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21.发明授权公开(公告)号：US07067284B1
公开(公告)日：2006-06-27
申请号：US09610551
申请日：2000-07-05
CPC分类号： C07K16/005 , C07K16/40 , C07K16/44 , C07K2317/55 , C07K2317/565 , C12N15/102 , C12N15/1086 , C12N15/1093
摘要： The present invention describes methods for producing antibody libraries, and particularly for increasing antibody library diversity by inducing mutagenesis within the CDR regions of immunoglobulin heavy or light chains that are displayed on the surface of filamentous phage particles comprising the library. The invention also describes oligonucleotides useful for increasing the library diversity, and universal light chains useful in the library production methods.
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公开(公告)号：US07011972B2
公开(公告)日：2006-03-14
申请号：US09908153
申请日：2001-07-18
CPC分类号： C07K14/72 , C07K14/4702 , C07K14/721 , C07K2319/00 , C12N15/63
摘要： Single chain, monomeric polypeptide gene switches are provided. The gene switches include ligand binding domains and at least one functional domain. Preferred functional domains are DNA binding domains and transcriptional regulating domains. Methods of regulating gene function using the switches are also provided.
摘要翻译： 提供单链，单体多肽基因开关。 基因切换包括配体结合结构域和至少一个功能结构域。 优选的功能结构域是DNA结合结构域和转录调节结构域。 还提供了使用开关调节基因功能的方法。
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公开(公告)号：US06589766B1
公开(公告)日：2003-07-08
申请号：US09965512
申请日：2001-09-25
IPC分类号： C12P726
CPC分类号： C12P7/26 , C12N9/0002
摘要： Catalytic antibodies, including 38C2 and 33F12, are capable of efficiently catalyzing a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular aldol reactions, and in some cases to catalyze their subsequent dehydration to yield aldol condensation products. A number of intramolecular aldol reactions have also been defined. Catalysis of all intramolecular aldol reactions examined yields the corresponding condensation products.
摘要翻译： 包括38C2和33F12在内的催化抗体能够有效地催化各种酮 - 酮，酮 - 醛，醛 - 酮和醛 - 醛分子间醛醇反应，并且在某些情况下催化它们随后的脱水以产生醛醇缩合 产品。 还定义了许多分子内醛醇反应。 所检测的所有分子内醛醇反应的催化产生相应的缩合产物。
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公开(公告)号：US06326176B1
公开(公告)日：2001-12-04
申请号：US09573753
申请日：2000-05-18
IPC分类号： C12P726
CPC分类号： C12P7/26 , C12N9/0002
摘要： Catalytic antibodies, including 38C2 and 33F12, are capable of efficiently catalyzing a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular aldol reactions, and in some cases to catalyze their subsequent dehydration to yield aldol condensation products. A number of intramolecular aldol reactions have also been defined. Catalysis of all intramolecular aldol reactions examined yields the corresponding condensation products.
摘要翻译： 包括38C2和33F12在内的催化抗体能够有效地催化各种酮 - 酮，酮 - 醛，醛 - 酮和醛 - 醛分子间醛醇反应，并且在某些情况下催化它们随后的脱水以产生醛醇缩合 产品。 还定义了许多分子内醛醇反应。 所检测的所有分子内醛醇反应的催化产生相应的缩合产物。
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公开(公告)号：US06294374B1
公开(公告)日：2001-09-25
申请号：US09415453
申请日：1999-10-08
IPC分类号： C12S1300
CPC分类号： C07D417/06 , C07B2200/07 , C07D277/24 , C07D277/34 , C07D277/36 , C07D493/04 , C12N9/0002 , C12P7/26 , C12P17/16 , C12P17/18 , C12P41/002
摘要： Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.
