公开(公告)号：US20140121119A1

公开(公告)日：2014-05-01

申请号：US13664370

申请日：2012-10-30

申请人： AMPLICON EXPRESS, INC.

发明人： Keith E. Stormo ,  QuanZhou Tao ,  Robert H. Bogden ,  Evan K. Hart

IPC分类号： C40B20/06

CPC分类号： C40B20/06 ,  B01J19/0046 ,  B01J2219/00315 ,  B01J2219/00319 ,  B01J2219/00542 ,  B01J2219/00592 ,  B01J2219/00722 ,  B01J2219/00725 ,  B01J2219/0074 ,  C40B20/02

摘要： A substance identification method includes combining substances into four or more intermediate subpools in wells of a subpool plate and repooling the intermediate subpools into a number of final screening pools based on a repooling design providing the subpooled substances in at least three different final screening pools. The repooling design determines coordinates locating well positions for the substances. Another substance identification method includes using a two-dimensional array of wells arranged in rows and a number of columns that is at least 1.5 times the rows. Substances in the wells are combined into a number of screening pools. Individual screening pools include substances from wells having a row identifier in common with one other well. A pooling design provides the pooled substances in two different screening pools. The pooling design determines coordinates locating well positions for the substances.

摘要翻译： 一种物质识别方法包括将物质组合成四个或更多个中间子池，并将中间子池再次化成多个最终筛选池，其基于在至少三个不同的最终筛选池中提供子化物质的再造设计。 修复设计确定了确定物质位置的坐标。 另一种物质识别方法包括使用排列成行和至少为行的1.5倍的列的二维阵列。 井中的物质组合成多个筛选池。 单独的筛选池包括具有与另一个井相同的行标识符的井的物质。 汇集的设计在两个不同的筛选池中提供汇集的物质。 池设计确定了确定物质位置的坐标。

公开(公告)号：US20090035312A1

公开(公告)日：2009-02-05

申请号：US12088670

申请日：2006-09-29

申请人： Arjan Willem Griffioen ,  Judith Rosina Van Beijnum

发明人： Arjan Willem Griffioen ,  Judith Rosina Van Beijnum

IPC分类号： A61K39/395 ,  A61K31/7052 ,  C40B20/06 ,  C07H21/00 ,  C07K14/00 ,  C07K16/00 ,  C12N15/63 ,  C12N1/19 ,  C12N1/21 ,  C12N5/06 ,  C12N1/15 ,  C12N5/04 ,  C12N5/00 ,  C12Q1/68 ,  G01N33/53 ,  C12Q1/02 ,  A01K67/00 ,  C12P21/00 ,  G01N1/30 ,  A61P35/00

CPC分类号： C07K14/82 ,  C12Q1/6886 ,  C12Q2600/136

摘要： Methods of identifying specific target molecules for design of anti-angiogenic and vascular targeting approaches are disclosed. Transcriptional profiles of tumor endothelial cells were compared with that of normal resting endothelial cells, normal but angiogenically activated placental endothelial cells, and cultured endothelial cells. Although the majority of transcripts were classified as general angiogenesis markers, 17 genes were identified that show specific overexpression in tumor endothelium. Antibody targeting of four cell-surface expressed or secreted products (vimentin, CD59, HMGB1 and IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. The results demonstrate the utility of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.

摘要翻译： 公开了鉴定用于设计抗血管生成和血管靶向方法的特异性靶分子的方法。 与正常静息内皮细胞，正常但血管生成活化的胎盘内皮细胞和培养的内皮细胞的肿瘤内皮细胞的转录曲线进行比较。 虽然大多数转录物被归类为一般的血管发生标记，但是17个基因被鉴定为在肿瘤内皮中表现出特异性的过度表达。 四种细胞表面表达或分泌产物（波形蛋白，CD59，HMGB1和IGFBP7）的抗体靶向在体外和体内抑制血管生成。 最后，靶向小鼠肿瘤模型中的内皮波形蛋白显着抑制肿瘤生长和降低微血管密度。 结果证明了用于抗癌治疗的特异性肿瘤内皮标记物的鉴定和随后靶向的实用性。

