JP2017500017A5 - - Google Patents
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- JP2017500017A5 JP2017500017A5 JP2016532136A JP2016532136A JP2017500017A5 JP 2017500017 A5 JP2017500017 A5 JP 2017500017A5 JP 2016532136 A JP2016532136 A JP 2016532136A JP 2016532136 A JP2016532136 A JP 2016532136A JP 2017500017 A5 JP2017500017 A5 JP 2017500017A5
- Authority
- JP
- Japan
- Prior art keywords
- culture
- cells
- liters
- item
- viable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 claims description 93
- 210000004027 cell Anatomy 0.000 claims description 67
- 230000001186 cumulative effect Effects 0.000 claims description 28
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 229910052742 iron Inorganic materials 0.000 claims description 13
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 claims description 11
- 238000010899 nucleation Methods 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 8
- 239000010949 copper Substances 0.000 claims description 8
- 230000010412 perfusion Effects 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002699 waste material Substances 0.000 claims description 7
- 239000011701 zinc Substances 0.000 claims description 7
- 229910052725 zinc Inorganic materials 0.000 claims description 7
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 5
- 108010050904 Interferons Proteins 0.000 claims description 4
- 102000014150 Interferons Human genes 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 229940079322 interferon Drugs 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 235000015097 nutrients Nutrition 0.000 claims description 4
- 102100023961 ADP-ribosylation factor-like protein 2-binding protein Human genes 0.000 claims description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 2
- 108010008165 Etanercept Proteins 0.000 claims description 2
- 101000757692 Homo sapiens ADP-ribosylation factor-like protein 2-binding protein Proteins 0.000 claims description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 2
- 101000934823 Homo sapiens Barttin Proteins 0.000 claims description 2
- 108010005716 Interferon beta-1a Proteins 0.000 claims description 2
- 229960002964 adalimumab Drugs 0.000 claims description 2
- 102000003802 alpha-Synuclein Human genes 0.000 claims description 2
- 108090000185 alpha-Synuclein Proteins 0.000 claims description 2
- 229940003504 avonex Drugs 0.000 claims description 2
- 229960000397 bevacizumab Drugs 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 2
- 229960002806 daclizumab Drugs 0.000 claims description 2
- 229960000403 etanercept Drugs 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 102000037865 fusion proteins Human genes 0.000 claims description 2
- 108020001507 fusion proteins Proteins 0.000 claims description 2
- 229960000598 infliximab Drugs 0.000 claims description 2
- 229950005751 ocrelizumab Drugs 0.000 claims description 2
- 239000012716 precipitator Substances 0.000 claims description 2
- 229960004641 rituximab Drugs 0.000 claims description 2
- 229960000575 trastuzumab Drugs 0.000 claims description 2
- 210000003501 vero cell Anatomy 0.000 claims description 2
- 239000002738 chelating agent Substances 0.000 claims 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361919629P | 2013-12-20 | 2013-12-20 | |
| US61/919,629 | 2013-12-20 | ||
| PCT/US2014/071701 WO2015095809A1 (en) | 2013-12-20 | 2014-12-19 | Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020000268A Division JP2020054388A (ja) | 2013-12-20 | 2020-01-06 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017500017A JP2017500017A (ja) | 2017-01-05 |
| JP2017500017A5 true JP2017500017A5 (show.php) | 2018-02-08 |
Family
ID=52347449
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016532136A Withdrawn JP2017500017A (ja) | 2013-12-20 | 2014-12-19 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
| JP2020000268A Withdrawn JP2020054388A (ja) | 2013-12-20 | 2020-01-06 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
| JP2022197095A Pending JP2023022317A (ja) | 2013-12-20 | 2022-12-09 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020000268A Withdrawn JP2020054388A (ja) | 2013-12-20 | 2020-01-06 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
| JP2022197095A Pending JP2023022317A (ja) | 2013-12-20 | 2022-12-09 | 生物薬剤フェドバッチ生産能力及び生産物品質を改善するための灌流シード培養の使用 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US20160289633A1 (show.php) |
| EP (1) | EP3083933B1 (show.php) |
