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    • 22. 发明授权
    • Noninvasive genetic immunization, expression products therefrom and uses thereof
    • 无创遗传免疫,其表达产物及其用途
    • US06348450B1
    • 2002-02-19
    • US09563826
    • 2000-05-03
    • De-chu C. TangDonald H. MarksDavid T. CurielZhongkai ShiKent Rigby van Kampen
    • De-chu C. TangDonald H. MarksDavid T. CurielZhongkai ShiKent Rigby van Kampen
    • A61K4800
    • A61K39/08A61K39/00A61K39/0011A61K39/12A61K39/145A61K48/00A61K2039/53A61K2039/54A61K2039/541A61K2039/542A61K2039/543A61K2039/55555A61K2039/60C12N2710/10343C12N2760/16134
    • Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, tetanus toxin C-fragment, anthrax protective antigen, HIV gp 120, human carcinoembryonic antigen, and/or a therapeutic, an immunomodulatory gene, such as co-stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector.
    • 公开和要求的是在动物中非侵入性遗传免疫的方法和/或在动物中诱导全身性免疫或治疗反应的方法,其产品及其用途。 所述方法可以包括使动物的皮肤与有效诱导动物体内免疫或治疗反应的量的载体接触。 载体可以包括并表达编码感兴趣的表位或基因产物的外源核酸分子。 全身免疫应答可以来自表位或基因产物。 核酸分子可以编码感兴趣的表位和/或感兴趣的抗原和/或刺激和/或调节免疫应答和/或刺激和/或调节表达的核酸分子,例如转录和/或翻译 ,例如内源和/或外源核酸分子的转录和/或翻译; 例如流感血凝素,流感核蛋白,破伤风毒素C片段,炭疽保护性抗原,HIV gp120,人癌胚抗原和/或治疗性免疫调节基因中的一种或多种,​​例如共刺激基因和/或 细胞因子基因。 可以通过在动物细胞中表达核酸分子的载体诱导免疫应答。 免疫应答可以针对病原体或肿瘤。 预防性疫苗或治疗性疫苗或免疫组合物可以包括载体。
    • 23. 发明授权
    • Ligands added to adenovirus fiber
    • 配体添加到腺病毒纤维中
    • US06312699B1
    • 2001-11-06
    • US08218369
    • 1994-03-28
    • David T. CurielJeffrey A. Engler
    • David T. CurielJeffrey A. Engler
    • A61K3923
    • C12N15/86A61K48/00C07K14/005C07K2319/00C12N15/87C12N2710/10322C12N2710/10343C12N2810/40
    • The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or strepavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence. The modified fiber protein is prepared by genetic engineering of the nucleotide sequence encoding the fiber protein, through the addition of new sequence at the carboxyl tail-encoding region which encodes the linker and the ligand. The N-terminus of the fiber protein is not altered in the preferred embodiment, although in some embodiments it may be desirable to inhibit uptake by the nucleus of the fiber protein, by deletion of nuclear targeting signals. The modified fiber protein can be utilized as part of a recombinant adenovirus for use in gene therapy.
    • 腺病毒的纤维蛋白已经通过在肽接头的羧基末端的连接被遗传改变,优选长达26个氨基酸长度,其形成无规卷曲,其可用于附着非腺病毒配体,其改变结合特异性 纤维蛋白。 配体的实例包括被靶细胞选择性结合以使经修饰的纤维蛋白质被受体介导的内吞作用内化的肽,以及可以作为通用偶联剂例如生物素或链霉亲和素的肽。 接头被设计成不干扰纤维蛋白质的正常三聚,以避免纤维蛋白质与靶细胞结合的空间位阻,并用作引入新肽序列的位点。 通过在编码接头和配体的羧基尾编码区添加新序列,通过编码纤维蛋白的核苷酸序列的遗传工程来制备修饰的纤维蛋白。 在优选的实施方案中,纤维蛋白质的N末端没有改变,尽管在一些实施方案中,可能需要抑制纤维蛋白质的细胞核的摄取,通过核靶向信号的缺失。 修饰的纤维蛋白可用作用于基因治疗的重组腺病毒的一部分。
    • 26. 发明授权
    • Methods for modulating protein function in cells using, intracellular
antibody homologues
    • 使用细胞内抗体同系物调节细胞中蛋白质功能的方法
    • US5910486A
    • 1999-06-08
    • US468252
    • 1995-06-06
    • David T. CurielJessy Deshane
    • David T. CurielJessy Deshane
    • A61K48/00C07K16/32
    • C07K16/32A61K2039/505A61K48/00C07K2317/622C12N2799/022
    • Methods and compositions for modulating protein function in a cell involving intracellular expression of an antibody homologue that binds to the protein within the cell are disclosed. In a preferred embodiment, an antibody homologue, such as a single chain Fv (sFv) fragment, is expressed within an intracellular compartment of a cell, such as the endoplasmic reticulum (ER), to inhibit cell surface expression of a membrane protein. Preferably, the cell is a malignant mammalian cell and the protein is a cell surface receptor oncoprotein, such as c-erbB2. Intracellular binding of the antibody homologue to the receptor oncoprotein inhibits its surface expression and, moreover, inhibits cell proliferation and cell survival. Isolated nucleic acid molecules encoding anti-c-erbB2 antibody homologues, as well as recombinant expression vectors and host cells incorporating these nucleic acid molecules, are also disclosed.
    • 公开了涉及在细胞内与蛋白质结合的抗体同系物的细胞内表达的细胞中调节蛋白质功能的方法和组合物。 在优选的实施方案中,抗体同系物,例如单链Fv(sFv)片段在细胞的细胞内隔室(例如内质网(ER))内表达,以抑制膜蛋白的细胞表面表达。 优选地,细胞是恶性哺乳动物细胞,并且蛋白质是细胞表面受体癌蛋白,例如c-erbB2。 抗体同源物与受体癌蛋白的细胞内结合抑制其表面表达,此外抑制细胞增殖和细胞存活。 还公开了编码抗c-erbB2抗体同系物的分离的核酸分子,以及重组表达载体和掺入这些核酸分子的宿主细胞。
    • 29. 发明授权
    • Ligands added to adenovirus fiber
    • 配体添加到腺病毒纤维中
    • US06683170B2
    • 2004-01-27
    • US09904599
    • 2001-07-13
    • David T. CurielJeffrey A. Engler
    • David T. CurielJeffrey A. Engler
    • C07H2104
    • C12N15/86A61K48/00C07K14/005C07K2319/00C12N15/87C12N2710/10322C12N2710/10343C12N2810/40
    • The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or strepavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence.
    • 腺病毒的纤维蛋白已经通过在肽接头的羧基末端的连接被遗传改变,优选长达26个氨基酸长度,其形成无规卷曲,其可用于附着非腺病毒配体,其改变结合特异性 纤维蛋白。 配体的实例包括被靶细胞选择性结合以使经修饰的纤维蛋白质被受体介导的内吞作用内化的肽,以及可以作为通用偶联剂例如生物素或链霉亲和素的肽。 接头被设计成不干扰纤维蛋白质的正常三聚,以避免纤维蛋白质与靶细胞结合的空间位阻,并用作引入新肽序列的位点。