JP2010000094A - 哺乳類細胞をインビトロで増殖させる改善法 - Google Patents
哺乳類細胞をインビトロで増殖させる改善法 Download PDFInfo
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- JP2010000094A JP2010000094A JP2009231190A JP2009231190A JP2010000094A JP 2010000094 A JP2010000094 A JP 2010000094A JP 2009231190 A JP2009231190 A JP 2009231190A JP 2009231190 A JP2009231190 A JP 2009231190A JP 2010000094 A JP2010000094 A JP 2010000094A
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Abstract
【解決手段】 本発明は、約1〜50 mmol/lの濃度の重炭酸もしくは三炭酸またはその塩の存在下で培養が行われることを特徴とする、動物細胞の培養時のグルコース消費および/または乳酸塩産生を減少させる方法であって、それにより重炭酸または三炭酸がクエン酸またはクエン酸塩である場合、この量のクエン酸またはクエン酸塩は、キレート複合体において鉄または別の遷移金属イオンに結合しない方法を提供する。
【選択図】 なし
Description
骨髄腫細胞系(Sp2/0)の細胞を融解して、10 Lバイオリアクターに接種するために、スピナーフラスコ中で約14日間2Lまで増殖させた。2日〜4日後、細胞を分割するか、または100 Lバイオリアクターに移して、さらに2日〜4日間培養した。100 Lバイオリアクターは、1000 L製造バイオリアクターのための接種用であった。それぞれの接種段階において、0.2〜0.4×106生存細胞/mLの開始細胞密度を用いた。
表1および表2は、クエン酸を添加したおよび添加していない実施の、グルコースの消費比速度およびCTIを示す(類似の結果はフマル酸塩を用いた場合にも認めることができる)。発酵は、1000 L規模の透析様式で行った。クエン酸塩を培地に加えると、グルコースの消費比速度は約44%減少し、CTIは約105%増加した。同時に乳酸塩の産生比速度は約60%減少した(表3および表4)。
骨髄腫細胞系の細胞を融解して(Sp2/0)、10 Lバイオリアクターに接種するためにスピナーフラスコにおいて2Lまで増殖させた。
表5および表6は、クエン酸を添加したおよび添加していない実施の、産生比速度およびCTIを示す。発酵は、10 Lの規模で流加培養様式で行った。クエン酸塩を培地に加えると、グルコースの消費比速度が約44%減少し、CTIが約241%増加した。同時に、乳酸塩の形成比速度は約52%減少した。このことは、クエン酸の添加によって、解糖を通してグルコースからの代謝の流れが阻害されることを示している。
Claims (4)
- 濃度が約1〜50 mmol/Lの重炭酸もしくは三炭酸(tricarbonic acid)またはその塩の存在下で、培養が行われることを特徴とする、動物細胞の培養中のグルコース消費および/または乳酸塩産生を減少させる方法であって、それにより重炭酸または三炭酸がクエン酸またはクエン酸塩である場合、この量の該クエン酸またはクエン酸塩は、キレート複合体において鉄または別の遷移金属イオンに結合しない方法。
- 重炭酸もしくは三炭酸またはその塩がクエン酸またはクエン酸塩であることを特徴とする、請求項1記載の方法。
- 動物細胞が哺乳類細胞であることを特徴とする、請求項1または2に記載の方法。
- 哺乳類細胞が骨髄腫、ハイブリドーマ、またはCHO細胞であることを特徴とする、請求項3記載の方法。
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EP02004366 | 2002-03-05 | ||
EP02004366.7 | 2002-03-05 |
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JP2003058803A Division JP4476554B2 (ja) | 2002-03-05 | 2003-03-05 | 哺乳類細胞をインビトロで増殖させる改善法 |
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JP2010000094A true JP2010000094A (ja) | 2010-01-07 |
JP5191970B2 JP5191970B2 (ja) | 2013-05-08 |
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JP2003058803A Expired - Lifetime JP4476554B2 (ja) | 2002-03-05 | 2003-03-05 | 哺乳類細胞をインビトロで増殖させる改善法 |
JP2009231190A Expired - Lifetime JP5191970B2 (ja) | 2002-03-05 | 2009-10-05 | 哺乳類細胞をインビトロで増殖させる改善法 |
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JP2003058803A Expired - Lifetime JP4476554B2 (ja) | 2002-03-05 | 2003-03-05 | 哺乳類細胞をインビトロで増殖させる改善法 |
Country Status (11)
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US (1) | US7390660B2 (ja) |
EP (1) | EP1342780B1 (ja) |
JP (2) | JP4476554B2 (ja) |
KR (1) | KR100576589B1 (ja) |
CN (1) | CN100398640C (ja) |
AT (1) | ATE304047T1 (ja) |
CA (1) | CA2417689C (ja) |
DE (1) | DE60301510T2 (ja) |
DK (1) | DK1342780T3 (ja) |
ES (1) | ES2248657T3 (ja) |
MX (1) | MXPA03001487A (ja) |
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KR20130101161A (ko) | 2005-01-05 | 2013-09-12 | 추가이 세이야쿠 가부시키가이샤 | 세포의 배양 방법 및 그 이용 |
DE102005046225B4 (de) * | 2005-09-28 | 2012-01-05 | Cellca Gmbh | Verbessertes Zellkulturmedium |
US8911964B2 (en) | 2006-09-13 | 2014-12-16 | Abbvie Inc. | Fed-batch method of making human anti-TNF-alpha antibody |
SG10201510384UA (en) | 2006-09-13 | 2016-01-28 | Abbvie Inc | Cell culture improvements |
TW200902708A (en) | 2007-04-23 | 2009-01-16 | Wyeth Corp | Methods of protein production using anti-senescence compounds |
