WO2005022148A1 - Methode de titrage in vitro d’un atnc et son application a une methode d’evaluation et/ou de controle d’un procede d’obtention d’un produit biologique - Google Patents
Methode de titrage in vitro d’un atnc et son application a une methode d’evaluation et/ou de controle d’un procede d’obtention d’un produit biologique Download PDFInfo
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- WO2005022148A1 WO2005022148A1 PCT/FR2004/002179 FR2004002179W WO2005022148A1 WO 2005022148 A1 WO2005022148 A1 WO 2005022148A1 FR 2004002179 W FR2004002179 W FR 2004002179W WO 2005022148 A1 WO2005022148 A1 WO 2005022148A1
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- atnc
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
Definitions
- the present invention relates to a method for in vitro titration of an unconventional transmissible agent (ATNC) using transgenic cell lines, its application to a method of evaluation and / or in vitro control of the efficiency of a method for obtaining or treating a biological product or one or more steps of such a process for the removal of an NCTA and its application to a method of evaluation and / or in vitro control of a decontamination procedure.
- ATNC unconventional transmissible agent
- TSEs Transmissible spongiform encephalopathies
- CNS central nervous system
- PrP prion protein
- PrPsc This abnormal pathogenic form of PrP, called PrPsc, results from a conformational change in the prion protein PrP.
- mice whose gene encoding PrPsc has been inactivated are very strongly resistant to experimental infection.
- mice and cell cultures expressing (or overexpressing) pathological transgenes, cloned from the PrP gene of subjects suffering from familial EST, or xeno-genes mimic the corresponding hereditary diseases or are sensitive to an innoculum.
- blood proteins such as cryoprecipitable plasma proteins (factor VIII, von Willebrand factor etc.). These would indeed be completely destroyed by known methods to reduce infectivity, for example in the presence of 1M NaOH. Since obtaining or processing biological products, such as plasma coagulation proteins, must incorporate viral elution / inactivation steps for use. therapeutic, the pharmaceutical industry of blood-derived drugs is now seeking to assess the theoretical risk of transmission of variant CJD by blood products. It is therefore necessary to develop a sensitive, specific and rapid titration method that can be used to evaluate the degree of elimination of the NCTA that can be provided by a step or a succession of steps implemented in the process.
- the method conventionally used uses an in vivo titration method with a sensitive line of golden hamsters, by intracerebral injection of different dilutions of a test product loaded with pathogenic prion.
- an infectious titer can be calculated and the reduction quotient of a given method can be calculated from an untreated reference.
- this method has the disadvantage of being long, expensive and not compatible with a development on an industrial scale which we want to quickly know the effectiveness vis-à-vis the elimination of the prion.
- ATNC-related infectivity assays are performed by intracerebral inoculation of laboratory animals, such as rodents that previously allowed adaptation of EST strains infecting other animal species, or transgenic mice expressing PrP. of the same species as the. source of infectivity.
- Some authors have compared the detection limit of immunochemical PrPsc detection techniques with that of in vivo and in vitro techniques (inoculation of transgenic cell cultures) for diagnostic purposes.
- US Pat. No. 6,150,583 in which transgenic animals expressing the labeled epitope PrP are provided.
- the techniques for detecting infectious agents can be done directly, such as in vitro and in vivo infectivity assay, and indirectly by the polymerase chain reaction steps.
- the evaluation of direct versus indirect techniques is a prerequisite for their experimental use for regulatory purposes.
- the Applicant has surprisingly shown, despite the still important lack of knowledge of the behavior of NCTAs, that the use of transgenic cell lines supporting the replication of DNA an ATNC allows the development of a titration method of this ATNC.
- This titration method may in particular be used for purposes of validating the effectiveness, with respect to the elimination of the considered NCTA, of processes for obtaining or treating biological products, such as, for example , proteins derived from the fractionation of blood plasma, foods, cosmetics or, more generally, any product presenting an environmental risk (for example animal meal). It can also be used to evaluate the effectiveness of equipment decontamination procedures, such as chromatography columns.
- the application of the titration method of an NCTA according to
- the invention allows the determination of the absolute titre of ATNC present in a biological matrix.
- ATNC represents any ATNC, such as those responsible in humans for familial or sporadic CJD, Kuru disease, or CJD variant found in young subjects, or those responsible for sheep scrapie or bovine or feline spongiform encephalopathy.
