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1. 发明授权

US08450454B2 Compositions for inhibiting ABAD/ABeta protein interaction 失效
标题翻译：用于抑制ABAD / ABeta蛋白质相互作用的组合物
公开(公告)号：US08450454B2
公开(公告)日：2013-05-28
申请号：US13006309
申请日：2011-01-13
申请人： Shi Du Yan , David M. Stern , Joyce W. Lustbader , Hao Wu
发明人： Shi Du Yan , David M. Stern , Joyce W. Lustbader , Hao Wu
IPC分类号： C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00 , C07K14/00
CPC分类号： C07K14/4711 , A61K38/00
摘要： This invention provides methods, compositions and articles of manufacture for inhibiting binding between Aβ protein and ABAD in cells. Uses of this invention include, for example, treating Alzheimer's disease; reducing free radical generation, DNA fragmentation, and cytochrome C release in cells; and preserving cell viability by preventing LDH release from a cell.
摘要翻译：本发明提供用于抑制细胞中Abeta蛋白和ABAD之间的结合的方法，组合物和制品。本发明的用途包括例如治疗阿尔茨海默病; 减少细胞中的自由基产生，DNA断裂和细胞色素C释放; 并通过阻止LDH从细胞释放而保持细胞活力。

2. 发明授权

US08067371B2 RAGE G82S-related methods and compositions for treating inflammatory disorders 失效
标题翻译： RAGE G82S相关的治疗炎性疾病的方法和组合物
公开(公告)号：US08067371B2
公开(公告)日：2011-11-29
申请号：US10840927
申请日：2004-05-07
申请人： Ann Marie Schmidt , David M. Stern
发明人： Ann Marie Schmidt , David M. Stern
IPC分类号： A61K38/00
CPC分类号： A61K38/177 , C12N15/1138 , C12N2310/11
摘要： This invention provides methods, compositions and articles of manufacture for inhibiting the onset of and treating inflammatory disorders such as rheumatoid arthritis. The instant invention is based on the blockade of RAGE G82S function.
摘要翻译：本发明提供了抑制炎症性疾病如类风湿性关节炎发作和治疗的方法，组合物和制品。本发明基于RAGE G82S功能的封锁。

3. 发明授权

US07919670B1 Transgenic mice over-expressing receptor for advanced glycation endproduct (RAGE) in brain and uses thereof 失效
标题翻译：用于脑中晚期糖基化终末产物（RAGE）的转基因小鼠过表达受体及其用途
公开(公告)号：US07919670B1
公开(公告)日：2011-04-05
申请号：US09638653
申请日：2000-08-14
申请人： David M. Stern , Ann Marie Schmidt , Shi Du Yan
发明人： David M. Stern , Ann Marie Schmidt , Shi Du Yan
IPC分类号： G01N33/00 , A01K67/027
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2217/052 , A01K2217/15 , A01K2217/206 , A01K2227/105 , A01K2267/035 , A01K2267/0356 , C07K14/70503 , C12N15/8509
摘要： The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter; and (b) a DNA sequence which encodes a receptor for advanced glycation endproducts (RAGE), wherein the promoter and the DNA sequence which encodes the receptor for advanced glycation endproducts (RAGE) are operatively linked to each other and integrated in the genome of the non-human animal, and wherein said non-human animal exhibits a reduced amount of cerebral tissue infarcted following a transient middle cerebral artery occlusion compared to an identical non-human animal lacking said DNA sequence.
摘要翻译：本发明提供一种转基因非人动物，其细胞含有DNA序列，其包含：（a）神经组织特异性启动子; （b）编码晚期糖基化终末产物（RAGE）的受体的DNA序列，其中编码晚期糖基化终产物（RAGE）的受体的启动子和DNA序列可操作地相互连接并整合到非人动物，并且其中所述非人动物与缺乏所述DNA序列的相同的非人动物相比，在短暂的大脑中动脉闭塞之后表现出减少的脑组织数量。

