公开(公告)号：US20140067280A1

公开(公告)日：2014-03-06

申请号：US13834685

申请日：2013-03-15

Applicant: Inova Health System

Inventor： Joseph Vockley ,  John Niederhuber

IPC: G06F19/18

CPC classification number: G06F19/18 ,  C40B30/02 ,  G06F19/14 ,  G06F19/22

Abstract: Ancestry has a significant impact on the major and minor alleles found in each nucleotide position within the genome. Due to mechanisms of inheritance, ancestral-specific information contained within the genome is conserved within members of an ancestry. For this reason, individuals within a specific ancestry are more likely to share alleles in their genomes with other members of the same ancestry. Functionally, the combination of alleles at all positions within a group of individuals defines that group as having a common ancestry. Moreover, the aggregation of differences between alleles at all positions distinguishes one ancestry from another. The genomic similarities and differences between ancestries provides a mechanism to generate reference genomes that are specific for each ancestry. Reference genomes that are specific to an ancestry can be used to increase the accuracy of whole genome sequencing, DNA-based diagnostics and therapeutic marker discovery and in a variety of real-world DNA-based applications.

Abstract translation: 祖先对基因组内每个核苷酸位置发现的主要和次要等位基因具有显着影响。 由于遗传机制，祖先特异性信息包含在基因组内，在祖先的成员中是保守的。 因此，特定祖先的个体更有可能与同一祖先的其他成员共享基因组中的等位基因。 功能上，一组个体内的所有位置上的等位基因的组合将该组定义为具有共同的祖先。 此外，所有位置的等位基因之间的差异的聚集将一个祖先与另一个祖先区分开。 祖先之间的基因组相似性和差异提供了生成对每个祖先特异的参考基因组的机制。 可以使用对祖先特异性的参考基因组来提高全基因组测序，基于DNA的诊断和治疗标记发现的准确性，以及各种真实的基于DNA的应用。

公开(公告)号：US20140038168A1

公开(公告)日：2014-02-06

申请号：US13881835

申请日：2011-10-27

Applicant: Andrey Vinnik ,  Peter Fedichev ,  Maxim Kholin ,  Christopher Molloy ,  Aron Katz

Inventor： Andrey Vinnik ,  Peter Fedichev ,  Maxim Kholin ,  Christopher Molloy ,  Aron Katz

IPC: C12N7/00 ,  C07C237/40 ,  C07K14/005 ,  G06F19/16

CPC classification number: G01N33/566 ,  A61K31/00 ,  C07C231/12 ,  C07C237/40 ,  C07C237/42 ,  C07C2601/14 ,  C07K14/005 ,  C07K16/1063 ,  C07K2317/14 ,  C12N7/00 ,  C12Q1/703 ,  C40B30/02 ,  G01N33/50 ,  G01N2333/162 ,  G01N2333/70514 ,  G01N2500/00 ,  G01N2500/02 ,  G06F19/16 ,  G06F19/706

Abstract: The present invention relates to a method of designing an inhibitor of the binding of HIV (human immunodeficiency virus) glycoprotein (gp)120 to a CD4-receptor or to the integrin alpha4 beta7 (a4b7). The inhibitor interacts with at least two amino acid residues comprised in six motifs within the 3-dimensional structure of gp120. Also provided are compounds, pharmaceutical compositions thereof and uses thereof in the development of an inhibitor of the binding of a HIV gp120 to a CD4-receptor or an integrin alpha4 beta7 (a4b7). The inhibitors are useful for the prevention or treatment of an HIV infection and/or diseases associated with an HIV infection.

Abstract translation: 本发明涉及一种设计HIV（人类免疫缺陷病毒）糖蛋白（gp）120与CD4受体或整联蛋白α4β7（a4b7）结合的抑制剂的方法。 抑制剂与gp120的三维结构内的六个基序中包含的至少两个氨基酸残基相互作用。 还提供了化合物，其药物组合物及其在开发HIV gp120与CD4受体或整联蛋白α4β7（a4b7）结合的抑制剂中的用途。 抑制剂可用于预防或治疗HIV感染和/或与HIV感染相关的疾病。

