JP2015500030A - 閉鎖バイオリアクタ - Google Patents
閉鎖バイオリアクタ Download PDFInfo
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- JP2015500030A JP2015500030A JP2014545915A JP2014545915A JP2015500030A JP 2015500030 A JP2015500030 A JP 2015500030A JP 2014545915 A JP2014545915 A JP 2014545915A JP 2014545915 A JP2014545915 A JP 2014545915A JP 2015500030 A JP2015500030 A JP 2015500030A
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Abstract
Description
これらのバイオリアクタは、構築および作動が高価なISO 14664 Class 8環境において一般に作動させられる。栄養培地を支持する容器内で全ての作動が実施される閉鎖バイオリアクタは、建設および維持がかなり安価な、あまり制御されていない環境またはISO 14644 Class 9環境で使用され得る。本発明は、バイオリアクタの使用を拡大するためおよびバイオリアクタをより手頃な価格にするための理想的な解法を提供する。これは、薬物およびワクチンを緊急に製造する場合、新しい薬物を開発する場合、臨床試験供給物を製造する場合、およびより低いコストで市販用の生物学的薬物を一般に生成する場合に、特に有用である。最後の考慮事項は、これらの薬物に対する革新的特許の満了後に市場に現れ始めたジェネリックの生物学的薬物として、近年非常に重要になっている。ジェネリック製造業者は、競合するためにより安価なコストでこれらの分子を製造することができなければならず、本発明はこの要求を満たす。
a.Novozymesの新たに特許されたDual Affinity Polypeptide技術プラットフォームは、プロテインAプロセスステップを、類似ではあるが使い捨ての技術で置き換える。
本発明では、非生物学的構成要素を含む組成物には、マイクロキャリア(例えば、多孔性または非多孔性であり得る、ポリマー球体、固体球体、ゼラチン質粒子、マイクロビーズおよびマイクロディスク)、特定の化学基(例えば、第3級アミン基)により帯電した架橋ビーズ(例えば、デキストラン)、非多孔性ポリマー繊維中に捕捉された細胞を含む2Dマイクロキャリア、3Dキャリア(例えば、多孔性繊維を含み得る、キャリア繊維、中空繊維、マルチカートリッジリアクタおよび半浸透性膜)、低減されたイオン交換能を有するマイクロキャリア、細胞、キャピラリーおよび凝集体(例えば、細胞の凝集体)を含む組成物が含まれるが、これらに限定されない。
種々の異なる生成物もまた、本発明に従って生成され得る。例示的な生成物には、タンパク質(例えば、抗体および酵素)、ワクチン、ウイルス生成物、ホルモン、免疫調節剤、代謝産物、脂肪酸、ビタミン、薬物、抗生物質、細胞および組織が含まれる。タンパク質の非限定的な例には、ヒト組織プラスミノーゲンアクチベーター(tPA)、血液凝固因子、増殖因子(例えば、インターフェロンおよびケモカインを含むサイトカイン)、接着分子、Bcl−2ファミリーのタンパク質、ポリヘドリン(polyhedrin)タンパク質、ヒト血清アルブミン、scFv抗体断片、ヒトエリスロポエチン、マウスモノクローナル重鎖7、マウスIgG2b/k、マウスIgG1、重鎖mAb、ブリオンジン(Bryondin)1、ヒトインターロイキン−2、ヒトインターロイキン−4、リシン、ヒトα1−アンチトリプシン、biscFv抗体断片、免疫グロブリン、ヒト顆粒球、刺激因子(hGM−CSF)、B型肝炎表面抗原(HBsAg)、ヒトリゾチーム、IL−12、およびHBsAgに対するmAbが含まれる。