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21. 发明授权

US07255258B2 System and associated friction stir welding (FSW) assembly, controller and method for performing a friction stir welding operation 有权
标题翻译：系统和相关的摩擦搅拌焊接（FSW）组件，用于进行摩擦搅拌焊接操作的控制器和方法
公开(公告)号：US07255258B2
公开(公告)日：2007-08-14
申请号：US10706480
申请日：2003-10-27
申请人： Dwight A. Burford , Edwin H. Fenn , Danny R. High , Robert M. Kay
发明人： Dwight A. Burford , Edwin H. Fenn , Danny R. High , Robert M. Kay
IPC分类号： B23K37/00 , B23K20/12 , B23K31/02
CPC分类号： B23K20/122 , B23K20/123
摘要： A system and associated friction stir welding (FSW) assembly, controller and method for performing a friction stir welding operation are provided. The friction stir welding system includes a FSW device, such as a CNC machine, that includes an actuator capable of moving a FSW tool relative to a workpiece. The system also includes a controller capable of controlling the FSW device to drive the actuator to move the FSW tool. In this regard, the actuator is capable of being driven such that the FSW tool is capable of performing a friction stir welding operation on the workpiece. The controller is capable of monitoring a torque of the actuator to thereby control the FSW device to drive the actuator such that the torque is maintained within a range about a torque setting.
摘要翻译：提供了一种系统和相关的摩擦搅拌焊接（FSW）组件，用于执行摩擦搅拌焊接操作的控制器和方法。摩擦搅拌焊接系统包括诸如CNC机器的FSW装置，其包括能够使FSW工具相对于工件移动的致动器。该系统还包括一个能够控制FSW装置来驱动执行机构以移动FSW工具的控制器。在这方面，致动器能够被驱动，使得FSW工具能够对工件执行摩擦搅拌焊接操作。控制器能够监视致动器的扭矩，从而控制FSW装置驱动致动器，使得转矩保持在扭矩设定范围内。

22. 发明授权

US06255458B1 High affinity human antibodies and human antibodies against digoxin 失效
标题翻译：高亲和力的人体抗体和针对地高辛的人抗体
公开(公告)号：US06255458B1
公开(公告)日：2001-07-03
申请号：US09042353
申请日：1998-03-13
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： C07K1600
CPC分类号： A01K67/0275 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K38/00 , C07K14/7051 , C07K16/00 , C07K16/1232 , C07K16/16 , C07K16/244 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/4291 , C07K16/44 , C07K16/462 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2319/00 , C12N5/163 , C12N15/00 , C12N15/113 , C12N15/85 , C12N15/8509 , C12N15/87 , C12N15/90 , C12N15/907
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.
摘要翻译：本发明涉及能够产生异源抗体的转基因非人动物和用于产生以大量亲和力结合人抗原的人序列抗体的方法。

23. 发明授权

US5877397A Transgenic non-human animals capable of producing heterologous antibodies of various isotypes 失效
标题翻译：能够产生各种同种型的异源抗体的转基因非人动物
公开(公告)号：US5877397A
公开(公告)日：1999-03-02
申请号：US308865
申请日：1994-09-19
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： A01K67/027 , A61K38/00 , C07K14/725 , C07K16/00 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C12N5/16 , C12N15/00 , C12N15/85 , C12N15/87 , C12N15/90 , C07H21/02 , C07H21/04
CPC分类号： A01K67/0275 , A01K67/0276 , A01K67/0278 , C07K14/7051 , C07K16/00 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/4291 , C07K16/44 , C12N15/00 , C12N15/85 , C12N15/8509 , C12N15/87 , C12N15/90 , C12N15/907 , C12N5/163 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K38/00 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C12N2800/206 , C12N2800/70 , C12N2830/30 , C12N2830/36 , C12N2830/85
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.
摘要翻译：本发明涉及能够产生具有失活的内源免疫球蛋白基因的异源抗体和转基因非人动物的转基因非人动物。在本发明的一个方面，内源性免疫球蛋白基因被反义多核苷酸和/或针对内源性免疫球蛋白的抗血清抑制。异源抗体由非人动物种类的基因组中通常不存在的免疫球蛋白基因编码。在本发明的一个方面，将含有未经排列的异源人免疫球蛋白重链序列的一个或多个转基因引入非人动物中，从而形成能够功能重排转基因免疫球蛋白序列并产生编码的各种同种型抗体的所有组成的转基因动物通过人免疫球蛋白基因。这样的异源人抗体是在B细胞中产生的，其后被永生化，例如通过与永生化细胞系如骨髓瘤融合，或者通过其它技术操纵这样的B细胞，使能够产生单克隆异源抗体的细胞系。本发明还涉及用于制备这种转基因非人动物的重链和轻链免疫球蛋白转基因以及用于破坏转基因动物内源性免疫球蛋白基因座的方法和载体。

