CA2191475A1 - A drug, containing one or more plasma derivatives - Google Patents

A drug, containing one or more plasma derivatives

Info

Publication number
CA2191475A1
CA2191475A1 CA002191475A CA2191475A CA2191475A1 CA 2191475 A1 CA2191475 A1 CA 2191475A1 CA 002191475 A CA002191475 A CA 002191475A CA 2191475 A CA2191475 A CA 2191475A CA 2191475 A1 CA2191475 A1 CA 2191475A1
Authority
CA
Canada
Prior art keywords
quality
assured
starting material
plasma
viruses
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002191475A
Other languages
French (fr)
Other versions
CA2191475C (en
Inventor
Johann Eibl
Otto Schwarz
Friedrich Dorner
Herwig Igel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxalta GmbH
Baxalta Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=3499516&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2191475(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2191475A1 publication Critical patent/CA2191475A1/en
Application granted granted Critical
Publication of CA2191475C publication Critical patent/CA2191475C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • C12Q1/701—Specific hybridization probes
    • C12Q1/706—Specific hybridization probes for hepatitis
    • C12Q1/707—Specific hybridization probes for hepatitis non-A, non-B Hepatitis, excluding hepatitis D
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • C12Q1/701—Specific hybridization probes
    • C12Q1/702—Specific hybridization probes for retroviruses
    • C12Q1/703—Viruses associated with AIDS
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • C12Q1/701—Specific hybridization probes
    • C12Q1/706—Specific hybridization probes for hepatitis
    • 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
    • G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6851—Quantitative amplification
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2496/00—Reference solutions for assays of biological material
    • G01N2496/05—Reference solutions for assays of biological material containing blood cells or plasma

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Virology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Communicable Diseases (AREA)
  • General Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • AIDS & HIV (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)

Abstract

The invention describes a drug containing one or more plasma derivatives as active substance or inactive ingredient, wherein the starting material or the intermediates incurred at the preparation of the plasma derivatives is not contaminated by one or more of various hematogenous viruses capable of reproduction, or has a virus load not exceeding a defined limiting value. The thus quality-assured starting material or intermediate, respectively, for the preparation of the finished plasma derivative is subsequently subjected to at least one further substantial virus depletion or virus inactivation step, respectively. The invention furthermore describes methods for the preparation of this drug as well as for the preparation of quality-assured starting materials or intermediates, respectively.

Claims (32)