血漿タンパク質の例には、フィブリノーゲン、アルファ−フェトプロテイン、トランスフェリン、アルブミン、補体C3およびアルファ−2−マクログロブリン、プロトロンビン、アンチトロンビンIII、アルファ−フェトプロテイン、補体C3およびフィブリノーゲン、インスリン、B型肝炎表面抗原、尿酸オキシダーゼ、グルカゴン、顆粒球マクロファージコロニー刺激因子、ヒルジン/デシルジン、アンジオスタチン、エラスターゼインヒビター、エンドスタチン、上皮増殖因子アナログ、インスリン様増殖因子−1、カリクレインインヒビター、α1−アンチトリプシン、腫瘍壊死因子、コラーゲンタンパク質のドメイン(コラーゲン糖タンパク質全体ではなく)、代謝副生成物を伴わないタンパク質、ヒトアルブミン、ウシアルブミン、トロンボモジュリン、トランスフェリン、血友病Aに関する第VIII因子(即ち、CHO細胞またはBHK細胞由来)、第VIIa因子(即ち、BHK由来)、血友病Bに関する第IX因子(即ち、CHO由来)、ヒト分泌型アルカリホスファターゼ、アプロチニン、ヒスタミン、ロイコトリエン、IgE受容体、N−アセチルグルコサミニルトランスフェラーゼ−IIIおよび抗血友病第VIII因子が含まれる。
バイオリアクタアセンブリ
本発明の種々の実施形態において有用なコンテナは、栄養培地を含むのに適した任意のサイズのものであり得る。例えば、このコンテナは、1〜40Lの間、40〜100Lの間、100〜200Lの間、200〜300Lの間、300〜500Lの間、500〜750Lの間、750〜1,000Lの間、1,000〜2,000Lの間、2,000〜5,000Lの間または5,000〜10,000Lの間の容量を有し得る。いくつかの例では、このコンテナは、1Lより大きい容量、または他の場合には、10L、20L、40L、100L、200L、500Lまたは1,000Lより大きい容量を有する。10,000Lより大きい容量もまた可能である。好ましくは、コンテナ容量は、約1Lから1000Lの間の範囲、より好ましくは、約5Lから500Lの間の範囲、なおより好ましくは5Lから200Lの間の範囲である。
Claims (24)
- 制御されない環境における使用に適した閉鎖バイオリアクタであって、
a.栄養培地と生物学的培養物とを含むコンテナ;
b.少なくとも1つの気体出口;
c.前記コンテナ内の気体を再循環させるためにチューブを介して前記気体出口に接続され、かつ気体の供給源にさらに接続された、少なくとも1つの気体入口;
d.少なくとも1つの液体ポート;
e.気体の前記供給源と前記気体入口との間に取り付けられた滅菌フィルタ;
f.前記滅菌フィルタ(e)と前記気体入口との間に取り付けられた止め栓;
g.前記液体ポートにおいて取り付けられた滅菌フィルタ;
h.滅菌フィルタ(g)と前記液体ポートとの間に取り付けられた止め栓;
i.前記気体出口と前記気体入口との間で接続された前記チューブ中に取り付けられた蠕動ポンプ;および
j.前記気体入口に接続され、かつ前記コンテナ中に設置された、少なくとも1つのスパージングフィルタ
を含む、閉鎖バイオリアクタ。 - ISO 14644 Class 9以上の制御されない環境中に存在する、請求項1に記載の閉鎖バイオリアクタ。
- 前記コンテナに支持を提供する外部支持ハウジングをさらに含む、請求項1に記載の閉鎖バイオリアクタ。
- 前記栄養培地が、気化、撹拌、揺動、振盪、振動および/または前記コンテナに対する圧縮によって混合される、請求項1に記載の閉鎖バイオリアクタ。
- 5μよりも大きい粒子を保持することが可能なフィルタ排出管をさらに含む、請求項1に記載の閉鎖バイオリアクタ。
- 前記生物学的培養物が、ヒト細胞、動物細胞、細菌、植物細胞、昆虫細胞、酵母または真菌である、請求項1に記載の閉鎖バイオリアクタ。
- 前記生物学的培養物が、前記生物学的培養物の代謝過程において二酸化炭素を生成する、請求項1に記載のバイオリアクタ。
- 前記生物学的培養物が、前記生物学的培養物の代謝過程のために二酸化炭素を必要とする、請求項1に記載のバイオリアクタ。
- 複数の遠隔操作されるセンサをさらに含む、請求項1に記載の閉鎖バイオリアクタ。
- 前記遠隔操作されるセンサが、酸素センサおよび二酸化炭素センサを含む、請求項9に記載の閉鎖バイオリアクタ。
- 前記栄養培地のための温度コントローラをさらに含む、請求項1に記載の閉鎖バイオリアクタ。
