CN1281366A - 致淀粉样病的预防和治疗 - Google Patents
致淀粉样病的预防和治疗 Download PDFInfo
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- CN1281366A CN1281366A CN98811731A CN98811731A CN1281366A CN 1281366 A CN1281366 A CN 1281366A CN 98811731 A CN98811731 A CN 98811731A CN 98811731 A CN98811731 A CN 98811731A CN 1281366 A CN1281366 A CN 1281366A
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Abstract
Description
未处理 | PBS | AN1792 | |
月龄 | 总Aβ Aβ42 (n) | 总Aβ Aβ42 (n) | 总Aβ Aβ42 (n) |
121518 | 1,600 1,300 (10)8,700 8,300 (10)22,200 18,500(10) | 8,600 7,200(9)19,000 15,900(12) | 1,600 1,300*(10)5,200** 4,000**(9) |
未治疗 | PBS | AN1792 | |
月龄 | 总Aβ Aβ42 (n) | 总Aβ Aβ42 (n) | 总Aβ Aβ42 (n) |
121518 | 15,500 11,100(10)51,500 44,400(10)80,800 64,200(10) | 40,100 35,700(9)65,400 57,100(12) | 24,500 22,100(10)50,900* 38,900**(9) |
未治疗 | PBS | AN1792 | |
月龄 | 总Aβ (n) | 总Aβ (n) | 总Aβ (n) |
121518 | 15.6 (10)27.7 (10)35.0 (10) | 20.8 (9)43.1 (12) | 21.7 (10)24.8* (9) |
表5 | |||
免疫原 | 共轭物 | Aβ氨基酸 | 应答数 |
Aβ1-5 | 是 | 5-聚体 | 0/7 |
Aβ1-12 | 是 | 12-聚体 | 1/8 |
Aβ13-28 | 是 | 16-聚体 | 1/9 |
Aβ25-35 | 11-聚体 | 1/9 | |
Aβ33-42 | 是 | 10-聚体 | 0/10 |
Aβ1-40 | 40-聚体 | 5/8 | |
Aβ1-42 | 42-聚体 | 9/9 | |
r Aβ1-42 | 42-聚体 | 8/8 | |
pBx6 | 0/8 | ||
PBS | 0-聚体 | 0/8 |
抗体 | 表位 |
2H3 | Aβ1-12 |
10D5 | Aβ1-12 |
266 | Aβ13-28 |
21F12 | Aβ33-42 |
小鼠多克隆抗人Aβ42 | 抗聚集态Aβ42 |
丁氢萘心定研究010的实验设计 | |||||
组 | Na | 佐剂b | 剂量 | 抗原 | 剂量(μg) |
1 | 10 | MPL | 12.5μg | AN1792 | 33 |
2 | 10 | MPL | 25μg | AN1792 | 33 |
3 | 10 | MPL | 50μg | AN1792 | 33 |
4 | 13 | MPL | 125μg | AN1792 | 33 |
5 | 13 | MPL | 50μg | AN1792 | 150 |
6 | 13 | MPL | 50μg | AN1528 | 33 |
7 | 10 | PBS | AN1792 | 33 | |
8 | 10 | PBS | 无 | ||
9 | 10 | 角鲨烯乳化 | 5% | AN1792 | 33 |
10 | 10 | 角鲨烯混合 | 5% | AN1792 | 33 |
11 | 10 | 明矾 | 2 mg | AN1792 | 33 |
12 | 13 | MPL+明矾 | 50μg/2 mg | AN1792 | 33 |
13 | 10 | QS21 | 5μg | AN1792 | 33 |
14 | 10 | QS21 | 10μg | AN1792 | 33 |
15 | 10 | QS21 | 25μg | AN1792 | 33 |
16 | 13 | QS21 | 25μg | AN1792 | 150 |
17 | 13 | QS21 | 25μg | AN1528 | 33 |
18 | 13 | QS21+MPL | 25μg/50μg | AN1792 | 33 |
19 | 13 | QS2H明矾 | 25μg/2 mg | AN1792 | 33 |
抗体的几何平均效价 | |||||
取血周数 | |||||
治疗组 | 2.9 | 5.0 | 8.7 | 12.9 | 16.7 |
1 | 248 | 1797 | 2577 | 6180 | 4177 |
2 | 598 | 3114 | 3984 | 5287 | 6878 |
3 | 1372 | 5000 | 7159 | 12333 | 12781 |
4 | 1278 | 20791 | 14368 | 20097 | 25631 |
5 | 3288 | 26242 | 13229 | 9315 | 23742 |
6 | 61 | 2536 | 2301 | 1442 | 4504 |
7 | 37 | 395 | 484 | 972 | 2149 |
8 | 25 | 25 | 25 | 25 | 25 |
9 | 25 | 183 | 744 | 952 | 1823 |
10 | 25 | 89 | 311 | 513 | 817 |
11 | 29 | 708 | 2618 | 2165 | 3666 |
12 | 198 | 1458 | 1079 | 612 | 797 |
13 | 38 | 433 | 566 | 1080 | 626 |
14 | 104 | 541 | 3247 | 1609 | 838 |
15 | 212 | 2630 | 2472 | 1224 | 1496 |
16 | 183 | 2616 | 6680 | 2085 | 1631 |
17 | 28 | 201 | 375 | 222 | 1540 |
18 | 31699 | 15544 | 23095 | 6412 | 9059 |
19 | 63 | 243 | 554 | 299 | 441 |
抗体的几何平均效价a | |||||
取血周数 | |||||
治疗 | 3.3 | 5.0 | 9.0 | 13.0 | 17.0 |
明矾/AN1792 | 102(12/21)b | 1,081(17/20) | 2,366(21/21) | 1,083(19/21) | 572(18/21) |
MPL/AN1792 | 6241(21/21) | 28,867(21/21) | 1,1242(21/21) | 5,665(20/20) | 8,204(20/20) |
QS21/AN1792 | 30(1/20) | 227(10/19) | 327(10/19) | 1,511(17/18) | 1,188(14/18) |
CFA/AN1792 | 10,076(15/15) | 61,279(15/15) | 75,386(15/15) | 41,628(15/15) | 30,574(15/15) |
明矾/AN1528 | 25(0/21) | 33(1/21) | 39(3/20) | 37(1/21) | 31(2/20) |
MPL/AN1528 | 184(15/21) | 2,591(20/21) | 1,653(21/21 ) | 1,156(20/20) | 3,099(20/20) |
QS21/AN1528 | 29(1/22) | 221(13/22) | 51(4/22) | 820(20/22) | 2,994(21/22) |
