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11. 发明申请

US20120237539A1 METHOD FOR MAKING TARGETED THERAPEUTIC AGENTS DIRECTED TO SOLUBLE TARGETS 审中-公开
标题翻译：制造针对可溶性目标的针对性治疗药物的方法
公开(公告)号：US20120237539A1
公开(公告)日：2012-09-20
申请号：US13455598
申请日：2012-04-25
申请人： Richard B. WILLIAMS , Robert GUERRERO
发明人： Richard B. WILLIAMS , Robert GUERRERO
IPC分类号： C12P21/00 , A61P37/04 , A61K39/00
CPC分类号： C12P19/34 , C12N15/1068 , C12N15/1075
摘要： Provided herein are methods for making targeted therapeutics that target soluble agents such as toxins, venoms, and factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments the targeted therapeutics comprise a portion that interacts with a soluble agent of interest and a second portion that interacts with a subject's immune system, which enables treatment of a patient for exposure to the soluble agent.
摘要翻译：本文提供了制备靶向治疗剂的方法，其靶向可溶性试剂，例如毒素，毒液和改变生理生物学途径的因子，以及使用这些治疗剂治疗患者或患者群体以减少，消除或灭活有害可溶性物质的方法，已经暴露了这样的患者或患者群体。在几个实施方案中，靶向治疗剂包含与感兴趣的可溶性药物相互作用的部分和与受试者的免疫系统相互作用的第二部分，其能够治疗患者暴露于可溶性试剂。

12. 发明申请

US20110212114A1 METHOD FOR MAKING TARGETED THERAPEUTIC AGENTS 有权
标题翻译：制造针对性治疗剂的方法
公开(公告)号：US20110212114A1
公开(公告)日：2011-09-01
申请号：US13016576
申请日：2011-01-28
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30 , C07K19/00 , A61P35/00 , A61P31/12 , A61P31/18
CPC分类号： C07K16/30 , C07K14/00 , C07K2319/30 , G01N33/531 , G01N33/6845
摘要： Provided herein are methods and kits for making a targeted therapeutic for treating a disease or condition. The therapeutic agents can be targeted to patient-specific disease markers. In one of these methods, the method includes obtaining a biological sample from a patient having the disease or condition, or who is at risk for developing the disease or condition. In this particular method, the sample includes a population of diseased cells, screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent. Some of the methods further include preparing a library with proteins linked to their cognate mRNAs. In certain of these methods, the preparation of the library includes providing at least two candidate mRNA molecules in which each of the mRNA molecules includes a cross-linker, translating at least two of the candidate mRNA molecules to generate at least one translated protein, and linking at least one of the candidate mRNA molecules to its corresponding translated protein via the cross-linker to form at least one cognate pair.
摘要翻译：本文提供了用于制备用于治疗疾病或病症的靶向治疗剂的方法和试剂盒。治疗剂可以靶向患者特异性疾病标记物。在这些方法之一中，该方法包括从具有疾病或病症的患者或患有发展疾病或病症风险的患者获得生物样品。在该特定方法中，样品包括患病细胞群，筛选包含与其同源mRNA相连的蛋白质的文库，以鉴定结合病变细胞的mRNA-蛋白质对，从鉴定的mRNA-蛋白质对分离一种或多种蛋白质，并将分离的蛋白质与治疗剂缀合。一些方法还包括用与其同源mRNA相连的蛋白质制备文库。在这些方法的某些中，文库的制备包括提供至少两个候选mRNA分子，其中每个mRNA分子包括交联剂，翻译候选mRNA分子中的至少两个以产生至少一个翻译的蛋白质，以及通过交联剂将候选mRNA分子中的至少一种与其相应的翻译蛋白连接以形成至少一个同源对。

