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1. 发明授权

US08372636B2 Yeast cell surface display of proteins and uses thereof 有权
公开(公告)号：US08372636B2
公开(公告)日：2013-02-12
申请号：US12316916
申请日：2008-12-16
申请人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
IPC分类号： C12N15/00
CPC分类号： C07K14/705 , C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 104 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. In effect, yeast has evolved a platform for protein-protein binding without steric hindrance from cell wall components. As one embodiment, attaching an scFv antibody fragment to the Aga2p agglutinin effectively mimics the cell surface display of antibodies by B cells in the immune system for affinity maturation in vivo. As another embodiment, T cell receptor mutants can be isolated by this method that are efficiently displayed on the yeast cell surface, providing a means of altering T cell receptor binding affinity and specificity by library screening.

2. 发明申请

US20110069878A1 HIGH SPEED OPTICAL INSPECTION SYSTEM WITH CAMERA ARRAY AND COMPACT, INTEGRATED ILLUMINATOR 有权
标题翻译：具有相机阵列和紧凑型集成照明器的高速光学检测系统
公开(公告)号：US20110069878A1
公开(公告)日：2011-03-24
申请号：US12886803
申请日：2010-09-21
申请人： Steven K. Case , Beverly Caruso , Carl E. Haugan , Steven A. Rose , David M. Kranz
发明人： Steven K. Case , Beverly Caruso , Carl E. Haugan , Steven A. Rose , David M. Kranz
IPC分类号： G06K9/00
CPC分类号： G06K9/2027 , G01N21/8806 , G01N21/8903 , G01N21/956 , G06K9/2036 , G06K9/209
摘要： An optical inspection system is provided for inspecting a workpiece including a feature to be inspected. The system includes a workpiece transport configured to transport the workpiece in a nonstop manner. An illuminator is configured to provide a first strobed illumination field type and a second strobed illumination field type. The illuminator includes a light pipe having a first end proximate the feature, and a second end opposite the first end and spaced from the first end. The light pipe also has at least one reflective sidewall. The first end has an exit aperture and the second end has at least one second end aperture to provide a view of the feature therethrough. An array of cameras is configured to digitally image the feature. The array of cameras is configured to generate a first plurality of images of the feature with the first illumination field and a second plurality of images of the feature with the second illumination field. A processing device is operably coupled to the illuminator and the array of cameras, the processing device is configured to store at least some of the first and second plurality of images and provide the first and second pluralities to an other device.
摘要翻译：提供了一种用于检查包括待检查特征的工件的光学检查系统。该系统包括被配置为以不间断方式输送工件的工件传送。照明器被配置为提供第一选通照明场类型和第二选通照明场类型。照明器包括具有靠近特征的第一端的光管和与第一端相对并与第一端间隔开的第二端。光管还具有至少一个反射侧壁。第一端具有出口孔，并且第二端具有至少一个第二端孔，以提供穿过其中的特征的视图。摄像机阵列被配置为对特征进行数字成像。相机阵列被配置为利用第一照明场和具有第二照明场的特征的第二多个图像来生成特征的第一多个图像。处理装置可操作地耦合到照明器和相机阵列，处理装置被配置为存储第一和第二多个图像中的至少一些，并且将第一和第二多个部件提供给另一个装置。

3. 发明授权

US07746481B2 Method for measuring center of rotation of a nozzle of a pick and place machine using a collimated laser beam 有权
标题翻译：使用准直激光束测量拾取和放置机器的喷嘴旋转中心的方法
公开(公告)号：US07746481B2
公开(公告)日：2010-06-29
申请号：US12051961
申请日：2008-03-20
申请人： David M. Kranz , David W. Duquette , Matthew W. Dawson
发明人： David M. Kranz , David W. Duquette , Matthew W. Dawson
IPC分类号： G01B11/24
CPC分类号： G01B11/272
摘要： A method of measuring and storing a center of rotation of a nozzle in a pick and place machine is provided. The method includes coupling an artifact to the nozzle. A substantially collimated laser beam is directed at the artifact, which is rotated while the collimated laser beam is energized. Edges of a shadow cast by the rotating artifact are detected and used to calculate error of a coordinate of the center of rotation of the nozzle. A coordinate of the center of rotation of the nozzle is calculated based upon a previous coordinate of the center of rotation and the error. The calculated coordinate of the center of rotation is stored for subsequent measurements.
摘要翻译：提供了一种在拾取和放置机器中测量和存储喷嘴的旋转中心的方法。该方法包括将假象耦合到喷嘴。基本上准直的激光束被引导到伪影，其在准直激光束通电时旋转。检测由旋转伪影投射的阴影的边缘，并用于计算喷嘴旋转中心坐标的误差。基于旋转中心和误差的先前坐标来计算喷嘴旋转中心的坐标。旋转中心的计算坐标存储用于后续测量。

