JPH09501693A - 組み換えインスリン様成長因子igf−i様ポリペプチドの再折りたたみ - Google Patents
組み換えインスリン様成長因子igf−i様ポリペプチドの再折りたたみInfo
- Publication number
- JPH09501693A JPH09501693A JP7507626A JP50762695A JPH09501693A JP H09501693 A JPH09501693 A JP H09501693A JP 7507626 A JP7507626 A JP 7507626A JP 50762695 A JP50762695 A JP 50762695A JP H09501693 A JPH09501693 A JP H09501693A
- Authority
- JP
- Japan
- Prior art keywords
- concentration
- igf
- salt
- composition
- buffer
- 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.)
- Granted
Links
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Classifications
-
- 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
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
-
- 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
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- 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
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.IGF−I、成長ホルモンおよびニューロトロフィンから構成される群か ら選択されたポリペプチド約0.1から15mg/mLをアルコールまたは極性 非プロトン溶媒約5〜40%(v/v)、約0.2から3Mのアルカリ土類、ア ルカリ金属またはアンモニウム塩、約0.1から9Mのカオトロピック試薬およ び約0.01から15μMの銅またはマンガン塩を含有するpH7〜12の緩衝 液中に含む組成物。 2.溶媒の濃度が約10〜30%(v/v)である請求項1の組成物。 3.ポリペプチドの濃度が約0.1から6mg/mLである請求項1の組成 物。 4.アルカリ土類、アルカリ金属またはアンモニウム塩の濃度が約0.2か ら2Mである請求項1の組成物。 5.カオトロピック試薬の濃度が約0.5から6Mである請求項1の組成物 。 6.銅塩またはマンガン塩の濃度が約0.01から5μMである請求項1の 組成物。 7.銅塩またはマンガン塩の濃度が約0.01から0.5μMである請求項 1の組成物。 8.溶媒がメタノール、エタノール、イソプロパノール、n−プロパノール 、t−ブタノール、ジメチルスルホキシド、ジメチルホルムアミド、N−メチル ピロリドン、テトラヒドロフラン、ジオキサン、グリセリン、アセトニトリルま たはプロピレングリコールである請求項1の組成物。 9.カオトロピック試薬が尿素である請求項1の組成物。 10.アルカリ土類、アルカリ金属またはアンモニウム塩が約0.5から2M のナトリム、カリウム、またはアンモニウム塩であるか、または約0.2から1 Mのマグネシウム塩である請求項1の組成物。 11.溶媒がエタノールであり、アルカリ土類、アルカリ金属またはアンモニ ウム塩が塩化物または硫酸塩であり、ポリペプチドの濃度が約0.2から5mg /mLの範囲にある請求項10の組成物。 12.アルカリ土類、アルカリ金属またはアンモニウム塩が塩化ナトリウムで あり、緩衝液のpHが約8から11までの範囲にある請求項11の組成物。 13.ポリペプチドがIGF−Iまたは成長ホルモンである請求項1の組成物 。 14.銅塩またはマンガン塩が塩化物または硫酸塩である請求項1の組成物。 15.銅塩が塩化銅である請求項14の組成物。 16.銅塩が約0.5μMの濃度で存在する請求項14の組成物。 17.緩衝液がオスモライトおよび還元剤も含有する請求項1の組成物。 18.緩衝液がグリシン、CAPSまたはCAPSOである請求項17の組成 物。 19.還元剤が濃度約1〜5mMのシステインまたはジチオスレイトールであ る請求項17の組成物。 20.緩衝液が濃度約20mMのグリシンまたはCAPSOであり、還元剤が 約1mMのジチオスレイトールであり、銅塩が塩化銅であり、カオトロピック試 薬が約1から3Mの尿素であり、緩衝液がpH約8.5から11の値を持つ請求 項19の組成物。 21.尿素が約2Mの濃度である請求項20の組成物。 22.再折りたたみ段階の間、アルコールまたは極性非プロトン溶媒約5〜4 0%(v/v)、約0.2から3Mのアルカリ土類、アルカリ金属またはアンモ ニウム塩、約0.1から9Mのカオトロピック試薬、および約0.01から15 μMの銅またはマンガン塩を含有するpH7〜12の緩衝液中にポリペプチドを 約0.1から15mg/mLの濃度で存在させるものである、宿主細胞に含有さ れるIGF−I、成長ホルモンおよびニューロトロフィンから構成される群から 選択されたポリペプチドの、誤った折りたたみを正しい折りたたみに折りたたみ 直す収率を向上させる方法。 23.宿主細胞が原核生物である請求項22の方法。 24.アルカリ土類、アルカリ金属またはアンモニウム塩が約0.5から2M のナトリウム、カリウムまたはアンモニウム塩であるか、または約0.2から1 Mのマグネシウム塩である請求項22の方法。 25.緩衝液がさらに還元剤およびオスモライトを含有する請求項22の方法 。 26.銅塩が塩化銅である請求項22の方法。 27.緩衝液がpH約8から11のCAPSOまたはグリシンであり、カオト ロピック試薬が約1から3Mの尿素であり、塩が塩化ナトリウムであり、溶媒が 約20%(v/v)濃度のエタノールまたはイソプロパノールであり、ポリペプ チドがIGF−Iであり、還元剤がジチオスレイトールまたはシステインであり 、オスモライトがショ糖またはグリセリンである請求項26の方法。 28.宿主細胞内に含有されている誤った折りたたみのIGF−Iを再活性化 する方法であって、 (イ)宿主細胞から該IGF−Iを分離すること、 (ロ)溶解に充分な濃度のカオトロピック試薬および還元剤を含むアルカリ性 緩衝液中に該IGF−Iを維持すること、および (ハ)アルコールまたは極性非プロトン溶媒約5〜40%(v/v)、約0. 2から3Mのアルカリ土類、アルカリ金属またはアンモニウム塩、約0.1から 9Mのカオトロピック試薬、および約0.01から15μMの銅またはマンガン 塩を含有するpH7〜12の折りたたみ用緩衝液中で溶解した該IGF−Iを約 0.1から15mg/mLの濃度でIGF−Iの再折りたたみが起きるように酸 素源を導入しつつインキュベーションすること を含む方法。 29.IGF−Iが原核生物から分離されたものである請求項28の方法。 