公开(公告)号：US20130310303A1

公开(公告)日：2013-11-21

申请号：US13981668

申请日：2012-01-26

Applicant: Hagit Eldar-Finkelman ,  Avital Licht-Murava ,  Batya Plotkin

Inventor： Hagit Eldar-Finkelman ,  Avital Licht-Murava ,  Batya Plotkin

IPC: C07K7/08 ,  C07K7/06

CPC classification number: C07K7/08 ,  A61K38/00 ,  A61K38/08 ,  A61K38/10 ,  C07K7/06 ,  C12N9/12 ,  C12N9/1205 ,  C12Q1/485 ,  C12Y207/11001 ,  C40B30/02 ,  G01N33/573 ,  G01N2333/912 ,  G01N2440/14 ,  G01N2500/04 ,  G01N2500/10

Abstract: Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3. Also disclosed are GSK-3 substrate competitive inhibitors which bind to the defined binding site subunit in the enzyme. Also disclosed are mutants of GSK-3 and uses thereof for identifying a putative GSK-3 substrate competitive inhibitor.

Abstract translation: 公开了GSK-3的新型肽抑制剂，含有其的组合物及其用途。 新型肽抑制剂是​​底物竞争性抑制剂，并且具有设计成与GSK-3中规定的结合位点亚基结合的氨基酸序列。 还公开了结合酶中限定的结合位点亚基的GSK-3底物竞争性抑制剂。 还公开了GSK-3的突变体及其用于鉴定推定的GSK-3底物竞争性抑制剂的用途。

公开(公告)号：US20130156754A1

公开(公告)日：2013-06-20

申请号：US13773485

申请日：2013-02-21

Applicant: Gregory Alan Lazar ,  Arthur J. Chirino ,  Wei Dang ,  John Desjarlais ,  Stephen K. Doberstein ,  Robert J. Hayes ,  Sher Bahadur Karki ,  Omid Vafa

Inventor： Gregory Alan Lazar ,  Arthur J. Chirino ,  Wei Dang ,  John Desjarlais ,  Stephen K. Doberstein ,  Robert J. Hayes ,  Sher Bahadur Karki ,  Omid Vafa

IPC: A61K39/395

CPC classification number: C07K16/283 ,  A61K39/395 ,  A61K39/3955 ,  A61K39/39566 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/22 ,  C07K16/2863 ,  C07K16/2875 ,  C07K16/2887 ,  C07K16/2893 ,  C07K16/2896 ,  C07K16/32 ,  C07K16/4291 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/41 ,  C07K2317/51 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/56 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/30 ,  C12P21/005 ,  C40B30/02 ,  G06F19/12 ,  G06F19/16 ,  G06F19/22

Abstract: The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

Abstract translation: 本发明涉及优化的Fc变体，其产生方法，以及包含优化的Fc变体的抗体和Fc融合体。

公开(公告)号：US08417462B2

公开(公告)日：2013-04-09

申请号：US12349955

申请日：2009-01-07

Applicant: Samuel Bogoch ,  Elenore S. Bogoch ,  Samuel Winston Bogoch ,  Anne Elenore Borsanyi

Inventor： Samuel Bogoch ,  Elenore S. Bogoch ,  Samuel Winston Bogoch ,  Anne Elenore Borsanyi

IPC: G01N33/50

CPC classification number: G06F19/16 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  A61K2039/53 ,  C07K14/005 ,  C07K14/195 ,  C07K14/205 ,  C07K14/21 ,  C07K14/22 ,  C07K14/24 ,  C07K14/245 ,  C07K14/255 ,  C07K14/26 ,  C07K14/27 ,  C07K14/28 ,  C07K14/285 ,  C07K14/30 ,  C07K14/305 ,  C07K14/31 ,  C07K14/315 ,  C07K14/32 ,  C07K14/33 ,  C07K14/335 ,  C07K14/34 ,  C07K14/345 ,  C07K14/35 ,  C07K14/355 ,  C07K14/36 ,  C07K14/37 ,  C07K14/38 ,  C07K14/385 ,  C07K14/39 ,  C07K14/40 ,  C07K14/405 ,  C07K14/415 ,  C07K14/44 ,  C07K14/445 ,  C07K14/47 ,  C12N2710/24122 ,  C12N2760/16022 ,  C12N2760/16122 ,  C40B30/02 ,  G06F19/22