24. 发明授权

US5814318A Transgenic non-human animals for producing heterologous antibodies 失效
公开(公告)号：US5814318A
公开(公告)日：1998-09-29
申请号：US96762
申请日：1993-07-22
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： A01K67/027 , A61K38/00 , C07K14/725 , C07K16/00 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C07K16/46 , C12N5/16 , C12N15/00 , C12N15/113 , C12N15/85 , C12N15/87 , C12N15/90 , A61K39/00 , C07H21/04
CPC分类号： A01K67/0275 , A01K67/0276 , A01K67/0278 , C07K14/7051 , C07K16/00 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/4291 , C07K16/44 , C07K16/462 , C12N15/00 , C12N15/113 , C12N15/85 , C12N15/8509 , C12N15/87 , C12N15/90 , C12N15/907 , C12N5/163 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K38/00 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2319/00 , C12N2800/206 , C12N2800/70 , C12N2830/30 , C12N2830/36 , C12N2830/85
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.

25. 发明授权

US5789650A Transgenic non-human animals for producing heterologous antibodies 失效
标题翻译：用于产生异源抗体的转基因非人动物
公开(公告)号：US5789650A
公开(公告)日：1998-08-04
申请号：US853408
申请日：1992-03-18
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： C07K16/00 , C12N15/00 , C07H19/04
CPC分类号： C07K16/00 , A01K2217/05 , C07K2317/21
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.
摘要翻译：本发明涉及能够产生具有失活的内源免疫球蛋白基因的异源抗体和转基因非人动物的转基因非人动物。在本发明的一个方面，内源性免疫球蛋白基因被反义多核苷酸和/或针对内源性免疫球蛋白的抗血清抑制。异源抗体由非人动物种类的基因组中通常不存在的免疫球蛋白基因编码。在本发明的一个方面，将含有未经排列的异源人免疫球蛋白重链序列的一个或多个转基因引入非人动物中，从而形成能够功能重排转基因免疫球蛋白序列并产生编码的各种同种型抗体的所有组成的转基因动物通过人免疫球蛋白基因。这样的异源人抗体是在B细胞中产生的，其后被永生化，例如通过用永生化细胞系如骨髓瘤进行融合，或通过其它技术操纵这样的B细胞以使能够产生单克隆异源抗体的细胞系。本发明还涉及用于制备这种转基因非人动物的重链和轻链免疫球蛋白转基因以及用于破坏转基因动物内源性免疫球蛋白基因座的方法和载体。

26. 发明授权

US5633425A Transgenic non-human animals capable of producing heterologous antibodies 失效
标题翻译：能够产生异源抗体的转基因非人动物
公开(公告)号：US5633425A
公开(公告)日：1997-05-27
申请号：US834539
申请日：1992-02-05
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： C07K14/725 , C07K16/00 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C12N15/00 , C12N15/85 , C12N15/87 , C12N15/90 , C07H21/04
CPC分类号： C12N15/8509 , A01K67/0276 , A01K67/0278 , C07K14/7051 , C07K16/00 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/44 , C12N15/00 , C12N15/85 , C12N15/87 , C12N15/907 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C12N2800/206 , C12N2800/70 , C12N2830/30 , C12N2830/36 , C12N2830/85
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal. The invention also includes methods to generate a synthetic immunoglobulin variable region gene segment repertoire used in transgene construction and methods to induce heterologous antibody production using animals containing heterologous rearranged or unrearranged heavy and light chain immunoglobulin transgenes.
摘要翻译：本发明涉及能够产生异源抗体的转基因非人动物，即由非人动物种类的基因组中通常不存在的免疫球蛋白重链和轻链基因编码的抗体。在本发明的一个方面，将编码未经修饰的异源人免疫球蛋白重链和轻链的转基因导入非人动物中，从而形成能产生人免疫球蛋白基因编码抗体的转基因动物。这样的异源人抗体是在B细胞中产生的，其后被永生化，例如通过用永生化细胞系如骨髓瘤进行融合，或通过其它技术操纵这样的B细胞来使能够产生单克隆异源抗体的细胞系。本发明还涉及用于制备这种转基因非人动物的重链和轻链免疫球蛋白转基因以及用于破坏转基因动物内源性免疫球蛋白基因座的方法和载体。本发明还包括产生用于转基因构建的合成免疫球蛋白可变区基因片段谱的方法和使用含有异源重排或未重排的重链和轻链免疫球蛋白转基因的动物诱导异源抗体产生的方法。

