A61K31/133 , A61K31/205 , A61K31/409 , A61K31/4164 , A61K31/43 , A61K31/4365 , A61K31/4709 , A61K31/496 , A61K31/519 , A61K31/675 , A61K33/44 , A61P9/00 , A61P13/12 , G01N33/49
CPC分类号： A61K31/616 , A61K31/00 , A61K31/13 , A61K31/133 , A61K31/205 , A61K31/409 , A61K31/4164 , A61K31/43 , A61K31/4365 , A61K31/4709 , A61K31/496 , A61K31/519 , A61K31/675 , A61K33/44 , A61P9/00 , A61P13/12 , G01N33/492 , G01N2800/32 , G01N2800/34 , G01N2800/52
摘要： Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

2. 发明授权

US11835503B2 TMA-formation inhibitor treatment for elevated TMA-containing compound diseases 有权
公开(公告)号：US11835503B2
公开(公告)日：2023-12-05
申请号：US17234229
申请日：2021-04-19
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen , Zeneng Wang , Bruce S. Levison
IPC分类号： G01N30/88 , C12Q1/18 , G01N33/68 , A61K31/4164 , A61K31/43 , A61K31/7036 , G01N30/72 , C12Q1/02 , A61K31/496
CPC分类号： G01N30/88 , A61K31/4164 , A61K31/43 , A61K31/496 , A61K31/7036 , C12Q1/025 , C12Q1/18 , G01N33/6893 , G01N30/7233 , G01N2030/8813 , G01N2030/8822 , G01N2800/04 , G01N2800/042 , G01N2800/044 , G01N2800/32 , G01N2800/323 , G01N2800/50 , G01N2800/52
摘要： The present invention provides markers and methods for determining whether a subject, particularly a human subject, has or is at risk of developing, a disease such as cardiovascular disease, diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD (Nonalcoholic Fatty Liver Disease) or NASH (Nonalcoholic Steatohepatitis) (e.g., within the ensuing year, two years, and/or three years). The present application also relates to the use of such markers and methods for monitoring the status of such diseases in a subject or the effects of therapeutic agents on subjects with such diseases.

3. 发明申请

US20220163540A1 DETECTION OF GLUCURONIDATED AND 3-BROMOTYROSINE 有权
公开(公告)号：US20220163540A1
公开(公告)日：2022-05-26
申请号：US17668261
申请日：2022-02-09
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen , Zeneng Wang
IPC分类号： G01N33/68
摘要： The present invention relates to methods, kits, and compositions for: i) detecting the level of 3-bromotyrosine in a sample that has been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine, and/or ii) detecting the level of 4-O-glucuronide-3-bromotyrosine, and/or the combined level of both 4-O-glucuronide-3-bromotyrosine and 3-bromotyrosine, in a sample that has not been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine. In certain embodiments, such detected levels are used to: i) identify the presence, severity, or risk of an eosinophilic disorder (e.g., asthma or a TH2-high eosinophilic disorder); ii) identify therapy effective for treating asthma or an eosinophilic disorder; or iii) identify patients suitable for treatment with therapeutic agents targeted to asthma or an eosinophilic disorder.

4. 发明授权

US10551372B2 Trimethylamine compounds as risk predictors of cardiovascular disease 有权
公开(公告)号：US10551372B2
公开(公告)日：2020-02-04
申请号：US15234050
申请日：2016-08-11
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen , Zeneng Wang , Bruce S. Levison
IPC分类号： G01N24/00 , G01N33/49 , G01N33/92 , G01N33/493 , H01J49/00
摘要： Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.

5. 发明申请

US20190038642A1 TREATING AND PREVENTING DISEASE WITH TMA AND TMAO LOWERING AGENTS 审中-公开
公开(公告)号：US20190038642A1
公开(公告)日：2019-02-07
申请号：US16159102
申请日：2018-10-12
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen
IPC分类号： A61K31/616 , A61K31/00 , G01N33/49 , A61K31/519 , A61K31/496 , A61K31/13 , A61K31/675 , A61P13/12 , A61K31/4365 , A61P9/00 , A61K31/43 , A61K31/4709 , A61K31/4164 , A61K31/205 , A61K31/133
摘要： Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

6. 发明申请

US20170266208A1 TREATING AND PREVENTING DISEASE WITH TMA AND TMAO LOWERING AGENTS 审中-公开
公开(公告)号：US20170266208A1
公开(公告)日：2017-09-21
申请号：US15610145
申请日：2017-05-31
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen
IPC分类号： A61K31/616 , A61K31/00 , G01N33/49
CPC分类号： A61K31/616 , A61K31/00 , A61K31/13 , A61K31/133 , A61K31/205 , A61K31/4164 , A61K31/43 , A61K31/4365 , A61K31/4709 , A61K31/496 , A61K31/519 , A61K31/675 , A61P9/00 , A61P13/12 , G01N33/492 , G01N2800/32 , G01N2800/34 , G01N2800/52
摘要： Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