- 前記コンテナが無菌である、請求項1に記載の閉鎖バイオリアクタ。
- 前記コンテナが使い捨てである、請求項1に記載の閉鎖バイオリアクタ。
- 前記コンテナが可撓性である、請求項1に記載の閉鎖バイオリアクタ。
- 前記コンテナが、生体適合性ポリマーを含む、請求項1に記載の閉鎖バイオリアクタ。
- 前記スパージングフィルタが、前記閉鎖バイオリアクタの作動の間に前記栄養培地中に浸漬される、請求項1に記載の閉鎖バイオリアクタ。
- ソーダ石灰、水酸化カルシウム、水酸化ナトリウム、水酸化カリウム、水酸化リチウム、ケイ酸リチウム、ジルコニウム酸リチウム(lithium zirconate)、酸化リチウム、活性炭、ゼオライトおよびイオン交換樹脂を含む吸収剤材料の群から選択される二酸化炭素吸収剤材料を含む、前記気体出口に接続されたインラインカートリッジをさらに含む、請求項1に記載の閉鎖バイオリアクタ。
- 生物学的生成物を生成するための方法であって、前記方法は:
a.コンテナを含む閉鎖バイオリアクタを提供するステップであって、前記閉鎖バイオリアクタが、
i.少なくとも1つの気体出口;
ii.前記コンテナ内の気体を再循環させるためにチューブを介して前記気体出口に接続された、少なくとも1つの気体入口;
iii.少なくとも1つの液体ポート;
iv.前記気体入口において取り付けられた滅菌フィルタ;
v.前記滅菌フィルタ(iv)と前記気体入口との間に取り付けられた止め栓;
vi.前記液体ポートにおいて取り付けられた滅菌フィルタ;
vii.前記滅菌フィルタ(vi)と前記液体ポートとの間に取り付けられた止め栓;
viii.前記気体出口と前記気体入口との間の前記チューブ中に取り付けられた蠕動ポンプ;
ix.前記気体入口に接続され、かつ前記コンテナ中に設置された、少なくとも1つのスパージングフィルタ;および
x.温度コントローラ
を含む、ステップ;
b.前記コンテナに栄養培地を添加するステップ;
c.5%〜100%の二酸化炭素を含む新鮮な気体の、前記気体入口への供給を接続し、前記供給をオンにするステップであって、前記新鮮な気体は、前記(a)(ix)のスパージングフィルタを通過して栄養培地中に入る、ステップ;
d.前記栄養培地において所定の濃度の二酸化炭素に達したときに、新鮮な気体の前記供給をオフに切り替えるステップ;
e.前記(a)(viii)の蠕動ポンプを始動させて、前記(a)(ii)の気体入口を介して、前記コンテナ中の気体を再循環させるステップ;
f.前記温度コントローラを起動させるステップ;
g.十分な量の生物学的培養物を前記栄養培地に添加するステップ;
h.時間間隔で、前記コンテナ中の前記栄養培地における前記生物学的培養物の密度を検出するステップ;
i.前記栄養培地中の二酸化炭素の濃度が所定のレベルより下に低下したときに新鮮な気体の流れを間欠的に始動させ、前記新鮮な気体の前記流れを、前記栄養培地中の二酸化炭素の濃度が所定のレベルに上がるまで継続させるステップ;ならびに
j.前記生物学的培養物および前記生物学的培養物により生成された生物学的生成物を、前記コンテナから取り出すステップ
を含む、方法。 - 生物学的生成物を生成するための方法であって、前記方法は:
a.コンテナを含む閉鎖バイオリアクタを提供するステップであって、前記閉鎖バイオリアクタが、
i.少なくとも1つの気体出口;
ii.前記コンテナ内の気体を再循環させるためにチューブを介して前記気体出口に接続された、少なくとも1つの気体入口;
iii.少なくとも1つの液体ポート;
iv.前記気体入口において取り付けられた滅菌フィルタ;
v.前記(iv)の滅菌フィルタと前記気体入口との間に取り付けられた止め栓;
vi.前記液体ポートにおいて取り付けられた滅菌フィルタ;
vii.前記(vi)の滅菌フィルタと前記液体ポートとの間に取り付けられた止め栓;
viii.前記気体出口と前記気体入口との間の前記チューブ中に取り付けられた蠕動ポンプ;
ix.前記気体入口に接続され、かつ前記コンテナ中に設置された、少なくとも1つのスパージングフィルタ;
x.温度コントローラ;および
xi.前記気体出口と前記気体入口との間に取り付けられた、二酸化炭素吸収剤材料を含むインラインカートリッジ、
を含む、ステップ;
