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1. 发明申请

US20090093024A1 Methods of generating libraries and uses thereof 有权
标题翻译：生成库的方法及其用途
公开(公告)号：US20090093024A1
公开(公告)日：2009-04-09
申请号：US12070904
申请日：2008-02-20
申请人： Peter M. Bowers , Andrew B. Cubitt , Robert A. Horlick
发明人： Peter M. Bowers , Andrew B. Cubitt , Robert A. Horlick
IPC分类号： C12P21/04 , C12P21/06 , C40B40/06
CPC分类号： C07K16/461 , C07K16/00 , C07K16/22 , C07K16/40 , C07K2317/21 , C07K2317/565 , C07K2317/92 , C40B50/06
摘要： This invention relates to methods for the generation of polynucleotide seed libraries and the use of these libraries in generating novel mutants of recombinant proteins and, more particularly, for generating focused libraries of recombinant human antibodies and screening for their affinity binding with target antigens.
摘要翻译：本发明涉及用于产生多核苷酸种子文库的方法，以及这些文库在产生重组蛋白质的新突变体中的用途，更具体地说，涉及产生重组人抗体的聚集文库并筛选其与靶抗原的亲和性结合。

2. 发明申请

US20090075378A1 Somatic hypermutation systems 审中-公开
标题翻译：体细胞超突变体系
公开(公告)号：US20090075378A1
公开(公告)日：2009-03-19
申请号：US12070905
申请日：2008-02-20
申请人： Robert A. Horlick , Andrew B. Cubitt , Peter M. Bowers
发明人： Robert A. Horlick , Andrew B. Cubitt , Peter M. Bowers
IPC分类号： C12N5/06 , C12N15/12 , C12N15/52 , C12N5/08 , C12N5/00 , C12N1/19 , C12N15/85 , C12N15/81
CPC分类号： C07K16/461 , C07K16/00 , C07K16/22 , C07K16/40 , C07K2317/21 , C07K2317/565 , C07K2317/92 , C40B50/06
摘要： The present application relates to somatic hypermutation (SHM) systems and synthetic genes. Synthetic genes can be designed using computer-based approaches to increase or decrease susceptibility of a polynucleotide to somatic hypermutation. Genes of interest are inserted into the vectors and subjected to activation-induced cytidine deaminase to induce somatic hypermutation. Proteins or portions thereof encoded by the modified genes can be introduced into a SHM system for somatic hypermutation and proteins or portions thereof exhibiting a desired phenotype or function can be isolated for in vitro or in vivo diagnostic or therapeutic uses.
摘要翻译：本申请涉及体细胞超突变（SHM）系统和合成基因。可以使用基于计算机的方法设计合成基因以增加或降低多核苷酸对体细胞超突变的易感性。将感兴趣的基因插入载体中并进行活化诱导的胞苷脱氨酶诱导体细胞超突变。由修饰的基因编码的蛋白质或其部分可以被引入用于体细胞超突变的SHM系统中，并且可以分离出表现出所需表型或功能的蛋白质或其部分用于体外或体内诊断或治疗用途。

3. 发明授权

US6046925A Photochromic fluorescent proteins and optical memory storage devices based on fluorescent proteins 失效
标题翻译：基于荧光蛋白的光致变色荧光蛋白和光学记忆存储装置
公开(公告)号：US6046925A
公开(公告)日：2000-04-04
申请号：US839685
申请日：1997-04-14
申请人： Roger Y. Tsien , Roger Heim , Andrew B. Cubitt , Robert M. Dickson , William E. Moerner
发明人： Roger Y. Tsien , Roger Heim , Andrew B. Cubitt , Robert M. Dickson , William E. Moerner
IPC分类号： C07K14/435 , G11B7/0045 , G11B7/005 , G11B7/0055 , G11B7/244 , G11B7/26 , G11C11/56 , G11C13/02 , G11C13/04
CPC分类号： G11C13/0019 , B82Y10/00 , C07K14/43595 , G11B7/00455 , G11B7/0052 , G11B7/244 , G11B7/26 , G11C11/5664 , G11C13/0014 , G11C13/04 , G11B2007/24624 , G11B7/00552
摘要： Photochromic fluorescent protein moiety having two or more stable states having excitation or emission spectra that are shifted from one wavelength region to another wavelength region in the two states are described. The photochromic material switches between states by irradiation with light of appropriate wavelengths. The two states are preferably stable at room temperature and in the dark. The switching between states can be reversible.
摘要翻译：描述具有两个或更多个稳定状态的光致变色荧光蛋白部分，其具有在两种状态下从一个波长区域移动到另一个波长区域的激发或发射光谱。光致变色材料通过用适当波长的光照射而在状态之间切换。两个状态优选在室温下和黑暗中稳定。状态之间的切换可以是可逆的。

