JP2015517506A - 安定化されたタンパク質溶液 - Google Patents
安定化されたタンパク質溶液 Download PDFInfo
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- JP2015517506A JP2015517506A JP2015511961A JP2015511961A JP2015517506A JP 2015517506 A JP2015517506 A JP 2015517506A JP 2015511961 A JP2015511961 A JP 2015511961A JP 2015511961 A JP2015511961 A JP 2015511961A JP 2015517506 A JP2015517506 A JP 2015517506A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K1/14—Extraction; Separation; Purification
- C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
Description
抗IL-20抗体を含有する溶液の限外濾過に関する最適化プログラムを実施するために、溶液Aを溶液B(5×保持液体積)に対してPellicon 3、Ultracel 30 K 膜、88 cm2モジュールを備えたAktacrossflow(ミリポア)でダイアフィルトレーションした。
溶液A:
100g/L 抗IL20
150mM スクロース
25mM Arg
25mM NaCl
33mM His
pH 6.5
溶液B:
25mM Arg
25mM NaCl
33mM His
pH 6.5
限外濾過中におけるHMWP(高分子量タンパク質:凝集物)の形成に対する、限外濾過前のスクロース添加の効果を調べるために、洗浄分画は元の保持液より濃度が実質的に低いとみることができるので、生成物を空けた後のカセットの洗浄からの幾つかの試料を含めて、HMWPの保持液中の飽和を測定した。洗浄分画のHMWP含有率は、それが、ゲルの構成-または保持液中には示されない集積層の物質を示すので、興味がある。総合した結果は、濃縮中にスクロースが存在する材料は、スクロースがmAbを保護するという理論に従ってHMWPのより低い含有率を有するということである。
限外濾過前のスクロース添加のタンパク質回収またはプロセスの収率に対する効果を調べるために、mAbの濃度を、保持液および生成物を空けた後のカセットの洗浄からの試料で測定した。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)タンパク質濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度タンパク質溶液に添加する工程と、
(b)高濃度タンパク質溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを前記高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む、方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む方法。
(a)抗体濃度が40g/Lから60g/Lの間であるときにスクロースを高濃度抗体溶液に添加する工程と、
(b)高濃度抗体溶液を限外濾過により濃縮する工程と
を含む方法。
Claims (13)
- 高濃度タンパク質溶液を限外濾過する方法であって、前記溶液のタンパク質濃度が40から60g/Lの間であるときにスクロースを前記溶液に添加した後で、限外濾過によりさらに濃縮する、方法。
- 高濃度限外濾過保持液中の計算タンパク質濃度と測定タンパク質濃度との間の差を減少させる、請求項1に記載の方法。
- 高濃度限外濾過保持液中の計算タンパク質濃度と測定タンパク質濃度との間の差が30%未満である、請求項1または2に記載の方法。
- スクロースの添加が、限外濾過される高濃度溶液を安定化する、請求項1に記載の方法。
- 高濃度限外濾過保持液中のHMWP凝集物のレベルが1%または1%未満である、請求項1または4に記載の方法。
- 限外濾過中のタンパク質の回収率を増大させる、請求項1に記載の方法。
- 限外濾過中のタンパク質の回収率が、限外濾過される高濃度タンパク質溶液中のタンパク質の全量の94%以上である、請求項1または6に記載の方法。
- 前記スクロースを高濃度タンパク質溶液に50mMから300mMの間の濃度で添加する、請求項1から7のいずれか一項に記載の方法。
- 前記タンパク質が抗体である、請求項1から8のいずれか一項に記載の方法。
- 前記抗体がモノクローナル抗体である、請求項1から9のいずれか一項に記載の方法。
- 前記抗体が抗IL-20モノクローナル抗体である、請求項1から10のいずれか一項に記載の方法。
- 医薬組成物に使用するための、請求項1から11までのいずれか一項に記載のタンパク質または抗体溶液中のタンパク質または抗体を濃縮する方法。
- 炎症性疾患を治療する方法であって、請求項12に規定の医薬組成物を患者に投与することを含む、方法。
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PCT/EP2013/055390 WO2013170977A1 (en) | 2012-05-14 | 2013-03-15 | Stabilised protein solutions |
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EP3184542A1 (en) | 2017-06-28 |
CA2873647A1 (en) | 2013-11-21 |
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CN104271600B (zh) | 2018-09-14 |
EP2850099A1 (en) | 2015-03-25 |
EP2850099B1 (en) | 2017-01-18 |
CN104271600A (zh) | 2015-01-07 |
US20150086566A1 (en) | 2015-03-26 |
AU2013262083A1 (en) | 2014-11-06 |
WO2013170977A1 (en) | 2013-11-21 |
US20230002443A1 (en) | 2023-01-05 |
ES2622558T3 (es) | 2017-07-06 |
JP6681711B2 (ja) | 2020-04-15 |
US11466051B2 (en) | 2022-10-11 |
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