Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or... – Inactivation or attenuation; producing viral subunits
Reexamination Certificate
1999-07-30
2002-06-04
Lankford, Jr., Leon B. (Department: 1651)
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
Inactivation or attenuation; producing viral subunits
C435S236000, C435S235100
Reexamination Certificate
active
06399356
ABSTRACT:
The invention relates to a process and an agent for the sanitization of contamination caused by viruses in cell cultures or tissues and of materials and equipment which can be contaminated with viruses. This contamination can be known (studies in virology) or unknown (studies with, for example, noninfected cell cultures or with tissue/organ explants from healthy humans or animals).
It is known that when working with human pathogenic viruses such as HIV, HBV or HCV, serious diseases such as AIDS or hepatitis can occur in the case of transfer to a sensitive recipient. This danger is particularly great in investigation and research laboratories in which work with human pathogenic viruses is carried out. In addition, the cell cultures available there can be an ideal nutrient medium for the replication of viruses and the viruses can be easily spread from one medium to another if it is not possible to reliably sanitize used materials and equipment again after virus contamination has taken place. During organ transplantation, viruses present in the organ can be transferred to the recipient of the transplant; on account of the avoidance of rejection reactions for immunosuppression of the recipient, which is customary and brought about medicinally, a virus infection which has taken place in this manner can lead to serious disorders. A particular type of organ transplantation is blood transfusion, which as is known can lead to the transfer of viruses.
In addition to physical sanitization processes, chemical sanitization processes have also already been proposed. A particularly frequently discussed chemical process is the SD (solvent/detergent) method. It is suitable for inactivating coated viruses, i.e. viruses which are surrounded by a lipid-containing membrane, but has the crucial disadvantage of being completely ineffective against all known uncoated viruses. For reasons of safety, there is therefore a great need to make available chemical sanitization processes which also reliably inactivate uncoated viruses.
In European patent application 0 720 851, a process for the inactivation of viruses with the aid of acridine or acridine derivatives, preferably in combination with benzalkonium chloride, has already been described, which can be carried out in the presence of proteins whose biological activity is not significantly impaired thereby. There is, however, furthermore a high need for agents which are able to eliminate contaminations caused by viruses selectively in tissues or cell cultures so that these can then be available again in a clean condition and can yield unadulterated investigation and research results. At the same time, there is a need for the sanitization of materials and equipment used in virology in order that no virus transfers from one medium to another can take place by means of them. Surprisingly, it has now been found that the differing requirements in the sanitization of a cell culture contaminated by viruses and the materials and equipment used in virology can be fulfilled by one and the same agent.
The invention relates to a process for the sanitization of contaminations caused by viruses in tissues or cell cultures, and of materials and equipment used in virology or in the production of biological materials, whose starting materials can be contaminated with viruses, in which for sanitization a solution of a substituted phenol or of a substituted phenol ether is used, which as substituents can carry one or two saturated or unsaturated hydrocarbon radicals which in each case can have up to 4 carbon atoms. The process mentioned can also be employed for the sanitization of organ transplants or in blood transfusions and plasma donations and other blood constituents or cellular blood components.
The substituted phenols or substituted phenol ethers employed in the process according to the invention have such a wide spectrum of action that they can be effectively employed not only against coated, but also against uncoated viruses. The phenolic compound employed here is preferably a compound from the group consisting of eugenol, isoeugenol, thymol, carvacrol, carvacrol methyl ether and menthol.
The phenolic compounds mentioned are dissolved in a suitable solvent, for example in a mixture of ethanol and water, in the ratio 1:10 to 10:1 and added to the contaminated cell culture in a total amount of less than 0.1% by weight, based on the contaminated substrate. The same solution, however, is also outstandingly suitable for sanitizing laboratory equipment contaminated with viruses, in particular chromatography columns and resins. In general, for the elimination of the virus contamination a solution is employed which contains the active compound in a concentration of 0.1 g/l to 0.001 g/l. The sanitization is preferably carried out at a temperature of 2 to 70° C. and at a pH of 5 to 9. A temperature range from 20 to 60° C. is very particularly preferred. In this temperature range, even after a time of action of only 10 minutes, the beginning of sanitization of the contaminated substrate can be detected. A satisfactory sanitization, however, usually requires a period of time of 2 to 6 hours, which only exceptionally has to be extended to up to 24 hours.
In general, it is not necessary to remove residual amounts of the substituted phenol or phenol ether after sanitization has been carried out. Should this be necessary, however, known methods are available for this, for example absorption on active carbon, dialysis or chromatographic processes.
A particular advantage of the process according to the invention for the sanitization of contaminations caused by viruses is the preservation to the greatest extent of the cell cultures or treated with it. The biological activities of the cell cultures or are not adversely affected thereby. The sanitization agent according to the invention has already exhibited its activity against retro-, toga-, flavi-, picorna-, herpes-, adeno-, reo-, influenza, parainfluenza, calici-, corona- or astroviruses.
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European Search Report for Appln. No. 99114405.6-2110, Nov. 25, 1999.
Bernhardt Dieter
Gröner Albrecht
Aventis Behring GmbH
Finnegan, Henderson Farabow, Garrett and Dunner L.L.P.
Lankford , Jr. Leon B.
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