摘要翻译： 通过反应性免疫针对β-二酮半抗原产生的三种单克隆醛缩酶抗体催化快速和高度对映选择性的醛缩醇反应，通过动力学拆分提供ent-9a-k。 化合物9a，9g和9k用0.005-0.0004mol％抗体催化剂以多克量分离。 对映体纯原料9a-k是构建埃坡霉素A-E（2-6）及其类似物包括13-烷基衍生物的有用合成物。 以前，在制备埃坡霉素A-D，2-5中报道了使用化合物9a作为合成子。 为了进一步扩展这种基于合成子的策略，从分别由大规模抗体制备的对映体纯的噻唑醛醇9g和9a开始合成埃坡霉素E，6,13-甲基埃博霉素C 7及其反式异构体 催化分解。
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26.发明授权公开(公告)号：US06210938B1
公开(公告)日：2001-04-03
申请号：US09458367
申请日：1999-12-09
申请人： Carlos F. Barbas , Richard A. Lerner , Guofu Zhong
发明人： Carlos F. Barbas , Richard A. Lerner , Guofu Zhong
IPC分类号： C12P726
CPC分类号： C07D417/06 , C07B2200/07 , C07D277/24 , C07D277/34 , C07D277/36 , C07D493/04 , C12N9/0002 , C12P7/26 , C12P17/16 , C12P17/18 , C12P41/002
摘要： Nine efficient aldolase antibodies were generated using hapten 2. This hapten combines, in a single molecule, structural components employed for reactive immunization with structural components employed for forming a transition state analog of the aldol reaction. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereo- selectivities opposite that of antibody 38C2.
摘要翻译： 使用半抗原2产生九种有效的醛缩酶抗体。该半抗原在单个分子中结合用于反应性免疫的结构组分与用于形成醛醇反应的过渡态类似物的结构组分。 这些抗体中的两种的表征显示它们是非常熟练的（比任何其他抗体催化剂优于1000倍）和用于醛醇醛和醛缩醇反应的对映选择性催化剂，并显示与抗体38C2相反的对映体和非对映体选择性。
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公开(公告)号：US6140466A
公开(公告)日：2000-10-31
申请号：US863813
申请日：1997-05-27
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K48/00 , A61P1/00 , A61P7/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P17/00 , A61P35/00 , A61P37/00 , A61P43/00 , C07H21/04 , C07K7/06 , C07K14/46 , C07K14/47 , C12N15/62 , C12P21/02 , C12Q1/02 , C12Q1/68 , C12Q1/70 , G01N33/569 , G01N33/68 , C07K14/435 , C07K14/005 , C07K14/415 , C12M15/00
CPC分类号： C07K14/46 , C07K14/4702 , C12N15/62 , C12Q1/68 , G01N33/5008 , G01N33/5011 , G01N33/502 , G01N33/56988 , G01N33/68 , A61K38/00 , A61K48/00 , C07K2319/00 , C07K2319/02 , C07K2319/09 , C07K2319/24 , C07K2319/42 , C07K2319/71 , C07K2319/73 , C07K2319/735 , C07K2319/81
摘要： Zinc finger proteins of the Cys.sub.2 His.sub.2 type represent a class of malleable DNA binding proteins which may be selected to bind diverse sequences. Typically, zinc finger proteins containing three zinc finger domains, like the murine transcription factor Zif268 and the human transcription factor Sp1, bind nine contiguous base pairs (bp). To create a class of proteins which would be generally applicable to target unique sites within complex genomes, the present invention provides a polypeptide linker that fuses two three-finger proteins. Two six-fingered proteins were created and demonstrated to bind 18 contiguous bp of DNA in a sequence specific fashion. Expression of these proteins as fusions to activation or repression domains allows transcription to be specifically up or down modulated within cells. Polydactyl zinc finger proteins are broadly applicable as genome-specific transcriptional switches in gene therapy strategies and the development of novel transgenic plants and animals. Such proteins are useful for inhibiting, activating or enhancing gene expression from a zinc finger-nucleotide binding motif containing promoter or other transcriptional control element, as well as a structural gene or RNA sequence.