4. 发明授权

US08685897B2 Methods of generating libraries and uses thereof 有权
标题翻译：生成库的方法及其用途
公开(公告)号：US08685897B2
公开(公告)日：2014-04-01
申请号：US13109106
申请日：2011-05-17
申请人： Peter M. Bowers , Andrew B. Cubitt , Robert A. Horlick
发明人： Peter M. Bowers , Andrew B. Cubitt , Robert A. Horlick
IPC分类号： C40B50/06
CPC分类号： C07K16/461 , C07K16/00 , C07K16/22 , C07K16/40 , C07K2317/21 , C07K2317/565 , C07K2317/92 , C40B50/06
摘要： This invention relates to methods for the generation of humanized antibodies, particularly a humanized antibody heavy chain protein and a humanized antibody light chain protein. The method comprises using cells that express or can be induced to express Activation Induced Cytidine Deaminase (AID).
摘要翻译：本发明涉及产生人源化抗体，特别是人源化抗体重链蛋白质和人源化抗体轻链蛋白质的方法。该方法包括使用表达或可诱导表达激活诱导的胞苷脱氨酶（AID）的细胞。

5. 发明申请

US20110191873A1 Methods of Protein Destabilization and Uses Thereof 审中-公开
标题翻译：蛋白质不稳定的方法及其用途
公开(公告)号：US20110191873A1
公开(公告)日：2011-08-04
申请号：US12938179
申请日：2010-11-02
申请人： Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
发明人： Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
IPC分类号： A01K67/00 , C12N5/10 , C07H21/04 , C12N1/00 , C07K19/00 , A01H5/00 , C12Q1/02 , C12Q1/37 , C12Q1/42 , C12Q1/48 , C12Q1/66 , C12N5/07 , C12N5/071 , C12N5/04
CPC分类号： C12Q1/485
摘要： This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译：本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。在一个实施方案中，本发明包括使用不可切割的多聚化泛素融合蛋白来使目标蛋白如报道分子部分不稳定。在该方法的一个方面，构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的连接体。在该实施方案中，接头的酶修饰导致报道蛋白与多聚泛素结构域的偶联的调节，导致报道部分稳定性的变化。然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。在另一个实施方案中，本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。在该方法的一个方面，靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联，并导致靶蛋白的稳定性和浓度增加。

6. 发明授权

US5925558A Assays for protein kinases using fluorescent protein substrates 失效
公开(公告)号：US5925558A
公开(公告)日：1999-07-20
申请号：US680876
申请日：1996-07-16
申请人： Roger Y. Tsien , Andrew B. Cubitt
发明人： Roger Y. Tsien , Andrew B. Cubitt
IPC分类号： C07K14/435 , C12N1/21 , C12Q1/48 , G01N33/58 , C12N15/62 , C07K19/00
CPC分类号： G01N33/582 , C07K14/43595 , C12Q1/48 , G01N2333/91205
摘要： This invention provides assays for protein kinase activity using fluorescent proteins engineered to include sequences that can be phosphorylated by protein kinases. The proteins exhibit different fluorescent properties in the non-phosphorylated and phosphorylated states.

7. 发明授权

US07824850B2 Methods of protein destabilization and uses thereof 有权
标题翻译：蛋白质不稳定的方法及其用途
公开(公告)号：US07824850B2
公开(公告)日：2010-11-02
申请号：US11821562
申请日：2007-06-22
申请人： Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
发明人： Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
IPC分类号： C12Q1/00 , C07K14/00
CPC分类号： C12Q1/485
摘要： This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译：本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。在一个实施方案中，本发明包括使用不可切割的多聚化泛素融合蛋白来使目标蛋白如报道分子部分不稳定。在该方法的一个方面，构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的连接体。在该实施方案中，接头的酶修饰导致报道蛋白与多聚泛素结构域的偶联的调节，导致报道部分稳定性的变化。然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。在另一个实施方案中，本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。在该方法的一个方面，靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联，并导致靶蛋白的稳定性和浓度增加。