- the invention thus relates to a method of in vitro titration of an ATNC in a biological product susceptible to be infected by this ATNC, characterized in that stable transgenic cells supporting the replication of said ATNC are brought into contact with the sample. and then cultured during one or more passages to amplify the amount of NCTA present in said biological product by replication of said ATNC.
- transgenic cell line for implementing the invention, also meeting the requirements and criteria defined below, makes it possible to meet the need to quantify the infectivity associated with NCTAs over a range of about 4. log, that is, from 1 to 10,000 infectious units in vitro. This may, for example, make it possible to satisfy the criteria for validating the efficiency of the processes for obtaining biological products with respect to the elimination of NCTAs.
- the use of such transgenic cell lines in the titration method according to the invention has many advantages, in particular that of considerably reducing the duration of the quantification of an ATNC present in the biological product, the results of the titration method according to the invention. the invention being correctly correlated with the in vivo reference methods.
- transgenic cell lines are established by combination. of a specific cell type and a particular transgene, by known techniques, necessary to provide an ideal environment for replication of the ATNC.
- Vilette et al. PNAS, March 2001, 98 (7), 4055-4059 have shown that transgenic and stable rabbit epithelial cells, expressing ovine PrP (transgene), are able to replicate ovine PrPsc after infection with extracts containing Sheep PrPsc.
- Such stable transgenic cells supporting the replication of an ATNC are likely to be used in the titration method according to the invention.
- Archer et al. (Journal of Virology, Jan. 2004, pp. 482-490) have constructed another type of stable cell line supporting replication of PrPsc.
- Their model consists of murine glial cells expressing ovine PrP and supporting replication of ovine PrPsc, MovS cells. These cells have proved to be particularly satisfactory in the titration method according to the invention.
- the transgenic cell line is advantageously used as a substrate for the in vitro titration of ATNC. These criteria are as follows: the adequacy between the replication rate or multiplication of the cells and the incubation time necessary to demonstrate an increase in PrPsc in the infected cells; the stability of the cells after they have come into contact with the infectious agent which can be demonstrated by the absence of cytotoxicity of the accumulation of PrPsc in the cells; their good sensitivity to infection, for example a low multiplicity of infection to obtain an accumulation of PrPsc in the cells exposed to the infectious agent.
- the stable transgenic cells supporting the replication of the ATNC are brought into contact, by methods known per se, with the biological product likely to be infected by this ATNC or with an infectious material containing the ATNC in as reference material.
- the infectious material represents an infectious biological material derived in particular from extracts of brains of animals infected with an NCTA, such as cattle or sheep. These cells are then cultured during one or more passages to allow the ATNC to replicate.
- a "passage" is the transplanting of a portion of the cells of one culture dish into another box containing new culture medium. Each passage therefore dilutes the cells that no longer have room to divide into another box and the time of culture in a box allows the NCTA to replicate.
- the transgenic cells may be brought into contact with at least one dilution of the biological product that may be infected with the ATNC in an aqueous solution.
- biologically acceptable in particular with several dilutions, especially with serial or successive dilutions. These dilutions make it possible to refine the quantification of infectivity in the sample tested.
- Several replicates of transgenic cells may be contacted with the same dilution of the biological product.
- the ATNC is detected at each passage, in particular by an immunochemical method known to those skilled in the art, especially by Western Blot or ELISA.
- the step of culturing stable transgenic cells potentially infected with the biological product is required for the replication of the ATNC so to amplify a quantity of ATNC insufficient to be detected by conventional methods (ELISA, Western-Blot).
- the ATNC titrated by the method according to the invention is the pathogenic prion protein PrPsc, ovine, bovine or human.
- the set of Western-blot results for the different dilutions and the different replicates can be analyzed by a statistical method known to those skilled in the art for establishing an infectious titer, such as for example the Spearman Kàrber method (Schmidt NJ , Emmous RW, Diagnosis Procedures for Viral, Rickettsial and Chlaveydial Infection, 1989, 6th Edition).
- the stable transgenic cells are rabbit epithelial cells, in particular rabbit epithelial cells of the Rov9 line (Vilette et al.) Or murine glial cells, in particular murine glial cells of the MovS6 line (Archer et al. ) .
- the biological product likely to be contaminated by an NCTA is selected from the group consisting of blood products and their derivatives, foods, cosmetics and any product presenting a risk to the environment.
