Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or... – Recovery or purification
Reexamination Certificate
1998-07-23
2001-02-27
Lankford, Jr., Leon B. (Department: 1651)
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
Recovery or purification
C435S235100, C210S660000, C536S118000
Reexamination Certificate
active
06194192
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a simple and convenient process for treating virus which is applicable in the area of research and pharmaceuticals is also directed to a series of inventions related thereto.
2. Description of the Related Art
Many diseases in mice, cattle, birds, monkeys and human being, etc. are caused by various viruses. An example of the representative virus diseases in human being is influenza and, in recent years, acquired immune deficiency syndrome (AIDS) induced by HIV (human immunodeficiency virus) which is a kind of retrovirus that has become a social problem.
On the other hand, as a development of genetic engineering, various virus vectors for introducing exogenous gene into cells have been developed. As viral vectors for introducing genes into cells of mammals including human being, vectors derived from retrovirus, adenovirus, adeno-associated virus, etc. have been practically used already and, further, a gene therapy as a remedy for human diseases utilizing said art has now been put to practical use. In addition, a means where exogenous gene introduced in insects or insect cells utilizing baculovirus is expressed to produce desired protein in large quantities has been receiving public attention.
Vaccine is one of the means for prevention and therapy of diseases caused by virus. Attenuated virus prepared by inactivating treatment of wild type virus or virus where pathogenicity is lowered and a part of constituting components of virus (such as surface protein of virus) are used as vaccine but, usually, purified virus is used as a material for the manufacture of such a vaccine. Therefore, a process for purification of virus which is applicable in an industrial scale and is highly reliable is needed.
It is necessary that the virus which is used as a vector for introducing the gene into cell keeps a sufficient purity and/or concentration and a simple and convenient process for purification and concentration of virus has a high practical value.
Further, blood for transfusion and pharmaceutical agents such as preparations derived blood may contain virus with which the blood donor was infected and there is a possibility that administration of such an agent to patients induces a viral infection. Contamination of such virus is a very serious problem in therapy and, if at all possible, such virus is to be removed completely. For such a purpose, some treatments for inactivating virus such as by heating the blood or the preparation at 60-80° C. are conducted but heating treatment may inactivate the components which are less stable to heat contained in said pharmaceutical agent and, accordingly, there has been a demand for developing milder and more effective process for removing the virus.
An object of the present invention is to offer an effective process for purifying and removing the virus which is applicable under the various situations as mentioned above and also to offer purified virus, a substance wherefrom virus is removed, and a virus-adsorbing carrier.
SUMMARY OF THE INVENTION
The present invention will be summarized to be as follows. Thus, the first feature of the present invention relates to a process for the purification of virus and is characterized in containing a step where the virus in a virus-containing sample is adsorbed with sulfated-fucose-containing polysaccharide(s) and/or degradation product(s) thereof.
The second feature of the present invention relates to a process for the removal of virus and is characterized in containing a step where the virus in the virus-containing sample is adsorbed with sulfated-fucose-containing polysaccharide(s) and/or degradation product(s) thereof.
The third feature of the present invention relates to a purified virus which is obtained by the process of the first feature and the fourth feature relates to a product where the virus is removed which is obtained by the process of the second feature.
Further, the fifth feature of the present invention relates to a carrier for adsorption of virus containing sulfated-fucose-containing polysaccharide(s) and/or degradation product(s) thereof.
The present inventors have conducted an intensive investigation for finding a process where only virus is isolated and purified or only virus is removed from a virus-containing material by a simple means and have found that sulfated-fucose-containing polysaccharide(s) and/or degradation product(s) thereof have/has a high affinity to various viruses and that the use of an affinity carrier containing the sulfate-fucose-containing polysaccharide or a degraded product thereof is capable of purifying or removing the virus by simple operations and, moreover, in high purity and recovery rate whereupon the present invention has been achieved.
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K. Tamayose et al., “A new strategy for large-scale preparation of high-titer recombinant adeno-associated virus vectors by using packaging cell lines and sulfonated cellulose”, Human Gene Therapy, vol. 7, pp. 507-513, Mar. 1, 1996.
P.F O'Neil et al., “Virus Harvesting and Affinity-Based Liquid Chromatography”, Bio/Technology, vol. 11, pp. 173-178, Feb. 1993.
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Asada Kiyozo
Hashino Kimikazu
Kato Ikunoshin
Ueno Takashi
Lankford , Jr. Leon B.
Takara Shuzo Co. Ltd.
Wenderoth , Lind & Ponack, L.L.P.
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