RU2730668C2 - Гуманизированные тау-антитела при болезни альцгеймера - Google Patents
Гуманизированные тау-антитела при болезни альцгеймера Download PDFInfo
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- RU2730668C2 RU2730668C2 RU2017120688A RU2017120688A RU2730668C2 RU 2730668 C2 RU2730668 C2 RU 2730668C2 RU 2017120688 A RU2017120688 A RU 2017120688A RU 2017120688 A RU2017120688 A RU 2017120688A RU 2730668 C2 RU2730668 C2 RU 2730668C2
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| WO2019161384A1 (en) * | 2018-02-19 | 2019-08-22 | New York University | Tau single domain antibodies |
| WO2019186276A2 (en) | 2018-03-28 | 2019-10-03 | Axon Neuroscience Se | Antibody-based methods of detecting and treating alzheimer's disease |
| KR102787585B1 (ko) * | 2018-05-03 | 2025-03-27 | 워싱턴 유니버시티 | 부위-특이적 타우 인산화에 기반한 진단 및 치료 방법 |
| BR112020023082A2 (pt) | 2018-05-15 | 2021-02-09 | Voyager Therapeutics, Inc. | composições e métodos para o tratamento de doença de parkinson |
| WO2020077380A1 (en) * | 2018-10-17 | 2020-04-23 | The University Of Queensland | Methods and compositions for treating tauopathies |
| SG11202104549TA (en) * | 2018-11-08 | 2021-05-28 | Prothena Biosciences Ltd | Antibodies recognizing tau |
| EP3918323A4 (en) | 2019-01-30 | 2022-12-28 | TrueBinding, Inc. | ANTI-GAL3 ANTIBODIES AND USES THEREOF |
| PE20212324A1 (es) | 2019-03-03 | 2021-12-14 | Prothena Biosciences Ltd | Anticuerpos que reconocen tau |
| TWI877179B (zh) * | 2019-06-27 | 2025-03-21 | 德商百靈佳殷格翰國際股份有限公司 | 抗-angpt2抗體 |
| JP7780200B2 (ja) * | 2019-08-13 | 2025-12-04 | ワシントン・ユニバーシティ | Ｍｔｂｒタウアイソフォームを検出する方法およびその使用 |
| WO2021048619A2 (en) | 2019-09-09 | 2021-03-18 | Axon Neuroscience Se | Biomarkers and treatments of alzheimer's disease and mild cognitive impairment |
| JP7668027B2 (ja) | 2019-09-10 | 2025-04-24 | ワシントン・ユニバーシティ | 部位特異的タウリン酸化をベースとする診断および処置のための血液ベースアッセイ |
| AU2020403021A1 (en) * | 2019-12-12 | 2022-06-23 | Alector Llc | Methods of use of anti-CD33 antibodies |
| WO2021173962A1 (en) * | 2020-02-28 | 2021-09-02 | Genemo, Inc. | Methods and materials for diagnosis and treatment of neuronal disorder |
| WO2021242776A2 (en) | 2020-05-26 | 2021-12-02 | Truebinding, Inc. | Methods of treating inflammatory diseases by blocking galectin-3 |
| WO2022066694A1 (en) * | 2020-09-22 | 2022-03-31 | Clarence Smith Kathleen E | Pharmaceutical combination for the treatment of human hypocholinergic disorders |
| CN112625129B (zh) * | 2020-11-26 | 2022-05-20 | 江苏荃信生物医药股份有限公司 | 一种抗人白介素23及包含其的试剂盒及其检测方法 |
| US20250034559A1 (en) | 2021-11-17 | 2025-01-30 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of tau-related disorders |
| KR20250044781A (ko) * | 2022-08-10 | 2025-04-01 | 주식회사 엔케이맥스 | 확장된 자연 살해 세포를 이용한 알츠하이머병 치료 방법 |
| CN120019071A (zh) | 2022-09-15 | 2025-05-16 | 沃雅戈治疗公司 | Tau结合化合物 |
| CA3237624A1 (en) * | 2023-07-28 | 2025-04-24 | Genentech, Inc. | NEW USES FOR OMALIZUMAB |
| WO2025122634A1 (en) | 2023-12-05 | 2025-06-12 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of tau-related disorders |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012049570A1 (en) * | 2010-10-11 | 2012-04-19 | Panima Pharmaceuticals Ag | Human anti-tau antibodies |
| WO2013041962A1 (en) * | 2011-09-19 | 2013-03-28 | Axon Neuroscience Se | Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease |
| RU2011152816A (ru) * | 2009-06-10 | 2013-07-20 | Ф.Хоффманн-Ля Рош Аг | ПРИМЕНЕНИЕ АНТИТЕЛА ПРОТИВ Tau pS422 ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ ГОЛОВНОГО МОЗГА |
| WO2014100600A2 (en) * | 2012-12-21 | 2014-06-26 | Biogen Idec Ma Inc. | Human anti-tau antibodies |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| HU196394B (en) | 1986-06-27 | 1988-11-28 | Richter Gedeon Vegyeszet | Process for preparing 2-halogenated ergoline derivatives |
