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    Methods for diagnosis of Clostridium difficile and methods and vectors for recombinant toxin expression
    1.
    发明申请
    Methods for diagnosis of Clostridium difficile and methods and vectors for recombinant toxin expression 失效
    艰难梭菌诊断方法及重组毒素表达的方法和载体

    公开(公告)号：US20110065123A1

    公开(公告)日：2011-03-17

    申请号：US12992330

    申请日：2009-05-15

    Applicant: Hanping Feng ,  Saul Tzipori ,  Guilin Yang

    Inventor： Hanping Feng ,  Saul Tzipori ,  Guilin Yang

    IPC: G01N33/53 ,  C12Q1/04 ,  C12P1/04 ,  C12N15/63 ,  C12N5/07

    CPC classification number: G01N33/56911 ,  G01N33/5014 ,  G01N33/5055 ,  G01N2333/33

    Abstract: Cell-based methods for rapid real time assay of a presence of Clostridium difficile toxin and/or cells are provided, using an assay having a toxin-enhancing antibody and a sensitive cell line carrying FcyR receptors, and kits for this assay. An ultrasensitive cell based immunocytotoxicity assay for detecting less then 1 pg/ml of C. difficile toxins in clinical samples. A TcdA-specific monoclonal antibody, AIH3, was found to significantly enhance the cytotoxicity of TcdA to macrophages and monocytes. The AIH3-dependent enhancement of glucosyltransferase activity, cytoskeleton disruption, and TNF-a production induced by TcdA was demonstrated also in RAW 264.7 cells. Methods for high level recombinant expression of C. difficile toxins in Bacillus cells, and vectors for expression, strains of Bacillus carrying the vectors are provided.

    Abstract translation: 使用具有毒素增强抗体和携带FcyR受体的敏感细胞系的测定法和用于该测定的试剂盒，提供了用于快速实时测定艰难梭菌毒素和/或细胞存在的基于细胞的方法。 用于在临床样品中检测少于1pg / ml的艰难梭菌毒素的基于超敏感的基于细胞的免疫细胞毒性测定。 发现TcdA特异性单克隆抗体AIH3显着增强TcdA对巨噬细胞和单核细胞的细胞毒性。 在RAW 264.7细胞中也证明了由TcdA诱导的葡萄糖基转移酶活性，细胞骨架破坏和TNF-α产生的AIH3依赖性增强。 提供了在芽孢杆菌细胞中高水平重组表达艰难梭菌毒素的方法和用于表达载体的载体载体的芽孢杆菌菌株。

    METHODS AND MICROARRAYS FOR DETECTING ENTERIC VIRUSES
    2.
    发明申请
    METHODS AND MICROARRAYS FOR DETECTING ENTERIC VIRUSES 审中-公开
    检测肠道病毒的方法和微观

    公开(公告)号：US20090136916A1

    公开(公告)日：2009-05-28

    申请号：US12191132

    申请日：2008-08-13

    Applicant: David W. Brown ,  John E. Herrmann ,  Saul Tzipori ,  Kerry B. Gunning

    Inventor： David W. Brown ,  John E. Herrmann ,  Saul Tzipori ,  Kerry B. Gunning

    IPC: C12Q1/70 ,  C40B60/10 ,  C07H21/02 ,  C07H21/04 ,  C40B50/14

    CPC classification number: C12Q1/701 ,  B01J2219/00387 ,  B01J2219/00529 ,  B01J2219/00608 ,  B01J2219/00612 ,  B01J2219/00637 ,  B01J2219/00659 ,  C12Q1/6881 ,  C12Q2531/107

    Abstract: The present invention relates to methods, microarrays and kits for detecting one or more human astrovirus serotypes in a sample (e.g., a fecal sample) from an individual. The method includes amplifying nucleic acid molecules of the sample with one or more primers, to thereby obtain an amplified nucleic acid product; contacting the amplified nucleic acid product with one or more serotype specific probes having a nucleic acid sequence that is specific for only one astrovirus serotype in the group of astroviruses being assessed, wherein the nucleic acid sequence includes between about 9 and 25 nucleic acid bases (e.g., SEQ ID NO: 5-24); and detecting the hybridization complex. The presence of hybridization complexes with a serotype specific probe indicates the presence of one or more specific astrovirus serotypes, and the absence of hybridization complexes with a serotype specific probe indicates the absence of the specific astrovirus serotype. Identification of the astrovirus serotypes allows for one to diagnose an individual infected with the serotype. The present invention further includes microarrays having any one of the astrovirus specific probe, or kits having microarrays and reagents for carrying out the assay.

    Abstract translation: 本发明涉及用于检测来自个体的样品（例如，粪便样品）中的一种或多种人星状病毒血清型的方法，微阵列和试剂盒。 该方法包括用一个或多个引物扩增样品的核酸分子，从而获得扩增的核酸产物; 使所述扩增的核酸产物与一种或多种血清型特异性探针接触，所述探针具有在所评估的星状病毒组中仅具有一种星状病毒血清型的核酸序列，其中所述核酸序列包含约9至25个核酸碱基（例如 ，SEQ ID NO：5-24）; 并检测杂交复合物。 与血清型特异性探针的杂交复合物的存在表明存在一种或多种特异性星状病毒血清型，并且与血清型特异性探针不存在杂交复合物表明不存在特异性星状病毒血清型。 识别星状病毒血清型允许一个诊断感染血清型的个体。 本发明还包括具有任何一种星状病毒特异性探针或具有微阵列的试剂盒和用于进行测定的试剂的微阵列。

    HUMAN NEUTRALIZING ANTIBODIES AGANST HEMOLYTIC UREMIC SYNDROME
    4.
    发明申请
    HUMAN NEUTRALIZING ANTIBODIES AGANST HEMOLYTIC UREMIC SYNDROME 有权
    人类中和抗体药物HEMOLYTIC UREMIC SYNDROME

    公开(公告)号：US20090068176A1

    公开(公告)日：2009-03-12

    申请号：US11933166

    申请日：2007-10-31

    Applicant: Saul Tzipori ,  Ramaswamy Balakrishnan ,  Arthur Donohue-Rolfe

    Inventor： Saul Tzipori ,  Ramaswamy Balakrishnan ,  Arthur Donohue-Rolfe

    IPC: A61K39/395 ,  A61P13/00

    CPC classification number: C07K16/1232 ,  A61K38/00

    Abstract: Human and humanized monoclonal antibodies which binds specifically to subunit A of Shiga like toxin II have been developed which are effective to prevent or ameliorate one or more symptoms of HUS in a human. Effective dosages for treatment or prevention range from approximately 0.1 to 5.0 mg of antibody/kg of patient weight. The examples demonstrate the preferred dosage ranges based on the pig model, and what is being tested in phase I clinical trials. Antibodies are preferably transfused over a period of two hours, although this will depend on the patient and the disease state at the time of treatment. Preferred dosages for treatment of humans are between 0.1 mg/kg-5.0 mg/kg of 5C120, or an equivalent dosage of another antibody to subunit A of STX2. In the most preferred embodiments, dosages of 0.1 mg/kg, 0.5 mg/kg, or 5.0 mg/kg of 5C12 (low dose, anticipated therapeutic dose based on animal data and high dose) are administered.

    Abstract translation: 已经开发了特异性结合志贺样毒素II的亚单位A的人和人源化单克隆抗体，其有效预防或改善人类中一种或多种HUS症状。 治疗或预防的有效剂量范围为约0.1至5.0mg抗体/ kg患者体重。 这些实施例证明了基于猪模型的优选剂量范围，以及在I期临床试验中正在测试的内容。 抗体优选在两小时内输注，尽管这取决于患者和治疗时的疾病状态。 用于治疗人的优选剂量为0.1mg / kg-5.0mg / kg的5C120，或与STX2的亚基A的另一种抗体的等效剂量。 在最优选的实施方案中，施用0.1mg / kg，0.5mg / kg或5.0mg / kg的5C12（基于动物数据和高剂量的低剂量预期治疗剂量）的剂量。

    Human neutralizing antibodies against hemolytic uremic syndrome
    6.
    发明授权
    Human neutralizing antibodies against hemolytic uremic syndrome 有权
    人溶解性尿毒症综合征中和抗体

    公开(公告)号：US07910096B2

    公开(公告)日：2011-03-22

    申请号：US11933166

    申请日：2007-10-31

    Applicant: Saul Tzipori ,  Ramaswamy Balakrishnan ,  Arthur Donohue-Rolfe

    Inventor： Saul Tzipori ,  Ramaswamy Balakrishnan ,  Arthur Donohue-Rolfe

    IPC: A61K39/00 ,  A61K39/395 ,  A61K39/40

    CPC classification number: C07K16/1232 ,  A61K38/00

    Abstract: Human and humanized monoclonal antibodies which binds specifically to subunit A of Shiga like toxin II have been developed which are effective to prevent or ameliorate one or more symptoms of HUS in a human. Effective dosages for treatment or prevention range from approximately 0.1 to 5.0 mg of antibody/kg of patient weight. The examples demonstrate the preferred dosage ranges based on the pig model, and what is being tested in phase I clinical trials. Antibodies are preferably transfused over a period of two hours, although this will depend on the patient and the disease state at the time of treatment. Preferred dosages for treatment of humans are between 0.1 mg/kg-5.0 mg/kg of 5C120, or an equivalent dosage of another antibody to subunit A of STX2. In the most preferred embodiments, dosages of 0.1 mg/kg, 0.5 mg/kg, or 5.0 mg/kg of 5C12 (low dose, anticipated therapeutic dose based on animal data and high dose) are administered.

    Abstract translation: 已经开发了特异性结合志贺样毒素II的亚单位A的人和人源化单克隆抗体，其有效预防或改善人类中一种或多种HUS症状。 治疗或预防的有效剂量范围为约0.1至5.0mg抗体/ kg患者体重。 这些实施例证明了基于猪模型的优选剂量范围，以及在I期临床试验中正在测试的内容。 抗体优选在两小时内输注，尽管这取决于患者和治疗时的疾病状态。 用于治疗人的优选剂量为0.1mg / kg-5.0mg / kg的5C120，或STX2的亚基A的另一种抗体的等效剂量。 在最优选的实施方案中，施用0.1mg / kg，0.5mg / kg或5.0mg / kg的5C12（基于动物数据和高剂量的低剂量预期治疗剂量）的剂量。

    Method and device for the concentration of multiple microorganisms and toxins from large liquid toxins
    10.
    发明授权
    Method and device for the concentration of multiple microorganisms and toxins from large liquid toxins 有权
    用于浓缩大量液体毒素的多种微生物和毒素的方法和装置

    公开(公告)号：US08614083B2

    公开(公告)日：2013-12-24

    申请号：US12602819

    申请日：2008-06-13

    Applicant: Saul Tzipori ,  Udi Zukerman ,  Gary Stacey

    Inventor： Saul Tzipori ,  Udi Zukerman ,  Gary Stacey

    IPC: C12N3/00

    CPC classification number: B01D21/262 ,  B01D21/302 ,  B01D2221/10 ,  B03C3/15 ,  B03C5/02 ,  B03C2201/26 ,  B04B5/10 ,  G01N1/4077

    Abstract: A method for the simultaneous concentration of multiple toxins from large volumes of water. The method includes the steps of providing a disposable separation centrifuge bowl, the centrifuge bowl including a positively charged material at it's inner core. A large water sample contaminated with toxins from a group consisting of protozoa, bacteria, bacterial spores, and toxins is delivered to the centrifuge bowl. A centrifugal force is applied to the separation bowl. The water sample is concentrated to remove large particles of the toxins in the bowl due to the centrifugal forces. The concentrated water sample is passes through the positively charged inner core to capture any remaining concentrated targets by electrostatic forces and the concentrated targets are eluted.

    Abstract translation: 从大量水中同时浓缩多种毒素的方法。 该方法包括提供一次性分离离心机碗的步骤，离心机碗在其内核处包含带正电荷的材料。 从原生动物，细菌，细菌孢子和毒素组成的组中被毒素污染的大量水样品被输送到离心机碗中。 离心力被施加到分离碗。 由于离心力，将水样品浓缩以除去碗中的大量毒素。 浓缩水样品通过带正电荷的内核，通过静电力捕获任何剩余的浓缩靶，并且浓缩的靶被洗脱。

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