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11. 发明授权

US4816513A Automated polypeptide synthesis process 失效
标题翻译：自动多肽合成过程
公开(公告)号：US4816513A
公开(公告)日：1989-03-28
申请号：US53324
申请日：1987-05-22
申请人： John Bridgham , Timothy G. Geiser , Michael W. Hunkapiller , Stephen B. H. Kent , Mark P. Marriott , Paul O. Ramstad , Eric S. Nordman
发明人： John Bridgham , Timothy G. Geiser , Michael W. Hunkapiller , Stephen B. H. Kent , Mark P. Marriott , Paul O. Ramstad , Eric S. Nordman
IPC分类号： C07K1/00 , B01J19/00 , C07K1/04 , C40B40/10 , C40B60/14 , C08L89/00 , C07C103/52
CPC分类号： C07K1/045 , B01J19/0046 , B01J2219/00286 , B01J2219/00389 , B01J2219/00484 , B01J2219/00488 , B01J2219/0049 , B01J2219/00495 , B01J2219/005 , B01J2219/0059 , B01J2219/00596 , B01J2219/00689 , B01J2219/00695 , B01J2219/00725 , C40B40/10 , C40B60/14
摘要： An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel. Also included in the synthesizer system is a vortexer for affecting total washing of materials in the reaction vessel and the reaction vessel itself, an automated peptide resin sampling system, and an autodelivery system for providing individual containers of amino acid to the synthesizer in the order desired in the peptide sequence. A liquid sensor system is also included to monitor transitions between gases and liquids in specific tubes in the synthesizer in order to provide input signals to the computer system for control purposes. The computer system software which controls the operation of the synthesizer is organized according to a series of menus which allows the user of the system to select individual cycles of operation for each vessel in the synthesizer. In addition, an algorithm has been developed which provides for optimum efficiency in the production of a peptide for any given selection of cycles.
摘要翻译：提供了一种用于仅使用单个耦合自动构建高纯度多达50个氨基酸长度的多肽的装置。该装置包括用于一次接收受保护的氨基酸的激活系统，其具有在其中激活每个氨基酸的共同血管（活化剂容器）。还包括用于含有固相肽合成中用于连接肽链的树脂的反应容器。还提供了在计算机控制下操作的转移系统，以将活化物质从活化系统转移到反应容器中，并将氨基酸，试剂，气体和溶剂从设备的一部分转移到另一部分。活化剂体系还包括温度控制的浓缩容器，其中活化剂溶剂被偶联溶剂代替以增强活化物质与反应容器中的肽链的偶联。还包括在合成器系统中的是用于影响反应容器和反应容器本身中的材料的全部洗涤的涡流器，自动化肽树脂取样系统和用于按合适的顺序向合成器提供单个氨基酸容器的自动输送系统在肽序列中。还包括液体传感器系统以监测合成器中特定管中的气体和液体之间的转换，以便为控制目的向计算机系统提供输入信号。控制合成器操作的计算机系统软件根据一系列菜单进行组织，这些菜单允许系统的用户为合成器中的每个容器选择各个操作周期。此外，已经开发了一种算法，其提供用于任何给定选择周期的肽的生产的最佳效率。

12. 发明授权

US07094871B2 Solid phase native chemical ligation of unprotected or N-terminal cysteine protected peptides in aqueous solution 失效
公开(公告)号：US07094871B2
公开(公告)日：2006-08-22
申请号：US09987655
申请日：2001-11-15
申请人： Lynne Canne , Stephen B. H. Kent , Reyna Simon
发明人： Lynne Canne , Stephen B. H. Kent , Reyna Simon
IPC分类号： C07K1/02
CPC分类号： C07K1/086 , C07K1/023 , C07K1/026 , C07K1/04 , C07K1/047
摘要： The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.

13. 发明授权

US06844161B2 Modular protein libraries and methods of preparation 失效
标题翻译：模块化蛋白质文库及其制备方法
公开(公告)号：US06844161B2
公开(公告)日：2005-01-18
申请号：US09144838
申请日：1998-08-31
申请人： Michael A. Siani , Jill Wilken , Reyna Simon , Stephen B. H. Kent
发明人： Michael A. Siani , Jill Wilken , Reyna Simon , Stephen B. H. Kent
IPC分类号： A61K38/00 , C07K1/04 , C07K14/52 , C12Q1/00 , C07K14/00 , G01N33/53
CPC分类号： C07K14/523 , A61K38/00 , C07K1/04 , C07K1/047 , C07K14/522
摘要： Novel proteins and protein libraries are disclosed. The proteins possess one or more functional protein modules from different parent protein molecules. The proteins and protein libraries are exemplified by the preparation of cross-over chemokines that contain various combinations of peptide segments derived from RANTES, SDS-1 and vMIP-I and to vMIP-II. The proteins and libraries are extremely pure and can be provided in non-limiting high yields suitable for diagnostic and high-throughput screening assays.
摘要翻译：公开了新的蛋白质和蛋白质文库。蛋白质具有来自不同亲本蛋白质分子的一种或多种功能性蛋白质模块。蛋白质和蛋白质文库的实例是制备交叉趋化因子，其含有衍生自RANTES，SDS-1和vMIP-1以及vMIP-II的肽段的各种组合。蛋白质和文库是非常纯的，可以提供非限制性高产量，适用于诊断和高通量筛选分析。

