CN101048512B - 抗淀粉样β肽抗体的生产 - Google Patents
抗淀粉样β肽抗体的生产 Download PDFInfo
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- CN101048512B CN101048512B CN2005800368972A CN200580036897A CN101048512B CN 101048512 B CN101048512 B CN 101048512B CN 2005800368972 A CN2005800368972 A CN 2005800368972A CN 200580036897 A CN200580036897 A CN 200580036897A CN 101048512 B CN101048512 B CN 101048512B
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Abstract
Description
部分 | 成分 | 含量 | 单位 |
I | 培养基4A-1 | 31.120 | g/L |
NucellinTM | 40.000 | ml/L | |
H/P贮存液 | 20.000 | ml/L | |
亚硒酸盐贮存液 | 2.000 | ml/L | |
PVA | 2.400 | g/L | |
NaH2PO4·H2O | 2.610 | g/L | |
MgSO4·7H2O | 0.430 | g/L | |
天冬氨酸 | 1.330 | g/L | |
谷氨酸 | 0.588 | g/L | |
亚油酸 | 0.840 | ml/L | |
硫辛酸 | 2.100 | ml/L | |
酪氨酸二钠盐(Mw 225) | 1.790 | g/L | |
1000×微量元素B | 6.000 | ml/L | |
葡萄糖 | 100.000 | g/L | |
谷氨酰胺 | 14.600 | g/L | |
pH至7.0 | |||
记录摩尔渗透压浓度 | 1064.000 | mOsm | |
II | 半胱氨酸(400mM) | 加入108ml微量元素D、0.25g FeSO4·7H2O |
至280ml半胱氨酸贮存液 | |||
III | 叶酸 | 720ml 6mM叶酸 |
部分 | 成分 | 含量 | 单位 |
I | 培养基4A-1 | 24.896 | g/L |
NucellinTM | 32.000 | ml/L | |
H/P贮存液 | 16.000 | ml/L | |
亚硒酸盐贮存液 | 1.600 | ml/L | |
PVA | 2.400 | g/L | |
NaH2PO4·H2O | 2.088 | g/L | |
MgSO4·7H2O | 0.344 | g/L | |
天冬氨酸 | 1.064 | g/L |
谷氨酸 | 0.470 | g/L | |
亚油酸 | 0.672 | ml/L | |
硫辛酸 | 1.680 | ml/L | |
酪氨酸二钠盐(Mw 225) | 1.432 | g/L | |
1000×微量元素B | 9.000 | ml/L | |
谷氨酰胺 | 6.280 | g/L | |
pH至7.0 | |||
记录摩尔渗透压浓度 | 295.000 | mOsm | |
II | 半胱氨酸(400mM) | 加入108ml微量元素D、0.25g FeSO4·7H2O至280ml半胱氨酸贮存液 | |
III | 叶酸 | 720ml 6mM叶酸 |
部分 | 成分 | 含量 | 单位 |
I | 培养基4A-1 | 24.896 | g/L |
NucellinTM | 32.000 | ml/L |
H/P贮存液 | 16.000 | ml/L | |
亚硒酸盐贮存液 | 1.600 | ml/L | |
PVA | 2.400 | g/L | |
NaH2PO4·H2O | 2.088 | g/L | |
MgSO4·7H2O | 0.344 | g/L | |
天冬氨酸 | 1.064 | g/L | |
谷氨酸 | 0.470 | g/L | |
亚油酸 | 0.672 | ml/L | |
硫辛酸 | 1.680 | ml/L | |
酪氨酸二钠盐(Mw 225) | 1.432 | g/L | |
1000×微量元素B | 9.000 | ml/L | |
葡萄糖 | 50.000 | g/L | |
谷氨酰胺 | 7.300 | g/L | |
pH至7.0 | |||
FeSO4·7H2O(1mM贮存液) | 15.000 | ml/L | |
记录摩尔渗透压浓度 | 607.000 | mOsm | |
II | 叶酸 | 720ml 6mM叶酸 | |
