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    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof
    1.
    发明授权
    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof 有权
    衍生自R9M的突变的免疫原性肽，编码其的多核苷酸及其治疗用途

    公开(公告)号：US07476719B2

    公开(公告)日：2009-01-13

    申请号：US10448521

    申请日：2003-05-30

    申请人： Hüseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  Franç is Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    发明人： Hüseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  Franç is Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    IPC分类号： A61K39/395 ,  A61K39/00 ,  C07K5/00

    CPC分类号： C07K14/4748 ,  A61K38/00 ,  A61K39/00

    摘要： The invention concerns the optimisation of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-Ile-Ala-Glu-Czs-Ile-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.

    摘要翻译： 本发明涉及野生R9M肽的优化和所得肽用于人类白血病的治疗性接种和/或预防性接种的用途。 更具体地，本发明涉及衍生自包含野生型R9M肽序列Arg-Ile-Ala-Glu-Cys-Ile-Leu-Gly-Met的人TEL / AML1融合蛋白的突变的免疫原性肽。 本发明还涉及编码突变的R9M免疫原性肽的多核苷酸，包含表达突变的R9M免疫原性肽的核酸序列的细胞表达载体和能够固定在至少一种所述肽/多核苷酸上的多克隆或单克隆抗体。 本发明还涉及所述肽，多核苷酸和/或抗体用于制备疫苗，抗肿瘤药物和组合物以及体内和体内刺激人体免疫应答的用途。

    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof
    2.
    发明授权
    Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof 有权
    衍生自R9M的突变的免疫原性肽，编码其的多核苷酸及其治疗用途

    公开(公告)号：US08303957B2

    公开(公告)日：2012-11-06

    申请号：US12314218

    申请日：2008-12-05

    申请人： Hüseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  François Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    发明人： Hüseyin Firat ,  Pierre Langlade-Demoyan ,  Etienne Vilmer ,  François Lemonnier ,  Pierre Rohrlich ,  Patricia Yotnda

    IPC分类号： A61K390/00

    CPC分类号： C07K14/4748 ,  A61K38/00 ,  A61K39/00

    摘要： The invention concerns the optimization of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukaemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-Ile-Ala-Glu-Czs-Ile-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.

    摘要翻译： 本发明涉及野生R9M肽的优化和所得肽用于人类白血病的治疗性接种和/或预防性接种的用途。 更具体地，本发明涉及衍生自包含野生型R9M肽序列Arg-Ile-Ala-Glu-Cys-Ile-Leu-Gly-Met的人TEL / AML1融合蛋白的突变的免疫原性肽。 本发明还涉及编码突变的R9M免疫原性肽的多核苷酸，包含表达突变的R9M免疫原性肽的核酸序列的细胞表达载体和能够固定在至少一种所述肽/多核苷酸上的多克隆或单克隆抗体。 本发明还涉及所述肽，多核苷酸和/或抗体用于制备疫苗，抗肿瘤药物和组合物以及体内和体内刺激人体免疫应答的用途。

    Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences
    4.
    发明授权
    Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences 失效
    杂种或嵌合多核苷酸，蛋白质和包含乙型肝炎病毒序列的组合物

    公开(公告)号：US07345026B2

    公开(公告)日：2008-03-18

    申请号：US10388337

    申请日：2003-03-14

    申请人： Hüseyin Firat ,  François Lemonnier ,  Pierre Langlade-Demoyen ,  Marie-Louise Michel ,  Andreas A. Suhrbier

    发明人： Hüseyin Firat ,  François Lemonnier ,  Pierre Langlade-Demoyen ,  Marie-Louise Michel ,  Andreas A. Suhrbier

    IPC分类号： A61K35/00 ,  C12N15/68

    CPC分类号： C07K14/005 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/292 ,  A61K48/00 ,  A61K2039/5258 ,  A61K2039/57 ,  C07K2319/00 ,  C07K2319/40 ,  C12N2730/10122 ,  C12N2730/10134

    摘要： H-2 class I negative, HLA-A2.1 transgeniic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.

