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1. 发明授权

US6025401A Method and agents for inhibiting protein aging 失效
标题翻译：抑制蛋白质老化的方法和试剂
公开(公告)号：US6025401A
公开(公告)日：2000-02-15
申请号：US62354
申请日：1998-04-17
申请人： Anthony Cerami , Yousef Al Abed , Richard J. Bucala , Peter C. Ulrich
发明人： Anthony Cerami , Yousef Al Abed , Richard J. Bucala , Peter C. Ulrich
IPC分类号： A61K31/045 , A61K31/11
CPC分类号： G01N33/6842
摘要： The present invention relates to compositions and methods for inhibiting the aging of amino-containing amino acid, peptides, proteins and biomolecules. Accordingly, a composition is disclosed which comprises an agent or compound capable of reacting with the glycosyl-amino moiety of the early glycosylation product (also known as the Amadori product or the Heyns product) formed by the reaction of glucose, or other reactive sugars, with an amino-containing peptide, protein or biomolecule, thus stabilizing this early glycosylation product, and preventing its further reaction to form open-chain, carbonyl-containing advanced glycosylation end products. Suitable agents may contain a reactive aldehyde group. A preferred agent is acetaldehyde. The method comprises contacting the target biomolecule with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制含氨基酸，肽，蛋白质和生物分子的老化的组合物和方法。因此，公开了一种组合物，其包含能够与葡萄糖或其它反应性糖反应形成的早期糖基化产物（也称为Amadori产物或Heyns商品）的糖基 - 氨基部分反应的试剂或化合物，含有氨基的肽，蛋白质或生物分子，从而稳定该早期糖基化产物，并防止其进一步反应形成开链的含羰基的高级糖基化终产物。合适的试剂可以含有反应性醛基。优选的试剂是乙醛。该方法包括使目标生物分子与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

2. 发明授权

US5770571A Method and agents for inhibiting protein aging 失效
公开(公告)号：US5770571A
公开(公告)日：1998-06-23
申请号：US746742
申请日：1996-11-15
申请人： Anthony Cerami , Yousef Al-Abed , Richard J. Bucala , Peter C. Ulrich
发明人： Anthony Cerami , Yousef Al-Abed , Richard J. Bucala , Peter C. Ulrich
IPC分类号： A23L3/3562 , A21D4/00 , A61K31/00 , A61K31/11 , A61K38/00 , A61K45/00 , A61P3/00 , A61P3/10 , A61P9/00 , A61P9/10 , A61P9/12 , A61P13/00 , A61P13/12 , A61P17/00 , A61P19/00 , A61P19/02 , A61P25/00 , A61P27/00 , A61P27/02 , A61P27/12 , A61P43/00 , C07H9/06 , C07H19/01 , G01N33/15 , G01N33/50 , G01N33/68 , C07K13/00 , C08J89/06
CPC分类号： G01N33/6842 , A61K31/11 , C07H19/01 , C07H9/06 , G01N33/68
摘要： The present invention relates to compositions and methods for inhibiting the aging of amino-containing amino acid, peptides, proteins and biomolecules. Accordingly, a composition is disclosed which comprises an agent or compound capable of reacting with the glycosyl-amino moiety of the early glycosylation product (also known as the Amadori product or the Heyns product) formed by the reaction of glucose, or other reactive sugars, with an amino-containing peptide, protein or biomolecule, thus stabilizing this early glycosylation product, and preventing its further reaction to form open-chain, carbonyl-containing advanced glycosylation end products. Suitable agents may contain a reactive aldehyde group. A preferred agent is acetaldehyde. The method comprises contacting the target biomolecule with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

