US20020034809A1 - Process for producing a plasma protein-containing medicament - Google Patents

Process for producing a plasma protein-containing medicament Download PDF

Info

Publication number
US20020034809A1
US20020034809A1 US09/254,288 US25428899A US2002034809A1 US 20020034809 A1 US20020034809 A1 US 20020034809A1 US 25428899 A US25428899 A US 25428899A US 2002034809 A1 US2002034809 A1 US 2002034809A1
Authority
US
United States
Prior art keywords
plasma
protein
citrate
medicament
exchanging
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.)
Abandoned
Application number
US09/254,288
Other languages
English (en)
Inventor
Wolfgang Teschner
Yendra Linnau
Sonja Svatos
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.)
Oesterreichisches Institut fuer Haemoderivate
Original Assignee
Immuno AG
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=3517640&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20020034809(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Immuno AG filed Critical Immuno AG
Assigned to IMMUNO AKTIENGESELLSCHAFT reassignment IMMUNO AKTIENGESELLSCHAFT ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: IGEL, HERWIG, LINNAU, YENDRA, SVATOS, SONJA, TESCHNER, WOLFGANG
Publication of US20020034809A1 publication Critical patent/US20020034809A1/en
Priority to US11/151,295 priority Critical patent/US8709492B2/en
Priority to US14/264,369 priority patent/US20140234292A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76—Albumins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum

Definitions

  • the invention relates to a method of preparing a plasma-protein-containing medicament from citrated plasma or from a citrate-containing plasma fraction, the medicament being substantially free from undesired metals.
  • albumin is the main component in plasma. Its therapeutic use has been known for a long time, an administration of albumin being indicated, e.g., in case of an acute loss of blood or plasma or in case of failure of the vasomotoric regulation. Since the osmotic pressure of a 20% (25%) albumin solution is approximately 4 times (5 times) that of normal human serum, the effect of albumin is mainly based on its ability to maintain the osmotic pressure.
  • Human albumin preparations are prepared from human plasma by multiple fractionation, e.g. by a fractionation according to Cohn, or they are prepared by means of recombinant methods. On account of various materials used during its preparation or when the albumin solution is stored in glass containers, aluminum gets into the albumin preparation so that the final content of aluminum in the respective preparations may be quite substantial.
  • Aluminum which constitutes one of the most frequently occurring elements in nature, has recently been increasingly associated with various diseases of the human body, primarily with diseases of the nervous and bone systems. Although the lungs and the gastro-intestinal tract form an efficient barrier for the uptake of aluminum, this barrier is no longer effective in patients receiving intravenous preparations, and the aluminum possibly present in the administered preparations may be taken up without hindrance. Thus, e.g., D. S. Milliner et al. (N. Engl. J. Med. (1985), 312, pp. 165-167) report that some albumin products comprising large amounts of aluminum have lead to diseases of the bones or to encephalitis. Aluminum is also increasingly associated with Alzheimer's disease.
  • the present invention has as its object to provide a novel and simple method of avoiding or reducing, respectively, undesired metals in plasma-protein-containing medicaments, in which both, the undesired metals are removed in the course of the preparation method and a contamination of the finished preparations during storage in metal-containing containers is prevented or reduced, respectively.
  • citrate ion-containing preparations are precipitated and subsequently taken up in a citrate ion free buffer, the new solution may still contain considerable portions of citrate ions. Since most of the fractionation methods in the recovery of pharmaceutical preparations from plasma—to which nearly always citrate is added during the extraction—comprise one or several precipiation steps, the inventive exchange method for citrate ions thus constitutes an interesting possibility for a simple, low-cost and efficient removal of citrate ions which can easily be incorporated into already established procedures.
  • the plasma fraction e.g. a fraction obtained according to the Cohn fractionation
  • albumin e.g., an albumin-containing precipitate from the Cohn fractionation is used.
  • the exchange step thus must be carried out under non-precipitating conditions, since otherwise—as has been mentioned—there will be a risk that the citrate can be removed only insufficiently because of its high affinity to the precipitated protein.
  • the exchange of the citrate will take place at an early time in the preparation method.
  • a medicament comprising one or several factors of coagulation and fibrinolysis, immunoglobulins, glycoproteins and/or albumin, is prepared.
  • fibrinogen, prothrombin, the factors V, VII, VIII, IX, X, XI, XII and XIII optionally in their activated form, von Willebrand factor, but also anticoagulants, such as heparin, heparinoids or cumarin derivatives, or fibrinolytic agents, such as streptokinase, urokinase, pro-urokinase, t-PA or plasmin, can be considered as the coagulation and fibrinolysis factors.
  • the immunoglobulins various preparations comprising immunoglobulins of the classes IgG, IgA, IgM and mixtures thereof, optionally in high titers, may be prepared.
  • glycoprotein orosomucoid may, e.g., be used.
  • a salt of an organic carboxylic acid having 2 to 20 carbon atoms is used for the exchange of the citrate, a caprylate or a tartrate or mixtures thereof being particularly preferred.
  • an organic mono- or dicarboxylic acid is to be understood as a mono- or dicarboxylate, since in any case the exchange of the citrate in solution will always be for the anion of the acid.
  • an organic mono- or dicarboxylic acid having 2 to 4 carbon atoms is used for exchanging the citrate.
  • the method according to the invention has proved particularly suitable for the preparation of plasma-protein-containing medicaments that exhibit excellent properties particularly in respect of their aluminum contamination by being substantially free from any detectable aluminum.
  • exchanging of the citrate must be effected under non-precipitating conditions.
  • the exchange step is effected during a diafiltration, ultrafiltration or during a chromatographic process, since these steps have proved particularly suitable for a simple, low-cost and effecient exchange.
  • the conditions during the exchange step depend on the method used and in particular will be chosen such that the exchange of the citrate and optionally also of citrate-bound metals will be as complete as possible. Therefore, the respective parameter which determine the method, in particular the temperature, the duration of the exchange step and the concentration of the respective mono- or dicarboxylate or mono- or dicarboxylic acid, respectively, have to be optimized.
  • the temperature will preferably be in a range of between 0 and 50° C., more preferred in a range of between 10 and 30° C., most preferred approximately at room temperature.
  • the respective period of time for the exchange is particularly dependent on the ratio of the volume to be exchanged to the membrane surface and on the temperature and preferably is at least 30 minutes, in particular the period of time will be in a range of between 30 minutes and several hours.
  • a parameter like the period of time will just as well depend on the respective exchange volume of the material in question.
  • the exchange volume will be at least 5 times, most preferred at least 30 times that of the starting solution, and the period of time for the exchange will be chosen accordingly.
  • the concentration of mono- or dicarboxylate or of mono- or dicarboxylic acid preferably is in a range of between 0.001 and 10 mol/l, most preferred in a range of between 0.001 and 1 mol/l.
  • Sodium caprylate e.g., is added at a concentration of between 1.0 mmol/l and 1.5 mol/l, preferably in a range of between 1.0 mmol/l and 25 mmol/l.
  • Sodium acetate e.g., is added at a concentration of between 1 mmol/l and 5.5 mol/l, preferably between 50 mmol/l and 1.0 mol/l.
  • the sodium salt of the hexanoic acid e.g., is added at a concentration of between 1.0 mmol/l and 1.0 mol/l, preferably in a range of between 5.0 mmol/l and 0.1 mol/l.
  • Sodium tartrate may be added at a concentration of between 1.0 mmol/l and 1.2 mol/l, preferably between 10.0 mmol/l and 0.2 mol/l.
  • salts of higher acids thus the efficient amounts can already be found in a range of from 0.001 to 0.1 mol/l, while salts of lower acids preferably are added at somewhat higher concentrations.
  • a further parameter which is decisive for the method is the pH of the solution.
  • it is at pH 6 to 8, most preferred at pH 6.5 to 7.5.
  • Beside carboxylate or carboxylic acid may be contained in the solution for increasing the ionic strength thereof.
  • inorganic salts such as, e.g., sodium or potassium salts
  • an at least 4% sodium chloride solution is contained.
  • various buffer salts may be contained.
  • materials for the respective exchange method in particular commercially available materials, such as, e.g., diafiltration membranes, ultrafiltration units, various chromatographic gels, molecular sieves and others may be used. All these materials may be based on organic or inorganic materials; they may be of synthetic of biological origin.
  • a preferred embodiment of the method according to the invention thus relates to a method in which the plasma-protein-containing solution is treated, preferably heat-treated, before and/or after the exchange so as to inactivate possibly present viruses.
  • Common virus inactivation treatments which may be used within the scope of the present method have been described in EP-0 159 311, EP-0 519 901 or in EP-0 674 531.
  • the plasma protein recovered is further subjected to a dialyses against a medium with a low salt content, e.g. water. This may provide an additional stabilizing effect for the plasma protein because of the presence of the mono- or dicarboxylate.
  • the recovery of the plama protein or plasma proteins and the finishing of the medicament preferably should be effected exclusively with citrate-free components so as to avoid the renewed contamination of the preparation with citrate ions which are responsible for a renewed contamination with metal ions in case of longer storage.
  • the method according to the invention has proved quite particularly suitable for removing aluminum ions or for preventing a renewed contamination with aluminum ions, respectively, during storage of the medicament.
  • metal ions from which it is known that they may contaminate plasma-protein-containing medicaments, such as aluminum-like metals, cadmium, zink, lead, iron and others, may efficiently be reduced.
  • an object of the present invention is also a plasma-protein-containing medicament which is obtainable according to the method of the invention and has a content of undesired metal of less than 100 ⁇ g/l, preferably less than 10 ⁇ g/l, in particular less than 200 ng/l, determined, e.g., by atomic absorption spectroscopy, this maximum content not being exceeded even after extended storage, even when stored for more than 5 years.
  • the plasma-protein-containing medicament of the invention may be stored in the most varying containers of the prior art.
  • Such containers may consist of glass, synthetic material, metals or combinations thereof.
  • the containers may also be specially pre-treated; thus, the surface may have been siliconized, e.g.
  • As the glasses both hard glasses and soft glasses (cf. e.g. glasses of the classification USP 23, p. 1781) may be used.
  • the plasma-protein-containing medicament of the invention has a low content of undesired metals when stored in hard glasses; particularly preferred the latter is less than 100 ⁇ g/l, more preferred less than 10 ⁇ g/l, most preferred less than 200 ng/l.
  • a precipitate of Cohn fractionation comprising albumin in a purity of >95% is dissolved 1+2 (w/v; 1kg in 2) in 50 g/l NaCl solution at a neutral pH.
  • the solution is continuously diafiltered with a regenerated cellulose membrane at +4° C. against water. At this, 0.1 mmol caprylate is added per g of protein.
  • Table 1 b) shows the aluminum decrease and the citrate decrease after diafiltration with the addition of 0.1 mmol caprylate. 1 b) with the addition of caprylate Aluminum content Citrate content ⁇ g/g ⁇ mol/g Sample Protein in % Protein in % Before 2.999 100.0 139.5 100.0 diafiltration Diaconcentrate 0.096 3.2 1.1 0.8
  • a precipitate of Cohn fractionation comprising albumin in a purity of >95% is dissolved 1+2 (w/v; 1 kg in 2 l) in 50 g/l NaCl solution at a neutral pH.
  • the solution is continuously diafiltered with a regenerated cellulose membrane at +4° C. against water. At this, 5 mmol acetate is added per g of protein.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US09/254,288 1996-09-16 1997-09-10 Process for producing a plasma protein-containing medicament Abandoned US20020034809A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US11/151,295 US8709492B2 (en) 1996-09-16 2005-06-14 Process for producing a plasma protein-containing medicament with reduced concentration of citrate and metals
US14/264,369 US20140234292A1 (en) 1996-09-16 2014-04-29 Process for Producing a Plasma Protein-Containing Medicament

