公开(公告)号：US06833237B1

公开(公告)日：2004-12-21

申请号：US10021338

申请日：2001-12-12

申请人： Elena Feinstein ,  Igor Mett ,  Sylvia G. Kachalsky ,  Svetlana Gorodin

发明人： Elena Feinstein ,  Igor Mett ,  Sylvia G. Kachalsky ,  Svetlana Gorodin

IPC分类号： C12Q100

CPC分类号： C07K14/705 ,  G01N2500/00

摘要： Genes and the proteins encoded thereby that are involved in stroke response and/or are regulated by FK506 are disclosed. These genes were discovered using in vivo or in vitro stroke models by determining which genes were differentially upregulated or downregulated upon treatment of the model with FK506. They were also found by a functional assay of genes specifically selected for conferring to cells resistance to hypoxia, dopamine or glutamate treatment. The disclosure includes such genes and proteins as well as analogs, salts and functional derivatives of such proteins, and DNA encoding such analogs, and methods of use. Methods for treating the effects of stroke, hypoxia and/or ischemia by regulating such genes or proteins are disclosed. Methods for screening for compounds capable of regulating the genes and proteins of the invention are also disclosed.

摘要翻译： 公开了基因和由其编码的涉及中风反应和/或由FK506调节的蛋白质。 使用体内或体外卒中模型，通过确定哪些基因在用FK506处理模型时差异上调或下调，发现这些基因。 它们也通过功能性测定法发现，其特异性选择用于赋予细胞对缺氧，多巴胺或谷氨酸处理的抗性。 本公开包括此类基因和蛋白质以及此类蛋白质的类似物，盐和功能性衍生物，以及编码此类类似物的DNA及其使用方法。 公开了通过调节这些基因或蛋白质来治疗中风，缺氧和/或缺血的作用的方法。 还公开了能够调节本发明的基因和蛋白质的化合物的筛选方法。

公开(公告)号：US06822081B2

公开(公告)日：2004-11-23

申请号：US09760379

申请日：2001-01-16

申请人： Holger Rauth ,  Richard Reinhardt ,  Eckhard Nordhoff ,  Markus Kalkum

发明人： Holger Rauth ,  Richard Reinhardt ,  Eckhard Nordhoff ,  Markus Kalkum

IPC分类号： C12Q100

CPC分类号： C07K1/20 ,  C07K1/30

摘要： The invention relates to a process for the isolation and/or purification of a proteinaceous material, wherein a solid phase comprising a mixture of hydrophobic and hydrophilic groups is used.

摘要翻译： 本发明涉及一种用于分离和/或纯化蛋白质物质的方法，其中使用包含疏水基团和亲水基团的混合物的固相。

公开(公告)号：US06818391B2

公开(公告)日：2004-11-16

申请号：US09915181

申请日：2001-07-24

申请人： Robert H. Edwards ,  Elizabeth E. Bellocchio ,  Robert T. Fremeau, Jr. ,  Richard J. Reimer

发明人： Robert H. Edwards ,  Elizabeth E. Bellocchio ,  Robert T. Fremeau, Jr. ,  Richard J. Reimer

IPC分类号： C12Q100

CPC分类号： C07K14/47 ,  A01K2217/075 ,  G01N2333/70571

摘要： This invention pertains to the identification of a novel class of glutamate transporters. In particular, this invention pertains to the discovery that proteins originally considered to perform an entirely different function (BNPI, DNPI, etc.), in fact, transport glutamate into synaptic vesicles. Designated VGLUT glutamate transporters, the transporters provide good targets with which to screen for modulators of glutamate uptake into synaptic vesicles.

摘要翻译： 本发明涉及一类新型谷氨酸转运蛋白的鉴定。 特别地，本发明涉及以下发现：实际上，原本被认为是完全不同的功能（BNPI，DNPI等）的蛋白质将谷氨酸转运到突触小泡中。 指定的VGLUT谷氨酸转运蛋白，转运蛋白提供了良好的目标，筛选谷氨酸摄取调节剂到突触小泡。

公开(公告)号：US06815172B1

公开(公告)日：2004-11-09

申请号：US10009660

申请日：2001-12-07

申请人： Joseph E. Martinez ,  George M. Carlone ,  Michael H. Hickey ,  Sandra Steiner

发明人： Joseph E. Martinez ,  George M. Carlone ,  Michael H. Hickey ,  Sandra Steiner

IPC分类号： C12Q100

CPC分类号： G01N33/56911 ,  G01N2333/22 ,  G01N2333/315 ,  Y10S436/80

摘要： Methods and compositions comprising immunoassays for the detection of functional antibodies and the analysis of vaccine efficacy are described. In particular, the present invention provides opsonophagocytic assays. The assays are useful for the rapid and simultaneous detection of multiple different functional antibodies. In preferred embodiments, the assays include fluorescent labels of multiple colors and/or intensities.

