[go: up one dir, main page]

WO1998003550A1 - Pasteurisation de solutions d'immunoglobulines - Google Patents

Pasteurisation de solutions d'immunoglobulines Download PDF

Info

Publication number
WO1998003550A1
WO1998003550A1 PCT/AU1997/000454 AU9700454W WO9803550A1 WO 1998003550 A1 WO1998003550 A1 WO 1998003550A1 AU 9700454 W AU9700454 W AU 9700454W WO 9803550 A1 WO9803550 A1 WO 9803550A1
Authority
WO
WIPO (PCT)
Prior art keywords
immunoglobulin
pasteurization
solution
aggregate
pasteurized
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.)
Ceased
Application number
PCT/AU1997/000454
Other languages
English (en)
Inventor
Joseph Bertolini
Germano Coppola
Jeffrey Raymond Davies
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.)
CSL Ltd
Original Assignee
CSL Ltd
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
Priority claimed from AUPO1112A external-priority patent/AUPO111296A0/en
Priority claimed from AUPO5462A external-priority patent/AUPO546297A0/en
Application filed by CSL Ltd filed Critical CSL Ltd
Priority to JP10506378A priority Critical patent/JP2000515857A/ja
Priority to AU34297/97A priority patent/AU3429797A/en
Priority to EP97930259A priority patent/EP0954534A1/fr
Publication of WO1998003550A1 publication Critical patent/WO1998003550A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators

