JP2020531516A - フォン・ウィルブランド因子のウイルスろ過の方法 - Google Patents
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Abstract
Description
(a)VWFと、少なくとも150mMの濃度の少なくとも1種の塩基性アミノ酸とを含む溶液を準備する工程;
(b)工程(a)の溶液を、細孔径が35nm以下であるフィルタに通すウイルスろ過にかける工程
を含む前記方法。
用語「フォン・ウィルブランド因子」または「VWF」は、本明細書で使用される場合、野生型VWFの生物活性またはVWFの少なくとも部分的な生物活性を有するあらゆるポリペプチドを指す。
本発明の工程(a)で言及される溶液は、VWFと、少なくとも150mMの塩基性アミノ酸または塩基性アミノ酸の組み合わせを含む。
用語「塩基性アミノ酸」は、本明細書で使用される場合、等電点が7超であるアミノ酸を指す。
本発明の方法で使用するフィルタは、公称細孔径が35nm以下である。好ましくは、このフィルタの公称細孔径は25nm以下である。より好ましくは、このフィルタの公称細孔径は22nm以下である。最も好ましくは、このフィルタの公称細孔径は20nm以下であり、例えば、15nm、16nm、17nm、18nm、または19nmである。本発明の方法で使用するフィルタの公称細孔径は好ましくは、15nm〜35nmの範囲、または16nm〜30nmの範囲、または17nm〜25nmの範囲、または18nm〜22nmの範囲である。
典型的には、本発明の方法に従うろ過をデッドエンドろ過として実行する。ろ過される溶液の量は10mL〜100Lの範囲、または100ml〜10Lの範囲、または0.5L〜5Lの範囲であり得る。
本発明のろ過プロセスにより、生物活性が高いVWFを含むろ液が得られる。
それぞれ「A」および「B」と名付けた2種の異なるrVWF溶液を、ウイルスろ過にかけた。このrVWFはVWF−アルブミン融合体であり、このアミノ酸配列は国際公開第2009/156137A1号パンフレットに記載されている。
VWFをウイルスろ過(VF)にかける際にカルシウムイオンがプラスの効果をもたらしたという報告がある。したがって、カルシウムイオンの存在下でもアルギニンがVWF収率を改善し得るかどうかを調べた。
Claims (21)
- フォン・ウィルブランド因子(VWF)を含む溶液をろ過する方法であって、
(a)VWFと、少なくとも1種の塩基性アミノ酸とを含む溶液を準備する工程であり、該溶液における前記少なくとも1種の塩基性アミノ酸の濃度は少なくとも150mMである、準備する工程;
(b)工程(a)の溶液を、細孔径が35nm以下であるフィルタに通すウイルスろ過にかける工程
を含む前記方法。 - 工程(a)の溶液中の前記VWFはVWFの高分子量多量体(HMWM)を含む、請求項1に記載の方法。
- 工程(b)におけるウイルスろ過中の圧力は0.5bar未満である、請求項1または2に記載の方法。
- 工程(a)で準備される溶液のpHは5.0〜9.0であり、特に6.0〜8.0である、請求項1または2に記載の方法。
- 工程(b)におけるウイルスろ過は15〜30℃、特に18〜28℃の温度で行う、請求項1〜4のいずれか1項に記載の方法。
- 工程(a)で準備される溶液における前記少なくとも1種の塩基性アミノ酸の濃度は、少なくとも300mM、少なくとも350mM、少なくとも400mM、少なくとも450mM、または少なくとも500mMである、請求項1〜5のいずれか1項に記載の方法。
- 工程(a)で準備される溶液における前記少なくとも1種の塩基性アミノ酸の濃度は、1,000mM未満、950mM未満、900mM未満、850mM未満、800mM未満、または750mM未満である、請求項1〜6のいずれか1項に記載の方法。
- 工程(a)で準備される溶液は、カルシウムイオンを、少なくとも50mM、少なくとも100mM、少なくとも200mM、少なくとも300mM、または少なくとも350mMの濃度でさらに含む、請求項1〜7のいずれか1項に記載の方法。
- フィルタは、細孔径が25nm以下、または20nm以下である、請求項1〜8のいずれか1項に記載の方法。
- フィルタは、細孔径が13nm〜35nm、13nm〜25nm、18nm〜22nm、または13nm〜17nmである、請求項1〜8のいずれか1項に記載の方法。
- VWFは、血漿由来のVWF、または組み換えにより得られたVWFである、請求項1〜10のいずれか1項に記載の方法。
- 工程(b)で得られるろ液における比RCo VWF/Ag VWFは、少なくとも0.75、少なくとも0.8、少なくとも0.9、少なくとも1.0、少なくとも1.1、または少なくとも1.2である、請求項1〜11のいずれか1項に記載の方法。
- 工程(b)で得られるろ液における比RCo VWF/Ag VWFは、工程(a)で準備される溶液における比RCo VWF/Ag VWFの少なくとも75%である、請求項1〜12のいずれか1項に記載の方法。
- ろ過後のVWF:Ag収率は少なくとも50%、少なくとも60%、少なくとも70%、または少なくとも75%である、請求項1〜13のいずれか1項に記載の方法。