公开(公告)号：US10240147B2

公开(公告)日：2019-03-26

申请号：US15106795

申请日：2014-12-11

申请人： Philochem AG

发明人： Willy Decurtins ,  Raphael Franzini ,  Dario Neri ,  Jörg Scheuermann ,  Moreno Wichert

IPC分类号： C12N15/10 ,  C40B20/06 ,  C40B40/06 ,  C40B50/10 ,  G01N33/58 ,  C12Q1/6874 ,  C07H21/02 ,  C07H21/04

摘要： This invention relates to the synthesis of nucleic acid-encoded chemical libraries using common adaptor sequences. Nucleic acid strands coupled to chemical moieties may be contacted with identifier oligonucleotides comprising coding sequences encoding the chemical moieties and an adaptor oligonucleotides, such that the adaptor oligonucleotide hybridizes to both the nucleic acid strands and the identifier oligonucleotides to allow ligation of the identifier oligonucleotides to the nucleic acid strands. The adaptor oligonucleotide is then removed. Nucleic acid-encoded chemical libraries, and methods of producing or screening such libraries are provided.

公开(公告)号：US09096952B2

公开(公告)日：2015-08-04

申请号：US13164153

申请日：2011-06-20

申请人： Robert Osborne ,  Andrew Slatter

发明人： Robert Osborne ,  Andrew Slatter

IPC分类号： C40B20/06 ,  C40B50/06 ,  C12N15/10

CPC分类号： C40B50/06 ,  C12N15/1093 ,  C12Q1/6806 ,  C12Q2521/101 ,  C12Q2525/191 ,  C12Q2563/179 ,  C12Q2525/151 ,  C12Q2525/185 ,  C12Q2525/204 ,  C12Q2531/131 ,  C12Q2535/138

摘要： Aspects of the present invention are drawn to methods and compositions for the genetic analysis of regions of interest (ROI) from one or more starting polynucleotide sample(s). In certain aspects, adapter tagged polynucleotide fragments from a plurality of initial polynucleotide samples are pooled, circularized and amplified to produce an immortalized library. Multiple ROI's from this immortalized library are amplified (e.g., in independent iPCR reactions) to generate amplicons, and, in some embodiments, pooled to form a pooled ROI amplicon sample. In certain embodiments, the amplicons for each ROI amplicon in the pooled ROI amplicon sample are present at known molar or mass ratios. The pooled ROI amplicon sample can be analyzed/processed as desired, e.g., sequenced using next generation sequencing technology.

摘要翻译： 本发明的方面涉及用于从一个或多个起始多核苷酸样品遗传分析感兴趣区域（ROI）的方法和组合物。 在某些方面，将来自多个初始多核苷酸样品的衔接子标记的多核苷酸片段合并，循环并扩增以产生永生化文库。 来自该永生化文库的多个ROI被扩增（例如，在独立的iPCR反应中）以产生扩增子，并且在一些实施方案中合并形成合并的ROI扩增子样品。 在某些实施方案中，合并的ROI扩增子样品中每个ROI扩增子的扩增子以已知的摩尔质量比存在。 可以根据需要对汇集的ROI扩增子样品进行分析/处理，例如使用下一代测序技术测序。

公开(公告)号：US20130018173A1

公开(公告)日：2013-01-17

申请号：US13547497

申请日：2012-07-12

申请人： John Simard

发明人： John Simard

IPC分类号： C40B20/06 ,  C40B40/02 ,  C07K16/00 ,  C40B50/06 ,  C40B40/08 ,  C07H21/04 ,  C40B40/06

CPC分类号： C07K16/005 ,  C07K16/24 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/56 ,  C12N15/1037 ,  C12N15/1096

摘要： Antigen-specific immunoglobulin V-regions are identified from a library of nucleic acids amplified using polymerase chain reaction using leader sequence-specific forward primers. The use of leader sequence primers allows all V-region sequences to be amplified (including those with extensive 5′ end mutations) without loss of the original 5′ V gene segment sequence. A second V-region library is made using a larger than conventional set of 5′ V-region primers. The sequence errors introduced into the amplification products by this method are corrected using sequence information obtained in the products amplified by the V-region primers to screen the library created using the leader sequence primers. Amino acid sequence information from fragments of donor immunoglobulins can be used to assist in the identification of nucleic acids encoding the heavy and light chains of donor antibodies as well as to design primers to amplify such nucleic acids.

