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31. 发明授权

US07776598B2 Methods and compositions for polypeptide engineering 有权
标题翻译：多肽工程的方法和组合物
公开(公告)号：US07776598B2
公开(公告)日：2010-08-17
申请号：US12069011
申请日：2008-02-05
申请人： Phillip A. Patten , Willem P. C. Stemmer
发明人： Phillip A. Patten , Willem P. C. Stemmer
IPC分类号： C12N15/00 , C12Q1/68 , C07H21/02 , C07H21/04
CPC分类号： C12N15/1031 , A61K38/45 , A61K48/00 , C07K14/43595 , C07K14/545 , C07K14/56 , C07K16/00 , C07K2317/565 , C07K2317/622 , C12N7/00 , C12N9/0069 , C12N9/1007 , C12N9/16 , C12N9/86 , C12N15/10 , C12N15/1027 , C12N15/1034 , C12N15/1037 , C12N15/1058 , C12N15/52 , C12N15/64 , C12N15/67 , C12N2795/14043 , C12N2795/14143 , C12Q1/6811 , C12Q1/6853 , C12Q1/686 , C40B40/02 , C40B40/08 , C40B50/06 , G01N33/68 , G01N33/6845
摘要： Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.
摘要翻译：提供了用于工业和药物兴趣的蛋白质进化的方法，包括用于进行重组和选择的方法。还公开了通过这些方法制备的组合物。

32. 发明申请

US20100144547A1 METHODS AND COMPOSITIONS FOR CELLULAR AND METABOLIC ENGINEERING 失效
标题翻译：细胞和代谢工程的方法和组合
公开(公告)号：US20100144547A1
公开(公告)日：2010-06-10
申请号：US12557812
申请日：2009-09-11
申请人： Jeremy Minshull , Willem P.C. Stemmer
发明人： Jeremy Minshull , Willem P.C. Stemmer
IPC分类号： C40B30/06
CPC分类号： C12N15/1027 , C12N15/1058
摘要： The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.
摘要翻译：本发明一般涉及新代谢途径的演变以及通过本文中称为递归序列重组的方法增强生物处理。递归序列重组需要执行重组和筛选或选择的“进化”个体基因，整个质粒或病毒，多基因簇或甚至全基因组的迭代循环。这些技术不需要传统的代谢工程方法所需的广泛的分析和计算。

33. 发明授权

US07718786B2 Process for obtaining recombined nucleotide sequences in vitro, libraries of sequences and sequences thus obtained 有权
标题翻译：在体外获得重组核苷酸序列的方法，由此获得的序列和序列的文库
公开(公告)号：US07718786B2
公开(公告)日：2010-05-18
申请号：US11143455
申请日：2005-06-03
申请人： Daniel Dupret , Jean-Michel Masson , Fabrice Lefevre
发明人： Daniel Dupret , Jean-Michel Masson , Fabrice Lefevre
IPC分类号： C07H21/02 , C12Q1/68
CPC分类号： C12N15/1027 , C07H21/02
摘要： Ligation-mediated method of recombining polynucleotides in vitro. Polynucleotides from a library are fragmented and the fragments are hybridized to an assembly template. The hybridized fragments are iteratively re-hybridized and ligated until the ends of the hybridized fragments are adjacent to the ends of other hybridized fragments on the assembly template. A final ligation produces recombined polynucleotides.
摘要翻译：体外重组多核苷酸的连接介导方法。来自文库的多核苷酸被片段化，并且片段与组装模板杂交。杂交的片段被迭代地重新杂交并连接，直到杂交片段的末端与组装模板上的其它杂交片段的末端相邻。最终连接产生重组多核苷酸。

