CN1359301A - 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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- CN1359301A CN1359301A CN00808117A CN00808117A CN1359301A CN 1359301 A CN1359301 A CN 1359301A CN 00808117 A CN00808117 A CN 00808117A CN 00808117 A CN00808117 A CN 00808117A CN 1359301 A CN1359301 A CN 1359301A
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Abstract
Description
未处理 | PBS | AN1792 | |
月龄 | Aβ Aβ42 (n) | 总Aβ Aβ42 (n) | Aβ Aβ42 (n) |
121518 | 1,600 1300 (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) | Aβ Aβ42 (n) |
121518 | 15,500 11,100 (10)51,500 44,400 (10)80,800 64,200 (10) | 40,100 35,70 (9)65,400 57,10 (12) | 24,50 22,100 (10)50,90* 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 | |
rAβ1-42 | 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 |
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 | 2mg | AN1792 | 33 |
12 | 13 | MPL+明矾 | 50μg/2mg | AN1792 | 33 |
13 | 10 | QS-21 | 5μg | AN1792 | 33 |
14 | 10 | QS-21 | 10μg | AN1792 | 33 |
15 | 10 | QS-21 | 25AN1792 | AN1792 | 33 |
16 | 13 | QS-21 | 25AN1792 | AN1792 | 150 |
17 | 13 | QS-21 | 25AN1792 | AN1528 | 33 |
18 | 13 | QS-21+MPL | 25μg/50μg | AN1792 | 33 |
19 | 13 | QS-21+明矾 | 25μg/2mg | 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) |
QS-21/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(1/20) | 31(2/20) |
MPL/AN1528 | 184(15/21) | 2,591(20/21) | 1,653(21/21) | 1,156(20/20) | 3,099(20/20) |
QS-21/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) |
佐剂 | 免疫原 | 稀释缓冲液 | 给药方式 | |
组1 | MPL-SE | AN1792-GCS(75μg) | PBS | SC(250μl) |
组2 | ISA51 | AN1792-GCS(75μg) | PBS | IP(400μl) |
组3 | QS21 | AN1792-GCS(75μg) | PBS | SC(250μl) |
组4 | QS21(简) | AN1792-GCS(75μg) | PBS | SC(250μl) |
组5 | PBS | ------- | ------- | SC(250μl) |
PBS | MPL-SE | ISA | QS-21 | QS-21(4) | |
平均值(纳克/克组织) | 7,335 | 1,236 | 3,026 | 2,389 | 2,996 |
范围(纳克/克组织) | 550-18,358 | 70-3,977 | 23-9,777 | 210-11,167 | 24-16,834 |
P值 | --- | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
N | 38 | 29 | 36 | 34 | 40 |
实验设计 | ||||
处理组 | Na | 处理抗体 | 抗体特异性 | 抗体同种型 |
1 | 9 | 无,仅PBS | NAb | NA |
2 | 10 | 多克隆 | Aβ1-42 | 混合的 |
3 | 0 | mAbc2H3 | Aβ1-12 | IgG1 |
4 | 8 | MAb 10D5 | Aβ1-16 | IgG1 |
5 | 6 | MAb 266 | Aβ13-28 | IgG1 |
6 | 8 | MAb 21F12 | Aβ33-42 | IgG2a |
皮层 | |||||||||
处理组 | Na | 中值 | 平均数 | ||||||
总Aβ | Aβ42 | 总Aβ | Aβ42 | ||||||
ELISA值b | P值c | %变化 | ELISA值 | P值 | %变化 | ELISA值 | ELISA值 | ||
PBS | 9 | 17818 | NAd | NA | 13802 | NA | NA | 16150+/-7456e | 12621+/-5738 |
多克隆抗Aβ42抗体 | 10 | 6160 | 0.0055 | -65 | 4892 | 0.0071 | -65 | 5912+/-4492 | 4454+/-3347 |
mAb 10D5 | 8 | 7915 | 0.1019 | -56 | 6214 | 0.0433 | -55 | 9695+/-6929 | 6943+/-3351 |
mAb 266 | 6 | 9144 | 0.1255 | -49 | 8481 | 0.1255 | -39 | 9204+/-9293 | 7489+/-6921 |
mAb 21F12 | 8 | 15158 | 0.2898 | -15 | 13578 | 0.7003 | -2 | 12481+/-7082 | 11005+/-6324 |
海马 | |||||||||
处理组 | Na | 中值 | 平均数 | ||||||
总Aβ | Aβ42 | 总Aβ | Aβ42 | ||||||
ELISA值b | P值c | %变化 | ELISA值 | P值 | %变化 | ELISA值 | ELISA值 | ||
PBS | 9 | 63389 | NAd | NA | 54429 | NA | NA | 58351+/-13308e | 52801+/-14701 |
多克隆抗Aβ42抗体 | 10 | 31706 | 0.0055 | -50 | 27127 | 0.0025 | -50 | 30058+/-22454 | 24853+/-18262 |
MAb 10D5 | 8 | 46779 | 0.0675 | -26 | 36290 | 0.0543 | -33 | 44581+/-18632 | 36465+/-17146 |
MAb 266 | 6 | 48689 | 0.0990 | -23 | 43034 | 0.0990 | -21 | 36419+/-27304 | 32919+/-25372 |
MAb 21F12 | 8 | 51563 | 0.7728 | -19 | 47961 | 0.8099 | -12 | 57327+/-28927 | 50305+/-23927 |
小脑 | |||||
处理组 | Na | 中值 | 平均数 | ||
总Aβ | 总Aβ | ||||
ELISA值 | P值 | %变化 | ELISA值 | ||
PBS | 9 | 30.64 | NAd | NA | 40.00+/-31.89e |
多克隆抗Aβ42抗体 | 10 | 17.61 | 0.0033 | -43 | 18.15+/-4.36 |
mAb 10D5 | 8 | 21.68 | 0.0675 | -29 | 27.29+/-19.43 |
mAb 266 | 6 | 16.59 | 0.0184 | -46 | 19.59+/-6.59 |
mAb21F12 | 8 | 29.80 | >0.9999 | -3 | 32.88+/-9.90 |
N-末端单克隆抗体3D610D522C86E1014A813-2818G1126622D12C-末端2G316C1121F12免疫血清兔(CFA)鼠(CFA)鼠(QS-21)猴(QS-21)鼠(MAP1-7) | 抗体 | 染色+++++------+++++ | 吞噬++++-------+++++ | |
表位1-53-63-75-104-1010-1816-2418-21-40-40/-42-421-63-73-71-5 | 同种型IgG2bIgG1IgG2aIgG1大鼠IgG1大鼠IgG1IgG1IgG2bIgG1IgG1IgG2a |
抗体 | 同种型 | 对聚集态Aβ的亲和力(pM) | 对β淀粉样斑的结合 | 离体的效率 | 体内效率 | |
单克隆 | 3D6 | IgG2b | 470 | + | + | + |
10D5 | IgG1 | 43 | + | + | + | |
16C11 | IgG1 | 90 | - | - | - | |
21F12 | IgG2a | 500 | - | - | - | |
TM2a | IgG1 | - | - | - | - | |
多克隆 | 1-42 | 混合 | 600 | + | + | + |
佐剂 | 免疫原 | 稀释缓冲液 | 给药方式 | |
组1 | CFA/IFA | MAP(Aβ1-7:TT)(100μg) | PBS | IP(400μl) |
组2 | QS21 | AN1792-GCS(75μg) | PBS | SC(250μl) |
组3 | PBS | ------ | --- | SC(250μl) |
PBS | MAP | QS-21 | |
平均值(纳克/克组织) | 7,335 | 3,692 | 2,389 |
范围(纳克/克组织) | 550-18,358 | 240-10,782 | 210-11,167 |
P值 | --- | 0.0003 | <0.0001 |
N | 38 | 30 | 34 |
组 | 实验设计a | 猴(M/F) | AN1792剂量(μg/剂) | QS21剂量(μg/剂) | 途径 |
1b | 1 | 4/4 | 0 | 0 | IM |
2 | 1 | 4/4 | 载体c | 50 | IM |
3 | 1 | 4/4 | 载体 | 100 | IM |
4 | 1 | 4/4 | 75 | 50 | IM |
5 | 1 | 4/4 | 300 | 50 | IM |
6 | 1 | 4/4 | 75 | 100 | IM |
7 | 1 | 4/4 | 300 | 100 | IM |
8 | 2 | 4/4 | 75 | 100 | IM |
9 | 2 | 4/4 | 300 | 100 | IM |
10 | 3 | 4/4 | 75 | 100 | IM |
11 | 3 | 4/4 | 300 | 100 | IM |
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 |
Claims (109)
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US09/322,289 US7964192B1 (en) | 1997-12-02 | 1999-05-28 | Prevention and treatment of amyloidgenic disease |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Families Citing this family (166)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1072897A (en) | 1995-12-12 | 1997-07-03 | Karolinska Innovations Ab | Peptide binding the klvff-sequence of amyloid beta |
AU743827B2 (en) * | 1997-04-09 | 2002-02-07 | Intellect Neurosciences, Inc. | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US6743427B1 (en) | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
JP2003509020A (ja) * | 1999-09-03 | 2003-03-11 | ラモット・ユニバーシティ・オーソリティ・フォー・アプライド・リサーチ・アンド・インダストリアル・ディベロップメント・リミテッド | プラーク形成疾患の診断、治療、予防に有用な薬剤、組成物、その使用法 |
US20020094335A1 (en) * | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
DK1237930T3 (da) | 1999-12-08 | 2007-03-19 | Intellect Neurosciences Inc | Kimære amyloid-beta-peptider |
EP1752472A3 (en) * | 1999-12-08 | 2007-04-25 | Intellect Neurosciences, Inc. | Chimeric amyloid beta peptides |
DE60114157T2 (de) * | 2000-02-21 | 2006-06-29 | Pharmexa A/S | Verfahren zur herabregulierung von amyloid |
CA2400838C (en) | 2000-02-21 | 2013-04-23 | Pharmexa A/S | Novel method for down-regulation of amyloid |
SI1481992T1 (sl) | 2000-02-24 | 2017-01-31 | Washington University St. Louis | Humanizirana protitelesa, ki vežejo amiloidni peptid beta |
PT1284998E (pt) | 2000-05-22 | 2005-06-30 | Univ New York | Eptideos imunogenicos sinteticos mas nao-amiloidogenicos homologos a beta-amiloides, destinados a induzir uma reaccao imunitaria contra os beta-amiloides e os depositos amiloides |
WO2002003911A2 (en) | 2000-07-07 | 2002-01-17 | Lars Lannfelt | Prevention and treatment of alzheimer's disease |
US20040038302A1 (en) * | 2000-09-19 | 2004-02-26 | Roger Nitsch | Methods and compounds for treating brain amyloidosis |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
TWI255272B (en) * | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
WO2002068955A1 (en) | 2001-02-23 | 2002-09-06 | Elan Pharmaceuticals, Inc. | Transgenic knockouts of bace-1 |
WO2002088307A2 (en) | 2001-04-30 | 2002-11-07 | Eli Lilly And Company | Humanized antibodies |
US7318923B2 (en) | 2001-04-30 | 2008-01-15 | Eli Lilly And Company | Humanized anti-βantibodies |
US6906169B2 (en) | 2001-05-25 | 2005-06-14 | United Biomedical, Inc. | Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide |
CA2451998A1 (en) * | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Anti-a.beta. antibodies |
DE60224200T2 (de) * | 2001-08-17 | 2008-07-10 | Eli Lilly And Co., Indianapolis | Assayverfahren für alzheimer-krankheit |
EP1519740A4 (en) * | 2001-08-17 | 2005-11-09 | Lilly Co Eli | FASTER IMPROVEMENT OF COGNITION IN DISEASES ASSOCIATED WITH A-BETA |
JP2005500389A (ja) * | 2001-08-17 | 2005-01-06 | イーライ・リリー・アンド・カンパニー | Aβに関連する病態および疾患を治療するための、可溶性Aβに高い親和性を有する抗体の使用 |
EP1944040B1 (en) * | 2001-08-17 | 2012-08-01 | Washington University | Assay method for Alzheimer's disease |
MY144532A (en) * | 2001-08-20 | 2011-09-30 | Lundbeck & Co As H | Novel method for down-regulation of amyloid |