1. A drug containing one or more plasma derivatives as active substance or auxiliary ingredient, characterized in that the starting material or the intermediates incurred in the preparation of the plasma derivatives are not contaminated by viruses or whose virus load of one or more hematogenous viruses capable of reproduction does not exceed a defined limiting value, - the absence of contamination by certain hematogenous viruses capable of reproduction being determined by an excess of virus-neutralizing antibodies in the starting material or in the intermediate, or by a protective immunity of the plasma donor at the time of the plasma donation, - otherwise the genome equivalents of the respective viruses of interest in the starting material or in the intermediate being determined by a quantifiable controlled and non-inhibited method for the detection or determination of nucleic acids, the thus quality-assured starting material or intermediate, respectively, for the preparation of the finished plasma derivative being subjected to at least one substantial virus depletion or virus inactivation step, and the finished quality-assured plasma derivative obtained being worked up to a drug by known methods.
2. A drug according to claim 1, characterized in that, for at least two viruses, preferably selected from the group HIV, HAV, HBV and HCV and, particularly, HIV and HCV, there is no virus contamination or the defined limiting value of the virus load is not exceeded.
3. A drug according to claim 1 or 2, characterized in that the defined limiting value of the viral load of the starting material or intermediate by hematogenous viruses capable of reproduction which is not exceeded is limited to a maximum of 500 genome equivalents, particularly to a maximum of 200 genome equivalents, preferably to 100 genome equivalents and especially preferably to 50 genome equivalents per ml of starting material or intermediate.
4. A drug according to any one of claims 1 to 3, characterized in that the virus inactivation or virus depletion is carried out by means of at least one method with a reduction factor of at least 4 during the preparation of the drug from the quality-assured starting material or quality-assured intermediate, respectively.
5. A quality-assured starting material for a drug according to any one of claims 1 to 4, characterized in that it is a quality-assured plasma pool, which optionally is prepared by mixing quality-assured minipools, which preferably consist of about 200 individual donations, into a quality-assured macropool, which preferably consists of about 2,000 individual donations.
6. A quality-assured starting material according to claim 5, characterized in that a quality-assured macropool is combined into a quality-assured multimacropool of up to 200,000 individual donations by mixing with a number of further quality-assured macropools.
7. A quality-assured starting material according to claim 5 or 6, characterized in that quality-assured minipools are obtained by mixing quality-assured small pools consisting of 2 to approximately 20 individual donations.
8. A quality-assured starting material for a drug according to any one of claims 1 to 7, characterized in that the absence of a virus load or the virus load not exceeding a defined limiting value is effected by - determining the genome equivalents of all the viruses of the group HIV, HBV, HCV, parvovirus and HAV, - determining the genome equivalents of all the viruses of the group HIV, HBV, HCV and parvovirus, as well as determining an excess of HAV antibodies, - determining the genome equivalents of all the viruses of the group HIV, HBV and HCV, as well as determining an excess of HAV and parvovirus antibodies, - determining the genome equivalents of all the viruses of the group HIV, HBV and HCV, as well as determining an excess of HAV antibodies, - determining the genome equivalents of all the viruses of the group HIV, HBV and HCV, as well as determining an excess of parvovirus antibodies, - determining the genome equivalents of all the viruses of the group HIV, HBV and HCV, - determining the genome equivalents of all the viruses of the group HIV and HCV, or - determining the genome equivalents of all the viruses of the group HIV and HCV, as well as determining an excess of HBV
antibodies.
9. Drugs prepared by the formulation from two or more finished plasma derivatives of claim 1.
10. A method for the preparation of a drug containing one or more plasma derivatives from a quality-assured starting material or from a quality-assured intermediate incurred in the preparation of the plasma derivatives, wherein the quality-assured starting material or intermediate, respectively, is not contaminated by one or more hematogenous viruses capable of reproduction or has a virus load at a level which does not exceed a defined limiting value, characterized in that, in the case of the determination of the genome equivalent of the respective virus by a quantifiable, controlled and non-inhibited method for the detection or determination of nucleic acids, the defined limiting value is selected, according to one or more of the following criteria:
- a detection limit of the nucleic acid amplification method(s) of at least 10,000 copies of the selected nucleic acid sequences;
- a certain number of genome equivalents, particularly a number of below 500 genome equivalents, preferably below 200 genome equivalents, more preferably below 100 genome equivalents, and especially preferably below 50 genome equivalents, per ml of starting material or intermediate, respectively.
11. A method according to claim 10, characterized in that more than one detection or determination system is used for nucleic acids, the detection or determination systems preferably being selected in a way that one system excludes falsely positive and an other system excludes falsely negative results.
12. A method according to claim 11, characterized in that at least two different PCR methods are used, at least one method serving for screening and at least one method serving for confirmation.
13. A method according to any one of claims 10 to 12, characterized in that the starting material or intermediate or the genome equivalents contained therein, respectively, are concentrated, preferably by lyophilization, adsorption or centrifugation.
14. A method according to any one of claims 10 to 13, characterized in that possibly present inhibitors of the amplification are removed or depleted in the starting material or in the intermediate.
15. A method according to any one of claims 10 to 14, characterized in that primer pairs specific for several viruses are used in the amplification, so that the presence of several different viruses can be assayed simultaneously.
16. A method according to any one of claims 10 to 15, characterized in that the primer pairs are selected in a way that they encode conserved genome sequences of the individual hematogenous viruses that are to be assayed, and their suitability is established on appropriate samples of a representative sample cross section of the viruses to be assayed.
