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    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG
    24.
    发明授权
    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG 有权
    改良的ESAT-6分子和改良的牛分枝杆菌BCG的疫苗株

    公开(公告)号：US08398991B2

    公开(公告)日：2013-03-19

    申请号：US11455929

    申请日：2006-06-20

    申请人： Roland Brosch ,  Priscille Brodin ,  Stewart Cole ,  Laleh Majlessi ,  Claude Leclerc

    发明人： Roland Brosch ,  Priscille Brodin ,  Stewart Cole ,  Laleh Majlessi ,  Claude Leclerc

    IPC分类号： A61K39/02

    CPC分类号： C07K14/35 ,  A61K39/04 ,  A61K2039/522 ,  C07K2319/20

    摘要： A genetically modified strain of M. tuberculosis or Mycobacterium bovis BCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Y51, Q55, Q56, N66, M83, V90, M93, or F94 in SEQ ID NO:1; or at least one mutation at Q3, F7 A13, L27, W42, G44, Y50, Q54, N65, N67, M82, V89, M92, or F93 in SEQ ID NO:2, or a deletion at the terminal end of less than 20 amino acids. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, AI4R, L28A, L29S, W43R, G45T, Q55I, Q56A, N66I, N67A, M83I, V90R, M93T, or F94Q in SEQ ID NO:1, and Q3L, F7I, A13R, L27A, L28S, W42R, Q44T, Q54I, N65I, M82I, V89R, M92T, and F93Q in SEQ ID NO:2. Similarly, the genetically modified strain may also secrete ESAT-6 with a hexa-histidine tag, tetra-cysteine tag, or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

    摘要翻译： 提供结核分枝杆菌或牛分枝杆菌BCG的遗传修饰菌株，其中所述遗传修饰菌株包含至少一个包含SEQ ID NO：1，SEQ ID NO：2或两者的经修饰的序列，或在T2处具有至少一个突变， SEQ ID NO：1中的Q4，F8，A14，L28，L29，W43，G45，Y51，Q55，Q56，N66，M83，V90，M93或F94; 或SEQ ID NO：2中的Q3，F7A13，L27，W42，G44，Y50，Q54，N65，N67，M82，V89，M92或F93的至少一个突变，或末端的缺失小于 20个氨基酸。 在优选实施方案中，突变是SEQ ID NO：1中的T2H，Q4L，F8I，AI4R，L28A，L29S，W43R，G45T，Q55I，Q56A，N66I，N67A，M83I，V90R，M93T或F94Q中的至少一种 ，以及SEQ ID NO：2中的Q3L，F7I，A13R，L27A，L28S，W42R，Q44T，Q54I，N65I，M82I，V89R，M92T和F93Q。 类似地，遗传修饰的菌株也可以分泌具有六组氨酸标签，四半胱氨酸标签或FLAG标签的ESAT-6，GFP-融合物或C末端的短截短小于20个氨基酸 。

    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG
    26.
    发明申请
    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG 有权
    改良的ESAT-6分子和改良的牛分枝杆菌BCG的疫苗株

    公开(公告)号：US20070009547A1

    公开(公告)日：2007-01-11

    申请号：US11455929

    申请日：2006-06-20

    申请人： Roland Brosch ,  Priscille Brodin ,  Stewart Cole ,  Laleh Majlessi ,  Claude Leclerc

    发明人： Roland Brosch ,  Priscille Brodin ,  Stewart Cole ,  Laleh Majlessi ,  Claude Leclerc

    IPC分类号： A61K39/04 ,  C12N1/21

    CPC分类号： C07K14/35 ,  A61K39/04 ,  A61K2039/522 ,  C07K2319/20

    摘要： A genetically modified strain of M. tuberculosis or Mycobacterium bovis BCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Q55, Q56, N66, M83, V90, M93, or F94. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, A14R, L28A, L29S, W43R, G45T, Y51, Q55I, Q56A, N66I, N66A, M83I, V90R, M93T, or F94Q. Similarly, the genetically modified strain may also secrete ESAT-6 with a a histidine tag, tetra-cysteine tag or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

