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    Method of using adenoviral vectors with increased persistence in vivo
    1.
    发明申请
    Method of using adenoviral vectors with increased persistence in vivo 审中-公开
    使用体内持续性增加的腺病毒载体的方法

    公开(公告)号：US20060140909A1

    公开(公告)日：2006-06-29

    申请号：US11208405

    申请日：2005-08-19

    申请人： Thomas Wickham ,  Masaki Akiyama ,  Jason Gall

    发明人： Thomas Wickham ,  Masaki Akiyama ,  Jason Gall

    IPC分类号： A61K48/00 ,  C12N15/861

    CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/405 ,  C12N2810/50

    摘要： The invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises slowly releasing into the bloodstream a dose of replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes. The normalized average bloodstream concentration of the adenovirus over 24 hours post-administration is at least about 1%. Alternatively, the normalized average bloodstream concentration over 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector. A method of destroying tumor cells in a mammal also is provided, as is a replication-deficient adenoviral vector comprising a serotype 5 or serotype 35 adenoviral genome with a serotype 41 fiber protein, wherein the replication-deficient adenoviral vector exhibits reduced native binding to integrins.

    摘要翻译： 本发明提供了在哺乳动物中表达外源核酸的方法。 该方法包括缓慢释放一定剂量的复制缺陷型或条件复制型腺病毒载体，其具有降低转导间皮细胞和肝细胞的能力。 给药后24小时内腺病毒的归一化平均血流浓度为至少约1％。 或者，给药后24小时内的标准化平均血流浓度比相当剂量的野生型腺病毒载体的归一化平均血流浓度高至少约5倍。 还提供了破坏哺乳动物肿瘤细胞的方法，以及包含血清型5或具有血清型41纤维蛋白的血清型35腺病毒基因组的复制缺陷型腺病毒载体，其中复制缺陷型腺病毒载体表现出降低的天然与整联蛋白结合 。

    Adenoviral vector-based vaccines
    4.
    发明申请
    Adenoviral vector-based vaccines 审中-公开
    基于腺病毒载体的疫苗

    公开(公告)号：US20060286121A1

    公开(公告)日：2006-12-21

    申请号：US11337866

    申请日：2006-01-23

    申请人： Jason Gall ,  Thomas Wickham ,  William Enright ,  Douglas Brough ,  Mohammed Zuber ,  C. King ,  Gary Nabel ,  Cheng Cheng

    发明人： Jason Gall ,  Thomas Wickham ,  William Enright ,  Douglas Brough ,  Mohammed Zuber ,  C. King ,  Gary Nabel ,  Cheng Cheng

    IPC分类号： A61K39/12 ,  A61K39/395

    CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K2039/5256 ,  C07K2319/00 ,  C12N2710/10343 ,  C12N2710/10345

    摘要： The invention provides a method of inducing an immune response in a mammal. The method comprises administering to the mammal a non-subgroup C adenoviral vector comprising an adenoviral fiber protein having an amino acid sequence comprising about 80% or more identity to an amino acid sequence encoding a subgroup C adenoviral fiber protein. The adenoviral vector further comprises a nucleic acid sequence encoding an antigen which is expressed in the mammal to induce an immune response. The invention further comprises a method of producing an adenoviral vector, and a composition comprising a serotype 41 or a serotype 35 adenoviral vector and a carrier. The invention also provides an adenoviral vector comprising a nucleic acid sequence encoding an adenoviral pIX protein operably linked to a heterologous expression control sequence, as well as a method of enhancing the stability and/or packaging capacity of an adenoviral vector.