4. 发明授权

US06909515B2 Multiple source alignment sensor with improved optics 有权
标题翻译：具有改进光学元件的多源对准传感器
公开(公告)号：US06909515B2
公开(公告)日：2005-06-21
申请号：US10649324
申请日：2003-08-27
申请人： David D. Madsen , David M. Kranz , Frederick M. Cash, II
发明人： David D. Madsen , David M. Kranz , Frederick M. Cash, II
IPC分类号： G01B11/03 , H05K13/04 , G01B11/14
CPC分类号： H05K13/0413 , H05K13/0813
摘要： Features of the present invention provide an optical layout that can accommodate the relatively strict enclosure requirements for compact component alignment sensor. Specifically, aspects of the present invention provide a single optical component that reduces the degree of divergence, and preferably substantially collimates light from the plurality of divergent light sources prior to entering the sensing field. In this regard, part count is kept low and the physical size of the optical train itself is relatively small.
摘要翻译：本发明的特征提供了一种光学布局，其可以适应紧凑的部件对准传感器的相对严格的外壳要求。具体地，本发明的方面提供了降低发散度的单个光学部件，并且优选地在进入感测场之前大体上准直来自多个发散光源的光。在这方面，部件数量保持较低，并且光学系统本身的物理尺寸相对较小。

5. 发明授权

US5977321A Heterodimeric T lymphocyte receptor subunit 失效
标题翻译：异二聚体T淋巴细胞受体亚单位
公开(公告)号：US5977321A
公开(公告)日：1999-11-02
申请号：US742539
申请日：1991-08-08
申请人： Haruo Saito , David M. Kranz , Herman N. Eisen , Susumu Tonegawa
发明人： Haruo Saito , David M. Kranz , Herman N. Eisen , Susumu Tonegawa
IPC分类号： C07K14/725 , C07K16/28
CPC分类号： C07K16/2809 , C07K14/7051
摘要： Disclosed is a heterodimeric T lymphocyte receptor subunit. The subunit consists of variable, joining, constant, transmembrane, and cytoplasmic regions.The structure, amino acid, and nucleotide sequence of the lymphocyte receptor subunit were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes.T cell receptor subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.
摘要翻译：公开了异二聚体T淋巴细胞受体亚基。亚基由可变，连接，恒定，跨膜和胞质区组成。使用衍生自功能性鼠细胞毒性T淋巴细胞克隆的cDNA克隆测定淋巴细胞受体亚基的结构，氨基酸和核苷酸序列。与这些cDNA相对应的基因在T细胞中特异性表达和重排，并且与免疫球蛋白V和C基因具有显着的序列同源性。 T细胞受体亚基可以从cDNA克隆产生。蛋白质分子可以进一步用于生产T细胞克隆特异性抗体。