- the invention also relates to the application of the titration method according to the invention to a method of evaluation and / or in vitro control of a process for obtaining or treating a biological product likely to be contaminated with an unconventional transmissible agent (NCTA).
- NCTA unconventional transmissible agent
- the titration method according to the invention has the capacity to be easily applicable to any type of process for obtaining or purifying biological products, in particular blood products, such as blood plasma derivatives, using chromatographies or nanofiltration, in particular the chromatographies described in patent EP 0 359 593 and in patent application WO 02092632.
- the implementation of the titration method according to the invention makes it possible to evaluate and / or to control the effectiveness of a process (or part of a process) for obtaining or treating, or even purifying, any biological product, which may be contaminated by an NCTA, in the elimination of this ATNC, by means of a titration using specific transgenic cell lines, promoting the replication of the ATNC, brought into contact with an infectious or potentially infectious material containing the ATNC to be tested.
- the amounts of NCTA are measured upstream and downstream of the process (or part of the process) whose performance with respect to the NCTA is to be assessed. By comparing the two measurements, the degree of elimination of the pathogen is determined.
- the implementation of the present method can be carried out during a process obtaining a biological product or in the context of an elimination treatment of the NCTA according to obtaining the biological product.
- the invention also relates to the application of the titration method according to the invention to a method of evaluation and / or in vitro control of a procedure for decontaminating a material.
- the ATNC titre of a biological product containing an NCTA is determined using the titration method of the invention.
- This infected biological product is then contacted with the material to be decontaminated and the decontamination procedure is applied to this material.
- the title of the biological product having undergone the decontamination procedure is again determined.
- the two titration measurements performed upstream and downstream of the decontamination procedure are compared to evaluate the effectiveness of the decontamination procedure.
- the ATNC-containing biological product is derived, for example, from brain extracts of animals infected with NCTA, such as cattle or sheep.
- the material may, for example, be a purification material, in particular a chromatography column.
- the decontamination procedure may, for example, be the sanitization of a chromatography column using sodium hydroxide.
- EXAMPLE 1 Titration of Cell Culture-Related NTDA Infectivity
- MovS6 cells (Archer F. et al., 2004) were selected as cells. supporting the replication of the ATNCs, and the Scrapie strain PG127 adapted to the Tg301 transgenic mice was used as a source of infectivity (Vilotte JL et al., Journal of Virology, Vol 75, No 13, p.5977-5984, 2001).
- the inoculum consisted of a brains homogenate of infected mice at 100 mg / ml.
- the cells were cultured in DMEM + HamF-12 supplemented with glutaine and fetal calf serum.
- the titration plates were prepared 24 hours before inoculation. Cells were seeded at 40,000 cells per well for a 96-well format (Experiment No. 1), and 100,000 cells for 24-well plates (Experiment Nos. 2 and 3). Serial dilutions of the mouse brain homogenate were prepared with culture medium, the dilution steps were 10 to 10 (Experiments # 1 and # 2), or 5 to 5 (Experiment # 3). . For each dilution of the inoculum, 5 wells of culture plate were infected.
- the cells were contacted with a certain volume of inoculum (50 to 150 ⁇ l) for a period of 12 hours to 4 days.
- Table 1 summarizes the experimental conditions for inoculation and cell expansion specific to each experiment.
- the inoculum was discarded and replaced with new culture medium and then the cells were kept in culture until the first passage during which a culture plate format change was made in order to keep half (experiment # 1), or all infected cells (Experiments 2 and 3).
- the culture medium was changed once a week and the cells transplanted with a ratio of 1 in 10, making it possible to perform analyzes on 90% of the cells at each passage.
- the labeled membranes were revealed by chemiluminescence. A sample was considered positive if the electrophoretic profile of the three forms of glycosylated PrPsc was visible on the autoradiogram.
- negative controls uninfected MovS ⁇ cells
- All the wells of culture plates were tested. When all the replicates of cell cultures inoculated with a given dilution of the inoculum were found to be positive for the PrPsc during two successive passages, these cultures were no longer tested during the following passages.
- the titre of a sample was calculated at the end of the cell culture by Spearman Kârber's method (Schmidt NJ and Emmons RW, Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infection 1989, 6th.