27. 发明授权

US5545806A Ransgenic non-human animals for producing heterologous antibodies 失效
标题翻译：用于产生异源抗体的致病非人动物
公开(公告)号：US5545806A
公开(公告)日：1996-08-13
申请号：US990860
申请日：1992-12-16
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： A01K67/027 , A61K38/00 , C07K14/725 , C07K16/00 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C12N5/16 , C12N15/00 , C12N15/85 , C12N15/87 , C12N15/90 , A61K39/00 , C07H21/64
CPC分类号： C12N15/907 , A01K67/0276 , C07K14/7051 , C07K16/00 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/4291 , C07K16/44 , C12N15/00 , C12N15/85 , C12N15/8509 , C12N15/87 , C12N15/90 , C12N5/163 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A01K2267/03 , A61K38/00 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C12N2800/206 , C12N2800/70 , C12N2830/30 , C12N2830/36 , C12N2830/85
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.
摘要翻译：本发明涉及能够产生具有失活的内源免疫球蛋白基因的异源抗体和转基因非人动物的转基因非人动物。在本发明的一个方面，内源性免疫球蛋白基因被反义多核苷酸和/或针对内源性免疫球蛋白的抗血清抑制。异源抗体由非人动物种类的基因组中通常不存在的免疫球蛋白基因编码。在本发明的一个方面，将含有未经排列的异源人免疫球蛋白重链序列的一个或多个转基因引入非人动物中，从而形成能够功能重排转基因免疫球蛋白序列并产生编码的各种同种型抗体的所有组成的转基因动物通过人免疫球蛋白基因。这样的异源人抗体是在B细胞中产生的，其后被永生化，例如通过与永生化细胞系如骨髓瘤融合，或者通过其它技术操纵这样的B细胞，使能够产生单克隆异源抗体的细胞系。本发明还涉及用于制备这种转基因非人动物的重链和轻链免疫球蛋白转基因以及用于破坏转基因动物内源性免疫球蛋白基因座的方法和载体。

28. 发明授权

US5347361A Rotation sensor output signal processor 失效
标题翻译：旋转传感器输出信号处理器
公开(公告)号：US5347361A
公开(公告)日：1994-09-13
申请号：US865128
申请日：1992-04-08
申请人： Robert M. Kay
发明人： Robert M. Kay
IPC分类号： G01C19/68 , G01C19/66 , G01C19/64
CPC分类号： G01C19/664
摘要： Angular motion sensor signals from an inertial integrating rate sensor are provided to a translation device that provides a translated output signal that is substantially the same as an input sensor signal translated in frequency by an amount equal to a reference frequency. The translated output signal is provided to a phase detector that provides a detector output signal indicative of phase differences between the translated output signal and a feedback signal. The phase detector output signal is provided to a voltage controlled oscillator which provides an oscillator output signal that is related to the phase detector output signal. The voltage controlled oscillator signal is provided to a counter that is capable of providing a count that is representative of a highly resolved measure of angular rotation. In addition, the counter is capable of providing the feedback signal that is related to the variable frequency output signal.
摘要翻译：来自惯性积分速率传感器的角运动传感器信号被提供给翻译装置，该翻译装置提供与经频率转换等于参考频率的量的输入传感器信号基本上相同的转换输出信号。转换的输出信号被提供给相位检测器，该相位检测器提供指示转换的输出信号和反馈信号之间的相位差的检测器输出信号。相位检测器输出信号被提供给压控振荡器，其提供与相位检测器输出信号相关的振荡器输出信号。压控振荡器信号被提供给能够提供表示高度分辨的角度旋转度量的计数的计数器。此外，计数器能够提供与可变频率输出信号相关的反馈信号。

29. 发明授权

US07722873B2 Heterologous antibodies which bind human CD4 有权
标题翻译：结合人类CD4的异源抗体
公开(公告)号：US07722873B2
公开(公告)日：2010-05-25
申请号：US11349724
申请日：2006-02-08
申请人： Nils Lonberg , Robert M. Kay , Dianne M. Fishwild
发明人： Nils Lonberg , Robert M. Kay , Dianne M. Fishwild
IPC分类号： A61K39/395
CPC分类号： A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2267/01 , C07K16/2812 , C07K2317/21 , C12N15/8509
摘要： The invention relates to transgenic non-human animals capable of producing high affinity human sequence antibodies. The invention is also directed to human sequence antibodies specific for human antigens, such as, human CD4. The invention also is directed to methods for producing human sequence antibodies.
摘要翻译：本发明涉及能够产生高亲和力的人序列抗体的转基因非人动物。本发明还涉及对人抗原特异的人类序列抗体，例如人CD4。本发明还涉及用于产生人序列抗体的方法。

30. 发明申请

US20090255002A1 Transgenic Non-Human Animals For Producing Chimeric Antibodies 失效
标题翻译：用于产生嵌合抗体的转基因非人动物
公开(公告)号：US20090255002A1
公开(公告)日：2009-10-08
申请号：US12239523
申请日：2008-09-26
申请人： Nils Lonberg , Robert M. Kay
发明人： Nils Lonberg , Robert M. Kay
IPC分类号： A01K67/027 , C12P21/00 , C12P21/04 , C12N5/06
CPC分类号： C07K16/462 , A01K67/0275 , A01K67/0276 , A01K67/0278 , A01K2217/05 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C12N15/8509
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.
摘要翻译：本发明涉及能够产生异源抗体的转基因非人动物和用于产生以大量亲和力结合人抗原的人序列抗体的方法。

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