EP1572894B1 (en) | 2001-11-21 | 2016-04-13 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto |
EP1975179A1 (en) * | 2001-12-26 | 2008-10-01 | Araclon Biotech, S.L. | Polyclonal antibodies, preparation method thereof and use of same |
AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
CA2477675C (en) * | 2002-03-05 | 2013-05-21 | Ramot At Tel-Aviv University Ltd. | Immunizing composition and method for inducing an immune response against the .beta.-secretase cleavage site of amyloid precursor protein |
MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
US20070134247A9 (en) * | 2002-04-12 | 2007-06-14 | Ramot At Tel Aviv University Ltd. | Prevention of brain inflammation as a result of induced autoimmune response |
PL209696B1 (pl) * | 2002-04-19 | 2011-10-31 | Univ Toronto | Peptyd, kompozycja peptydowa, kompozycja immunogenna, zastosowania kompozycji immunogennej oraz sposób określania czy związek stanowi inhbitor odkładania się i tworzenia włókienek amyloidu |
EP1501531B1 (en) * | 2002-04-25 | 2009-01-07 | Eli Lilly And Company | Method for treating anxiety in older subjects |
EP1911765A3 (en) * | 2002-07-24 | 2008-04-23 | Innogenetics N.V. | Prevention, treatment and diagnosis of diseases associated with Beta-Amyloid formation and/or aggregation |
WO2010011999A2 (en) * | 2008-07-25 | 2010-01-28 | The Regents Of The University Of California | Methods and compositions for eliciting an amyloid-selective immune response |
AU2003279216A1 (en) * | 2002-10-09 | 2004-05-04 | Rinat Neuroscience Corp. | Methods of treating alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof |
US8697082B2 (en) | 2002-11-01 | 2014-04-15 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
US9034337B2 (en) * | 2003-10-31 | 2015-05-19 | Prothena Biosciences Limited | Treatment and delay of outset of synucleinopathic and amyloidogenic disease |
US20080014194A1 (en) | 2003-10-31 | 2008-01-17 | Elan Pharmaceuticals, Inc. | Prevention and Treatment of Synucleinopathic and Amyloidogenic Disease |
TW200509968A (en) | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
US8506959B2 (en) | 2002-11-01 | 2013-08-13 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
FR2846667B1 (fr) * | 2002-11-06 | 2004-12-31 | Pasteur Institut | Fragments variables d'anticorps de camelides a chaine unique diriges contre le peptide beta-amyloide 1-42 et leurs applications pour le diagnostic et le traitement des maladies neuroagregatives |
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
US20060188512A1 (en) * | 2003-02-01 | 2006-08-24 | Ted Yednock | Active immunization to generate antibodies to solble a-beta |
ES2344645T3 (es) | 2003-02-10 | 2010-09-02 | Applied Molecular Evolution, Inc. | Moleculas de union al abeta. |
US8663650B2 (en) | 2003-02-21 | 2014-03-04 | Ac Immune Sa | Methods and compositions comprising supramolecular constructs |
CA2519511A1 (en) * | 2003-03-17 | 2004-09-30 | Wyeth Holdings Corporation | Mutant cholera holotoxin as an adjuvant and an antigen carrier protein |
US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
ES2246105B1 (es) * | 2003-05-08 | 2007-03-01 | Araclon Biotech, S.L. | Uso de anticuerpos para el tratamiento de enfermedades amiloideas. |
US7358331B2 (en) | 2003-05-19 | 2008-04-15 | Elan Pharmaceuticals, Inc. | Truncated fragments of alpha-synuclein in Lewy body disease |
EP1480041A1 (en) * | 2003-05-22 | 2004-11-24 | Innogenetics N.V. | Method for the prediction, diagnosis and differential diagnosis of Alzheimer's disease |
TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
JP4888876B2 (ja) | 2003-06-13 | 2012-02-29 | 田平 武 | アルツハイマー病の治療のための組換えアデノ随伴ウィルスベクター |
US7807171B2 (en) | 2003-07-25 | 2010-10-05 | Ac Immune Sa | Therapeutic vaccine targeted against P-glycoprotein 170 for inhibiting multidrug resistance in the treatment of cancers |
WO2005047860A2 (en) | 2003-11-08 | 2005-05-26 | Elan Pharmaceuticals, Inc. | Antibodies to alpha-synuclein |
AU2004299501B2 (en) | 2003-12-17 | 2010-12-23 | Wyeth Llc | Immunogenic peptide carrier conjugates and methods of producing same |
PL2336147T3 (pl) | 2003-12-17 | 2015-01-30 | Janssen Alzheimer Immunotherap | Immunogenne koniugaty A beta z nośnikiem peptydowym i sposoby ich otrzymywania |
GB0410220D0 (en) | 2004-05-07 | 2004-06-09 | Kirkham Lea Ann | Mutant pneumolysin proteins |
SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
AT500483B1 (de) * | 2004-07-13 | 2006-01-15 | Mattner Frank Dr | Set zur vorbeugung oder behandlung der alzheimer'schen erkrankung |
US20060024667A1 (en) * | 2004-07-29 | 2006-02-02 | Karen Manucharyan | Compositions and methods for Alzheimer's disease |
TWI355389B (en) | 2004-07-30 | 2012-01-01 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide a |
MX2007001679A (es) | 2004-08-09 | 2007-05-23 | Elan Pharm Inc | Prevencion y tratamiento de la enfermedad sinucleinopatica y amiloidogenica. |
JP2008509915A (ja) * | 2004-08-11 | 2008-04-03 | ウイスコンシン アラムナイ リサーチ フオンデーシヨン | Aβの効果を低減する方法およびそのための組成物 |
EP1787998A4 (en) * | 2004-08-11 | 2008-08-27 | Mitsubishi Chem Corp | ANTIBODIES AND USE RELATING THERETO |
TWI374935B (en) | 2004-08-27 | 2012-10-21 | Pfizer Ireland Pharmaceuticals | Production of α-abeta |
TWI384069B (zh) | 2004-08-27 | 2013-02-01 | Pfizer Ireland Pharmaceuticals | 多胜肽之製法 |
TWI364458B (en) | 2004-08-27 | 2012-05-21 | Wyeth Res Ireland Ltd | Production of tnfr-lg |
EP1797182A2 (en) * | 2004-10-05 | 2007-06-20 | Wyeth a Corporation of the State of Delaware | Methods and compositions for improving recombinant protein production |
PE20061329A1 (es) | 2004-12-15 | 2006-12-08 | Neuralab Ltd | Anticuerpos ab humanizados para mejorar la cognicion |
WO2006066171A1 (en) * | 2004-12-15 | 2006-06-22 | Neuralab Limited | Amyloid βετα antibodies for use in improving cognition |
GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
WO2006113347A2 (en) * | 2005-04-13 | 2006-10-26 | The University Of Tennessee Research Foundation | Diagnostic and therapeutic potential of immune globulin intravenous (igiv) products |
UY29504A1 (es) | 2005-04-29 | 2006-10-31 | Rinat Neuroscience Corp | Anticuerpos dirigidos contra el péptido amiloide beta y métodos que utilizan los mismos. |
BRPI0610093A2 (pt) * | 2005-05-05 | 2008-12-09 | Merck & Co Inc | composiÇço farmacÊutica, e, mÉtodo para prevenir ou tratar uma doenÇa associada com os depàsitos de amilàides de alfa-beta no cÉrebro de um paciente |
EA201100177A1 (ru) * | 2005-06-17 | 2011-06-30 | Элан Фарма Интернэшнл Лимитед | СПОСОБЫ ОЧИСТКИ АНТИТЕЛ К β-АМИЛОИДУ |
RS53270B2 (sr) | 2005-11-30 | 2018-05-31 | Abbvie Deutschland | Monoklonalna antitela protiv amiloidnog beta proteina i njihova upotreba |
AU2006319358B2 (en) | 2005-11-30 | 2012-01-19 | AbbVie Deutschland GmbH & Co. KG | Anti-Abeta globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
NO345996B1 (no) | 2005-12-12 | 2021-12-13 | Ac Immune Sa | A beta 1-42-spesifikke monoklonale antistoffer med terapeutiske egenskaper. |
CN102659943B (zh) | 2005-12-12 | 2015-07-01 | 豪夫迈·罗氏有限公司 | 抗体可变区的糖基化 |
WO2007090126A2 (en) * | 2006-01-30 | 2007-08-09 | Invitrogen Corporation | Compositions and methods for detecting and quantifying toxic substances in disease states |
EP1996227A2 (en) * | 2006-02-24 | 2008-12-03 | CHIESI FARMACEUTICI S.p.A. | Anti-amyloid immunogenic compositions, methods and uses |
WO2007108756A1 (en) | 2006-03-23 | 2007-09-27 | Bioarctic Neuroscience Ab | Improved protofibril selective antibodies and the use thereof |
US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
US8357781B2 (en) * | 2006-06-01 | 2013-01-22 | Janssen Alzheimer Immunotherapy | Neuroactive fragments of APP |
EP3988566A1 (en) * | 2006-07-14 | 2022-04-27 | AC Immune SA | Humanized antibody against amyloid beta |
RS53160B (en) * | 2006-07-14 | 2014-06-30 | Ac Immune S.A. | HUMANIZED BETA AMILOID ANTIBODY |
PL2468770T3 (pl) * | 2006-07-14 | 2018-07-31 | Ac Immune S.A. | Humanizowane przeciwciało przeciw amyloidowi beta |
PL2074145T3 (pl) * | 2006-10-02 | 2017-11-30 | Ac Immune S.A. | Humanizowane przeciwciało przeciw amyloidowi beta |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
EP2426143B1 (en) * | 2007-01-05 | 2017-06-28 | University of Zurich | Method of providing disease-specific binding molecules and targets |