7. 发明授权

US09694020B2 Treating and preventing disease with TMA and TMAO lowering agents 有权
公开(公告)号：US09694020B2
公开(公告)日：2017-07-04
申请号：US14866398
申请日：2015-09-25
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen
IPC分类号： A61K31/00 , A61K31/616 , G01N33/49
CPC分类号： A61K31/616 , A61K31/00 , A61K31/13 , A61K31/133 , A61K31/205 , A61K31/4164 , A61K31/43 , A61K31/4365 , A61K31/4709 , A61K31/496 , A61K31/519 , A61K31/675 , A61P9/00 , A61P13/12 , G01N33/492 , G01N2800/32 , G01N2800/34 , G01N2800/52
摘要： Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

8. 发明申请

US20160349236A1 TRIMETHYLAMINE COMPOUNDS AS RISK PREDICTORS OF CARDIOVASCULAR DISEASE 审中-公开
标题翻译：作为心血管疾病风险预防剂的三甲胺化合物
公开(公告)号：US20160349236A1
公开(公告)日：2016-12-01
申请号：US15234050
申请日：2016-08-11
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen , Zeneng Wang , Bruce S. Levison
IPC分类号： G01N33/49 , H01J49/00 , G01N33/493
摘要： Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.
摘要翻译：提供测试受试者患有或发展心血管疾病风险的方法。所述方法包括使用分析装置来确定从受试者获得的生物样品中胆碱相关的含三甲胺的化合物如三甲胺N-氧化物，胆碱或甜菜碱的含量，并比较胆碱相关的含三甲胺的化合物在受试者的生物样本中达到对照值。如果胆碱相关的含三甲胺的化合物的含量高于对照值，则测试对象具有心血管疾病的风险的特征就更高。还提供了鉴定患有动脉粥样硬化性心血管疾病并发症风险的受试者的方法，以及使用胆碱相关的含三甲胺化合物水平的心血管疾病患者评价心血管治疗剂的功效的方法。

9. 发明申请

US20160089387A1 TREATING AND PREVENTING DISEASE WITH TMA AND TMAO LOWERING AGENTS 有权
标题翻译：用TMA和TMAO降低剂治疗和预防疾病
公开(公告)号：US20160089387A1
公开(公告)日：2016-03-31
申请号：US14866398
申请日：2015-09-25
申请人： The Cleveland Clinic Foundation
发明人： Stanley L. Hazen
IPC分类号： A61K31/616 , G01N33/49
CPC分类号： A61K31/616 , A61K31/00 , A61K31/13 , A61K31/133 , A61K31/205 , A61K31/4164 , A61K31/43 , A61K31/4365 , A61K31/4709 , A61K31/496 , A61K31/519 , A61K31/675 , A61P9/00 , A61P13/12 , G01N33/492 , G01N2800/32 , G01N2800/34 , G01N2800/52
摘要： Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.
摘要翻译：本文提供的是用于减轻受试者中三甲胺（TMA）或三甲胺正氧化物（TMAO）的产生的药物治疗诸如肾和/或心血管疾病的疾病的组合物，系统和方法。在某些实施方案中，试剂是：i）3,3-二甲基-1-丁醇（DMB）或DMB衍生物或相关化合物，ii）乙酰水杨酸或其衍生物（例如，用于递送至结肠的肠溶衣和 /或盲肠）; iii）黄素单加氧酶3（FMO3）抑制剂; iv）肠道TMA裂解酶抑制剂; v）抗生素或抗微生物剂; vi）益生菌或益生元; vii）抗血小板药; 或viii）TMA和/或TMAO螯合剂。

10. 发明授权

US09051393B2 Oxidant resistant apolipoprotein A-1 and mimetic peptides 有权
标题翻译：抗氧化剂载脂蛋白A-1和模拟肽
公开(公告)号：US09051393B2
公开(公告)日：2015-06-09
申请号：US13967046
申请日：2013-08-14
申请人： The Cleveland Clinic Foundation
发明人： Jonathan D. Smith , Stanley L. Hazen
IPC分类号： C07K14/775 , A61K31/22 , A61K31/366 , A61K31/40 , A61K38/17 , A61K38/00
CPC分类号： C07K14/775 , A61K31/22 , A61K31/366 , A61K31/40 , A61K38/00 , A61K38/1709
摘要： A method of ameliorating one or more symptoms of an inflammatory condition in a subject comprises the step of administering to the subject a therapeutically effective amount of a polypeptide that is capable promoting cholesterol efflux from lipid loaded cells, the polypeptide consisting of the amino acid sequence of SEQ ID NO:1, in which each X in SEQ ID NO:1 is a phenylalanine amino acid.
摘要翻译：一种改善受试者中一种或多种炎症状态症状的方法包括向受试者施用治疗有效量的能够促进胆固醇从负载脂质的细胞中流出的多肽的步骤，所述多肽由 SEQ ID NO：1，其中SEQ ID NO：1中的每个X是苯丙氨酸氨基酸。

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