JP2009543550A - 糖タンパク質の生産 - Google Patents
糖タンパク質の生産 Download PDFInfo
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- JP2009543550A JP2009543550A JP2009519501A JP2009519501A JP2009543550A JP 2009543550 A JP2009543550 A JP 2009543550A JP 2009519501 A JP2009519501 A JP 2009519501A JP 2009519501 A JP2009519501 A JP 2009519501A JP 2009543550 A JP2009543550 A JP 2009543550A
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Abstract
Description
「アミノ酸」:「アミノ酸」という用語は、本明細書では、ポリペプチドの形成において通常用いられる20の自然に存在するアミノ酸、またはこれらのアミノ酸の類似体もしくは誘導体または自然に存在しないアミノ酸のいずれかをさす。本発明のアミノ酸を、培地中で細胞培養に提供する。培地中に提供されるアミノ酸は、塩または水和物形態として提供することができる。
培地組成
糖タンパク質
凝固因子
抗体
酵素
成長因子および他のシグナリング分子
レセプター
宿主細胞中への糖タンパク質の発現のための遺伝子の導入
細胞
細胞の培養
発現された糖タンパク質の単離
免疫原性組成物
医薬処方
(実施例2:rFIXペプチドマッピングの小規模調査)
(実施例3:培地添加剤のrFIXペプチドマップに対する影響の小規模研究)
(実施例4:抗ABeta培地サンプルのN結合型オリゴ糖分析)
(実施例5:抗ベータマンガン研究サンプルのN結合型オリゴ糖分析)
Claims (30)
- 糖タンパク質を細胞培養において生産する方法であって:
約10nMから600nMの間のマンガンを含む細胞培地中、糖タンパク質の発現を可能にするために十分な条件および時間で、目的のタンパク質をコード化する遺伝子を含有する哺乳動物細胞を培養することを含み、発現された糖タンパク質のグリコシル化パターンは、マンガンが欠失している以外は同じ培地中、それ以外は同じ条件下で観察されるグリコシル化パターンよりも広範囲に及ぶ方法。 - 約10nMから600nMの間のマンガンを含む細胞培地中で目的の糖タンパク質をコード化する遺伝子を含有する哺乳動物細胞を培養する段階;
培養が第一温度範囲で維持される場合、約20%〜80%の範囲内の生存細胞密度に細胞が繁殖することを可能にするために十分な時間の第一期間の間、第一温度で培養を維持する段階;
培養を第二温度範囲にシフトさせる段階(ここで、第二温度範囲の少なくとも1つの温度は、第一温度範囲の最低温度よりも低い);
培養を第二期間中、糖タンパク質の発現を可能にするために十分な条件および時間維持する段階(ここで、発現された糖タンパク質のグリコシル化パターンは、マンガンが欠失している以外は同じ培地中でそれ以外は同じ条件下で観察されるグリコシル化パターンよりも広範囲に及ぶ)
を含む、請求項1記載の方法。 - 前記第一温度範囲が、約30から42℃の温度範囲を含む、請求項2記載の方法。
- 前記第一温度範囲が、約37℃の温度を含む、請求項3記載の方法。
- 前記第二温度範囲が、約25から41℃の温度範囲を含む、請求項2から4のいずれか1項記載の方法
- 前記第二温度範囲が、約31℃の温度を含む、請求項5記載の方法。
- 前記第一シフト段階後に、培養を第三温度または温度範囲にシフトさせることを含む第二シフト段階をさらに含み、前記第三温度または温度範囲の少なくとも1つの温度が前記第二温度範囲の最低温度よりも低い、請求項2から6のいずれか1項記載の方法。
- 前記第三温度範囲が、約25〜40℃である温度範囲を含む、請求項7記載の方法。
- 前記細胞培地が、約20から200nMの間のマンガンを含む、請求項1から8のいずれか1項記載の方法。
- 前記細胞培地が約40nMマンガンを含む、請求項9記載の方法。
- 前記細胞培地が約8mM以下の初期濃度でグルタミンを含む、請求項1から10のいずれか1項記載の方法。
- 前記細胞培地の初期グルタミン濃度が4mM以下である、請求項11記載の方法。
- 細胞培養の体積が少なくとも約500Lである、請求項1から12のいずれか1項記載の方法。
- 前記細胞培養に、初期細胞培養が始まった後に、フィード培地が提供される、請求項1から13のいずれか1項記載の方法。
- 前記細胞培養に、補助成分がさらに提供される、請求項1から14のいずれか1項記載の方法。
- 前記補助成分が、ホルモンおよび/または他の成長因子、無機イオン、緩衝液、ビタミン、ヌクレオシドもしくはヌクレオチド、微量元素、アミノ酸、脂質、グルコースまたは他のエネルギー源、およびその組み合わせからなる群から選択される、請求項15記載の方法。
- 前記細胞培養に約2グラム/リットルのグルコースが添加される、請求項16記載の方法。
- 前記細胞培地が合成培地である、請求項1から17のいずれか1項記載の方法。
- 目的の糖タンパク質が凝固因子IXを含む、請求項1から18のいずれか1項記載の方法。
- 前記凝固因子IXが組み換えヒト凝固因子IXである、請求項19記載の方法。
- 目的の糖タンパク質が抗ABeta抗体を含む、請求項1から18のいずれか1項記載の方法。
- 前記抗ABeta抗体がモノクローナル抗体である、請求項21記載の方法。
- 前記抗ABeta抗体がヒト化抗ABetaペプチドIgG1モノクローナル抗体である、請求項22記載の方法。
- 約10から600nMの間のマンガンを含む細胞培地。
- 約20から200nMの間のマンガンを含む、請求項24記載の細胞培地。
- 約40nMマンガンを含む、請求項25記載の細胞培地。
- 前記細胞培地が約8mM以下の初期濃度でグルタミンを含む、請求項24から26のいずれか1項記載の細胞培地。
- 前記初期グルタミン濃度が約4mM以下である、請求項27記載の細胞培地。
- 前記培地が合成培地である、請求項24から28のいずれか1項記載の細胞培地。
- 請求項1から23のいずれか1項記載の方法により得られる糖タンパク質。
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