| US4880935A (en) | 1986-07-11 | 1989-11-14 | Icrf (Patents) Limited | Heterobifunctional linking agents derived from N-succinimido-dithio-alpha methyl-methylene-benzoates |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
| FI102355B1 (fi) | 1988-02-11 | 1998-11-30 | Bristol Myers Squibb Co | Menetelmä yhdistävän välikappaleen omaavien antrasykliini-immunokonjugaattien valmistamiseksi |
| US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
| US5766883A (en) | 1989-04-29 | 1998-06-16 | Delta Biotechnology Limited | Polypeptides |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| US5112596A (en) | 1990-04-23 | 1992-05-12 | Alkermes, Inc. | Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability |
| US5268164A (en) | 1990-04-23 | 1993-12-07 | Alkermes, Inc. | Increasing blood-brain barrier permeability with permeabilizer peptides |
| US5278299A (en) | 1991-03-18 | 1994-01-11 | Scripps Clinic And Research Foundation | Method and composition for synthesizing sialylated glycosyl compounds |
| US6797492B2 (en) | 1991-05-17 | 2004-09-28 | Merck & Co., Inc. | Method for reducing the immunogenicity of antibody variable domains |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| WO1993010260A1 (en) | 1991-11-21 | 1993-05-27 | The Board Of Trustees Of The Leland Stanford Junior University | Controlling degradation of glycoprotein oligosaccharides by extracellular glycosisases |
| US5262522A (en) | 1991-11-22 | 1993-11-16 | Immunex Corporation | Receptor for oncostatin M and leukemia inhibitory factor |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| AU677216B2 (en) | 1992-07-27 | 1997-04-17 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Targeting of liposomes to the blood-brain barrier |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| US5457035A (en) | 1993-07-23 | 1995-10-10 | Immunex Corporation | Cytokine which is a ligand for OX40 |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| CU22615A1 (es) | 1994-06-30 | 2000-02-10 | Centro Inmunologia Molecular | Procedimiento de obtención de anticuerpos monoclonales murinos menos inmunogénicos. anticuerpos monoclonales obtenidos |
| CA2142190C (fr) | 1995-02-14 | 1998-01-27 | Marc Lessard | Conduite d'exfiltration d'air use |
| US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| DK1516628T3 (da) | 1995-07-27 | 2013-09-08 | Genentech Inc | Stabil, isotonisk lyofiliseret proteinformulering |
| DE69626849T2 (de) | 1995-12-22 | 2003-12-24 | Bristol-Myers Squibb Co., Princeton | Verzweigte hydrazongruppen enthaltende kuppler |
| GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
| WO1998044955A1 (en) | 1997-04-09 | 1998-10-15 | Mindset Ltd. | Recombinant antibodies specific for beta-amyloid ends, dna encoding and methods of use thereof |
| GB2339430A (en) | 1997-05-21 | 2000-01-26 | Biovation Ltd | Method for the production of non-immunogenic proteins |
| JP2002506353A (ja) | 1997-06-24 | 2002-02-26 | ジェネンテック・インコーポレーテッド | ガラクトシル化糖タンパク質の方法及び組成物 |
| WO1999022764A1 (en) | 1997-10-31 | 1999-05-14 | Genentech, Inc. | Methods and compositions comprising glycoprotein glycoforms |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| US6242195B1 (en) | 1998-04-02 | 2001-06-05 | Genentech, Inc. | Methods for determining binding of an analyte to a receptor |
| DK1068241T3 (da) | 1998-04-02 | 2008-02-04 | Genentech Inc | Antistofvarianter og fragmenter deraf |
| US6528624B1 (en) | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
| PT1071700E (pt) | 1998-04-20 | 2010-04-23 | Glycart Biotechnology Ag | Modificação por glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
| ES2694002T3 (es) | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
| ATE326700T1 (de) | 1999-09-09 | 2006-06-15 | Max Planck Gesellschaft | SCREENING NACH INHIBITOREN VON ßGEPAARTEN HELIKALEN FILAMENTENß |