- Table 2 summarizes the results obtained in experiment no. 2, and again shows the evolution of the percentage of positivity of each of the replicates of the infected culture by each dilution of the inoculum (from 10 -3 to 10-7). It can be seen that the time to onset of PrPsc in cultures is inversely proportional to the infectivity dose with which the cultures were inoculated. Thus, the cultures having received the 10 -3 dilution of the • noculum had PrP sc from passage 2, whereas it was necessary to wait for an additional passage so that 100% of the cultures having received the dilution 10 were positive. The inoculum titre calculated for this experiment was 5.5 TCID 50 / ml. Table 2. Results of the titration experiment n ° 2.
- Table 3 summarizes the results obtained in the experiment No. 3.
- no dilution of the inoculum was reduced to 1/5, and dilutions tested were 10 ⁇ ⁇ 10 ⁇ 6/8 # L ⁇ maximum titre was obtained in passage 6, and the calculated titre was 6.43 TCID50 / ml.
- the system meets the current requirements for limiting tests with laboratory animals in favor of cell culture substitution methods, for example.
- the proposed system can be implemented in a P2 laboratory, unlike animal testing, which requires more expensive and more complex P3 laboratory confinement.
- EXAMPLE 2 Calculation of a Reduction Factor Associated with a Purification Step of a Biological Medicine Which could be Contaminated by an NCTA
- a nanofiltration step was chosen as an example of a step of a production process.
- the filter chosen was a PLANOVA 15 N (ASAHI ASEI) filter with a porosity of 15 nm and a surface area of 0.01 m.
- the product to be filtered chosen was human albumin at 0.2 g / l, in 0.01 M trisodium citrate dihydrate buffer, 0.12 M glycine, L-lysine (monochloride) 0.016 M, calcium chloride dihydrate 0.001 M, 0.17 M sodium chloride, osmolarity 490-510 mosmol / kg, pH 6.90-7.10.
- the nanofiltration was carried out at a pressure of 500 ⁇ 100 mbar at 25 ° C.
- the filter was balanced before nanofiltration of the product with 40 ml of dilution buffer of human albumin.
- the product to be filtered experimentally overloaded was prepared in sufficient quantity to take an aliquot to quantify the infectivity present in the product before nanofiltration.
- a total volume of about 40 ml of filtrate was recovered downstream of the nanofiltration, and titrated to determine the amount of infectivity in the product after nanofiltration.
- the experimental overloaded starting material and the filtered product were diluted 1/3 in culture medium before being stored at -80 ° C while waiting for their titration.
- the samples were titrated according to the experimental conditions of Experiment No. 3 described in the first example.
- Table 4 summarizes the titration results of the four samples generated during this nanofiltration experiment. Samples of overloaded starting material had titres of 4.67 log TCID50 / mL for tests 1 and 2. No residual infectivity was detected in the filtrate samples.
- the loading of these samples was calculated according to the Poisson's Law at 0.28 log TCID50 / ml from the volume of the smallest dilution of the inoculated sample.
- the total charge presents in the samples were calculated by multiplying their charge by their respective volume, and the reduction factor was calculated by dividing the feedstock present in the starting material, or initial sample, before the nanofiltration by that present in the filtrates. Clearance factors were calculated from the calculated amount of infectivity added in the experimental overload.
- the difference between the clearance factor and the reduction factor makes it possible to demonstrate, when it is greater than one log, the interference of the starting material with the ability of the titration system to detect infectivity in this product. Table 5 summarizes these calculations.
- the reduction factors associated with the elimination of infectivity present in the brain seed used to overload the starting material were> 4.24 and> 4.22 log for trials 1 and 2, respectively. No interference from the starting material was demonstrated by the calculation of clearance factors.
- a calculated from the total load in the experimental overload.
- b calculated from the initial load measured in the starting material.
- c volume taking into account the removal of the aliquot fraction intended for the titration of the initial sample.
- d no infectivity detected: detection limit calculated by Poisson 's law.