3. 发明授权

US06410598B1 Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis 失效
标题翻译：用于高级糖基化终末产物介导的淀粉样变性调节的组合物和方法
公开(公告)号：US06410598B1
公开(公告)日：2002-06-25
申请号：US08477364
申请日：1995-06-07
申请人： Michael P. Vitek , Anthony Cerami , Richard J. Bucala , Peter C. Ulrich , Helen Vlassara , Xini Zhang
发明人： Michael P. Vitek , Anthony Cerami , Richard J. Bucala , Peter C. Ulrich , Helen Vlassara , Xini Zhang
IPC分类号： A01N3752
CPC分类号： A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/425 , A61K31/655 , A61K38/00 , C07K14/4711 , C07K14/575
摘要： The present invention relates generally to the non-enzymatic glycosylation of amyloidogenic proteins and the consequent formation of advanced glycosylation endproducts (AGEs). It has been found that formation of AGE-amyloidogenic proteins can enhance amyloidosis. The invention further relates to compositions and methods for the prevention and treatment of amyloidosis associated with amyloid diseases, particularly neurodegenerative disease and Type II diabetes, and more particularly Alzheimer's disease. In a specific example, aggregation of an amyloidogenic peptide, &bgr;AP, is enhanced by the glycosylation reaction of &bgr;AP to form AGE-&bgr;AP as defined herein. Accordingly, the invention extends to a method for modulating the in vivo aggregation of amyloid polypeptides and associated amyloidosis by controlling the formation and presence of AGE-amyloid polypeptide. A corresponding diagnostic utility comprises the measurement of the course and extent of amyloidosis by a measurement of the presence and amount of AGEs and particularly, AGE-amyloid. An assay is included that may use the AGE-amyloid polypeptide of the present invention to identify disease states characterized by the presence of AGE-amyloid. Additionally, such an assay can be utilized to monitor therapy and thus adjust a dosage regimen for a given disease state characterized by the presence of AGE-amyloid.
摘要翻译：本发明一般涉及淀粉样蛋白形成蛋白的非酶糖基化，从而形成晚期糖基化终产物（AGEs）。已经发现AGE-淀粉样蛋白生成蛋白的形成可以增强淀粉样变性。本发明进一步涉及用于预防和治疗与淀粉样蛋白病，特别是神经变性疾病和II型糖尿病，更特别是阿尔茨海默病有关的淀粉样变性的组合物和方法。在具体实例中，通过βAP的糖基化反应来增强淀粉样蛋白原肽βAP的聚集，从而形成如本文所定义的AGE-βAP。因此，本发明延伸到通过控制AGE-淀粉样蛋白多肽的形成和存在来调节淀粉样蛋白多肽的体内聚集和相关淀粉样变性的方法。相应的诊断实用程序包括测量AGEs，特别是AGE-淀粉样蛋白的存在和量的淀粉样变性的过程和程度。包括可以使用本发明的AGE-淀粉样蛋白多肽来鉴定以AGE-淀粉样蛋白的存在为特征的疾病状态的测定。另外，这种测定可用于监测治疗，并因此调整特征在于AGE-淀粉样蛋白存在的给定疾病状态的剂量方案。

