CA2755927A1 - Method for purifying recombinant fsh - Google Patents
Method for purifying recombinant fsh Download PDFInfo
- Publication number
- CA2755927A1 CA2755927A1 CA2755927A CA2755927A CA2755927A1 CA 2755927 A1 CA2755927 A1 CA 2755927A1 CA 2755927 A CA2755927 A CA 2755927A CA 2755927 A CA2755927 A CA 2755927A CA 2755927 A1 CA2755927 A1 CA 2755927A1
- Authority
- CA
- Canada
- Prior art keywords
- chromatography
- fsh
- anion exchange
- exchange chromatography
- recombinant
- 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.)
- Abandoned
Links
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Classifications
-
- 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
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
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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
- C07K1/18—Ion-exchange chromatography
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- 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
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction 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
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Reproductive Health (AREA)
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09157133.1 | 2009-04-01 | ||
| EP09157133 | 2009-04-01 | ||
| PCT/EP2010/002111 WO2010115586A2 (en) | 2009-04-01 | 2010-04-01 | Method for purifying recombinant fsh |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2755927A1 true CA2755927A1 (en) | 2010-10-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2755927A Abandoned CA2755927A1 (en) | 2009-04-01 | 2010-04-01 | Method for purifying recombinant fsh |
Country Status (26)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5845170B2 (ja) * | 2009-04-01 | 2016-01-20 | ラティオファーム ゲーエムベーハー | 組換えｆｓｈを精製する方法 |
| CN103570820B (zh) * | 2012-08-06 | 2015-11-18 | 齐鲁制药有限公司 | 一种重组人促卵泡激素的纯化方法 |
| KR101516054B1 (ko) * | 2012-11-21 | 2015-05-06 | 씨제이헬스케어 주식회사 | 신규한 지속형 인간 성장호르몬 단량체를 제조하는 방법 |
| CN103059125B (zh) * | 2012-12-27 | 2015-08-12 | 浙江海正药业股份有限公司 | 重组人促卵泡激素的纯化方法 |
| CN103539860B (zh) * | 2013-11-01 | 2014-12-03 | 广州优联康医药科技有限公司 | 一种长效重组人促卵泡激素融合蛋白 |
| CN103539861B (zh) * | 2013-11-01 | 2015-02-18 | 广州联康生物科技有限公司 | 长效重组人促卵泡激素融合蛋白 |
| CA2945591A1 (en) * | 2014-04-18 | 2015-10-22 | Cadila Healthcare Limited | Novel purification process of gonadotropin |
| CN104479005B (zh) * | 2014-09-05 | 2017-10-31 | 上海丽珠制药有限公司 | 一种促性腺激素纯化的方法 |
| CN105461799A (zh) * | 2015-12-31 | 2016-04-06 | 哈药集团技术中心 | 一种重组人促卵泡生成素的纯化方法 |
| CN106117342B (zh) * | 2016-07-07 | 2020-01-03 | 江西浩然生物医药有限公司 | 一种高纯度尿促卵泡素的制备方法 |
| RU2694598C1 (ru) * | 2018-08-07 | 2019-07-16 | Федеральное государственное бюджетное учреждение науки институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук (ИБХ РАН) | Клеточная линия huFSHKKc6 - продуцент рекомбинантного человеческого фолликулостимулирующего гормона (ФСГ) и способ получения ФСГ с использованием данной линии |
| KR102752765B1 (ko) * | 2019-12-26 | 2025-01-14 | 주식회사 엘지화학 | 여포 자극 호르몬의 정제 방법 |
| KR102283871B1 (ko) * | 2021-03-02 | 2021-08-02 | 한국원자력연구원 | 크로마토그래피를 이용한 무담체 홀뮴-166의 분리 방법, 분리 장치 및 이에 의하여 분리된 무담체 홀뮴-166 |
| CN113372433B (zh) * | 2021-03-12 | 2022-10-11 | 上海景泽生物技术有限公司 | 纯化fsh方法 |
| CN114591414A (zh) * | 2022-03-24 | 2022-06-07 | 江西浩然生物制药有限公司 | 一种人绒毛膜促性腺激素的制备方法 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4923805A (en) | 1983-11-02 | 1990-05-08 | Integrated Genetics, Inc. | Fsh |
| US6455282B1 (en) * | 1983-11-02 | 2002-09-24 | Genzyme Corporation | Cells, vectors and methods for producing biologically active TSH |
| US4840896A (en) | 1983-11-02 | 1989-06-20 | Integrated Genetics, Inc. | Heteropolymeric protein |
| IT1206302B (it) | 1987-06-26 | 1989-04-14 | Serono Cesare Ist Ricerca | Ormone follicolo-stimolante urinario |
| CA2018676C (en) | 1989-06-20 | 2003-05-06 | Christie A. Kelton | Novel heteropolymeric protein production methods |
