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    Methods for recording the reaction history of a solid support
    2.
    发明授权
    Methods for recording the reaction history of a solid support 失效
    用于记录固体支持物的反应历史的方法

    公开(公告)号：US5968736A

    公开(公告)日：1999-10-19

    申请号：US480821

    申请日：1995-06-07

    申请人： W. Clark Still ,  Michael H. Wigler ,  Michael H. J. Ohlmeyer ,  Lawrence W. Dillard ,  John C. Reader

    发明人： W. Clark Still ,  Michael H. Wigler ,  Michael H. J. Ohlmeyer ,  Lawrence W. Dillard ,  John C. Reader

    IPC分类号： G01N33/566 ,  C07B61/00 ,  C07C43/225 ,  C07C205/59 ,  C07C245/14 ,  C07C317/28 ,  C07D243/24 ,  C07D521/00 ,  C07H21/00 ,  C07K1/00 ,  C07K1/04 ,  C40B70/00 ,  G01N33/532 ,  G01N33/543 ,  G01N33/68 ,  G01N33/53

    CPC分类号： G01N33/68 ,  C07D243/24 ,  C07H21/00 ,  C07K1/047 ,  C40B50/16 ,  G01N33/532 ,  G01N33/54353 ,  B01J2219/00572 ,  C07B2200/11 ,  C40B40/00 ,  C40B70/00

    摘要： Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle. The reaction history of the particles which are positive for the characteristic can be determined by the release of the tags and analysis to define the reaction history of the particle.

    摘要翻译： 提供了编码的组合化学，其中使用有机分子记录顺序合成方案，其定义了反应物的选择和阶段，作为相同或不同的信息位。 可以在多级合成中产生各种产物，例如低聚物和合成的非重复有机分子。 方便地，化合物的嵌套族可以用作标识符，其中取代基的数目和/或位置定义了选择。 或者，可以使用可检测的官能团，例如放射性同位素，荧光剂，卤素等，其中两个不同基团的存在和比例可用于限定阶段或选择。 特别地，可以使用多个标识符来提供二进制或更高代码，以便仅限定几个可拆卸标签来定义多个选择。 可以筛选颗粒以获得感兴趣的特征，特别是结合亲和力，其中产物可以与颗粒分离或保留在颗粒上。 对特征呈阳性的颗粒的反应历程可以通过标签的释放和分析来确定以确定颗粒的反应历程。

    Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules
    3.
    发明授权
    Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules 失效
    产生包含多种抗体DNA扩增的抗体基因库的方法以及使用这些文库生产多种抗原结合分子的方法

    公开(公告)号：US5780225A

    公开(公告)日：1998-07-14

    申请号：US315269

    申请日：1994-09-29

    申请人： Michael H. Wigler ,  Joseph A. Sorge

    发明人： Michael H. Wigler ,  Joseph A. Sorge

    IPC分类号： C12N15/10 ,  C12Q1/68 ,  C12P21/00

    CPC分类号： C12Q1/6811 ,  C12N15/10 ,  C07K2319/00

    摘要： A method of producing libraries of genes encoding antigen-combining molecules or antibodies; a method of producing antigen-combining molecules which does not require an in vivo procedure; a method of obtaining antigen-combining molecules of selected specificity which does not require an in vivo procedure; vectors useful in the present method; and antigen-combining molecules produced by the method. The antigen-combining molecules are useful for the detection, quantitation, purification and neutralization of antigens, as well as for diagnostic, therapeutic and prophylactic purposes.

    摘要翻译： 一种产生编码抗原结合分子或抗体的基因文库的方法; 生产不需要体内程序的抗原结合分子的方法; 获得不需要体内过程的所选特异性的抗原结合分子的方法; 本方法有用的载体; 和通过该方法产生的抗原结合分子。 抗原结合分子可用于抗原的检测，定量，纯化和中和，以及用于诊断，治疗和预防目的。

    Method of identifying virtual representations of nucleotide sequences
    5.
    发明授权
    Method of identifying virtual representations of nucleotide sequences 有权
    识别核苷酸序列的虚拟表示的方法