4. 发明申请

US20080214453A1 Methods for treating inflammation 审中-公开
标题翻译：治疗炎症的方法
公开(公告)号：US20080214453A1
公开(公告)日：2008-09-04
申请号：US11894503
申请日：2007-08-20
申请人： David M. Stern , Kevan Herold , Shi Du Yan , Ann Marie Schmidt , Ira Lamster
发明人： David M. Stern , Kevan Herold , Shi Du Yan , Ann Marie Schmidt , Ira Lamster
IPC分类号： A61K38/16 , A61P29/00
CPC分类号： A61K31/00 , A61K38/1774 , A61K2039/505 , C07K16/18 , Y10S514/825
摘要： The present invention provides a method for treating inflammation in a subject which comprises administering to the subject soluble receptor for advanced glycation endproduct (sRAGE) in an amount effective to inhibit binding of advanced glycation endproducts (AGEs) to RAGE thereby treating inflammation in the subject. The present invention also provides for a method for treating inflammation in a subject which comprises administering to the subject an agent in an amount effective to inhibit the interaction between receptor for advanced glycation endproduct (RAGE) and its ligand thereby treating inflammation in the subject.
摘要翻译：本发明提供了一种用于治疗受试者的炎症的方法，其包括以有效抑制晚期糖基化终产物（AGE）与RAGE结合的量向受试者可溶性受体施用晚期糖基化终产物（sRAGE），从而治疗受试者的炎症。本发明还提供了一种用于治疗受试者的炎症的方法，其包括以有效抑制晚期糖基化终产物（RAGE）的受体与其配体之间的相互作用的量向受试者施用试剂，由此治疗受试者的炎症。

5. 发明申请

US20090060925A1 Rage Fusion Proteins and Methods of Use 审中-公开
标题翻译：愤怒的融合蛋白和使用方法
公开(公告)号：US20090060925A1
公开(公告)日：2009-03-05
申请号：US11630916
申请日：2005-08-03
申请人： Adnan M.M. Mjalli , Ye Edward Tian , Jeffrey C. Webster , Robert Rothlein , David M. Stern , Ann Marie Schmidt , Shi Du Yan
发明人： Adnan M.M. Mjalli , Ye Edward Tian , Jeffrey C. Webster , Robert Rothlein , David M. Stern , Ann Marie Schmidt , Shi Du Yan
IPC分类号： A61K39/395 , C07K14/00 , C07K16/00 , C12N15/63 , A61P3/10 , A61P25/28 , A61P29/00 , A61P13/12 , A61P35/00 , A61P9/00 , G01N33/53 , C07H21/00 , A61K38/16
CPC分类号： C07K16/2803 , A61K38/00 , C07K14/705 , C07K2319/30 , G01N33/6893 , G01N33/6896 , G01N2500/00 , G01N2800/042
摘要： Disclosed are RAGE fusion proteins comprising RAGE polypeptide sequences linked to a second, non-RAGE polypeptide. The RAGE fusion protein may utilize a RAGE polypeptide domain comprising a RAGE ligand binding site and an interdomain linker directly linked to an immunoglobulin CH2 domain. Such fusion proteins may provide specific, high affinity binding to RAGE ligands. Also disclosed is the use of the RAGE fusion proteins as therapeutics for RAGE-mediated pathologies.
摘要翻译：公开了包含与第二非RAGE多肽连接的RAGE多肽序列的RAGE融合蛋白。 RAGE融合蛋白可以利用包含RAGE配体结合位点和直接连接到免疫球蛋白CH2结构域的域间连接体的RAGE多肽结构域。这样的融合蛋白可以提供与RAGE配体的特异的高亲和力结合。还公开了RAGE融合蛋白作为RAGE介导的病理学的治疗剂的用途。