Definitions

  • This invention relates to the heat treatment, more particularly the pasteurization of immunoglobulin solutions, and in particular it relates to the pasteurization of Immunoglobulin G (IgG) solutions.
  • IgG Immunoglobulin G
  • Pasteurization can be used as a method to inactivate viruses in the manufacture of IgG solutions for therapeutic use. It is preferable, however, that the process be carried out under conditions which maintain the physiological function of the immunoglobulin and that it produces a stable product without the need for additional purification.
  • Hirao etal. (1989) describe a process for pasteurizing IgG under similar conditions to those of Magnin et al. with inclusion of sorbitol to stabilise IgG during pasteurization.
  • the preferred method involves pasteurization (preferably at 60°C for 10 hours) under conditions of low ionic strength (0.001 or less), a pH range of 4.5 to 6.5, and a sorbitol concentration of 10% to 70% w/v. Protein concentration according to the method is not restricted and the process is deemed to work over a concentration range of 0.1 to 30% w/v.
  • Nowak et al. (1992) describes a process for pasteurizing IgG (60°C, 10 hours) using high concentrations of sucrose and glycine to stabilise IgG during pasteurization.
  • the stabilisers are removed and the IgG is then treated either by low pH incubation in the presence of pepsin or by S sulphonation resulting in a modified immunoglobulin.
  • the modification to the immunoglobulin molecule reduces complement activating IgG aggregates and allows compliance with pharmacopoeial requirements for anticomplementary activity.
  • an immunoglobulin solution such as an IgG solution
  • a process for the pasteurization of an immunoglobulin solution which comprises heating the solution at a temperature of 50°C to 70°C for a period of from 1 to 20 hours, at a pH of 4.0 to 6.0 in the presence of 20 to 40% w/v sorbitol or 25 to 45% w/v sucrose, and wherein the protein concentration of the solution is approximately 3% w/v or less.
  • the pasteurization process is carried out at low ionic strength (conductivity of 1.OmS/cm or less; more preferably, conductivity of less than 0.3mS/cm at 25°C).
  • the present invention also extends to a pasteurized immunoglobulin preparation prepared by the process broadly described above.
  • the present invention provides a process for the production of a pasteurized immunoglobulin preparation which retains its therapeutic effectiveness, and in particular a preparation in which the level of aggregate and anti-complementary activity is within therapeutically acceptable limits.
  • purified immunoglobulin preparations are pasteurized, for example at 60°C for 10h, and then formulated and dispensed without the need for additional purification to remove aggregate or modification to reduce anti-complementary activity.
  • the process of the present invention where sorbitol is used as a stabilizer during pasteurization utilises similar conditions to those broadly described by Hirao et al. (1989) except protein concentration is recognised as a critical parameter in this process.
  • the immunoglobulin solution is pasteurized at 50°C to 70°C (preferably at 60°C), for a period of 1 to 20 hours (preferably 10 hours), at a pH of 4.0 to 6.0 (preferably 4.0 to 5.0), in the presence of 20 to 40% w/v (preferably 20- 33% w/v), sorbitol and at protein concentration of approximately 3% w/v or less.
  • the immunoglobulin solution is pasteurized at 50°C to 70°C (preferably at 60 °C), for a period of 1 to 20 hours (preferably 10 hours), at a pH of 4.0 to 6.0 (preferably 4.4 to 5.4), in the presence of 25 to 45% w/v (preferably 30 to 40% w/v) sucrose, and at a protein concentration of approximately 3% w/v or less.
  • higher protein concentrations e.g. 5% w/v, result in unacceptable aggregate generation and a tendency for product to further aggregate during storage if formulated as a liquid preparation.
  • the immunoglobulin solution is derived by a chromatographic process, it is pasteurized at a protein concentration of less than 3% w/v in the presence of 20-33% w/v sorbitol at a pH of 4.8 and at a conductivity of less than 0.3mS/cm.
  • the immunoglobulin solution is derived by Cohn fractionation, it is pasteurized at a concentration of less than 2% w/w in the presence of 20-30% w/v sorbitol at a pH of 4.8 and a conductivity of less than 0.3mS/cm.
  • chromatographically purified immunoglobulin is pasteurized at a protein concentration of less than 2% w/v in the presence of 30-45% sucrose at a pH of 4.4 to 5.2.
  • the sorbitol or sucrose is removed from the pasteurized immunoglobulin by diafiltration, and the immunoglobulin is formulated and is dispensed at 6% w/v protein concentration in 10% w/v maltose at pH 4.0-6.0, preferably pH 4.25-5.5.