    摘要翻译： 使用H-2 I型阴性，HLA-A2.1转基因HHD小鼠进行HLA-A2.1限制性人肿瘤相关CTL表位的免疫原性的比较评估。 在IFA中注射到小鼠中的这些表位肽之间建立了等级关系，其全局与其结合和稳定HLA-A2.1分子的能力相关。 辅助肽的共注射增强了大多数CTL应答。 相比之下，仍然表达自己的I类分子的经典HLA I类转基因小鼠在大多数情况下并不在相同的实验条件下产生H.A.-A2.1限制性CTL应答。 在HHD小鼠中比较了可接受的临床应用的不同单表位免疫策略。 重组的Ty病毒样颗粒或编码与乙型肝炎病毒中膜包膜蛋白融合的表位的DNA得到最好的结果。 使用后一种方法和基于黑素瘤的多表位构建体，可以在单个动物中同时诱导针对五种不同表位的CTL应答。 因此，HHD小鼠为基于肽的癌症免疫治疗的临床前评估提供了通用的动物模型。

    USE OF TRIPLEX STRUCTURE DNA IN TRANSFERRING NUCLEOTIDE SEQUENCES
    6.
    发明申请
    USE OF TRIPLEX STRUCTURE DNA IN TRANSFERRING NUCLEOTIDE SEQUENCES 有权
    TRIPLEX结构DNA在转移核苷酸序列中的应用

    公开(公告)号：US20120095083A1

    公开(公告)日：2012-04-19

    申请号：US12813375

    申请日：2010-06-10

    申请人： Pierre Charneau ,  Véronique Zennou ,  Hüseyin Firat

    发明人： Pierre Charneau ,  Véronique Zennou ,  Hüseyin Firat

    IPC分类号： A61K31/7088 ,  A61P37/04 ,  A61P31/14 ,  C12N5/10

    CPC分类号： C12N15/87 ,  A01K2217/05 ,  A61K48/00 ,  A61K2039/51 ,  C07K14/4748 ,  C12N7/00 ,  C12N15/86 ,  C12N2740/16043 ,  C12N2740/16062 ,  C12N2830/50 ,  C12N2840/20 ,  C12N2840/203

    摘要： A method to induce an immune response in a host in need thereof, comprises administering to the host, recombinant lentiviral vector particles comprising: a) a GAG polypeptide or a functional GAG-polypeptide derivative; b) a POL polypeptide or a functional POL-polypeptide derivative ; c) an ENV polypeptide or a functional ENV-polypeptide derivative; and d) a recombinant polynucleotide. The recombinant polynucleotide comprises a transgene placed under the control of regulatory signals for transcription and expression, regulatory signals, of lentiviral origin, for reverse transcription, expression and packaging, and a polynucleotide comprising a cis-acting central initiation region (cPPT) and a cis-acting termination region (CTS). The regions are of lentiviral origin and are inserted in a functional orientation with the regulatory signals of lentiviral origin. The polynucleotide forms a DNA triplex during reverse transcription.

    摘要翻译： 在有需要的宿主中诱导免疫应答的方法包括向宿主施用重组慢病毒载体颗粒，其包含：a）GAG多肽或功能性GAG-多肽衍生物; b）POL多肽或功能性POL-多肽衍生物; c）ENV多肽或功能性ENV-多肽衍生物; 和d）重组多核苷酸。 重组多核苷酸包含置于转录和表达的调控信号控制下的转基因，慢病毒起源的调控信号，用于逆转录，表达和包装，以及包含顺式作用中枢起始区（cPPT）和顺式 作用终止区域（CTS）。 这些区域是慢病毒来源的，并且以具有慢病毒起源的调节信号的功能方向插入。 多核苷酸在逆转录过程中形成DNA三链体。

    Use of triplex structure DNA in transferring nucleotide sequences
    7.
    发明授权
    Use of triplex structure DNA in transferring nucleotide sequences 失效
    三重结构DNA在转移核苷酸序列中的应用

    公开(公告)号：US06682907B1

    公开(公告)日：2004-01-27

    申请号：US09688990

    申请日：2000-10-17

    申请人： Pierre Charneau ,  Véronique Zennou ,  Hüseyin Firat

    发明人： Pierre Charneau ,  Véronique Zennou ,  Hüseyin Firat

    IPC分类号： C12P2106

    CPC分类号： C12N15/87 ,  A01K2217/05 ,  A61K48/00 ,  A61K2039/51 ,  C07K14/4748 ,  C12N7/00 ,  C12N15/86 ,  C12N2740/16043 ,  C12N2740/16062 ,  C12N2830/50 ,  C12N2840/20 ,  C12N2840/203

    摘要： A recombinant vector comprising a polynucleotide containing a cis-acting central initiation region (cPPT) and a cis-acting termination region (CTS) is disclosed. These regions are of retroviral or retroviral-like origin. The vector further comprises a defined nucleotide sequence (transgene or sequence of interest) and regulatory signals for reverse transcription, expression, and packaging, wherein the regulatory signals are of retroviral or retroviral-like origin. In some embodiments the vector is incorporated into compositions for therapeutic purposes. In other embodiments the vector is incorporated into immunogenic compositions, The vector is also useful for methods such as ex vivo transfection or ex vivo transduction of non-mitotic differentiated cells.