摘要翻译： 从使用前导序列特异性前向引物的聚合酶链反应扩增的核酸文库鉴定抗原特异性免疫球蛋白V-区。 使用前导序列引物可以扩增所有的V区序列（包括具有5'末端突变的突变），而不损失原始的5'V基因片段序列。 使用大于5'V区引物的常规集合制备第二个V区文库。 通过该方法引入扩增产物的序列差异使用在由V区引物扩增的产物中获得的序列信息进行校正，以筛选使用前导序列引物产生的文库。 供体免疫球蛋白片段的氨基酸序列信息可用于帮助鉴定编码供体抗体重链和轻链的核酸，以及设计引物以扩增此类核酸。

公开(公告)号：US08513164B2

公开(公告)日：2013-08-20

申请号：US11642593

申请日：2006-12-21

申请人： Achim Knappik ,  Peter Pack ,  Liming Ge ,  Simon Moroney ,  Andreas Plückthun

发明人： Achim Knappik ,  Peter Pack ,  Liming Ge ,  Simon Moroney ,  Andreas Plückthun

IPC分类号： C40B20/06 ,  C40B30/04

CPC分类号： C07K1/047 ,  C07K16/00 ,  C07K16/005 ,  C07K16/18 ,  C07K16/242 ,  C07K16/26 ,  C07K16/2854 ,  C07K16/2896 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2319/00 ,  C12N15/10 ,  C12N15/1037 ,  C40B40/02

摘要： The present invention relates to a method of identifying one or more genes encoding one or more proteins having an optimized property. In particular, the method comprises expressing a collection of genes and screening for a desired property, identifying a plurality of genes having the desired property, and replacing one or more one or more sub-sequences of each of said genes with a different, compatible genetic sub-sequence, and screening again in order to identify genes encoding proteins having an optimized property.

摘要翻译： 本发明涉及鉴定编码一种或多种具有优化特性的蛋白质的一种或多种基因的方法。 特别地，所述方法包括表达基因的集合并筛选所需的性质，鉴定具有所需性质的多个基因，并用不同的相容遗传基因替换每个所述基因的一个或多个子序列 亚序列和再次筛选，以便鉴定编码具有优化特性的蛋白质的基因。

公开(公告)号：US20090123452A1

公开(公告)日：2009-05-14

申请号：US11825627

申请日：2007-07-05

申请人： Edwin L. Madison

发明人： Edwin L. Madison

IPC分类号： A61K38/48 ,  C40B20/04 ,  C40B30/04 ,  C40B20/06 ,  C40B40/10 ,  C12N15/63 ,  C07K14/00 ,  A61P9/00 ,  A61P25/00 ,  A61P7/02 ,  C12N1/00 ,  C07H21/00 ,  C12N9/48 ,  C12N9/72 ,  A61K38/49

CPC分类号： C12N15/1037 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/21 ,  C07K2319/23 ,  C07K2319/30 ,  C07K2319/41 ,  C07K2319/42 ,  C12N9/50 ,  C12N9/6408 ,  C12N9/6462 ,  C12Q1/37 ,  C12Y304/21073 ,  C12Y304/21109 ,  G01N33/6842

摘要： Methods for identifying modified proteases with modified substrate specificity or other properties are provided. The methods screen candidate and modified proteases by contacting them with a substrate, such as a serpin, an alpha macroglobulins or a p35 family protein or modified serpins and modified p35 family members or modified alpha macroglobulins, that, upon cleavage of the substrate, traps the protease by forming a stable complex. Also provided are modified proteases.