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ATA1633/96 1996-09-16
AT0163396A AT403989B (de) 1996-09-16 1996-09-16 Verfahren zur herstellung eines plasmaprotein-hältigen arzneimittels

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/AT1997/000197 A-371-Of-International WO1998012225A2 (de) 1996-09-16 1997-09-10 Verfarhen zur herstellung eines plasmaprotein-hältigen arzneimittels

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/151,295 Continuation US8709492B2 (en) 1996-09-16 2005-06-14 Process for producing a plasma protein-containing medicament with reduced concentration of citrate and metals

Publications (1)

Publication Number Publication Date
US20020034809A1 true US20020034809A1 (en) 2002-03-21

Family

ID=3517640

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/254,288 Abandoned US20020034809A1 (en) 1996-09-16 1997-09-10 Process for producing a plasma protein-containing medicament
US11/151,295 Expired - Lifetime US8709492B2 (en) 1996-09-16 2005-06-14 Process for producing a plasma protein-containing medicament with reduced concentration of citrate and metals
US14/264,369 Abandoned US20140234292A1 (en) 1996-09-16 2014-04-29 Process for Producing a Plasma Protein-Containing Medicament

Family Applications After (2)

Application Number Title Priority Date Filing Date
US11/151,295 Expired - Lifetime US8709492B2 (en) 1996-09-16 2005-06-14 Process for producing a plasma protein-containing medicament with reduced concentration of citrate and metals
US14/264,369 Abandoned US20140234292A1 (en) 1996-09-16 2014-04-29 Process for Producing a Plasma Protein-Containing Medicament

Country Status (24)