III | 半胱氨酸(400mM) | 加入108ml微量元素D、0.25g FeSO4·7H2O至280ml半胱氨酸贮存液 |
成分 | 含量 | 单位 |
培养基4A-1 | 24.896 | g/L |
NucellinTM | 32.000 | ml/L |
H/P贮存液 | 16.000 | ml/L |
亚硒酸盐贮存液 | 1.600 | ml/L |
PVA | 2.400 | g/L |
NaH2PO4·H2O | 2.088 | g/L |
MgSO4·7H2O | 0.344 | g/L |
天冬氨酸 | 1.064 | g/L |
谷氨酸 | 0.470 | g/L |
亚油酸 | 0.672 | ml/L |
硫辛酸 | 1.680 | ml/L |
酪氨酸二钠盐(Mw 225) | 1.432 | g/L |
葡萄糖 | 66.700 | g/L |
谷氨酰胺 | 7.300 | g/L |
叶酸 | 70.560 | mg/L |
酸性半胱氨酸(400mM) | 6.250 | ml/L |
FeSO4贮存液(1mM) | 23.000 | ml/L |
1000×微量元素B | 9.000 | ml/L |
1000×微量元素D | 3.300 | ml/L |
预期pH 6.11 | 调为7.0 | |
记录摩尔渗透压浓度 | 724.000 | mOsm |
对照方法 | 无谷氨酰胺补料方法 | |
起始培养基谷氨酰胺(mM) | 13mM | 13mM |
谷氨酰胺补料 | 第4天,5mM | 不加谷氨酰胺 |
补料培养基 | 培养基5(含37.5mM谷氨酰胺) | 不含谷氨酰胺的培养基5 |
补料方案 | 从第5天每天4% | 从第5天每天4% |
温度调为31℃ | 第4天 | 第5天 |
对照方法 | 低谷氨酰胺方法 | |
起始培养基谷氨酰胺(mM) | 13mM | 4mM |
谷氨酰胺补料 | 第4天,5mM | 不补加谷氨酰胺 |
补料培养基 | 培养基5(含37.5mM | 不含谷氨酰胺的培养基5 |
谷氨酰胺) | ||
补料方案 | 从第5天起每日4% | 从第5天起每日4% |
温度调为31℃ | 第4天 | 第5天 |
GluGln | 改良培养基6+43g/L葡萄糖+4.82g/L谷氨酰胺(对照) |
GluGlu | 改良培养基6+43g/L葡萄糖+4.82g/L谷氨酸 |
GluAsp | 改良培养基6+43g/L葡萄糖+4.36g/L天冬酰胺 |
GluGlyGln | 改良培养基6+43g/L葡萄糖+6.71g/L甘氨酰谷氨酰胺 |
GalGlu | 改良培养基6+43g/L半乳糖+4.82g/L谷氨酰胺 |
GalGln | 改良培养基6+43g/L半乳糖+4.82g/L谷氨酸 |
GalAsp | 改良培养基6+43g/L半乳糖+4.36g/L天冬酰胺 |
GalGlyGln | 改良培养基6+43g/L半乳糖+6.71g/L甘氨酰谷氨酰胺 |
Glu | 培养基6+43g/L葡萄糖 |
分子量 | 培养基7 | 培养基8 | 分批培养基 | |
氨基酸 | mM | mM | mM | |
L-丙氨酸 | 89.0 | 1.08 | 2.4 | 0.2 |
L-精氨酸 | 174.0 | 6.84 | 13.2 | 4 |
L-天冬酰胺一水合物 | 150.0 | 4.76 | 21.4 | 7.5 |
L-天冬氨酸 | 133.0 | 2.40 | 6 | 1.65 |
L-半胱氨酸盐酸盐一水合物 | 176.0 | 0.40 | 0 | 0.4 |
L-胱氨酸二盐酸盐 | 313 | 0.95 | 1.875 | 1 |
L-谷氨酸 | 147.0 | 1.08 | 2.4 | 1.08 |
L-谷氨酰胺 | 146.0 | 13.00 | 37.5 | 4 |
甘氨酸 | 75.0 | 1.28 | 2.4 | 1.54 |
L-组氨酸盐酸盐一水合物 | 210.0 | 1.76 | 4.2 | 1.76 |
L-异亮氨酸 | 131.0 | 4.76 | 10.8 | 2.83 |
L-亮氨酸 | 131.0 | 6.52 | 15.6 | 4.7 |
盐酸赖氨酸 | 182.0 | 5.20 | 12 | 5.2 |
L-甲硫氨酸 | 149.0 | 1.96 | 4.8 | 2.6 |
L-苯丙氨酸 | 165.0 | 2.60 | 6 | 2.2 |
L-脯氨酸 | 115.0 | 3.24 | 7.2 | 4.1 |
L-丝氨酸 | 105.0 | 8.60 | 18 | 8.6 |
L-苏氨酸 | 119.0 | 4.32 | 9.6 | 3.2 |
L-色氨酸 | 204.0 | 0.78 | 1.92 | 1.04 |
二水合L-酪氨酸二钠 | 261.0 | 2.16 | 4.8 | 1.75 |
L-缬氨酸 | 117.0 | 4.32 | 9.6 | 4 |
