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1. 发明申请

US20050069928A1 Methods for synthesis of defined polynucleotides 审中-公开
标题翻译：合成定义的多核苷酸的方法
公开(公告)号：US20050069928A1
公开(公告)日：2005-03-31
申请号：US10911239
申请日：2004-08-03
申请人： Jeffrey Nelson , John Mulligan , John Tabone
发明人： Jeffrey Nelson , John Mulligan , John Tabone
IPC分类号： A61K48/00 , C07H21/04 , C12N15/10 , C12P19/34 , C12Q1/68
CPC分类号： C12N15/1031
摘要： 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.
摘要翻译：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。

2. 发明申请

US20060134638A1 Error reduction in automated gene synthesis 审中-公开
标题翻译：自动基因合成中的错误减少
公开(公告)号：US20060134638A1
公开(公告)日：2006-06-22
申请号：US10816459
申请日：2004-04-01
申请人： John Mulligan , John Tabone
发明人： John Mulligan , John Tabone
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/68 , C12Q1/6806 , C12Q2565/125 , C12Q2537/107 , C12Q2521/514 , C12Q2537/113
摘要： 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.
摘要翻译：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。

3. 发明申请

US20060057566A1 METHODS AND COMPOSITIONS FOR ANALYZING NUCLEIC ACID MOLECULES UTILIZING SIZING TECHNIQUES 有权
标题翻译：用于分析使用尺寸技术的核酸分子的方法和组合物
公开(公告)号：US20060057566A1
公开(公告)日：2006-03-16
申请号：US10465524
申请日：2003-06-19
申请人： Jeffrey Van Ness , John Tabone , J. Howbert , John Mulligan
发明人： Jeffrey Van Ness , John Tabone , J. Howbert , John Mulligan
IPC分类号： C12Q1/68 , C08G63/91
CPC分类号： C07H21/00 , C07B2200/11 , C12Q1/6825 , C12Q1/6846 , C12Q1/6872 , C40B40/00 , C12Q2563/149 , C12Q2563/113 , C12Q2563/167 , C12Q2525/191
摘要： Tags and linkers specifically designed for a wide variety of nucleic acid reactions are disclosed, which are suitable for a wide variety of nucleic acid reactions wherein separation of nucleic acid molecules based upon size is required.
摘要翻译：公开了针对各种核酸反应专门设计的标签和接头，其适用于各种各样的核酸反应，其中需要基于尺寸分离核酸分子。

4. 发明申请

US20080009613A1 Methods and compositions for determining the sequence of nucleic acid molecules 有权
标题翻译：用于确定核酸分子序列的方法和组合物
公开(公告)号：US20080009613A1
公开(公告)日：2008-01-10
申请号：US11821531
申请日：2007-06-21
申请人： Jeffrey Van Ness , John Tabone , J. Howbert , John Mulligan
发明人： Jeffrey Van Ness , John Tabone , J. Howbert , John Mulligan
IPC分类号： C07C229/00 , C07C205/00 , C07D211/30 , C07H21/04
CPC分类号： C07H21/00 , C07B2200/11 , C07D211/78 , C07H21/04 , C12Q1/6872 , C12Q1/6874 , C40B40/00 , Y10T436/24 , C12Q2565/629 , C12Q2563/167
摘要： Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.
摘要翻译：提供方法和化合物，包括其组合物，用于确定核酸分子的序列。该方法允许同时测定多个核酸序列。该化合物用作标签以产生与选定的靶核酸分子互补的标记的核酸片段。每个标签与特定核苷酸相关，并且在优选实施方案中可通过质谱法检测。在通过连续长度分离标记的片段之后，从标记的片段切割标签。在优选的实施方案中，通过质谱检测标签，并由此确定核酸分子的序列。方法的各个步骤可以以自动格式使用，例如通过并入系统。

5. 发明申请

US20050080086A1 Pharmaceutical uses and synthesis of diketopiperazines 审中-公开
标题翻译：二酮哌嗪的药物用途和合成
公开(公告)号：US20050080086A1
公开(公告)日：2005-04-14
申请号：US10884540
申请日：2004-07-02
申请人： Jim Boyce , J. Howbert , John Tabone
发明人： Jim Boyce , J. Howbert , John Tabone
IPC分类号： A61P29/00 , C07D487/04 , A61K31/498
CPC分类号： C07D487/04 , Y10S436/804 , Y10S436/815 , Y10T436/147777 , Y10T436/24
摘要： The synthesis of novel diketopiperazines, their use in inhibiting cellular events such as those involving NFK-α, NFK-β and in the treatment of inflammation events, a combinatorial library of diverse diketopiperazines and process for their synthesis as a library and as individual compounds. In particular novel diketopiperazines are disclosed including their synthesis and use in cellular events such as activation of the transcription factor, nuclear factor, TNF-α, TNF-β and also apoptosis.
摘要翻译：新型二酮哌嗪的合成，它们用于抑制诸如涉及NFK-α，NFK-β的细胞事件和用于治疗炎症事件的细胞事件，用于多种二酮哌嗪的组合文库以及作为文库和作为单独化合物合成的方法。特别地公开了新的二酮哌嗪，其包括其在细胞事件中的合成和使用，例如转录因子的激活，核因子，TNF-α，TNF-β以及细胞凋亡。

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