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Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES04786344T ES2374816T3 (es) | 2003-08-25 | 2004-08-23 | Método de titulación in vitro de un atnc y su aplicación en un método de evaluación y/o control de un procedimiento de obtención de un producto biológico. |
AT04786344T ATE528646T1 (de) | 2003-08-25 | 2004-08-23 | Verfahren zur in-vitro-titration eines ncta und anwendung davon in einem verfahren zur bewertung und/oder überwachung eines herstellungsverfahrens für ein biologisches produkt |
DK04786344.4T DK1658494T3 (da) | 2003-08-25 | 2004-08-23 | Fremgangsmåde til en in vitro titrering af en NCTA og anvendelse deraf i en fremgangsmåde til evalueringen og/eller monitorering af en biologisk produktproduktionsfremgangsmåde |
US10/569,341 US7727728B2 (en) | 2003-08-25 | 2004-08-23 | Method for the in vitro titration of an NCTA application thereof in a method for the evaluation and/or monitoring of a biological product production method |
EP04786344A EP1658494B1 (fr) | 2003-08-25 | 2004-08-23 | Methode de titrage in vitro d'un atnc et son application a une methode d'evaluation et/ou de controle d'un procede d'obtention d'un produit biologique |
PL04786344T PL1658494T3 (pl) | 2003-08-25 | 2004-08-23 | Sposób miareczkowania in vitro NTCA i jego zastosowanie w sposobie oceny i/lub kontroli sposobu wytwarzania produktu biologicznego |
AU2004269188A AU2004269188B2 (en) | 2003-08-25 | 2004-08-23 | Method for the in vitro titration of an NCTA and application thereof in a method for the evaluation and/or monitoring of a biological product production method |
BRPI0413897-0A BRPI0413897A (pt) | 2003-08-25 | 2004-08-23 | método para titulação in vitro de um atnc e sua aplicação a um método de avaliação e/ou de controle de um processo para obtenção de um produto biológico |
JP2006524391A JP2007503209A (ja) | 2003-08-25 | 2004-08-23 | NCTAのinvitro滴定方法、及び、生物学的産物を生産する方法の評価及び/またはモニタリング方法へのそれらの適用 |
CA2536688A CA2536688C (fr) | 2003-08-25 | 2004-08-23 | Titrage in vitro d'un agent transmissible non conventionnel avec des cellules transgeniques stables en supportant la replication |
IL173850A IL173850A (en) | 2003-08-25 | 2006-02-21 | Method for the in vitro titration of an ncta and application thereof in a method for the evaluation and/or monitoring of a biological product production method |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0310126 | 2003-08-25 | ||
FR0310126A FR2859222B1 (fr) | 2003-08-25 | 2003-08-25 | Methode d'evaluation et/ou de controle d'un procede d'obtention d'un produit biologique susceptible d'etre contamine par un agent transmissible non conventionnel (atnc) |
Publications (1)
Publication Number | Publication Date |
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WO2005022148A1 true WO2005022148A1 (fr) | 2005-03-10 |
Family
ID=34130588
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/FR2004/002179 WO2005022148A1 (fr) | 2003-08-25 | 2004-08-23 | Methode de titrage in vitro d’un atnc et son application a une methode d’evaluation et/ou de controle d’un procede d’obtention d’un produit biologique |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP1658494B1 (fr) |
JP (1) | JP2007503209A (fr) |
AT (1) | ATE528646T1 (fr) |
AU (1) | AU2004269188B2 (fr) |
BR (1) | BRPI0413897A (fr) |
CA (1) | CA2536688C (fr) |
DK (1) | DK1658494T3 (fr) |
ES (1) | ES2374816T3 (fr) |
FR (1) | FR2859222B1 (fr) |
IL (1) | IL173850A (fr) |
PL (1) | PL1658494T3 (fr) |
WO (1) | WO2005022148A1 (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006117483A2 (fr) * | 2005-05-04 | 2006-11-09 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Materiel infectieux synthetique et standardise de type prion et ses utilisations en tant qu’inoculum infectant |
WO2010072969A1 (fr) | 2008-12-22 | 2010-07-01 | Lfb-Biotechnologies | Procede de detection d'une infection par prion |