    摘要翻译： 本发明提供在哺乳动物中诱导免疫应答的方法。 该方法包括向哺乳动物施用非亚组C腺病毒载体，其包含具有与编码亚组C腺病毒纤维蛋白的氨基酸序列具有约80％或更高同一性的氨基酸序列的腺病毒纤维蛋白。 腺病毒载体还包含编码在哺乳动物中表达以诱导免疫应答的抗原的核酸序列。 本发明还包括产生腺病毒载体的方法和包含血清型41或血清型35腺病毒载体和载体的组合物。 本发明还提供了一种腺病毒载体，其包含编码与异源表达控制序列可操作地连接的腺病毒pIX蛋白的核酸序列，以及增强腺病毒载体的稳定性和/或包装能力的方法。

    METHOD OF USING ADENOVIRAL VECTORS WITH INCREASED IMMUNOGENICITY IN VIVO
    7.
    发明申请
    METHOD OF USING ADENOVIRAL VECTORS WITH INCREASED IMMUNOGENICITY IN VIVO 审中-公开
    使用腺病毒载体在体内具有增加的免疫原性的方法

    公开(公告)号：US20080069836A1

    公开(公告)日：2008-03-20

    申请号：US11678947

    申请日：2007-02-26

    申请人： Gary Nabel ,  Cheng Cheng ,  Jason Gall ,  Thomas Wickham

    发明人： Gary Nabel ,  Cheng Cheng ,  Jason Gall ,  Thomas Wickham

    IPC分类号： A61K39/00 ,  A61P37/04 ,  C12N15/63

    CPC分类号： C12N15/86 ,  A61K39/00 ,  C12N2710/10343 ,  Y02A50/412

    摘要： The invention provides a method of inducing an immune response in a mammal. The method comprises administering to the mammal an adenoviral vector comprising (a) a subgroup C fiber protein wherein a native coxsackievirus and adenovirus receptor (CAR)-binding site is disrupted, (b) a subgroup C penton base protein wherein a native integrin-binding site is disrupted, and (c) a nucleic acid sequence encoding at least one antigen derived from an infectious agent other than an adenovirus which is expressed in the mammal to induce an immune response.

    摘要翻译： 本发明提供在哺乳动物中诱导免疫应答的方法。 该方法包括向哺乳动物施用腺病毒载体，其包含（a）亚组C纤维蛋白，其中天然柯萨奇病毒和腺病毒受体（CAR）结合位点被破坏，（b）亚基C戊聚糖碱基蛋白，其中天然整联蛋白结合 位点被破坏，和（c）编码至少一种来源于哺乳动物中表达的腺病毒以外的感染因子的抗原以诱导免疫应答的核酸序列。

    Cancer Treatments with Radiation and Immunocytokines
    9.
    发明申请
    Cancer Treatments with Radiation and Immunocytokines 审中-公开
    癌症治疗与放射和免疫细胞因子

    公开(公告)号：US20100330029A1

    公开(公告)日：2010-12-30

    申请号：US12603363

    申请日：2009-10-21

    申请人： Thomas Wickham ,  Ulrike Gnad-Vogt ,  Sylvia Holden ,  Stephan G. Klinz ,  Karl-Josef Kallen

    发明人： Thomas Wickham ,  Ulrike Gnad-Vogt ,  Sylvia Holden ,  Stephan G. Klinz ,  Karl-Josef Kallen

    IPC分类号： A61K38/20 ,  A61P35/00 ,  A61P37/04

    CPC分类号： A61K38/2013 ,  A61K38/208 ,  A61N5/10

    摘要： The present invention is directed to a method for treating tumors and cancer cells by administering an immunocytokine following radiation treatment. This combination of treatments can stimulate an immune response at irradiated and non-irradiated sites, which is useful in eradicating cancer cells that have spread from the site of the primary tumor. In addition, immunocytokines can be administered at a dose that is less that the maximum tolerated dose, which reduces the side effects associated with immunocytokine therapy.

    摘要翻译： 本发明涉及通过在放射治疗后施用免疫细胞因子来治疗肿瘤和癌细胞的方法。 这种治疗组合可以刺激照射和非照射部位的免疫应答，这对于根除从原发肿瘤部位扩散的癌细胞是有用的。 此外，免疫细胞因子可以以小于最大耐受剂量的剂量施用，这降低了与免疫细胞因子疗法相关的副作用。