IL199534A (en) | 2007-01-05 | 2013-01-31 | Univ Zuerich | An isolated human antibody capable of detecting a neoepitope in a disease-related protein, a polynucleotide encoding an antibody, a vector containing the polynucleotide, a host cell containing the polynucleotide or vector, a preparation containing the antibody and related methods and uses. |
EP2121754B1 (en) | 2007-01-18 | 2015-02-11 | Eli Lilly and Company | Pegylated amyloid beta fab |
PL2583978T3 (pl) | 2007-02-23 | 2016-07-29 | Prothena Biosciences Ltd Co | Profilaktyka i leczenie chorób synukleinopatycznych i amyloidogennych |
US8147833B2 (en) * | 2007-02-23 | 2012-04-03 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
PT2118300E (pt) | 2007-02-23 | 2015-09-22 | Univ California | Prevenção e tratamento da doença sinucleinopática e amiloidogénica |
EP2486928A1 (en) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
AU2008220785B2 (en) | 2007-03-01 | 2013-02-21 | Vivoryon Therapeutics N.V. | New use of glutaminyl cyclase inhibitors |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
AU2008248780B2 (en) | 2007-05-02 | 2013-01-31 | F. Hoffmann-La Roche Ag | Method for stabilizing a protein |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
ES2498040T3 (es) * | 2007-07-27 | 2014-09-24 | Janssen Alzheimer Immunotherapy | Tratamiento de enfermedades amiloidogénicas con anticuerpos anti-beta humanizados |
ES2445590T3 (es) | 2007-10-05 | 2014-03-04 | Genentech, Inc. | Uso de anticuerpo anti-amiloide beta en enfermedades oculares |
JO3076B1 (ar) * | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
CN102016059B (zh) | 2007-12-28 | 2014-10-22 | 依兰制药公司 | 淀粉样变性的治疗和预防 |
EP2106802A1 (en) * | 2008-04-02 | 2009-10-07 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Modified peptides as synthetic vaccines in amyloid-associated disease |
AT509611B1 (de) * | 2008-06-12 | 2012-04-15 | Affiris Forschungs-Und Entwicklungs Gmbh | Vakzin |
AT506819B1 (de) * | 2008-06-12 | 2011-06-15 | Affiris Forschungs Und Entwicklungs Gmbh | Vakzin zur behandlung von alzheimer-krankheit |
EP2145898A1 (en) * | 2008-07-15 | 2010-01-20 | CHIESI FARMACEUTICI S.p.A. | Anti-amyloid immunogenic compositions, methods and uses |
US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
CA2746778C (en) | 2008-12-19 | 2019-04-23 | University Of Zurich | Human anti-alpha-synuclein autoantibodies |
US8614297B2 (en) | 2008-12-22 | 2013-12-24 | Hoffmann-La Roche Inc. | Anti-idiotype antibody against an antibody against the amyloid β peptide |
WO2010101950A1 (en) | 2009-03-02 | 2010-09-10 | Catholic Healthcare West | Diagnostic devices and methods of use |
EP2475428B1 (en) | 2009-09-11 | 2015-07-01 | Probiodrug AG | Heterocylcic derivatives as inhibitors of glutaminyl cyclase |
JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
SG183369A1 (en) | 2010-03-03 | 2012-09-27 | Boehringer Ingelheim Int | Biparatopic abeta binding polypeptides |
JP5688745B2 (ja) | 2010-03-10 | 2015-03-25 | プロビオドルグ エージー | グルタミニルシクラーゼ(qc、ec2.3.2.5)の複素環阻害剤 |
MX336196B (es) | 2010-04-15 | 2016-01-11 | Abbvie Inc | Proteinas de union a amiloide beta. |
US8541596B2 (en) | 2010-04-21 | 2013-09-24 | Probiodrug Ag | Inhibitors |
BR112013002297A2 (pt) | 2010-07-30 | 2016-05-24 | Ac Immune Sa | anticorpos humanizados seguros e funcionais |
EP3527220A1 (en) | 2010-08-12 | 2019-08-21 | AC Immune S.A. | Vaccine engineering |
WO2012024187A1 (en) | 2010-08-14 | 2012-02-23 | Abbott Laboratories | Amyloid-beta binding proteins |
EP2632434A1 (en) | 2010-10-26 | 2013-09-04 | AC Immune S.A. | Liposome-based construct comprising a peptide modified through hydrophobic moieties |
ES2628596T3 (es) | 2010-11-29 | 2017-08-03 | Akershus Universitetssykehus | Procedimientos y composiciones para monitorizar la actividad fagocítica |
WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
AU2012272790B2 (en) | 2011-06-23 | 2016-10-06 | Biogen International Neuroscience Gmbh | Anti-alpha synuclein binding molecules |
CN103781919B9 (zh) | 2011-06-27 | 2017-09-15 | 卫材R&D管理有限公司 | 指示阿尔茨海默氏病的微rna生物标志物 |
US9926353B2 (en) | 2011-07-19 | 2018-03-27 | New York University | Immunotherapeutic modulation of amyloidogenic disease using non-fibrillogenic, non-amyloidogenic polymerized proteins and peptides |
WO2013013056A1 (en) | 2011-07-19 | 2013-01-24 | New York University | Method for treating amyloid disease |
GB201113570D0 (en) | 2011-08-05 | 2011-09-21 | Glaxosmithkline Biolog Sa | Vaccine |
CA2853531C (en) * | 2011-10-28 | 2020-03-10 | Neotope Biosciences Limited | Humanized antibodies that recognize alpha-synuclein |
EP2802602B1 (en) * | 2012-01-11 | 2019-03-27 | Arizona Board of Regents, a Body Corporate of the State of Arizona acting for and on behalf of Arizona State University | Bispecific antibody fragments for neurological disease proteins and methods of use |
EP3320914B1 (en) * | 2012-09-10 | 2020-12-30 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | T-helper 1 adjuvant for treating amyotrophic lateral sclerosis |
JP6674888B2 (ja) | 2013-03-13 | 2020-04-01 | プロセナ バイオサイエンシーズ リミテッド | タウ免疫療法 |
US9102752B2 (en) | 2013-03-15 | 2015-08-11 | United Biomedical, Inc. | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
EP2873679A1 (en) | 2013-11-13 | 2015-05-20 | F.Hoffmann-La Roche Ag | Camelid single-domain antibody directed against amyloid bêta and methods for producing conjugates thereof |
EP2873680A1 (en) | 2013-11-13 | 2015-05-20 | F.Hoffmann-La Roche Ag | Oligopeptide and methods for producing conjugates thereof |
WO2015165961A1 (en) | 2014-04-29 | 2015-11-05 | Affiris Ag | Treatment and prevention of alzheimer's disease (ad) |
WO2016005328A2 (en) * | 2014-07-07 | 2016-01-14 | AbbVie Deutschland GmbH & Co. KG | IMMUNOGENIC PRODUCTS BASED ON MUTEIN AMYLOID ß (Aß) AMINO ACID SEQUENCES AND USES THEREOF |
BR112016030774A2 (pt) | 2014-07-10 | 2018-01-16 | Bioarctic Neuroscience Ab | anticorpo ou fragmento de ligação a antígeno do mesmo, uso de um anticorpo, métodos para redução da quantidade de protofibrilas de ?? em um indivíduo, para tratamento e/ou para profilaxia de uma doença, para medição da quantidade de protofibrilas de ?? e/ou de proteína ?? agregada em uma pessoa, e para diagnóstico de uma doença, e, composição farmacêutica |
MA41115A (fr) | 2014-12-02 | 2017-10-10 | Biogen Int Neuroscience Gmbh | Procédé de traitement de la maladie d'alzheimer |
HRP20220304T1 (hr) | 2015-06-24 | 2022-05-13 | F. Hoffmann - La Roche Ag | Anti-transferinska receptorska protutijela s prilagođenim afinitetom |
EP3356406A1 (en) | 2015-10-02 | 2018-08-08 | H. Hoffnabb-La Roche Ag | Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use |
AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
EP3374379A4 (en) | 2015-11-09 | 2019-05-15 | The University Of British Columbia | N-TERMINAL EPITOPES IN BETA-AMYLOID AND CONFORMATIONALLY SELECTIVE ANTIBODIES THEREOF |
CN108350053A (zh) * | 2015-11-09 | 2018-07-31 | 英属哥伦比亚大学 | 淀粉样蛋白β表位及其抗体 |
KR20180085736A (ko) | 2015-11-09 | 2018-07-27 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 아밀로이드 베타 중간-영역 내 에피토프 및 이에 대해 구조적으로 선택성인 항체 |
US10188749B2 (en) | 2016-04-14 | 2019-01-29 | Fred Hutchinson Cancer Research Center | Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers |
JP7194985B2 (ja) | 2016-05-02 | 2022-12-23 | プロセナ バイオサイエンシーズ リミテッド | タウ認識抗体 |
PT3452507T (pt) | 2016-05-02 | 2022-12-20 | Prothena Biosciences Ltd | Imunoterapia anti-tau |
KR102471787B1 (ko) | 2016-05-02 | 2022-11-29 | 프로테나 바이오사이언시즈 리미티드 | 타우 인식 항체 |
WO2018057999A1 (en) * | 2016-09-22 | 2018-03-29 | William Marsh Rice University | Molecular hybridization probes for complex sequence capture and analysis |
US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
EP3672631B9 (en) | 2017-08-22 | 2023-06-28 | Biogen MA Inc. | Pharmaceutical compositions containing anti-beta amyloid antibodies |
ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
EP3935083A4 (en) | 2019-03-03 | 2022-11-30 | Prothena Biosciences Limited | ANTIBODIES RECOGNIZING TAU PROTEIN |
Family Cites Families (364)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE878999A (fr) * | 1979-09-26 | 1980-03-26 | Herstal Sa | Canon composite et procede pour sa fabrication |
US4902506A (en) | 1983-07-05 | 1990-02-20 | The University Of Rochester | Immunogenic conjugates |
