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1. 发明授权

US06998475B1 Variants of traf2 which act as an inhibitor of tnf-alpha (tnfα) signaling pathway 失效
标题翻译：作为tnf-α（tnfalpha）信号通路抑制剂的traf2变体
公开(公告)号：US06998475B1
公开(公告)日：2006-02-14
申请号：US10018030
申请日：2000-04-06
申请人： George H. Searfoss, III , Marco F. Pagnoni , Yuri D. Ivashchenko , Kun Guo , Kenneth L. Clark
发明人： George H. Searfoss, III , Marco F. Pagnoni , Yuri D. Ivashchenko , Kun Guo , Kenneth L. Clark
IPC分类号： C12N5/10 , C12N15/12 , C12N15/63 , C07K14/705
CPC分类号： C07K14/705 , C07K14/4703
摘要： The present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF α signaling path-way. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as “TRAF2 truncated” or “TRAF2TR” and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as “TRAF2 truncated-deleted” or “TRAF2TD”. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF α signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF α binding.
摘要翻译：本发明涉及TRAF2的变体，其表现出抑制TNFα信号传导途径的能力。特别地，申请人已经分离了以下称为“TRAF2截短”或“TRAF2TR”的TRAF2和具有增强的显性阴性的TRAF2表达构建体（以下称为“TRAF2截短缺失”或“TRAF2TD”）的剪接变体。 TRAF2TR和TRAF2TD均具有抑制TNFα信号通路的能力，并且在TRAF2TD中，这种能力大大增强，大大降低了对TNFα结合的反应。

2. 发明授权

US07332593B2 Variants of TRAF2 which act as an inhibitor of TNF-alpha (TNFα) signaling pathway 失效
标题翻译：作为TNF-α（TNFalpha）信号通路抑制剂的TRAF2的变体
公开(公告)号：US07332593B2
公开(公告)日：2008-02-19
申请号：US11294246
申请日：2005-12-05
申请人： George H. Searfoss, III , Marco F. Pagnoni , Yuri D. Ivashchenko , Kun Guo , Kenneth L. Clark
发明人： George H. Searfoss, III , Marco F. Pagnoni , Yuri D. Ivashchenko , Kun Guo , Kenneth L. Clark
IPC分类号： C12N5/10 , C12N15/12 , C12N15/63
CPC分类号： C07K14/705 , C07K14/4703
摘要： The present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF α signaling pathway. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as “TRAF2 truncated” or “TRAF2TR” and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as “TRAF2 truncated-deleted” or “TRAF2TD”. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF α signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF α binding.
摘要翻译：本发明涉及TRAF2的变体，其表现出抑制TNFα信号通路的能力。特别地，申请人已经分离了以下称为“TRAF2截短”或“TRAF2TR”的TRAF2和具有增强的显性阴性的TRAF2表达构建体（以下称为“TRAF2截短缺失”或“TRAF2TD”）的剪接变体。 TRAF2TR和TRAF2TD均具有抑制TNFα信号通路的能力，并且在TRAF2TD中，这种能力大大增强，大大降低了对TNFα结合的反应。

3. 发明申请

US20120034188A1 Akt Nucleic Acids, Polypeptides, and Uses Thereof 审中-公开
标题翻译： Akt核酸，多肽及其用途
公开(公告)号：US20120034188A1
公开(公告)日：2012-02-09
申请号：US13195392
申请日：2011-08-01
申请人： Kun Guo , Marco F. Pagnoni , Kenneth L. Clark , Yuri D. Ivashchenko
发明人： Kun Guo , Marco F. Pagnoni , Kenneth L. Clark , Yuri D. Ivashchenko
IPC分类号： A61K48/00 , C07K16/40 , A61P9/10 , G01N33/53 , C12Q1/68 , C12N5/07 , C12N9/12 , A61K35/76
CPC分类号： C12N9/1205 , A61K48/00 , C07K14/47 , C12N2799/021 , C12N2799/022 , C12N2799/027 , C12N2799/028
摘要： The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.
摘要翻译：本发明涉及人Akt3蛋白和多肽。本发明还涉及编码人Akt3的分离的核酸，含有它们的载体和其治疗用途，特别是用于基因治疗。 Akt3的表达抑制与缺氧，凋亡或坏死相关的细胞死亡。

