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    • 1. 发明申请
    • Error reduction in automated gene synthesis
    • 自动基因合成中的错误减少
    • US20060134638A1
    • 2006-06-22
    • US10816459
    • 2004-04-01
    • John MulliganJohn Tabone
    • John MulliganJohn Tabone
    • C12Q1/68C12P19/34
    • C12Q1/6827C12Q1/68C12Q1/6806C12Q2565/125C12Q2537/107C12Q2521/514C12Q2537/113
    • In embodiments of the present invention, methods are provided for removing double-stranded oligonucleotide (e.g., DNA) molecules containing one or more sequence errors, generated during nucleic acid synthesis, from a population of correct oligonucleotide duplexes. In one embodiment, the oligonucleotides are generated enzymatically. Heteroduplex (containing mismatched bases) oligonucleotides may be created by denaturing and reannealing the population of duplexes. The reannealed oligonucleotide duplexes are contacted with a mismatch recognition protein that interacts with (e.g., binds and/or cleaves) the duplexes containing a base pair mismatch. The oligonucleotide heteroduplexes that have interacted with such a protein are separated, simultaneously with contacting or sequentially in a separate step, from homoduplexes. These methods are also used in another embodiment to remove heteroduplex oligonucleotides (e.g., DNA) that are formed directly from chemical nucleic acid synthesis. In other embodiments of the present invention, kits and compositions useful for the methods are provided.
    • 在本发明的实施方案中,提供了从正确的寡核苷酸双链体的群体中去除含有在核​​酸合成期间产生的一个或多个序列错误的双链寡核苷酸(例如DNA)分子的方法。 在一个实施方案中,寡核苷酸是酶促产生的。 异源双链(含有错配的碱基)寡核苷酸可以通过使双链体群变性和再退火来产生。 重新退火的寡核苷酸双链体与与包含碱基对失配的双链体相互作用(例如,结合和/或切割)的错配识别蛋白质接触。 已经与这种蛋白质相互作用的寡核苷酸异源双链体与同源双链体在单独步骤中接触或顺序地分离。 这些方法也用于另一个实施方案中以去除直接从化学核酸合成形成的异源双链寡核苷酸(例如DNA)。 在本发明的其它实施方案中,提供了可用于该方法的试剂盒和组合物。
    • 4. 发明申请
    • Methods for synthesis of defined polynucleotides
    • 合成定义的多核苷酸的方法
    • US20050069928A1
    • 2005-03-31
    • US10911239
    • 2004-08-03
    • Jeffrey NelsonJohn MulliganJohn Tabone
    • Jeffrey NelsonJohn MulliganJohn Tabone
    • A61K48/00C07H21/04C12N15/10C12P19/34C12Q1/68
    • C12N15/1031
    • Disclosed is a significantly improved synthetic method of producing a set of mutagenized progeny polynucleotides which contain at least one substituted codon encoding for each of the 20 naturally encoded amino acids or any selected subset thereof. This in turn, similarly provides a method for producing from a parental template polypeptide, a set of mutagenized progeny polypeptides in which all 20 naturally encoded amino acids is represented at each original amino acid position or any selected subset thereof. The methods described herein enable the synthesis of defined, complex mixtures of oligonucleotides, in instances where the incorporation of degenerate bases is impractical. These oligonucleotide mixtures are useful for a variety of applications such as recombination methods, site-saturation mutagenesis, or the like.
    • 公开了一种显着改进的合成方法,其生产一组诱变的后代多核苷酸,其含有至少一个编码20个天然编码氨基酸或其任何选定子集中的每一个的取代密码子。 这反过来类似地提供了从亲本模板多肽,一组诱变的后代多肽产生的方法,其中在每个原始氨基酸位置或其任何选定的亚组中表示所有20个天然编码的氨基酸。 在简并碱基的掺入是不实际的情况下,本文描述的方法能够合成寡核苷酸的限定的复杂混合物。 这些寡核苷酸混合物可用于各种应用,例如重组方法,位点饱和诱变等。
    • 8. 发明授权
    • Automated polymer-synthesis system
    • 自动聚合物合成系统
    • US08361396B2
    • 2013-01-29
    • US12932334
    • 2011-02-22
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • B01J19/00G01N21/00
    • B01J19/0046B01J2219/00286B01J2219/00315B01J2219/0036B01J2219/00414B01J2219/00423B01J2219/00722
    • Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.
    • 本发明的实施方案涉及自动聚合物合成系统,其包括离散的试剂 - 溶液添加,等待时间和试剂 - 溶液 - 排出子系统,这些子系统共同显着增加生产量并减少子系统空闲时间。 代表本发明实施例的自动化 - 聚合物合成系统另外包括在多个输入路径上可以接收载波或输出到多个不同输出路径的点处的交换机。 代表本发明实施例的自动化 - 聚合物 - 合成系统通常包括除了主回路之外的输入支线和输出支线,允许仅去除已完成的聚合物的载流子和新的载流子输入,使得载流子穿过自动化 - 聚合物合成系统彼此独立。
    • 10. 发明申请
    • Method and apparatus for providing dynamic traffic control within a communications network
    • 用于在通信网络内提供动态业务控制的方法和装置
    • US20060206606A1
    • 2006-09-14
    • US11074988
    • 2005-03-08
    • Ali IlogluHan NguyenJohn MulliganKevin D'Souza
    • Ali IlogluHan NguyenJohn MulliganKevin D'Souza
    • G06F15/173
    • H04L41/0893H04L45/04H04L45/42
    • A method and apparatus for providing traffic management through dynamic and granular definitions of route groups. Within a communications network, a traffic routing control unit (e.g., an intelligent route service control point (IRSCP)) creates route group assignments for each route within a customers network in accordance with a customer's routing plan, determines protocol control values to be set within each edge router of the network to fulfill the group assignments, and uses border gateway protocol (BGP) to set the protocol control values in the edge routers to facilitate fulfilling the route group assignments. Using the traffic routing control unit and programming the protocol control values of the edge routers, enables the network to be flexibly defined and the traffic routing within the network to have very granular control.
    • 一种用于通过路由组的动态和粒度定义来提供流量管理的方法和装置。 在通信网络内,业务路由控制单元(例如,智能路由业务控制点(IRSCP))根据客户的路由计划为客户网络内的每个路由创建路由组分配,确定要在其中设置的协议控制值 网络的每个边缘路由器完成组分配,并使用边界网关协议(BGP)在边缘路由器中设置协议控制值,以便于完成路由组分配。 使用流量路由控制单元和编程边缘路由器的协议控制值,可以灵活定义网络,网络内的流量路由具有非常细微的控制。