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    REGULATORS OF NFAT
    3.
    发明申请
    REGULATORS OF NFAT 有权
    NFAT调节器

    公开(公告)号：US20110269174A1

    公开(公告)日：2011-11-03

    申请号：US13161307

    申请日：2011-06-15

    申请人： Anjana RAO ,  Stefan Feske ,  Patrick Hogan ,  Yousang Gwack

    发明人： Anjana RAO ,  Stefan Feske ,  Patrick Hogan ,  Yousang Gwack

    IPC分类号： C12Q1/02 ,  C12N5/10

    CPC分类号： C07K14/4702 ,  A61K35/12 ,  C07H21/04 ,  C07K16/18 ,  C12N5/16 ,  C12N15/63 ,  C12N15/907 ,  C12N2510/00 ,  C12Q1/00 ,  G01N33/5041

    摘要： Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein. Methods of identifying an agent that modulates intracellular calcium, methods to screen for an agent that modulates NFAT regulator function, methods to diagnose unexplained immunodeficiency in a subject, and methods for identifying an agent for treating or preventing a disease or disorder associated with a NFAT regulator protein or calcium signaling are also disclosed.

    摘要翻译： 公开了鉴定调节NFAT调节蛋白的试剂的方法。 一种这样的方法包括使至少一种测试试剂与包含至少一种NFAT调节蛋白或其片段或衍生物的重组细胞接触，评估测试试剂对NFAT调节蛋白的活性，相互作用，表达或结合的影响，或 片段或衍生物，并鉴定对NFAT调节蛋白或其片段或衍生物的活性，相互作用，表达或结合具有影响的测试剂，其中所鉴定的测试剂的特征在于调节NFAT调节剂 蛋白。 识别调节细胞内钙的试剂的方法，筛选调节NFAT调节功能的试剂的方法，诊断受试者中不明原因的免疫缺陷的方法，以及用于鉴定用于治疗或预防与NFAT调节相关的疾病或病症的药剂的方法 蛋白质或钙信号传导也被公开。

    METHODS OF DELIVERY OF AGENTS TO LEUKOCYTES AND ENDOTHELIAL CELLS
    5.
    发明申请
    METHODS OF DELIVERY OF AGENTS TO LEUKOCYTES AND ENDOTHELIAL CELLS 审中-公开
    向白细胞介素和内皮细胞递送药物的方法

    公开(公告)号：US20110177155A1

    公开(公告)日：2011-07-21

    申请号：US12674504

    申请日：2008-08-20

    申请人： Dan Peer ,  Motomu Shimaoka

    发明人： Dan Peer ,  Motomu Shimaoka

    IPC分类号： A61K9/127 ,  C12N5/00 ,  C12N5/071

    CPC分类号： A61K31/337 ,  A61K31/7088 ,  A61K45/06 ,  A61K47/6913 ,  A61K47/6929 ,  B82Y5/00 ,  A61K2300/00

    摘要： The present invention generally relates to methods and compositions for the simultaneous delivery of at least one insoluble agent and at least one soluble agent to a cell. In particular the present invention relates to methods and compositions for the dual delivery of an insoluble agent and a soluble agent to a particular target cell, for example, a leukocyte or endothelial cell. In particular, methods and compositions for simultaneous delivery of a hydrophilic (i.e. soluble) agent and/or a hydrophobic (i.e. insoluble) agent to a leukocyte cell or endothelia cell are disclosed.

    摘要翻译： 本发明一般涉及用于将至少一种不溶性试剂和至少一种可溶性试剂同时递送至细胞的方法和组合物。 特别地，本发明涉及用于将不溶性试剂和可溶性试剂双重递送至特定靶细胞例如白细胞或内皮细胞的方法和组合物。 特别地，公开了将亲水（即可溶性）试剂和/或疏水性（即不溶性）试剂同时递送至白细胞或内皮细胞的方法和组合物。

    Vaccine Nanotechnology
    6.
    发明申请
    Vaccine Nanotechnology 审中-公开
    疫苗纳米技术