6. 发明授权

US5547668A Conjugates of folate anti-effector cell antibodies 失效
标题翻译：叶酸抗效应细胞抗体的缀合物
公开(公告)号：US5547668A
公开(公告)日：1996-08-20
申请号：US435175
申请日：1995-05-05
申请人： David M. Kranz , Edward J. Roy , Todd A. Patrick
发明人： David M. Kranz , Edward J. Roy , Todd A. Patrick
IPC分类号： A61K35/14 , A61K47/48 , C07K16/28 , A61K39/395 , C21P21/08
CPC分类号： A61K47/48561 , C07K16/2809
摘要： The present invention provides a process of targeting folate-receptor-positive tumor cells for lysis by binding a conjugate of folate and an anti-T-cell-receptor antibody or an anti-Fc receptor antibody to those cells. A process of lysing folate-receptor-positive tumor cells comprising exposing the cells to a folate/anti-T-cell-receptor antibody in the presence of a population of T-cells is also provided. A process of lysing folate-receptor-positive tumor cells comprising exposing the cells to a folate/anti-Fc receptor antibody in the presence of a population of natural killer cells, monocytes, or macrophages is also provided. Still further, the present invention provides a conjugate of folate to an anti-T-cell-receptor antibody or an anti-Fc receptor antibody.
摘要翻译：本发明提供了通过将叶酸和抗T细胞受体抗体或抗Fc受体抗体的缀合物与这些细胞结合来靶向叶酸受体阳性肿瘤细胞进行裂解的方法。还提供了裂解叶酸受体阳性肿瘤细胞的方法，包括在存在T细胞群的情况下将细胞暴露于叶酸/抗T细胞受体抗体。还提供了裂解叶酸受体阳性肿瘤细胞的方法，包括在存在天然杀伤细胞，单核细胞或巨噬细胞的情况下将细胞暴露于叶酸/抗-Fc受体抗体。此外，本发明提供叶酸与抗T细胞受体抗体或抗Fc受体抗体的缀合物。

7. 发明申请

US20090280560A1 Yeast cell surface display of proteins and uses thereof 有权
标题翻译：蛋白质的酵母细胞表面展示及其用途
公开(公告)号：US20090280560A1
公开(公告)日：2009-11-12
申请号：US12316916
申请日：2008-12-16
申请人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
IPC分类号： C12N15/63 , C07K9/00 , C07K16/00 , C07K14/725
CPC分类号： C07K14/705 , C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 104 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. In effect, yeast has evolved a platform for protein-protein binding without steric hindrance from cell wall components. As one embodiment, attaching an scFv antibody fragment to the Aga2p agglutinin effectively mimics the cell surface display of antibodies by B cells in the immune system for affinity maturation in vivo. As another embodiment, T cell receptor mutants can be isolated by this method that are efficiently displayed on the yeast cell surface, providing a means of altering T cell receptor binding affinity and specificity by library screening.
摘要翻译：本发明提供了一种遗传方法，用于以能够与大分子结合的形式将多肽连接到酵母细胞壁。将该方法与荧光激活细胞分选相结合提供了选择具有增加或降低的对另一分子的亲和力，改变的特异性或条件结合的蛋白质的方法。还提供了目的多肽的N末端与酵母Aga2p细胞壁蛋白的C末端的遗传融合的方法。每个酵母细胞的外壁可以显示大约104个蛋白质凝集素。天然凝集素用作特异性粘附接触，以在交配期间融合相反交配型的酵母细胞。实际上，酵母已经发展出蛋白质 - 蛋白质结合的平台，而没有来自细胞壁组分的空间位阻。作为一个实施方案，将scFv抗体片段连接到Aga2p凝集素上有效地模拟了免疫系统中B细胞的抗体的细胞表面显示，用于体内的亲和力成熟。作为另一个实施方案，可以通过这种方法分离T细胞受体突变体，其有效地显示在酵母细胞表面上，提供通过文库筛选来改变T细胞受体结合亲和力和特异性的方法。

8. 发明授权

US07465787B2 Yeast cell surface display of proteins and uses thereof 有权
标题翻译：蛋白质的酵母细胞表面展示及其用途
公开(公告)号：US07465787B2
公开(公告)日：2008-12-16
申请号：US10738454
申请日：2003-12-16
申请人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
IPC分类号： C07K14/37 , C07K14/39 , C07K16/28 , C07K16/46 , C07K17/00 , C07K17/02 , C07K17/06 , C12Q1/02 , C12Q1/68 , C12N1/19 , C12N15/63 , C12N15/64
CPC分类号： C07K14/705 , C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 10 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. In effect, yeast has evolved a platform for protein-protein binding without steric hindrance from cell wall components.
摘要翻译：本发明提供了一种遗传方法，用于以能够与大分子结合的形式将多肽连接到酵母细胞壁。将该方法与荧光激活细胞分选相结合提供了选择具有增加或降低的对另一分子的亲和力，改变的特异性或条件结合的蛋白质的方法。还提供了目的多肽的N末端与酵母Aga2p细胞壁蛋白的C末端的遗传融合的方法。每个酵母细胞的外壁可以显示约10个蛋白质凝集素。天然凝集素用作特异性粘附接触，以在交配期间融合相反交配型的酵母细胞。实际上，酵母已经发展出蛋白质 - 蛋白质结合的平台，而没有来自细胞壁组件的空间位阻。