- ろ過後のRCo VWF収率は少なくとも40%、少なくとも45%、少なくとも50%、または少なくとも55%である、請求項1〜14のいずれか1項に記載の方法。
- 工程(a)で準備される溶液、および工程(b)で得られるろ液は、多量体電気泳動により分析した場合に、VWFの低多量体(1〜5のバンド)、VWFの中間多量体(6〜10のバンド)、およびVWFの大多量体(HMWM、高分子量多量体、11超のバンド)を含み、但し、工程(b)で得られるろ液における大多量体の相対量は、工程(a)で準備される溶液における総VWF含有量および工程(b)で得られるろ液における総VWF含有量それぞれと比較して、少なくとも70%、少なくとも75%、少なくとも80%、または少なくとも85%である、請求項1〜15のいずれか1項に記載の方法。
- 前記少なくとも1種のアミノ酸は、アルギニン、リシン、ヒスチジン、オルニチン、およびこれらの組み合わせからなる群から選択され、好ましくは、塩基性アミノ酸はアルギニンである、請求項1〜16のいずれか1項に記載の方法。
- 工程(a)で準備される溶液は、VWFに加えて因子VIII(FVIII)を含む、請求項1〜17のいずれか1項に記載の方法。
- 請求項1〜18のいずれか1項に記載の方法により得ることができるVWFのろ過溶液。
- 請求項1〜18のいずれか1項に記載の方法により得ることができるVWFを含む組成物。
- VWFを精製する方法であって、請求項1〜18のいずれか1項に記載の方法を含む前記方法。
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US (1) | US20200199176A1 (ja) |
EP (1) | EP3672644A1 (ja) |
JP (1) | JP2020531516A (ja) |
KR (1) | KR20200038309A (ja) |
CN (1) | CN110997015A (ja) |
AU (1) | AU2018321131B2 (ja) |
BR (1) | BR112020002234A2 (ja) |
CA (1) | CA3072003A1 (ja) |
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US20230080241A1 (en) * | 2020-02-14 | 2023-03-16 | Tranexamic Technologies, Llc | Methods and compositions for antimicrobial use of synthetic lysine analogs, derivatives, and mimetics, and prodrugs |
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- 2018-08-23 AU AU2018321131A patent/AU2018321131B2/en active Active
- 2018-08-23 KR KR1020207008290A patent/KR20200038309A/ko not_active Application Discontinuation
- 2018-08-23 JP JP2020511237A patent/JP2020531516A/ja active Pending
- 2018-08-23 US US16/640,568 patent/US20200199176A1/en active Pending
- 2018-08-23 EP EP18755485.2A patent/EP3672644A1/en active Pending
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- 2018-08-23 CA CA3072003A patent/CA3072003A1/en active Pending
- 2018-08-23 CN CN201880054246.3A patent/CN110997015A/zh active Pending
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EP3672644A1 (en) | 2020-07-01 |
KR20200038309A (ko) | 2020-04-10 |
CA3072003A1 (en) | 2019-02-28 |
AU2018321131B2 (en) | 2024-06-13 |
US20200199176A1 (en) | 2020-06-25 |
CN110997015A (zh) | 2020-04-10 |
AU2018321131A1 (en) | 2020-04-09 |
SG11202000695RA (en) | 2020-03-30 |
BR112020002234A2 (pt) | 2020-07-28 |
WO2019038350A1 (en) | 2019-02-28 |
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