6. 发明申请

US20080260717A1 Methods for Reducing Seizure-Induced Neuronal Damage 审中-公开
标题翻译：降低癫痫发作神经元损伤的方法
公开(公告)号：US20080260717A1
公开(公告)日：2008-10-23
申请号：US10577382
申请日：2004-10-28
申请人： Shi Du Yan , Guy McKhann , David M. Stern
发明人： Shi Du Yan , Guy McKhann , David M. Stern
IPC分类号： A61K39/395 , A61K31/7052 , A61P25/00
CPC分类号： C07K14/70503 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A61K48/00 , C12N15/8509
摘要： This invention provides a method for treating a subject either during or soon after a seizure, in order to reduce the extent of neuronal damage in the subject resulting from the seizure comprising administering to the subject, either during or soon after the seizure, a therapeutically effective amount of an inhibitor of receptor for advanced glycation endproducts (RAGE), so as to thereby reduce the extent of neuronal damage in the subject. This invention further provides a method for inhibiting neuronal damage which would otherwise result from a seizure in a subject predisposed to having a seizure, comprising administering to the subject a prophylactically effective amount of an inhibitor of receptor for advanced glycation endproducts (RAGE), so as to inhibit neuronal damage which would otherwise result from a seizure in the event the subject were to suffer a seizure.
摘要翻译：本发明提供了一种在癫痫发作期间或之后治疗受试者的方法，以便减少由于癫痫发作引起的受试者神经元损伤的程度，包括在癫痫发作期间或之后对受试者施用治疗有效的用于晚期糖基化终产物（RAGE）的受体抑制剂的量，从而减少受试者的神经元损伤的程度。本发明进一步提供了一种抑制神经元损伤的方法，否则这些损伤将由预先发生癫痫发作的受试者的癫痫发作引起，其包括向受试者施用预防有效量的晚期糖基化终末产物受体抑制剂（RAGE），以便以抑制在受试者遭受癫痫发作的情况下由于癫痫发作而导致的神经元损伤。

7. 发明授权

US07060870B1 Transgenic mice over-expressing ABAD and mutant APP in brain as model of Alzheimer's disease and uses thereof 失效
标题翻译：在阿尔茨海默病模型中过表达ABAD和突变体APP的转基因小鼠及其用途
公开(公告)号：US07060870B1
公开(公告)日：2006-06-13
申请号：US09638647
申请日：2000-08-14
申请人： David M. Stern , Shi Du Yan
发明人： David M. Stern , Shi Du Yan
IPC分类号： C12N15/00 , G01N33/00
CPC分类号： C07K14/4711 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/0312 , C07K14/49 , C12N9/0006 , C12N15/8509 , C12N2830/008
摘要： The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter operatively linked to a DNA sequence which encodes amyloid-beta peptide alcohol dehydrogenase (ABAD), and (b) a nerve tissue specific promoter operatively linked to a DNA sequence encoding a mutant human amyloid precursor protein hAPP695, hAPP751 and hAPP770 bearing mutations linked to familial Alzheimer's disease in humans, wherein the non-human animal exhibits at least one phenotype from the group consisting of: reduced basal synaptic transmission; inhibited synaptic plasticity; increased neuronal stress; elevated 4-hydroxynonenal in cerebral cortex; increased heme oxygenase type I in cerebral cortex; decreased synaptophysin in cerebral cortex; decreased micortubule-associated protein 2 in cerebral cortex; and increased levels of activated caspase 3 antigen in cortical neurons.
摘要翻译：本发明提供一种转基因非人动物，其细胞含有DNA序列，其包含：（a）与编码淀粉样蛋白-β肽醇脱氢酶（ABAD）的DNA序列有效连接的神经组织特异性启动子，和（b）神经组织特异性启动子可操作地连接到编码人类淀粉样蛋白前体蛋白hAPP695，hAPP751和hAPP770的DNA序列，其携带与人类家族性阿尔茨海默氏病相关的突变，其中非人动物表现出至少一种表型，所述表型包括：还原基底突触传播; 抑制突触可塑性; 增加神经元压力; 大脑皮质中升高的4-羟基壬烯醛; 增加大脑皮层I型血红素加氧酶; 大脑皮层突触素减少; 大脑皮质中微管蛋白相关蛋白2减少; 和皮质神经元中激活的半胱天冬酶3抗原水平的增加。

