EP0971727A1 - Herstellungsverfahren für intravenöses serumglobulin sowie das erhaltene produkt - Google Patents

Herstellungsverfahren für intravenöses serumglobulin sowie das erhaltene produkt

Info

Publication number
EP0971727A1
EP0971727A1 EP98961803A EP98961803A EP0971727A1 EP 0971727 A1 EP0971727 A1 EP 0971727A1 EP 98961803 A EP98961803 A EP 98961803A EP 98961803 A EP98961803 A EP 98961803A EP 0971727 A1 EP0971727 A1 EP 0971727A1
Authority
EP
European Patent Office
Prior art keywords
gamma globulin
solution
globulin solution
fraction
detergent
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.)
Withdrawn
Application number
EP98961803A
Other languages
English (en)
French (fr)
Other versions
EP0971727A4 (de
Inventor
Raja R. Mamidi
Andranik Bagdasarian
Kazuo Takechi
Gorgonio Canaveral
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.)
Grifols Shared Services North America Inc
Original Assignee
Alpha Therapeutic Corp
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
Application filed by Alpha Therapeutic Corp filed Critical Alpha Therapeutic Corp
Publication of EP0971727A1 publication Critical patent/EP0971727A1/de
Publication of EP0971727A4 publication Critical patent/EP0971727A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • 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
    • C07K16/065—Purification, fragmentation
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an integral, multi-step commercial process for the production of intravenously administrable immune serum globulin containing IgG ( ⁇ -globulin) as the main ingredient.
  • Patent 4,876,088 by Hirao et al. describes the preparation of intravenously injectable ⁇ -globulin solution from Cohn Fraction II + III paste in which the paste is suspended in water, its pH adjusted to 5.5 and centrifuged, with the supernatant then being heat treated for viral inactivation in the presence of 33% w/v of sorbitol, followed by PEG fractionation (6%/12%) which would remove heat denatured protein and then by other purification steps including DEAE- Sephadex ion exchange chromatography.
  • PEG fractionation is carried out on the heat treated solution.
  • PEG fractionation is a well known procedure in the art of purification of immune globulin in order to separate the desired IgG monomer and dimer from IgG aggregate and from other impurities naturally occurring in the starting plasma protein fraction.
  • the PEG fractionation also accomplishes a separation between the desired IgG monomer and di er, and unwanted denatured protein products produced by the heat treatment. These denatured protein products are denatured prekallikrein, plasminogen, plasmin, IgA, IgM and aggregates. Any of the PEG fractionation procedures documented in the prior art can be used. In general, two stages of PEG fractionation are carried out.
  • the filtrate will then have its pH adjusted to about 8.0 to 9.0, preferably about 8.5 to 8.9, and additional PEG added for final concentration of about 10 to 15%, preferably about 12%.
  • the precipitate formed, which is purified immunoglobulin, is removed by filtration and/or centrifugation.
  • the solution to be subjected to the solvent- detergent should be treated for removal of all particulate matter, which can include denatured protein. Therefore, it is preferred to filter the solution with a 1 micron or finer filter prior to solvent-detergent addition. This will also reduce the likelihood of virus being present within a large particle and thereby possibly avoiding exposure to the solvent-detergent.
  • the anionic exchanger to be used comprises anion exchanging groups bonded to an insoluble carrier.
  • the anion exchanging groups include diethylaminoethyl (DEAE) , a quaternary aminoethyl (QAE) group, etc.
  • the insoluble carrier includes agarose, cellulose, dextran, polyacrylamide, etc.
  • Usable cationic exchangers are carboxy methyl Sephadex (CM-Sephadex) CM-cellulose, SP-Sephadex, CM- Sepharose and S-Sepharose.
  • the pH of the 6% PEG suspension was adjusted to 5.7 with 0.5 N sodium hydroxide and the suspension was mixed for 2 hours.
  • Acid wash Celite 535 was added to a final concentration of 1.5% and the suspension was mixed for 1 hour.
  • the precipitate along with the Celite was removed by filtration.
  • the pH of the filtrate was adjusted to 8.8 with 0.5 N sodium hydroxide, and the PEG concentration adjusted to 12% with the addition of 50% PEG solution.
  • the pH of the 12% PEG suspension was readjusted to 8.8, the suspension being mixed for 1 hour and filtered to collect the purified immune globulin paste. About 251 g of purified immune globulin paste was recovered.
  • D-sorbitol was added and final adjustments were made to yield a solution with composition of about 100 mg/mL of IgG and about 50 mg/mL D-sorbitol.
  • the solution was split into 2 parts, part A and part B.
  • the pH of part A was adjusted to 5.4 and part B was adjusted to pH 4.3.
  • the solutions of part A and part B were then individually sterile filtered through sterilized bacterial retentive filters and filled into vials.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
EP98961803A 1997-12-24 1998-12-07 Herstellungsverfahren für intravenöses serumglobulin sowie das erhaltene produkt Withdrawn EP0971727A4 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US99795297A 1997-12-24 1997-12-24
US997952 1997-12-24
PCT/US1998/025208 WO1999033484A1 (en) 1997-12-24 1998-12-07 Production process for intravenous immune serum globulin and resultant product

