CA2675340C - Diagnosis and treatment of alzheimer's and other neurodementing diseases - Google Patents
Diagnosis and treatment of alzheimer's and other neurodementing diseases Download PDFInfo
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- CA2675340C CA2675340C CA2675340A CA2675340A CA2675340C CA 2675340 C CA2675340 C CA 2675340C CA 2675340 A CA2675340 A CA 2675340A CA 2675340 A CA2675340 A CA 2675340A CA 2675340 C CA2675340 C CA 2675340C
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
Landscapes
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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| EP07000521A EP1944315A1 (en) | 2007-01-11 | 2007-01-11 | Prophylaxis and therapy of alzheimer's disease and other neurodementing diseases |
| EP07000507A EP1944314A1 (en) | 2007-01-11 | 2007-01-11 | Diagnosis of Alzheimer's disease and other neurodementing disorders |
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| US98166707P | 2007-10-22 | 2007-10-22 | |
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| PCT/IB2008/000456 WO2008084402A2 (en) | 2007-01-11 | 2008-01-11 | Diagnosis and treatment of alzheimer's and other neurodementing diseases |
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| CA2675340A1 CA2675340A1 (en) | 2008-07-17 |
| CA2675340C true CA2675340C (en) | 2018-07-31 |
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| US20090280114A1 (en) * | 2002-04-12 | 2009-11-12 | Ramot At Tel Aviv University Ltd. | Prevention of brain inflammation as a result of induced autoimmune response |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| ES2527661T3 (es) | 2005-11-30 | 2015-01-28 | Abbvie Inc. | Método de exploración, proceso para purificar oligómeros Abeta no difundibles, anticuerpos selectivos contra dichos oligómeros Abeta no difundibles y un proceso para fabricar dichos anticuerpos |
| KR101667623B1 (ko) | 2005-11-30 | 2016-10-19 | 애브비 인코포레이티드 | 아밀로이드 베타 단백질에 대한 모노클로날 항체 및 이의 용도 |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| US8895004B2 (en) | 2007-02-27 | 2014-11-25 | AbbVie Deutschland GmbH & Co. KG | Method for the treatment of amyloidoses |
| EP2143447A1 (en) * | 2008-07-11 | 2010-01-13 | Universität Konstanz | Bioconjugates comprising Aß-autoantibody-specific epitopes for active immunotherapy and diagnosis of Alzheimer's disease |
| AU2010216512B2 (en) * | 2009-02-20 | 2016-06-30 | 2-Bbb Medicines B.V. | Glutathione-based drug delivery system |
| KR101095630B1 (ko) * | 2009-06-17 | 2011-12-19 | 주식회사 이노파마스크린 | 베타 아밀로이드 펩타이드와 ｖｅｇｆ의 상호작용을 억제하는 물질을 탐색 방법 및 그에 의해서 탐색된 저해제 |
| DE102009034119A1 (de) * | 2009-07-20 | 2011-01-27 | Philipps-Universität Marburg | Verfahren, insbesondere Enzyme-linked Immunosorbent Assay (ELISA), zum in vitro Nachweis von Amyloid beta Autoantikörpern, Mikrotiterplatte und Testkit |
| DK2462131T3 (en) | 2009-08-07 | 2015-01-05 | American Life Science Pharmaceuticals Inc | Preparations and Methods for Treating Beta-Amyloid-Related Diseases |
| MX360403B (es) | 2010-04-15 | 2018-10-31 | Abbvie Inc | Proteinas de union a amiloide beta. |
| MX358739B (es) | 2010-08-14 | 2018-09-03 | Abbvie Inc Star | Proteinas de union a amiloide beta. |
| GB201112056D0 (en) | 2011-07-14 | 2011-08-31 | Univ Leuven Kath | Antibodies |
| ES2496341T3 (es) * | 2011-10-04 | 2014-09-18 | Affiris Ag | Procedimiento para detectar anticuerpos Aß-específicos en una muestra biológica |