  • Figure 1 shows: (a) Dependence of aggregate generation on pH in immunoglobulin during pasteurization at 60°C for 10 hours.
  • Figure 2 shows the effect of protein concentration an sorbitol concentration on aggregate generation during pasteurization at 60 C C for 10 hours.
  • Immunoglobulin Purification Immunoglobulins were purified from normal plasma pools using Cohn fractionation or chromatographic methods. Cohn fractionated product
  • Chromatographically purified immunoglobulin was purified using Cohn fractionation to remove fibrinogen (Fraction I) followed by ion exchange chromatography.
  • Immunoglobulin Bulk Concentrate Following purification by either method, preparations were concentrated to appropriately 10% w/v and diafiltered at pH 4.8, followed by dilution to achieve a conductivity of ⁇ 0.3mS/cm (unless stated otherwise in the Examples).
  • the pasteurized solution was diafiltered to remove sorbitol while maintaining pH at 4.25 to 4.8 and then formulated as a 6% w/v solution in 10% w/v maltose at pH 4.25 to pH 5.5.
  • Aggregate content was measured by size exclusion chromatography using a TSK3000 column (60cm X 0.5cm) with 0.1 M phosphate pH 7.0 as running buffer with samples diluted in 0.1 phosphate (BP 1988) or 0.5% NaCl (BP 1994) and a flow rate of 0.5ml/min. Elution of proteins was monitored at 280nm.
  • Anticomplementary Activity (ACA) assay According to the BP (1994) method, ACA activity is assayed by mixing the immunoglobulin preparation under assay with guinea pig complement. Any aggregated IgG will bind to complement resulting in neutralisation of complement activity. The remaining activity is determined by monitoring lysis of sheep red blood cells.
  • Activity is expressed as a percentage of complement consumed against a complement control solution not exposed to immunoglobulin.
  • an analogous but modified method was used.
  • Serial dilutions of the immunoglobulin preparation were mixed with human complement and the amount of complement remaining determined by monitoring lysis of sheep red blood cells.
  • Results were expressed as CH 50 /mg where CH 50 refers to 50% haemolytic units of complement. This assay has been correlated with the BP assay and the limit of 10 CH 50 /mg is within the BP limit for anticomplementary activity.
  • Immunoglobulins must have an Fc function of greater than 60% of this standard to meet BP requirements (BP 1994).
  • Immunoglobulin bulk concentrate prepared by Cohn fractionation was diluted to 1 % w/v adjusted to pH 4.0, 4.2, 4.8 or 5.0 and pasteurized at 60°C for 10 hours in the absence of any stabilizer.
  • Figure 1 (a) shows the aggregate content obtained at each condition.
  • the data illustrates that under these conditions pasteurization of IgG results in an inordinate level of aggregation for IV infusion, rendering the product clinically unacceptable as it exceeds the pharmacopoeial limit for an intravenous immunoglobulin preparation of ⁇ 3% aggregate.
  • Figure 1 (b) shows that the material pasteurized without sorbitol at 0.5% or 1 % w/v IgG and formulated at 6% w/v IgG in 10% maltose at pH 5.5 exhibits a high initial aggregate content and further increases over 13 days at both 8°C and 25°C.
  • Example 2 Pasteurization of immunoglobulin in the presence of sorbitol.
  • Immunoglobulin bulk concentrate derived by the chromatographic process was formulated in various concentrations of sorbitol ranging from 0% to 30% w/v, at various protein concentrations ranging from 1 % to 4% w/v.
  • the pH was adjusted to 4.8 and the solutions pasteurized at 60°C for 10 hours.
  • Figure 2 shows that increasing sorbitol concentrations stabilise immunoglobulin during pasteurization thus resulting in less aggregate formation.
  • Figure 2b it can be seen that at a protein concentration of 1 % w/v in the presence of 30% w/v sorbitol, no significant aggregation occurs. Even at 2% in 20% sorbitol, aggregate content remains less than 2.0%, which is within specifications for intravenous IgG ( ⁇ 3%).
  • Example 3 Comparison of aggregate formation following pasteurization of Cohn and chromatographically purified immunoglobulin preparations.
  • Immunoglobulin bulk concentrates from Cohn and chromatographically purified immunoglobulin preparations were formulated at 1 to 30% w/v IgG concentration in 15 to 30% w/v sorbitol at pH 4.8 and pasteurized at 60°C for 10 hours. Aggregate formation was monitored in the pasteurized product by size exclusion chromatography.
  • Cohn fractionation which involves differential ethanol precipitation, is more labile during the pasteurization process and must be pasteurized at a lower protein concentration or higher sorbitol concentration. This may reflect perturbation of the immunoglobulin molecule by the relatively harsh fractionation conditions, resulting in increased sensitivity of the molecule to heat denaturation.