Abstract: A method and system are disclosed for identifying and/or locating complex patterns in an amino acid sequence stored in a computer file or database. According to an aspect of the present invention, techniques are provided to facilitate queries of protein databases. For protein descriptions received in response to the queries, embodiments of the present invention may scan the received protein descriptions to identify and locate Replikin patterns. A Replikin pattern is defined to be a sequence of 7 to about 50 amino acids that include the following three (3) characteristics, each of which may be recognized by an embodiment of the present invention: (1) the sequence has at least one lysine residue located six to ten amino acid residues from a second lysine residue; (2) the sequence has at least one histidine residue; and (3) at least 6% of the amino acids in the sequence are lysine residues.

Abstract translation: 公开了用于识别和/或定位存储在计算机文件或数据库中的氨基酸序列中的复杂模式的方法和系统。 根据本发明的一个方面，提供了用于促进蛋白质数据库查询的技术。 对于响应于查询而接收到的蛋白质描述，本发明的实施例可以扫描接收到的蛋白质描述以识别和定位Replikin模式。 复制素模式被定义为7至约50个氨基酸的序列，其包括以下三（3）个特征，每个特征可以被本发明的实施方案识别：（1）序列具有至少一个赖氨酸 残基位于第二赖氨酸残基6至10个氨基酸残基; （2）该序列具有至少一个组氨酸残基; 和（3）序列中至少6％的氨基酸是赖氨酸残基。

公开(公告)号：US08404838B2

公开(公告)日：2013-03-26

申请号：US13157472

申请日：2011-06-10

Applicant: Garland R. Marshall ,  Linda J. Pike ,  Robert Yang

Inventor： Garland R. Marshall ,  Linda J. Pike ,  Robert Yang

IPC: C07D473/00

CPC classification number: C07D241/38 ,  C07D241/46 ,  C07D401/06 ,  C07D409/06 ,  C07D473/24 ,  C07D487/04 ,  C40B30/02 ,  G06F19/16 ,  G06F19/706

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

公开(公告)号：US20120322717A9

公开(公告)日：2012-12-20

申请号：US12454765

申请日：2009-05-22

Applicant: Dakai Liu ,  Xiaofeng Li ,  Richard Jin ,  Yuaxin Liang ,  Wei Cheng ,  Riddhi Bhattacharyya ,  Guangrong Zhang

Inventor： Dakai Liu ,  Xiaofeng Li ,  Richard Jin ,  Yuaxin Liang ,  Wei Cheng ,  Riddhi Bhattacharyya ,  Guangrong Zhang

IPC: A61K38/02 ,  C07C309/53 ,  C07C235/56 ,  C07D251/70 ,  C07C229/66 ,  A61K31/538 ,  A61K31/196 ,  A61K31/185 ,  A61K31/277 ,  A61K31/53 ,  A61K31/245 ,  A61K31/366 ,  A61K31/12 ,  A61K31/165 ,  A61K31/167 ,  A61K31/505 ,  A61K31/122 ,  A61K31/235 ,  A61K31/05 ,  A61K31/365 ,  A61K31/343 ,  A61P31/12 ,  A61P25/00 ,  A61P19/00 ,  A61P35/00 ,  A61P3/08 ,  A61P3/06 ,  G01N33/00 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/542 ,  C40B30/04 ,  C40B30/02 ,  C12N5/10 ,  C12Q1/66 ,  C07D265/38

CPC classification number: G01N33/6845 ,  A61K31/536 ,  A61K31/538 ,  C07D265/28 ,  C07D265/34 ,  C07D265/38 ,  C40B30/02 ,  G01N2800/36

Abstract: The present invention relates to the field of therapeutic methods to screen for compounds on the basis of their ability to influence Wnt activity. The screening process is applied to both a physical library of a series of compounds and a virtual library of compounds that affect Wnt activity. In one aspect, the virtual screening process could be carried out where a permutational library of small peptides is substituted for the small organic molecules. The inventive methods may be used to empirically test for effects on Wnt activity and may also be applied to any pair of proteins involved in protein-protein interactions.