4. 发明授权

US5935927A Compositions and methods for stimulating amyloid removal in amyloidogenic diseases using advanced glycosylation endproducts 失效
标题翻译：使用高级糖基化终产物刺激淀粉样变性疾病中淀粉样蛋白去除的组合物和方法
公开(公告)号：US5935927A
公开(公告)日：1999-08-10
申请号：US501127
申请日：1996-08-10
申请人： Michael P. Vitek , Anthony Cerami , Richard J. Bucala , Peter C. Ulrich , Helen Vlassara , Xini Zhang
发明人： Michael P. Vitek , Anthony Cerami , Richard J. Bucala , Peter C. Ulrich , Helen Vlassara , Xini Zhang
IPC分类号： G01N33/68 , A61K31/047 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/425 , A61K31/428 , A61K31/655 , A61K31/7028 , A61K31/715 , A61K38/00 , A61K38/16 , A61K39/395 , A61K45/00 , A61P3/08 , A61P3/10 , A61P9/00 , A61P25/00 , A61P25/28 , A61P43/00 , C07D277/82 , C07D417/12 , C07H15/26 , C07K14/47 , C07K14/575 , A61K31/135 , A61K31/70
CPC分类号： A61K31/425 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/655 , C07K14/4711 , C07K14/575 , A61K38/00
摘要： The present invention relates generally to methods and compositions for treating amyloidogenic diseases such as Alzheimer's disease and the development of type II diabetes, in which deposition of amyloid in organs such as the brain and pancreas interfere with neurological function and insulin release, respectively. The methods and compositions are directed toward increasing the activity of scavenger cells within the body at recognizing and removing amyloid deposits from affected tissues and organs. Scavenger cells may be targeted to amyloid deposits by means of spontaneously-occurring chemical modifications called advanced glycosylation endproducts (AGEs). Compositions are described which increase scavenger cell activity towards AGE-modified amyloid. Amyloid removal may also be enhanced by increasing AGE levels in amyloid deposits within the body by administering AGE-modified amyloid targeting agents, which after becoming situated at sites containing amyloid, subsequently attract scavenger cells to degrade attendant amyloid. These methods and associated compositions result in a decrease in the extent of amyloid deposits in tissues, reducing the attendant pathology.
摘要翻译： PCT No.PCT / US95 / 01380 Sec。 371日期：1996年8月10日 102（e）日期1996年8月10日PCT提交1995年2月2日PCT公布。第WO95 / 20979号公报日期：1995年8月10日本发明一般涉及用于治疗淀粉样变性疾病如阿尔茨海默氏病和II型糖尿病发展的方法和组合物，其中淀粉样蛋白沉积在诸如脑和胰腺的器官中干扰神经功能和胰岛素释放，分别。所述方法和组合物旨在增加识别和去除受影响组织和器官中的淀粉样蛋白沉积物中体内清除细胞的活性。清除细胞可以通过称为晚期糖基化终产物（AGE）的自发发生的化学修饰来靶向淀粉样蛋白沉积物。描述了增加AGE修饰的淀粉样蛋白的清除细胞活性的组合物。通过施用AGE修饰的淀粉样蛋白靶向剂，其在位于含有淀粉样蛋白的位点后，随后吸引清道细胞降解伴随的淀粉样蛋白，也可以通过增加体内淀粉样蛋白沉积物中的AGE水平来增强淀粉样蛋白的去除。这些方法和相关组合物导致组织中淀粉样蛋白沉积的程度降低，减少伴随的病理。

5. 发明授权

US5733933A Methods and materials for the diagnosis and treatment of conditions such as stroke 失效
公开(公告)号：US5733933A
公开(公告)日：1998-03-31
申请号：US473009
申请日：1995-06-07
申请人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
发明人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
IPC分类号： A61K31/155 , A61K38/17 , A61K39/00 , A61Q11/00 , C07K16/28 , G01N33/573 , G01N33/92
CPC分类号： G01N33/92 , A61K31/155 , A61K38/1709 , A61K39/0005 , C07K16/28 , G01N33/573 , A61K2039/6081 , G01N2333/922 , G01N2800/2871 , G01N2800/324
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 AGE-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, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.

6. 发明申请

US20100184091A1 Method for determining MIF content 审中-公开
标题翻译：确定MIF内容的方法
公开(公告)号：US20100184091A1
公开(公告)日：2010-07-22
申请号：US12477889
申请日：2009-06-03
申请人： Richard J. Bucala , Robert A. Mitchell , Jurgen Bernhagen , Thierry F. Calandra , Anthony Cerami
发明人： Richard J. Bucala , Robert A. Mitchell , Jurgen Bernhagen , Thierry F. Calandra , Anthony Cerami
IPC分类号： G01N33/53
CPC分类号： C12N15/113 , A01K2217/05 , A01K2217/075 , A01K2267/03 , A01K2267/0337 , A61K48/00 , A61K2039/505 , C07K14/52 , C07K14/575 , C07K14/72 , C07K16/24 , C07K16/26 , C07K2317/73 , C07K2317/76 , C12N15/1136 , C12N15/1138 , C12N15/8509 , Y02A50/412
摘要： The present invention relates to diagnostic methods for determining migration inhibitory factor (MIF) mRNA content in a sample, wherein MIF is human MIF polypeptide having a molecular weight of approximately 12.5 kDa and kits for detecting MIF.
摘要翻译：本发明涉及用于确定样品中迁移抑制因子（MIF）mRNA含量的诊断方法，其中MIF是分子量约为12.5kDa的人MIF多肽和用于检测MIF的试剂盒。