| JP (3) | JP2017500017A (show.php) |
| WO (1) | WO2015095809A1 (show.php) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3083933B1 (en) | 2013-12-20 | 2026-01-21 | Biogen MA Inc. | Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality |
| TWI743024B (zh) | 2014-06-06 | 2021-10-21 | 美商健臻公司 | 灌注培養方法及其用途 |
| TW202246486A (zh) * | 2014-06-09 | 2022-12-01 | 美商健臻公司 | 種子罐培養法(seed train processes)及其用途 |
| JP2018531619A (ja) * | 2015-11-02 | 2018-11-01 | アレス トレーディング ソシエテ アノニム | 灌流様式において組換えたんぱく質の生産プロファイルを調節する方法 |
| WO2017132185A1 (en) | 2016-01-26 | 2017-08-03 | Boehringer Ingelheim International Gmbh | Linked perfusion to continuous-flow stirred-tank reactor cell culture system |
| US20180057784A1 (en) | 2016-08-27 | 2018-03-01 | 3D Biotek, Llc | Bioreactor |
| JP2020533983A (ja) * | 2017-09-15 | 2020-11-26 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 目的のポリペプチドのラージスケールの製造間のオンラインバイオマス静電容量モニタリング |
| IL273549B2 (en) | 2017-10-06 | 2023-10-01 | Lonza Ag | Automated control of cell culture using Raman spectroscopy |
| IL273150B2 (en) | 2017-10-16 | 2025-02-01 | Regeneron Pharma | Drip Bioreactor and methods of using it |
| KR20200083564A (ko) * | 2017-11-13 | 2020-07-08 | 암젠 인크 | 단백질 산물을 제조하는 방법 |
| EP3724229A1 (en) * | 2017-12-11 | 2020-10-21 | Amgen Inc. | Continuous manufacturing process for bispecific antibody products |
| CN110241012B (zh) * | 2018-03-09 | 2022-11-01 | 嘉和生物药业有限公司 | 一种生物大分子上游分阶段截留的生产方法、生产模块及在生产中的应用 |
| EP3787771A1 (en) * | 2018-04-29 | 2021-03-10 | REGENXBIO Inc. | Scalable clarification process for recombinant aav production |
| US12071607B2 (en) * | 2018-06-01 | 2024-08-27 | Lonza Ltd. | Midscale model for organic growth and phasing |
| WO2020086408A1 (en) | 2018-10-26 | 2020-04-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A high-yield perfusion-based transient gene expression bioprocess |
| JP7453151B2 (ja) * | 2018-11-02 | 2024-03-19 | 協和キリン株式会社 | 液体培地の調製方法 |
| EP3914696A4 (en) * | 2019-01-25 | 2022-12-14 | Biogen MA Inc. | SEED CULTIVATION METHOD FOR THE PRODUCTION OF AAV |
| WO2020208050A1 (en) * | 2019-04-11 | 2020-10-15 | Merck Patent Gmbh | Cell culture media comprising keto acids |
| EP4008774A4 (en) * | 2019-07-16 | 2023-09-27 | Innovent Biologics (Suzhou) Co., Ltd. | CELL CULTURE METHOD AND ITS APPLICATION BASED ON CONTINUOUS AND HIGH DENSITY INOCULATION |
| JP2022543781A (ja) * | 2019-08-01 | 2022-10-14 | ブリストル－マイヤーズ スクイブ カンパニー | フェッドバッチ細胞培養におけるタンパク質産生性の改良方法 |
| WO2022125523A1 (en) * | 2020-12-08 | 2022-06-16 | Partner Therapeutics, Inc. | Manufacture of granulocyte macrophage-colony stimulating factor |
| CA3218684A1 (en) | 2021-05-03 | 2022-11-10 | Boehringer Ingelheim International Gmbh | Method for producing spesolimab |
| WO2023114901A2 (en) | 2021-12-15 | 2023-06-22 | Oxford Biomedica Solutions Llc | Methods and compositions for the production of adeno-associated virus |
| TW202342740A (zh) * | 2022-03-07 | 2023-11-01 | 美商奧崔基尼克斯製藥公司 | 改良的批量aav生產系統和方法 |
| EP4584363A1 (en) * | 2022-09-06 | 2025-07-16 | Amgen Inc. | Lean perfusion cell culture methods |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
| EP1892296A1 (en) | 1988-09-02 | 2008-02-27 | Dyax Corporation | Generation and selection of recombinant varied binding proteins |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| EP0435911B1 (en) | 1988-09-23 | 1996-03-13 | Cetus Oncology Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ATE185601T1 (de) | 1990-07-10 | 1999-10-15 | Cambridge Antibody Tech | Verfahren zur herstellung von spezifischen bindungspaargliedern |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| ES2113940T3 (es) | 1990-12-03 | 1998-05-16 | Genentech Inc | Metodo de enriquecimiento para variantes de proteinas con propiedades de union alteradas. |
| CA2105300C (en) | 1991-03-01 | 2008-12-23 | Robert C. Ladner | Process for the development of binding mini-proteins |
| IE921169A1 (en) | 1991-04-10 | 1992-10-21 | Scripps Research Inst | Heterodimeric receptor libraries using phagemids |
| WO1992022653A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
| DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
| DK1024191T3 (da) | 1991-12-02 | 2008-12-08 | Medical Res Council | Fremstilling af autoantistoffer fremvist på fag-overflader ud fra antistofsegmentbiblioteker |
