JP2016523877A - 方法 - Google Patents
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Classifications
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/363—Anion-exchange
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/30—Extraction; Separation; Purification by precipitation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Engineering & Computer Science (AREA)
- Water Supply & Treatment (AREA)
Abstract
Description
(a)IgG、他の免疫グロブリンおよび/または他のタンパク質混入物を含み、pHが3.5〜5.2の間であり、総タンパク質濃度が少なくとも10g/Lである酸性溶液を用意すること;
(b)該溶液の伝導率を1.5mS/cm未満に維持しつつ、pHを5.2〜6.2に調整すること;
(c)該溶液を少なくとも15分間インキュベートすること;ならびに
(d)任意の沈殿物を除去すること
を含む前記方法である。
(a)IgG、他の免疫グロブリンおよび/または他のタンパク質混入物を含み、pHが3.5〜5.2の間、好ましくは4.0〜5.0、より好ましくは4.6〜4.8であり、総タンパク質濃度が少なくとも10g/L、好ましくは約10〜50g/L、より好ましくは約10〜40g/L、さらにより好ましくは15〜30g/L、最も好ましくは20〜25g/Lである酸性溶液を用意する工程。
(1)オクタン酸(OA)分画、
(2)低pHインキュベーション、
(3)pHシフトおよび深層濾過、
(4)陰イオン交換クロマトグラフィー、
(5)ウイルス濾過、および
(6)限外濾過/ダイアフィルトレーションによる濃縮。
(i)深層濾過前にpHを変更すること(pHシフト)で行う予備精製。該工程は、仕上げのクロマトグラフィー工程前に非常に低い伝導率で行い、IgAおよびIgMの大部分を沈殿させ、かつIgGの共沈を最小限に抑える;
(ii)陰イオン交換クロマトグラフィー工程に用いる緩衝系の変更。
凍結NA沈殿物(PPT)の一部を適量の酢酸ナトリウム緩衝液に再懸濁し、pHを4.8で一定に保ちつつ、NA PPT懸濁液を室温でIgGの大部分が溶解するまで数時間撹拌した。
本発明によるpHシフト工程およびクロマトグラフィー緩衝系の最適化を組み込むことによって、(a)に記載された方法を改良した。
同じ出発中間体からのタンパク質収量に関する2つの方法の比較は表1〜3に示す。低pHインキュベーション(pH4)後のIgG収量を100%に設定した。
Claims (21)
- IgG、他の免疫グロブリンおよび/または他のタンパク質混入物を含む溶液からの精製方法におけるIgGの収量を増加させる方法であって、
(a)IgG、他の免疫グロブリンおよび/または他のタンパク質混入物を含み、pHが3.5〜5.2の間であり、総タンパク質濃度が少なくとも10g/Lである酸性溶液を用意すること;
(b)該溶液の伝導率を1.5mS/cm未満に維持しつつ、pHを5.2〜6.2に調整すること;
(c)該溶液を少なくとも15分間インキュベートすること;ならびに
(d)任意の沈殿物を除去すること
を含む前記方法。 - IgGを含む溶液は血漿由来の抗体を含む、請求項1に記載の方法。
- IgGを含む溶液はヒト血漿またはヒト脱クリオ血漿のエタノール分画によって得られる、請求項1または請求項2に記載の方法。
- IgGを含む溶液はオクタン酸沈殿から得た上清である、請求項3に記載の方法。
- 工程(a)における溶液は限外濾過ダイアフィルトレーションによって清澄化されている、請求項1〜4のいずれか1項に記載の方法。
- 工程(a)における溶液のpHは、3.9〜5.0、好ましくは3.9〜4.6、最も好ましくは3.9〜4.3である、請求項1〜5のいずれか1項に記載の方法。
- 工程(a)におけるタンパク質濃度は、10〜50g/Lの間、好ましくは20〜25g/Lの間である、請求項1〜6のいずれか1項に記載の方法。
- 工程(b)におけるpHは5.6〜6.0、好ましくは5.8〜6.0に調整される、請求項1〜7のいずれか1項に記載の方法。
- 工程(b)におけるpH調整は、カルボキシル基の有無にかかわらず、少なくとも1種の多水酸化アミン化合物の添加によって行われる、請求項1〜8のいずれか1項に記載の方法。
- 工程(b)における伝導率は、250mMを超える濃度、好ましくは500mMを超える濃度、より好ましくは750mMを超える濃度、最も好ましくは約1Mの濃度のトリスを用いて調整される、請求項1〜9のいずれか1項に記載の方法。
- 工程(b)における伝導率は、1.0mS/cm未満、好ましくは0.8mS/cm未満、より好ましくは0.2〜0.5mS/cmの間である、請求項1〜10のいずれか1項に記載の方法。
- 工程(b)におけるpHは5.6〜6.0に調整され、伝導率は0.2〜0.5mS/cmの間である、請求項1〜11のいずれか1項に記載の方法。
- 工程(c)におけるインキュベーション時間は、72時間まで、48時間まで、24時間まで、好ましくは12時間まで、より好ましくは6時間まで、最も好ましくは15分〜90分の間である、請求項1〜12のいずれか1項に記載の方法。
- 工程(c)におけるインキュベーションは室温で行われる、請求項1〜13のいずれか1項に記載の方法。
- 工程(d)における沈殿物は深層濾過によって除去される、請求項1〜14のいずれか1項に記載の方法。