14. 发明授权

US06228654B1 Methods for structure analysis of oligosaccharides 失效
标题翻译：寡糖结构分析方法
公开(公告)号：US06228654B1
公开(公告)日：2001-05-08
申请号：US08647405
申请日：1996-05-09
申请人： Brian T. Chait , Ying-Ming Zhao , Stephen B. H. Kent
发明人： Brian T. Chait , Ying-Ming Zhao , Stephen B. H. Kent
IPC分类号： G01N3348
CPC分类号： G01N33/66 , G01N2400/10 , Y10T436/143333 , Y10T436/24 , Y10T436/25125
摘要： A method of increasing the sensitivity and efficiency of MALDI-MS analysis of an oligosaccharide which comprises derivatization, prior to analysis by MALDI-MS, of said oligosaccharide by efficient ligation to a basic aminooxyacetylpeptide by oxime formation reaction to result in the formation of a glycoconjugate.
摘要翻译：提高寡糖的MALDI-MS分析的灵敏度和效率的方法，其包括通过MALDI-MS分析所述寡糖之前通过肟形成反应与碱性氨基氧乙酰肽有效连接导致糖缀合物的形成而衍生化。

15. 发明授权

US5854389A Process for preparing modified proteins 失效
标题翻译：制备修饰蛋白的方法
公开(公告)号：US5854389A
公开(公告)日：1998-12-29
申请号：US312662
申请日：1994-09-26
申请人： Stephen B. H. Kent , Martina Schnolzer-Rackwitz
发明人： Stephen B. H. Kent , Martina Schnolzer-Rackwitz
IPC分类号： C07K1/04 , C07K1/06 , C07K1/10 , C07K1/107 , C07K1/113 , C07K7/02 , C07K14/16 , C12N9/50
CPC分类号： C07K14/005 , C07K1/04 , C07K1/1075 , C07K1/1077 , C07K7/02 , C12N9/506 , C12N2740/16222 , Y02P20/582
摘要： Process for the preparation of modified proteins comprising the coupling of a first peptide segment having a haloacyl group at the N-terminus thereof with a second peptide segment having a carbonylthiol group at the C-terminus thereof are disclosed. Novel modified proteins produced by the process are also disclosed.
摘要翻译：公开了制备修饰蛋白质的方法，该修饰蛋白质包括其N-末端具有卤代酰基的第一肽段与C末端具有羰硫基的第二肽链的偶合。还公开了通过该方法产生的新型修饰的蛋白质。

16. 发明授权

US4668476A Automated polypeptide synthesis apparatus 失效
标题翻译：自动多肽合成仪
公开(公告)号：US4668476A
公开(公告)日：1987-05-26
申请号：US592638
申请日：1984-03-23
申请人： John Bridgham , Timothy G. Geiser , Michael W. Hunkapiller , Stephen B. H. Kent , Mark P. Marriott , Paul O. Ramstad , Eric S. Nordman
发明人： John Bridgham , Timothy G. Geiser , Michael W. Hunkapiller , Stephen B. H. Kent , Mark P. Marriott , Paul O. Ramstad , Eric S. Nordman
IPC分类号： C07K1/00 , B01J19/00 , C07K1/04 , C40B40/10 , C40B60/14 , C07K1/08
CPC分类号： C07K1/045 , B01J19/0046 , B01J2219/00286 , B01J2219/00389 , B01J2219/00484 , B01J2219/00488 , B01J2219/0049 , B01J2219/00495 , B01J2219/005 , B01J2219/0059 , B01J2219/00596 , B01J2219/00689 , B01J2219/00695 , B01J2219/00725 , C40B40/10 , C40B60/14
摘要： An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another.

17. 发明授权

US09285372B2 Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins 有权
标题翻译：用于鉴定特异性结合靶蛋白的D-肽化合物的方法和组合物
公开(公告)号：US09285372B2
公开(公告)日：2016-03-15
申请号：US13294078
申请日：2011-11-10
申请人： Dana Ault-Riche , Stephen B. H. Kent , Sachdev S. Sidhu , Maruti Uppalapati
发明人： Dana Ault-Riche , Stephen B. H. Kent , Sachdev S. Sidhu , Maruti Uppalapati
IPC分类号： C40B30/04 , G01N33/68 , C07K14/315
CPC分类号： G01N33/6845 , C07K1/00 , C07K14/315 , C40B30/04
摘要： Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins are provided. Aspects of the methods include screening libraries of 20 residue or more L-peptidic compounds for specific binding to 40 residue or more D-target proteins. Once a L-peptidic compound has been identified that specifically binds to the D-target protein, the D-enantiomer of that compound may be produced.
摘要翻译：提供了用于鉴定特异性结合靶蛋白的D-肽化合物的方法和组合物。方法的方面包括筛选20个残基或更多的L-肽化合物的文库，用于特异性结合40个残基或更多个D靶蛋白。一旦确定了特异性结合D靶蛋白的L-肽化合物，就可以生产该化合物的D-对映异构体。