    公开(公告)号：US20100233251A1

    公开(公告)日：2010-09-16

    申请号：US12681814

    申请日：2008-10-12

    申请人： Ulrich H. Von Andrian ,  Omid C. Farokhzad ,  Robert S. Langer ,  Tobias Junt ,  Ashley Moseman ,  Liangfang Zhang ,  Pamela Basto ,  Matteo Iannacone ,  Frank Alexis

    发明人： Ulrich H. Von Andrian ,  Omid C. Farokhzad ,  Robert S. Langer ,  Tobias Junt ,  Ashley Moseman ,  Liangfang Zhang ,  Pamela Basto ,  Matteo Iannacone ,  Frank Alexis

    IPC分类号： A61K9/127 ,  A61K9/14 ,  A61K39/00

    摘要： The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

    摘要翻译： 本发明提供用于将纳米载体递送至免疫系统细胞的组合物和系统。 本发明提供能够刺激T细胞和/或B细胞中的免疫应答的疫苗纳米载体，在一些实施方案中，包含至少一种免疫调节剂，并且任选地包含至少一种靶向部分和任选的至少一种免疫刺激剂。 本发明提供包含本发明疫苗纳米载体的药物组合物。 本发明提供了设计，制造和使用本发明疫苗纳米载体及其药物组合物的方法。 本发明提供了预防和/或治疗疾病，病症和病症的方法，包括向有需要的受试者施用至少一种本发明的疫苗纳米载体。

    STABILIZED LOW AFFINITY CONFORMATION OF INTEGRINS FOR DRUG DISCOVERY
    8.
    发明申请
    STABILIZED LOW AFFINITY CONFORMATION OF INTEGRINS FOR DRUG DISCOVERY 有权
    稳定低浓度组合的药物发现

    公开(公告)号：US20100167418A1

    公开(公告)日：2010-07-01

    申请号：US12645958

    申请日：2009-12-23

    申请人： Timothy A. Springer ,  Bing Hao Luo

    发明人： Timothy A. Springer ,  Bing Hao Luo

    IPC分类号： G01N33/53 ,  C07K14/00

    CPC分类号： G01N33/5032 ,  C07K14/70546 ,  G01N33/566 ,  G01N33/6872 ,  G01N2333/70546 ,  G01N2333/70557 ,  G01N2500/04

    摘要： The methods and compositions described herein are based, in part, on the discovery that the introduction of a disulfide bond into an integrin polypeptide by the substitution of at least one cysteine residue in the polypeptide permits stabilization of the integrin in a “closed/inactive” state. This stabilizing disulfide bond permits integrins to be screened for a candidate molecule that can bind to the closed state. In particular, this approach can be used to screen for agents that bind to the closed state of an integrin polypeptide, and are useful as therapeutic treatments to prevent integrin activation.

    摘要翻译： 本文描述的方法和组合物部分地基于以下发现：通过取代多肽中的至少一个半胱氨酸残基将二硫键引入整联蛋白多肽，可使整联蛋白稳定在“闭合/不活动” 州。 这种稳定的二硫键允许整合素筛选可以结合到封闭状态的候选分子。 特别地，该方法可用于筛选结合整联蛋白多肽的闭合状态的试剂，并且可用作防止整联蛋白活化的治疗性处理。

    TARGETED DELIVERY TO LEUKOCYTES USING NON-PROTEIN CARRIERS
    9.
    发明申请
    TARGETED DELIVERY TO LEUKOCYTES USING NON-PROTEIN CARRIERS 审中-公开
    使用非蛋白载体的目标交付给白蛋白

    公开(公告)号：US20100008937A1

    公开(公告)日：2010-01-14

    申请号：US12298367

    申请日：2007-04-25

    申请人： Dan Peer ,  Motomu Shimaoka

    发明人： Dan Peer ,  Motomu Shimaoka

    IPC分类号： A61K47/48 ,  C07H21/02 ,  C07K2/00 ,  A61K9/127 ,  A61K38/02 ,  A61K39/395 ,  C12N5/00 ,  A61K35/00

    CPC分类号： C12N15/87 ,  A61K2039/55555 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2320/32