Country Link
US (3) US20020034809A1 (cs)
EP (1) EP0927195B1 (cs)
JP (1) JP2001500867A (cs)
KR (1) KR20000036002A (cs)
CN (1) CN1230967A (cs)
AR (1) AR009582A1 (cs)
AT (2) AT403989B (cs)
AU (1) AU732519B2 (cs)
BR (1) BR9712044A (cs)
CA (1) CA2265936C (cs)
CZ (1) CZ91199A3 (cs)
DE (1) DE59710700D1 (cs)
DK (1) DK0927195T3 (cs)
ES (1) ES2206701T3 (cs)
HU (1) HUP0002265A3 (cs)
ID (1) ID21224A (cs)
IL (1) IL128770A0 (cs)
IN (1) IN187314B (cs)
MX (1) MXPA99002144A (cs)
NO (1) NO991198L (cs)
PL (1) PL332159A1 (cs)
PT (1) PT927195E (cs)
SK (1) SK32899A3 (cs)
WO (1) WO1998012225A2 (cs)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040191231A1 (en) * 1997-11-12 2004-09-30 Friedrich Braun Medicinal product for the promotion of wound healing
WO2004054607A3 (de) * 2002-12-18 2004-10-07 Bio Prod & Bio Eng Ag Stabile therapeutische proteine
US20060160720A1 (en) * 2003-05-23 2006-07-20 Novo Nordisk A/S Protein stabilization in solution

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2103236B1 (es) * 1996-01-30 1998-04-16 Grifols Grupo Sa Albumina humana terapeutica con baja capacidad para la fijacion de aluminio.
AT408946B (de) * 1999-02-18 2002-04-25 Immuno Ag Verwendung von orosomucoid zur herstellung einer pharmazeutischen präparation
JP2003040798A (ja) * 2001-07-26 2003-02-13 Nihon Pharmaceutical Co Ltd 低アルミニウム含有アルブミン製剤およびその製造法
ES2325653T3 (es) 2001-12-21 2009-09-11 Novo Nordisk Health Care Ag Composicion liquida de polipeptidos del factor vii.
US7897734B2 (en) 2003-03-26 2011-03-01 Novo Nordisk Healthcare Ag Method for the production of proteins
JP5653572B2 (ja) 2003-08-14 2015-01-14 ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト 第ｖｉｉ因子ポリペプチドの液状水性医薬組成物
ES2294976B1 (es) * 2007-11-12 2008-12-16 Grifols, S.A. "procedimiento de obtencion de albumina humana de alta eficacia para su uso en terapia de detoxificacion".
EP3835420A1 (en) 2011-12-05 2021-06-16 Factor Bioscience Inc. Methods and products for transfecting cells
US8497124B2 (en) 2011-12-05 2013-07-30 Factor Bioscience Inc. Methods and products for reprogramming cells to a less differentiated state
ES2381828B1 (es) * 2012-03-20 2012-11-16 Grifols, S.A. PROCEDIMIENTO PARA OBTENER UNA COMPOSICION DE IgG MEDIANTE TRATAMIENTO TERMICO
CA3067735A1 (en) 2017-08-17 2019-02-21 Just Biotherapeutics, Inc. Method of purifying glycosylated protein from host cell galectins and other contaminants

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5846930A (en) * 1996-01-30 1998-12-08 Grupo Grifols, S.A. Therapeutic human albumin having a low aluminium binding capacity

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE384134C (de) * 1921-05-07 1923-10-25 Chemisch Pharmazeutische Werke Verfahren zur Herstellung eines Kamillenextraktes
DE2331854A1 (de) * 1973-06-22 1975-01-16 Greither Salus Haus Dr Otto Verfahren zur herstellung standardisierter arzneimittel aus kamillenblueten
FR2630115B1 (fr) * 1988-04-14 1994-10-28 Merieux Inst Procede de stabilisation des solutions d'albumine humaine et solution obtenue
SE500110C2 (sv) * 1989-06-27 1994-04-18 Kabi Pharmacia Ab Sätt att rena ett protein från därtill bundna flervärda metalljoner
US5250663A (en) * 1990-04-19 1993-10-05 Miles Inc. Preparing essentially monomeric normal human serum albumin
JP2949846B2 (ja) * 1990-11-30 1999-09-20 吉富製薬株式会社 アルブミン製剤の保存方法
US5561115A (en) * 1994-08-10 1996-10-01 Bayer Corporation Low temperature albumin fractionation using sodium caprylate as a partitioning agent
US5744586A (en) * 1996-06-26 1998-04-28 Alpha Therapeutic Corporation Manufacturing process for the production of purified transferrin
US5886154A (en) 1997-06-20 1999-03-23 Lebing; Wytold R. Chromatographic method for high yield purification and viral inactivation of antibodies