  • the chromatographically purified material is more stable during the pasteurization process, and higher protein concentration and lower sorbitol concentrations can be used during the pasteurization process.
  • Table 2 presents the antibody titre, Fc function, ACA and aggregate content of pasteurized intravenous immunoglobulin.
  • Chromatographically purified intravenous immunoglobulin was pasteurized at a protein concentration of ⁇ 3% w/v in the presence of 30% w/v sorbitol at pH 4.8. Following pasteurization, sorbitol was removed by diafiltration and the immunoglobulin formulated at 6% w/v protein, 10% w/v maltose, pH 4.25.
  • Data for a non-pasteurized intravenous immunoglobulin product purified by Cohn fractionation and formulated as described above is presented for comparison.
  • Diphtheria antitoxin (lU/ml) 1 .9 1 .2 2.1 2.0 (1-2.9)
  • Table 3 presents characterisation data (antibody titre, Fc function, aggregate content) of pasteurized Cohn fractionated immunoglobulin, using the same conditions of pasteurization and subsequent formulation.
  • Table 4 presents the aggregate content of chromatographically purified immunoglobulin following storage at 4°C for 13 and 52 weeks.
  • Table 4 Aggregate content in pasteurized chromatographically purified immunoglobulin during storage at 4°C.
  • IP004 IP-005 IP006 Non-pasteurised immunoglobulin
  • the potential of the pasteurization step to inactivate viruses was evaluated using the following model viruses:
  • Sindbis virus as a model for the enveloped viruses HIV and HCV
  • bovine viral diarrhoea virus BVDV
  • DHBV duck hepatitis B virus
  • EMC encephalomyocarditis
  • Theilar's virus as a model for non-enveloped viruses e.g. hepatitis A virus (HAV);
  • Immunoglobulin bulk solution derived from the chromatographic or Cohn process was diluted to 2% w/v protein made 30% w/v with sorbitol and adjusted to pH 4.8. Samples prepared as described above were spiked with virus and pasteurized at 60°C for 10 hours. The results of the inactivation studies are presented in Table 5, and demonstrate the substantial inactivation of both enveloped and non-enveloped viruses achieved during pasteurization.
  • Intramuscular immunoglobulin (IMIG) products are commonly derived from Cohn
  • IMIG-VI is manufactured from diafiltered Supernatant III, the pure immunoglobulin preparation resulting from Cohn fractionation.
  • Viral inactivation is effected by pasteurisation at a protein concentration of 0.5-2.0% w/v IgG in the presence of 30% w/v sorbitol at pH 4.8.
  • the pasteurised IgG is concentrated and diafiltered to remove sorbitol, and then formulated to a protein concentration of 16% w/v with glycine added to 22.5mg/ml and pH adjusted to 6.5.
  • IMIG-VI The characteristics of three batches of normal IMIG-VI incorporating pasteurisation, and of batches produced by the alternative process are shown in Tables 6 and 7.
  • IMIG-VI and IMIG were similar in most parameters measured. Antibody titers were similar for both products.
  • IMIG-VI contains a higher aggregate content than IMIG, yet lower ACA compared to the IMIG product.
  • Protease activity demonstrated by PKA and kallikrein was lower in IMIG-VI, whilst plasminogen was not observed in either.
  • CH50 refers to 50% haemolytic units of complement.
  • Chromatographically purified immunoglobulin was subjected to pasteurisation at 60°C for 10 hours in the presence of sucrose. Three studies were conducted. For Studies 1 and 2 chromatographically purified immunoglobulin that had been stored for 5 months as an 8% solution at 4°C and pH 4.8 was used as the source material. For Study 3 freshly prepared chromatographically purified immunoglobulin was used.
  • Acceptable conditions for pasterization are: sucrose at a concentration of 30%-45% (w/v), pure immunoglobulin solutions at a concentrations up to at least 2% w/v and a pH range of at least pH4.4 to 5.2.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Cette invention concerne un procédé de pasteurisation d'une solution d'immunoglobulines, et notamment une solution de gammaglobulines, qui consiste à chauffer la solution à une température comprise entre 50 °C et 70 °C pendant un laps de temps compris entre 1 et 20 heures, à un pH compris entre 4,0 et 6,0, et en présence de 20 à 40 % en poids de sorbitol ou de 25 à 45 % en poids de saccharose, la concentration en protéines de la solution étant approximativement inférieure ou égale à 3 % en poids.
PCT/AU1997/000454 1996-07-18 1997-07-18 Pasteurisation de solutions d'immunoglobulines Ceased WO1998003550A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP10506378A JP2000515857A (ja) 1996-07-18 1997-07-18 免疫グロブリン溶液の低温殺菌
AU34297/97A AU3429797A (en) 1996-07-18 1997-07-18 Pasteurization of immunoglobulin solutions
EP97930259A EP0954534A1 (fr) 1996-07-18 1997-07-18 Pasteurisation de solutions d'immunoglobulines