4. 发明授权

US06881555B2 AKT nucleic acids, polypeptides, and uses thereof 有权
标题翻译： AKT核酸，多肽及其用途
公开(公告)号：US06881555B2
公开(公告)日：2005-04-19
申请号：US09526043
申请日：2000-03-14
申请人： Kun Guo , Marco F. Pagnoni , Kenneth L. Clark , Yuri D. Ivashchenko
发明人： Kun Guo , Marco F. Pagnoni , Kenneth L. Clark , Yuri D. Ivashchenko
IPC分类号： A61K48/00 , C07K14/47 , C12N9/12 , C12N15/12 , C12P21/06 , C12N11/00 , C12N11/02 , C12N11/04 , C12N11/14
CPC分类号： C12N9/1205 , A61K48/00 , C07K14/47 , C12N2799/021 , C12N2799/022 , C12N2799/027 , C12N2799/028
摘要： The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.
摘要翻译：本发明涉及人Akt3蛋白和多肽。本发明还涉及编码人Akt3的分离的核酸，含有它们的载体和其治疗用途，特别是用于基因治疗。 Akt3的表达抑制与缺氧，凋亡或坏死相关的细胞死亡。

5. 发明授权

US07989584B2 AKT nucleic acids, polypeptides, and uses thereof 有权
标题翻译： AKT核酸，多肽及其用途
公开(公告)号：US07989584B2
公开(公告)日：2011-08-02
申请号：US12633984
申请日：2009-12-09
申请人： Kun Guo , Kenneth L. Clark , Yuri D. Ivashchenko , Marco Pagnoni
发明人： Kun Guo , Kenneth L. Clark , Yuri D. Ivashchenko , Marco Pagnoni
IPC分类号： C07K14/17 , C07K19/00 , C12N15/12
CPC分类号： C12N9/1205 , A61K48/00 , C07K14/47 , C12N2799/021 , C12N2799/022 , C12N2799/027 , C12N2799/028
摘要： The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.
摘要翻译：本发明涉及人Akt3蛋白和多肽。本发明还涉及编码人Akt3的分离的核酸，含有它们的载体和其治疗用途，特别是用于基因治疗。 Akt3的表达抑制与缺氧，凋亡或坏死相关的细胞死亡。

6. 发明授权

US07662628B2 Human Akt3 nucleic acid and uses thereof 有权
标题翻译：人Akt3核酸及其用途
公开(公告)号：US07662628B2
公开(公告)日：2010-02-16
申请号：US11063691
申请日：2005-02-23
申请人： Kun Guo , Kenneth L. Clark , Yuri D. Ivashchenko , Marco Pagnoni
发明人： Kun Guo , Kenneth L. Clark , Yuri D. Ivashchenko , Marco Pagnoni
IPC分类号： C12N15/09 , C12Q1/70
CPC分类号： C12N9/1205 , A61K48/00 , C07K14/47 , C12N2799/021 , C12N2799/022 , C12N2799/027 , C12N2799/028
摘要： The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.
摘要翻译：本发明涉及人Akt3蛋白和多肽。本发明还涉及编码人Akt3的分离的核酸，含有它们的载体和其治疗用途，特别是用于基因治疗。 Akt3的表达抑制与缺氧，凋亡或坏死相关的细胞死亡。