CH652145A5 (de) | 1982-01-22 | 1985-10-31 | Sandoz Ag | Verfahren zur in vitro-herstellung von hybridomen welche humane monoklonale antikoerper erzeugen. |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4634666A (en) | 1984-01-06 | 1987-01-06 | The Board Of Trustees Of The Leland Stanford Junior University | Human-murine hybridoma fusion partner |
US5158769A (en) | 1984-03-07 | 1992-10-27 | New York Blood Center, Inc. | Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers |
US5417986A (en) | 1984-03-16 | 1995-05-23 | The United States Of America As Represented By The Secretary Of The Army | Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres |
US5208036A (en) | 1985-01-07 | 1993-05-04 | Syntex (U.S.A.) Inc. | N-(ω, (ω-1)-dialkyloxy)- and N-(ω, (ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4666829A (en) | 1985-05-15 | 1987-05-19 | University Of California | Polypeptide marker for Alzheimer's disease and its use for diagnosis |
US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
US4713366A (en) | 1985-12-04 | 1987-12-15 | The Ohio State University Research Foundation | Antigenic modification of polypeptides |
US5096706A (en) | 1986-03-25 | 1992-03-17 | National Research Development Corporation | Antigen-based treatment for adiposity |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5278049A (en) | 1986-06-03 | 1994-01-11 | Incyte Pharmaceuticals, Inc. | Recombinant molecule encoding human protease nexin |
US5231170A (en) | 1986-08-27 | 1993-07-27 | Paul Averback | Antibodies to dense microspheres |
US5220013A (en) | 1986-11-17 | 1993-06-15 | Scios Nova Inc. | DNA sequence useful for the detection of Alzheimer's disease |
US5187153A (en) | 1986-11-17 | 1993-02-16 | Scios Nova Inc. | Methods of treatment using Alzheimer's amyloid polypeptide derivatives |
US5223482A (en) | 1986-11-17 | 1993-06-29 | Scios Nova Inc. | Recombinant Alzheimer's protease inhibitory amyloid protein and method of use |
US4879213A (en) | 1986-12-05 | 1989-11-07 | Scripps Clinic And Research Foundation | Synthetic polypeptides and antibodies related to Epstein-Barr virus early antigen-diffuse |
EP0832981A1 (en) | 1987-02-17 | 1998-04-01 | Pharming B.V. | DNA sequences to target proteins to the mammary gland for efficient secretion |
US4912206A (en) | 1987-02-26 | 1990-03-27 | The United States Of America As Represented By The Department Of Health And Human Services | CDNA clone encoding brain amyloid of alzheimer's disease |
EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
JPS63245689A (ja) * | 1987-03-31 | 1988-10-12 | Suntory Ltd | ヒトアミロイド関連蛋白モノクロ−ナル抗体 |
US4883666A (en) * | 1987-04-29 | 1989-11-28 | Massachusetts Institute Of Technology | Controlled drug delivery system for treatment of neural disorders |
US5229490A (en) | 1987-05-06 | 1993-07-20 | The Rockefeller University | Multiple antigen peptide system |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5245015A (en) | 1991-04-26 | 1993-09-14 | Tanox Biosystems, Inc. | Monoclonal antibodies which neutralize HIV-1 through reaction with a conformational epitope in vitro |
US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
US5583112A (en) | 1987-05-29 | 1996-12-10 | Cambridge Biotech Corporation | Saponin-antigen conjugates and the use thereof |
US5645820A (en) | 1987-06-24 | 1997-07-08 | Autoimmune, Inc. | Treatment of autoimmune diseases by aerosol administration of autoantigens |
US5849298A (en) | 1987-06-24 | 1998-12-15 | Autoimmune Inc. | Treatment of multiple sclerosis by oral administration of bovine myelin |
US5869054A (en) | 1987-06-24 | 1999-02-09 | Autoimmune Inc. | Treatment of multiple sclerosis by oral administration of autoantigens |
US5641474A (en) | 1987-06-24 | 1997-06-24 | Autoimmune, Inc. | Prevention of autoimmune diseases by aerosol administration of autoantigens |
US5571500A (en) | 1987-06-24 | 1996-11-05 | Autoimmune, Inc. | Treatment of autoimmune diseases through administration by inhalation of autoantigens |
US5571499A (en) | 1987-06-24 | 1996-11-05 | Autoimmune, Inc. | Treatment of autoimmune diseases by aerosol administration of autoantigens |
US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
US5231000A (en) * | 1987-10-08 | 1993-07-27 | The Mclean Hospital | Antibodies to A4 amyloid peptide |
US5089603A (en) | 1989-06-21 | 1992-02-18 | Tanox Biosystems, Inc. | Antigenic epitopes present on membrane-bound but not secreted iga |
US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
US5576184A (en) * | 1988-09-06 | 1996-11-19 | Xoma Corporation | Production of chimeric mouse-human antibodies with specificity to human tumor antigens |
JPH04501719A (ja) | 1988-11-10 | 1992-03-26 | インペリアル・キヤンサー・リサーチ・テクノロジー・リミテツド | ポリペプチド |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
CA2006700A1 (en) | 1989-01-17 | 1990-07-17 | Antonello Pessi | Synthetic peptides and their use as universal carriers for the preparation of immunogenic conjugates suitable for the development of synthetic vaccines |
US5227159A (en) * | 1989-01-31 | 1993-07-13 | Miller Richard A | Anti-idiotype antibodies reactive with shared idiotopes expressed by B cell lymphomas and autoantibodies |
US5262332A (en) | 1989-04-05 | 1993-11-16 | Brigham And Women's Hospital | Diagnostic method for Alzheimer's disease: examination of non-neural tissue |
HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
IT1237764B (it) | 1989-11-10 | 1993-06-17 | Eniricerche Spa | Peptidi sintetici utili come carriers universali per la preparazione di coniugati immunogenici e loro impiego per lo sviluppo di vaccini sintetici. |
US5633076A (en) | 1989-12-01 | 1997-05-27 | Pharming Bv | Method of producing a transgenic bovine or transgenic bovine embryo |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
ATE139258T1 (de) | 1990-01-12 | 1996-06-15 | Cell Genesys Inc | Erzeugung xenogener antikörper |
US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
EP0527823A1 (en) | 1990-04-24 | 1993-02-24 | The Regents Of The University Of California | Purification, detection and methods of use of protease nexin-2 |
US5753624A (en) | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
CA2081482C (en) | 1990-04-27 | 2000-11-21 | Ellis L. Kline | Method and composition for treatment of central nervous system disease states associated with abnormal amyloid beta protein molecular organization |
GB9009548D0 (en) * | 1990-04-27 | 1990-06-20 | Celltech Ltd | Chimeric antibody and method |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
EP0600866B1 (en) | 1990-06-01 | 1997-12-03 | Chiron Corporation | Compositions and methods for identifying biologically active molecules |
US5593970A (en) | 1990-06-11 | 1997-01-14 | Biochem Pharma Inc. | Heterocyclic anthracycline analogs |
ATE260974T1 (de) | 1990-06-15 | 2004-03-15 | Scios Inc | Transgenes, nicht-menschliches säugetier das die amyloidbildende pathologie der alzheimerschen krankheit zeigt |
CA2085897A1 (en) | 1990-06-19 | 1991-12-20 | George Pieczenik | Nonpathogenic variant virus |
GB9014932D0 (en) | 1990-07-05 | 1990-08-22 | Celltech Ltd | Recombinant dna product and method |
WO1992020791A1 (en) | 1990-07-10 | 1992-11-26 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5780587A (en) | 1990-08-24 | 1998-07-14 | President And Fellows Of Harvard College | Compounds and methods for inhibiting β-protein filament formation and neurotoxicity |
US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
NZ239643A (en) | 1990-09-17 | 1996-05-28 | North American Vaccine Inc | Vaccine containing bacterial polysaccharide protein conjugate and adjuvant (c-nd-che-a-co-b-r) with a long chain alkyl group. |
US5702906A (en) | 1990-09-25 | 1997-12-30 | Genentech, Inc. | Antibodies to neurotrophic factor-4 (NT-4) |
EP0553244B8 (en) | 1990-10-05 | 2005-06-08 | Celldex Therapeutics, Inc. | Targeted immunostimulation with bispecific reagents |
GB9023352D0 (en) | 1990-10-26 | 1990-12-05 | Lynxvale Ltd | Vaccinia vectors,vaccinia genes and expression products thereof |
DE69233774D1 (de) | 1991-01-21 | 2009-12-10 | Elan Pharm Inc | Prüfung und Modell für Alzheimers-Krankheit |
PT501882E (pt) | 1991-03-01 | 2000-12-29 | Merial Sas | Processo de imunoneutralizacao anti-lhrm de animais domesticos machos nao castrados e peptido para esse fim |
US5192753A (en) | 1991-04-23 | 1993-03-09 | Mcgeer Patrick L | Anti-rheumatoid arthritic drugs in the treatment of dementia |