    公开(公告)号：US08694263B2

    公开(公告)日：2014-04-08

    申请号：US10851779

    申请日：2004-05-21

    申请人： Michael H Wigler ,  John Healy ,  Robert Lucito

    发明人： Michael H Wigler ,  John Healy ,  Robert Lucito

    IPC分类号： G01N33/48

    CPC分类号： C07H21/04

    摘要： The invention provides oligonucleotide probes that can be used to hybridize to a representation of nucleic acid sequences. Compositions containing the probes such as microarrays are also provided. The invention also provides methods of using these probes and compositions in therapeutic, diagnostic, and research applications. Systems and methods for using a word counting algorithm that can quickly and accurately count the number of times a particular string of characters (i.e., nucleotides) appears in a nucleotide sequence (e.g., a genome) are provided. This algorithm can be used to identify the oligonucleotide probes of the invention. The algorithm uses a transform of a genome and an auxiliary data structure to count the number of times a particular word occurs in the genome.

    摘要翻译： 本发明提供可用于与核酸序列表示杂交的寡核苷酸探针。 还提供了包含探针如微阵列的组合物。 本发明还提供了在治疗，诊断和研究应用中使用这些探针和组合物的方法。 提供了使用字计数算法的系统和方法，其可以快速且准确地计算特定字符串（即，核苷酸）出现在核苷酸序列（例如基因组）中的次数。 该算法可用于鉴定本发明的寡核苷酸探针。 该算法使用基因组和辅助数据结构的变换来计算特定词在基因组中发生的次数。

    Cloning by complementation and related processes
    7.
    发明授权
    Cloning by complementation and related processes 有权
    通过互补和相关过程进行克隆

    公开(公告)号：US6069240A

    公开(公告)日：2000-05-30

    申请号：US146249

    申请日：1998-09-03

    申请人： Michael H. Wigler ,  John J. Colicelli

    发明人： Michael H. Wigler ,  John J. Colicelli

    IPC分类号： C12N9/16 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C12N9/16

    摘要： Disclosed are methods for detecting mammalian genes encoding proteins which can function in microorganisms, particularly yeast, to modify, complement, or suppress a genetic defect associated with an identifiable phenotypic alteration or characteristic in the microorganism. Disclosed also are mammalian DNA sequences cloned by the above method, as well as polypeptide products of the expression of the DNA sequences in procaryotic or eucaryotic host cells and antibody substances which are specifically immunoreactive with said expression products. More specifically, the present invention relates to methods for cloning mammalian genes which encode products which modify, complement or suppress a genetic defect in a biochemical pathway in which cAMP participates or in a biochemical pathway which is controlled, directly or indirectly, by a RAS-related protein, to products (RNA, proteins) encoded by the mammalian genes cloned in this manner, and to antibodies which can bind the encoded proteins.

    摘要翻译： 公开了用于检测哺乳动物基因的方法，所述哺乳动物基因编码可在微生物，特别是酵母中发挥作用的蛋白质，以修饰，补充或抑制与微生物中可识别的表型改变或特征相关的遗传缺陷。 还公开了通过上述方法克隆的哺乳动物DNA序列，以及原核或真核宿主细胞中DNA序列表达的多肽产物和与所述表达产物特异性免疫反应的抗体物质。 更具体地，本发明涉及用于克隆哺乳动物基因的方法，所述哺乳动物基因编码修饰，补体或抑制cAMP参与的生物化学途径中的遗传缺陷或直接或间接受RAS- 与由这种方式克隆的哺乳动物基因编码的产物（RNA，蛋白质）以及能结合编码蛋白质的抗体。

    Methods of determining the structure of a compound encoded by identifiers having tags
    8.
    发明授权
    Methods of determining the structure of a compound encoded by identifiers having tags 失效
    确定具有标签的标识符编码的化合物的结构的方法

    公开(公告)号：US5789172A

    公开(公告)日：1998-08-04

    申请号：US680716

    申请日：1996-07-11

    申请人： W. Clark Still ,  Michael H. Wigler ,  Michael H. J. Ohlmeyer ,  Lawrence W. Dillard ,  John C. Reader

    发明人： W. Clark Still ,  Michael H. Wigler ,  Michael H. J. Ohlmeyer ,  Lawrence W. Dillard ,  John C. Reader

    IPC分类号： G01N33/566 ,  C07B61/00 ,  C07C43/225 ,  C07C205/59 ,  C07C245/14 ,  C07C317/28 ,  C07D243/24 ,  C07D521/00 ,  C07H21/00 ,  C07K1/00 ,  C07K1/04 ,  C40B70/00 ,  G01N33/532 ,  G01N33/543 ,  G01N33/68 ,  C12Q1/68 ,  G01N33/53

    CPC分类号： G01N33/68 ,  C07D243/24 ,  C07H21/00 ,  C07K1/047 ,  C40B50/16 ,  G01N33/532 ,  G01N33/54353 ,  B01J2219/00572 ,  C07B2200/11 ,  C40B40/00 ,  C40B70/00

    摘要： Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle. The reaction history of the particles which are positive for the characteristic can be determined by the release of the tags and analysis to define the reaction history of the particle.

