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    SYNTHETIC STREPTOCOCCUS PNEUMONIAE VACCINE
    143.
    发明申请
    SYNTHETIC STREPTOCOCCUS PNEUMONIAE VACCINE 审中-公开
    合成环孢菌素疫苗

    公开(公告)号：US20140248303A1

    公开(公告)日：2014-09-04

    申请号：US14220947

    申请日：2014-03-20

    Applicant: St. Jude Children's Research Hospital

    Inventor： Karim C. El Kasmi ,  Brad Jordan ,  Richard Kriwacki ,  Beth Mann ,  Carlos J. Orihuela ,  Elaine Tuomanen

    IPC: C07K14/315

    CPC classification number: C07K14/3156 ,  A61K39/00

    Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R21 or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope. Compositions further include isolated nucleic acid molecules that encode the polypeptides of the invention, immunogenic compositions and vaccines comprising the disclosed polypeptides, and antibodies specific for these polypeptides.

    Abstract translation: 提供了预防和治疗肺炎球菌感染的组合物和方法。 组合物包括包含对应于CbpA的R21或R22结构域的氨基酸序列或这些结构域之一的共有序列及其变体和片段的新型多肽，其中所述多肽以期望的构象，特别是环构象稳定。 本发明的多肽可被工程化以包含第一和第二半胱氨酸残基，由此导致二硫键的形成，从而将多肽稳定在所需构象。 或者，可以修饰本发明的多肽以在多肽内存在的第一和第二氨基酸残基之间产生合成连接，其中所述合成连接使所述多肽以所需构象稳定。 本发明的多肽还可以包含T细胞表位的氨基酸序列。 组合物还包括编码本发明多肽的分离的核酸分子，包含所公开的多肽的免疫原性组合物和疫苗以及对这些多肽特异的抗体。

    Pre-and post therapy gene expression profiling to identify drug targets
    145.
    发明申请
    Pre-and post therapy gene expression profiling to identify drug targets 审中-公开
    治疗前和治疗后基因表达谱鉴定药物靶标

    公开(公告)号：US20030224422A1

    公开(公告)日：2003-12-04

    申请号：US10407790

    申请日：2003-04-04

    Applicant: St. Jude Children's Research Hospital, Inc.

    Inventor： William Edward Evans ,  Mary V. Relling

    IPC: C12Q001/68

    CPC classification number: C12Q1/6886 ,  C12Q1/6809 ,  C12Q2600/106 ,  C12Q2600/158 ,  C12Q2565/501

    Abstract: A general method for identifying biological targets for improving currently available therapies is provided. Target genes and their expression products are identified based on their response to therapy as determined through pre- and post-therapy expression profiles. In another aspect, differences in expression profiles between responsive and nonresponsive patients are taken into account to identify potential new targets for the development of novel medications or treatments. The invention also provides methods for comparing therapies to predict which will have the best therapeutic efficacy and/or the least potential deleterious. The methods taught are specifically applied to identify targets for improving treatment of acute lymphoblastic leukemia.

    Abstract translation: 提供了用于鉴定改善目前可用疗法的生物靶标的一般方法。 目标基因及其表达产物是根据通过治疗前和治疗后表达谱确定的对治疗的反应来鉴定的。 另一方面，考虑到反应性和非反应性患者之间的表达谱的差异，以确定用于开发新药物或治疗的潜在新目标。 本发明还提供了用于比较治疗以预测哪些具有最佳治疗功效和/或最不利潜在的方法。 所教导的方法专门用于鉴定改善急性淋巴细胞白血病治疗的靶点。

    Lymphocyte surface receptor that binds CAML and methods of use thereof
    146.
    发明申请
    Lymphocyte surface receptor that binds CAML and methods of use thereof 审中-公开
    结合CAML的淋巴细胞表面受体及其使用方法

    公开(公告)号：US20030082173A1

    公开(公告)日：2003-05-01

    申请号：US10293816

    申请日：2002-11-12

    Applicant: St. Jude Children's Research Hospital, Inc.