17. A method according to any one of claims 10 to 16, characterized in that, in order to check the method for detecting or determining, respectively, nucleic acids in a sample, before or while carrying out the method, one or several internal standards or reference preparations, respectively, are added to the sample, the standards being determined or detected, respectively, in one and the same test vessel simultaneously with viral genomes or genome sequences possibly present .
18. A method for the preparation of a plasma pool as a quality-assured starting material with an assured, limited load of one or more hematogenous viruses capable of reproduction, from two or more individual donations, which is characterized by the following steps for the determination of the genome equivalents:
- taking samples from n individual donations, - combining the individual donation samples to m sample pools and - detecting the amount of viral genomes or genome sequences present in these sample pools by means of a quantifiable, controlled and non-inhibited method for the detection or determination, respectively, of nucleic acids, whereupon those individual donations (ng), whose detected amount of viral genomes or genome sequences in the sample pool lies below a certain limiting value, are combined into a quality-assured plasma pool, and those individual donations (na), whose detected amount of viral genomes or genome sequences in the sample pool is larger than or equal to the limiting value, are subjected to a further treatment or are eliminated, n and m being positive integers.
19. A method according to claim 18, characterized in that - samples are taken once more for the further treatment of the eliminated na individual donations and these individual donation samples are combined to ma sample pools, na and ma being positive integers with ma 2, and the ratio of ma :
na being larger than the ratio of m : n and - the amount of viral genomes or genome sequences in these sample pools is detected once more by means of a quantifiable, controlled and non-inhibited method for the detection or determination, respectively, of nucleic acids, whereupon those individual donations, whose detected amount of viral genomes or genome sequences in the sample pool lies below a certain limiting value, are combined into a quality-assured plasma pool and those individual donations, whose detected amount of viral genomes or genome sequences is larger than or equal to the limiting value, are subjected to a further treatment or are eliminated, and the method is repeated until the number of individual donations, which are to be treated further or eliminated, has reached or fallen below a set number.
20. A method according to claim 18 or 19, characterized in that n is equal to 2 to 200,000, preferably to 20 to 20,000, particularly preferably to 200 to 2,000, and especially to 200, m is between 1 and 100,000, preferably between 2 and 1,000, and that the set number of individual donations finally to be excluded in accordance with claim 11 is 100, preferably 10, and particularly preferably 1.
21. A method according to any one of claims 18 to 20, characterized in that the individual donations combined into a quality-assured plasma pool, are combined with further, quality-assured plasma pools, so that a quality-assured minipool, macropool or multimacropool is provided.
22. A method according to any one of claims 18 to 21, characterized in that the sample pools are assayed for virus neutralizing antibodies to the viruses to be assayed in addition to the detection or determination, respectively, of nucleic acids, and that those individual donations, in whose sample pool the virus-neutralizing antibodies to corresponding viruses cannot be detected, are subjected to a further treatment or eliminated.
23. A method according to claim 22, characterized in that, for the further treatment, the individual donations are analyzed once again in smaller sub-groups analogous to the method of claim 19.
24. A quality-assured starting material or intermediate, obtainable by a method according to any one of claims 10 to 23.
25. A quality-assured plasma pool, obtainable by a method according to any one of claims 18 to 23.
26. A quality-assured, finished plasma derivative, obtainable from a quality-assured starting material or intermediate, respectively, according to claim 24 by a substantial virus depletion or virus inactivation step, respectively, the plasma derivative preferably having been assayed once again for viral genome equivalents or virus-neutralizing antibodies, respectively.
27. A drug, obtainable from a quality-assured, finished plasma derivative from human plasma by pharmaceutical formulation steps.
28. A method for the preparation of drugs containing one or more plasma derivatives, which are free from various hematogenous viruses capable of reproduction, characterized by the following method steps:
- providing a starting material or an intermediate incurred at the preparation of the plasma derivatives, derived from human plasma, - assuring the quality of the starting material or intermediate by detecting the absence of viral contamination by hematogenous viruses capable of reproduction or by detecting that such a contamination is present in an amount not exceeding a particular limiting value, - the absence of a virus load by certain hematogenous viruses capable of reproduction being determined by an excess of virus- neutralizing antibodies in the starting material or intermediate, or by a protective immunity of the plasma donor at the time of the plasma donation, - otherwise the genome equivalents of the respective viruses of interest being determined in the starting material or in the intermediate, - subjecting the thus quality-assured starting material or intermediate to at least one further substantial virus depletion or virus inactivation step before the finishing of the plasma derivatives and - working up the quality-assured, finished plasma derivative obtained into a drug by means of methods known per se.
29. A method according to claim 28, characterized in that the quality assurance is carried out for each intermediate which is to be subjected to a substantial virus depletion or virus inactivation step.
30. A quality-assured starting material or intermediate, respectively, obtainable by mixing quality-assured starting materials or intermediates, respectively, for a drug according to any one of claims 1 to 4 prior to their further processing to a quality-assured starting material or a quality-assured intermediate pool, respectively.
31. A drug according to claim 1 or 2, characterized in that the virus inactivation or virus depletion is carried out by means of a protein-preserving method which has a reduction factor of not more than 4, so as to inactivate or eliminate, respectively, the hematogenous viruses capable of reproduction possibly present.
32. A drug according to claim 31, characterized in that a single virus inactivation or virus depletion, respectively, is sufficient to inactivate or eliminate, respectively, hematogenous viruses capable of reproduction possibly present.
CA2191475A 1995-05-08 1996-05-06 A drug, containing one or more plasma derivatives Expired - Lifetime CA2191475C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AT0077895A AT406019B (en) 1995-05-08 1995-05-08 METHOD FOR PRODUCING A MEDICINAL PRODUCT CONTAINING ONE OR MORE PLASMA DERIVATIVES
ATA778/95 1995-05-08
PCT/AT1996/000089 WO1996035437A1 (en) 1995-05-08 1996-05-06 Medicament of assured quality, containing one or more plasma derivatives

