JP5145241B2 - 可変領域におけるグリコシル化を有するアミロイドβに対する抗体 - Google Patents
可変領域におけるグリコシル化を有するアミロイドβに対する抗体 Download PDFInfo
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- JP5145241B2 JP5145241B2 JP2008543748A JP2008543748A JP5145241B2 JP 5145241 B2 JP5145241 B2 JP 5145241B2 JP 2008543748 A JP2008543748 A JP 2008543748A JP 2008543748 A JP2008543748 A JP 2008543748A JP 5145241 B2 JP5145241 B2 JP 5145241B2
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| EP05027090.9 | 2005-12-12 | ||
| EP05027090 | 2005-12-12 | ||
| PCT/EP2006/011914 WO2007068429A1 (en) | 2005-12-12 | 2006-12-11 | Antibodies against amyloid beta 4 with glycosylated in the variable region |
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| JP2009520691A JP2009520691A (ja) | 2009-05-28 |
| JP2009520691A5 JP2009520691A5 (enExample) | 2010-01-14 |
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| AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| KR20080090408A (ko) | 2005-11-30 | 2008-10-08 | 아보트 러보러터리즈 | 항-Aβ 글로불로머 항체, 이의 항원-결합 잔기, 상응하는하이브리도마, 핵산, 벡터, 숙주 세포, 당해 항체의 제조방법, 당해 항체를 포함하는 조성물, 당해 항체의 용도 및당해 항체의 사용 방법 |
| SG10201706600VA (en) | 2005-11-30 | 2017-09-28 | Abbvie Inc | Monoclonal antibodies and uses thereof |
| BRPI0619605B8 (pt) * | 2005-12-12 | 2021-05-25 | Hoffmann La Roche | composições compreendendo moléculas de anticorpos contra amilóide beta4 com glicosilação na região variável, usos das mesmas, método de preparação de uma molécula de anticorpo, e kit |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| CN101553504A (zh) * | 2006-12-11 | 2009-10-07 | 豪夫迈·罗氏有限公司 | Aβ抗体胃肠外制剂 |
| WO2008104386A2 (en) | 2007-02-27 | 2008-09-04 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
| US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
| US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
| EP2167540B1 (en) | 2007-06-29 | 2018-02-14 | F. Hoffmann-La Roche AG | Heavy chain mutant leading to improved immunoglobulin production |
| US9163249B2 (en) | 2007-08-20 | 2015-10-20 | Glaxo Group Limited | Production methods |
| CA2701793C (en) | 2007-10-05 | 2017-04-25 | Genentech, Inc. | Use of anti-amyloid beta antibody in ocular diseases |
| NZ585516A (en) * | 2007-12-21 | 2012-07-27 | Hoffmann La Roche | Anti-cd20 antibody formulation |
| CN102076865B (zh) * | 2008-05-02 | 2016-03-16 | 西雅图基因公司 | 用于制造核心岩藻糖基化降低的抗体和抗体衍生物的方法和组合物 |
| US20140213465A1 (en) * | 2011-12-02 | 2014-07-31 | Plaxgen, Inc. | Plaque array methods and compositions for forming and detecting plaques |
| US20120282654A1 (en) * | 2009-04-29 | 2012-11-08 | Schering Corporation | Antibody purification |
| US20130116413A1 (en) * | 2009-12-29 | 2013-05-09 | Dr. Reddy's Laboratories, Inc. | Purification of proteins |
| WO2011107507A1 (en) | 2010-03-03 | 2011-09-09 | Boehringer Ingelheim International Gmbh | Biparatopic abeta binding polypeptides |
| EP2558494B1 (en) | 2010-04-15 | 2018-05-23 | AbbVie Inc. | Amyloid-beta binding proteins |
| CN103179981B (zh) | 2010-07-30 | 2017-02-08 | Ac免疫有限公司 | 安全和功能性的人源化抗β‑淀粉样蛋白抗体 |
| US9062101B2 (en) | 2010-08-14 | 2015-06-23 | AbbVie Deutschland GmbH & Co. KG | Amyloid-beta binding proteins |
| US20140302532A1 (en) | 2011-04-12 | 2014-10-09 | Quanterix Corporation | Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury |
| SG11201401360XA (en) * | 2011-10-25 | 2014-05-29 | Onclave Therapeutics Ltd | Antibody formulations and methods |
| NZ626955A (en) | 2012-03-08 | 2016-01-29 | Hoffmann La Roche | Abeta antibody formulation |
| CA2879496C (en) * | 2012-08-29 | 2024-01-09 | F. Hoffmann-La Roche Ag | Blood brain barrier shuttle |
| CN102998454A (zh) * | 2012-12-11 | 2013-03-27 | 华中师范大学 | 一种检测生物体内邻苯二甲酸二丁酯相对含量的方法 |
| US9587022B2 (en) | 2012-12-18 | 2017-03-07 | The Rockefeller University | Glycan-modified anti-CD4 antibody with improved HIV-1 neutralizing activity |
| CN105228650B (zh) | 2012-12-18 | 2018-11-16 | 美国洛克菲勒大学 | 用于hiv预防和治疗的聚糖修饰的抗-cd4抗体 |