维生素 | uM | uM | uM | |
生物素 | 244.0 | 8.31 | 20.4 | 11 |
D-泛酸钙 | 476.0 | 46.06 | 112.8 | 46.06 |
氯化胆碱 | 139.0 | 632.2 | 1548 | 840 |
叶酸 | 441.0 | 58.8 | 144 | 58.8 |
I-肌醇 | 180.0 | 686 | 1680 | 911 |
烟酰胺 | 122.0 | 161.7 | 396 | 215 |
盐酸吡哆醇 | 206.0 | 88.15 | 240 | 88 |
盐酸吡哆醛 | 203.0 | 10 | 0 | 10 |
核黄素 | 376.0 | 5.37 | 13.2 | 1.1 |
盐酸硫胺素 | 337.0 | 63.7 | 274.7 | 117 |
维生素B12 | 1355.0 | 4.9 | 12 | 7.8 |
无机盐 | ||||
NaCl | 58.5 | 18.8mM | ||
KCl | 74.6 | 4.2mM | 4.19mM | |
CaCl2 | 111 | 1.05mM | 1.05mM | |
亚硒酸钠 | 173 | 27ug/L | 60ug/L | 60ug/L |
NaH2PO4·H2O | 142 | 4.68mM | 11mM | 4.68mM |
Na2HPO4 | 138 | 0.5mM | 0.3986mM | |
MgSO4 | 120 | 1.15mM | 1.05mM | 1.15mM |
MgCl2 | 95 | 0.3mM | 0.3mM | |
FeSO4·7H2O | 278 | 9uM | 24.675uM | 9uM |
Fe(NO3)3·9H2O | 404 | 0.125uM | 0.124um | |
ZnSO4·7H2O | 287 | 9.2uM | 17uM | 9.2um |
CuSO4 | 160 | 0.05uM | 0.074uM | 0.064um |
NaHCO3 | 84 | 23.8mM | 23.8mM | |
其它 | ||||
葡萄糖 | 180 | 16g/L | 38.3g/L | 15g/L |
聚乙烯醇 | 2.56g/L | 2.4g/L | 2.56g/L | |
氢化可的松 | 363 | 0.23mg/L | 0.43mg/L | 0.28mg/L |
二盐酸腐胺 | 161 | 6.4mg/L | 12mg/L | 7.7mg/L |
丙酮酸钠 | 110 | 500uM | 500uM | |
亚油酸 | 280 | 0.81uM | 1.8uM | 0.81uM |
硫辛酸 | 206 | 2.7uM | 6uM | 2.7uM |
NucellinTM | 54mg/L | 120mg/L | 50mg/L | |
1000×微量元素B | 1.5ml/L | 6.75ml/L | 1.5ml/L |
微量元素 | μg/L | nM |
(NH4)6Mo7O24·4H2O | 123.60 | 100.00 |
AlCl3·6H2O | 0.48 | 2.00 |
H3BO3 | 6.18 | 100.00 |
CrCl3 | 7.92 | 50.00 |
CuSO4·5H2O | 49.94 | 200.00 |
GeO2 | 0.21 | 2.00 |
KBr | 0.24 | 2.00 |
KI | 16.60 | 100.00 |
LiCl | 0.08 | 2.00 |
MnSO4·H2O | 16.90 | 100.00 |
Na2SiO3·9H2O | 142.03 | 500.00 |
NaF | 0.08 | 2.00 |
NH4VO3 | 1.17 | 10.00 |
NiSO4·6H2O | 2.63 | 10.00 |
RbCl | 0.24 | 2.00 |
SnCl2·2H2O | 0.45 | 2.00 |
亚硒酸钠 | 34.58 | 200.00 |
补料 | |||||||||
培养基 | Asn | Gln | 第3天 | 第4天 | 第5天 | 第6天 | 第7天 | 第10天 | 第11天 |
培养基3 | 14mM | 4mM | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 10%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln |
培养基3 | 14mM | 4mM | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln | 10%培养基5-Gln | 3.3%培养基5-Gln | 3.3%培养基5-Gln |
培养基1 | 14mM | 4mM | 8%培养基5-Gln | 12%培养基5-Gln | 8%培养基5-Gln | ||||