Publications (2)

Publication Number Publication Date
CA2191475A1 true CA2191475A1 (en) 1996-11-14
CA2191475C CA2191475C (en) 2010-09-14

Family

ID=3499516

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2191475A Expired - Lifetime CA2191475C (en) 1995-05-08 1996-05-06 A drug, containing one or more plasma derivatives

Country Status (10)

Country Link
EP (1) EP0769954B2 (en)
JP (2) JPH10502943A (en)
AT (2) AT406019B (en)
CA (1) CA2191475C (en)
DE (1) DE59610626D1 (en)
DK (1) DK0769954T4 (en)
ES (1) ES2203688T5 (en)
IL (1) IL118188A (en)
NO (1) NO322186B1 (en)
WO (1) WO1996035437A1 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5780222A (en) 1995-04-10 1998-07-14 Alpha Therapeutic Corporation Method of PCR testing of pooled blood samples
AT403477B (en) * 1996-04-30 1998-02-25 Immuno Ag BIOLOGICAL MATERIAL FREE OF VIRAL AND MOLECULAR PATHOGENES AND METHOD FOR THE PRODUCTION THEREOF
AU741141B2 (en) * 1997-11-04 2001-11-22 Roche Diagnostics Gmbh Specific and sensitive method for detecting nucleic acids
DE19752898A1 (en) * 1997-11-28 1999-08-05 Centeon Pharma Gmbh Method for the detection of high concentrations of four in blood plasma and / or blood serum by means of the polymerase chain reaction
AT407160B (en) * 1998-06-04 2001-01-25 Immuno Ag METHOD FOR DETERMINING ANTIGENS
AU774118B2 (en) 1999-02-12 2004-06-17 Baxter Healthcare Sa A method for producing a preparation based on fibrinogen and fibronectin as well as protein compositions obtainable according to this method
AT410218B (en) 1999-08-20 2003-03-25 Baxter Ag METHOD FOR PRODUCING A QUALITY-ASSURED POOL OF BIOLOGICAL SAMPLES
PL1711513T3 (en) * 2003-12-01 2014-12-31 Novo Nordisk Healthcare Ag Nanofiltration of factor vii solutions to remove virus
DE102005054206B4 (en) * 2005-11-14 2010-07-15 Roth, Willi, Prof. Dr. Method and apparatus for automated processing of pooled samples
AU2016315836A1 (en) * 2015-09-02 2018-02-15 Ep Minerals, Llc Regenerated media useful in the treatment of fermented liquids

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0447984A1 (en) * 1990-03-20 1991-09-25 Abbott Laboratories Hyperimmune globulin against hepatitis C virus and method for making same
WO1992001714A1 (en) † 1990-07-24 1992-02-06 Yamanouchi Pharmaceutical Co., Ltd. Non-a non-b hepatitis virus antigen
JP3114731B2 (en) * 1990-08-14 2000-12-04 国立感染症研究所長 Peptide antigen for detecting hepatitis C virus antibody and method of using the same
JPH04300000A (en) * 1991-03-27 1992-10-23 Teijin Ltd Method for determining nucleic acid
AT402891B (en) * 1991-06-20 1997-09-25 Immuno Ag METHOD FOR PRODUCING AN INACTIVATED BLOOD PRODUCT
AU4248193A (en) † 1992-05-15 1993-12-13 New England Deaconess Hospital Quantitation of viral rna by competitive polymerase chain reaction
EP0586112A3 (en) * 1992-08-14 1994-09-14 Pharma Gen S A Control of pcr mediated detection of micro-organisms
DK0590327T3 (en) * 1992-09-11 2003-07-28 Hoffmann La Roche Detection of nucleic acids in blood
CA2159044A1 (en) * 1994-09-26 1996-03-27 Falko-Guenter Falkner Method of quantitating nucleic acids

Also Published As

Publication number Publication date
DE59610626D1 (en) 2003-09-04
ES2203688T5 (en) 2011-07-01
DK0769954T4 (en) 2011-04-04
CA2191475C (en) 2010-09-14
EP0769954A1 (en) 1997-05-02
JP2008247913A (en) 2008-10-16
EP0769954B2 (en) 2011-03-09
ES2203688T3 (en) 2004-04-16
NO322186B1 (en) 2006-08-28
ATE245989T1 (en) 2003-08-15
ATA77895A (en) 1999-06-15
NO970050L (en) 1997-01-07
JPH10502943A (en) 1998-03-17
DK0769954T3 (en) 2003-11-17
NO970050D0 (en) 1997-01-07
IL118188A (en) 2000-07-16
IL118188A0 (en) 1996-09-12
EP0769954B1 (en) 2003-07-30
WO1996035437A1 (en) 1996-11-14
AT406019B (en) 2000-01-25

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