9. 发明授权

US06759243B2 High affinity TCR proteins and methods 有权
标题翻译：高亲和力TCR蛋白和方法
公开(公告)号：US06759243B2
公开(公告)日：2004-07-06
申请号：US09731242
申请日：2000-12-06
申请人： David M. Kranz , K. Dane Wittrup , Phillip D. Holler
发明人： David M. Kranz , K. Dane Wittrup , Phillip D. Holler
IPC分类号： C12N510
CPC分类号： C40B40/02 , C07K14/7051 , C12N15/1037 , G01N33/68 , G01N33/6842 , G01N33/6854 , G01N2333/39
摘要： T cell receptors (TCRs) that have higher affinity for a ligand than wild type TCRs are provided. These high affinity TCRs are formed by mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants of the T cell receptor protein coding sequence; transforming the T cell receptor mutant coding sequence into yeast cells; inducing expression of the T cell receptor mutant coding sequence on the surface of yeast cells; and selecting those cells expressing T cell receptor mutants that have higher affinity for the peptide/MHC ligand than the wild type T cell receptor protein. The high affinity TCRs can be used in place of an antibody or single chain antibody.
摘要翻译：提供了比野生型TCR对配体具有更高亲和力的T细胞受体（TCR）。通过诱变T细胞受体蛋白质编码序列产生T细胞受体蛋白编码序列突变体的杂色群体，形成这些高亲和性TCR。将T细胞受体突变体编码序列转化为酵母细胞; 在酵母细胞表面诱导T细胞受体突变体编码序列的表达; 并选择那些表达与野生型T细胞受体蛋白相比对肽/ MHC配体具有更高亲和力的T细胞受体突变体的细胞。高亲和性TCR可用于代替抗体或单链抗体。

10. 发明授权

US06699658B1 Yeast cell surface display of proteins and uses thereof 失效
标题翻译：蛋白质的酵母细胞表面展示及其用途
公开(公告)号：US06699658B1
公开(公告)日：2004-03-02
申请号：US09009388
申请日：1998-01-20
申请人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
IPC分类号： C12Q168
CPC分类号： C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 104 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. In effect, yeast has evolved a platform for protein-protein binding without steric hindrance, from cell wall components. As one embodiment, attaching an scFv antibody fragment to the Aga2p agglutinin effectively mimics the cell surface display of antibodies by B cells in the immune system for affinity maturation in vivo. As another embodiment, T cell receptor mutants can be isolated by this method that are efficiently displayed on the yeast cell surface, providing a means of altering T cell receptor binding affinity and specificity by library screening.
摘要翻译：本发明提供了一种遗传方法，用于以能够与大分子结合的形式将多肽连接到酵母细胞壁。将该方法与荧光激活细胞分选相结合提供了选择具有增加或降低的对另一分子的亲和力，改变的特异性或条件结合的蛋白质的方法。还提供了目的多肽的N末端与酵母Aga2p细胞壁蛋白的C末端的遗传融合的方法。每个酵母细胞的外壁可显示约10 4个蛋白质凝集素。天然凝集素用作特异性粘附接触，以在交配期间融合相反交配型的酵母细胞。实际上，酵母已经发展出蛋白质 - 蛋白质结合的平台，没有空间位阻，来自细胞壁组分。作为一个实施方案，将scFv抗体片段连接到Aga2p凝集素上有效地模拟了免疫系统中B细胞的抗体的细胞表面显示，用于体内的亲和力成熟。作为另一个实施方案，可以通过这种方法分离T细胞受体突变体，其有效地显示在酵母细胞表面上，提供通过文库筛选来改变T细胞受体结合亲和力和特异性的方法。

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