EP2188371B1 (en) * | 2007-08-09 | 2017-12-20 | Wyeth LLC | Use of perfusion to enhance production of fed-batch cell culture in bioreactors |
AU2009347206C1 (en) | 2008-10-20 | 2016-12-08 | Abbvie Inc. | Isolation and purification of antibodies using Protein A affinity chromatography |
CA2738499A1 (en) | 2008-10-20 | 2010-04-29 | Abbott Laboratories | Viral inactivation during purification of antibodies |
DK2493922T3 (en) | 2009-10-26 | 2017-04-24 | Hoffmann La Roche | Process for preparing a glycosylated immunoglobulin |
ES2710543T3 (es) | 2010-12-27 | 2019-04-25 | Kyowa Hakko Kirin Co Ltd | Método para preparar una disolución acuosa que contiene medio de cultivo y agente quelante |
EP2702077A2 (en) | 2011-04-27 | 2014-03-05 | AbbVie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
US9206390B2 (en) | 2012-09-02 | 2015-12-08 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
CA2905010A1 (en) | 2013-03-12 | 2014-09-18 | Abbvie Inc. | Human antibodies that bind human tnf-alpha and methods of preparing the same |
WO2014151878A2 (en) | 2013-03-14 | 2014-09-25 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
WO2014159579A1 (en) | 2013-03-14 | 2014-10-02 | Abbvie Inc. | MUTATED ANTI-TNFα ANTIBODIES AND METHODS OF THEIR USE |
EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
HUE039551T2 (hu) | 2013-10-11 | 2019-01-28 | Regeneron Pharma | Metabolikusan optimalizált sejttenyészet |
US11390663B2 (en) | 2013-10-11 | 2022-07-19 | Regeneron Pharmaceuticals, Inc. | Metabolically optimized cell culture |
US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
JPWO2015155975A1 (ja) | 2014-04-07 | 2017-04-13 | 東洋製罐グループホールディングス株式会社 | 動物細胞用培養液、及び培養容器 |
WO2023167863A1 (en) | 2022-03-02 | 2023-09-07 | Regeneron Pharmaceuticals, Inc. | Manufacturing process for high titer antibody |
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- 2003-01-30 CA CA002417689A patent/CA2417689C/en not_active Expired - Fee Related
- 2003-02-18 MX MXPA03001487A patent/MXPA03001487A/es active IP Right Grant
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- 2003-03-04 DK DK03004806T patent/DK1342780T3/da active
- 2003-03-04 DE DE60301510T patent/DE60301510T2/de not_active Expired - Lifetime
- 2003-03-04 ES ES03004806T patent/ES2248657T3/es not_active Expired - Lifetime
- 2003-03-04 AT AT03004806T patent/ATE304047T1/de active
- 2003-03-04 EP EP03004806A patent/EP1342780B1/en not_active Expired - Lifetime
- 2003-03-05 CN CNB031070604A patent/CN100398640C/zh not_active Expired - Fee Related
- 2003-03-05 KR KR1020030013580A patent/KR100576589B1/ko not_active IP Right Cessation
- 2003-03-05 JP JP2003058803A patent/JP4476554B2/ja not_active Expired - Lifetime
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Also Published As
Publication number | Publication date |
---|---|
CA2417689C (en) | 2006-05-09 |
DE60301510D1 (de) | 2005-10-13 |
JP4476554B2 (ja) | 2010-06-09 |
ES2248657T3 (es) | 2006-03-16 |
MXPA03001487A (es) | 2005-09-08 |
US7390660B2 (en) | 2008-06-24 |
KR100576589B1 (ko) | 2006-05-04 |
US20030175951A1 (en) | 2003-09-18 |
KR20030074204A (ko) | 2003-09-19 |
EP1342780A1 (en) | 2003-09-10 |
CN100398640C (zh) | 2008-07-02 |
CA2417689A1 (en) | 2003-09-05 |
JP5191970B2 (ja) | 2013-05-08 |
EP1342780B1 (en) | 2005-09-07 |
DK1342780T3 (da) | 2005-12-12 |
ATE304047T1 (de) | 2005-09-15 |
CN1442478A (zh) | 2003-09-17 |
DE60301510T2 (de) | 2006-06-14 |
JP2003250533A (ja) | 2003-09-09 |
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