JPWO2016153041A1 - 銅イオン制御製造方法 - Google Patents
銅イオン制御製造方法 Download PDFInfo
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- JPWO2016153041A1 JPWO2016153041A1 JP2017508467A JP2017508467A JPWO2016153041A1 JP WO2016153041 A1 JPWO2016153041 A1 JP WO2016153041A1 JP 2017508467 A JP2017508467 A JP 2017508467A JP 2017508467 A JP2017508467 A JP 2017508467A JP WO2016153041 A1 JPWO2016153041 A1 JP WO2016153041A1
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Abstract
Description
(1)細胞を含む種培地を初発培地に添加し、初発培地中で細胞の培養を開始する細胞の培養方法であって、初発培地に生物由来培地用添加物が添加されていること、および、当該初発培地の細胞培養開始時の銅含量が0.02ppm以下であることを特徴とする、細胞の培養方法。
(2)当該初発培地の細胞培養開始時の銅含量が0.015ppm以下であることを特徴とする、(1)の培養方法。
(3)初発培地に、銅含量が1ppm以下である生物由来培地用添加物が添加されていることを特徴とする、(1)又は(2)の培養方法。
(4)初発培地に加える種培地にも、銅含量が1ppm以下である生物由来培地用添加物が添加されていることを特徴とする、(3)の細胞の培養方法。
(5)培養方法が、バッチ培養、流加培養(Fed-batch培養)、連続培養、回分培養または半回分培養である、(1)〜(4)のいずれかに記載の培養方法。
(6)培養方法が、流加培養(Fed-batch培養)である、(1)〜(4)のいずれかに記載の培養方法。
(7)初発培地に加える流加培地に、銅含量が3ppm以下である生物由来培地用添加物が添加されていることを特徴とする、(6)の培養方法。
(8)流加培地由来の銅イオンが、培養終了時の培地中で0.08ppm以下である、(6)又は(7)の培養方法。
(9)培養終了時の培地中の銅イオンが0.1pmm以下である、(6)〜(8)のいずれかに記載の培養方法。
(10)生物由来培地用添加物が、動植物由来培地用添加物である(1)〜(9)のいずれかに記載の培養方法。
(11)生物由来培地用添加物が、魚由来培地用添加物である(1)〜(9)のいずれかに記載の培養方法。
(12)生物由来培地用添加物が、魚肉加水分解物である(1)〜(9)のいずれかに記載の培養方法。
(13)培地に添加される生物由来培地用添加物が、予め、銅含量が測定されたものである、(1)〜(12)のいずれかに記載の培養方法。
(14)細胞が動物細胞である、(1)〜(13)のいずれかに記載の培養方法。
(15)細胞が哺乳動物細胞である、(14)の培養方法。
(16)哺乳動物細胞がCHO細胞である、(15)の培養方法。
(17)細胞が所望のタンパク質をコードする遺伝子を導入したものである、(1)〜(16)の培養方法。
(18)所望のタンパク質が抗体である、(17)の培養方法。
(19)抗体がトシリズマブである、(18)の培養方法。
(20)初発培地に、銅含量が測定された生物由来培地用添加物が添加されていることを特徴とする細胞の培養方法。
(21)培養方法が、バッチ培養、流加培養(Fed-batch培養)、連続培養、回分培養または半回分培養である、(20)の培養方法。
(22)培養方法が、流加培養(Fed-batch培養)である、(20)の培養方法。
(23)以下の工程を含む、細胞の培養方法;
1)予め、培地に添加する生物由来培地用添加物の銅含量を測定する工程
2)測定された上記添加物のうち、銅含量が1ppm以下である添加物を選んで、初発培地に添加する工程。
(24)以下の工程を含む、細胞の流加培養方法;
1)予め、培地に添加する生物由来培地用添加物の銅含量を測定する工程
2)測定された上記添加物のうち、銅含量が1ppm以下である添加物を選んで、種培地若しくは初発培地に添加する工程。
3)測定された上記添加物のうち、銅含量が3ppm以下である添加物を選んで、流加培地に添加する工程。
(25)(1)〜(24)のいずれかに記載の培養方法を用いて、タンパク質を製造する方法。
(26)以下の工程を含む、所望のタンパク質を含有する医薬組成物を製造する方法:
1)(25)の製造方法で所望のタンパク質を製造する工程、及び