| WO2001062801A2 (en) | 2000-02-24 | 2001-08-30 | Washington University | Humanized antibodies that sequester amyloid beta peptide |
| US6514221B2 (en) | 2000-07-27 | 2003-02-04 | Brigham And Women's Hospital, Inc. | Blood-brain barrier opening |
| AU2001286930A1 (en) | 2000-08-30 | 2002-03-13 | The Board Of Trustees Of The Leland Stanford Junior University | Glucocorticoid blocking agents for increasing blood-brain barrier permeability |
| US7034036B2 (en) | 2000-10-30 | 2006-04-25 | Pain Therapeutics, Inc. | Inhibitors of ABC drug transporters at the blood-brain barrier |
| US20030083299A1 (en) | 2000-11-04 | 2003-05-01 | Ferguson Ian A. | Non-invasive delivery of polypeptides through the blood-brain barrier |
| DE10121982B4 (de) | 2001-05-05 | 2008-01-24 | Lts Lohmann Therapie-Systeme Ag | Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung |
| US20030129186A1 (en) | 2001-07-25 | 2003-07-10 | Biomarin Pharmaceutical Inc. | Compositions and methods for modulating blood-brain barrier transport |
| CA2838062C (en) | 2001-08-03 | 2015-12-22 | Roche Glycart Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
| NZ532526A (en) | 2001-10-25 | 2007-01-26 | Genentech Inc | Compositions comprising a glycoprotein having a Fc region |
| US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
| US20030162695A1 (en) | 2002-02-27 | 2003-08-28 | Schatzberg Alan F. | Glucocorticoid blocking agents for increasing blood-brain barrier permeability |
| DE60320258T2 (de) | 2002-07-12 | 2009-06-25 | Axon Neuroscience Forschungs- Und Entwicklungs Gmbh | Transgenes tier welches das trunkierte alzheimer tau protein exprimiert |
| JP4741838B2 (ja) | 2002-07-31 | 2011-08-10 | シアトル ジェネティクス，インコーポレーテッド | 癌、自己免疫疾患または感染症を治療するための薬物結合体およびその使用 |
| CA2791165C (en) | 2002-12-03 | 2015-02-24 | Blanchette Rockefeller Neurosciences Institute | A conjugate comprising cholesterol linked to tetracycline |
| CA2511606A1 (en) | 2002-12-24 | 2004-07-15 | Neurochem (International) Limited | Therapeutic formulations for the treatment of beta-amyloid related diseases |
| JP2007505142A (ja) | 2003-09-10 | 2007-03-08 | セダーズ−シナイ メディカル センター | 血液脳関門を通過する薬剤のカリウムチャネル媒介性送達 |
| CN104998273A (zh) | 2003-11-06 | 2015-10-28 | 西雅图基因公司 | 能够与配体偶联的单甲基缬氨酸化合物 |
| US7691962B2 (en) | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
| EP3088004B1 (en) | 2004-09-23 | 2018-03-28 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| WO2012045882A2 (en) * | 2010-10-07 | 2012-04-12 | Ac Immune S.A. | Pharmaceutical composition |
| KR102132041B1 (ko) * | 2012-04-05 | 2020-07-09 | 에이씨 이뮨 에스.에이. | 인간화된 타우 항체 |
| RS61431B1 (sr) * | 2014-11-19 | 2021-03-31 | Axon Neuroscience Se | Humanizovana antitela na tau u alchajmerovoj bolesti |
-
2015
- 2015-11-18 RS RS20210132A patent/RS61431B1/sr unknown
- 2015-11-18 PL PL15837211T patent/PL3221349T3/pl unknown
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- 2015-11-18 CA CA2966964A patent/CA2966964A1/en not_active Abandoned
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- 2017-04-25 IL IL251921A patent/IL251921B/en unknown
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2011152816A (ru) * | 2009-06-10 | 2013-07-20 | Ф.Хоффманн-Ля Рош Аг | ПРИМЕНЕНИЕ АНТИТЕЛА ПРОТИВ Tau pS422 ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ ГОЛОВНОГО МОЗГА |
| WO2012049570A1 (en) * | 2010-10-11 | 2012-04-19 | Panima Pharmaceuticals Ag | Human anti-tau antibodies |
| WO2013041962A1 (en) * | 2011-09-19 | 2013-03-28 | Axon Neuroscience Se | Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease |
| WO2014100600A2 (en) * | 2012-12-21 | 2014-06-26 | Biogen Idec Ma Inc. | Human anti-tau antibodies |
Non-Patent Citations (1)
| Title |
|---|
| YAGHOUB SAFDARI et al., Antibody humanization methods - a review and update, Biotechnology and Genetic Engineering Reviews, 2013, Vol. 29, No. 2, pp.175-186. * |
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