Globo H and related anti-cancer vaccines with novel glycolipid adjuvants
    402.
    发明授权
    Globo H and related anti-cancer vaccines with novel glycolipid adjuvants 有权
    Globo H和具有新型糖脂佐剂的相关抗癌疫苗

    公开(公告)号:US08268969B2

    公开(公告)日:2012-09-18

    申请号:US12537129

    申请日:2009-08-06

    Abstract: Immunogenic compositions, cancer vaccines and methods for treating cancer are provided. Compositions comprising: (a) a glycan such as Globo H or an immunogenic fragment thereof, wherein the glycan is conjugated with a carrier protein by a linker such as para-nitrophenyl; and (b) an adjuvant comprising glycolipid capable of binding CD1d on a dendritic cell, such as an α-galactosyl-ceramide derivative, wherein the immunogenic composition induces an immune response that induces a higher relative level of IgG isotype antibodies as compared to IgM isotype antibodies, are provided. Immunogenic compositions comprising the carrier protein diphtheria toxin cross-reacting material 197 (DT-CRM197) and the adjuvant C34 are provided. Antibodies generated by immunogenic compositions disclosed herein further neutralize at least one of the antigens Globo H, stage-specific embryonic antigen-3 (SSEA-3) and stage-specific embryonic antigen-4 (SSEA-4). Therapeutics against breast cancer stem cells comprising immunogenic compositions comprising Globo H, SSEA-3 or SSEA-4 conjugated with DT-CRM197.

    Abstract translation: 提供免疫原性组合物,癌症疫苗和治疗癌症的方法。 组合物,其包含:(a)聚糖如Globo H或其免疫原性片段,其中所述聚糖通过诸如对硝基苯基之类的接头与载体蛋白缀合; 和(b)包含能够结合树突状细胞上的CD1d的糖脂如α-半乳糖基 - 神经酰胺衍生物的佐剂,其中所述免疫原性组合物诱导与IgM同种型相比诱导更高相对水平的IgG同种型抗体的免疫应答 抗体。 提供了包含载体蛋白质白喉毒素交叉反应材料197(DT-CRM197)和佐剂C34的免疫原性组合物。 由本文公开的免疫原性组合物产生的抗体进一步中和至少一种抗原Globo H,阶段特异性胚胎抗原-3(SSEA-3)和阶段特异性胚胎抗原-4(SSEA-4)。 包括含有与DT-CRM197缀合的Globo H,SSEA-3或SSEA-4的免疫原性组合物的乳腺癌干细胞的治疗剂。

    Mass spectrometer and methods for detecting large biomolecules
    404.
    发明授权
    Mass spectrometer and methods for detecting large biomolecules 有权
    质谱仪和检测大生物分子的方法

    公开(公告)号:US08258464B2

    公开(公告)日:2012-09-04

    申请号:US12785945

    申请日:2010-05-24

    CPC classification number: H01J49/025 H01J49/0027

    Abstract: A mass spectrometer and methods for obtaining the mass spectrum of a single macromolecular or biomolecular ion in a mass spectrometer. The methods include creating single macromolecular or biomolecular primary ions in an ion trap by ionization of a macromolecule or biomolecule; ejecting half of the primary ions for detection with a first charge detector; ejecting half of the primary ions to impact upon a conversion dynode, thereby creating secondary ions for detection with charge amplification detector such as a channeltron or an electromultiplier or an MCP.

    Abstract translation: 质谱仪和在质谱仪中获得单个大分子或生物分子离子的质谱的方法。 该方法包括通过大分子或生物分子的离子化在离子阱中产生单个大分子或生物分子一级离子; 用第一电荷检测器喷射一半的初级离子用于检测; 喷射一半的初级离子以冲击转换倍增极,从而产生二次离子,以便用电荷放大检测器(例如通道电极或电倍增管或MCP)进行检测。

    COMPOSTIONS AND METHODS FOR IDENTIFYING RESPONSE TARGETS AND TREATING FLAVIVIRUS INFECTION RESPONSES
    405.
    发明申请
    COMPOSTIONS AND METHODS FOR IDENTIFYING RESPONSE TARGETS AND TREATING FLAVIVIRUS INFECTION RESPONSES 有权
    识别反应目标和治疗FLAVIVIRUS感染反应的组合物和方法

    公开(公告)号:US20120213770A1

    公开(公告)日:2012-08-23

    申请号:US13106046

    申请日:2011-05-12

    Abstract: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

    Abstract translation: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白,确定病原体(例如黄病毒)通过聚糖结合结合的受体。 一旦确定了受体,就可以确定与特定受体结合的作用,其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此,在登革热病毒和日本脑炎病毒的情况下,当病原体与DLVR1 / CLEC5A受体结合时,TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌,而不影响负责病毒清除的细胞因子分泌,从而将感染小鼠的存活率从零增加到约50%。

    Anti-C epsilon mX antibodies capable of binding to human mIgE on B Lymphocytes
    406.
    发明申请
    Anti-C epsilon mX antibodies capable of binding to human mIgE on B Lymphocytes 有权
    能够结合B淋巴细胞上人mIgE的抗CεmX抗体

