Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or... – Inactivation or attenuation; producing viral subunits
Patent
1994-11-02
1997-02-11
Housel, James C.
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
Inactivation or attenuation; producing viral subunits
4241841, 4242111, 4242141, 4242151, 4242221, 4242291, 4242331, 435239, C12N 704
Patent
active
056020236
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to pharmaceutical products containing stabilized, live virus for the therapy of viral diseases and malignancies and to the process for the production of such products. The present invention also relates to a purified virus vaccine and the purification procedure therefor.
Hungarian Patents #197 517 and #197 846 describe the use of certain live, apathogenic viruses in the therapy of various human diseases of vital origin. Thus, patent #197 517 provides a pharmaceutical product containing attenuated Newcastle disease virus suitable for the therapy of herpes, rabies, AIDS and malignancies. Patent #197 846 describes a pharmaceutical product containing attenuated Gumboro virus suitable for the treatment of hepatitis, rabies, and other diseases of viral origin and malignancies. Although both Gumboro and Newcastle disease viruses cause poultry diseases, the vaccines containing these attenuated viruses are in commercial use. The above patents describe the therapeutic application of these vaccines.
Since the purity of veterinary vaccines do not meet human purity requirements, infections and complications may result as untoward side effects. Moreover, the stability of veterinary vaccines may also be poor. The present invention is intended to provide a process to obtain purified, apathogenic viruses suitable for human therapy as well as a lyophilized product which is stable for long periods without apparent loss of effectiveness.
Recently, it has been found that other apathogenic viruses can also be used in the therapy of human diseases of vital origin. It has been proven, according to the present invention, that any attenuated virus apathogenic for humans can be used, alone or in combination, in the treatment of viral diseases. These may be veterinary, in particular, fowl viruses, or human viruses; e.g.; arian paramyxovirus, avian herpesvirus, avian rotavirus, avian bronchitis, avian encephalitis, avian bursitis (Gumboro) virus, Marek's disease virus, parvovirus, Newcastle disease virus as well as human paramyxovirus, human parvovirus and human adenovirus.
The invention relates to attenuated viruses apathogenic to humans which are effective in the treatment of diseases of viral origin and malignancies, e.g., as follows: AIDS, carcinoma of the rectum, bladder, breast, colon, cervix, esophagus, pancreas, bronchus, liver, kidney and stomach, gynecological cancers, head and neck cancers, lymphomas, malignant melanoma, myeloma, immune deficiency due to irradiation, multiple sclerosis, influenza, common cold and related diseases of viral origin, herpes genitalis and labialis, warts, collagen diseases, acute and chronic hepatitis (B and C), and symptoms following bone marrow transplantation.
The viruses suitable for the above therapeutic purposes may be obtained as usual, e.g., from fibroblast or other cell line cultures or allanto-amniotic fluid of egg embryos. The allanto-amniotic fluid can be obtained from infected hen eggs. The fluid is purified by centrifugation and the supernatant is pelleted by ultracentrifuge. The sediment is rehydrated and sedimented over sucrose gradient, ultracentrifuged again and the pellet is rehydrated and lyophilized.
In a preferred embodiment of the invention the allantois fluid is centrifuged by approximately 5000.times. g, the pellet is discarded and the supernatant is used (if necessary a filtration step can be included). The virus is pelleted from this supernatant by ultracentrifugation (the ultracentrifugation depends on the r.p.m. and time, and may vary over a wide range, usually 35,000.times. g for 1 hour). The supernatant is discarded and the pellet is resuspended in a small volume of buffer solution. For appropriate homogeneity a relative longer period of mixing is required.
This homogeneous suspension is layered over a high concentration of sucrose and ultracentrifuged at 90,000-100,000.times. g (minimal g: 60,000). The supernatant is discarded and the pellet is rehydrated and lyophilized.
Another object of the invention is stabilization of the virus p
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Friedman Stuart J.
Housel James C.
Masood Khalid
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