PBS+硫柳汞 | 25(0/16) | 33(2/16) | 39(4/16) | 37(3/16) | 47(4/16) |
PBS | 25(0/16) | 25(0/16) | 25(0/15) | 25(0/12) | 25(0/16) |
表1 | |||||||||
50%最大光密度时的效价 | |||||||||
聚集态Aβ注射的小鼠 | |||||||||
PDAPP的月龄 | 小鼠100 | 小鼠101 | 小鼠102 | 小鼠103 | 小鼠104 | 小鼠105 | 小鼠106 | 小鼠107 | 小鼠108 |
4 | 70000 | 150000 | 15000 | 120000 | 1000 | 15000 | 50000 | 80000 | 100000 |
6 | 15000 | 65000 | 30000 | 55000 | 300 | 15000 | 15000 | 50000 | 60000 |
8 | 20000 | 55000 | 50000 | 50000 | 400 | 15000 | 18000 | 50000 | 60000 |
10 | 40000 | 20000 | 60000 | 50000 | 900 | 15000 | 50000 | 20000 | 40000 |
12 | 25000 | 30000 | 60000 | 40000 | 2700 | 20000 | 70000 | 25000 | 20000 |
两种免疫原的PBS注射小鼠 | |||||||||
效价为1/100 | |||||||||
PDAPP的月龄 | 小鼠113 | 小鼠114 | 小鼠115 | 小鼠116 | 小鼠117 | ||||
6 | <4x bkg | <4x bkg | <4x bkg | <4x bkg | <4x bkg | ||||
10 | 5x bkg | <4x bkg | <4x bkg | <4x bkg | <4x bkg | ||||
12 | <4x bkg | <4x bkg | <4x bkg | <4x bkg | <4x bkg |
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- 2004-08-20 US US10/923,471 patent/US8535673B2/en not_active Expired - Fee Related
- 2004-08-20 US US10/923,474 patent/US20050048049A1/en not_active Abandoned
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- 2004-08-20 US US10/923,605 patent/US20050249727A1/en not_active Abandoned
- 2004-08-20 US US10/923,267 patent/US20050191292A1/en not_active Abandoned
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- 2004-09-02 US US10/933,559 patent/US6972127B2/en not_active Expired - Lifetime
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2005
- 2005-02-14 US US11/058,757 patent/US20050142132A1/en not_active Abandoned
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- 2005-10-07 US US11/245,524 patent/US20060034858A1/en not_active Abandoned
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- 2005-11-30 JP JP2005346462A patent/JP4677333B2/ja not_active Expired - Lifetime
- 2005-11-30 JP JP2005346511A patent/JP4677334B2/ja not_active Expired - Lifetime
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2007
- 2007-01-12 HK HK07100441.8A patent/HK1095265A1/xx not_active IP Right Cessation
- 2007-02-13 HK HK07101687.9A patent/HK1094535A1/xx not_active IP Right Cessation
- 2007-08-20 US US11/842,113 patent/US8034348B2/en not_active Expired - Fee Related
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2008
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2009
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2010
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2011
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- 2011-10-11 US US13/271,081 patent/US20120276116A1/en not_active Abandoned
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2013
- 2013-09-03 US US14/017,177 patent/US20140227274A1/en not_active Abandoned
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WO2004050876A1 (fr) * | 2002-11-29 | 2004-06-17 | Agtc Gene Technology Company Ltd. | Vaccin genique concernant un adenovirus recombinant convenant a la therapie et la prophylaxie de la maladie d'alzheimer, et utilisation correspondante |
CN100450551C (zh) * | 2002-11-29 | 2009-01-14 | 中国医学科学院基础医学研究所 | 用于治疗和预防阿尔茨海默病的重组腺相关病毒基因疫苗及其用途 |
CN104098695A (zh) * | 2007-10-29 | 2014-10-15 | 道健康生活医药株式会社 | 抗体及其应用 |
CN104098695B (zh) * | 2007-10-29 | 2018-09-07 | 道健康生活医药株式会社 | 抗体及其应用 |
CN102895659A (zh) * | 2011-07-29 | 2013-01-30 | 复旦大学 | 一种防治老年痴呆症复合疫苗及其制备方法 |
WO2013017053A1 (zh) * | 2011-07-29 | 2013-02-07 | 复旦大学 | 一种防治老年痴呆症复合疫苗及其制备方法 |
CN102895659B (zh) * | 2011-07-29 | 2014-10-29 | 复旦大学 | 一种防治老年痴呆症复合疫苗及其制备方法 |
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