CA2096888C - Process for the inactivation of viruses in preparations of proteins - Google Patents
Process for the inactivation of viruses in preparations of proteins Download PDFInfo
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- CA2096888C CA2096888C CA002096888A CA2096888A CA2096888C CA 2096888 C CA2096888 C CA 2096888C CA 002096888 A CA002096888 A CA 002096888A CA 2096888 A CA2096888 A CA 2096888A CA 2096888 C CA2096888 C CA 2096888C
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
- A61L2/0023—Heat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/04—Heat
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
- C12N7/04—Inactivation or attenuation; Producing viral sub-units
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16661—Methods of inactivation or attenuation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32611—Poliovirus
- C12N2770/32661—Methods of inactivation or attenuation
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention relates to a process for the inactivation of viruses in a solution of proteins by brief heating.
Description
~~~a~~~
BEHFdIIdGWERICB ARTIENGESF~~.LSCHAE'T 92/B 013J - Ma 924 Dr. Ha/hg Process for the inactivation of viruses in preparations Of proteins The invention relates to a process for the inactivation of viruses in preparations of proteins. To do this, a solution of the preparation of a protein is briefly heated.
Proteins within the meaning of the invention are placen-tal proteins, gleams proteins, proteins from cell cul-tures or from microbial fermentations. An example of a protein of this type is tissue thromboplastin.
The reagents employed for the Quick determination of the prothrombin time contain tissue thromboplastin as active constituent. The prothrombin time is an important screen ing test in the diagnosis of coagulation disorders.
In addition, the therapeutic use of tissue thromboplastin as FVIII bypassing agent has been suggested for the treatment of hemophiliacs with inhibitors. The virus safety of the preparation is an indispensable pre-requisite for this use. However, virus safety is also required on use of tissue thromboplastin as diagnostic aid, having regard to the preservation of the health of the user.
At present, tissue thromboplastins for preparing pro-thrombin time reagents are normally obtained from brain or placenta of mammals. Contaminations by viruses such as HBV, HCV, HIV fox preparations of human origin or by the agent causing BSE in the case of cattle cannot in prin-ciple be ruled out with preparations of this type. This means that a process for virus inactivation in tissue thromboplastin preparations has great importance.
~r~.3 ~ ~ ~.~ i~6 ~ ~~
BEHFdIIdGWERICB ARTIENGESF~~.LSCHAE'T 92/B 013J - Ma 924 Dr. Ha/hg Process for the inactivation of viruses in preparations Of proteins The invention relates to a process for the inactivation of viruses in preparations of proteins. To do this, a solution of the preparation of a protein is briefly heated.
Proteins within the meaning of the invention are placen-tal proteins, gleams proteins, proteins from cell cul-tures or from microbial fermentations. An example of a protein of this type is tissue thromboplastin.
The reagents employed for the Quick determination of the prothrombin time contain tissue thromboplastin as active constituent. The prothrombin time is an important screen ing test in the diagnosis of coagulation disorders.
In addition, the therapeutic use of tissue thromboplastin as FVIII bypassing agent has been suggested for the treatment of hemophiliacs with inhibitors. The virus safety of the preparation is an indispensable pre-requisite for this use. However, virus safety is also required on use of tissue thromboplastin as diagnostic aid, having regard to the preservation of the health of the user.
At present, tissue thromboplastins for preparing pro-thrombin time reagents are normally obtained from brain or placenta of mammals. Contaminations by viruses such as HBV, HCV, HIV fox preparations of human origin or by the agent causing BSE in the case of cattle cannot in prin-ciple be ruled out with preparations of this type. This means that a process for virus inactivation in tissue thromboplastin preparations has great importance.
~r~.3 ~ ~ ~.~ i~6 ~ ~~
To date, attempts at virus inactivation by established processes (detergents, hypochlorite, UV/gamma irradiation etc.) have failed because of the great sensitivity of the preparations. In particular, all attempts at pasteur ization or dry heating have been unsuccessful.
It has emerged, surprisingly, that a brief heating, for example in an apparatus disclosed in Chem.-Ing.-Tech. 62 (1990), 486~487 (German Patent Application 39 05 066), has no adverse effect on the properties of tissue thromboplastin but, on the other hand, completely inacti-vates viruses. In the known processes for virus inacti-vation (pasteurization, "dry heating"), heating is customarily carried out for at least one minutes, but usually for several hours.
The invention relates to a process for the inactivation of viruses in a preparation of a protein from the group of placental proteins, plasma proteins or proteins prepared in cell culture or microbially, which comprises heating a solution of this preparation for a short time.
Heating is carried out with indirect heating in a heat exchanger. Suitable heat exchangers have any desired type of construction, such as plate exchangers or tubular exchangers.
A heat exchanger as disclosed in German Patent Appli-ration 39 05 066 is particularly suitable because, while the heat transfer coefficient is high, a short residence time and a lower wall temperature is possible.
This heat exchanger is a heat exchange module composed of stacked metal foils with spacers arranged between them, 3U the metal foils being composed of metal cards which are provided with at least 2 openings on each of the opposite sides, the spacers being composed of fabric cards with GT,; F1 F1, ja S~ ( I
~' ' ~ '..1~ c~ ~? C~ CI
It has emerged, surprisingly, that a brief heating, for example in an apparatus disclosed in Chem.-Ing.-Tech. 62 (1990), 486~487 (German Patent Application 39 05 066), has no adverse effect on the properties of tissue thromboplastin but, on the other hand, completely inacti-vates viruses. In the known processes for virus inacti-vation (pasteurization, "dry heating"), heating is customarily carried out for at least one minutes, but usually for several hours.
The invention relates to a process for the inactivation of viruses in a preparation of a protein from the group of placental proteins, plasma proteins or proteins prepared in cell culture or microbially, which comprises heating a solution of this preparation for a short time.
Heating is carried out with indirect heating in a heat exchanger. Suitable heat exchangers have any desired type of construction, such as plate exchangers or tubular exchangers.
A heat exchanger as disclosed in German Patent Appli-ration 39 05 066 is particularly suitable because, while the heat transfer coefficient is high, a short residence time and a lower wall temperature is possible.
This heat exchanger is a heat exchange module composed of stacked metal foils with spacers arranged between them, 3U the metal foils being composed of metal cards which are provided with at least 2 openings on each of the opposite sides, the spacers being composed of fabric cards with GT,; F1 F1, ja S~ ( I
~' ' ~ '..1~ c~ ~? C~ CI
openings which are coincident with the metal cards so that the openings form tubular channels when the cards are stacked, the encircling rim of the fabric cards and an annular area of the fabric which encloses some of the openings being filled with sealing agent, there being alternation of the openings with and without sealing agent in a row of a fabric card and in the case of the tubular channels.
The heating temperature can be between +45°C and +95°C, but preferably between +65°C and ~0°C.
In order that the fed-in liquid can be heated in the minimum time to the particular heating temperature and subsequently cooled down again in the same time, the apparatus in which heating is carried out is expediently equipped with a connector each for heating medium and cooling medium.
The constructional design of the heat exchangers ought to be such that the difference between the heating temper-ature for the solution and the temperature of the heating medium is a minimum, which results in minimum damage to the product because of the low wall temperature resulting therefrom.
The heating and/or cooling time should be less than seconds, but preferably less than 5 seconds. The dwell 25 time can be between 0.1 and 20 s, but preferably between 0.5 and 5 seconds.
The protein, preparation can be, for example, a therapeu tic agent containing tissue thromboplastin, or a diag nostic agent containing tissue thromboplastin, for 30 example a prothrombin time reagent.
In the following example, the virus inactivation by brief heating is shown, without limiting the invention, by the 2~J~°~U
The heating temperature can be between +45°C and +95°C, but preferably between +65°C and ~0°C.
In order that the fed-in liquid can be heated in the minimum time to the particular heating temperature and subsequently cooled down again in the same time, the apparatus in which heating is carried out is expediently equipped with a connector each for heating medium and cooling medium.
The constructional design of the heat exchangers ought to be such that the difference between the heating temper-ature for the solution and the temperature of the heating medium is a minimum, which results in minimum damage to the product because of the low wall temperature resulting therefrom.
The heating and/or cooling time should be less than seconds, but preferably less than 5 seconds. The dwell 25 time can be between 0.1 and 20 s, but preferably between 0.5 and 5 seconds.
The protein, preparation can be, for example, a therapeu tic agent containing tissue thromboplastin, or a diag nostic agent containing tissue thromboplastin, for 30 example a prothrombin time reagent.
In the following example, the virus inactivation by brief heating is shown, without limiting the invention, by the 2~J~°~U
example of RThromborel S, a prothrombin time reagent con-taining tissue thromboplastin from human placenta of Behringwerke AG. The success of the inactivation was examined. Complete virus inactivation was found at a heating temperature above 45°C, preferably at least 65°C.
The diagnostic properties of the briefly heated reagent were compared with those of untreated aThromborel S. No disadvantageous changes in these properties were observed at least up to a heating temperature of 75°C.
Example Procedure for the brief heating For this, two heat exchangers (W 1.1 and W 1.2, Fig. 1) were mounted in a common fixing device which essentially corresponds to commercially available ultrafiltration cassette holders. The heat exchangers had a modular ' construction and were separated from one another by a specially constructed spacer plate.
This made it possible to connect the heat exchangers in such a way that the fed-in liquid was heated to the particular heating temperature within 2 seconds and subsequently cooled down again in the same time. For this purpose, the apparatus was equipped with a connector each for heating medium and cooling medium. The dwell time at the said heating temperature was about 1.5 seconds.
Before the process started, the entire system on the product side was flushed with water and heated to the operating temperature. For this, the pump P1 (Fig. 1) transported heating medium through the system until the required heating temperature was reached. It was then changed from water to the solution to be heated, and in control tests the pump P2 was subsequently switched on to meter the virus suspension. Samples were taken before heating and after the experimentally determined minimum test time of 20 or 48 seconds.
The diagnostic properties of the briefly heated reagent were compared with those of untreated aThromborel S. No disadvantageous changes in these properties were observed at least up to a heating temperature of 75°C.
Example Procedure for the brief heating For this, two heat exchangers (W 1.1 and W 1.2, Fig. 1) were mounted in a common fixing device which essentially corresponds to commercially available ultrafiltration cassette holders. The heat exchangers had a modular ' construction and were separated from one another by a specially constructed spacer plate.
This made it possible to connect the heat exchangers in such a way that the fed-in liquid was heated to the particular heating temperature within 2 seconds and subsequently cooled down again in the same time. For this purpose, the apparatus was equipped with a connector each for heating medium and cooling medium. The dwell time at the said heating temperature was about 1.5 seconds.
Before the process started, the entire system on the product side was flushed with water and heated to the operating temperature. For this, the pump P1 (Fig. 1) transported heating medium through the system until the required heating temperature was reached. It was then changed from water to the solution to be heated, and in control tests the pump P2 was subsequently switched on to meter the virus suspension. Samples were taken before heating and after the experimentally determined minimum test time of 20 or 48 seconds.
Results of the virus iaaactivatioa (Table 1j As a control, a solution of tissue thromboplastin was passed at room temperature through the system. The results show that a virus inactivation of more than 5 powers of ten was achieved in all tests on the coat-free and heat-resistant poliovirus. The inactivation was likewise eomplete in the case of the herpesvirus BSA-1.
The inactivation was examined for 2 different initial titers (about 3.5 and 5.0) and was complete in both case.
By contrast, in the control experiment, virus inacti-vation was undetectable or only low.
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w ~ M o0 6n ,-~ eo ~~ ~ ~r p . . .
o O M 6n N M 6n 6ri M u1 .~~~g ~u 611 v-1 O O O O O O O O
M 6n V V V V V V V Y
AN
.a acs .-a t~ u1 .-~ ~a ~ O ~' a . . . o . o . .
M 6n M Lf1 If1 M !C1 !d1 M 611 4a -U
C ~ hN N ~ 1NC ~ o O Oh 1u1., ~'x~
N
O
.-I O .-1 O O ~ O O r-1 O
. . . . . . . . .
p 1C h 1D p h 10 00 h 6D h ri n OaD Ca0 Op0 O ~ ~ O Op0 ~ Oa0 'd' d' d' 01 e9~ e9~ CI1 e1' sr a n I
.L1 N N N N N N 117 u1 N N
H H H
0 .~ .; t3 ~ ~ n rj .0 ~,~3~~~?~c~
Comparison of briefly heated with untreated tissue thromboplastin RThromborel S was briefly heated at various temperatures in the above system without metering in virus suspension.
Untreated material served as control. All the prepar ations were freeze-dried and reconstituted before testing in the same volume of distilled water. The results which are presented below were obtained with a representative batch.
To construct the reference plots (k'ig. 2 ) , standard human plasma from Uehringwerke AG was employed undiluted and diluted with isotonic sodium chloride solution as sample.
Sample (100 ~l) and reagent (200 ~1) were mixed and the clotting time was measured in a Schnitger & Gross coagulometer. The reference plots for heated and untreated RThromborel S are essentially identical.
The sensitivity of prothrombin time reagents is expressed by ISI (international sensitivity index). The ISI values for heated and untreated RThromborel S, determined on plasma from healthy subjects and subjects undergoing oral anticoagulation, compared with a reference thromboplastin are indistinguishable (Tab. 2).
Table 2 International Sensitivity Index Determination 1 Determination Control 1.09 1.09 65C 1.12 1.09 75C 1.10 1.12 80C I 1.10 1.10 A~ ~i l.) To characterise the sensitivity of heated and untreated RThromborel S to the coagulation factors II, V, VTT and X, standard human plasma was mixed with the appropriate coagulation factor-deficient plasma from Behringwerke AG
to adjust the activities of the relevant factor to between 5 and 100 of normal. The clotting times of the mixtures (100 ~cl) were determined after additions of 200 ~cl of heated or untreated ~Thromborel S in a Schnitger & Gross coagulometer. The clotting time is plotted against the content of factor II and F VII, respectively, as a percentage of normal in Fig. 3 and 4p this revealed that the sensitivity to the tested factors was as good as for the control. The sensitivities for factor V and factor X (snot shown) were indistinguishable within the accuracy of measurement.
The inactivation was examined for 2 different initial titers (about 3.5 and 5.0) and was complete in both case.
By contrast, in the control experiment, virus inacti-vation was undetectable or only low.
~~~r)~ ~' I
w ~ M o0 6n ,-~ eo ~~ ~ ~r p . . .
o O M 6n N M 6n 6ri M u1 .~~~g ~u 611 v-1 O O O O O O O O
M 6n V V V V V V V Y
AN
.a acs .-a t~ u1 .-~ ~a ~ O ~' a . . . o . o . .
M 6n M Lf1 If1 M !C1 !d1 M 611 4a -U
C ~ hN N ~ 1NC ~ o O Oh 1u1., ~'x~
N
O
.-I O .-1 O O ~ O O r-1 O
. . . . . . . . .
p 1C h 1D p h 10 00 h 6D h ri n OaD Ca0 Op0 O ~ ~ O Op0 ~ Oa0 'd' d' d' 01 e9~ e9~ CI1 e1' sr a n I
.L1 N N N N N N 117 u1 N N
H H H
0 .~ .; t3 ~ ~ n rj .0 ~,~3~~~?~c~
Comparison of briefly heated with untreated tissue thromboplastin RThromborel S was briefly heated at various temperatures in the above system without metering in virus suspension.
Untreated material served as control. All the prepar ations were freeze-dried and reconstituted before testing in the same volume of distilled water. The results which are presented below were obtained with a representative batch.
To construct the reference plots (k'ig. 2 ) , standard human plasma from Uehringwerke AG was employed undiluted and diluted with isotonic sodium chloride solution as sample.
Sample (100 ~l) and reagent (200 ~1) were mixed and the clotting time was measured in a Schnitger & Gross coagulometer. The reference plots for heated and untreated RThromborel S are essentially identical.
The sensitivity of prothrombin time reagents is expressed by ISI (international sensitivity index). The ISI values for heated and untreated RThromborel S, determined on plasma from healthy subjects and subjects undergoing oral anticoagulation, compared with a reference thromboplastin are indistinguishable (Tab. 2).
Table 2 International Sensitivity Index Determination 1 Determination Control 1.09 1.09 65C 1.12 1.09 75C 1.10 1.12 80C I 1.10 1.10 A~ ~i l.) To characterise the sensitivity of heated and untreated RThromborel S to the coagulation factors II, V, VTT and X, standard human plasma was mixed with the appropriate coagulation factor-deficient plasma from Behringwerke AG
to adjust the activities of the relevant factor to between 5 and 100 of normal. The clotting times of the mixtures (100 ~cl) were determined after additions of 200 ~cl of heated or untreated ~Thromborel S in a Schnitger & Gross coagulometer. The clotting time is plotted against the content of factor II and F VII, respectively, as a percentage of normal in Fig. 3 and 4p this revealed that the sensitivity to the tested factors was as good as for the control. The sensitivities for factor V and factor X (snot shown) were indistinguishable within the accuracy of measurement.
Claims (4)
1. A process for the inactivation of viruses in a preparation of a protein selected from the group consisting of placental proteins, plasma proteins, proteins prepared in cell culture and proteins prepared by microbes, which comprises indirectly heating a solution of the protein preparation in a heat exchanger at a temperature between +65°C and +80°C with a heating and cooling time of 2 seconds and a dwell time between 0.1 and 20 seconds.
2. The process as claimed in claim 1, wherein a solution of tissue thromboplastin is heated.
3. The process as claimed in claim 1 or 2, wherein the dwell time is between 0.5 and 5 seconds.
4. The process as claimed in any one of claims 1-3, wherein heating is carried out in a heat exchange module composed of stacked metal foils with spacers arranged between them, the metal foils being composed of metal cards which are provided with a least 2 openings on each of the opposite sides, the spacers being composed of fabric cards with openings which are coincident with the metal cards so that the openings form tubular channels when the metal cards and the fabric cards are stacked, the encircling rim of the fabric cards and an annular area of the fabric which encloses some of the openings being filled with sealing agent, there being alternation of the opening with and without sealing agent in a row of a fabric card and in the case of the tubular channels.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4217355.8 | 1992-05-26 | ||
| DE4217355 | 1992-05-26 | ||
| DE4240103A DE4240103A1 (en) | 1992-05-26 | 1992-11-28 | Process for inactivating viruses in protein preparations |
| DEP4240103.8 | 1992-11-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2096888A1 CA2096888A1 (en) | 1993-11-27 |
| CA2096888C true CA2096888C (en) | 2004-04-27 |
Family
ID=25915149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002096888A Expired - Fee Related CA2096888C (en) | 1992-05-26 | 1993-05-25 | Process for the inactivation of viruses in preparations of proteins |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0571771B2 (en) |
| JP (1) | JP3650410B2 (en) |
| KR (1) | KR940005805A (en) |
| AT (1) | ATE194648T1 (en) |
| AU (1) | AU3876793A (en) |
| CA (1) | CA2096888C (en) |
| DE (2) | DE4240103A1 (en) |
| ES (1) | ES2149791T5 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180119084A1 (en) * | 2015-04-20 | 2018-05-03 | Ge Healthcare Bio-Sciences Corp. | Inactivation of Viruses |
| US11052165B2 (en) | 2015-04-20 | 2021-07-06 | Global Life Sciences Solutions Usa Llc | Method for virus clearance |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19720853A1 (en) | 1997-05-17 | 1998-11-19 | Dade Behring Marburg Gmbh | Increasing the FVII sensitivity of a thromboplastin reagent |
| NL1016029C2 (en) * | 2000-08-28 | 2002-03-01 | Gelatine Smits Beheer B V | Method of eliminating disease causing agents by applying heating. |
| IL155935A0 (en) * | 2000-11-24 | 2003-12-23 | Breath Ltd | A method of sterilizing a pharmaceutical composition |
| US10323494B2 (en) | 2015-07-23 | 2019-06-18 | General Electric Company | Hydrocarbon production system and an associated method thereof |
| US10047596B2 (en) | 2015-07-23 | 2018-08-14 | General Electric Company | System and method for disposal of water produced from a plurality of wells of a well-pad |
| US10077646B2 (en) | 2015-07-23 | 2018-09-18 | General Electric Company | Closed loop hydrocarbon extraction system and a method for operating the same |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3473407D1 (en) * | 1983-05-02 | 1988-09-22 | Immuno Ag | Method of inactivating pathogens |
| US4695454A (en) * | 1985-04-01 | 1987-09-22 | New York Blood Center, Inc. | Process for preparing hepatitis B surface antigen containing particles in novel forms which are highly immunogenic |
| IE81149B1 (en) * | 1987-02-12 | 2000-05-03 | Genentech Inc | Methods and deoxyribonucleic acid for the preparation of tissue factor protein |
| DE3905066A1 (en) * | 1989-02-18 | 1990-08-23 | Behringwerke Ag | HEAT EXCHANGER MODULE |
| FR2664165B1 (en) * | 1990-07-03 | 1992-10-16 | Lille Transfusion Sanguine | COMPOSITION FOR STABILIZING BLOOD PLASMA DURING PASTEURIZATION. |
-
1992
- 1992-11-28 DE DE4240103A patent/DE4240103A1/en not_active Withdrawn
-
1993
- 1993-04-28 ES ES93106848T patent/ES2149791T5/en not_active Expired - Lifetime
- 1993-04-28 AT AT93106848T patent/ATE194648T1/en not_active IP Right Cessation
- 1993-04-28 DE DE59310073T patent/DE59310073D1/en not_active Expired - Lifetime
- 1993-04-28 EP EP93106848A patent/EP0571771B2/en not_active Expired - Lifetime
- 1993-05-24 KR KR1019930008933A patent/KR940005805A/en not_active Application Discontinuation
- 1993-05-25 JP JP12248093A patent/JP3650410B2/en not_active Expired - Fee Related
- 1993-05-25 AU AU38767/93A patent/AU3876793A/en not_active Abandoned
- 1993-05-25 CA CA002096888A patent/CA2096888C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180119084A1 (en) * | 2015-04-20 | 2018-05-03 | Ge Healthcare Bio-Sciences Corp. | Inactivation of Viruses |
| US11052165B2 (en) | 2015-04-20 | 2021-07-06 | Global Life Sciences Solutions Usa Llc | Method for virus clearance |
| US11274274B2 (en) | 2015-04-20 | 2022-03-15 | Global Life Sciences Solutions Usa Llc | Inactivation of viruses |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2149791T3 (en) | 2000-11-16 |
| CA2096888A1 (en) | 1993-11-27 |
| KR940005805A (en) | 1994-03-22 |
| AU3876793A (en) | 1993-12-02 |
| ATE194648T1 (en) | 2000-07-15 |
| EP0571771B2 (en) | 2004-10-20 |
| EP0571771A3 (en) | 1994-07-06 |
| EP0571771A2 (en) | 1993-12-01 |
| DE59310073D1 (en) | 2000-08-17 |
| EP0571771B1 (en) | 2000-07-12 |
| DE4240103A1 (en) | 1993-12-02 |
| ES2149791T5 (en) | 2005-05-16 |
| JP3650410B2 (en) | 2005-05-18 |
| JPH0665091A (en) | 1994-03-08 |
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