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    Synthetic Streptococcus pneumoniae vaccine
    56.
    发明授权
    Synthetic Streptococcus pneumoniae vaccine 有权
    合成型肺炎链球菌疫苗

    公开(公告)号：US09249199B2

    公开(公告)日：2016-02-02

    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: A61K39/00 ,  A61K39/02 ,  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。 组合物包括新型多肽，其包含对应于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，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。

    METHODS AND COMPOSITIONS FOR THE TREATMENT OF GLUTAMINE-ADDICTED CANCERS
    57.
    发明申请
    METHODS AND COMPOSITIONS FOR THE TREATMENT OF GLUTAMINE-ADDICTED CANCERS 审中-公开
    用于治疗谷氨酰胺治疗癌症的方法和组合物

    公开(公告)号：US20160022708A1

    公开(公告)日：2016-01-28

    申请号：US14774380

    申请日：2014-03-13

    Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

    Inventor： Kevin Freeman

    IPC: A61K31/655 ,  A61K31/635 ,  A61K31/404 ,  A61K45/06 ,  A61K31/167

    CPC classification number: A61K31/655 ,  A61K31/167 ,  A61K31/404 ,  A61K31/635 ,  A61K45/06 ,  A61K2300/00

    Abstract: Provided herein are methods for a novel combination therapy for treating a glutamine-addicted cancer in a subject in need thereof, which comprises the administration of a glutaminase antagonist and a pro-apoptotic compound. Specific glutaminase antagonists and pro-apoptotic compounds are provided. In some embodiments, the glutaminase antagonist is 6-diazo-5-oxo-1-norleucine (DON) and the pro-apoptotic compound is a Bcl-2 family member antagonist. In some embodiments, the pro-apoptotic compound is obatoclax mesylate, navitoclax, or fenretinide. In some embodiments, the glutamine-addicted cancer is a cancer in which Myc is deregulated. In some embodiments, the cancer is a pediatric cancer.

    Abstract translation: 本文提供了用于治疗有需要的受试者中的谷氨酰胺上瘾癌症的新型联合疗法的方法，其包括施用谷氨酰胺酶拮抗剂和促凋亡化合物。 提供特异性谷氨酰胺酶拮抗剂和促凋亡化合物。 在一些实施方案中，谷氨酰胺酶拮抗剂是6-重氮-5-氧代-1-正亮氨酸（DON），促凋亡化合物是Bcl-2家族成员拮抗剂。 在一些实施方案中，促凋亡化合物是甲磺酸盐，纳米复合体或芬维A胺。 在一些实施方案中，谷氨酰胺上瘾的癌症是其中Myc被释放调节的癌症。 在一些实施方案中，癌症是儿科癌症。

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