培养基9 | 20mM | 4mM | 5%培养基5-Gln |
培养基 | Asn | Gln | 补料 | 氨基酸(起始)/(总量) | 离子/总氨基酸 |
3培养基 | 14mM | 4mM | 34%培养基5-Gln | 34mM/64mM | 1.75 |
培养基9 | 20mM | 4mM | 5%培养基5-Gln | 91.4mM/94.3mM | .72 |
培养基1 | 14mM | 4mM | 31.6%培养基5-Gln | 78mM/96.4mM | .74 |
标准化滴度 | Gln>15,Gln<2 | 2<Gln<15 |
平均值 | 0.724649917 | 1.033147493 |
方差 | 0.013326655 | 0.036834109 |
观测数量 | 7 | 12 |
合并方差 | 0.028537361 | |
假设均值差异 | 0 | |
df | 17 | |
t统计量 | -3.839791986 | |
单尾P(T<=t) | 0.000656219 | |
单尾t临界 | 1.739606432 | |
双尾P(T<=t) | 0.001312438 | |
双尾t临界 | 2.109818524 |
标准化滴度 | Asn+Gln>36,Asn+Gln<16 | 16<Asn+Gln<36 |
平均值 | 0.735066584 | 1.027071104 |
方差 | 0.012061148 | 0.041504987 |
观测数量 | 7 | 12 |
合并方差 | 0.031113044 | |
假设均值差异 | 0 | |
df | 17 | |
t统计量 | -3.480816823 | |
单尾P(T<=t) | 0.001430281 | |
单尾t临界 | 1.739606432 |
双尾P(T<=t) | 0.002860561 | |
双尾t临界 | 2.109818524 |
批号 | 描述 | 起始培养基 | 补料量 | Gln补料? | 接种来源 | 接种密度(活细胞/ml) |
1 | 1期 | 培养基10 | 38%* | 是 | 摇摆袋 | 0.2x106 |
2 | 富集培养基,高Gln(1) | 培养基1 | 16% | 是 | 摇摆袋 | 0.2x106 |
3 | 富集培养基,高Gln(2) | 培养基1 | 16% | 是 | 摇摆袋 | 0.2x106 |
4 | 富集培养基,低Gln | 培养基1 | 15% | 否 | 摇摆袋 | 0.2x106 |
5 | 平衡培养基,低Gln(1) | 培养基12 | 10% | 否 | 摇摆袋 | 0.2x106 |
6 | 平衡培养基,低Gln(2) | 培养基12 | 9% | 否 | 摇摆袋 | 0.2x106 |
7 | 平衡培养基,低Gln,密集接种 | 培养基12 | 5% | 否 | 高密度生物反应器 | 2.0x106 |
Claims (50)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US60493604P | 2004-08-27 | 2004-08-27 | |
US60/604,936 | 2004-08-27 | ||
PCT/US2005/030364 WO2006026408A2 (en) | 2004-08-27 | 2005-08-26 | Production of anti-amyloid beta antibodies |
Publications (2)
Publication Number | Publication Date |
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CN101048512A CN101048512A (zh) | 2007-10-03 |
CN101048512B true CN101048512B (zh) | 2013-04-17 |
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Country Status (27)
Country | Link |
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US (1) | US7335491B2 (zh) |
EP (2) | EP1781803B1 (zh) |
JP (3) | JP2008511328A (zh) |
KR (1) | KR100998857B1 (zh) |
CN (1) | CN101048512B (zh) |
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