8. 发明授权

US06994974B1 Intracellular amyloid-beta binding (ERAB) polypeptide-related assays 失效
标题翻译：细胞内淀粉样蛋白-β结合（ERAB）多肽相关测定
公开(公告)号：US06994974B1
公开(公告)日：2006-02-07
申请号：US09394204
申请日：1999-09-10
申请人： David M. Stern , Shi Du Yan
发明人： David M. Stern , Shi Du Yan
IPC分类号： G01N33/53
CPC分类号： C12N9/0006 , A01K2217/05 , A61K38/00 , C07K16/40 , C07K2317/54 , C07K2319/00 , C12Y101/01036 , C12Y101/01053 , C12Y101/01062 , G01N33/6896
摘要： The present invention provides an isolated nucleic acid encoding an endoplasmic reticulum associated amyloid-beta peptide binding (ERAB) polypeptide. The ERAB polypeptide may comprise human ERAB polypeptide. The present invention provides a purified ERAB polypeptide, as well as a method for treating a neurodegenerative condition in a subject which comprises administering to the subject an agent in amount effective to inhibit ERAB polypeptide binding to amyloid-beta peptide so as to thereby treat the neurodegenerative condition.
摘要翻译：本发明提供编码与内质网相关的淀粉样蛋白-β肽结合（ERAB）多肽的分离的核酸。 ERAB多肽可以包含人ERAB多肽。本发明提供纯化的ERAB多肽，以及治疗受试者神经变性病症的方法，其包括以有效抑制ERAB多肽与淀粉样蛋白-β肽结合的量向受试者施用试剂，从而治疗神经变性条件。

9. 发明授权

US06825164B1 Method to increase cerebral blood flow in amyloid angiopathy 失效
标题翻译：增加淀粉样血管病中脑血流量的方法
公开(公告)号：US06825164B1
公开(公告)日：2004-11-30
申请号：US09638648
申请日：2000-08-14
申请人： David M. Stern , Ann Marie Schmidt , Shi Du Yan , Berislav Zlokovic
发明人： David M. Stern , Ann Marie Schmidt , Shi Du Yan , Berislav Zlokovic
IPC分类号： A01N6100
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0312 , A61K38/00 , A61K2039/505 , C07K14/4711 , C07K14/70503 , C12N2830/008
摘要： The present invention provides a method for decreasing cerebral vasoconstriction in a subject suffering from chronic or acute cerebral amyloid angiopathy which comprises administering to the subject an inhibitor of receptor for advanced glycation endproduct (RAGE) in an effective amount to inhibit transcytosis of amyloid &bgr; peptides across the blood-brain barrier in the subject, thereby decreasing cerebral vasoconstriction in the subject. The invention further provides for a method for ameliorating neurovascular stress in a subject which comprises administering to the subject an effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE), so as to increase cerebral blood flow in the subject, thereby ameliorating neurovascular stress in the subject.
摘要翻译：本发明提供一种降低患有慢性或急性脑淀粉样变性血管病的受试者的脑血管收缩的方法，该方法包括向受试者施用有效量的晚期糖基化终产物（RAGE）的受体抑制剂以抑制淀粉样蛋白β肽的转胞吞作用受试者的血脑屏障，从而减少受试者的脑血管收缩。本发明还提供了一种改善受试者的神经血管应激的方法，其包括对受试者施用有效量的晚期糖基化终末产物（RAGE）受体抑制剂，以增加受试者的脑血流量，从而改善神经血管主题压力。

10. 发明授权

US06790443B2 Method for treating symptoms of diabetes 失效
公开(公告)号：US06790443B2
公开(公告)日：2004-09-14
申请号：US08755235
申请日：1996-11-22
申请人： David M. Stern , Ann Marie Schmidt
发明人： David M. Stern , Ann Marie Schmidt
IPC分类号： A61K39395
CPC分类号： C07K16/2803 , A61K38/00 , A61K38/1709 , C07K14/70503
摘要： The present invention provides a method for treating symptoms of diabetes in a diabetic subject which comprises administering to the subject a therapeutically effective amount of an agent which inhibits binding of advanced glycation endproducts to any receptor for advanced glycation endproducts so as to treat chronic symptoms of diabetes in the subject.

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