| BR112015019341A2 (pt) | 2013-02-13 | 2017-08-22 | Lab Francais Du Fractionnement | Anticorpo anti-tnf-alfa, composição que compreende o anticorpo, método para produzir uma população de anticorpos, células epiteliais da glândula mamária, mamífero não humano transgênico, e, composição de anticorpo anti-tnf monoclonal |
| JP6169885B2 (ja) | 2013-05-07 | 2017-07-26 | 株式会社日立製作所 | 精製装置及び精製方法 |
| CN105722532A (zh) | 2013-09-13 | 2016-06-29 | 豪夫迈·罗氏有限公司 | 包含纯化的重组多肽的方法和组合物 |
| BR112016004437A2 (pt) | 2013-09-13 | 2017-10-17 | Genentech Inc | métodos de imunoteste e de seleção de linhagem de células, anticorpos e kit |
| EP3072506B1 (en) | 2013-11-22 | 2022-04-20 | The University of Tokyo | Carrier for drug delivery and conjugate, composition containing same, and method for administering same |
| WO2015155694A1 (en) | 2014-04-08 | 2015-10-15 | Prothena Biosciences Limited | Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein |
| WO2015165961A1 (en) | 2014-04-29 | 2015-11-05 | Affiris Ag | Treatment and prevention of alzheimer's disease (ad) |
| IL302486A (en) | 2015-06-24 | 2023-06-01 | Hoffmann La Roche | Antibodies against the transnephrine receptor with adapted affinity |
| FR3038517B1 (fr) | 2015-07-06 | 2020-02-28 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Utilisation de fragments fc modifies en immunotherapie |
| PL3337812T3 (pl) * | 2015-08-21 | 2021-10-11 | F. Hoffmann-La Roche Ag | Sposób zmniejszenia zawartości białek komórki gospodarza w chromatografii powinowactwa |
| JP6657392B2 (ja) | 2015-10-02 | 2020-03-04 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 二重特異性抗ヒトcd20/ヒトトランスフェリン受容体抗体及び使用方法 |
| 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 |
| EP3155958B1 (en) * | 2015-10-16 | 2021-11-17 | Roche Diabetes Care GmbH | A method for operating a system and a system |
| CN108350051A (zh) | 2015-11-09 | 2018-07-31 | 英属哥伦比亚大学 | 淀粉样蛋白β中的N-末端表位及其构象选择性抗体 |
| AU2016354688B2 (en) | 2015-11-09 | 2021-12-16 | The University Of British Columbia | Epitopes in Amyloid beta mid-region and conformationally-selective antibodies thereto |
| CA3004498A1 (en) | 2015-11-09 | 2017-05-18 | Neil R. Cashman | Amyloid beta epitopes and antibodies thereto |
| US10792477B2 (en) * | 2016-02-08 | 2020-10-06 | Orbusneich Medical Pte. Ltd. | Drug eluting balloon |
| EP3427183A1 (en) * | 2016-03-10 | 2019-01-16 | Genomic Vision | Method of curvilinear signal detection and analysis and associated platform |
| US11326182B2 (en) | 2016-04-29 | 2022-05-10 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| TWI735600B (zh) | 2016-07-01 | 2021-08-11 | 美商美國禮來大藥廠 | 抗-N3pGlu類澱粉β肽抗體及其用途 |
| EP3484919A4 (en) | 2016-07-18 | 2020-03-04 | The University of British Columbia | ANTI-BETA-AMYLOID ANTIBODIES |
| 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 |
| AU2018277333B2 (en) * | 2017-05-30 | 2021-09-16 | Morinaga Milk Industry Co., Ltd. | Composition for improving brain function |
| US12286469B2 (en) | 2017-07-18 | 2025-04-29 | The University Of British Columbia | Humanized antibodies binding to amyloid-beta (A-beta) |
| JP7330164B2 (ja) | 2017-07-18 | 2023-08-21 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | アミロイドベータに対する抗体 |
| CN108048477A (zh) * | 2017-12-15 | 2018-05-18 | 南京理工大学 | 基于大肠杆菌表达系统的制备多肽的方法 |
| EP3778875A1 (en) | 2019-08-14 | 2021-02-17 | MaxiVax SA | Immortalized myoblast cell lines and uses thereof |
| JP2023535024A (ja) | 2020-07-23 | 2023-08-15 | オター プロシーナ リミテッド | 抗aベータ抗体 |
| KR20230109674A (ko) * | 2020-11-16 | 2023-07-20 | 에프. 호프만-라 로슈 아게 | Fab 고 만노스 당형 |
| 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 |
| CN114591429B (zh) * | 2022-05-07 | 2022-08-09 | 北京第一生物化学药业有限公司 | 结合β-淀粉样蛋白的抗体及其用途 |
| TW202434629A (zh) | 2023-01-26 | 2024-09-01 | 愛爾蘭商歐薩爾普羅席納有限公司 | 以抗類澱粉β (ABETA)抗體治療神經病症之方法 |
| WO2025032070A1 (en) | 2023-08-09 | 2025-02-13 | F. Hoffmann-La Roche Ag | Anti-a-beta protein antibodies, methods and uses thereof |