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
AUPO1112A AUPO111296A0 (en) 1996-07-18 1996-07-18 Pasteurization of immunoglobulin solutions
AUPO1112 1996-07-18
AUPO5462A AUPO546297A0 (en) 1997-03-05 1997-03-05 Pasteurization of immunoglobulin solutions
AUPO5462 1997-03-05

Publications (1)

Publication Number Publication Date
WO1998003550A1 true WO1998003550A1 (fr) 1998-01-29

Family

ID=25645219

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU1997/000454 Ceased WO1998003550A1 (fr) 1996-07-18 1997-07-18 Pasteurisation de solutions d'immunoglobulines

Country Status (5)

Country Link
EP (1) EP0954534A1 (fr)
JP (1) JP2000515857A (fr)
KR (1) KR20000067911A (fr)
CA (1) CA2261291A1 (fr)
WO (1) WO1998003550A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003088999A1 (fr) * 2002-04-22 2003-10-30 Mitsubishi Pharma Corporation Procede de production d'une preparation d'immunoglobuline
WO2009092383A3 (fr) * 2008-01-22 2009-10-01 Multimerics Aps Produits et méthodes pour prévenir une infection
US7729423B2 (en) * 2003-04-04 2010-06-01 Avid Technology, Inc. Fixed bit rate, intraframe compression and decompression of video
US10307483B2 (en) 2016-10-21 2019-06-04 Amgen Inc. Pharmaceutical formulations and methods of making the same
US11607451B2 (en) 2005-06-14 2023-03-21 Amgen Inc. Self-buffering antibody formulations

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0035204A2 (fr) * 1980-03-05 1981-09-09 Miles Inc. Compositions pasteurisées de protéines thérapeutiquement actives
US4845199A (en) * 1986-07-09 1989-07-04 Green Cross Corporation Process for heat treating chemically unmodified gamma-globulin
US4849508A (en) * 1986-11-25 1989-07-18 Connaught Laboratories Limited Pasteurization of immunoglobulin solutions
EP0605219A1 (fr) * 1992-12-25 1994-07-06 JCR PHARMACEUTICALS Co., LTD. Produits contenants des protéins de lait comme constiuants actifs, et procédé pour préparer ces produits

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0035204A2 (fr) * 1980-03-05 1981-09-09 Miles Inc. Compositions pasteurisées de protéines thérapeutiquement actives
US4845199A (en) * 1986-07-09 1989-07-04 Green Cross Corporation Process for heat treating chemically unmodified gamma-globulin
US4849508A (en) * 1986-11-25 1989-07-18 Connaught Laboratories Limited Pasteurization of immunoglobulin solutions
EP0605219A1 (fr) * 1992-12-25 1994-07-06 JCR PHARMACEUTICALS Co., LTD. Produits contenants des protéins de lait comme constiuants actifs, et procédé pour préparer ces produits