7. 发明授权

US07196089B2 EP4 receptor antagonists 失效
标题翻译： EP4受体拮抗剂
公开(公告)号：US07196089B2
公开(公告)日：2007-03-27
申请号：US10766030
申请日：2004-01-29
申请人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
发明人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
IPC分类号： A61K31/341 , A61K31/443 , A61K31/506 , C07D239/34 , C07D405/10 , C07D307/91 , C07D307/68
CPC分类号： C07D307/54 , A61K31/34 , A61K31/341 , A61K31/4155 , A61K31/443 , C07D307/64 , C07D307/68 , C07D405/12 , C07D407/12 , C07D409/12 , C07D413/12 , C07D417/12 , C07D417/14
摘要： Compounds of formula (I): wherein: R2 is H or an optionally substituted C1-4 alkyl group; Y is either —(CH2)n—X—, where n is 1 or 2 and X is O, S, S(═O), S(═O)2, or NRN1, where RN1 is selected from H or optionally substituted C1-4 alkyl, or Y is —C(═O)NRN2—, where RN2 is selected from H, and optionally substituted C1-7 alkyl or C5-20 aryl; R3 is an optionally substituted C6 aryl group linked to a further optionally substituted C6 aryl group, wherein if both C6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a C1-3 alkylene group; and R5 is either: (i) carboxy; (ii) a group of formula (II): or (iii) a group of formula (III): wherein R is optionally substituted C1-7 alkyl, C5-20 aryl or NRN3RN4, where RN3 and RN4 are independently selected from optionally substituted C1-4 alkyl; (iv) tetrazol-5-yl.
摘要翻译：式（I）的化合物：

8. 发明授权

US4214917A Process of forming a semiconductor memory cell with continuous polysilicon run circuit elements 失效
标题翻译：形成具有连续多晶硅运行电路元件的半导体存储单元的工艺
公开(公告)号：US4214917A
公开(公告)日：1980-07-29
申请号：US876726
申请日：1978-02-10
申请人： Kenneth L. Clark , George S. Leach , Robert W. Howard
发明人： Kenneth L. Clark , George S. Leach , Robert W. Howard
IPC分类号： H01L21/02 , H01L21/321 , H01L21/3215 , H01L21/768 , H01L21/8244 , H01L27/11 , H01L21/26 , H01L21/283 , H01L29/78
CPC分类号： H01L28/20 , H01L21/321 , H01L21/32155 , H01L21/768 , H01L27/11 , H01L27/1112 , Y10S148/02 , Y10S148/133 , Y10S148/141 , Y10S257/904
摘要： A process is described for forming a plurality of polysilicon runs on the surface of a semiconductor substrate, such as a silicon substrate, at least one of the polysilicon runs having a resistor portion formed therein, and at least one of the polysilicon runs forming the conductive gate electrode of a self-aligned insulated silicon gate field effect device. A specific embodiment of the process involves forming protective oxide layer on the substrate with depressions or wells therein to define active area regions of field effect devices, depositing a layer of polysilicon to overly the protective oxide layers, implanting dopant ions in the polysilicon layer to establish an initial conductivity of the polysilicon corresponding to resistor material, patterning the polysilicon layer to define desired polysilicon runs, with at least one of the polysilicon runs traversing across the gate region and gate oxide of a field effect device to serve as the gate electrode thereof; establishing an oxide layer over the surface and then removing oxide to both expose the active areas of the field effect devices where not protected by the polysilicon gate electrodes and also to define a remaining resistor mask of the oxide which overlies and protects the resistor portions of the polysilicon runs; and applying dopant to render the unprotected portions of the polysilicon runs highly conductive relative to the oxide masked resistor portions thereof and to simultaneously dope the exposed active areas of field effect devices.
摘要翻译：描述了在诸如硅衬底的半导体衬底的表面上形成多个多晶硅延伸的工艺，其中形成有电阻器部分的多晶硅行程中的至少一个，并且至少一个多晶硅流程形成导电自对准绝缘硅栅场效应器件的栅电极。该方法的具体实施方案包括在衬底上形成保护性氧化物层，其中具有凹陷或凹槽，以限定场效应器件的有源区域，将多晶硅层沉积在过度的保护氧化物层上，在多晶硅层中注入掺杂剂离子以建立形成与电阻材料相对应的多晶硅的初始电导率，图案化多晶硅层以限定期望的多晶硅延伸，其中至少一个多晶硅延伸穿过栅极区域和场效应器件的栅极氧化物以用作其栅电极; 在表面上建立氧化物层，然后去除氧化物，以暴露不受多晶硅栅电极保护的场效应器件的有源区，并且还限定氧化物的剩余电阻掩模，其覆盖并保护多晶硅运行; 并且施加掺杂剂以使得多晶硅的未受保护部分相对于其氧化物掩模的电阻器部分高度导电，并且同时掺杂暴露的场效应器件的有源区域。