Publications (2)

Publication Number Publication Date
EP0971727A1 true EP0971727A1 (de) 2000-01-19
EP0971727A4 EP0971727A4 (de) 2005-01-19

Family

ID=25544595

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98961803A Withdrawn EP0971727A4 (de) 1997-12-24 1998-12-07 Herstellungsverfahren für intravenöses serumglobulin sowie das erhaltene produkt

Country Status (15)

Country Link
EP (1) EP0971727A4 (de)
JP (1) JP2001514672A (de)
KR (1) KR20000075562A (de)
CN (1) CN1214042C (de)
AR (1) AR018260A1 (de)
AU (1) AU747893B2 (de)
BR (1) BR9807598A (de)
CA (1) CA2281938A1 (de)
CO (1) CO4970799A1 (de)
IL (1) IL131471A0 (de)
MY (1) MY117328A (de)
RU (1) RU2198668C2 (de)
TW (1) TW546144B (de)
UA (1) UA64742C2 (de)
WO (1) WO1999033484A1 (de)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2270044T3 (en) 1998-06-09 2015-01-26 Csl Behring Ag Liquid immunoglobulin G (IgG) product
IL146433A0 (en) * 1999-06-15 2002-07-25 Alpha Therapeutic Corp A process for the preparation of an intravenously-administerable gamma globulin solution
JP2004525077A (ja) * 2000-09-28 2004-08-19 リサーチ　コーポレイション　テクノロジーズ，インコーポレイテッド イムノグロブリンｇ強化血漿画分の経口投与による免疫媒介性疾病の治療
ES2184594B1 (es) * 2001-01-17 2004-01-01 Probitas Pharma Sa Procedimiento para la produccion de gammaglobulina g humana inactivada de virus.
US6893639B2 (en) * 2001-10-19 2005-05-17 Hemacare Corporation Method for high yield purification of immune globulins from blood plasma and blood plasma intermediates
JP5525118B2 (ja) 2002-09-11 2014-06-18 中外製薬株式会社 タンパク質精製方法
TWI391399B (zh) 2005-05-25 2013-04-01 Hoffmann La Roche 測定溶離多肽之鹽濃度之方法
KR100791502B1 (ko) * 2006-09-29 2008-01-03 한스바이오메드 주식회사 바이러스 불활화된 무세포 인체 이식재 생산방법
US8980610B2 (en) * 2008-11-20 2015-03-17 Biogen Idec Ma Inc. Arginine inactivation of viruses
IL212911A0 (en) * 2011-05-16 2011-07-31 Omrix Biopharmaceuticals Ltd Immunoglobulin reduced in thrombogenic contaminants and preparation thereof
ES2381828B1 (es) * 2012-03-20 2012-11-16 Grifols, S.A. PROCEDIMIENTO PARA OBTENER UNA COMPOSICION DE IgG MEDIANTE TRATAMIENTO TERMICO
CA2941230C (en) 2014-03-11 2020-08-25 Green Cross Holdings Corporation Method for purifying immunoglobulin
CN107880116B (zh) * 2016-09-30 2023-02-03 盖立复集团公司 用于制备免疫球蛋白的方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4431833C1 (de) * 1994-09-07 1995-05-18 Blutspendedienst Der Drk Lande Verfahren zur Herstellung eines AHF-Konzentrates

