CN1211485C - 生产重组白蛋白的方法 - Google Patents
生产重组白蛋白的方法 Download PDFInfo
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- CN1211485C CN1211485C CNB008032920A CN00803292A CN1211485C CN 1211485 C CN1211485 C CN 1211485C CN B008032920 A CNB008032920 A CN B008032920A CN 00803292 A CN00803292 A CN 00803292A CN 1211485 C CN1211485 C CN 1211485C
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- TZMFJUDUGYTVRY-UHFFFAOYSA-N pentane-2,3-dione Chemical compound CCC(=O)C(C)=O TZMFJUDUGYTVRY-UHFFFAOYSA-N 0.000 description 1
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- RYVMUASDIZQXAA-UHFFFAOYSA-N pyranoside Natural products O1C2(OCC(C)C(OC3C(C(O)C(O)C(CO)O3)O)C2)C(C)C(C2(CCC3C4(C)CC5O)C)C1CC2C3CC=C4CC5OC(C(C1O)O)OC(CO)C1OC(C1OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OCC(O)C(O)C1O RYVMUASDIZQXAA-UHFFFAOYSA-N 0.000 description 1
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- VZPXDCIISFTYOM-UHFFFAOYSA-K trisodium;1-amino-4-[4-[[4-chloro-6-(3-sulfonatoanilino)-1,3,5-triazin-2-yl]amino]-3-sulfonatoanilino]-9,10-dioxoanthracene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=2C(=O)C3=CC=CC=C3C(=O)C=2C(N)=C(S([O-])(=O)=O)C=C1NC(C=C1S([O-])(=O)=O)=CC=C1NC(N=1)=NC(Cl)=NC=1NC1=CC=CC(S([O-])(=O)=O)=C1 VZPXDCIISFTYOM-UHFFFAOYSA-K 0.000 description 1
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Images
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3804—Affinity chromatography
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/362—Cation-exchange
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/363—Anion-exchange
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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
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- 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
- C07K14/76—Albumins
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- 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
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
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Abstract
Description
发酵pH | 上清液湿重(g/L-1) |
5.5 | 9.9(2.4,6) |
6.3-6.5 | 3.4(1.0,13) |
发酵pH | 上清液湿重(g/L-1) |
5.5 | 36.3 |
6.5 | 4.7 |
溶液 | 成分 | 浓度(g.L-1) | pH | 导电性(mS.cm-1) | |
编号 | 名称 | ||||
CS01 | SP-FF平衡液/洗柱液3/DE-FF平衡液 | CH3COOH | 1.85 | 5.45-4.65 | 1.9-2.2 |
NaOH(27%(w/w)) | 4.00 | ||||
CS02 | SP-FF洗柱液1 | CH3COOH | 3.00 | 3.9-4.1 | 0.6-0.8 |
NaOH(27%(w/w)) | 1.19 | ||||
CS03 | SP-FF洗柱液2 | CH3COOH | 1.62 | 3.9-4.1 | 125-165 |
NaOH(27%(w/w)) | 1.19 | ||||
NaCl | 117 | ||||
CS04 | SP-FF洗脱液/DE-FF预平衡液 | CH3COOH | 5.13 | 5.4-5.6 | 5.0-6.0 |
NaOH(27%(w/w)) | 11.5 | ||||
辛酸 | 0.721 | ||||
CS05 | 脱盐液 | NaCl | 58.4 | 5-9 | 75-95 |
Polysorbate 80 | 5.00 | ||||
CS06 | 0.5M NaOH | NaOH(27%(w/w)) | 74.1 | >12 | 80-120 |
CS07 | 20mM NaOH | NaOH(27%(w/w)) | 2.96 | >12 | 3.5-5.5 |
CS08 | DE-FF洗柱液 | K2B4O7.4H2O | 4.80 | 9.0-9.4 | 2.5-3.5 |
CS09 | DE-FF洗脱液 | K2B4O7.4H2O | 33.6 | 9.2-9.5 | 15.0-18.0 |
CS10 | DBA平衡液/洗涤液 | CH3COONH4 | 19.3 | 8.7-9.1 | 18-22 |
NaOH(27%(w/w)) | 5.93 | ||||
CS11 | DBA洗脱液 | NaCl | 117 | 6.7-7.1 | 125-165 |
NaOH(27%(w/w)) | 14.1 | ||||
H3PO4(85%(w/w)) | 5.79 | ||||
CS14 | 2M辛酸钠 | NaOH(27%(w/w)) | 281 | 7.8-8.4 | - |
辛酸 | 288 | ||||