b.前記コンテナに栄養培地を添加するステップ;
c.5%〜100%の酸素を含む新鮮な気体の供給を接続し、前記供給をオンにするステップであって、前記新鮮な気体は、前記(a)(ix)のスパージングフィルタを通過して前記栄養培地中に入る、ステップ;
d.前記栄養培地において所定の濃度の酸素に達したときに、新鮮な気体の前記供給をオフに切り替えるステップ;
e.前記(a)(viii)の蠕動ポンプを始動させて、前記(a)(ii)の気体入口を介して、前記コンテナ中の気体を再循環させるステップ;
f.前記温度コントローラを起動させるステップ;
g.十分な量の生物学的培養物を前記栄養培地に添加するステップ;
h.時間間隔で、前記コンテナ中の前記栄養培地における前記生物学的培養物の密度を検出するステップ;
i.前記栄養培地中の二酸化炭素の濃度が所定のレベルより下に低下したときに新鮮な気体の流れを間欠的に始動させ、前記新鮮な気体の前記流れを、前記栄養培地中の二酸化炭素の濃度が所定のレベルに上がるまで継続させるステップ;ならびに
j.前記生物学的培養物および前記生物学的培養物により生成された生物学的生成物を、前記コンテナから取り出すステップ
を含む、方法。 - 前記コンテナの内側の圧力が、前記新鮮な気体の間欠的な前記流れによって所定の範囲内に維持される、請求項18または19に記載の生物学的生成物を生成するための方法。
- 前記生物学的培養物が哺乳動物細胞である、請求項18に記載の生物学的生成物を生成するための方法。
- 前記生物学的培養物が細菌である、請求項19に記載の生物学的生成物を生成するための方法。
- 前記コンテナが、フィルタ排出管をさらに含む、請求項18または19に記載の生物学的生成物を生成するための方法。
- 前記栄養培地中の前記生物学的生成物を捕捉することが可能な樹脂が、前記液体ポートを介して添加され、そして前記生物学的生成物が前記樹脂によって捕捉された後に、前記栄養培地が前記フィルタ排出管を介して排出される、請求項23に記載の生物学的生成物を生成するための方法。
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EP4048293A4 (en) | 2019-10-21 | 2023-12-06 | Flaskworks, LLC | SYSTEMS AND METHODS FOR CELL GROWING |
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GB1153114A (en) * | 1967-02-06 | 1969-05-21 | Ajinomoto Kk | Fermentation processes and apparatus for Carrying Out the same |
JP2009539408A (ja) * | 2006-06-16 | 2009-11-19 | エクセレレックス インク. | ガス供給構造体、泡制御システム、及び折り畳み可能な袋体容器及びバイオリアクタ用袋体成形方法並びに物品 |
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AU2012348297A1 (en) | 2014-06-26 |
US9469671B2 (en) | 2016-10-18 |
CN104066833B (zh) | 2016-08-24 |
CN104066833A (zh) | 2014-09-24 |
EP2788470A4 (en) | 2015-10-14 |
CA2857954A1 (en) | 2013-06-13 |
HK1201551A1 (en) | 2015-09-04 |
WO2013085682A1 (en) | 2013-06-13 |
JP6066500B2 (ja) | 2017-01-25 |
US20120077243A1 (en) | 2012-03-29 |
HK1201869A1 (en) | 2015-09-11 |
EP2788470A1 (en) | 2014-10-15 |
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