AU655823B2 (en) | 1991-05-08 | 1995-01-12 | Crucell Switzerland Ag | Immunostimulating and immunopotentiating reconstituted influenza virosomes and vaccines containing them |
US5858657A (en) | 1992-05-15 | 1999-01-12 | Medical Research Council | Methods for producing members of specific binding pairs |
DE69230142T2 (de) | 1991-05-15 | 2000-03-09 | Cambridge Antibody Tech | Verfahren zur herstellung von spezifischen bindungspaargliedern |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
DE69233254T2 (de) | 1991-06-14 | 2004-09-16 | Genentech, Inc., South San Francisco | Humanisierter Heregulin Antikörper |
US5434050A (en) | 1991-08-13 | 1995-07-18 | Regents Of The University Of Minnesota | Labelled β-amyloid peptide and methods of screening for Alzheimer's disease |
US5283185A (en) | 1991-08-28 | 1994-02-01 | University Of Tennessee Research Corporation | Method for delivering nucleic acids into cells |
AU669489B2 (en) | 1991-09-18 | 1996-06-13 | Affymax Technologies N.V. | Method of synthesizing diverse collections of oligomers |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5837268A (en) | 1991-10-16 | 1998-11-17 | University Of Saskatchewan | GnRH-leukotoxin chimeras |
AU3328493A (en) | 1991-12-17 | 1993-07-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5679348A (en) | 1992-02-03 | 1997-10-21 | Cedars-Sinai Medical Center | Immunotherapy for recurrent HSV infections |
EP1958646A1 (en) | 1992-02-11 | 2008-08-20 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Dual carrier immunogenic construct |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
US5604102A (en) | 1992-04-15 | 1997-02-18 | Athena Neurosciences, Inc. | Methods of screening for β-amyloid peptide production inhibitors |
US5441870A (en) | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
US5851787A (en) | 1992-04-20 | 1998-12-22 | The General Hospital Corporation | Nucleic acid encoding amyloid precursor-like protein and uses thereof |
CA2118508A1 (en) | 1992-04-24 | 1993-11-11 | Elizabeth S. Ward | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
PT652758E (pt) | 1992-06-18 | 2000-04-28 | Harvard College | Vacinas de toxina da difteria |
EP0761231B1 (en) | 1992-06-25 | 2000-01-12 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Vaccine composition containing adjuvants |
US5766846A (en) | 1992-07-10 | 1998-06-16 | Athena Neurosciences | Methods of screening for compounds which inhibit soluble β-amyloid peptide production |
US6610493B1 (en) | 1993-06-17 | 2003-08-26 | Brigham And Women's Hospital | Screening compounds for the ability to alter the production of amyloid-β peptide |
US5837672A (en) | 1992-07-10 | 1998-11-17 | Athena Neurosciences, Inc. | Methods and compositions for the detection of soluble β-amyloid peptide |
IL102687A (en) | 1992-07-30 | 1997-06-10 | Yeda Res & Dev | Conjugates of poorly immunogenic antigens and synthetic pepide carriers and vaccines comprising them |
US6261569B1 (en) | 1992-08-27 | 2001-07-17 | Deakin Research Limited | Retro-, inverso- and retro-inverso synthetic peptide analogues |
US5958883A (en) | 1992-09-23 | 1999-09-28 | Board Of Regents Of The University Of Washington Office Of Technology | Animal models of human amyloidoses |
EP0665897B1 (en) | 1992-10-01 | 2003-07-09 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
AU5358494A (en) | 1992-10-13 | 1994-05-09 | Duke University | Method of inhibiting binding of amyloid precursor protein to beta-amyloid protein |
US5605811A (en) | 1992-10-26 | 1997-02-25 | Athena Neurosciences, Inc. | Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein |
EP0667959B1 (en) | 1992-10-26 | 2003-08-13 | Elan Pharmaceuticals, Inc. | Methods for identifying inhibitors of the production of beta-amyloid peptide |
US5972336A (en) | 1992-11-03 | 1999-10-26 | Oravax Merieux Co. | Urease-based vaccine against helicobacter infection |
US6210671B1 (en) | 1992-12-01 | 2001-04-03 | Protein Design Labs, Inc. | Humanized antibodies reactive with L-selectin |
WO1994012629A1 (en) | 1992-12-02 | 1994-06-09 | Baylor College Of Medicine | Episomal vectors for gene therapy |
ATE199392T1 (de) | 1992-12-04 | 2001-03-15 | Medical Res Council | Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung |
KR100307289B1 (ko) | 1993-01-22 | 2001-12-28 | 제임스 에스. 쿼크 | Qs-21을 함유하는 강글리오사이드-klh 접합체 백신 |
US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
US5750349A (en) | 1993-01-25 | 1998-05-12 | Takeda Chemical Industries Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
US5358708A (en) | 1993-01-29 | 1994-10-25 | Schering Corporation | Stabilization of protein formulations |
US5472693A (en) | 1993-02-16 | 1995-12-05 | The Dow Chemical Company | Family of anti-carcinoembryonic antigen chimeric antibodies |
CA2115811A1 (en) | 1993-02-17 | 1994-08-18 | Claus Krebber | A method for in vivo selection of ligand-binding proteins |
CA2115900A1 (en) * | 1993-02-22 | 1994-08-23 | Gerald W. Becker | Pharmaceutical screens and antibodies |
ATE386800T1 (de) | 1993-03-17 | 2008-03-15 | Us Gov Health & Human Serv | Immunogene chimäre umfassend nucleinsäuresequenzen, die signalsequenzpeptide des endoplasmatischen reticulums und mindestens ein anderes peptid codieren, deren verwendung in impfstoffen und zur behandlung von krankheiten |
WO1994021288A1 (en) | 1993-03-18 | 1994-09-29 | Cytimmune Sciences, Inc. | Composition and method for reducing toxicity of biologically-active factors |
AU685443B2 (en) | 1993-03-23 | 1998-01-22 | Smithkline Beecham Biologicals (Sa) | Vaccine compositions containing 3-O deacylated monophosphoryl lipid A |
IT1270939B (it) | 1993-05-11 | 1997-05-26 | Angeletti P Ist Richerche Bio | Procedimento per la preparazione di immunogeni e reagenti diagnostici,e immunogeni e reagenti diagnostici cosi' ottenibili. |
US5723130A (en) | 1993-05-25 | 1998-03-03 | Hancock; Gerald E. | Adjuvants for vaccines against respiratory syncytial virus |
WO1994028412A1 (en) | 1993-05-28 | 1994-12-08 | The Miriam Hospital | Composition and method for in vivo imaging of amyloid deposits |
JPH08510756A (ja) | 1993-06-04 | 1996-11-12 | ホワイトヘッド インスティチュート フォー バイオメディカル リサーチ | ストレス蛋白質とその使用 |
US5464823A (en) | 1993-07-20 | 1995-11-07 | The Regents Of The University Of California | Mammalian antibiotic peptides |
CA2146667A1 (en) | 1993-08-18 | 1995-02-23 | Adolf Hoess | Lipopolysaccharide-binding and neutralizing peptides |
DK96493D0 (da) | 1993-08-26 | 1993-08-26 | Mouritsen Og Elsner Aps | Fremgangsmaade til at inducere antistofresponser mod selvproteiner og autovaccine fremstillet ved fremgangsmaaden |
AU705889B2 (en) | 1993-08-26 | 1999-06-03 | Regents Of The University Of California, The | Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory peptides |
WO1995006407A1 (en) | 1993-08-30 | 1995-03-09 | The Regents Of The University Of California | Novel component of amyloid in alzheimer's disease and methods for use of same |
ATE286510T1 (de) | 1993-09-07 | 2005-01-15 | Smithkline Beecham Corp | In der behandlung von il4 auslösenden krankheiten nützliche rekombinante il4 antikörper |
US5652334A (en) | 1993-09-08 | 1997-07-29 | City Of Hope | Method for design of substances that enhance memory and improve the quality of life |
US5385887A (en) | 1993-09-10 | 1995-01-31 | Genetics Institute, Inc. | Formulations for delivery of osteogenic proteins |
DK0735893T3 (da) | 1993-09-14 | 2009-03-09 | Pharmexa Inc | PAN DR-bindende peptider til styrkelse af immunsvaret |
US5470951A (en) | 1993-09-29 | 1995-11-28 | City Of Hope | Peptides for antagonizing the effects of amyloid βprotein |
US5858981A (en) | 1993-09-30 | 1999-01-12 | University Of Pennsylvania | Method of inhibiting phagocytosis |
AU7979094A (en) | 1993-10-22 | 1995-05-08 | Genentech Inc. | Methods and compositions for microencapsulation of adjuvants |
WO1995012608A1 (en) | 1993-11-02 | 1995-05-11 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
US5744368A (en) | 1993-11-04 | 1998-04-28 | Research Foundation Of State University Of New York | Methods for the detection of soluble amyloid β-protein (βAP) or soluble transthyretin (TTR) |
US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
US5434170A (en) | 1993-12-23 | 1995-07-18 | Andrulis Pharmaceuticals Corp. | Method for treating neurocognitive disorders |