CS15 | 乙酸 | CH3COOH | 1045 | - | - |
CS17 | DE-FF2平衡液/洗柱液 | CH3COOH | 1.50 | 4.5-4.7 | 0.85-1.05 |
NaOH(27%(w/w)) | 1.66 | ||||
CS18 | 主动方式DE-FF2洗脱液 | NaH2PO4.2H2O | 8.58 | 6.8-7.0 | 5.5-6.5 |
NaOH(27%(w/w)) | 4.07 | ||||
CS19 | SP-FF2平衡液/洗柱液 | CH3COOH | 1.80 | 5.2-5.4 | 1.8-2.1 |
NaOH(27%(w/w)) | 3.52 | ||||
CS20 | PBA平衡液/洗柱液 | 甘氨酸 | 7.51 | 8.3-8.6 | 18-22 |
NaCl | 5.84 | ||||
NaOH(27%(w/w)) | 0.95 | ||||
CaCl2.2H2O | 7.35 | ||||
CS21 | 20%(w/w)乙酸 | CH3COOH | 205 | 1.9-2.2 | 1.8-2.0 |
H2O | 820 | ||||
CS22 | 终pH调节液 | Na2HPO4 | 71.0 | 11.2-11.4 | 43-49 |
NaOH(27%(w/w)) | 37.0 | ||||
EXO4 | 终pH调节液(碱性) | NaOH(27%(w/w)) | 42.6 | ≥12 | 80-120 |
H2O | 970 | ||||
EXO5 | 终pH调节液(酸性) | HCl(37%w/w) | 19.7 | ≤1.5 | 60-90 |
H2O | 982 |
特异性基因缺失 | A600 | WW(g.L-1离心液) |
于pH5.5生长 | ||
pmt1-/hsp150-/yap3- | 1.39(0.52,24) | 12.4(4.9,23) |
hsp150-/yap3- | 1.11(0.62,9) | 9.1(2.9,7) |
yap3- | 0.58(0.34,10) | 3.9(2.0,10) |
于pH6.4或6.5生长 | ||
pmt1-/hsp150-/yap3- | 0.41(0.17,6) | 2.6(0.8,6) |
hsp150-/yap3- | 0.47(0.19,8) | 4.6(1.4,7) |
yap3- | 0.41(0.08,6) | 2.1(0.8,6) |
发酵pH | 上清液湿重含量(g.L-1) |
5.5 | 10.0(2.3,4) |
6.3-6.5 | 4.6(1.4,7) |
样品 | Amadori产品摩尔数/摩尔白蛋白 |
A | 0.79 |
B | 0.76 |
C | 0.41 |
D | 0.48 |
E | 0.46 |
F | 0.22 |
G | 0.41 |
H | 0.37 |
I | 0.54 |
J | 0.76 |
K | 0.84 |
L | 0.50 |
M | 0.43 |
N | 0.59 |
O | 0.41 |
P | 0.18 |
Q | 0.24 |
R | 0.04 |
[镍]/[rHA](μg/g) | ||
样品 | 第1批 | 第2批 |
PBA上样物 | 0.73 | 0.74 |
PBA流通液和淋洗液 | 0.41 | 0.43 |
SP-FF2上样物 | 0.06 | 0.06 |
SP-FF2流通液和淋洗液 | <0.03 | <0.03 |
DE-FF2流通液和淋洗液 | 0.14 | 0.28 |
ConA-结合的rHA(%上样量) | |||||||||
第1批 | 第2批 | 第3批 | 第4批 | 第5批 | |||||
PBAFT&W | 0.14 | PBAFT&W | 0.16 | PBAFT&W | 0.15 | PBAFT&W | 0.13 | PBAFT&W | 0.55 |
SP-FF2FT&W | 0.10 | SP-FF2FT&W | 0.12 | SP-FF2FT&W | 0.14 | SP-FF2FT&W | 0.09 | SP-FF2FT&W | 0.32 |
终产物 | 0.10 | 终产物 | 0.11 | 终产物 | 0.12 | 终产物 | 0.07 | 终产物 | 0.28 |
样品 | A350 | A403 | A500 |
1 | 9.95×10-3 | 4.10×10-3 | 0.8×10-3 |
2 | 9.25×10-3 | 5.36×10-3 | 1.1×10-3 |
3 | 7.40×10-3 | 3.26×10-3 | 0.6×10-3 |
4 | 7.20×10-3 | 3.60×10-3 | 0.6×10-3 |
5 | 8.68×10-3 | 4.08×10-3 | 0.8×10-3 |
6 | 11.45×10-3 | 6.26×10-3 | 1.2×10-3 |
7 | 7.20×10-3 | 3.70×10-3 | 0.8×10-3 |
8 | 6.82×10-3 | 4.78×10-3 | 1.8×10-3 |
样品 | mol.mol-1 |
A | 0.82 |
B | 0.77 |
C | 0.77 |
D | 0.85 |
E | 0.90 |
Claims (18)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB9902000A GB9902000D0 (en) | 1999-01-30 | 1999-01-30 | Process |
GB9902000.0 | 1999-01-30 |
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CN2004100050153A Division CN1526732B (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
CN2005101086585A Division CN1810834B (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
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CN1211485C true CN1211485C (zh) | 2005-07-20 |
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CNA2006101006640A Pending CN1974599A (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
CN2005101086585A Expired - Lifetime CN1810834B (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
CNB008032920A Expired - Lifetime CN1211485C (zh) | 1999-01-30 | 2000-01-31 | 生产重组白蛋白的方法 |
CN2004100050153A Expired - Lifetime CN1526732B (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