    摘要翻译： 提供了编码的组合化学，其中使用有机分子记录顺序合成方案，其定义了反应物的选择和阶段，作为相同或不同的信息位。 可以在多级合成中产生各种产物，例如低聚物和合成的非重复有机分子。 方便地，化合物的嵌套族可以用作标识符，其中取代基的数目和/或位置定义了选择。 或者，可以使用可检测的官能团，例如放射性同位素，荧光剂，卤素等，其中两个不同基团的存在和比例可用于限定阶段或选择。 特别地，可以使用多个标识符来提供二进制或更高代码，以便仅限定几个可拆卸标签来定义多个选择。 可以筛选颗粒以获得感兴趣的特征，特别是结合亲和力，其中产物可以与颗粒分离或保留在颗粒上。 对特征呈阳性的颗粒的反应历程可以通过标签的释放和分析来确定以确定颗粒的反应历程。

    Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
    9.
    发明授权
    Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials 失效
    将DNA插入真核细胞并生产蛋白质材料的方法

    公开(公告)号：US4399216A

    公开(公告)日：1983-08-16

    申请号：US124513

    申请日：1980-02-25

    申请人： Richard Axel ,  Michael H. Wigler ,  Saul J. Silverstein

    发明人： Richard Axel ,  Michael H. Wigler ,  Saul J. Silverstein

    IPC分类号： C12N5/00 ,  C12N15/00 ,  C12N15/85 ,  C12N15/87 ,  C12P21/00 ,  C12P21/02 ,  C12Q1/02 ,  C12Q1/04 ,  C12Q1/68

    CPC分类号： C12N15/87 ,  C12N15/85 ,  C12P21/02 ,  Y10S435/811 ,  Y10S435/948

    摘要： The present invention relates to processes for inserting DNA into eucaryotic cells, particularly DNA which includes a gene or genes coding for desired proteinaceous materials for which no selective criteria exist. The insertion of such DNA molecules is accomplished by cotransforming eucaryotic cells with such DNA together with a second DNA which corresponds to a gene coding for a selectable marker.The invention further relates to processes for inserting into eucaryotic cells a multiplicity of DNA molecules including genes coding for desired proteinaceous materials by cotransformation with the desired genes and with amplifiable genes for a dominant selectable marker in the presence of successively higher amounts of an inhibitor. Alternatively, the insertion of multiple copies of desired genes is accomplished by transformation using DNA molecules formed by ligating a DNA molecule including the desired gene to a DNA molecule which includes an amplifiable gene coding for a dominant selectable phenotype such as a gene associated with resistance to a drug in the presence of successively higher amounts of an agent such as a drug against which the gene confers resistance so that only those eucaryotic cells into which multiple copies of the amplifiable gene have been inserted survive.

    摘要翻译： 本发明涉及将DNA插入真核细胞的方法，特别是包括编码没有选择性标准的所需蛋白质材料的基因或基因的DNA。 这样的DNA分子的插入通过与这样的DNA共转化真核细胞以及对应于编码选择标记的基因的第二DNA来实现。 本发明还涉及在真核细胞中插入多个DNA分子的方法，所述多个DNA分子包括编码所需蛋白质材料的基因，通过与期望的基因共转化，并且在连续更高量的抑制剂存在下，具有用于显性选择标记的可扩增基因。 或者，通过使用通过将包含所需基因的DNA分子连接到DNA分子而形成的DNA分子进行转化来实现，所述DNA分子包括编码显性可选择表型的可扩增基因，例如与抗性相关的基因 在连续更多量的药物存在下的药物，所述药物如基因赋予抗性的药物，使得只有插入了可扩增基因的多个拷贝的真核细胞才能存活。