| US5021160A (en) * | 1990-01-09 | 1991-06-04 | Gelman Sciences, Inc. | Strongly acidic microporous membranes for cation exchange |
| DE4440587A1 (de) | 1994-11-14 | 1996-05-15 | Fliether Karl Gmbh & Co | Basquill-Schloß |
| US6261823B1 (en) * | 1996-12-13 | 2001-07-17 | Schering Corporation | Methods for purifying viruses |
| AU747179B2 (en) | 1997-06-25 | 2002-05-09 | Merck Serono Sa | Disulfide cross-linked glycoprotein hormone analogs, their preparation and use |
| US6414123B1 (en) * | 1997-10-21 | 2002-07-02 | Vitro Diagnostics, Inc. | Method for purifying FSH |
| US5990288A (en) * | 1997-10-21 | 1999-11-23 | Vitro Diagnostics, Inc. | Method for purifying FSH |
| ATE358139T1 (de) | 1999-04-16 | 2007-04-15 | Inst Massone S A | Verfahren zur herstelllung von gonadotropin- zusammensetzungen |
| WO2001058493A1 (en) | 2000-02-11 | 2001-08-16 | Maxygen Aps | Conjugates of follicle stimulating hormones |
| US7157277B2 (en) * | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| AU2003240832A1 (en) | 2002-05-31 | 2003-12-19 | E.I. Du Pont De Nemours And Company | Copolymers having tunable energy levels and color of emission |
| WO2004087213A1 (en) | 2003-04-02 | 2004-10-14 | Ares Trading S.A. | Liquid pharmaceutical formulations of fsh and lh together with a non-ionic surfactant |
| ATE446314T1 (de) * | 2003-12-22 | 2009-11-15 | Ares Trading Sa | Methode zur reinigung von fsh |
| EP1809663B1 (en) | 2004-11-09 | 2008-09-17 | Ares Trading S.A. | Method for purifying fsh |
| TW200728316A (en) * | 2005-12-09 | 2007-08-01 | Ares Trading Sa | Method for purifying FSH or a FSH mutant |
| JP5199112B2 (ja) * | 2005-12-09 | 2013-05-15 | アレス トレーディング ソシエテ アノニム | Ｆｓｈ又はｆｓｈ変異体を精製するための方法 |
| CN101720332B (zh) | 2007-06-28 | 2014-08-13 | 拉蒂奥法姆有限责任公司 | 生产促卵泡激素的细胞克隆 |
| 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. |
| JP5845170B2 (ja) * | 2009-04-01 | 2016-01-20 | ラティオファーム ゲーエムベーハー | 組換えｆｓｈを精製する方法 |
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- 2010-04-01 JP JP2012502514A patent/JP5845170B2/ja not_active Expired - Fee Related
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- 2010-04-01 EP EP10713424.9A patent/EP2414380B1/en active Active
- 2010-04-01 PT PT107134249T patent/PT2414380E/pt unknown
- 2010-04-01 MX MX2011010480A patent/MX2011010480A/es unknown
- 2010-04-01 RS RS20150682A patent/RS54318B1/sr unknown
- 2010-04-01 KR KR1020117025974A patent/KR101761168B1/ko not_active Expired - Fee Related
- 2010-04-01 US US13/262,622 patent/US9096683B2/en not_active Expired - Fee Related
- 2010-04-01 NZ NZ595661A patent/NZ595661A/xx not_active IP Right Cessation
- 2010-04-01 PL PL10713424T patent/PL2414380T3/pl unknown
- 2010-04-01 WO PCT/EP2010/002111 patent/WO2010115586A2/en not_active Ceased
- 2010-04-01 HU HUE10713424A patent/HUE025959T2/en unknown
- 2010-04-01 UA UAA201112796A patent/UA106369C2/ru unknown
- 2010-04-01 ES ES10713424.9T patent/ES2552055T3/es active Active
- 2010-04-01 AU AU2010234028A patent/AU2010234028B2/en not_active Ceased
- 2010-04-01 DK DK10713424.9T patent/DK2414380T3/en active
- 2010-04-01 CA CA2755927A patent/CA2755927A1/en not_active Abandoned
- 2010-04-01 ME MEP-2015-172A patent/ME02277B/me unknown
- 2010-04-01 CN CN201080022681.1A patent/CN102448979B/zh active Active
- 2010-04-01 HR HRP20151086TT patent/HRP20151086T1/hr unknown
- 2010-04-01 SI SI201031050T patent/SI2414380T1/sl unknown
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2011
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- 2015-09-09 JP JP2015177674A patent/JP6231056B2/ja not_active Expired - Fee Related
- 2015-10-30 CY CY20151100971T patent/CY1116963T1/el unknown
- 2015-11-04 SM SM201500276T patent/SMT201500276B/it unknown
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
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