JP7097433B2 - 宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 - Google Patents
宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/165—Extraction; Separation; Purification by chromatography mixed-mode chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Medicinal Chemistry (AREA)
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- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201762546558P | 2017-08-17 | 2017-08-17 | |
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| PCT/US2018/046919 WO2019036626A1 (en) | 2017-08-17 | 2018-08-17 | PROCESS FOR PURIFYING GLYCOSYLATED PROTEIN FROM GALECTINES AND OTHER HOST CELL CONTAMINANTS |
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| JP2020531411A JP2020531411A (ja) | 2020-11-05 |
| JPWO2019036626A5 JPWO2019036626A5 (https=) | 2022-05-09 |
| JP2020531411A5 JP2020531411A5 (https=) | 2022-05-09 |
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| MY (1) | MY199833A (https=) |
| WO (1) | WO2019036626A1 (https=) |
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| DK3668985T3 (da) | 2017-08-17 | 2021-09-20 | Just Evotec Biologics Inc | Fremgangsmåde til rensning af glycosyleret protein fra værtscellegalectiner og andre urenheder |
| US11180540B2 (en) * | 2019-12-06 | 2021-11-23 | Regeneron Pharmaceuticals, Inc. | Anti-VEGF protein compositions and methods for producing the same |
| JP2023525034A (ja) | 2020-05-08 | 2023-06-14 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Ｖｅｇｆトラップおよびミニトラップならびに眼障害およびがんの治療方法 |
| WO2023192926A2 (en) * | 2022-03-30 | 2023-10-05 | Ionis Pharmaceuticals, Inc. | Methods for separating certain oligonucleotide compounds |
| TW202502843A (zh) * | 2023-03-17 | 2025-01-16 | 日商丸善石油化學股份有限公司 | 聚合物之製造方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008543868A (ja) | 2005-06-17 | 2008-12-04 | ワイス | Ｆｃ領域含有タンパク質を精製する方法 |
| JP2010516651A (ja) | 2007-01-17 | 2010-05-20 | メルク セローノ ソシエテ アノニム | Ｆｃ含有タンパク質の精製のための方法 |
| JP2011530606A (ja) | 2008-08-14 | 2011-12-22 | メルク・シャープ・エンド・ドーム・コーポレイション | プロテインａアフィニティークロマトグラフィーを用いる抗体の精製方法 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| 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 |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| WO1990001063A1 (en) | 1988-07-23 | 1990-02-08 | Delta Biotechnology Limited | New secretory leader sequences |
| AU632065B2 (en) | 1988-09-23 | 1992-12-17 | Novartis Vaccines And Diagnostics, Inc. | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| US5429746A (en) | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
| AT403989B (de) | 1996-09-16 | 1998-07-27 | Immuno Ag | Verfahren zur herstellung eines plasmaprotein-hältigen arzneimittels |
| EP0950067B1 (en) | 1996-11-27 | 2007-08-29 | Genentech, Inc. | Affinity purification of polypeptide on protein a matrix |
| US6022952A (en) | 1998-04-01 | 2000-02-08 | University Of Alberta | Compositions and methods for protein secretion |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| CA2350226C (en) | 1998-11-20 | 2012-04-24 | Fuso Pharmaceutical Industries, Ltd. | Protein expression vector and utilization thereof |
| JP2002538841A (ja) | 1999-03-18 | 2002-11-19 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | ２７個のヒト分泌タンパク質 |
| US7306799B2 (en) | 1999-06-08 | 2007-12-11 | Regeneron Pharmaceuticals, Inc. | Use of VEGF inhibitors for treatment of eye disorders |
| CN100523187C (zh) | 1999-06-08 | 2009-08-05 | 里珍纳龙药品有限公司 | 具有改善的药物动力学特性的修饰嵌合多肽 |
| US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
| US7303746B2 (en) | 1999-06-08 | 2007-12-04 | Regeneron Pharmaceuticals, Inc. | Methods of treating eye disorders with modified chimeric polypeptides |
| AU2003210802B2 (en) | 2002-02-05 | 2009-09-10 | Genentech Inc. | Protein purification |
| DE602004026343D1 (de) | 2003-10-24 | 2010-05-12 | Amgen Inc | Verfahren zur aufreinigung von proteinen in einer durchflussfraktion aus der chromatographie mit hydrophoben wechselwirkungen |
| FR2894146B1 (fr) | 2005-12-07 | 2008-06-06 | Ifremer | Utilisation d'un polysaccharide excrete par l'espece vibrio diabolicus a des fins d'ingenierie des tissus conjonctifs non mineralises |
| WO2007109163A2 (en) | 2006-03-16 | 2007-09-27 | Amgen Inc | Wash buffer and method of using |
