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1. 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。

2. 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。

3. 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。

4. 发明申请

US20120291145A1 TRANSGENIC MICE OVER-EXPRESSING RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCT (RAGE) IN BRAIN AND USES THEREOF 审中-公开
标题翻译：转基因小鼠过度表达受体，用于脑内高级糖化终产物（RAGE）及其用途
公开(公告)号：US20120291145A1
公开(公告)日：2012-11-15
申请号：US13362542
申请日：2012-01-31
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： A01K67/027 , G01N33/566 , G01N21/64 , A61K49/00
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。

5. 发明授权

US08124829B2 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：US08124829B2
公开(公告)日：2012-02-28
申请号：US12908832
申请日：2010-10-20
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 , A01K67/00 , A01K67/033 , A01K67/027 , C12N15/00
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。

6. 发明申请

US20110126298A1 Transgenic Mice Over-Expressing Receptor For Advanced Glycation Endproduct (RAGE) In Brain And Uses Thereof 失效
标题翻译：转基因小鼠过表达受体高级糖化终产物（RAGE）在大脑及其应用
公开(公告)号：US20110126298A1
公开(公告)日：2011-05-26
申请号：US12908832
申请日：2010-10-20
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： A01K67/027 , G01N33/48
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。

7. 发明申请

US20090028882A1 Methods of inhibiting binding of beta-sheet fibril to rage and consequences thereof 审中-公开
标题翻译：抑制β-片原纤维结合的愤怒及其后果的方法
公开(公告)号：US20090028882A1
公开(公告)日：2009-01-29
申请号：US12009572
申请日：2008-01-18
申请人： David M. Stern , Shi Du Yan , Ann Marie Schmidt
发明人： David M. Stern , Shi Du Yan , Ann Marie Schmidt
IPC分类号： A61K38/16 , A61K39/395 , A61P25/00
CPC分类号： C07K16/2803 , A61K2039/505 , C07K2317/54
摘要： This invention provides a method of inhibiting the binding of beta-sheet fibril to RAGE on the surface of a cell which comprises contacting the cell with a binding-inhibiting amount of a compound capable of inhibiting binding of beta-sheet fibril to RAGE so as to thereby inhibit binding of beta-sheet fibril to RAGE.In one embodiment, the beta-sheet fibril is amyloid fibril. In one embodiment, the compound is sRAGE or a fragment thereof. In another embodiment, the compound is an anti-RAGE antibody or portion thereof.This invention provides the above method wherein the inhibition of binding of the beta-sheet fibril to RAGE has the consequences of decreasing the load of beta-sheet fibril in the tissue, inhibiting fibril-induced programmed cell death, and inhibiting fibril-induced cell stress.This invention also provides methods of determining whether a compound inhibits binding of a beta-sheet fibril to RAGE on the surface of a cell.
摘要翻译：本发明提供一种抑制细胞表面上的β-片原纤维与RAGE的结合的方法，其包括将细胞与结合抑制量的能够抑制β-片原纤维结合的化合物与RAGE接触，以便从而抑制β-片原纤维与RAGE的结合。在一个实施方案中，β-片原纤维是淀粉样蛋白原纤维。在一个实施方案中，化合物是sRAGE或其片段。在另一个实施方案中，化合物是抗RAGE抗体或其部分。本发明提供了上述方法，其中抑制β-片原纤维与RAGE的结合具有降低组织中β-片原纤维负荷，抑制原纤维诱导的程序性细胞死亡和抑制原纤维诱导的细胞应激的后果。本发明还提供了确定化合物是否抑制β片原纤维与细胞表面上的RAGE结合的方法。

8. 发明授权

US07258857B2 Rage-related methods for treating inflammation 失效
标题翻译：愤怒相关的治疗炎症的方法
公开(公告)号：US07258857B2
公开(公告)日：2007-08-21
申请号：US09872185
申请日：2001-06-01
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： A61K39/395 , C07K16/28
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。

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

US06677299B2 Method to increase cerebral blood flow in amyloid angiopathy 有权
公开(公告)号：US06677299B2
公开(公告)日：2004-01-13
申请号：US09992955
申请日：2001-11-05
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.

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