    公开(公告)号:US20120207746A1

    公开(公告)日:2012-08-16

    申请号:US13203483

    申请日:2010-02-25

    Abstract: The invention pertains to the generation and utility of antibodies that can bind effectively to CεmX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The CεmX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP peptide at the C-terminal of CεmX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL and HSGQQQGLPRAAGGSVPHPR, of CεmX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

    Abstract translation: 本发明涉及能够在人B淋巴细胞表面表达的膜结合IgE(mIgE)上有效结合C& mX结构域的抗体的产生和应用。 已经提出位于人膜结合的ε链上的CH4结构域和C末端膜锚定肽之间的52个氨基酸残基的Cys区域作为用于免疫靶向表达mIgE的B细胞的抗原位点。 以前报道的已报道的单克隆抗体,包括结合C C端的C端的RADWPGPP肽的α20已被发现与人B细胞上的mIgE结合不良。 我们已经发现,只有对特定片段特异性的单克隆抗体(如GLAGGSAQSQRAPDRVL和HSGQQGLPRAAGGSVPHPR)可以与人类B细胞有效结合,因此具有靶向这些B细胞用于治疗IgE介导的疾病的效用。

    PHOSPHORYLATION AND MUTATIONS OF ANAPLASTIC LYMPHOMA KINASE AS A DIAGNOSTIC AND THERAPEUTIC TARGET IN LUNG CANCER
    407.
    发明申请
    PHOSPHORYLATION AND MUTATIONS OF ANAPLASTIC LYMPHOMA KINASE AS A DIAGNOSTIC AND THERAPEUTIC TARGET IN LUNG CANCER 审中-公开
    作为诊断和治疗目标的肺癌患者的磷酸化和突变

    公开(公告)号:US20120129869A1

    公开(公告)日:2012-05-24

    申请号:US13294588

    申请日:2011-11-11

    Abstract: The invention related to the use of high-density loss of heterozygosity (LOH) mapping in lung adenocarcinoma to identify intragenic LOH and driver mutations in different domains of ALK resulted in enhanced tumor growth in xenografted mouse. Mutant (H694R and E1384K) ALKs showed activation of Y1604 ALK and downstream AKT, STAT3 and ERK signaling pathways. Increases of oncogenic signalings resulted in enhanced cell proliferation, colony-formation, cell-migration and tumor-growth in xenografted mouse. Western blot and immunohistochemistry analysis using antibody against phospho-Y1604 ALK on 11 lung cancer cell-lines and 263 cancer specimens indicated ALK activation in all lung cancers regardless of tumor stages. Treating mutant-bearing mice with ALK inhibitor WHI-P 154 resulted in tumor shrinkage, metastasis suppression, and improved survival. Hyperphosphorylation of Y1604 ALK occurred early and continuously throughout tumor progression and could be used as a biomarker to detect lung cancer. Oncogenic ALK point mutations could be treatment targets for lung cancer.

    Abstract translation: 本发明涉及在肺腺癌中使用高密度损失的杂合性(LOH)作图来识别ALK的不同结构域的内源性LOH和驱动突变导致异种移植小鼠中肿瘤生长增强。 突变体(H694R和E1384K)ALKs显示Y1604 ALK和下游AKT,STAT3和ERK信号通路的激活。 致癌信号的增加导致异种移植小鼠中增强的细胞增殖,集落形成,细胞迁移和肿瘤生长。 在11个肺癌细胞系和263个癌症标本上使用抗磷酸化Y1604 ALK的抗体进行蛋白质印迹和免疫组织化学分析,表明所有肺癌均不影响肿瘤阶段的ALK活化。 用ALK抑制剂WHI-P 154处理带突变体的小鼠导致肿瘤缩小,转移抑制和改善的存活。 Y1604 ALK的过度磷酸化在肿瘤进展期间早期和连续发生,可用作肺癌的生物标志物。 致癌性ALK点突变可能是肺癌的治疗靶点。

    Glycopeptide-Functionalized Nanoparticles Arrays for Capturing and Detecting Biomolecules
    408.
    发明申请
    Glycopeptide-Functionalized Nanoparticles Arrays for Capturing and Detecting Biomolecules 有权
    用于捕获和检测生物分子的糖肽官能化纳米颗粒阵列

    公开(公告)号:US20120129707A1

    公开(公告)日:2012-05-24

    申请号:US12949052

    申请日:2010-11-18

    Abstract: A surface-enhanced Raman spectroscopic (SERS) system for detecting a biomolecule. The system includes a substrate, an array of nanoparticles disposed on the substrate, each being partially embedded in the substrate and having a non-embedded surface, and a linking agent disposed on the non-embedded surface of each of the nanoparticles. The array of nanoparticles has a uniform interparticle gap of 1-50 nm and the linking agent is capable of binding to the biomolecule.

    Abstract translation: 用于检测生物分子的表面增强拉曼光谱(SERS)系统。 该系统包括衬底,布置在衬底上的纳米颗粒阵列,每个纳米颗粒部分地嵌入衬底中并具有非嵌入表面,以及设置在每个纳米颗粒的非嵌入表面上的连接剂。 纳米颗粒阵列具有1-50nm的均匀颗粒间隙,并且连接剂能够结合生物分子。

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