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28.发明授权Chimeric zinc finger recombinases optimized for catalysis by directed evolution 失效通过定向进化优化催化的嵌合锌指重组酶公开(公告)号：US08685687B2
公开(公告)日：2014-04-01
申请号：US12309096
申请日：2007-07-05
IPC分类号： C12N9/00
CPC分类号： C12N9/22 , A01K2217/05 , C07K2319/81 , C12N15/1082
摘要： The present invention is directed to chimeric recombinases comprising a serine recombinase operatively linked to a zinc finger nucleotide binding domain such that the chimeric recombinase protein catalyzes site-specific recombination at a DNA site specifically bound by the zinc finger nucleotide binding domain. The serine recombinase can be one of several naturally occurring serine recombinases. The invention also includes nucleic acids encoding the chimeric recombinases, vectors including the nucleic acids, host cells transformed or transfected with the vectors, methods of using the chimeric recombinases to carry out recombination, methods of using substrate-linked protein evolution to generate additional chimeric recombinases, methods of using the chimeric recombinases for gene therapy, and pharmaceutical compositions.
摘要翻译： 本发明涉及包含与锌指核苷酸结合结构域有效连接的丝氨酸重组酶的嵌合重组酶，使得嵌合重组酶蛋白在由锌指核苷酸结合结构域特异性结合的DNA位点处催化位点特异性重组。 丝氨酸重组酶可以是几种天然存在的丝氨酸重组酶之一。 本发明还包括编码嵌合重组酶的核酸，包括核酸的载体，用载体转化或转染的宿主细胞，使用嵌合重组酶进行重组的方法，使用底物连接蛋白进化产生另外的嵌合重组酶的方法 ，使用嵌合重组酶进行基因治疗的方法和药物组合物。
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29.发明授权Multispecific antibody targeting and multivalency through modular recognition domains 有权多特异性抗体靶向和通过模块识别域的多值公开(公告)号：US08454960B2
公开(公告)日：2013-06-04
申请号：US13135754
申请日：2011-07-14
IPC分类号： C07K16/28 , C07K16/30 , C07K14/00 , A61K38/16 , A61K39/395
CPC分类号： C07K16/468 , A61K2039/505 , C07K14/515 , C07K14/52 , C07K14/70557 , C07K14/72 , C07K16/22 , C07K16/2848 , C07K16/2863 , C07K16/32 , C07K16/40 , C07K2317/31 , C07K2317/73 , C07K2319/00 , C12N9/0002
摘要： Antibodies containing one or more modular recognition domains (MRDs) that can be used to target the antibodies to specific sites are described. The use of antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also described.
摘要翻译： 描述了可以用于将抗体靶向特定位点的含有一个或多个模块识别结构域（MRD）的抗体。 还描述了使用含有一个或多个模块识别结构域的抗体来治疗疾病，以及制备含有一个或多个模块识别结构域的抗体的方法。
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30.发明申请公开(公告)号：US20120329067A1
公开(公告)日：2012-12-27
申请号：US13574223
申请日：2011-01-21
申请人： Carlos F. Barbas III , Jing Guo
发明人： Carlos F. Barbas III , Jing Guo
IPC分类号： C12N9/22 , C40B30/06 , C40B10/00 , C12N15/01 , C12P19/34 , C12N5/09 , C12N15/87 , C12Q1/68 , C12N5/00
CPC分类号： C12Q1/34 , C12N9/22 , C12N15/87 , C12Q1/6897 , G01N2333/922 , G01N2500/00
摘要： Provided herein are zinc linger nucleases having altered, arid in particular, improved catalytic activity and methods of generating such nucleases. Accordingly, there are provided methods for identifying improved catalytic activity of a ZFN by expressing a mutated zinc finger nuclease in a cell containing a reporter construct with a toxic gene, and a zinc finger nuclease cleavage site that is recognized by the ZFN. Survival of the cell is positively correlated with catalytic activity of the ZFN; thus, libraries of mutated ZFKs may be selected for altered catalytic activity based on relative survival rates, Methods of using identified ZFNs are also provided.
摘要翻译： 本文提供了具有改变，特别是改进的催化活性和产生这种核酸酶的方法的锌连环核酸酶。 因此，提供了通过在含有具有毒性基因的报道构建体的细胞中表达突变的锌指核酸酶以及通过ZFN识别的锌指核酸酶切割位点来鉴定ZFN的改善的催化活性的方法。 细胞存活与ZFN的催化活性呈正相关; 因此，可以基于相对存活率选择突变的ZFK文库以改变催化活性，还提供使用鉴定的ZFN的方法。
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