    摘要： Disclosed are delivery agents for selective delivery to leukocytes. The leukocyte-selective delivery agents comprise a targeting moiety that selectively binds LFA-I, a non-protein carrier moiety covalently linked to the targeting moiety and a therapeutic agent associated with the carrier moiety. The non-protein carrier moiety comprises a liposome, a micelle, or a polymeric nanoparticle comprised of PLA or PLGA. The delivery agent may be further selective for activated leukocytes by using a targeting moiety that selectively binds LFA-I in its activated conformation. The targeting moiety may comprise an antibody or functional fragment thereof such as an scFV. Appropriate therapeutic agents include a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. Additional examples of therapeutic agents are a small RNA, an antagomir, an LNA, or an antisense oligonucleotide. One such therapeutic agent is an RNA interference molecule such as siRNA, dsRNA, stRNA, shRNA, miRNA. Specific delivery agents are provided. Methods for in vivo, in vitro and ex vivo leukocyte-selective delivery using the delivery agents are also disclosed.

    摘要翻译： 公开了用于选择性递送至白细胞的递送剂。 白细胞选择性递送剂包含选择性结合LFA-1的靶向部分，LFA-1是与靶向部分共价连接的非蛋白质载体部分和与载体部分相关联的治疗剂。 非蛋白质载体部分包含脂质体，胶束或由PLA或PLGA组成的聚合物纳米颗粒。 通过使用选择性结合其活化构象中的LFA-1的靶向部分，递送剂可以进一步选择性地活化白细胞。 靶向部分可以包含抗体或其功能片段，例如scFV。 合适的治疗剂包括核酸，小分子，多肽，抗体或其功能片段。 治疗剂的其它实例是小RNA，antagomir，LNA或反义寡核苷酸。 一种这样的治疗剂是RNA干扰分子，例如siRNA，dsRNA，stRNA，shRNA，miRNA。 提供特定的递送剂。 还公开了使用递送剂的体内，体外和离体白细胞选择性递送的方法。

    Method to Treat Flavivirus Infection with siRNA
    10.
    发明申请
    Method to Treat Flavivirus Infection with siRNA 审中-公开
    用siRNA治疗黄病毒感染的方法

    公开(公告)号：US20090047338A1

    公开(公告)日：2009-02-19

    申请号：US12089015

    申请日：2006-10-05

    申请人： Manjunath N. Swamy ,  Premlata Shankar ,  Priti Kumar ,  Sang-Kyung Lee

    发明人： Manjunath N. Swamy ,  Premlata Shankar ,  Priti Kumar ,  Sang-Kyung Lee

    IPC分类号： A61K9/127 ,  A61K31/7105 ,  A61P31/00

    CPC分类号： C12N15/1131 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2740/15043 ,  C12N2770/24111

    摘要： The present invention is directed to methods of treating flavivirus mediated diseases using siRNAs. The invention is based upon our findings in a mouse model that siRNAs directed against sequences conserved among multiple flaviviruses prevents and treats flavivirus infections. Accordingly, the present invention provides an isolated siRNA comprising a sense RNA and an antisense RNA strand or a single strand. The sense and the antisense RNA strands, or the single RNA strand, form an RNA duplex, and wherein the RNA strand comprises a nucleotide sequence identical to a target sequence of about 15 to about 30 contiguous nucleotides in flavivirus mRNA or mutant or variant thereof.

    摘要翻译： 本发明涉及使用siRNA治疗黄病毒介导的疾病的方法。 本发明基于我们在小鼠模型中的发现，其针对多个黄病毒中保守的序列的siRNA阻止和治疗黄病毒感染。 因此，本发明提供了包含有义RNA和反义RNA链或单链的分离的siRNA。 有义和反义RNA链或单RNA链形成RNA双链体，其中RNA链包含与黄病毒mRNA或其突变体或变体中约15至约30个连续核苷酸的靶序列相同的核苷酸序列。