US5877218A (en) | 1994-01-10 | 1999-03-02 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
CA2182311A1 (en) | 1994-01-27 | 1995-08-03 | Karen Hsiao | Transgenic non-human mammals with progressive neurologic disease |
US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
EP0802797A1 (en) | 1994-02-03 | 1997-10-29 | The Picower Institute For Medical Research | Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis |
AUPM411994A0 (en) | 1994-02-25 | 1994-03-24 | Deakin Research Limited | Epitopes |
US5795954A (en) | 1994-03-04 | 1998-08-18 | Genentech, Inc. | Factor VIIa inhibitors from Kunitz domain proteins |
US6270757B1 (en) | 1994-04-21 | 2001-08-07 | Genetics Institute, Inc. | Formulations for IL-11 |
US6372716B1 (en) | 1994-04-26 | 2002-04-16 | Genetics Institute, Inc. | Formulations for factor IX |
JPH10500112A (ja) | 1994-05-06 | 1998-01-06 | ファーマコピーア,インコーポレイテッド | 組合せ ジヒドロベンゾピラン ライブラリー |
CA2191101C (en) * | 1994-05-25 | 2001-08-07 | Ellis L. Kline | Materials and methods for treatment of plaquing diseases |
US5505947A (en) | 1994-05-27 | 1996-04-09 | The University Of North Carolina At Chapel Hill | Attenuating mutations in Venezuelan Equine Encephalitis virus |
US5622701A (en) | 1994-06-14 | 1997-04-22 | Protein Design Labs, Inc. | Cross-reacting monoclonal antibodies specific for E- and P-selectin |
US5663046A (en) | 1994-06-22 | 1997-09-02 | Pharmacopeia, Inc. | Synthesis of combinatorial libraries |
US5798100A (en) | 1994-07-06 | 1998-08-25 | Immunomedics, Inc. | Multi-stage cascade boosting vaccine |
US6417178B1 (en) | 1994-07-19 | 2002-07-09 | University Of Pittsburgh | Amyloid binding nitrogen-linked compounds for the antemortem diagnosis of alzheimer's disease, in vivo imaging and prevention of amyloid deposits |
NZ290089A (en) | 1994-07-27 | 1999-05-28 | Queensland Inst Med Res | Recombinant polyepitope cytotoxic t lymphocyte (ctl) vaccines |
DE69535562T2 (de) | 1994-09-16 | 2008-06-26 | Cancer Research Institute Of Contra Costa | Rekombinantpeptide hergeleitet vom mc3 antikörper gegen ba46, verfahren zu deren verwendung und verfahren zur humanisierung von antikörperpeptiden |
US5872005A (en) | 1994-11-03 | 1999-02-16 | Cell Genesys Inc. | Packaging cell lines for adeno-associated viral vectors |
US6114133A (en) | 1994-11-14 | 2000-09-05 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41) |
US5589154A (en) * | 1994-11-22 | 1996-12-31 | Rutgers, The State University Of New Jersey | Methods for the prevention or treatment of vascular hemorrhaging and Alzheimer's disease |
US5688651A (en) | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
JP2000510813A (ja) | 1995-02-06 | 2000-08-22 | ジェネテイックス・インスティテュート・インコーポレイテッド | Il−12用処方 |
US5786180A (en) | 1995-02-14 | 1998-07-28 | Bayer Corporation | Monoclonal antibody 369.2B specific for β A4 peptide |
US5624937A (en) | 1995-03-02 | 1997-04-29 | Eli Lilly And Company | Chemical compounds as inhibitors of amyloid beta protein production |
US6303567B1 (en) | 1995-03-14 | 2001-10-16 | Praecis Pharmaceuticals, Inc . | Modulators of β-amyloid peptide aggregation comprising D-amino acids |
DE69621607T2 (de) | 1995-03-14 | 2003-01-02 | Praecis Pharm Inc | VERBINDUNGEN MIT AGGREGATIONS-MODULIERENDEN WIRKUNG AUF DAS AMYLOiD PROTEIN |
US5817626A (en) | 1995-03-14 | 1998-10-06 | Praecis Pharmaceuticals Incorporated | Modulators of beta-amyloid peptide aggregation |
US5854215A (en) | 1995-03-14 | 1998-12-29 | Praecis Pharmaceuticals Incorporated | Modulators of β-amyloid peptide aggregation |
EP0871755A1 (en) | 1995-03-23 | 1998-10-21 | Cantab Pharmaceuticals Research Limited | Vectors for gene delivery |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
US7153510B1 (en) | 1995-05-04 | 2006-12-26 | Yale University | Recombinant vesiculoviruses and their uses |
EP0827544B1 (en) | 1995-05-23 | 2004-08-18 | MorphoSys AG | Multimeric proteins |
US5948763A (en) | 1995-06-07 | 1999-09-07 | New York University | Peptides and pharmaceutical compositions thereof for treatment of disorders or diseases associated with abnormal protein folding into amyloid or amyloid-like deposits |
US5910427A (en) | 1995-06-22 | 1999-06-08 | La Jolla Institute For Allergy And Immunology | Antigen non-specific glycosylation inhibiting factor derivatives |
ATE214603T1 (de) | 1995-06-30 | 2002-04-15 | American Cyanamid Co | Stabile makrolide und makrolide imptstoff- zusammensetzungen |
DE69635207T2 (de) | 1995-07-07 | 2006-06-22 | Darwin Molecular Corp. | Auf Chromosom 1 lokalisiertes Gen dessen Genprodukt mit der Alzheimerschen Krankheit assoziiert ist. |
AUPN443995A0 (en) | 1995-07-27 | 1995-08-17 | Csl Limited | Papillomavirus polyprotein |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
DK1143006T3 (da) | 1995-08-18 | 2008-07-14 | Morphosys Ip Gmbh | Vektorer/DNA-sekvenser fra humane kombinatoriske antistofbiblioteker |
AU6898996A (en) | 1995-08-21 | 1997-03-12 | Cytrx Corporation | Compositions and methods for growth promotion |
ATE263374T1 (de) | 1995-09-14 | 2004-04-15 | Univ California | Für natives prp-sc spezifische antikörper |
US5731284A (en) | 1995-09-28 | 1998-03-24 | Amgen Inc. | Method for treating Alzheimer's disease using glial line-derived neurotrophic factor (GDNF) protein product |
US5985242A (en) | 1995-10-27 | 1999-11-16 | Praecis Pharmaceuticals, Inc. | Modulators of β-amyloid peptide aggregation comprising D-amino acids |
US5750361A (en) | 1995-11-02 | 1998-05-12 | The Regents Of The University Of California | Formation and use of prion protein (PRP) complexes |
ATE246808T1 (de) | 1995-11-10 | 2003-08-15 | Elan Corp Plc | Peptide, die den transport über gewebe erhöhen und verfahren zu ihrer identifizierung und verwendung |
WO1997018855A1 (en) | 1995-11-21 | 1997-05-29 | Eduard Naumovich Lerner | Device for enhanced delivery of biologically active substances and compounds in an organism |
AU1072897A (en) | 1995-12-12 | 1997-07-03 | Karolinska Innovations Ab | Peptide binding the klvff-sequence of amyloid beta |
JPH09178743A (ja) * | 1995-12-27 | 1997-07-11 | Oriental Yeast Co Ltd | 可溶性appの定量法 |
US6015662A (en) | 1996-01-23 | 2000-01-18 | Abbott Laboratories | Reagents for use as calibrators and controls |
US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
US6096313A (en) | 1996-02-09 | 2000-08-01 | Ludwig Institute For Cancer Research | Compositions containing immunogenic molecules and granulocyte-macrophage colony stimulating factor, as an adjuvant |
EP0883686A1 (en) | 1996-02-26 | 1998-12-16 | Morphosys Gesellschaft für Proteinoptimierung mbH | Novel method for the identification of nucleic acid sequences encoding two or more interacting (poly)peptides |
US6150091A (en) | 1996-03-06 | 2000-11-21 | Baylor College Of Medicine | Direct molecular diagnosis of Friedreich ataxia |
KR20000005120A (ko) | 1996-03-29 | 2000-01-25 | 스칸드레트 존 디 | 파라폭스바이러스 벡터 |
AU713067B2 (en) | 1996-04-03 | 1999-11-25 | Anergen, Inc. | Cyclic peptide vaccines for treatment and prevention of diabetes |
WO1997040147A1 (en) | 1996-04-19 | 1997-10-30 | The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services | Antigenically reactive regions of the hepatitis a virus polyprotein |
US6284533B1 (en) | 1996-05-01 | 2001-09-04 | Avant Immunotherapeutics, Inc. | Plasmid-based vaccine for treating atherosclerosis |
DE69726003T2 (de) | 1996-07-16 | 2004-08-26 | Andreas Plückthun | Immunglobulin-superfamilie domainen und fragmente mit erhöhter löslichkeit |
JP2000516090A (ja) | 1996-07-26 | 2000-12-05 | スローン―ケッタリング インスティチュート フォー キャンサー リサーチ | 遺伝子的免疫化のための方法と試薬 |
US7147851B1 (en) | 1996-08-15 | 2006-12-12 | Millennium Pharmaceuticals, Inc. | Humanized immunoglobulin reactive with α4β7 integrin |
EP1586584A1 (en) | 1996-08-27 | 2005-10-19 | Praecis Pharmaceuticals Incorporated | Modulators of beta-amyloid peptide aggregation comprising D-amino acids |
US6057367A (en) | 1996-08-30 | 2000-05-02 | Duke University | Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses |
US6797495B2 (en) | 1996-11-05 | 2004-09-28 | The Regents Of The University Of California | Somatic cells with ablated PrP gene and methods of use |
US6022859A (en) | 1996-11-15 | 2000-02-08 | Wisconsin Alumni Research Foundation | Inhibitors of β-amyloid toxicity |
WO1998022120A1 (en) | 1996-11-19 | 1998-05-28 | The Wistar Institute Of Anatomy & Biology | Diagnostic and therapeutic reagents for alzheimer's disease |