摘要翻译： 描述了包含用于检测功能性抗体的免疫测定和疫苗功效分析的方法和组合物。 特别地，本发明提供调理吞噬试验。 该测定法可用于快速和同时检测多种不同功能的抗体。 在优选实施方案中，测定包括多种颜色和/或强度的荧光标记。

公开(公告)号：US06808875B2

公开(公告)日：2004-10-26

申请号：US10155536

申请日：2002-05-24

申请人： Marc K. Hellerstein

发明人： Marc K. Hellerstein

IPC分类号： C12Q100

CPC分类号： A61K31/665 ,  C12Q1/48 ,  C12Q1/68 ,  C12Q1/6809 ,  C12Q1/70 ,  G01N33/5005 ,  G01N33/5088 ,  G01N33/60

摘要： The present invention relates to methods for measuring the proliferation and destruction rates of cells by measuring deoxyribonucleic acid (DNA) synthesis and/or destruction. In particular, the methods utilize non-radioactive stable isotope labels to endogenously label DNA synthesized through the de novo nucleotide synthesis pathway in a cell. The amount of label incorporated in the DNA is measured as an indication of cellular proliferation. The decay of labeled DNA over time is measured as an indication of cellular destruction. Such methods do not involve radioactivity or potentially toxic metabolites, and are suitable for use both in vitro and in vivo. Therefore, the invention is useful for measuring cellular proliferation or cellular destruction rates in humans for the diagnosis, prevention, or management of a variety of disease conditions in which cellular proliferation or cellular destruction is involved. The invention also provides methods for measuring proliferation or destruction of T cells in a subject infected with human immunodeficiency virus (HIV) and methods of screening an agent for a capacity to induce or inhibit cellular proliferation or destruction. In addition, the invention provides methods for measuring cellular proliferation in a proliferating population which utilize both radioactive isotope labels and stable isotopes to endogenously label DNA through the de novo nucleotide synthesis pathway.

摘要翻译： 本发明涉及通过测量脱氧核糖核酸（DNA）合成和/或破坏来测量细胞的增殖和破坏率的方法。 特别地，该方法利用非放射性稳定同位素标记来内生标记通过细胞中从头核苷酸合成途径合成的DNA。 测量结合在DNA中的标记量作为细胞增殖的指示。 随着时间的推移，标记的DNA的衰变被测量为细胞破坏的指示。 这些方法不涉及放射性或潜在的毒性代谢物，并且适用于体外和体内。 因此，本发明可用于测量人类的细胞增殖或细胞破坏率，用于诊断，预防或管理涉及细胞增殖或细胞破坏的各种疾病状况。 本发明还提供了测量感染人类免疫缺陷病毒（HIV）的受试者的T细胞增殖或破坏的方法以及筛选诱导或抑制细胞增殖或破坏能力的试剂的方法。 此外，本发明提供了用于测量增殖群体中的细胞增殖的方法，其利用放射性同位素标记和稳定同位素来通过从头核苷酸合成途径内源性标记DNA。

公开(公告)号：US06797460B2

公开(公告)日：2004-09-28

申请号：US09930600

申请日：2001-08-15

申请人： Daniel S. Sem ,  Maurizio Pellecchia ,  Anna Tempczyk-Russell

发明人： Daniel S. Sem ,  Maurizio Pellecchia ,  Anna Tempczyk-Russell

IPC分类号： C12Q100

CPC分类号： C12Q1/00 ,  C12Q1/32 ,  C12Q1/485 ,  G01N33/53 ,  G01N33/542 ,  G01N33/6803 ,  G01N2500/00 ,  G01N2500/20 ,  Y10T436/24