2)工程1)で製造した所望のタンパク質を、医薬的に許容される担体及び添加剤と混合して製剤化することにより、医薬組成物を製造する工程。
(27)(1)〜(24)のいずれかに記載の培養方法を用いて、所望のタンパク質のC末端のアミド体の生成を抑制する方法。
(28)所望のタンパク質が抗体である(27)の方法。
培地組成及び調製法は以下のとおりである。
培地組成及び調製法は以下のとおりである。
培地組成及び調製法は以下のとおりである。
培地組成及び調製法は以下のとおりである。
なお、本実施例では、重回帰分析の結果、種培養培地に含まれる銅含量が目的変数に影響を及ぼさないことが示された。
Claims (28)
- 細胞を含む種培地を初発培地に添加し、初発培地中で細胞の培養を開始する細胞の培養方法であって、
初発培地に生物由来培地用添加物が添加されていること、および、当該初発培地の細胞培養開始時の銅含量が0.02ppm以下であることを特徴とする、細胞の培養方法。 - 当該初発培地の細胞培養開始時の銅含量が0.015ppm以下であることを特徴とする、請求項1記載の培養方法。
- 初発培地に、銅含量が1ppm以下である生物由来培地用添加物が添加されていることを特徴とする、請求項1又は2記載の培養方法。
- 初発培地に加える種培地に、銅含量が1ppm以下である生物由来培地用添加物が添加されていることを特徴とする、請求項3記載の培養方法。
- 培養方法が、バッチ培養、流加培養(Fed-batch培養)、連続培養、回分培養または半回分培養である、請求項1〜4のいずれかに記載の培養方法。
- 培養方法が、流加培養(Fed-batch培養)である、請求項1〜4のいずれかに記載の培養方法。
- 初発培地に加える流加培地に、銅含量が3ppm以下である生物由来培地用添加物が添加されていることを特徴とする、請求項6記載の培養方法。
- 流加培地由来の銅イオンが、培養終了時の培地中で0.08ppm以下である、請求項6又は7記載の培養方法。
- 培養終了時の培地中の銅イオンが0.1ppm以下である、請求項6〜8のいずれかに記載の培養方法。
- 生物由来培地用添加物が、動植物由来培地用添加物である請求項1〜9のいずれかに記載の培養方法。
- 生物由来培地用添加物が、魚由来培地用添加物である請求項1〜9のいずれかに記載の培養方法。
- 生物由来培地用添加物が、魚肉加水分解物である請求項1〜9のいずれかに記載の培養方法。
- 培地に添加される生物由来培地用添加物が、予め、銅含量が測定されたものである請求項1〜12のいずれかに記載の培養方法。
- 細胞が動物細胞である請求項1〜13のいずれかに記載の培養方法。
- 細胞が哺乳動物細胞である請求項14記載の培養方法。
- 哺乳動物細胞がCHO細胞である請求項15記載の培養方法。
- 細胞が所望のタンパク質をコードする遺伝子を導入したものである請求項1〜16のいずれかに記載の培養方法。
- 所望のタンパク質が抗体である請求項17記載の培養方法。
- 抗体がトシリズマブである請求項18記載の培養方法。
- 初発培地に、銅含量が測定された生物由来培地用添加物が添加されていることを特徴とする細胞の培養方法。
- 培養方法が、バッチ培養、流加培養(Fed-batch培養)、連続培養、回分培養または半回分培養である、請求項20記載の培養方法。
- 培養方法が、流加培養(Fed-batch培養)である、請求項20記載の培養方法。
- 以下の工程を含む、細胞の培養方法;
1)予め、培地に添加する生物由来培地用添加物の銅含量を測定する工程
2)測定された上記添加物のうち、銅含量が1ppm以下である添加物を選んで、初発培地に添加する工程。 - 以下の工程を含む、細胞の流加培養方法;
1)予め、培地に添加する生物由来培地用添加物の銅含量を測定する工程
2)測定された上記添加物のうち、銅含量が1ppm以下である添加物を選んで、種培地若しくは初発培地に添加する工程。
3)測定された上記添加物のうち、銅含量が3ppm以下である添加物を選んで、流加培地に添加する工程。 - 請求項1〜24のいずれかの培養方法を用いて、タンパク質を製造する方法。
- 以下の工程を含む、所望のタンパク質を含有する医薬組成物を製造する方法:
1)請求項25の製造方法で所望のタンパク質を製造する工程、及び
2)工程1)で製造した所望のタンパク質を、医薬的に許容される担体及び添加剤と混合して製剤化することにより、医薬組成物を製造する工程。 - 請求項1〜24のいずれかの培養方法を用いて、所望のタンパク質のC末端のアミド体の生成を抑制する方法。
- 所望のタンパク質が抗体である請求項27記載の方法。
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