13. 发明授权

US07351812B2 In vitro evolution of nucleic acids and encoded polypeptide 有权
标题翻译：核酸和编码多肽的体外进化
公开(公告)号：US07351812B2
公开(公告)日：2008-04-01
申请号：US11064067
申请日：2005-02-23
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C07H21/02 , C12P19/26
CPC分类号： G01N33/6845 , G01N33/58 , G01N2458/10
摘要： This invention relates to methods and reagents for selecting a desired protein or nucleic acid molecule by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties.
摘要翻译：本发明涉及通过将已知或未知序列的mRNA与其翻译的蛋白质连接以形成同源对来选择所需蛋白质或核酸分子的方法和试剂。基于蛋白质或核酸的所需性质选择同源对。该方法还包括通过扩增所选择的同源对的核酸部分，引入核酸的变异，翻译核酸，将核酸连接到其蛋白质以形成第二个同源物，从而演化期望的蛋白质或核酸分子并且基于所需的属性重新选择该同源对。

14. 发明授权

US06962781B1 In vitro evolution of nucleic acids and encoded polypeptide 有权
标题翻译：核酸和编码多肽的体外进化
公开(公告)号：US06962781B1
公开(公告)日：2005-11-08
申请号：US09859809
申请日：2001-05-17
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C12N15/00 , C12Q1/68 , G01N33/58 , G01N33/68
CPC分类号： G01N33/6845 , G01N33/58 , G01N2458/10
摘要： This invention relates to methods and reagents for selecting a desired protein or nucleic acid molecule by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties.
摘要翻译：本发明涉及通过将已知或未知序列的mRNA与其翻译的蛋白质连接以形成同源对来选择所需蛋白质或核酸分子的方法和试剂。基于蛋白质或核酸的所需性质选择同源对。该方法还包括通过扩增所选择的同源对的核酸部分，引入核酸的变异，翻译核酸，将核酸连接到其蛋白质以形成第二个同源物，从而演化期望的蛋白质或核酸分子并且基于所需的属性重新选择该同源对。

15. 发明授权

US4178957A Dishwasher fill system 失效
标题翻译：洗碗机灌装系统
公开(公告)号：US4178957A
公开(公告)日：1979-12-18
申请号：US962060
申请日：1978-11-20
申请人： Robert E. Hoffman , Richard B. Williams , Carl J. Wright
发明人： Robert E. Hoffman , Richard B. Williams , Carl J. Wright
IPC分类号： A47L15/42 , F16K21/18 , B08B3/02 , D06F39/08
CPC分类号： A47L15/4244 , A47L15/0023 , A47L2401/09 , A47L2501/01 , Y10T137/729 , Y10T137/7297 , Y10T137/7368 , Y10T137/86445
摘要： A dishwasher fill system providing a combination fill control system and timer fill sequence that assures a predetermined minimum quantity of water is present in the dishwashing chamber regardless of the water fill flow rate and the household waterline pressure. The system provides two assured fill levels with a predetermined minimum water level fill cycle portion for a rinse fill and an increased minimum level fill cycle portion for a wash fill. If the rinse fill water level is below its minimum quantity after a predetermined run time, first switch means will energize the timer motor and the fill valve will remain open until said rinse fill minimum level is reached. A fill sensor switch at this point will turn off the water valve and energize the timer motor. During wash fill portions of the cycle the system is as described above with the addition that second switch means will energize the timer motor and the water valve will remain open for a predetermined number of seconds longer than for the minimum fill cycle portion, thereby filling the chamber to its wash fill level.
摘要翻译：洗碗机填充系统提供组合填充控制系统和确定预定最小量的水的定时器填充顺序，无论填充流量和家用水线压力如何，均存在于洗碗室中。该系统提供两个确定的填充水平，其具有用于冲洗填充物的预定最小水位填充循环部分和用于洗涤填充物的增加的最小水平填充循环部分。如果在预定运行时间之后冲洗补水水位低于其最小量，则第一开关装置将给定时器马达通电，并且填充阀将保持打开，直到达到冲洗填充最小水平。此时，填充传感器开关将关闭水阀，并为定时电机通电。在循环的洗涤填充部分期间，系统如上所述，另外，第二开关装置将使定时电动机通电，并且水阀将比最小填充循环部分保持打开预定秒数，从而填充室到其洗涤水位。

