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    Perfusion system and a method for the large scale production of virus or virus antigen
    1.
    发明授权
    Perfusion system and a method for the large scale production of virus or virus antigen 失效
    灌注系统和大规模生产病毒或病毒抗原的方法

    公开(公告)号：US5719051A

    公开(公告)日：1998-02-17

    申请号：US357292

    申请日：1994-12-13

    申请人： Wolfgang Mundt ,  Noel Barrett ,  Friedrich Dorner ,  Johann Eibl

    发明人： Wolfgang Mundt ,  Noel Barrett ,  Friedrich Dorner ,  Johann Eibl

    IPC分类号： A61K39/12 ,  C12N7/02 ,  C12N7/01

    CPC分类号： C12N7/00 ,  A61K39/12 ,  C12N2531/00 ,  C12N2770/24134 ,  C12N2770/24151

    摘要： The invention resides in a matrix, i.e. in a carrier material, with human or animal cells adherently bound thereto, the cells being infected with virus. It has shown that surface-dependent cells suitable for virus propagation remain adherently bound to a matrix even in the virus-infected state, continuously produce virus antigen over relatively long periods of time and deliver them into the culture medium. For producing TBE virus antigen by growing tick-borne encephalitis (TBE) virus in cell cultures, a surface-dependent permanent cell line, preferably the Vero cell line ATCC CCL 81, is inoculated with TBE virus, and the cells are kept bound to carriers in a non-lyric serum-free system while maintaining the cell growth, so as to maintain antigen formation, whereupon the antigen-containing medium is separated form the carrier-bound cells and, in a known manner, is processed to a galencially acceptable preparation by concentration, inactivation and purification.

    摘要翻译： 本发明涉及一种基质，即在载体材料中，与人或动物细胞贴壁结合，细胞被病毒感染。 已经表明，即使在病毒感染状态下，适用于病毒传播的表面依赖性细胞仍保持与基质结合，在相对长的时间内连续产生病毒抗原并将其输送到培养基中。 为了通过在细胞培养物中生长蜱传导性脑炎（TBE）病毒来生产TBE病毒抗原，表面依赖的永久性细胞系（优选Vero细胞系ATCC CCL 81）用TBE病毒接种，并且细胞保持与载体结合 在保持细胞生长的同时，在非抒情的无血清系统中，从而保持抗原形成，由此将含抗原的培养基从载体结合的细胞分离，并以已知的方式加工成半衰期可接受的制剂 通过浓缩，灭活和纯化。

    Method for controlling the infectivity of viruses
    9.
    发明授权
    Method for controlling the infectivity of viruses 失效
    控制病毒感染性的方法

    公开(公告)号：US5756341A

    公开(公告)日：1998-05-26

    申请号：US483522

    申请日：1995-06-07

    申请人： Otfried Kistner ,  Noel Barrett ,  Wolfgang Mundt ,  Friedrich Dorner

    发明人： Otfried Kistner ,  Noel Barrett ,  Wolfgang Mundt ,  Friedrich Dorner

    IPC分类号： A61K39/00 ,  A61K39/145 ,  A61K39/15 ,  A61K39/245 ,  C07K14/11 ,  C12N7/00 ,  C12N7/02

    CPC分类号： A61K39/145 ,  A61K39/12 ,  A61K39/245 ,  C07K14/005 ,  C12N7/00 ,  A61K2039/5252 ,  A61K2039/55505 ,  A61K39/00 ,  C12N2500/90 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16163 ,  C12N2760/16222 ,  C12N2760/16234 ,  C12N2760/16251 ,  C12N2760/16261 ,  C12N2760/16263

    摘要： A method for producing Influenza and other viruses and vaccines derived therefrom utilizes serum-free cultured vertebrate cells or vertebrate biomass aggregates to both eliminate the necessity to use costly methods requiring whole chicken embryos and, optionally, to provide proteases suitable for the activation of a wide variety of viruses. In one aspect, the method comprises the periodic or continuous removal of "treatment portions" of virus-containing culture medium into an "augmentation loop" for treatment with a broad range of substances, such as proteases that augment the activation of the virus. Use of the loop allows utilization of such substances at high concentrations while eliminating their cell toxic effects. Another aspect of the invention provides for the alteration of cleavage sites in virus proteins to thereby render them more susceptible to activation in culture. Thus, the method provides for the high yield production of many viruses that can be easily scaled up to continuous large scale production volumes and for resultant vaccines which are free of egg proteins and are much more economical to produce.

    摘要翻译： 用于生产流感和其他病毒的方法及其衍生的疫苗利用无血清培养的脊椎动物细胞或脊椎动物生物质聚集体，以消除使用需要全部鸡胚胎的昂贵方法的必要性，并且任选地提供适于激活广泛的蛋白酶 各种病毒。 在一个方面，该方法包括将含有病毒的培养基的“处理部分”定期或连续地移除到用于增加病毒活化的广泛范围的物质例如蛋白酶的“增加环”中。 循环使用可以高浓度地利用这些物质，同时消除它们的细胞毒性作用。 本发明的另一方面提供了病毒蛋白中切割位点的改变，从而使得它们更容易受到培养中的活化。 因此，该方法提供了可以容易地扩大到连续大规模生产体积的许多病毒的高产量生产以及没有蛋蛋白并且生产更经济的所得疫苗。