30.IGF−Iが宿主細胞の周辺細胞質から分離されたものである請求項2 9の方法。 31.IGF−Iが折りたたみ用緩衝液中に濃度約0.1〜5mg/mLで存 在する請求項28の方法。 32.折りたたみ用緩衝液がさらに還元剤を含有する請求項28の方法。 33.工程(ハ)で、カオトロピック試薬が濃度約1から3Mの尿素であり、 還元剤が濃度約1から5Mのジチオスレイトールまたはシステインであり、pH が約8から11である請求項32の方法。 34.工程(ハ)で、カオトロピック試薬が濃度約0.1から0.5Mの塩酸 グアニジンであり、還元剤が濃度約1から5Mのジチオスレイトールまたはシス テインであり、pHが約8から11である請求項32の方法。 35.溶媒がメタノール、エタノール、イソプロパノール、n−プロパノール 、t−ブタノール、ジメチルスルホキシド、ジメチルホルムアミド、N−メチル ピロリドン、テトラヒドロフラン、ジオキサン、グリセリン、アセトニトリルま たはプロピレングリコールである請求項28の方法。 36.溶媒がエタノールまたはイソプロパノールであり、濃度が約20%(v /v)である請求項28の方法。 37.アルカリ土類、アルカリ金属またはアンモニウム塩がNaCl、Na2 SO4、MgCl2、MgSO4、NH4Cl、または(NH4)2SO4であり、銅 またはマンガン塩が塩化物または硫酸塩である請求項28の方法。 38.折りたたみ用緩衝液がpH約10〜11で、約20mM濃度のグリシン であって、約20%のエタノール、約1MのNaCl、約1mMのジチオスレイ トール、約2Mの尿素、および約0.01〜0.5mMの塩化銅を含む請求項2 8の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/110,664 | 1993-08-20 | ||
US08/110,664 US5663304A (en) | 1993-08-20 | 1993-08-20 | Refolding of misfolded insulin-like growth factor-I |
PCT/US1994/009120 WO1995006064A1 (en) | 1993-08-20 | 1994-08-15 | Refolding of polypeptides like recombinant insulin-like growth factor igf-i |
Publications (2)
Publication Number | Publication Date |
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JPH09501693A true JPH09501693A (ja) | 1997-02-18 |
JP3648242B2 JP3648242B2 (ja) | 2005-05-18 |
Family
ID=22334224
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP50762695A Expired - Lifetime JP3648242B2 (ja) | 1993-08-20 | 1994-08-15 | 組み換えインスリン様成長因子igf−i様ポリペプチドの再折りたたみ |
Country Status (10)
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US (3) | US5663304A (ja) |
EP (2) | EP0714406B1 (ja) |
JP (1) | JP3648242B2 (ja) |
AT (2) | ATE264872T1 (ja) |
CA (1) | CA2168552C (ja) |
DE (2) | DE69434919T2 (ja) |
DK (2) | DK0714406T3 (ja) |
ES (2) | ES2280857T3 (ja) |
PT (2) | PT1486511E (ja) |
WO (1) | WO1995006064A1 (ja) |
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- 1994-08-15 AT AT94927917T patent/ATE264872T1/de active
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US8906648B2 (en) | 2005-12-22 | 2014-12-09 | Genentech, Inc. | Recombinant production of vascular endothelial growth factor |
JP2009543882A (ja) * | 2006-07-14 | 2009-12-10 | ジェネンテック・インコーポレーテッド | 組み換えタンパク質の再折り畳み |
US9200030B2 (en) | 2006-07-14 | 2015-12-01 | Genentech, Inc. | Refolding of recombinant proteins |
US9994612B2 (en) | 2006-07-14 | 2018-06-12 | Genentech, Inc. | Refolding of recombinant proteins |
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DE69433724D1 (de) | 2004-05-27 |
ES2219649T3 (es) | 2004-12-01 |
DE69433724T2 (de) | 2005-04-28 |
ATE352568T1 (de) | 2007-02-15 |
EP1486511A1 (en) | 2004-12-15 |
CA2168552A1 (en) | 1995-03-02 |
DK1486511T3 (da) | 2007-05-29 |
ATE264872T1 (de) | 2004-05-15 |
WO1995006064A1 (en) | 1995-03-02 |
DE69434919T2 (de) | 2007-11-29 |
EP0714406B1 (en) | 2004-04-21 |
JP3648242B2 (ja) | 2005-05-18 |
US5808006A (en) | 1998-09-15 |
DE69434919D1 (de) | 2007-03-15 |
US5663304A (en) | 1997-09-02 |
PT714406E (pt) | 2004-09-30 |
PT1486511E (pt) | 2007-04-30 |
EP1486511B1 (en) | 2007-01-24 |
EP0714406A1 (en) | 1996-06-05 |
DK0714406T3 (da) | 2004-07-26 |
CA2168552C (en) | 2000-02-15 |
US5756672A (en) | 1998-05-26 |
ES2280857T3 (es) | 2007-09-16 |
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