    摘要翻译： 提供结核分枝杆菌或牛分枝杆菌BCG的遗传修饰菌株，其中所述遗传修饰菌株包含至少一个包含SEQ ID NO：1，SEQ ID NO：2或两者的经修饰的序列，或在T2处具有至少一个突变， Q4，F8，A14，L28，L29，W43，G45，Q55，Q56，N66，M83，V90，M93或F94。 在优选的实施方案中，突变是T2H，Q4L，F8I，A14R，L28A，L29S，W43R，G45T，Y51，Q55I，Q56A，N66I，N66A，M83I，V90R，M93T或F94Q中的至少一种。 类似地，遗传修饰的菌株也可以在小于20个氨基酸的C末端分泌具有组氨酸标签，四半胱氨酸标签或FLAG标签，GFP融合物或短截短的ESAT-6。

    THERAPY OF CANCER BASED ON TARGETING ADAPTIVE, INNATE AND/OR REGULATORY COMPONENT OF THE IMMUNE RESPONSE
    29.
    发明申请
    THERAPY OF CANCER BASED ON TARGETING ADAPTIVE, INNATE AND/OR REGULATORY COMPONENT OF THE IMMUNE RESPONSE 有权
    根据免疫应答的自适应，消除和/或法规组成部分治疗癌症

    公开(公告)号：US20080152665A1

    公开(公告)日：2008-06-26

    申请号：US11778267

    申请日：2007-07-16

    申请人： Claude Leclerc ,  Pedro Berraondo Lopez

    发明人： Claude Leclerc ,  Pedro Berraondo Lopez

    IPC分类号： A61K39/00 ,  A61K38/02 ,  A61K38/08 ,  A61P35/04 ,  A61K38/16

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/0011 ,  A61K39/12 ,  A61K2039/555 ,  A61K2039/55511 ,  A61K2039/55516 ,  A61K2039/55555 ,  A61K2039/55561 ,  A61K2039/572 ,  A61K2039/585 ,  A61K2039/70 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/33 ,  C07K2319/40 ,  C12N7/00 ,  C12N9/88 ,  C12N2710/20022 ,  C12N2710/20034 ,  C12N2710/20071 ,  C12Y406/01001

    摘要： The invention relates to a kit of parts, suitable for use in a therapy of cancer, wherein said kit comprises:(i) a recombinant protein comprising one or several polypeptides bearing one or several epitopes of one or several tumor-associated antigens, said polypeptides being inserted in the same or different permissive sites of an adenylate cyclase (CyaA) protein or of a fragment thereof, wherein said CyaA fragment retains the property of said adenylate cyclase protein to target Antigen Presenting Cells or a mixture of such recombinant proteins wherein at least one of said epitopes, or tumor associated antigens, or insertion sites of CyaA protein, or fragment of said CyaA protein is different between the various recombinant proteins in the mixture; and said kit of parts further comprises at least one of the following compounds; (ii) an agent, suitable for modulating a regulatory immune response in a patient ad optionally; (iii) an adjuvant component suitable for activating the innate immune response in a patient.

    摘要翻译： 本发明涉及一种适合用于癌症治疗的试剂盒，其中所述试剂盒包括：（i）包含一个或几个携带一个或几个肿瘤相关抗原表位的多肽的重组蛋白，所述多肽 插入腺苷酸环化酶（CyaA）蛋白或其片段的相同或不同的允许位点，其中所述CyaA片段保留所述腺苷酸环化酶蛋白质的特性以靶向抗原呈递细胞或其重要蛋白质的混合物，其中至少 所述表位之一或肿瘤相关抗原或CyaA蛋白的插入位点或所述CyaA蛋白的片段在混合物中的各种重组蛋白之间是不同的; 并且所述试剂盒的部分还包含至少一种以下化合物; （ii）任选的适于调节患者的调节免疫应答的药剂; （iii）适合于激活患者中先天免疫应答的辅助成分。