US6962984B2 (en) | 1996-12-05 | 2005-11-08 | Nihon University | IgA nephropathy-related DNA |
US6218506B1 (en) | 1997-02-05 | 2001-04-17 | Northwestern University | Amyloid β protein (globular assembly and uses thereof) |
US20030068316A1 (en) | 1997-02-05 | 2003-04-10 | Klein William L. | Anti-ADDL antibodies and uses thereof |
EA199900758A1 (ru) | 1997-03-03 | 2000-04-24 | Бёрингер Ингельхайм Фармасьютиклс, Инк. | Малые молекулы, полезные при лечении воспалительных заболеваний |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
US5798102A (en) | 1997-03-04 | 1998-08-25 | Milkhaus Laboratory, Inc. | Treatment of cardiomyopathy |
EP1005368B1 (en) | 1997-03-10 | 2009-09-02 | Ottawa Hospital Research Institute | Use of nucleic acids containing unmethylated CpG dinucleotide in combination with alum as adjuvants |
US20020086847A1 (en) | 1997-04-09 | 2002-07-04 | Mindset Biopharmaceuticals (Usa) | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
AU743827B2 (en) * | 1997-04-09 | 2002-02-07 | Intellect Neurosciences, Inc. | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
US8173127B2 (en) | 1997-04-09 | 2012-05-08 | Intellect Neurosciences, Inc. | Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof |
US6787319B2 (en) | 1997-04-16 | 2004-09-07 | American Home Products Corp. | β-amyloid peptide-binding proteins and polynucleotides encoding the same |
EP1003531B1 (en) | 1997-05-20 | 2007-08-22 | Ottawa Health Research Institute | Processes for preparing nucleic acid constructs |
ES2190087T3 (es) | 1997-06-13 | 2003-07-16 | Genentech Inc | Formulacion estabilizada de un anticuerpo. |
WO1999000150A2 (en) | 1997-06-27 | 1999-01-07 | Regents Of The University Of California | Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor |
EP1001987B1 (en) | 1997-08-01 | 2010-12-15 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Composition and method for the detection of diseases associated with amyloid-like fibril or protein aggregate formation |
EP1005569A2 (en) | 1997-08-01 | 2000-06-07 | MorphoSys AG | Novel method and phage for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex |
ES2500490T3 (es) | 1997-08-29 | 2014-09-30 | Antigenics Inc. | Composiciones que comprenden el adyuvante QS-21 y polisorbato o ciclodextrina como excipiente |
US6175057B1 (en) | 1997-10-08 | 2001-01-16 | The Regents Of The University Of California | Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy |
US20010016053A1 (en) * | 1997-10-10 | 2001-08-23 | Monte A. Dickson | Multi-spectral imaging sensor |
US6710226B1 (en) * | 1997-12-02 | 2004-03-23 | Neuralab Limited | Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics |
US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US6743427B1 (en) | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
US20080050367A1 (en) * | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
US7179892B2 (en) | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
EP1033998B1 (en) | 1997-12-03 | 2005-10-19 | Neuralab, Ltd. | Suppressing beta-amyloid-related changes in alzheimer's disease |
FR2777015B3 (fr) | 1998-02-23 | 2000-09-15 | Financ De Biotechnologie | Procede et moyens pour l'obtention de modeles cellulaires et animaux de maladies neurodegeneratives |
US6528624B1 (en) | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
US20050059802A1 (en) | 1998-04-07 | 2005-03-17 | Neuralab Ltd | Prevention and treatment of amyloidogenic disease |
US20050059591A1 (en) | 1998-04-07 | 2005-03-17 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
CA2327505A1 (en) | 1998-04-28 | 1999-11-04 | Smithkline Beecham Corporation | Monoclonal antibodies with reduced immunogenicity |
US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
US6432710B1 (en) | 1998-05-22 | 2002-08-13 | Isolagen Technologies, Inc. | Compositions for regenerating tissue that has deteriorated, and methods for using such compositions |
US6727349B1 (en) | 1998-07-23 | 2004-04-27 | Millennium Pharmaceuticals, Inc. | Recombinant anti-CCR2 antibodies and methods of use therefor |
US6126967A (en) * | 1998-09-03 | 2000-10-03 | Ascent Pediatrics | Extended release acetaminophen particles |
EP1117421B2 (en) | 1998-10-05 | 2014-03-19 | Bavarian Nordic Inc. | Methods for therapeutic vaccination |
WO2000023082A1 (en) | 1998-10-19 | 2000-04-27 | Yeda Research And Development Co. Ltd. | Treatment of systemic lupus erythematosus by down-regulating the autoimmune response to autoantigens |
US7112661B1 (en) | 1998-10-30 | 2006-09-26 | The Research Foundation Of State University Of New York | Variable heavy chain and variable light chain regions of antibodies to human platelet glycoprotein Ib alpha |
GB2348203B (en) | 1998-11-04 | 2002-06-19 | Imp College Innovations Ltd | Solube beta-forms of prion proteins, methods of preparation and use |
DE69915697T2 (de) | 1999-01-19 | 2005-01-13 | Pharmacia & Upjohn Co., Kalamazoo | Packungsverfahren für Oxidationsempfindliche Medikamente |
JP2002535289A (ja) | 1999-01-22 | 2002-10-22 | ドウアリング,マシユー・ジヨン | 神経疾患のワクチン媒介治療 |
US7629311B2 (en) | 1999-02-24 | 2009-12-08 | Edward Lewis Tobinick | Methods to facilitate transmission of large molecules across the blood-brain, blood-eye, and blood-nerve barriers |
US7282570B2 (en) | 1999-04-20 | 2007-10-16 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
DE60037800D1 (de) | 1999-05-05 | 2008-03-06 | Neurochem Int Ltd | Stereoselektive antifibrillogene peptide |
US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
PE20010212A1 (es) | 1999-06-01 | 2001-02-22 | Neuralab Ltd | Composiciones del peptido a-beta y procesos para producir las mismas |
JP5249482B2 (ja) | 1999-06-16 | 2013-07-31 | ボストン・バイオメデイカル・リサーチ・インステイテユート | インビボのβ−アミロイドレベルの免疫学的制御 |
EP1368486A4 (en) | 1999-07-15 | 2009-04-01 | Genetics Inst Llc | IL-11 FORMULATIONS |
WO2001010900A2 (en) | 1999-08-04 | 2001-02-15 | University Of Southern California | Globular assembly of amyloid beta protein and uses thereof |
JP2003509020A (ja) | 1999-09-03 | 2003-03-11 | ラモット・ユニバーシティ・オーソリティ・フォー・アプライド・リサーチ・アンド・インダストリアル・ディベロップメント・リミテッド | プラーク形成疾患の診断、治療、予防に有用な薬剤、組成物、その使用法 |
US6294171B2 (en) | 1999-09-14 | 2001-09-25 | Milkhaus Laboratory, Inc. | Methods for treating disease states comprising administration of low levels of antibodies |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
KR20080059676A (ko) | 1999-11-29 | 2008-06-30 | 뉴로겜 인터내셔널 리미티드 | 알츠하이머 및 아밀로이드 관련 질병의 예방 및 치료용백신 |
US20020094335A1 (en) | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
DK1237930T3 (da) | 1999-12-08 | 2007-03-19 | Intellect Neurosciences Inc | Kimære amyloid-beta-peptider |
US6399314B1 (en) | 1999-12-29 | 2002-06-04 | American Cyanamid Company | Methods of detection of amyloidogenic proteins |
DE60114157T2 (de) | 2000-02-21 | 2006-06-29 | Pharmexa A/S | Verfahren zur herabregulierung von amyloid |
CA2400838C (en) | 2000-02-21 | 2013-04-23 | Pharmexa A/S | Novel method for down-regulation of amyloid |
SI1481992T1 (sl) | 2000-02-24 | 2017-01-31 | Washington University St. Louis | Humanizirana protitelesa, ki vežejo amiloidni peptid beta |
US7485616B2 (en) | 2000-04-05 | 2009-02-03 | University Of Tennessee Research Foundation | Methods of investigating, diagnosing, and treating amyloidosis |
CA2396762A1 (en) | 2000-04-13 | 2001-10-25 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and qs-21 |
KR100360985B1 (ko) | 2000-04-26 | 2002-11-18 | 주식회사 동진쎄미켐 | 레지스트 스트리퍼 조성물 |
PT1284998E (pt) | 2000-05-22 | 2005-06-30 | Univ New York | Eptideos imunogenicos sinteticos mas nao-amiloidogenicos homologos a beta-amiloides, destinados a induzir uma reaccao imunitaria contra os beta-amiloides e os depositos amiloides |
WO2002003911A2 (en) | 2000-07-07 | 2002-01-17 | Lars Lannfelt | Prevention and treatment of alzheimer's disease |
US20020009445A1 (en) | 2000-07-12 | 2002-01-24 | Yansheng Du | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
EP1172378A1 (en) | 2000-07-12 | 2002-01-16 | Richard Dr. Dodel | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
US20030092145A1 (en) | 2000-08-24 | 2003-05-15 | Vic Jira | Viral vaccine composition, process, and methods of use |
DK1317479T3 (da) | 2000-09-06 | 2009-11-23 | Aventis Pharma Sa | Fremgangsmåder og sammensætninger for sygdomme, der er associeret med amyloidosis |