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CNA2006101006640A Pending CN1974599A (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
CN2005101086585A Expired - Lifetime CN1810834B (zh) | 1999-01-30 | 2000-01-31 | 制备高纯度白蛋白溶液的方法 |
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Country Status (16)
Country | Link |
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US (3) | US7993877B2 (zh) |
EP (3) | EP2272961A1 (zh) |
JP (3) | JP4586150B2 (zh) |
KR (2) | KR100886554B1 (zh) |
CN (4) | CN1974599A (zh) |
AT (1) | ATE416254T1 (zh) |
AU (2) | AU763899B2 (zh) |
CA (1) | CA2359705C (zh) |
DE (1) | DE60040967D1 (zh) |
DK (1) | DK2048234T3 (zh) |
ES (1) | ES2317827T3 (zh) |
GB (1) | GB9902000D0 (zh) |
HK (2) | HK1096691A1 (zh) |
MX (1) | MXPA01007719A (zh) |
SG (2) | SG174629A1 (zh) |
WO (1) | WO2000044772A2 (zh) |
Families Citing this family (84)
Publication number | Priority date | Publication date | Assignee | Title |
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GB9902000D0 (en) | 1999-01-30 | 1999-03-17 | Delta Biotechnology Ltd | Process |
EP1276756A4 (en) | 2000-04-12 | 2004-06-09 | Human Genome Sciences Inc | ALBUMIN FUSION PROTEINS |
ITBO20010426A1 (it) * | 2001-07-06 | 2003-01-06 | Alfa Wassermann Spa | Processo per la purificazione di proteine farmacologicamente attive mediante cromatografia in scambio cationico |
US7176278B2 (en) | 2001-08-30 | 2007-02-13 | Biorexis Technology, Inc. | Modified transferrin fusion proteins |
ES2545090T3 (es) | 2001-12-21 | 2015-09-08 | Human Genome Sciences, Inc. | Proteínas de fusión de albúmina y GCSF |
GB0202633D0 (en) * | 2002-02-05 | 2002-03-20 | Delta Biotechnology Ltd | Stabilization of protein preparations |
KR20040095217A (ko) | 2002-02-07 | 2004-11-12 | 델타 바이오테크놀로지 리미티드 | 알부민-융합 항-혈관신생 펩타이드 |
SE526227C2 (sv) * | 2002-05-15 | 2005-08-02 | North China Pharmaceutical Group | Metod för rening av rekombinant humant serumalbumin |
GB0217033D0 (en) | 2002-07-23 | 2002-08-28 | Delta Biotechnology Ltd | Gene and polypeptide sequences |
GB0304576D0 (en) | 2003-02-28 | 2003-04-02 | Lonza Biologics Plc | Protein a chromatography |
ES2380022T3 (es) | 2003-12-03 | 2012-05-07 | Monika KRÖZ | Proteínas de fusión a interleucina-11 |
GB0329681D0 (en) | 2003-12-23 | 2004-01-28 | Delta Biotechnology Ltd | Gene expression technique |
GB0329722D0 (en) * | 2003-12-23 | 2004-01-28 | Delta Biotechnology Ltd | Modified plasmid and use thereof |
JP2008523829A (ja) * | 2004-12-22 | 2008-07-10 | ノボザイムス アクティーゼルスカブ | 血清アルブミンの組換え生成 |
EP1831375B1 (en) | 2004-12-23 | 2014-07-16 | Novozymes Biopharma DK A/S | Gene expression technique |
WO2007063129A2 (en) * | 2005-12-02 | 2007-06-07 | Novozymes A/S | Insolation of peptides , polypeptides and proteins |
JP2007284425A (ja) * | 2006-03-20 | 2007-11-01 | Nokodai Tlo Kk | タンパク質の精製方法 |
JP5670634B2 (ja) * | 2006-07-13 | 2015-02-18 | アッパートン リミティド | タンパク質性物質の粒子の製造方法 |
WO2008012629A2 (en) | 2006-07-24 | 2008-01-31 | Biorexis Pharmaceutical Corporation | Exendin fusion proteins |
JP5256199B2 (ja) | 2006-08-07 | 2013-08-07 | テヴァ バイオファーマシューティカルズ ユーエスエー,インコーポレーティッド | アルブミン−インスリン融合タンパク質 |
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2003
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