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    Method for producing influenza virus and vaccine
    4.
    发明授权
    Method for producing influenza virus and vaccine 失效
    生产流感病毒和疫苗的方法

    公开(公告)号：US5698433A

    公开(公告)日：1997-12-16

    申请号：US684729

    申请日：1996-07-22

    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： C07K14/005 ,  A61K39/12 ,  A61K39/145 ,  A61K39/15 ,  A61K39/245 ,  C12N7/00 ,  A61K2039/5252 ,  A61K2039/55505 ,  A61K39/00 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16151 ,  C12N2760/16234

    摘要： A method of producing an influenza virus and vaccines derived from the virus utilizes cultured vertebrate biomass aggregates comprising a plurality of cell types derived from a plurality of vertebrate tissues and is particularly suitable for use with chicken embryo cultures. The method both eliminates the necessity to use costly methods requiring whole chicken embryos and provides proteases suitable for the activation of a wide variety of viruses. After infecting the cells of the culture with an influenza virus, which is preferably modified to create a cleavage site in the hemagglutinin of the virus, a substance such as a protease is introduced that cleaves the hemagglutinin. The culture then is incubated under conditions that permit growth of the virus. The method provides also for the augmentation of virus activation in the culture by the continuous or batchwise removal of culture media, treatment of the media with substances such as proteases which increase cellular activation, attenuation of any undesired effects of the augmentation and return of the augmented media to the culture. The vaccines produced from the harvested virus therefore are free of egg proteins and are much more economical to produce. The methodology of the present invention allows the large scale continuous production of many viruses to a high titre.

    摘要翻译： 生产流感病毒的方法和源自病毒的疫苗利用培养的脊椎动物生物质聚集体，其包含多种衍生自多个脊椎动物组织的细胞类型，并且特别适用于鸡胚培养。 该方法既消除了使用需要全部鸡胚胎的昂贵方法的必要性，并提供了适用于激活各种病毒的蛋白酶。 在用流感病毒感染培养物的细胞后，其优选被修饰以在病毒的血凝素中产生切割位点，引入了裂解血凝素的诸如蛋白酶的物质。 然后将培养物在允许病毒生长的条件下孵育。 该方法还用于通过连续或分批地去除培养基来增加培养物中的病毒活化，用诸如增加细胞活化的蛋白酶的物质处理培养基，减少增加的任何不期望的影响和增加的 媒体对文化。 因此，从收获的病毒产生的疫苗不含蛋蛋白，并且生产更经济。 本发明的方法允许大规模连续生产许多病毒到高滴度。

    Method for controlling the infectivity of viruses
    5.
    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。

    Method for producing viruses and vaccines in serum-free culture
    6.
    发明授权
    Method for producing viruses and vaccines in serum-free culture 失效
    在无血清培养中生产病毒和疫苗的方法

    公开(公告)号：US5753489A

    公开(公告)日：1998-05-19

    申请号：US487046

    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 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16151 ,  C12N2760/16162 ,  C12N2760/16163

    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。