16. 发明授权

US07410761B2 System for rapid identification and selection of nucleic acids and polypeptides, and method thereof 有权
标题翻译：用于快速鉴定和选择核酸和多肽的系统及其方法
公开(公告)号：US07410761B2
公开(公告)日：2008-08-12
申请号：US10847087
申请日：2004-05-17
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12N15/1034 , C12N15/1062
摘要： This invention relates generally to systems and methods for identifying and selecting, desired proteins or nucleic acid molecules by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties. Modified MRNAs operable to crosslink to tRNAs are also provided. Methods of producing a psoralen monoadduct or a crosslink are also provided.
摘要翻译：本发明一般涉及通过将mRNA与已知或未知序列连接到其翻译的蛋白质以形成同源对来鉴定和选择所需蛋白质或核酸分子的系统和方法。基于蛋白质或核酸的所需性质选择同源对。该方法还包括通过扩增所选择的同源对的核酸部分，引入核酸的变异，翻译核酸，将核酸连接到其蛋白质以形成第二个同源物，从而演化期望的蛋白质或核酸分子并且基于所需的属性重新选择该同源对。还提供了可操作地与tRNA交联的修饰MRNA。还提供了补骨脂素单加成物或交联剂的制备方法。

17. 发明授权

US4009801A Washing agent dispenser for dishwasher 失效
标题翻译：洗碗机洗衣机分配器
公开(公告)号：US4009801A
公开(公告)日：1977-03-01
申请号：US549907
申请日：1975-02-14
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： A47L15/44 , B67D5/08
CPC分类号： A47L15/4409
摘要： A multiple charge dispenser has two compartments on the inner panel of a dishwasher door. A semi-circular lid selectively automatically or manually uncovers one or both of the compartments. The lid is integral with one end of a pivot shaft which extends through the inner panel to receive a latch plate on the other side of the panel. Lid and latch plate are spring-biased to pivot together from a CLOSED position to an OPEN position with an INTERMEDIATE position therebetween. Such positions are defined by CLOSED, INTERMEDIATE and OPEN dispensing cam stops formed along an inboard side of the latch plate. A detent, normally stationary relative to the pivotal movement of the latch plate, is yieldably, normally biased toward the inboard side of the latch plate to engage sequentially each one of the cam stops as the latch plate pivots past the detent. The latch plate has an outboard pause stop cantilevered from the inboard side thereof and pivotally between the CLOSED and INTERMEDIATE dispensing cam stops. A solenoid is energized to shuttle the detent away from said inboard side for successively, automatically releasing the CLOSED and INTERMEDIATE dispensing cam stops to successively uncover the compartments. With the solenoid deenergized, the compartments may be selectively uncovered by pivoting the lid manually. As the lid is thus pivoted, the cam stops on the latch plate act to cam the yielding detent in a direction away from the inboard side for successively, manually releasing the CLOSED and INTERMEDIATE dispensing cam stops so that the compartments may be spring-biasingly successively uncovered.
摘要翻译：多个电荷分配器在洗碗机门的内板上具有两个隔间。选择性地自动或手动地露出一个或两个隔间的半圆形盖。盖子与枢转轴的一端是一体的，其延伸穿过内板以在面板的另一侧上容纳闩锁板。盖板和闩锁板被弹簧偏置以从闭合位置枢转到OPEN位置，其间具有INTERMEDIATE位置。这样的位置是通过闭锁，中间和打开分配凸轮挡块来限定的，沿着锁闩板的内侧形成。通常相对于闩锁板的枢转运动静止的制动器可屈服地通常朝向闩锁板的内侧偏置，以在闩锁板枢转经过制动器时顺序地接合每个凸轮挡块。闩锁板具有从其内侧悬臂悬伸的外侧停止挡块，并且在CLOSED和INTERMEDIATE分配凸轮挡块之间枢转。螺线管被通电以使制动器远离所述内侧，以便连续地自动释放闭合和中间分配凸轮挡块以依次露出隔间。在螺线管断电的情况下，可以通过手动旋转盖来选择性地覆盖隔间。当盖因此枢转时，闩锁板上的凸轮停止作用以使制动棘爪沿远离内侧的方向凸起，以便连续地手动释放闭合和中间分配凸轮止动件，使得隔间可以弹簧偏置地连续裸露。

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