    STREPTAVIDIN AND BIOTIN-BASED ANTIGEN DELIVERY SYSTEM
    30.
    发明申请
    STREPTAVIDIN AND BIOTIN-BASED ANTIGEN DELIVERY SYSTEM 审中-公开
    STREPTAVIDIN和基于生物基因的抗原递送系统

    公开(公告)号：US20130121958A1

    公开(公告)日：2013-05-16

    申请号：US13517429

    申请日：2010-12-12

    申请人： Claude Leclerc ,  Laleh Majlessi ,  Hui Dong ,  Peter Sebo ,  Ondrej Stanek

    发明人： Claude Leclerc ,  Laleh Majlessi ,  Hui Dong ,  Peter Sebo ,  Ondrej Stanek

    IPC分类号： A61K39/39

    CPC分类号： A61K39/39 ,  A61K39/04 ,  A61K2039/625 ,  G01N33/505 ,  G01N2333/36 ,  Y02A50/412 ,  Y02A50/466

    摘要： The present invention provides an innovative versatile system, which allows delivery of one or several antigens or biologically active molecules into or onto targeted subset of cells. The invention is in particular directed to a combination of compounds and in particular to a composition, which comprises: (i) a fusion polypeptide comprising a streptavidin (SA) or avidin polypeptide and one or several effector molecule(s), wherein said fusion polypeptide retains the property of SA and avidin polypeptides to bind biotin; (ii) biotinylated targeting molecule(s), which are capable of targeting subset(s) of cells and/or cell surface molecule(s), and in particular dendritic cells (DC), subsets of DC and/or surface molecule(s) (including surface receptor(s)) of DC. The combination of the invention is suitable for use for targeting, in vivo, in vitro or ex vivo, of one or several effector molecule(s) to subset(s) of cells and/or cell surface molecule(s), and in particular for diagnosing or immunomonitoring a disease in a mammal or in prophylactic treatment and especially in vaccination and in therapy including in immunotherapy. The combination of the invention is also intended for use in vivo or ex vivo, for inducing a T cell immune response in bone marrow of naive donors before transplantation, or for activation and/or expansion of a T cell immune response in bone marrow of already immunized donors. The invention also relates to a method for the production of a fusion polypeptide of the invention and to a kit for a diagnostic test of a disease in a mammal, for immunomonitoring a disease in a mammal or for the prevention or treatment of a disease in a mammal.

    摘要翻译： 本发明提供了一种创新的通用系统，其允许将一种或几种抗原或生物活性分子递送到靶细胞的子集中或靶向细胞的子集。 本发明特别涉及化合物，特别是组合物的组合，其包含：（i）包含链霉抗生物素蛋白（SA）或抗生物素蛋白多肽和一种或几种效应分子的融合多肽，其中所述融合多肽 保留SA和抗生物素蛋白多肽结合生物素的性质; （ii）生物素化的靶向分子，其能够靶向细胞和/或细胞表面分子的子集，特别是树突状细胞（DC），DC和/或表面分子的子集（s） ）（包括表面受体）。 本发明的组合适用于靶向，体内，体外或体外的一种或几种效应分子与细胞和/或细胞表面分子的子集，特别是 用于诊断或免疫监测哺乳动物的疾病或预防性治疗，特别是在免疫接种和包括免疫治疗在内的治疗中。 本发明的组合也旨在用于体内或离体，用于在移植前的初始供体的骨髓中诱导T细胞免疫应答，或用于在已经在骨髓中激活和/或扩增T细胞免疫应答 免疫供体。 本发明还涉及生产本发明的融合多肽的方法和用于哺乳动物疾病的诊断试验的试剂盒，用于免疫监测哺乳动物的疾病或预防或治疗哺乳动物的疾病 哺乳动物。