| KR101190573B1 (ko) * | 2011-10-07 | 2012-10-18 | 대한민국 | 혈액 내 아밀로이드-베타 항체에 특이적으로 결합하는 신규 Ａβ２２（ｐＥ）－４２ 펩티드를 유효성분으로 포함하는 치매 진단용 키트 |
| CN104662423A (zh) * | 2012-03-13 | 2015-05-27 | 杨森阿尔茨海默氏症免疫治疗公司 | 阿兹海默氏病的诊断、预后和监测中的寡聚体Aβ |
| AU2013203043B2 (en) * | 2013-03-15 | 2016-10-06 | Takeda Pharmaceutical Company Limited | Methods to produce a human plasma-derived igg preparation enriched in brain disease-related natural iggs |
| WO2015111430A1 (ja) * | 2014-01-21 | 2015-07-30 | 株式会社 島津製作所 | Ａｐｐ切断型ペプチドの測定方法 |
| WO2015121339A1 (en) * | 2014-02-14 | 2015-08-20 | RUHR-UNIVERSITäT BOCHUM | Biosensor for conformation and secondary structure analysis |
| US10035823B2 (en) | 2014-09-29 | 2018-07-31 | The Regents Of The University Of California | Compositions for expanding regulatory T cells (TREG), and treating autoimmune and inflammatory diseases and conditions |
| ES2663623T3 (es) * | 2015-01-12 | 2018-04-16 | Heraeus Deutschland GmbH & Co. KG | Uso de una composición eléctricamente conductora como adhesivo eléctricamente conductor para conectar mecánica y eléctricamente conductores eléctricos con los contactos eléctricos de células solares |
| ES2834484T3 (es) | 2016-11-21 | 2021-06-17 | Univ Ruhr Bochum | Método para la preselección de fármacos para enfermedades de plegamiento incorrecto de proteínas |
| WO2019023247A1 (en) | 2017-07-25 | 2019-01-31 | Immutics, Inc. | TREATMENT OF CANCER BY BLOCKING THE INTERACTION OF TIM-3 AND ITS LIGAND |
| EP3728323A4 (en) * | 2017-12-19 | 2022-01-26 | Surrozen Operating, Inc. | ANTI-FRIZZLED ANTIBODIES AND METHODS OF USE |
| EP3731867A4 (en) | 2017-12-19 | 2022-04-06 | Surrozen Operating, Inc. | Anti-lrp5/6 antibodies and methods of use |
| US11773171B2 (en) * | 2017-12-19 | 2023-10-03 | Surrozen Operating, Inc. | WNT surrogate molecules and uses thereof |
| AU2020214796A1 (en) | 2019-01-30 | 2021-07-29 | Truebinding, Inc. | Anti-Gal3 antibodies and uses thereof |
| US12281166B2 (en) | 2020-05-26 | 2025-04-22 | Truebinding, Inc. | Methods of treating inflammatory diseases by blocking Galectin-3 |
| WO2022104280A1 (en) | 2020-11-16 | 2022-05-19 | Surrozen Operating, Inc. | Liver-specific wnt signal enhancing molecules and uses thereof |
| AU2022227686A1 (en) | 2021-02-25 | 2023-07-27 | Lyell Immunopharma, Inc. | Ror1 targeting chimeric antigen receptor |
| TW202300517A (zh) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | 抗類澱粉β抗體及其用途 |
| WO2022251048A1 (en) | 2021-05-24 | 2022-12-01 | Eli Lilly And Company | Anti-amyloid beta antibodies and uses thereof |
| AR133829A1 (es) | 2023-09-15 | 2025-11-05 | Othair Prothena Ltd | Agentes penetrantes de células y usos de los mismos |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| CA1339014C (en) | 1987-10-08 | 1997-03-25 | Ronald E. Majocha | Antibodies to a4 amyloid peptide |
| WO1990003430A1 (en) | 1988-09-23 | 1990-04-05 | Cetus Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| ATE297465T1 (de) | 1991-11-25 | 2005-06-15 | Enzon Inc | Verfahren zur herstellung von multivalenten antigenbindenden proteinen |
| ATE239797T1 (de) * | 1993-01-25 | 2003-05-15 | Takeda Chemical Industries Ltd | Antikörper gegen beta-amyloid oder derivative davon und seine verwendung |
| US7427392B1 (en) | 1994-11-14 | 2008-09-23 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| DE69839808D1 (de) | 1997-04-09 | 2008-09-11 | Intellect Neurosciences Inc | Für die termini des beta-amyloids spezifische, rekombinante antikörper, dafür kodierende dna und verfahren zu ihrer verwendung |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| 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 |
| US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| PT1237930E (pt) | 1999-12-08 | 2007-02-28 | Intellect Neurosciences Inc | Péptidos beta amiloides quiméricos |
| US20020182660A1 (en) | 2000-02-18 | 2002-12-05 | Fong Kei-Lai L. | N- and C-terminus specific immunoassays for full length beta-amyloid peptide-Abeta(1-40), Abeta(1-39), Abeta(1-40), Abeta(1-42) , and Abeta(1-43) |
| US20030083277A1 (en) | 2000-02-24 | 2003-05-01 | Hersh Louis B. | Use of insulin degrading enzyme (IDE) for the treatment of alzheimer's disease in patients |
| CZ304211B6 (cs) | 2000-02-24 | 2014-01-08 | Washington University | Humanizovaná protilátka, její fragment a jejich použití, polynukleová kyselina, expresní vektor, buňka a farmaceutický prostředek |
| EP2281843B1 (en) * | 2000-06-16 | 2016-10-12 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to BLyS |
| EP1172378A1 (en) | 2000-07-12 | 2002-01-16 | Richard Dr. Dodel | Human beta-amyloid antibody and use thereof for 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 |
| 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 |
| 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 |
| US20030082191A1 (en) | 2001-08-29 | 2003-05-01 | Poduslo Joseph F. | Treatment for central nervous system disorders |
| US20050208050A1 (en) * | 2001-11-09 | 2005-09-22 | Gerd Multhaup | Compounds for the diagnosis/prevention/treatment of alzheimer's disease |
| US20050227941A1 (en) | 2001-12-17 | 2005-10-13 | Karen Duff | Sequestration of ass 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 |
| MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| EP1523499A2 (en) | 2002-07-24 | 2005-04-20 | Innogenetics N.V. | Fragments of beta-amyloid as targets for vaccination against alzheimer disease |
| JP2006516535A (ja) | 2002-09-12 | 2006-07-06 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、カリフォルニア | 異なる配列のタンパク質から形成されたアミロイドに共通する高分子量凝集中間体に対して特異的な免疫原および対応する抗体 |
| CA2501091A1 (en) | 2002-10-01 | 2004-04-15 | Northwestern University | Amyloid beta-derived diffusible ligands (addls), addl-surrogates, addl-binding molecules, and uses thereof |
| US20040146512A1 (en) | 2002-10-09 | 2004-07-29 | Arnon Rosenthal | Methods of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof |
| US20050106626A1 (en) | 2002-10-20 | 2005-05-19 | George Pieczenik | Ligand binding of amyloid peptide protein epitope |
| CA2505991C (en) * | 2002-11-15 | 2018-02-27 | Genmab A/S | Human monoclonal antibodies against cd25 |
| AU2003303198A1 (en) | 2002-12-19 | 2004-07-14 | 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 |
| EP1666061A1 (en) | 2003-09-09 | 2006-06-07 | Takeda Pharmaceutical Company Limited | Use of antibody |
| AU2004272112A1 (en) | 2003-09-12 | 2005-03-24 | The Regents Of The University Of California | Monoclonal antibodies specific for conformational epitopes of prefibrillar aggregates |
| KR20120108061A (ko) * | 2003-11-28 | 2012-10-04 | 다이엑스 코포레이션 | 아포지단백질 ｅ의 ｃ말단 단편에 결합하는 항체 |
| DK1720909T3 (da) | 2004-02-23 | 2012-01-30 | Lilly Co Eli | Anti-Abeta antistof |
| SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
| CA2573293A1 (en) | 2004-07-10 | 2006-02-16 | Alexion Pharmaceuticals, Inc. | Methods for discovering antibodies specific to cancer cells and antibodies discovered thereby |
| WO2006040153A2 (en) | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Single domain camelide anti -amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenarative neural diseases such as alzheimer's disease |
| WO2006047254A1 (en) | 2004-10-22 | 2006-05-04 | Regents Of The University Of Minnesota | Assemblies of oligomeric amyloid beta protein and uses thereof |
| EP2465872A3 (en) | 2004-10-25 | 2012-12-19 | Merck Sharp & Dohme Corporation | Anti-ADDL antibodies and uses thereof |
| WO2006066171A1 (en) * | 2004-12-15 | 2006-06-22 | Neuralab Limited | Amyloid βετα antibodies for use in improving cognition |
| BRPI0519596B1 (pt) * | 2004-12-21 | 2022-01-18 | Astrazeneca Ab | Agente de ligação alvejado, anticorpo monoclonal que se liga a angiopoietina-2, molécula de ácido nucleico, vetor, e, uso do agente de ligação alvejado |
| WO2006081171A1 (en) | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
| UY29350A1 (es) | 2005-01-28 | 2006-08-31 | Wyeth Corp | Formulaciones liquidas estabilizadasde polipeptido |
| CA2599792A1 (en) | 2005-03-05 | 2006-09-14 | Abbott Gmbh & Co. Kg | Screening method, process for purifying of non-diffusible a-beta oligomers, selective antibodies against said non-diffusible a-beta oligomers and a process for manufacturing of said antibodies |
| ES2318918B1 (es) | 2005-04-01 | 2010-02-16 | Biotherapix Molecular Medicines, S.L.U. | Anticuerpos humanos con capacidad de union al peptido beta-amiloide y sus aplicaciones. |
| UY29504A1 (es) | 2005-04-29 | 2006-10-31 | Rinat Neuroscience Corp | Anticuerpos dirigidos contra el péptido amiloide beta y métodos que utilizan los mismos. |
| EP1951892A4 (en) | 2005-11-22 | 2009-01-14 | Univ Pennsylvania | ANTIBODY TREATMENT OF ALZHEIMER'S DISEASE AND RELATED DISEASES |
| KR101667623B1 (ko) | 2005-11-30 | 2016-10-19 | 애브비 인코포레이티드 | 아밀로이드 베타 단백질에 대한 모노클로날 항체 및 이의 용도 |
| KR101591206B1 (ko) | 2005-12-12 | 2016-02-04 | 에이씨 이뮨 에스.에이. | 치료적 특성을 갖는 베타 1-42 특이적인 단일클론성 항체 |
| HRP20110203T4 (hr) | 2006-03-23 | 2014-05-09 | Bioarctic Neuroscience Ab | Poboljšana protutijela selektivna za protofibrile i njihova primjena |
| AU2008206923A1 (en) * | 2007-01-17 | 2008-07-24 | Merck Serono S.A. | Process for the purification of Fc-containing proteins |
| PL2246427T3 (pl) * | 2008-02-08 | 2017-06-30 | Immunas Pharma, Inc. | Przeciwciała zdolne do wiązania się swoiście do oligomerów amyloidu beta i ich stosowanie |
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| WO2008084402A2 (en) | 2008-07-17 |
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| WO2008084402A8 (en) | 2009-08-27 |
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| US20120039897A1 (en) | 2012-02-16 |
| EP2104682A2 (en) | 2009-09-30 |
| JP2010515717A (ja) | 2010-05-13 |
| CA2675340A1 (en) | 2008-07-17 |
| AU2008204335A1 (en) | 2008-07-17 |
| ES2610474T3 (es) | 2017-04-27 |
| DK2104682T3 (en) | 2017-01-16 |
| AU2008204335B2 (en) | 2013-06-13 |
| TW200844110A (en) | 2008-11-16 |
| US8491903B2 (en) | 2013-07-23 |
| US7939075B2 (en) | 2011-05-10 |
| US20120040382A1 (en) | 2012-02-16 |
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