| US5667988A (en) | 1992-01-27 | 1997-09-16 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| US5856179A (en) | 1994-03-10 | 1999-01-05 | Genentech, Inc. | Polypeptide production in animal cell culture |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| AU5632296A (en) | 1995-04-27 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| CA2219486A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| JP4215172B2 (ja) | 1996-12-03 | 2009-01-28 | アムジェン フレモント インク． | 複数のＶ▲下Ｈ▼およびＶ▲下κ▼領域を含むヒトＩｇ遺伝子座を有するトランスジェニック哺乳動物、ならびにそれから産生される抗体 |
| CA2225189C (en) | 1997-03-06 | 2010-05-25 | Queen's University At Kingston | Canine factor viii gene, protein and methods of use |
| WO2002040544A2 (en) | 2000-11-14 | 2002-05-23 | Board Of Regents, University Of Texas Systems | Mutant human factor ix with an increased resistance to inhibition by heparin |
| AU2002232726A1 (en) | 2000-12-20 | 2002-07-01 | Bayer Pharmaceuticals Corporation | A device and method for seed-train expansion of mammalian cells |
| US20040254106A1 (en) | 2001-09-04 | 2004-12-16 | Carr Francis J. | Modified factor ix |
| EP1486785B1 (en) | 2002-02-21 | 2011-03-30 | Tokyo Gas Company Limited | Test agents for evaluating pharmacological effect of drug, and method and reagents for screening drug having excellent administration effect and/or little side effect from among drugs comprising enzymes, enzyme inhibitors or receptor ligands and/or prodrugs thereof |
| US7355008B2 (en) | 2003-01-09 | 2008-04-08 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
| AU2004205631A1 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
| US7348004B2 (en) | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| ES2456015T3 (es) * | 2004-03-05 | 2014-04-21 | Dsm Ip Assets B.V. | Procedimiento para cultivar células mediante perfusión continua y flujo tangencial alternante |
| TWI384069B (zh) * | 2004-08-27 | 2013-02-01 | Pfizer Ireland Pharmaceuticals | 多胜肽之製法 |
| EP2423306A1 (en) | 2006-06-19 | 2012-02-29 | Catalyst Biosciences, Inc. | Modified coagulation factor IX polypeptides and use thereof for treatment |
| MX345141B (es) * | 2006-09-13 | 2017-01-18 | Abbvie Inc * | Mejoras de cultivos celulares. |
| US7700734B2 (en) | 2007-01-09 | 2010-04-20 | Shu-Wha Lin | Recombinant human factor IX and use thereof |
| US20110154516A1 (en) | 2007-10-15 | 2011-06-23 | Stafford Darrel W | Human factor ix variants with an extended half life |
| CA2721362A1 (en) | 2008-04-16 | 2009-11-19 | Bayer Healthcare Llc | Site-directed modification of factor ix |
| SG189790A1 (en) | 2008-04-16 | 2013-05-31 | Bayer Healthcare Llc | Modified factor ix polypeptides and uses thereof |
| CN102105582A (zh) | 2008-04-21 | 2011-06-22 | 诺沃-诺迪斯克有限公司 | 高糖基化人凝血因子ix |
| SG189793A1 (en) * | 2008-04-23 | 2013-05-31 | Symphogen As | Methods for manufacturing a polyclonal protein |
| AU2009257336B2 (en) * | 2008-06-13 | 2016-01-28 | Janssen Biotech, Inc. | Methods for obtaining high viable cell density in mammalian cell culture |
| EP2506868B1 (en) | 2009-12-06 | 2017-11-15 | Bioverativ Therapeutics Inc. | Factor viii-fc chimeric and hybrid polypeptides, and methods of use thereof |
| SG182618A1 (en) * | 2010-01-25 | 2012-08-30 | Ventria Bioscience | Methods & compositions for improving protein production |
| WO2012006623A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Systems for factor viii processing and methods thereof |
| HRP20191305T1 (hr) | 2010-07-09 | 2019-10-18 | Bioverativ Therapeutics Inc. | Preradive jednolančane molekule i polipeptidi izrađeni koristeći iste |
| SG186856A1 (en) | 2010-07-09 | 2013-02-28 | Biogen Idec Hemophilia Inc | Factor ix polypeptides and methods of use thereof |
| WO2012128703A1 (en) | 2011-03-18 | 2012-09-27 | Ge Healthcare Bio-Sciences Ab | Flexible bag for cultivation of cells |
| KR102558247B1 (ko) | 2011-07-01 | 2023-07-24 | 암젠 인크 | 포유동물 세포 배양 |
| EP3083933B1 (en) | 2013-12-20 | 2026-01-21 | Biogen MA Inc. | Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality |
-
2014
- 2014-12-19 EP EP14827357.6A patent/EP3083933B1/en active Active
- 2014-12-19 JP JP2016532136A patent/JP2017500017A/ja not_active Withdrawn
- 2014-12-19 WO PCT/US2014/071701 patent/WO2015095809A1/en not_active Ceased
- 2014-12-19 US US15/038,698 patent/US20160289633A1/en not_active Abandoned
-
2020
- 2020-01-06 JP JP2020000268A patent/JP2020054388A/ja not_active Withdrawn
-
2022
- 2022-12-09 JP JP2022197095A patent/JP2023022317A/ja active Pending
-
2025
- 2025-01-17 US US19/027,281 patent/US20250382568A1/en active Pending
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