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Accession Number 108:226822; & JP,A,62 283 933 (SHOWA), 9 December 1987. *
CHEMICAL ABSTRACTS, Accession Number 115:15573; & JP,A,02 304 030 (HEISEI), 17 December 1990. *
JOURNAL OF MEDICAL VIROLOGY, Volume 36, No. 3, 1992, NOWAK et al., "Virus Safety of Human Immunoglobulins", pages 209-216. *
VOX SANGUINIS, Volume 56, 1989, UEMURA et al., "Inactivation and Elimination of Viruses During the Fractionation of an Intravenous Immunoglobulin Preparation", pages 155-161. *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003088999A1 (fr) * 2002-04-22 2003-10-30 Mitsubishi Pharma Corporation Procede de production d'une preparation d'immunoglobuline
US7729423B2 (en) * 2003-04-04 2010-06-01 Avid Technology, Inc. Fixed bit rate, intraframe compression and decompression of video
US11607451B2 (en) 2005-06-14 2023-03-21 Amgen Inc. Self-buffering antibody formulations
WO2009092383A3 (fr) * 2008-01-22 2009-10-01 Multimerics Aps Produits et méthodes pour prévenir une infection
US8475789B2 (en) 2008-01-22 2013-07-02 Multimerics Aps Products and methods to prevent infections
US9259440B2 (en) 2008-01-22 2016-02-16 Multimerics Aps Methods for passive immunization
US10307483B2 (en) 2016-10-21 2019-06-04 Amgen Inc. Pharmaceutical formulations and methods of making the same
US11491223B2 (en) 2016-10-21 2022-11-08 Amgen Inc. Pharmaceutical formulations and methods of making the same
US12214013B2 (en) 2016-10-21 2025-02-04 Amgen Inc. Methods of treatment of arthritis and/or psoriasis with pharmaceutical formulations of etanercept

Also Published As

Publication number Publication date
KR20000067911A (ko) 2000-11-25
EP0954534A1 (fr) 1999-11-10
CA2261291A1 (fr) 1998-01-29
JP2000515857A (ja) 2000-11-28

Similar Documents

Publication Publication Date Title
CA1268707A (fr) Procede d'inactivation des virus dans l'immunoglobuline
US4440679A (en) Pasteurized therapeutically active protein compositions
EP0073371B1 (fr) Globuline de sérum immunisant injectable par voie intraveineuse et son procédé de préparation
JP3512163B2 (ja) ウイルス不活化能の決定法
US4849508A (en) Pasteurization of immunoglobulin solutions
EP0035204A2 (fr) Compositions pasteurisées de protéines thérapeutiquement actives
CA1340211C (fr) Methode pour inactiver un virus a enveloppe lipidique dans une solution therapeutique
JP3145696B2 (ja) 分泌型免疫グロブリンａ製剤の製造法
JPH0348169B2 (fr)
JP3133338B2 (ja) ウイルス的に安全な生物学的組成物の調製方法
JPS63145237A (ja) 耐ウィルス性、貯蔵安定性、静脈内適合性の免疫グロブリンｇ製剤の製造方法
JPS61191622A (ja) γ−グロブリンの加熱処理方法
US5770199A (en) Method for virus inactivation in the presence of polyalkylene glycol as well as the pharmaceutical preparation obtained therewith
AU737566B2 (en) An immunotolerant prothrombin complex preparation
JPH03204822A (ja) 非変性静脈内投与可能なＩｇＭ―及び／又は／ＩｇＡ―含有免疫グロブリン製剤及びその製造方法
CA2094347C (fr) Methode de production d'une preparation de facteur viii
IL172844A (en) Process for obtaining cryoprecipitable proteins including a virus inactivation step
AU709608B2 (en) Preparation of virally inactivated intravenously injectable immune serum globulin
WO1998003550A1 (fr) Pasteurisation de solutions d'immunoglobulines
Sisti et al. Preparation of lyophilized and liquid intravenous immunoglobulin G: development and scale‐up
AU2018269656B2 (en) C1-esterase inhibitor preparation
CA1207662A (fr) Produits biologiques exempts de virus de l'hepatite b et du virus nona-nonb
US5248767A (en) Process for the preparation of a pasteurized immunoglobulin preparation using ethanol
EP0449897B1 (fr) Proteine pure de facteur i et procede de production
JPS62289523A (ja) 静脈投与用免疫グロブリンの加熱処理方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP KR NZ SG US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 333682

Country of ref document: NZ

ENP Entry into the national phase

Ref document number: 2261291

Country of ref document: CA

Kind code of ref document: A

Ref document number: 2261291

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1019997000368

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1997930259

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 09214906

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 1997930259

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1019997000368

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1997930259

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1019997000368

Country of ref document: KR