摘要： Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

摘要翻译： 用于快速鉴定可以在共同配体位点和特异性配体位点处结合酶的候选药物的方法，导致高亲和力结合。 双重配体药物候选物从聚焦的组合文库筛选，其中优化核心结构上的特异性变异点。 通过与共同配体位点结合的配体的哪个原子被鉴定为接近特异性配体位点来鉴定最佳的变化点。 结果，接近特异性配体位点的原子然后可以用作变异点，以产生可以结合共同配体位点和特异性配体位点的高亲和力药物候选物的聚焦组合文库。 然后，文库中的不同候选物可以对共享相似共同配体位点的许多相关酶具有高亲和力。

公开(公告)号：US06790608B2

公开(公告)日：2004-09-14

申请号：US09780576

申请日：2001-02-09

申请人： Olivier Civelli ,  Hans-Peter Nothacker ,  Zhiwei Wang ,  Rainer Reinscheid

发明人： Olivier Civelli ,  Hans-Peter Nothacker ,  Zhiwei Wang ,  Rainer Reinscheid

IPC分类号： C12Q100

CPC分类号： G01N33/66

摘要： The present invention provides an isolated nucleic acid molecule containing a nucleotide sequence which encodes an ADP-glucose receptor, and isolated polynucleotides therefrom. Also provided is an isolated ADP-glucose receptor polypeptide, an isolated immunogenic peptide therefrom, and antibodies specific therefor. The invention also provides a method of identifying an ADP-glucose receptor agonist or antagonist, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detection of a G-protein coupled signal in response to ADP-glucose, and identifying a candidate compound that alters production of the signal. Further provided is a method of identifying an ADP-glucose receptor ligand, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detecting selective binding of ADP-glucose to ADP-glucose receptor, and identifying a candidate compound that selectively binds the ADP-glucose receptor. Also provided are methods of diagnosing or determining susceptibility to ADP-glucose receptor associated conditions, by detecting in a sample from the individual expression of ADP glucose receptor nucleic acid molecules or polypeptides.

摘要翻译： 本发明提供了分离的核酸分子，其含有编码ADP-葡萄糖受体的核苷酸序列及其分离的多核苷酸。 还提供了分离的ADP-葡萄糖受体多肽，其中分离的免疫原性肽及其特异性抗体。 本发明还提供了通过在适于检测响应于ADP-葡萄糖的G蛋白偶联信号的条件下使ADP-葡萄糖受体与一种或多种候选化合物接触来鉴定ADP-葡萄糖受体激动剂或拮抗剂的方法，以及 识别改变信号产生的候选化合物。 进一步提供的是通过在适于检测ADP-葡萄糖与ADP-葡萄糖受体的选择性结合的条件下将ADP-葡萄糖受体与一种或多种候选化合物接触并鉴定候选化合物来鉴定ADP-葡萄糖受体配体的方法 选择性结合ADP-葡萄糖受体。 还提供了通过在来自ADP葡萄糖受体核酸分子或多肽的个体表达的样品中检测来诊断或确定对ADP-葡萄糖受体相关病症易感性的方法。

公开(公告)号：US06790606B1

公开(公告)日：2004-09-14

申请号：US09495448

申请日：2000-01-31

申请人： Lester F. Lau

发明人： Lester F. Lau

IPC分类号： C12Q100

CPC分类号： G01N33/5029 ,  A01K2217/05 ,  A61K38/00 ,  A61K48/00 ,  C07K14/475 ,  C12N2799/026 ,  G01N33/5008 ,  G01N33/5044 ,  G01N33/5055 ,  G01N33/5064 ,  G01N33/5073 ,  G01N33/68

摘要： Polynucleotides encoding mammalian ECM signaling molecules affecting the cell adhesion, migration, and proliferation activities characterizing such complex biological processes as angiogenesis, chondrogenesis, and oncogenesis, are provided. The polynucleotide compositions include DNAs and RNAs comprising part, or all, of an ECM signaling molecule coding sequence, or biological equivalents. Polypeptide compositions are also provided. The polypeptide compositions comprise mammalian ECM signaling molecules, peptide fragments, inhibitory peptides capable of interacting with receptors for ECM signaling molecules, and antibody products recognizing Cyr61. Also provided are methods for producing mammalian ECM signaling molecules. Further provided are methods for using mammalian ECM signaling molecules to screen for, and/or modulate, disorders associated with angiogenesis, chondrogenesis, and oncogenesis; ex vivo methods for using mammalian ECM signaling molecules to prepare blood products are also provided.