9. 发明授权

US07858644B2 EP4 receptor antagonists 失效
标题翻译： EP4受体拮抗剂
公开(公告)号：US07858644B2
公开(公告)日：2010-12-28
申请号：US12360954
申请日：2009-01-28
申请人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
发明人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
IPC分类号： A61K31/4418 , A61K31/422 , A61K31/34
CPC分类号： C07D307/54 , A61K31/34 , A61K31/341 , A61K31/4155 , A61K31/443 , C07D307/64 , C07D307/68 , C07D405/12 , C07D407/12 , C07D409/12 , C07D413/12 , C07D417/12 , C07D417/14
摘要： Compounds of formula (I): wherein: R2 is H or an optionally substituted C1-4 alkyl group; Y is either —(CH2)n—X—, where n is 1 or 2 and X is O, S, S(═O), S(═O)2, or NRN1, where RN1 is selected from H or optionally substituted C1-4 alkyl, or Y is —C(═O)NRN2—, where RN2 is selected from H, and optionally substituted C1-7 alkyl or C5-20 aryl; R3 is an optionally substituted C6 aryl group linked to a further optionally substituted C6 aryl group, wherein if both C6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a C1-3 alkylene group; and R5 is either: (i) carboxy; (ii) a group of formula (II): or (iii) a group of formula (III): wherein R is optionally substituted C1-7 alkyl, C5-20 aryl or NRN3RN4, where RN3 and RN4 are independently selected from optionally substituted alkyl; (iv) tetrazol-5-yl.
摘要翻译：式（I）化合物：其中：R2是H或任选取代的C 1-4烷基; Y是 - （CH 2）n -X-，其中n是1或2，X是O，S，S（= O），S（= O）2或NRN1，其中RN1选自H或任选取代 C 1-4烷基或Y是-C（= O）NRN 2 - ，其中RN 2选自H和任选取代的C 1-7烷基或C 5-20芳基; R3是与另外任意取代的C 6芳基连接的任意取代的C6芳基，其中如果两个C 6芳基都是苯环，则两个环之间可能有一个氧桥，与两个环上的连接相邻; A是单键或C1-3亚烷基; 并且R 5是：（i）羧基; （ii）式（II）的基团：或（iii）式（III）的基团：其中R是任选取代的C 1-7烷基，C 5-20芳基或NRN 3 R N 4，其中RN 3和RN 4独立地选自任选取代的烷基; （ⅳ）四唑-5-基。

10. 发明授权

US07507754B2 EP4 receptor antagonists 失效
公开(公告)号：US07507754B2
公开(公告)日：2009-03-24
申请号：US11889570
申请日：2007-08-14
申请人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
发明人： Alexander W. Oxford , Richard J. Davis , Robert A. Coleman , Kenneth L. Clark , David E. Clark , Neil V. Harris , Garry Fenton , George Hynd , Keith A. J. Stuttle , Jonathan M. Sutton , Christopher G. Newton
IPC分类号： A61K31/443 , A61K31/343 , A61K31/341 , C07D405/12 , C07D307/91 , C07D307/68
CPC分类号： C07D307/54 , A61K31/34 , A61K31/341 , A61K31/4155 , A61K31/443 , C07D307/64 , C07D307/68 , C07D405/12 , C07D407/12 , C07D409/12 , C07D413/12 , C07D417/12 , C07D417/14
摘要： Compounds of formula (I): wherein: R2 is H or an optionally substituted C1-4 alkyl group; Y is either —(CH2)n—X—, where n is 1 or 2 and X is O, S, S(═O), S(═O)2, or NRN1, where RN1 is selected from H or optionally substituted C1-4 alkyl, or Y is —C(═O)NRN2—, where RN2 is selected from H, and optionally substituted C1-7 alkyl or C5-20 aryl; R3 is an optionally substituted C6 aryl group linked to a further optionally substituted C6 aryl group, wherein if both C6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a C1-3 alkylene group; and R5 is either: (i) carboxy; (ii) a group of formula (II): (iii) a group of formula (III): wherein R is optionally substituted C1-7 alkyl, C5-20 aryl or NRN3RN4, where RN3 and RN4 are independently selected from optionally substituted C1-4 alkyl; (iv) tetrazol-5-yl.

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