18. 发明授权

US08618049B2 Ester insulin 有权
标题翻译：酯类胰岛素
公开(公告)号：US08618049B2
公开(公告)日：2013-12-31
申请号：US13394646
申请日：2010-09-07
申请人： Stephen B. H. Kent , Youhei Soma
发明人： Stephen B. H. Kent , Youhei Soma
IPC分类号： A61K38/28 , A61P3/04 , A61P3/10 , A61P3/08 , C07K14/62
CPC分类号： A61K38/28
摘要： Compositions and methods related to ester insulin or derivatives thereof are provided. The compositions include GluA4-ThrB30 ester insulin, in which side chains of GluA4 and ThrB30 of native human insulin or an insulin analogue such as insulin lispro are covalently linked via a single ester bond. The ester insulin is efficiently folded, forming the desired disulfides. The ThrB30-GluA4 ester bond can be cleaved in vitro or in vivo to give the desired folded insulin with full biological activity. The ester insulin is readily prepared by total chemical synthesis, and amendable to cost-effective, large scale manufacturing. Also provided are pharmaceutical compositions and kits for use in practicing the subject methods. Also provided are methods of using the subject compositions and kits in the treatment of a variety of different disease conditions, particularly glucose metabolic disorders such as diabetes and obesity.
摘要翻译：提供了与酯胰岛素或其衍生物相关的组合物和方法。组合物包括GluA4-ThrB30酯胰岛素，其中天然人胰岛素的GluA4和ThrB30的侧链或胰岛素类似物如赖脯胰岛素通过单一酯键共价连接。酯胰岛素被有效地折叠，形成所需的二硫化物。 ThrB30-GluA4酯键可以在体外或体内裂解，以产生具有完全生物活性的所需的折叠胰岛素。酯类胰岛素通过全面的化学合成容易地制备，并且可以经济高效，大规模生产。还提供了用于实践本发明方法的药物组合物和试剂盒。还提供了使用主题组合物和试剂盒来治疗各种不同疾病状况，特别是葡萄糖代谢紊乱如糖尿病和肥胖症的方法。

19. 发明授权

US08034900B2 Water-soluble thioester and selenoester compounds and methods for making and using the same 失效
标题翻译：水溶性硫酯和硒酯化合物及其制备和使用方法
公开(公告)号：US08034900B2
公开(公告)日：2011-10-11
申请号：US10541078
申请日：2003-12-30
申请人： Leslie Philip Miranda , Stephen B. H. Kent
发明人： Leslie Philip Miranda , Stephen B. H. Kent
IPC分类号： A61K38/00
CPC分类号： C07K14/001 , C07C327/32 , C07C391/00 , C07K1/04 , C07K1/086 , C07K1/088 , C07K1/10
摘要： Water-soluble thioester and selenoester compounds, their generators, as well as methods for making and using the same, are provided. The subject thioester and selenoester compounds are characterized by including an amino acid synthon having a C-terminal group bonded to a water-soluble polymer through a thioester or selenoester linkage. Solid phase resins and protocols for generating the subject compounds are also provided. The subject water soluble thioester and selenoester compounds and generators find use in a variety of different applications, including thioester or selenoester mediated chemical ligation reactions.
摘要翻译：提供了水溶性硫酯和硒酯化合物，它们的发生剂，以及制备和使用它们的方法。受试者硫酯和硒酯化合物的特征在于包括具有通过硫酯或硒酸酯键与水溶性聚合物键合的C-端基的氨基酸合成子。还提供了用于产生本发明化合物的固相树脂和方案。本发明的水溶性硫酯和硒酯化合物和发生器可用于各种不同的应用，包括硫酯或硒酯介导的化学连接反应。

20. 发明授权

US07341874B2 Method for detecting post-translation modifications of peptides 失效
标题翻译：检测肽后翻译修饰的方法
公开(公告)号：US07341874B2
公开(公告)日：2008-03-11
申请号：US10792176
申请日：2004-03-02
申请人： Brian T. Chait , Ronald Beavis , Rong Wang , Stephen B. H. Kent
发明人： Brian T. Chait , Ronald Beavis , Rong Wang , Stephen B. H. Kent
IPC分类号： G01N33/00
CPC分类号： G01N33/6842 , C07K1/107 , C07K1/128 , G01N33/6824 , Y10T436/24 , Y10T436/25 , Y10T436/255
摘要： This invention provides for novel methods of identifying covalent modifications of an amino acid residue in a polypeptide chain by detecting mass differences.
摘要翻译：本发明提供了通过检测质量差异来鉴定多肽链中氨基酸残基的共价修饰的新方法。

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