34. 发明授权

US07629170B2 Evolution of whole cells and organisms by recursive sequence recombination 有权
公开(公告)号：US07629170B2
公开(公告)日：2009-12-08
申请号：US11506215
申请日：2006-08-17
申请人： Stephen delCardayre , Matthew B. Tobin , Willem P. C. Stemmer , Jon E. Ness , Jeremy S. Minshull , Phillip A. Patten , Venkiteswatan Mani Subramanian , Linda A. Castle , Claus M. Krebber , Steven H. Bass , Ying-Xin Zhang , Anthony R. Cox , Gjalt W. Huisman , Ling Yuan , Joseph A. Affholter
发明人： Stephen delCardayre , Matthew B. Tobin , Willem P. C. Stemmer , Jon E. Ness , Jeremy S. Minshull , Phillip A. Patten , Venkiteswatan Mani Subramanian , Linda A. Castle , Claus M. Krebber , Steven H. Bass , Ying-Xin Zhang , Anthony R. Cox , Gjalt W. Huisman , Ling Yuan , Joseph A. Affholter
IPC分类号： C12N15/00 , C12N15/87 , C12N15/63
CPC分类号： C12R1/465 , A01K2267/02 , C07K14/245 , C12N15/1027 , C12N15/8271 , C12N15/8273 , C12N15/8279 , C12N15/90 , C12P17/162 , C12Q1/6811 , C12Q1/6827
摘要： The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.

35. 发明申请

US20090149331A1 Methods and compositions for polypeptide engineering 有权
公开(公告)号：US20090149331A1
公开(公告)日：2009-06-11
申请号：US12069011
申请日：2008-02-05
申请人： Phillip A. Patten , Willem P.C. Stemmer
发明人： Phillip A. Patten , Willem P.C. Stemmer
IPC分类号： C40B10/00
CPC分类号： C12N15/1031 , A61K38/45 , A61K48/00 , C07K14/43595 , C07K14/545 , C07K14/56 , C07K16/00 , C07K2317/565 , C07K2317/622 , C12N7/00 , C12N9/0069 , C12N9/1007 , C12N9/16 , C12N9/86 , C12N15/10 , C12N15/1027 , C12N15/1034 , C12N15/1037 , C12N15/1058 , C12N15/52 , C12N15/64 , C12N15/67 , C12N2795/14043 , C12N2795/14143 , C12Q1/6811 , C12Q1/6853 , C12Q1/686 , C40B40/02 , C40B40/08 , C40B50/06 , G01N33/68 , G01N33/6845
摘要： Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.

36. 发明授权

US07534564B2 Methods and compositions for polypeptide engineering 失效
公开(公告)号：US07534564B2
公开(公告)日：2009-05-19
申请号：US10646221
申请日：2003-08-22
申请人： Phillip A. Patten , Willem P. C. Stemmer
发明人： Phillip A. Patten , Willem P. C. Stemmer
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12N15/1031 , A61K38/45 , A61K48/00 , C07K14/43595 , C07K14/545 , C07K14/56 , C07K16/00 , C07K2317/565 , C07K2317/622 , C12N7/00 , C12N9/0069 , C12N9/1007 , C12N9/16 , C12N9/86 , C12N15/10 , C12N15/1027 , C12N15/1034 , C12N15/1037 , C12N15/1058 , C12N15/52 , C12N15/64 , C12N15/67 , C12N2795/14043 , C12N2795/14143 , C12Q1/6811 , C12Q1/6853 , C12Q1/686 , C40B40/02 , C40B40/08 , C40B50/06 , G01N33/68 , G01N33/6845
摘要： Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.

37. 发明授权

US07452666B2 Synthesis of DNA 失效
标题翻译： DNA的合成
公开(公告)号：US07452666B2
公开(公告)日：2008-11-18
申请号：US10394911
申请日：2003-03-21
申请人： Raymond P. Mariella, Jr.
发明人： Raymond P. Mariella, Jr.
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12N15/1031 , C07H21/00 , C12N15/1027 , C12Q1/686 , C12Q2533/107 , C12Q2521/101
摘要： A method of synthesizing a desired double-stranded DNA of a predetermined length and of a predetermined sequence. Preselected sequence segments that will complete the desired double-stranded DNA are determined. Preselected segment sequences of DNA that will be used to complete the desired double-stranded DNA are provided. The preselected segment sequences of DNA are assembled to produce the desired double-stranded DNA.
摘要翻译：合成预定长度和预定序列的所需双链DNA的方法。确定将完成所需双链DNA的预选序列片段。提供将用于完成所需双链DNA的预选择的DNA序列。组装DNA的预选区段序列以产生所需的双链DNA。