7. 发明授权

US5846796A Blood-borne mesenchymal cells 失效
标题翻译：血源间充质细胞
公开(公告)号：US5846796A
公开(公告)日：1998-12-08
申请号：US488241
申请日：1995-06-07
申请人： Anthony Cerami , Richard J. Bucala
发明人： Anthony Cerami , Richard J. Bucala
IPC分类号： A61K35/12 , A61K39/00 , C12N5/0775 , C12N15/63
CPC分类号： C12N5/0665 , A61K2035/124 , A61K2039/5158 , C12N2501/22
摘要： The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.
摘要翻译：本发明涉及表达包含结缔组织成纤维细胞典型的特定标志物的表面标志物的独特特征的血液载体哺乳动物细胞群，并且在本文中称为“血源性间充质细胞”。特别地，它涉及这种血源间充质细胞的分离，表征和用途。本发明的细胞可以通过其不同的大小，形态，细胞表面表型和生物活性来区别于外周血白细胞，并且同样可以通过其他表面表型标记物与结缔组织成纤维细胞区分开来。这些细胞在培养物中增殖，并且如在动物模型中所证明的那样，能够从血液迁移到伤口部位。因此，这种血源性间充质细胞可以具有广泛的应用，包括但不限于促进伤口愈合，组织重塑和用于基因治疗。

8. 发明授权

US5733524A Methods and materials for the diagnosis and treatment of conditions such as stroke 失效
标题翻译：用于诊断和治疗诸如中风的病症的方法和材料
公开(公告)号：US5733524A
公开(公告)日：1998-03-31
申请号：US479673
申请日：1995-06-07
申请人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
发明人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
IPC分类号： A61K31/155 , A61K38/17 , A61K39/00 , A61Q11/00 , C07K16/28 , G01N33/573 , G01N33/92 , A61K49/00 , G01N31/00 , G01N33/48
CPC分类号： A61K31/155 , A61K31/00 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K31/70 , A61K38/1709 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/43 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , G01N33/6893 , G01N33/92 , A61K2039/6081 , G01N2333/922 , G01N2800/2871 , G01N2800/324
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 AGE-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, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.
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，高级糖基化终产物例如AGE-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，脂褐素的异常形成和各种疾病状态如糖尿病，动脉粥样硬化和中风。公开了使用抑制AGE-脂质形成的药物治疗中风的方法，特别是抑制中风的梗死面积。另外，公开了可用于减小梗死面积大小和严重程度的神经保护剂筛选方法。

9. 发明授权

US5869534A 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，以及从其衍生的诊断和治疗方法和材料
公开(公告)号：US5869534A
公开(公告)日：1999-02-09
申请号：US29417
申请日：1993-03-11
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
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 AGE-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，高级糖基化终产物例如AGE-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。

10. 发明授权

US5804446A Blood-borne mesenchymal cells 失效
公开(公告)号：US5804446A
公开(公告)日：1998-09-08
申请号：US488111
申请日：1995-06-07
申请人： Anthony Cerami , Richard J. Bucala
发明人： Anthony Cerami , Richard J. Bucala
IPC分类号： A61K35/12 , A61K39/00 , C12N5/0775 , C12N5/00 , C12N5/02
CPC分类号： C12N5/0665 , A61K2035/124 , A61K2039/5158 , C12N2501/22
摘要： The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.

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