Abstract translation: 本发明涉及根据其影响Wnt活性的能力筛选化合物的治疗方法领域。 筛选过程适用于一系列化合物的物理文库和影响Wnt活性的化合物的虚拟文库。 一方面，虚拟筛选过程可以在小肽的置换文库替代小有机分子的地方进行。 本发明的方法可用于经验性地测试对Wnt活性的影响，并且还可以应用于涉及蛋白质 - 蛋白质相互作用的任何一对蛋白质。

公开(公告)号：US08145430B2

公开(公告)日：2012-03-27

申请号：US11373684

申请日：2006-03-10

Applicant: Richard A. Friesner ,  Robert Murphy

Inventor： Richard A. Friesner ,  Robert Murphy

IPC: G06G7/48 ,  G06G7/58

CPC classification number: G06F19/706 ,  C40B30/02 ,  G06F19/16 ,  G06F19/18 ,  G06F19/26

Abstract: A computer-implemented method for calculating a value representative of interaction (VRI) of a proposed ligand with a specified receptor. Hydrophobic interactions between one or more ligand atoms and one or more receptor atoms are scored by a method that awards a bonus for the presence of hydrophobic enclosure of one or more ligand atoms by the receptor. Also, charge-charge hydrogen bonds between a ligand and a receptor are scored by setting a default value for a charge-charge hydrogen bond and awarding a bonus above the default value when one or more specialized predetermined charge-charge hydrogen bond criteria is satisfied. Various charge-charge hydrogen bond criteria are used. Zwitterions, charge, salvation, geometry and electrostatic energy are accounted for.

Abstract translation: 一种计算机实现的方法，用于计算代表所提及的配体与指定受体的相互作用（VRI）的值。 通过一种方法来评估一个或多个配体原子和一个或多个受体原子之间的疏水相互作用，所述方法为受体的一个或多个配体原子的疏水封闭的存在赋予奖励。 此外，通过设定充电氢氢键的默认值，并且当满足一个或多个专门的预定充电氢键标准时，将奖金高于默认值来评分配体和受体之间的充电氢键。 使用各种充电氢键标准。 两性离子，电荷，溶剂化，几何形状和静电能量。

公开(公告)号：US20110320176A1

公开(公告)日：2011-12-29

申请号：US12971132

申请日：2010-12-17

Applicant: Emmanuel Haldoupis ,  Seda Keskin ,  Sankar Nair ,  David S. Shol

Inventor： Emmanuel Haldoupis ,  Seda Keskin ,  Sankar Nair ,  David S. Shol

IPC: G06F17/10

CPC classification number: G06F19/704 ,  C40B30/02

Abstract: This invention relates to a method for characterizing the pores of reticulated framework structures and using these characteristics to predict the actual performance characteristics of the reticulated framework structures as membranes for gas separation, and other purposes.

Abstract translation: 本发明涉及一种用于表征网状骨架结构的孔的方法，并使用这些特征来预测网状骨架结构作为气体分离膜和其它目的的实际性能特征。

公开(公告)号：US20110312919A1

公开(公告)日：2011-12-22

申请号：US13157472

申请日：2011-06-10

Applicant: Garland R. Marshall ,  Linda J. Pike ,  Robert Yang

Inventor： Garland R. Marshall ,  Linda J. Pike ,  Robert Yang

IPC: A61K31/498 ,  A61K31/655 ,  C12N5/09 ,  A61P35/00 ,  A61K31/517 ,  C12N9/99 ,  A61K31/381 ,  A61K31/52

CPC classification number: C07D241/38 ,  C07D241/46 ,  C07D401/06 ,  C07D409/06 ,  C07D473/24 ,  C07D487/04 ,  C40B30/02 ,  G06F19/16 ,  G06F19/706

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract translation: 该教导涉及鉴定酪氨酸受体激酶如EGFR的二聚化抑制剂的方法。 所述方法包括在数字计算机上提供包含RTK的细胞外二聚化结构域的复合物的分子模型，将化学数据库与分子模型对接，评估由数据库包含的化合物，以及鉴定一种或多种高得分化合物 。 所述方法还包括在体外测试化合物的RTK抑制活性，并测试化合物作为RTK抑制剂的特异性。 还公开了通过所述方法选择的化合物和使用该化合物的治疗方法。 公开了以剂量依赖性方式抑制EGF受体激酶活化的两种化合物（NSC11241和NSC56452）。