摘要翻译： 提供用于鉴定修饰的底物特异性或其它性质的修饰蛋白酶的方法。 通过使筛选候选物和修饰的蛋白酶与底物（例如丝氨酸蛋白酶抑制剂，α巨球蛋白或p35家族蛋白质或修饰的丝氨酸蛋白酶和修饰的p35家族成员或修饰的α巨球蛋白）接触来筛选候选物和修饰的蛋白酶，在基底切割时， 蛋白酶通过形成稳定的复合物。 还提供了修饰的蛋白酶。

公开(公告)号：US20080026947A1

公开(公告)日：2008-01-31

申请号：US11704090

申请日：2007-02-08

申请人： William Gmeiner

发明人： William Gmeiner

IPC分类号： C40B20/04 ,  C40B20/06

CPC分类号： C40B20/04 ,  C40B20/06

摘要： The present invention provides a method of generating a nucleic acid, which specifically binds to an extracellular surface protein expressed by a cell of interest, and which nucleic acid comprises a compound of interest to be delivered to the cell of interest.

摘要翻译： 本发明提供了一种产生核酸的方法，所述核酸特异性结合由感兴趣的细胞表达的细胞外表面蛋白质，并且该核酸包含待递送至感兴趣的细胞的感兴趣的化合物。

公开(公告)号：US20100273660A1

公开(公告)日：2010-10-28

申请号：US12617624

申请日：2009-11-12

申请人： Lars Zender ,  Wen Xue ,  Scott Powers ,  Scott W. Lowe

发明人： Lars Zender ,  Wen Xue ,  Scott Powers ,  Scott W. Lowe

IPC分类号： C40B20/06 ,  C07K16/00 ,  C40B50/04 ,  C40B40/06 ,  C12N5/09 ,  C12Q1/68 ,  G01N33/574

CPC分类号： A01K67/0271 ,  A01K2217/058 ,  A01K2267/0331 ,  C07K14/4747 ,  C12N15/1079 ,  C12N15/8509 ,  C12N2510/04 ,  C12N2517/02 ,  C12N2799/027 ,  C12Q1/6886 ,  C12Q2600/154 ,  C12Q2600/178 ,  G01N33/5044 ,  G01N33/5067 ,  G01N33/5088 ,  G01N33/57415 ,  G01N33/57438 ,  G01N2500/00 ,  G01N2800/50 ,  G01N2800/52

摘要： In some aspects, the invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal.The present invention also provides methods for identifying and validating tumor suppressor genes by screening pools of shRNAs that target genomic regions deleted in human cancers, such as human hepatocellular carcinomas. The present invention also provides validated tumor suppressor genes, and methods of inhibiting cell proliferation and/or tumor growth, for example by expression of such tumor suppressor genes.

摘要翻译： 在一些方面，本发明提供了用于肝细胞癌的遗传易处的非人动物模型。 该模型除其他外，有助于理解肝癌的分子机制，了解导致化学耐药性或预后不良的遗传改变，以及鉴定和评估针对肝细胞癌的新疗法。 本发明的肝癌模型通过改变肝细胞以增加癌基因表达，减少肿瘤抑制基因表达或两者并通过将所得肝细胞移植到受体非人动物中来制备。 本发明还提供了通过筛选靶向人类癌症中缺失的基因组区域（例如人肝细胞癌）的shRNA的鉴定和验证肿瘤抑制基因的方法。 本发明还提供了经过验证的肿瘤抑制基因，以及例如通过表达这种肿瘤抑制基因来抑制细胞增殖和/或肿瘤生长的方法。

公开(公告)号：US20090270264A1

公开(公告)日：2009-10-29

申请号：US12421124

申请日：2009-04-09

申请人： Thomas L. Overson

发明人： Thomas L. Overson

IPC分类号： C40B20/06 ,  C40B60/10

CPC分类号： G16B20/00 ,  C40B20/06 ,  C40B60/10

摘要： A total forensic DNA casework management system and method for the deconvolution of mixed DNA samples using a novel, 3-rule algorithm to determine the proportional allele sharing of the sample's contributors. The process is fully document, can assess and process DNA anomalies and artifacts, and transforms raw STR data to produce final DNA profile types, peak height ratios, proportions, fitting criteria and associated graphs.

摘要翻译： 一个全面的法医DNA个案工作管理系统和混合DNA样本的去卷积方法，采用新颖的3规则算法来确定样本贡献者的比例等位基因共享。 该过程是完整的文件，可以评估和处理DNA异常和伪像，并转换原始的STR数据，以产生最终的DNA分布类型，峰高比，比例，拟合标准和相关图。