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5846930A (en) * 1996-01-30 1998-12-08 Grupo Grifols, S.A. Therapeutic human albumin having a low aluminium binding capacity

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040191231A1 (en) * 1997-11-12 2004-09-30 Friedrich Braun Medicinal product for the promotion of wound healing
US8268362B2 (en) 1997-11-12 2012-09-18 Bio-Products & Bio-Engineering Aktiengesellschaft Medicinal product for the promotion of wound healing
WO2004054607A3 (de) * 2002-12-18 2004-10-07 Bio Prod & Bio Eng Ag Stabile therapeutische proteine
US20060009376A1 (en) * 2002-12-18 2006-01-12 Johann Eibl Stable therapeutic proteins
US20110009324A1 (en) * 2002-12-18 2011-01-13 Johann Eibl Stable Therapeutic Proteins
US20060160720A1 (en) * 2003-05-23 2006-07-20 Novo Nordisk A/S Protein stabilization in solution
US8536127B2 (en) 2003-05-23 2013-09-17 Novo Nordisk Healthcare Ag Protein stabilization in solution

Also Published As

Publication number Publication date
JP2001500867A (ja) 2001-01-23
IL128770A0 (en) 2000-01-31
AT403989B (de) 1998-07-27
NO991198L (no) 1999-05-14
BR9712044A (pt) 1999-08-24
IN187314B (cs) 2002-03-23
EP0927195A2 (de) 1999-07-07
AU4289997A (en) 1998-04-14
NO991198D0 (no) 1999-03-11
PT927195E (pt) 2004-01-30
MXPA99002144A (es) 2005-04-28
AR009582A1 (es) 2000-04-26
EP0927195B1 (de) 2003-09-03
DK0927195T3 (da) 2003-11-24
AU732519B2 (en) 2001-04-26
KR20000036002A (ko) 2000-06-26
WO1998012225A3 (de) 1998-04-23
ID21224A (id) 1999-05-06
HUP0002265A2 (hu) 2000-11-28
PL332159A1 (en) 1999-08-30
ATA163396A (de) 1997-12-15
US20050249815A1 (en) 2005-11-10
CZ91199A3 (cs) 1999-06-16
ES2206701T3 (es) 2004-05-16
CA2265936C (en) 2008-04-22
SK32899A3 (en) 1999-08-06
WO1998012225A2 (de) 1998-03-26
ATE248857T1 (de) 2003-09-15
DE59710700D1 (de) 2003-10-09
CN1230967A (zh) 1999-10-06
US20140234292A1 (en) 2014-08-21
CA2265936A1 (en) 1998-03-26
US8709492B2 (en) 2014-04-29
HUP0002265A3 (en) 2003-01-28

Similar Documents

Publication Publication Date Title
US20140234292A1 (en) Process for Producing a Plasma Protein-Containing Medicament
EP0315968B2 (en) Plasma and recombinant protein formulations in low ionic strength media
KR970010923B1 (ko) 혈장단백질의 크로마토그래피 분리법
EP0037078B1 (en) Process for heat treatment of aqueous solution containing human blood coagulation factor xiii
EP0314095B1 (en) Plasma and recombinant protein formulation in high ionic strength media
CA2033969C (en) Albumin preparation and process for producing same
US6239261B1 (en) Pasteurized, purified von Willebrand factor concentrate and a process for the preparation thereof
CA2052809A1 (en) Process for producing secretory immunoglobulin a preparations
US4562072A (en) Process for the pasteurization of antihemophilic cryoprecipitate (AHC) and antihemophilic cryoprecipitate prepared thereby
EP0148843B2 (en) A concentrate of the antihemophilic factor viii and a process for producing it
EP0559895B1 (en) Albumin preparation and preservation thereof
AU659301B2 (en) A method of producing a factor VIII preparation
US4814435A (en) Method of producing a factor VIII (AHF) containing fraction
US6063909A (en) Preparation of factor IX
EP0685491A2 (en) Process for producing albumin preparation
JPS61189228A (ja) 血液凝固第８因子製剤の製法
US5989593A (en) Method for producing antithrombin-III, method for purifying it, and preparation containing it
EP0116571B1 (en) Method for making gamma globulin-containing compositions
JPH01305036A (ja) 血漿蛋白成分の加熱処理方法および血漿蛋白成分製剤

Legal Events

Date Code Title Description
AS Assignment

Owner name: IMMUNO AKTIENGESELLSCHAFT, AUSTRIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TESCHNER, WOLFGANG;LINNAU, YENDRA;SVATOS, SONJA;AND OTHERS;REEL/FRAME:010530/0510

Effective date: 19990319

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION