DE60108111T2 - Synthetische immunogene jedoch nicht amyloidogene peptide, die homolog zu amyloid beta sind und deren verwendung zur induktion einer immunantwort gegen amyloid beta und amyloidaggregate - Google Patents
Synthetische immunogene jedoch nicht amyloidogene peptide, die homolog zu amyloid beta sind und deren verwendung zur induktion einer immunantwort gegen amyloid beta und amyloidaggregate Download PDFInfo
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- DE60108111T2 DE60108111T2 DE60108111T DE60108111T DE60108111T2 DE 60108111 T2 DE60108111 T2 DE 60108111T2 DE 60108111 T DE60108111 T DE 60108111T DE 60108111 T DE60108111 T DE 60108111T DE 60108111 T2 DE60108111 T2 DE 60108111T2
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Landscapes
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| US205578P | 2000-05-22 | ||
| PCT/US2001/016322 WO2001090182A2 (en) | 2000-05-22 | 2001-05-22 | Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits |
Publications (2)
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| DE60108111D1 DE60108111D1 (de) | 2005-02-03 |
| DE60108111T2 true DE60108111T2 (de) | 2005-12-08 |
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| DE60108111T Expired - Lifetime DE60108111T2 (de) | 2000-05-22 | 2001-05-22 | Synthetische immunogene jedoch nicht amyloidogene peptide, die homolog zu amyloid beta sind und deren verwendung zur induktion einer immunantwort gegen amyloid beta und amyloidaggregate |
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| US7588766B1 (en) | 2000-05-26 | 2009-09-15 | Elan Pharma International Limited | 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 |
| US6761888B1 (en) * | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
| US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US6905686B1 (en) | 1997-12-02 | 2005-06-14 | Neuralab Limited | Active immunization for treatment of alzheimer's disease |
| US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | 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 |
| US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
| US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | 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 |
| US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
| US7148324B1 (en) * | 1998-12-14 | 2006-12-12 | Dendreon Corporation | Compositions and methods for enhancement of major histocompatibility complex class I restricted antigen presentation |
| 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 | |
| DK1259251T3 (da) * | 2000-02-21 | 2006-03-06 | Pharmexa As | Hidtil ukendt fremgangsmåde til nedregulering af amyloid |
| KR20080017471A (ko) * | 2000-02-21 | 2008-02-26 | 파멕사 에이/에스 | 아밀로이드의 하향-조절을 위한 신규한 방법 |
| EP1309341A2 (en) | 2000-07-07 | 2003-05-14 | Lars Lannfelt | Prevention and treatment of alzheimer's disease |
| 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 |
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| US7097837B2 (en) * | 2001-02-19 | 2006-08-29 | Pharmexa A/S | Synthetic vaccine agents |
| US6815175B2 (en) | 2001-03-16 | 2004-11-09 | Cornell Research Foundation, Inc. | Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder |
| WO2002074931A2 (en) * | 2001-03-20 | 2002-09-26 | University Of Chicago | Inhibitors and disassemblers of fibrillogenesis |
| MY144532A (en) * | 2001-08-20 | 2011-09-30 | Lundbeck & Co As H | Novel method for down-regulation of amyloid |
| US7479482B2 (en) | 2001-11-21 | 2009-01-20 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid β, prion protein, amylin, α-synuclein, or polyglutamine repeats for induction of an immune response thereto |
| MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| AU2003256578A1 (en) * | 2002-07-17 | 2004-02-02 | Intellect Neurosciences, Inc. | Peptides and methods of screening immunogenic peptide vaccines against alzheimer's disease |
| CA2506037A1 (en) * | 2002-11-14 | 2004-06-10 | Adherex Technologies, Inc. | Compounds and methods for modulating desmosomal and atypical cadherin-mediated cell adhesion |
| US20070010435A1 (en) * | 2002-12-19 | 2007-01-11 | New York University | Method for treating amyloid disease |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| GB0310270D0 (en) * | 2003-05-03 | 2003-06-11 | Univ Edinburgh | Biomolecular devices |
| TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
| EP2479184A3 (en) * | 2003-12-17 | 2013-09-04 | Janssen Alzheimer Immunotherapy | Beta immunogenic peptide carrier conjugates and methods of producing the same |
| SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
| RU2007116346A (ru) * | 2004-10-06 | 2008-11-20 | Хироши МОРИ (JP) | Мутированный амилоидный белок |
| EP1838348B1 (en) | 2004-12-15 | 2013-06-26 | Janssen Alzheimer Immunotherapy | Humanized amyloid beta antibodies for use in improving cognition |
| ES2396555T3 (es) * | 2004-12-15 | 2013-02-22 | Janssen Alzheimer Immunotherapy | Anticuerpos que reconocen péptido beta amiloide |
| PE20061401A1 (es) * | 2004-12-15 | 2006-12-23 | Neuralab Ltd | ANTICUERPOS Aß PARA MEJORAR LA COGNICION |
| CA2607004C (en) | 2005-05-05 | 2016-01-26 | Sensient Flavors Inc. | Production of beta-glucans and mannans |
| EP1954718B1 (en) * | 2005-11-30 | 2014-09-03 | AbbVie Inc. | Anti-a 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 |
| RU2432362C2 (ru) | 2005-11-30 | 2011-10-27 | Эбботт Лэборетриз | Моноклональные антитела и их применения |
| EP2325209A3 (en) | 2006-03-23 | 2011-08-03 | BioArtic 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 |
| US20090123488A1 (en) * | 2006-08-14 | 2009-05-14 | Thymon, Llc | Compositions and methods for the treatment and prophylaxis of Alzheimer's disease |
| WO2008021295A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of multiple strains and subtypes of hiv-1 |
| US8188046B2 (en) | 2006-10-16 | 2012-05-29 | University Of South Florida | Amyloid beta peptides and methods of use |
| US8455626B2 (en) * | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| US20100173277A1 (en) * | 2007-02-15 | 2010-07-08 | Fukuoka University | Agent for Suppressing Rejection in Organ Transplantation Comprising Anti-HMGB-1 Antibody |
| WO2008099913A1 (ja) * | 2007-02-15 | 2008-08-21 | Kumamoto University | ヒトhmgb-1に特異的に結合する抗体を有効成分として含有する治療剤 |
| JP5241518B2 (ja) * | 2007-02-15 | 2013-07-17 | 国立大学法人九州大学 | 抗ｈｍｇｂ−１抗体を含む間質性肺疾患治療剤 |
| EP2486928A1 (en) * | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
| US7618944B2 (en) * | 2007-03-01 | 2009-11-17 | Intezyne Technologies, Inc. | Encapsulated amyloid-beta peptides |
| 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 |
| US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| DK2182983T3 (da) | 2007-07-27 | 2014-07-14 | Janssen Alzheimer Immunotherap | Behandling af amyloidogene sygdomme med humaniserede anti-abeta antistoffer |
| JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
| PT2207568T (pt) | 2007-11-16 | 2017-09-01 | Univ Rockefeller | Anticorpos específicos para a forma de protofibrilha da proteína beta-amilóide |