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Publication number Priority date Publication date Assignee Title
DE2604759C2 (de) * 1976-02-07 1983-06-01 SCHURA Blutderivate GmbH & Co KG, 4150 Krefeld Verfahren zur Gewinnung von iv-verträglichen Γglobulinen
US4820805A (en) * 1983-07-14 1989-04-11 New York Blood Center, Inc. Undenatured virus-free trialkyl phosphate treated biologically active protein derivatives
US4835257A (en) * 1984-07-07 1989-05-30 Armour Pharma Gmbh Process for preparing gamma globulin suitable for intravenous administration using peg and a citrate buffer
FR2582515B1 (fr) * 1985-05-30 1988-11-04 Merieux Inst Procede de preparation de gamma-gobulines administrables par voie intraveineuse et gamma-globulines obtenues
JPH0662436B2 (ja) * 1986-05-19 1994-08-17 株式会社ミドリ十字 静注用免疫グロブリン製剤の製造方法
US4841023A (en) * 1986-06-25 1989-06-20 New York Blood Center, Inc. Inactivation of viruses in labile protein-containing compositions using fatty acids
DE3825429C2 (de) * 1988-07-27 1994-02-10 Biotest Pharma Gmbh Verfahren zur Herstellung eines intravenös verabreichbaren polyklonalen Immunglobulin-Präparates mit hohem IgM-Gehalt
CA2007545A1 (en) * 1989-01-13 1990-07-13 Yahiro Uemura Production method for protein-containing composition
JP2965069B2 (ja) * 1989-01-13 1999-10-18 吉富製薬株式会社 蛋白質含有組成物の製造方法
EP0431129B1 (de) * 1989-06-15 1996-05-29 Rorer International (Overseas) Inc. Verfahren zur inaktivierung von viren in mit viren verunreinigten pharmazeutischen zusammensetzungen
US5177194A (en) * 1990-02-01 1993-01-05 Baxter International, Inc. Process for purifying immune serum globulins
JP3145696B2 (ja) * 1990-10-05 2001-03-12 日本ケミカルリサーチ株式会社 分泌型免疫グロブリンａ製剤の製造法
US5110910A (en) * 1991-03-25 1992-05-05 Miles Inc. Virucidal euglobulin precipitation
JP4003235B2 (ja) * 1994-09-30 2007-11-07 三菱ウェルファーマ株式会社 静注用免疫グロブリン製剤の製造方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4431833C1 (de) * 1994-09-07 1995-05-18 Blutspendedienst Der Drk Lande Verfahren zur Herstellung eines AHF-Konzentrates

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
G]RTLER L: "ÄPossibilities of virus inactivation of pooled fresh plasma with tri-n-butylphosphate (TNBP) detergents (SD procedure)Ü" INFUSIONSTHERAPIE UND TRANSFUSIONSMEDIZIN. AUG 1994, vol. 21 Suppl 1, August 1994 (1994-08), pages 77-79, XP008039494 ISSN: 1019-8466 *
GAO F ET AL: "Enhancement in the safety of immune globulins prepared from high-risk plasma." VOX SANGUINIS. 1993, vol. 64, no. 4, 1993, pages 204-209, XP008036384 ISSN: 0042-9007 *
KOTITSCHKE R ET AL: "DOPPELT VIRUSINAKTIVIERTES FAKTOR-VIII-KONZENTRAT. VIRUSVALIDIERUNGUND IMMUNOLOGISCHE BEWERTUNG DES FVIII SDH" HAEMOSTASEOLOGIE, STUTTGART, DE, vol. 14, no. 2, 1994, pages 100-103, XP002040295 ISSN: 0720-9355 *
See also references of WO9933484A1 *
UEMURA Y ET AL: "INACTIVATION AND ELIMINATION OF VIRUSES DURING THE FRACTIONATION OFAN INTRAVENOUS IMMUNOGLOBULIN PREPARATION: LIQUID HEAT TREATMENT AND POLYETHYLENE GLYCOL FRACTIONATION" VOX SANGUINIS, S. KARGER AG, BASEL, CH, vol. 56, 1989, pages 155-161, XP002931112 ISSN: 0042-9007 *

Also Published As

Publication number Publication date
CA2281938A1 (en) 1999-07-08
MY117328A (en) 2004-06-30
AU747893B2 (en) 2002-05-30
AU1703899A (en) 1999-07-19
JP2001514672A (ja) 2001-09-11
KR20000075562A (ko) 2000-12-15
BR9807598A (pt) 2000-02-22
AR018260A1 (es) 2001-11-14
TW546144B (en) 2003-08-11
CO4970799A1 (es) 2000-11-07
WO1999033484A1 (en) 1999-07-08
EP0971727A4 (de) 2005-01-19
CN1214042C (zh) 2005-08-10
CN1252729A (zh) 2000-05-10
IL131471A0 (en) 2001-01-28
UA64742C2 (uk) 2004-03-15
RU2198668C2 (ru) 2003-02-20

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Inventor name: CANAVERAL, GORGONIO

Inventor name: TAKECHI, KAZUO

Inventor name: BAGDASARIAN, ANDRANIK

Inventor name: MAMIDI, RAJA, R.

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