    Inventor： Richard J. Bram ,  Gotz Von Bulow

    IPC: G01N033/567 ,  A61K039/395

    CPC classification number: C07K16/2878 ,  A01K2217/075 ,  A61K38/00 ,  C07K14/70578 ,  C07K2317/75 ,  Y02A50/411 ,  Y10S530/82

    Abstract: A novel lymphocyte receptor protein, its DNA sequence, and its role in the calcium activation pathway is described. The protein, or genetically engineered constructs encoding it, are shown to increase lymphocyte response, and to identify ligands of the protein receptor. Antibodies to the proteins of the invention are generated for diagnostic therapeutics. The protein and DNA can also be used for diagnostic purposes and for identifying agents for modulating the calcium induced activation pathway. A particular advantage of the present invention is that it provides lymphocyte activation of receptor found on all B cells, but only on a subset of T cells. The receptor can thus be targeted to specifically regulate B cell responses without affecting mature T cell activity. Such targeting specificity is always advantageous, particularly where an increase or decrease of antibody production is desired, e.g., during an infection (increase) or to avoid immune complex deposition complications (rheumatoid arthritis, glomerulonephritis, and other auto immune conditions).

    Abstract translation: 描述了一种新型淋巴细胞受体蛋白，其DNA序列及其在钙激活途径中的作用。 显示蛋白质或编码它的遗传工程化构建体可增加淋巴细胞反应，并鉴定蛋白质受体的配体。 生成本发明蛋白质的抗体用于诊断治疗。 蛋白质和DNA也可用于诊断目的，并用于鉴定用于调节钙诱导的激活途径的药剂。 本发明的一个特别优点在于它提供了在所有B细胞上发现的受体的淋巴细胞活化，但是仅提供在T细胞的一个子集上。 因此受体可以被靶向以特异性调节B细胞应答而不影响成熟的T细胞活性。 这种靶向特异性总是有利的，特别是在需要增加或减少抗体产生的情况下，例如在感染（增加）期间或避免免疫复合物沉积并发症（类风湿性关节炎，肾小球性肾炎和其他自身免疫病症）时。

    DNA transfection system for the generation of infectious influenza virus
    147.
    发明申请
    DNA transfection system for the generation of infectious influenza virus 有权
    用于产生感染性流感病毒的DNA转染系统

    公开(公告)号：US20020164770A1

    公开(公告)日：2002-11-07

    申请号：US09844517

    申请日：2001-04-27

    Applicant: St. Jude Children's Research Hospital

    Inventor： Erich Hoffmann

    IPC: C12Q001/70 ,  C12N009/22 ,  C12N015/86 ,  C12N015/74 ,  C12N015/63 ,  C12N015/00 ,  C12N007/00

    CPC classification number: C07K14/005 ,  A61K2039/5252 ,  A61K2039/5254 ,  C12N7/00 ,  C12N2720/00063 ,  C12N2760/16122 ,  C12N2760/16151 ,  C12N2760/16163 ,  C12N2760/16222 ,  C12N2760/16263 ,  C12N2760/18663 ,  C12N2770/24263 ,  C12N2800/107 ,  C12N2800/40 ,  C12N2830/205 ,  C12N2830/34 ,  C12N2830/36 ,  C12N2830/85

    Abstract: The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuraminidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus. Attenuated or inactivated RNA viruses produced by the present invention may be administered to a patient in need of vaccination by any of several routes including intranasally or intramuscularly.

    Abstract translation: 本发明基于用于病毒RNA的有效细胞内合成的双重启动子系统（优选RNA pol I-pol II系统）的开发。 所得到的基于最小质粒的系统可用于合成任何RNA病毒，优选具有负单链RNA基因组的病毒。 当将系统的质粒引入合适的宿主细胞时，产生系统的病毒产物。 该系统的一个应用是生产用作疫苗抗原的减毒重配流感病毒。 通过共转染质粒产生的重配病毒可以包含编码来自目前感染群体的流感病毒的表面糖蛋白血凝素和神经氨酸酶的基因以及来自减毒流感病毒的内部基因。 本发明的优点是其多功能性; 该系统可以快速且容易地适应于合成任何RNA病毒的减毒版本。 通过本发明产生的减毒或灭活的RNA病毒可以通过包括鼻内或肌肉内的几种途径中的任何途径施用于需要接种疫苗的患者。

    Highly efficient gene transfer into human repopulating stem cells by RD114 pseudotyped retroviral vector particles
    148.
    发明申请
    Highly efficient gene transfer into human repopulating stem cells by RD114 pseudotyped retroviral vector particles 失效
    通过RD114假型逆转录病毒载体颗粒将高效基因转移到人类重建干细胞中

    公开(公告)号：US20010051375A1

    公开(公告)日：2001-12-13

    申请号：US09801302

    申请日：2001-03-07

    Applicant: St. Jude Children's Research Hospital

    Inventor： Patrick F. Kelly ,  Elio F. Vanin

    IPC: A61K048/00 ,  A01K067/027 ,  C12N015/867

    CPC classification number: C12N15/86 ,  A61K48/00 ,  A61K2035/124 ,  C12N2740/13043 ,  C12N2740/13045 ,  C12N2810/6054 ,  C12N2840/203

    Abstract: The present invention pertains to a method for efficiently introducing exogenous genes into stem cells, particularly human stem cells. The method optionally includes the steps of inducing the proliferation of target cells by pre-stimulation with cytokines and/or growth factors, followed by incubating these cells with RD114-pseudotyped vector particles. In a specific embodiment, the vector particles are retronectin-immobilized or ultracentrifugation-concentrated retroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein. The present invention further discloses a method for somatic gene therapy, which can be used for various therapeutic applications and involves introducing a gene of interest contained within the retroviral genome into human repopulating stem cells followed by introducing these cells into a human host. Finally, the present invention discloses a method for monitoring the efficiency of the stem cell-mediated gene transfer based on detecting the presence of the genes (or the expression products) of the retroviral vector in various stem cell-derived lineages of the host.

    Abstract translation: 本发明涉及一种有效地将外源基因引入干细胞，特别是人干细胞的方法。 该方法可选地包括以下步骤：通过用细胞因子和/或生长因子预刺激诱导靶细胞的增殖，随后用RD114假型载体颗粒温育这些细胞。 在一个具体实施方案中，载体颗粒是用猫内源性逆转录病毒（RD114）包膜蛋白假型分离的固定链球菌素固定化或超速离心浓缩的逆转录病毒载体颗粒。 本发明还公开了一种用于体细胞基因治疗的方法，其可用于各种治疗应用，并且涉及将逆转录病毒基因组中包含的感兴趣基因导入人重新填充干细胞，随后将这些细胞引入人宿主中。 最后，本发明公开了一种监测干细胞介导的基因转移效率的方法，该方法基于检测宿主各种干细胞衍生谱系中逆转录病毒载体的基因（或表达产物）的存在。

    Factor VIII Sequences
    150.
    发明申请
    Factor VIII Sequences 有权

    公开(公告)号：US20250108093A1

    公开(公告)日：2025-04-03

    申请号：US18828841

    申请日：2024-09-09

    Applicant: UCL Business Ltd ,  ST. Jude Children's Research Hospital

    Inventor： Amit Nathwani ,  Jenny McIntosh ,  Edward Tuddenham ,  Andrew Davidoff

    IPC: A61K38/37 ,  A01K67/0275 ,  A61K48/00 ,  C07K14/755

    Abstract: There is provided a nucleic acid molecule comprising a nucleotide sequence encoding for a functional factor VIII protein, wherein the portion of the nucleotide sequence encoding for the B domain of the factor VIII protein is between 90 and 111 nucleotides in length and encodes for an amino acid sequence comprising a sequence having at least 85% identity to SEQ ID NO: 4 and which comprises six asparagine residues. Also provided is a functional factor VIII protein, a vector comprising the above nucleic acid molecule, a host cell, a transgenic animal, a method of treating haemophilia, e.g. haemophilia A, and a method for the preparation of a parvoviral gene delivery vector.

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