| US7998927B2 (en) | 2006-06-23 | 2011-08-16 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| CL2008002054A1 (es) | 2007-07-17 | 2009-05-29 | Hoffmann La Roche | Metodo para la regeneracion de una columna de cromatografia de intercambio cationico despues de la elusion de eritropoyetina monopeguilada y metodo para obtener una eritropoyetina monopeguilada, incorporando el metodo de regeneracion de la columna de intercambio cationico. |
| AU2009347206C1 (en) | 2008-10-20 | 2016-12-08 | Abbvie Inc. | Isolation and purification of antibodies using Protein A affinity chromatography |
| BRPI0919879A2 (pt) | 2008-10-29 | 2016-02-16 | Wyeth Llc | métodos para purificação de moléculas de ligação a antígeno de domínio único |
| WO2011038894A1 (en) | 2009-10-01 | 2011-04-07 | F. Hoffmann-La Roche Ag | Protein a chromatography |
| ES2813398T3 (es) * | 2009-10-20 | 2021-03-23 | Abbvie Inc | Aislamiento y purificación de anticuerpos anti-IL-13 usando cromatografía de afinidad a Proteína A |
| EP2513134B1 (en) | 2009-12-18 | 2017-09-06 | Novartis AG | Wash solution and method for affinity chromatography |
| CN103429609A (zh) | 2010-12-08 | 2013-12-04 | 安姆根有限公司 | 在氨基酸存在下的离子交换层析 |
| TW201823460A (zh) | 2012-05-29 | 2018-07-01 | 美商再生元醫藥公司 | 生產細胞株增強子 |
| AU2015273049B2 (en) * | 2014-06-13 | 2019-11-14 | Lupin Limited | Process for the purification of TNFR:Fc fusion protein |
| EP3236772A4 (en) * | 2014-12-22 | 2018-10-17 | Alexion Pharmaceuticals, Inc. | Methods of purifying recombinant proteins |
| TW201702380A (zh) * | 2015-02-27 | 2017-01-16 | 再生元醫藥公司 | 宿主細胞蛋白質修飾 |
| AU2016261854B2 (en) | 2015-05-12 | 2022-05-26 | Regeneron Pharmaceuticals, Inc. | Multimeric protein purity determination |
| CN106749660B (zh) * | 2016-12-27 | 2020-02-14 | 嘉和生物药业有限公司 | 单克隆抗体下游纯化过程中有效去除宿主蛋白的方法 |
| DK3668985T3 (da) | 2017-08-17 | 2021-09-20 | Just Evotec Biologics Inc | Fremgangsmåde til rensning af glycosyleret protein fra værtscellegalectiner og andre urenheder |
| JP2022520793A (ja) * | 2019-02-15 | 2022-04-01 | ジャスト－エヴォテック バイオロジックス、インコーポレイテッド | 自動バイオ製造システム、施設、及びプロセス |
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2018
- 2018-08-17 DK DK18778588.6T patent/DK3668985T3/da active
- 2018-08-17 CN CN201880052805.7A patent/CN111344410B/zh active Active
- 2018-08-17 ES ES18778588T patent/ES2887046T3/es active Active
- 2018-08-17 JP JP2020505786A patent/JP7097433B2/ja active Active
- 2018-08-17 EP EP18778588.6A patent/EP3668985B1/en active Active
- 2018-08-17 MY MYPI2019007631A patent/MY199833A/en unknown
- 2018-08-17 CA CA3067735A patent/CA3067735A1/en active Pending
- 2018-08-17 WO PCT/US2018/046919 patent/WO2019036626A1/en not_active Ceased
- 2018-08-17 KR KR1020207007328A patent/KR102578087B1/ko active Active
- 2018-08-18 US US16/630,458 patent/US11358983B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008543868A (ja) | 2005-06-17 | 2008-12-04 | ワイス | Ｆｃ領域含有タンパク質を精製する方法 |
| JP2010516651A (ja) | 2007-01-17 | 2010-05-20 | メルク セローノ ソシエテ アノニム | Ｆｃ含有タンパク質の精製のための方法 |
| JP2011530606A (ja) | 2008-08-14 | 2011-12-22 | メルク・シャープ・エンド・ドーム・コーポレイション | プロテインａアフィニティークロマトグラフィーを用いる抗体の精製方法 |
Non-Patent Citations (5)
| Title |
|---|
| Atsuhiro Kanda et al.，Scientific Reports，2015年12月09日，5:17946，p. 1-11 |
| G. Joucla et al.，Journal of Chrmatography B，2013年，Vol. 942-943，p. 126-133 |
| Kerstin A. Heyl et al.，Biochemical and Biophysical Research Communications，2016年，Vol. 479，p. 86-90 |
| Nabila Aboulaich et al.，Biotehnol. Prog.，2014年07月26日，Vol. 30, No. 5，p. 1114-1124 |
| Santosh Kumar Patnaik et al.，Glycobiology，2005年11月29日，Vol.16, No. 4，pp. 305-317 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3668985B1 (en) | 2021-06-16 |
| JP2020531411A (ja) | 2020-11-05 |
| US20210163528A1 (en) | 2021-06-03 |
| WO2019036626A1 (en) | 2019-02-21 |
| ES2887046T3 (es) | 2021-12-21 |
| KR20200037396A (ko) | 2020-04-08 |
| US11358983B2 (en) | 2022-06-14 |
| CN111344410B (zh) | 2023-09-15 |
| MY199833A (en) | 2023-11-24 |
| KR102578087B1 (ko) | 2023-09-18 |
| EP3668985A1 (en) | 2020-06-24 |
| CA3067735A1 (en) | 2019-02-21 |
| DK3668985T3 (da) | 2021-09-20 |
| CN111344410A (zh) | 2020-06-26 |
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