38. 发明申请

US20080227649A1 Methods and compositions for cellular and metabolic engineering 有权
标题翻译：细胞和代谢工程的方法和组成
公开(公告)号：US20080227649A1
公开(公告)日：2008-09-18
申请号：US12011767
申请日：2008-01-28
申请人： Jeremy Minshull , Willem P.C. Stemmer
发明人： Jeremy Minshull , Willem P.C. Stemmer
IPC分类号： C40B10/00
CPC分类号： C12N15/1027 , C12N15/1058
摘要： The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.
摘要翻译：本发明一般涉及新代谢途径的演变以及通过本文中称为递归序列重组的方法增强生物处理。递归序列重组需要执行重组和筛选或选择的“进化”个体基因，整个质粒或病毒，多基因簇或甚至全基因组的迭代循环。这些技术不需要传统的代谢工程方法所需的广泛的分析和计算。

39. 发明授权

US07332308B1 Incrementally truncated nucleic acids and methods of making same 有权
标题翻译：增量截短的核酸及其制备方法
公开(公告)号：US07332308B1
公开(公告)日：2008-02-19
申请号：US09718465
申请日：2000-11-15
申请人： Stephen J. Benkovic , Marc Ostermeier , Stefan Lutz , Andrew E. Nixon
发明人： Stephen J. Benkovic , Marc Ostermeier , Stefan Lutz , Andrew E. Nixon
IPC分类号： C12N15/64 , C12N5/10 , C12Q1/68 , C07H21/02
CPC分类号： C12N15/102 , C12N15/1027 , C12N15/1058
摘要： A series of methods that utilize the incremental truncation of nucleic acids are described to create a plurality of modified nucleic acids and hybrid polypeptides. A plurality of substantially all possible single base-pair deletions of a given nucleic acid sequence is created. A method of making shuffled incremental truncated nucleic acids, which is independent of nucleic acid sequence homology, is also described. These methods can be used in protein engineering, protein folding, protein evolution, and the chemical synthesis of novel hybrid proteins and polypeptides.
摘要翻译：描述了利用核酸增量截短的一系列方法来产生多个经修饰的核酸和杂合多肽。产生给定核酸序列的多个基本上所有可能的单碱基对缺失。还描述了制造与核酸序列同源性无关的洗牌的增量截短核酸的方法。这些方法可用于蛋白质工程，蛋白质折叠，蛋白质进化和新型杂合蛋白质和多肽的化学合成。

40. 发明申请

US20080003642A1 CREATION OF DIVERSITY IN POLYPEPTIDES 审中-公开
标题翻译：多糖生物多样性的创造
公开(公告)号：US20080003642A1
公开(公告)日：2008-01-03
申请号：US11624750
申请日：2007-01-19
申请人： Allan Svendsen , Lars Beier
发明人： Allan Svendsen , Lars Beier
IPC分类号： C12P21/04 , A21D10/00 , C12N9/00
CPC分类号： A21D8/042 , C12N9/1048 , C12N9/2417 , C12N15/1027 , C12N15/1058 , C12N15/1089
摘要： The inventors realized that the diversity generated by conventional methods may be limited by steric hindrance between amino acid residues in the three-dimensional structures of the resulting polypeptides. The steric hindrance may occur between amino acid residues at widely different positions in the amino acid sequences, e.g. between residues in two different domains of the 3D structure, and resulting polypeptides which include such steric hindrance may never be observed in the conventional recombination methods because they may be ex-pressed in poor yields or may have poor activity or stability. The inventors developed a method to identify and alleviate such steric hindrance in the resulting polypeptides. In an alignment of the three-dimensional structures, steric hindrance is indicated when residues from two different structures are located within a certain distance. Pairs of residues at corresponding positions in the amino acid sequences are not considered, and residues close to the surface (high solvent accessibility) are considered to be less prone to steric hindrance.
摘要翻译：发明人意识到，通过常规方法产生的多样性可能受到所得多肽的三维结构中的氨基酸残基之间的空间位阻的限制。空间位阻可以发生在氨基酸序列中广泛不同位置的氨基酸残基之间，例如，在3D结构的两个不同结构域中的残基之间，以及包含这种空间位阻的所得多肽在常规重组方法中可能永远不会被观察到，因为它们可能以较差的产率被压制或者可能具有差的活性或稳定性。发明人开发了鉴定和减轻所得多肽中这种空间位阻的方法。在三维结构的排列中，当来自两个不同结构的残基位于一定距离内时，指示空间位阻。不考虑氨基酸序列中对应位置的残基对，并且靠近表面的残留物（高溶剂可及性）被认为不太容易发生空间位阻。

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