IT1319277B1 (it) | 2000-10-24 | 2003-09-26 | Chiesi Farma Spa | Proteine di fusione utili per il trattamento di immunizzazione dellamalattia di alzheimer. |
IL139308A0 (en) | 2000-10-26 | 2001-11-25 | Marikovsky Moshe | Peptides from amyloid precursor protein which inhibit tumor growth and metastasis |
WO2002064084A2 (en) | 2000-11-02 | 2002-08-22 | Cornell Research Foundation, Inc. | In vivo multiphoton diagnostic detection and imaging of a neurodegenerative disease |
PT1346041E (pt) | 2000-11-27 | 2007-06-05 | Praecis Pharm Inc | Agentes terapêuticos e métodos para a sua utilização no tratamento de uma doença amiloidogénica. |
TWI255272B (en) | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
AU2002246734A1 (en) | 2000-12-27 | 2002-08-12 | University Of Texas Health Science Center Houston | Prion isomers, methods of making, methods of using, and compositions and products comprising prion isomers |
FI20002897A (fi) * | 2000-12-29 | 2002-06-30 | Nokia Corp | Elektroninen laite ja välineet irrotettavan yksikön varmistamiseksi toiminta-asentoon |
US20020160394A1 (en) | 2001-01-24 | 2002-10-31 | Bayer Corporation | Regulation of transthyretin to treat obesity |
DE60121729T2 (de) | 2001-04-19 | 2007-11-29 | Dr. Hermann Schätzl | Prion Proteindimere für Impfungen |
US7318923B2 (en) | 2001-04-30 | 2008-01-15 | Eli Lilly And Company | Humanized anti-βantibodies |
WO2002088307A2 (en) | 2001-04-30 | 2002-11-07 | Eli Lilly And Company | Humanized antibodies |
US6906169B2 (en) | 2001-05-25 | 2005-06-14 | United Biomedical, Inc. | Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide |
GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
WO2003000714A2 (en) | 2001-06-22 | 2003-01-03 | Panacea Pharmaceuticals, Inc. | Compositions and methods for preventing protein aggregation in neurodegenerative diseases |
JP4317010B2 (ja) | 2001-07-25 | 2009-08-19 | ピーディーエル バイオファーマ,インコーポレイティド | IgG抗体の安定な凍結乾燥医薬製剤 |
US20030135035A1 (en) | 2001-08-09 | 2003-07-17 | Mark Shannon | Human ZZAP1 protein |
EP1519740A4 (en) | 2001-08-17 | 2005-11-09 | Lilly Co Eli | FASTER IMPROVEMENT OF COGNITION IN DISEASES ASSOCIATED WITH A-BETA |
JP2005500389A (ja) | 2001-08-17 | 2005-01-06 | イーライ・リリー・アンド・カンパニー | Aβに関連する病態および疾患を治療するための、可溶性Aβに高い親和性を有する抗体の使用 |
CA2451998A1 (en) | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Anti-a.beta. antibodies |
US20030082191A1 (en) | 2001-08-29 | 2003-05-01 | Poduslo Joseph F. | Treatment for central nervous system disorders |
US7002711B2 (en) * | 2001-08-31 | 2006-02-21 | Kabushiki Kaisha Toshiba | Image reading device and method |
US7781413B2 (en) | 2001-10-31 | 2010-08-24 | Board Of Regents, The University Of Texas System | SEMA3B inhibits tumor growth and induces apoptosis in cancer cells |
CN1292655C (zh) | 2001-11-08 | 2007-01-03 | 蛋白质设计实验室股份有限公司 | IgG抗体稳定的液态药物制剂 |
EP1572894B1 (en) | 2001-11-21 | 2016-04-13 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto |
AU2002366355A1 (en) | 2001-12-17 | 2003-06-30 | New York State Office Of Mental Health | SEQUESTRATION OF ABeta IN THE PERIPHERY IN THE ABSENCE OF IMMUNOMODULATING AGENT AS A THERAPEUTIC APPROACH FOR THE TREATMENT OR PREVENTION OF BETA-AMYLOID RELATED DISEASES |
AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
WO2003072736A2 (en) | 2002-02-21 | 2003-09-04 | Duke University | Reagents and treatment methods for autoimmune diseases |
MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
DE60336902D1 (de) | 2002-07-19 | 2011-06-09 | Cytos Biotechnology Ag | Impfstoffzusammensetzungen enthaltende amyloid beta 1-6 antigenarrays |
EP1911765A3 (en) | 2002-07-24 | 2008-04-23 | Innogenetics N.V. | Prevention, treatment and diagnosis of diseases associated with Beta-Amyloid formation and/or aggregation |
WO2004031400A2 (en) | 2002-10-01 | 2004-04-15 | Northwestern University | Amyloid beta-derived diffusible ligands (addls), addl-surrogates, addl-binding molecules, and uses thereof |
US20060019850A1 (en) | 2002-10-31 | 2006-01-26 | Korzenski Michael B | Removal of particle contamination on a patterned silicon/silicon dioxide using dense fluid/chemical formulations |
FR2846667B1 (fr) | 2002-11-06 | 2004-12-31 | Pasteur Institut | Fragments variables d'anticorps de camelides a chaine unique diriges contre le peptide beta-amyloide 1-42 et leurs applications pour le diagnostic et le traitement des maladies neuroagregatives |
US20040191243A1 (en) | 2002-12-13 | 2004-09-30 | Bei Chen | System and method for stabilizing antibodies with histidine |
US6787129B1 (en) | 2003-01-13 | 2004-09-07 | Zenitech Llc | Castor polyester as gloss agents in anionic systems |
US20060188512A1 (en) | 2003-02-01 | 2006-08-24 | Ted Yednock | Active immunization to generate antibodies to solble a-beta |
ES2344645T3 (es) | 2003-02-10 | 2010-09-02 | Applied Molecular Evolution, Inc. | Moleculas de union al abeta. |
KR101208291B1 (ko) | 2003-04-04 | 2012-12-05 | 노파르티스 아게 | 고농도 항체 및 단백질 제형 |
EP1480041A1 (en) | 2003-05-22 | 2004-11-24 | Innogenetics N.V. | Method for the prediction, diagnosis and differential diagnosis of Alzheimer's disease |
TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
WO2005002444A1 (en) | 2003-07-07 | 2005-01-13 | Agency For Science, Technology And Research | Method and apparatus for extracting third ventricle information |
WO2005014041A2 (en) | 2003-07-24 | 2005-02-17 | Novartis Ag | Use of an amyloid beta dna vaccine for the treatment and/or prevention of amyloid diseases |
WO2005026211A2 (en) | 2003-09-05 | 2005-03-24 | Eli Lilly And Company | Anti-ghrelin antibodies |
CA2445743A1 (en) | 2003-10-08 | 2005-04-08 | The University Of British Columbia | Methods for modulating neuronal responses |
AU2004299501B2 (en) | 2003-12-17 | 2010-12-23 | Wyeth Llc | Immunogenic peptide carrier conjugates and methods of producing same |
PL2336147T3 (pl) | 2003-12-17 | 2015-01-30 | Janssen Alzheimer Immunotherap | Immunogenne koniugaty A beta z nośnikiem peptydowym i sposoby ich otrzymywania |
TWI355389B (en) | 2004-07-30 | 2012-01-01 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide a |
EP1797182A2 (en) | 2004-10-05 | 2007-06-20 | Wyeth a Corporation of the State of Delaware | Methods and compositions for improving recombinant protein production |
WO2006047670A2 (en) | 2004-10-26 | 2006-05-04 | Wyeth | Methods for assessing antibodies to neurodegenerative disease-associated antigens |
PE20061329A1 (es) | 2004-12-15 | 2006-12-08 | Neuralab Ltd | Anticuerpos ab humanizados para mejorar la cognicion |
WO2006066171A1 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Amyloid βετα antibodies for use in improving cognition |
ES2396555T3 (es) | 2004-12-15 | 2013-02-22 | Janssen Alzheimer Immunotherapy | Anticuerpos que reconocen péptido beta amiloide |
US20060240486A1 (en) | 2004-12-15 | 2006-10-26 | Johnson-Wood Kelly L | Immunoprecipitation-based assay for predicting in vivo efficacy of beta-amyloid antibodies |
WO2006066118A2 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Contextual fear test for predicting efficacy of alzheimer immunotherapeutic treatment |
GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
PE20061201A1 (es) | 2005-01-28 | 2006-11-03 | Wyeth Corp | Formulaciones liquidas estabilizadas de polipeptido |
EA201100177A1 (ru) | 2005-06-17 | 2011-06-30 | Элан Фарма Интернэшнл Лимитед | СПОСОБЫ ОЧИСТКИ АНТИТЕЛ К β-АМИЛОИДУ |
FR2887558B1 (fr) | 2005-06-28 | 2007-08-17 | Aubert & Duval Soc Par Actions | Composition d'acier inoxydable martensitique, procede de fabrication d'une piece mecanique a partir de cet acier et piece ainsi obtenue |
EP1910364B1 (en) | 2005-07-18 | 2012-03-21 | Merck Sharp & Dohme Corp. | Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease |
WO2010044803A1 (en) | 2008-10-17 | 2010-04-22 | Elan Pharma International Limited | Treatment of amyloidogenic diseases |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
JP2011526240A (ja) | 2007-04-18 | 2011-10-06 | ヤンセン アルツハイマー イミュノセラピー | 脳アミロイド血管症の予防および治療 |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
CN102016059B (zh) * | 2007-12-28 | 2014-10-22 | 依兰制药公司 | 淀粉样变性的治疗和预防 |
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CN104122400A (zh) * | 2014-07-01 | 2014-10-29 | 上海依科赛生物制品有限公司 | 一种人体β淀粉样蛋白检测试剂盒及其用途 |
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