| RU2546234C2 (ru) * | 2008-07-01 | 2015-04-10 | Де Стат Дер Недерланден, Верт.Дор Де Министер Ван Ввс | Вакцина против интермедиата с амилоидным сворачиванием |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| TWI508976B (zh) * | 2009-04-21 | 2015-11-21 | Univ Rockefeller | 對β－類澱粉蛋白之基原纖維形式具專一性之抗體 |
| WO2010129674A2 (en) | 2009-05-05 | 2010-11-11 | New York University | Immunotherapy targeting of the shared abnormal conformational state of amyloidogenic peptides/proteins |
| JP5917394B2 (ja) * | 2009-06-10 | 2016-05-11 | ニューヨーク・ユニバーシティ | 病理学的タウタンパク質の免疫学的標的化方法 |
| CN101920008B (zh) * | 2009-06-15 | 2013-07-31 | 浙江仙琚制药股份有限公司 | 包含Aβ40多肽和铝佐剂的制剂以及纯化Aβ40多肽的方法 |
| WO2011130377A2 (en) | 2010-04-15 | 2011-10-20 | Abbott Laboratories | Amyloid-beta binding proteins |
| EP3533803B1 (en) | 2010-08-14 | 2021-10-27 | AbbVie Inc. | Anti-amyloid-beta antibodies |
| WO2013013056A1 (en) | 2011-07-19 | 2013-01-24 | New York University | Method for treating amyloid disease |
| 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 |
| JO3537B1 (ar) | 2014-07-10 | 2020-07-05 | Bioarctic Neuroscience Ab | أجسام مضادة لييفية أولية لاميلويد بيتا الببتيد ab المحسنة |
| US11970521B2 (en) * | 2016-08-20 | 2024-04-30 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Neuroprotective beta amyloid core peptides and peptidomimetic derivatives |
| CN119053345A (zh) | 2022-02-28 | 2024-11-29 | 特瑞德姆生物科技有限责任两合公司 | 由至少一种β-葡聚糖或甘露聚糖组成或包含至少一种β-葡聚糖或甘露聚糖的偶联物 |
| CA3243636A1 (en) | 2022-02-28 | 2023-08-31 | Tridem Bioscience Gmbh & Co Kg | CONJUGATED COMPRISING AT LEAST ONE β-GLUCANE OR ONE MANNANA |
Family Cites Families (7)
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|---|---|---|---|---|
| DE69521700T2 (de) | 1994-05-25 | 2001-10-25 | John Mcmichael | Mittel und methoden zur behandlung von plaque-krankheiten |
| US5688651A (en) * | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
| 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 |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic 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 |
| CA2312475C (en) | 1997-12-03 | 2010-08-03 | Brigham And Women's Hospital | Method of suppressing .beta.-amyloid-related changes in alzheimer's disease |
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2001
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- 2001-05-22 US US09/861,847 patent/US6713450B2/en not_active Expired - Lifetime
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- 2001-05-22 PT PT01941526T patent/PT1284998E/pt unknown
- 2001-05-22 CN CNB018100058A patent/CN1249085C/zh not_active Expired - Fee Related
- 2001-05-22 AU AU7487301A patent/AU7487301A/xx active Pending
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| PT1284998E (pt) | 2005-06-30 |
| ES2238049T3 (es) | 2005-08-16 |
| IL152625A0 (en) | 2003-06-24 |
| AU7487301A (en) | 2001-12-03 |
| AU2001274873B2 (en) | 2006-10-05 |
| WO2001090182A3 (en) | 2002-05-23 |
| JP2003534351A (ja) | 2003-11-18 |
| NZ521939A (en) | 2004-04-30 |
| EP1284998B1 (en) | 2004-12-29 |
| CA2408925A1 (en) | 2001-11-29 |
| CN1249085C (zh) | 2006-04-05 |
| IL152625A (en) | 2009-12-24 |
| DE60108111D1 (de) | 2005-02-03 |
| ATE286072T1 (de) | 2005-01-15 |
| US20090081204A1 (en) | 2009-03-26 |
| US20040043935A1 (en) | 2004-03-04 |
| US6713450B2 (en) | 2004-03-30 |
| US7427655B2 (en) | 2008-09-23 |
| CN1444598A (zh) | 2003-09-24 |
| ZA200207992B (en) | 2003-07-02 |
| WO2001090182A2 (en) | 2001-11-29 |
| US7700107B2 (en) | 2010-04-20 |
| US20020077288A1 (en) | 2002-06-20 |
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