8. 发明授权

US6054321A Long wavelength engineered fluorescent proteins 失效
标题翻译：长波长工程荧光蛋白
公开(公告)号：US6054321A
公开(公告)日：2000-04-25
申请号：US911825
申请日：1997-08-15
申请人： Roger Y. Tsien , S. James Remington , Andrew B. Cubitt , Roger Heim , Mats F. Ormo
发明人： Roger Y. Tsien , S. James Remington , Andrew B. Cubitt , Roger Heim , Mats F. Ormo
IPC分类号： C12N15/09 , C07H21/04 , C07K14/435 , C07K16/00 , C07K17/00 , C12N1/15 , C12N1/19 , C12N1/20 , C12N1/21 , C12N5/00 , C12N5/06 , C12N5/10 , C12N9/00 , C12N15/00 , C12P21/02 , C12Q1/68 , G01N33/00
CPC分类号： C07K14/43595 , Y10S435/968 , Y10T436/2525
摘要： This invention provides functional engineered fluorescent proteins with varied fluorescence characteristics that can be easily distinguished from currently existing green and blue fluorescent proteins. In one embodiment the invention provides for the three dimensional structure and atomic coordinates of an Aequorea green fluorescent protein and methods for their use. In one embodiment, this invention provides a computational method of modeling the three dimensional structure of any other fluorescent protein based on the three dimensional structure of an Aequorea green fluorescent protein.
摘要翻译：本发明提供具有变化的荧光特性的功能改造的荧光蛋白，其可以容易地与目前存在的绿色和蓝色荧光蛋白区分开。在一个实施方案中，本发明提供了Aequorea绿色荧光蛋白的三维结构和原子坐标及其使用方法。在一个实施方案中，本发明提供了基于Aequorea绿色荧光蛋白的三维结构对任何其它荧光蛋白的三维结构建模的计算方法。

9. 发明申请

US20110287485A1 METHODS OF GENERATING LIBRARIES AND USES THEREOF 有权
标题翻译：生成图书馆的方法及其用途
公开(公告)号：US20110287485A1
公开(公告)日：2011-11-24
申请号：US13109106
申请日：2011-05-17
申请人： PETER M. BOWERS , ANDREW B. CUBITT , ROBERT A. HORLICK
发明人： PETER M. BOWERS , ANDREW B. CUBITT , ROBERT A. HORLICK
IPC分类号： C12P21/00 , C12P21/08
CPC分类号： C07K16/461 , C07K16/00 , C07K16/22 , C07K16/40 , C07K2317/21 , C07K2317/565 , C07K2317/92 , C40B50/06
摘要： This invention relates to methods for the generation of humanized antibodies, particularly a humanized antibody heavy chain protein and a humanized antibody light chain protein. The method comprises using cells that express or can be induced to express Activation Induced Cytidine Deaminase (AID).
摘要翻译：本发明涉及产生人源化抗体，特别是人源化抗体重链蛋白质和人源化抗体轻链蛋白质的方法。该方法包括使用表达或可诱导表达激活诱导的胞苷脱氨酶（AID）的细胞。

10. 发明申请

US20110183855A1 SOMATIC HYPERMUTATION SYSTEMS 审中-公开
标题翻译： SOMATIC HYPERMUTATION系统
公开(公告)号：US20110183855A1
公开(公告)日：2011-07-28
申请号：US12972328
申请日：2010-12-17
申请人： Robert A. Horlick , Andrew B. Cubitt , Peter M. Bowers
发明人： Robert A. Horlick , Andrew B. Cubitt , Peter M. Bowers
IPC分类号： C40B10/00 , C07K16/00 , C07K14/00 , C12N9/00 , C07K14/195 , C07K14/435 , C07K14/52 , C07K14/575
CPC分类号： C07K16/461 , C07K16/00 , C07K16/22 , C07K16/40 , C07K2317/21 , C07K2317/565 , C07K2317/92 , C40B50/06
摘要： The present application relates to somatic hypermutation (SHM) systems and synthetic genes. Synthetic genes can be designed using computer-based approaches to increase or decrease susceptibility of a polynucleotide to somatic hypermutation. Genes of interest are inserted into the vectors and subjected to activation-induced cytidine deaminase to induce somatic hypermutation. Proteins or portions thereof encoded by the modified genes can be introduced into a SHM system for somatic hypermutation and proteins or portions thereof exhibiting a desired phenotype or function can be isolated for in vitro or in vivo diagnostic or therapeutic uses.
摘要翻译：本申请涉及体细胞超突变（SHM）系统和合成基因。可以使用基于计算机的方法设计合成基因以增加或降低多核苷酸对体细胞超突变的易感性。将感兴趣的基因插入载体中并进行活化诱导的胞苷脱氨酶诱导体细胞超突变。由修饰的基因编码的蛋白质或其部分可以被引入用于体细胞超突变的SHM系统中，并且可以分离出表现出所需表型或功能的蛋白质或其部分用于体外或体内诊断或治疗用途。

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