摘要翻译： 提供了编码哺乳动物ECM信号分子的多核苷酸，其影响表征诸如血管生成，软骨形成和肿瘤形成等复杂生物学过程的细胞粘附，迁移和增殖活性。 多核苷酸组合物包括包含ECM信号分子编码序列或生物等同物的部分或全部的DNA和RNA。 还提供了多肽组合物。 多肽组合物包含哺乳动物ECM信号分子，肽片段，能够与ECM信号分子的受体相互作用的抑制肽，以及识别Cyr61的抗体产物。 还提供了用于产生哺乳动物ECM信号分子的方法。 还提供了使用哺乳动物ECM信号分子筛选和/或调节与血管发生，软骨形成和肿瘤发生相关的病症的方法; 还提供了使用哺乳动物ECM信号分子来制备血液制品的离体方法。

公开(公告)号：US06790604B1

公开(公告)日：2004-09-14

申请号：US09110376

申请日：1998-05-12

申请人： Stefan A. Cohen ,  Untae Kim ,  David P. Montesanti

发明人： Stefan A. Cohen ,  Untae Kim ,  David P. Montesanti

IPC分类号： C12Q100

CPC分类号： G01N33/57415 ,  C12Q1/6886 ,  C12Q2600/118 ,  G01N33/57419

摘要： A method of predicting the lymphotropic metastatic potential of a solid non-lymphoid tumor. The percentage of cells of each of a plurality of representative samples of the tumor which express lymphoid gene products is determined. The metastatic potential is predicted to be low when no tumor cells in all of the samples are detected to express lymphoid gene products. The metastatic potential is predicted to be high when a high percentage of tumor cells in at least one of the samples are detected to express lymphoid gene products. A solid non-lymphoid tumor is treated by systemically administering a substance comprising a therapeutically effective amount of a molecule linked to a toxin, radionuclide, or chemotherapeutic agent and having binding specificity for a tumor specific lymphoid gene product idiotype. The lymphotropic metastatic potential of a primary solid non-lymphoid tumor is predicted by sub-cutaneously injecting cells from the tumor into at least one anti-AsGMI-treated nude mouse and examining the mouse for tumors at sites other than the site of injection.

摘要翻译： 一种预测固体非淋巴样肿瘤淋巴细胞转移潜能的方法。 确定表达淋巴样基因产物的肿瘤的多个代表性样品中的每一个的细胞百分数。 当没有检测到所有样品中的肿瘤细胞表达淋巴样基因产物时，转移潜力被预测为低。 当检测至少一个样品中的高百分比的肿瘤细胞以表达淋巴样基因产物时，预测转移潜力很高。 通过全身施用含有治疗有效量的与毒素，放射性核素或化学治疗剂连接的分子并对肿瘤特异性淋巴样基因产物特异性具有结合特异性的物质来治疗固体非淋巴样肿瘤。 原发性固体非淋巴样肿瘤的淋巴细胞转移潜能可以通过将细胞从皮下皮下注入到至少一种抗AsGMI处理的裸小鼠中并将小鼠用于注射部位以外的位置来检测。

公开(公告)号：US06787302B2

公开(公告)日：2004-09-07

申请号：US10087200

申请日：2002-03-01

申请人： James E. Fleming ,  Jason Buck Somes

发明人： James E. Fleming ,  Jason Buck Somes

IPC分类号： C12Q100

CPC分类号： G01N33/5005 ,  C12Q1/04 ,  C12Q1/06 ,  G01N33/5094 ,  Y10S435/975

摘要： This invention describes methods and kits for detecting and quantifying viable cells in a sample using fluorescent dyes that can be internalized predominantly by viable cells and have fluorescent properties measurably altered when bound to target components. These methods and kits provide a rapid and cost-effective means of detecting potential biological threats in the field.

摘要翻译： 本发明描述了使用荧光染料检测和定量样品中活细胞的方法和试剂盒，其可以主要由活细胞内化，并且当与靶组分结合时具有可测量改变的荧光性质。 这些方法和试剂盒提供了一种快速和经济有效的方法来检测该领域潜在的生物威胁。