    摘要翻译： 公开了包含含有顺式作用中心起始区（cPPT）和顺式作用终止区（CTS）的多核苷酸的重组载体。 这些区域是逆转录病毒或逆转录病毒样起源的。 载体还包含定义的核苷酸序列（转基因或感兴趣的序列）和用于逆转录，表达和包装的调节信号，其中调节信号是逆转录病毒或逆转录病毒样起源的。 在一些实施方案中，将载体并入用于治疗目的的组合物中。 在其它实施方案中，载体被并入免疫原性组合物中。载体也可用于非有丝分裂细胞分离细胞的离体转染或离体转导等方法。

    Lentiviral vectors for the preparation of immunotherapeutical compositions
    8.
    发明授权
    Lentiviral vectors for the preparation of immunotherapeutical compositions 有权
    用于制备免疫治疗组合物的慢病毒载体

    公开(公告)号：US08349606B2

    公开(公告)日：2013-01-08

    申请号：US13104380

    申请日：2011-05-10

    申请人： Pierre Charneau ,  Hüseyin Firat ,  Véronique Zennou

    发明人： Pierre Charneau ,  Hüseyin Firat ,  Véronique Zennou

    IPC分类号： C12N15/00 ,  A61K39/12 ,  C12Q1/70

    CPC分类号： C12N15/867 ,  A61K48/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/57 ,  C07K14/35 ,  C12N15/86 ,  C12N2740/16043 ,  C12N2740/16134 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203

    摘要： The invention relates to an immunogenic composition comprising a recombinant vector characterized in that it comprises a polynucleotide comprising the cis-acting central initiation region (cPPT) and the cis-acting termination region (CTS), these regions being of retroviral or retroviral-like origin, said vector comprising in addition a defined nucleotide sequence (transgene or sequence of interest) and regulatory signals of retrotranscription, expression and encapsidation of retroviral or retroviral-like origin, wherein the composition is capable of inducing or of stimulating a cell-mediated response for instance a CTL (Cytotoxic T Lymphocytes) response or a CD4 response, against one or several epitopes encoded by the transgene sequence present in the vector.

    摘要翻译： 本发明涉及包含重组载体的免疫原性组合物，其特征在于其包含包含顺式作用中枢起始区（cPPT）和顺式作用终止区（CTS）的多核苷酸，这些区域是逆转录病毒或逆转录病毒样起源 所述载体另外包含定义的核苷酸序列（转基因或感兴趣的序列）以及逆转录病毒或逆转录病毒样起源的逆转录，表达和壳化的调控信号，其中所述组合物能够诱导或刺激细胞介导的应答 例如针对由载体中存在的转基因序列编码的一个或多个表位的CTL（细胞毒性T淋巴细胞）应答或CD4应答。

    Lentiviral vectors for the preparation of immunotherapeutical compositions
    10.
    发明授权
    Lentiviral vectors for the preparation of immunotherapeutical compositions 有权
    用于制备免疫治疗组合物的慢病毒载体

    公开(公告)号：US07968332B2

    公开(公告)日：2011-06-28

    申请号：US10313038

    申请日：2002-12-06

    申请人： Pierre Charneau ,  Hüseyin Firat ,  Véronique Zennou

    发明人： Pierre Charneau ,  Hüseyin Firat ,  Véronique Zennou

    IPC分类号： C12N15/00 ,  A61K39/12 ,  C12Q1/70

    CPC分类号： C12N15/867 ,  A61K48/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/57 ,  C07K14/35 ,  C12N15/86 ,  C12N2740/16043 ,  C12N2740/16134 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203

    摘要： The invention relates to an immunogenic composition comprising a recombinant vector characterized in that it comprises a polynucleotide comprising the cis-acting central initiation region (cPPT) and the cis-acting termination region (CTS), these regions being of retroviral or retroviral-like origin, said vector comprising in addition a defined nucleotide sequence (transgene or sequence of interest) and regulatory signals of retrotranscription, expression and encapsidation of retroviral or retroviral-like origin, wherein the composition is capable of inducing or of stimulating a cell-mediated response for instance a CTL (Cytotoxic T Lymphocytes) response or a CD4 response, against one or several epitopes encoded by the transgene sequence present in the vector.

    摘要翻译： 本发明涉及包含重组载体的免疫原性组合物，其特征在于其包含包含顺式作用中枢起始区（cPPT）和顺式作用终止区（CTS）的多核苷酸，这些区域是逆转录病毒或逆转录病毒样起源 所述载体另外包含定义的核苷酸序列（转基因或感兴趣的序列）以及逆转录病毒或逆转录病毒样起源的逆转录，表达和壳化的调控信号，其中所述组合物能够诱导或刺激细胞介导的应答 例如针对由载体中存在的转基因序列编码的一个或多个表位的CTL（细胞毒性T淋巴细胞）应答或CD4应答。