- 工程(d)後、その樹脂に混入物を結合するが、IgGを結合しない条件下でイオン交換クロマトグラフィー工程が行われる、請求項1〜15のいずれか1項に記載の方法。
- イオン交換クロマトグラフィーは陰イオン交換クロマトグラフィーである、請求項16に記載の方法。
- 溶液の伝導率をさらに調整することなく、イオン交換クロマトグラフィーを行う、請求項16または請求項17に記載の方法。
- ウイルス不活化工程をさらに含む、請求項1〜18のいずれか1項に記載の方法。
- ウイルス不活化工程は低pH処理である、請求項19に記載の方法。
- 低pH処理は工程(a)の前に行われる、請求項20に記載の方法。
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KR102691585B1 (ko) * | 2015-08-21 | 2024-08-05 | 에프. 호프만-라 로슈 아게 | 친화성 크로마토그래피에서의 숙주 세포 단백질 감소 방법 |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1129494A (ja) * | 1997-06-20 | 1999-02-02 | Bayer Corp | 抗体の高収率精製およびウイルス不活性化のためのクロマトグラフイー法 |
JP2002517516A (ja) * | 1998-06-09 | 2002-06-18 | スタテンズ セーラム インスティテュート | 静脈投与用免疫グロブリン及び他の免疫グロブリン生成物の製造法 |
JP2008500959A (ja) * | 2004-01-30 | 2008-01-17 | スオメン プナイネン リスティ ヴェリパルヴェル | ウイルスについて安全な免疫グロブリンの製造方法 |
JP2010519507A (ja) * | 2007-02-16 | 2010-06-03 | ワットマン インコーポレイテッド | 制御された移転生体試料採取装置およびその装置を使用する方法 |
JP2011006489A (ja) * | 2002-09-11 | 2011-01-13 | Chugai Pharmaceut Co Ltd | タンパク質精製方法 |
JP2012054208A (ja) * | 2010-09-03 | 2012-03-15 | Toyota Central R&D Labs Inc | 水溶液系二次電池 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT373523B (de) * | 1982-03-23 | 1984-01-25 | Voest Alpine Ag | Vorrichtung zum querteilen bewegter blechbaender |
EP0447585B2 (de) | 1990-03-22 | 2003-05-07 | Biotest Pharma Gmbh | Verfahren zur Herstellung eines intravenös verträglichen Immunglobulin-G-Präparates |
US5886157A (en) | 1994-02-10 | 1999-03-23 | Vanderbilt University | Expression and purification of human cytochrome P450 |
DE19825334A1 (de) | 1998-06-05 | 1999-12-09 | Basf Ag | Verfahren zur Herstellung hochreaktiver Polyisobutene |
KR100501263B1 (ko) | 1998-06-09 | 2005-07-18 | 스태튼스 세룸 인스티튜트 | 정맥 주사용 면역글로불린의 제조 방법 및 그 외의 면역글로불린 제품 |
CN102250240B (zh) * | 2011-06-27 | 2013-07-31 | 山东泰邦生物制品有限公司 | 一种从血浆分离组分ⅰ+ⅲ中纯化人免疫球蛋白的方法 |
EP2636681A1 (en) * | 2012-03-09 | 2013-09-11 | CSL Behring AG | Process for enriching IgA |
-
2014
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1129494A (ja) * | 1997-06-20 | 1999-02-02 | Bayer Corp | 抗体の高収率精製およびウイルス不活性化のためのクロマトグラフイー法 |
JP2002517516A (ja) * | 1998-06-09 | 2002-06-18 | スタテンズ セーラム インスティテュート | 静脈投与用免疫グロブリン及び他の免疫グロブリン生成物の製造法 |
JP2011006489A (ja) * | 2002-09-11 | 2011-01-13 | Chugai Pharmaceut Co Ltd | タンパク質精製方法 |
JP2008500959A (ja) * | 2004-01-30 | 2008-01-17 | スオメン プナイネン リスティ ヴェリパルヴェル | ウイルスについて安全な免疫グロブリンの製造方法 |
JP2010519507A (ja) * | 2007-02-16 | 2010-06-03 | ワットマン インコーポレイテッド | 制御された移転生体試料採取装置およびその装置を使用する方法 |
JP2012054208A (ja) * | 2010-09-03 | 2012-03-15 | Toyota Central R&D Labs Inc | 水溶液系二次電池 |
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