JP2012501638A (ja) * | 2008-09-05 | 2012-01-26 | エルエフベ−バイオテクノロジース | プリオンを発現する安定な細胞クローン |
EP2732827A1 (fr) | 2012-11-20 | 2014-05-21 | Franklab | Procédé de détermination de l'aptitude d'une formulation à inactiver un ATNC |
WO2014184317A1 (fr) | 2013-05-15 | 2014-11-20 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Procédé d'inactivation d'une protéine prion |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2929290B1 (fr) * | 2008-03-27 | 2010-05-07 | Lfb Biotechnologies | Methode de detection et/ou de titrage in vitro d'un agent transmissible non conventionnel |
CA3091348A1 (fr) * | 2018-02-19 | 2019-08-22 | Bayer Healthcare Llc | Membrane filtrante modifiee et procede |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6605445B1 (en) * | 1999-02-22 | 2003-08-12 | Bayer Corporation | Rapid method of determining clearance of prion protein |
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2003
- 2003-08-25 FR FR0310126A patent/FR2859222B1/fr not_active Expired - Fee Related
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2004
- 2004-08-23 PL PL04786344T patent/PL1658494T3/pl unknown
- 2004-08-23 EP EP04786344A patent/EP1658494B1/fr not_active Expired - Lifetime
- 2004-08-23 JP JP2006524391A patent/JP2007503209A/ja active Pending
- 2004-08-23 DK DK04786344.4T patent/DK1658494T3/da active
- 2004-08-23 WO PCT/FR2004/002179 patent/WO2005022148A1/fr active Application Filing
- 2004-08-23 ES ES04786344T patent/ES2374816T3/es not_active Expired - Lifetime
- 2004-08-23 AU AU2004269188A patent/AU2004269188B2/en not_active Ceased
- 2004-08-23 CA CA2536688A patent/CA2536688C/fr not_active Expired - Fee Related
- 2004-08-23 BR BRPI0413897-0A patent/BRPI0413897A/pt not_active IP Right Cessation
- 2004-08-23 AT AT04786344T patent/ATE528646T1/de active
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2006
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2006117483A2 (fr) * | 2005-05-04 | 2006-11-09 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Materiel infectieux synthetique et standardise de type prion et ses utilisations en tant qu’inoculum infectant |
FR2885369A1 (fr) * | 2005-05-04 | 2006-11-10 | Lab Francais Du Fractionnement | Materiel infectieux synthetique et standardise de type prion et ses utilisations en tant qu'inoculum infectant. |
WO2006117483A3 (fr) * | 2005-05-04 | 2006-12-28 | Lab Francais Du Fractionnement | Materiel infectieux synthetique et standardise de type prion et ses utilisations en tant qu’inoculum infectant |
JP2008539709A (ja) * | 2005-05-04 | 2008-11-20 | ラボラトワール フランセ デュ フラクショヌマン エ デ ビオテクノロジ | 合成性であり標準化されたプリオン感染性物質、及び感染接種物としてのその使用。 |
KR101168467B1 (ko) * | 2005-05-04 | 2012-07-26 | 라보라토이레 프란카이스 듀 프락티온네멘트 에트 데스 바이오테크놀로지스 소시에테 애너님 | 합성된 표준화 프리온 감염성 물질 및 감염성 접종물로써의이의 용도 |
JP2012501638A (ja) * | 2008-09-05 | 2012-01-26 | エルエフベ−バイオテクノロジース | プリオンを発現する安定な細胞クローン |
WO2010072969A1 (fr) | 2008-12-22 | 2010-07-01 | Lfb-Biotechnologies | Procede de detection d'une infection par prion |
EP2732827A1 (fr) | 2012-11-20 | 2014-05-21 | Franklab | Procédé de détermination de l'aptitude d'une formulation à inactiver un ATNC |
WO2014184317A1 (fr) | 2013-05-15 | 2014-11-20 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Procédé d'inactivation d'une protéine prion |
Also Published As
Publication number | Publication date |
---|---|
IL173850A (en) | 2012-02-29 |
AU2004269188A1 (en) | 2005-03-10 |
FR2859222A1 (fr) | 2005-03-04 |
ATE528646T1 (de) | 2011-10-15 |
DK1658494T3 (da) | 2012-01-09 |
CA2536688C (fr) | 2012-11-06 |
JP2007503209A (ja) | 2007-02-22 |
BRPI0413897A (pt) | 2006-10-24 |
ES2374816T3 (es) | 2012-02-22 |
FR2859222B1 (fr) | 2006-01-27 |
AU2004269188B2 (en) | 2011-04-07 |
CA2536688A1 (fr) | 2005-03-10 |
PL1658494T3 (pl) | 2012-05-31 |
IL173850A0 (en) | 2006-07-05 |
EP1658494B1 (fr) | 2011-10-12 |
EP1658494A1 (fr) | 2006-05-24 |
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