公开(公告)号：US20050032734A1

公开(公告)日：2005-02-10

申请号：US10838659

申请日：2004-05-03

申请人： Arthur Krieg ,  Heather Davis ,  Tong Wu ,  Joachim Schorr

发明人： Arthur Krieg ,  Heather Davis ,  Tong Wu ,  Joachim Schorr

IPC分类号： A61K39/29 ,  A61K39/39 ,  A61K48/00 ,  C12N15/861

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/292 ,  A61K39/39 ,  A61K48/00 ,  A61K2039/53 ,  A61K2039/55561 ,  A61K2039/57 ,  C12N2710/10343 ,  C12N2730/10134

摘要： The present invention shows that DNA vaccine vectors can be improved by removal of CpG-N motifs and optional addition of CpG-S motifs. In addition, for high and long-lasting levels of expression, the optimized vector should include a promoter/enhancer that is hot down-regulated by the cytokines induced by the immunostimulatory CpG motifs. Vectors and methods of use for immunostimulation are provided herein. The invention also provides improved gene therapy vectors by determining the CpG-N and CpG-S motifs present in the construct, removing stimulatory CpG (CpG-S) motifs and/or inserting neutralizing CpG (CpG-N) motifs, thereby producing a nucleic acid construct providing enhanced expression of the therapeutic polypeptide. Methods of use for such vectors are also included herein.

摘要翻译： 本发明显示可以通过除去CpG-N基序和任选添加CpG-S基序来改善DNA疫苗载体。 此外，对于高和长期表达水平，优化的载体应包括由免疫刺激性CpG基序诱导的细胞因子热下调的启动子/增强子。 本文提供了用于免疫刺激的载体和方法。 本发明还通过确定构建体中存在的CpG-N和CpG-S基序，除去刺激性CpG（CpG-S）基序和/或插入中和CpG（CpG-N）基序，从而产生核酸 提供治疗性多肽的增强的表达。 这些载体的使用方法也包括在本文中。

公开(公告)号：US06339068B1

公开(公告)日：2002-01-15

申请号：US09082649

申请日：1998-05-20

申请人： Arthur M. Krieg ,  Heather L. Davis ,  Tong Wu ,  Joachim Schorr

发明人： Arthur M. Krieg ,  Heather L. Davis ,  Tong Wu ,  Joachim Schorr

IPC分类号： A61K4800

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/292 ,  A61K39/39 ,  A61K48/00 ,  A61K2039/53 ,  A61K2039/55561 ,  A61K2039/57 ,  C12N2710/10343 ,  C12N2730/10134

摘要： The present invention shows that DNA vaccine vectors can be improved by removal of CpG-N motifs and optional addition of CpG-S motifs. In addition, for high and long-lasting levels of expression, the optimized vector should include a promoter/enhancer that is not down-regulated by the cytokines induced by the immunostimulatory CpG motifs. Vectors and methods of use for immunostimulation are provided herein. The invention also provides improved gene therapy vectors by determining the CpG-N and CpG-S motifs present in the construct, removing stimulatory CpG (CpG-S) motifs and/or inserting neutralizing CpG (CpG-N) motifs, thereby producing a nucleic acid construct providing enhanced expression of the therapeutic polypeptide. Methods of use for such vectors are also included herein.

摘要翻译： 本发明显示可以通过除去CpG-N基序和任选添加CpG-S基序来改善DNA疫苗载体。 此外，对于高和长期的表达水平，优化的载体应包括不被免疫刺激性CpG基序诱导的细胞因子下调的启动子/增强子。 本文提供了用于免疫刺激的载体和方法。 本发明还通过确定构建体中存在的CpG-N和CpG-S基序，除去刺激性CpG（CpG-S）基序和/或插入中和CpG（CpG-N）基序，从而产生核酸 提供治疗性多肽的增强的表达。 这些载体的使用方法也包括在本文中。

公开(公告)号：US5862995A

公开(公告)日：1999-01-26

申请号：US626128

申请日：1996-04-01

申请人： Tong Wu

发明人： Tong Wu

IPC分类号： F02M55/02 ,  F02M57/02 ,  F02M59/44 ,  F02M61/16 ,  F02M63/00 ,  F02M59/00

CPC分类号： F02M59/44 ,  F02M57/02 ,  F02M59/445 ,  F02M2200/22 ,  Y10S277/935 ,  Y10S277/94

摘要： A fuel injector assembly for an internal combustion engine includes an injector body having a control valve in fluid communication with a source of fuel. A fuel nozzle assembly is employed to disperse fuel from the assembly. A high pressure fuel passage provides fluid communication between the control valve and the fuel nozzle assembly. The high pressure fuel passage has at least one end opening through the injector body and having an inner diameter. A shape memory alloy plug seals the open end of the fuel passage. The plug has a first diameter smaller than the inner diameter when inserted into the open end and a second diameter in sealing engagement with the inner diameter upon undergoing a metallurgical phase change from martinsite to austenite such that the plug generates a seal with the fuel passage. In addition, a method of making the fuel injector assembly employing a shape memory alloy plug to seal the high pressure fuel passage is also disclosed.

摘要翻译： 用于内燃机的燃料喷射器组件包括具有与燃料源流体连通的控制阀的喷射器主体。 使用燃料喷嘴组件来分散来自组件的燃料。 高压燃料通道提供控制阀和燃料喷嘴组件之间的流体连通。 高压燃料通道具有通过喷射器主体的至少一个端部开口并且具有内径。 形状记忆合金塞密封燃料通道的开口端。 塞子当插入开口端时具有小于内径的第一直径，以及当经历从马氏体到奥氏体的冶金相变时与内径密封接合的第二直径，使得塞与燃料通道产生密封。 此外，还公开了使用形状记忆合金塞密封高压燃料通道的燃料喷射器组件的制造方法。