| WO2025032069A1 (en) | 2023-08-09 | 2025-02-13 | F. Hoffmann-La Roche Ag | Mono and multispecific anti-trem2 antibodies, methods and uses thereof |
| CN117783359B (zh) * | 2023-12-28 | 2024-12-31 | 中国计量科学研究院 | 一种基于串联质谱的转基因蛋白多靶同检方法 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4666829A (en) | 1985-05-15 | 1987-05-19 | University Of California | Polypeptide marker for Alzheimer's disease and its use for diagnosis |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| US5811310A (en) | 1986-09-30 | 1998-09-22 | Albert Einstein College Of Medicine Of Yeshiva Univ. | The Alz-50 monoclonal antibody and diagnostic assay for alzheimer's disease |
| GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
| CA1339014C (en) | 1987-10-08 | 1997-03-25 | Ronald E. Majocha | Antibodies to a4 amyloid peptide |
| JP2780507B2 (ja) | 1991-03-29 | 1998-07-30 | 松下電器産業株式会社 | 内燃機関用フィルタ再生装置 |
| US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
| WO1994017197A1 (fr) | 1993-01-25 | 1994-08-04 | Takeda Chemical Industries, Ltd. | ANTICORPS DIRIGE CONTRE LE β-AMYLOIDE OU UN DERIVE DE CE DERNIER ET SON UTILISATION |
| US5443953A (en) * | 1993-12-08 | 1995-08-22 | Immunomedics, Inc. | Preparation and use of immunoconjugates |
| GB9416007D0 (en) * | 1994-08-08 | 1994-09-28 | Erba Carlo Spa | Anthracyclinone derivatives |
| US5688651A (en) | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
| AU5976996A (en) * | 1995-06-06 | 1996-12-24 | Stemcell Therapeutics L.L.C. | Glycoprotein gp105 on bl3 hematopoietic stem cells |
| CA2229043C (en) | 1995-08-18 | 2016-06-07 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Protein/(poly)peptide libraries |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic 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 |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| AU781292B2 (en) * | 1999-03-04 | 2005-05-12 | Praecis Pharmaceuticals Incorporated | Modulators of beta-amyloid peptide aggregation comprising D-amino acids |
| DK1409654T3 (da) | 1999-06-16 | 2008-12-08 | Boston Biomedical Res Inst | Immunologisk styring af beta-amyloid-niveauer in vivo |
| AU6722300A (en) | 1999-08-31 | 2001-03-26 | Ramot University Authority For Applied Research And Industrial Development Ltd. | Peptides and substances, methods and devices using same for diagnosing and treating neurodegenerative disorders |
| AU784312B2 (en) | 1999-11-29 | 2006-03-09 | Bellus Health (International) Limited | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
| US20020094335A1 (en) | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
| EP1125905A1 (en) | 2000-02-16 | 2001-08-22 | Pepscan Systems B.V. | Segment synthesis |
| KR100767146B1 (ko) | 2000-02-24 | 2007-10-15 | 워싱톤 유니버시티 | Aβ 펩티드를 격리시키는 인간화 항체 |
| CA2313828A1 (en) | 2000-08-01 | 2002-02-01 | Institut De Recherches Cliniques De Montreal/Ircm | Post-translational processing of .beta.-secretase (bace): the pro-and transmembrane/cytosolic domains affect its cellular activity and amyloid a.beta. production |
| PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
| CA2436789A1 (en) | 2000-12-19 | 2002-08-22 | Palatin Technologies, Inc. | Identification of target-specific folding sites in peptides and proteins |
| ES2312569T3 (es) | 2001-04-30 | 2009-03-01 | Eli Lilly And Company | Anticuerpos humanizados. |
| ATE420114T1 (de) | 2001-04-30 | 2009-01-15 | Lilly Co Eli | Humanisierte antikörper die das beta-amyloid peptid erkennen& x9; |
| ES2391905T3 (es) * | 2001-08-17 | 2012-11-30 | Washington University | Método de ensayo para la enfermedad de alzheimer |
| US20040192898A1 (en) * | 2001-08-17 | 2004-09-30 | Jia Audrey Yunhua | Anti-abeta antibodies |
| 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 |
| MXPA05003621A (es) | 2002-10-09 | 2005-10-19 | Rinat Neuroscience Corp | Metodos de tratamiento de la enfermedad de alzheimer usando anticuerpos dirigidos contra el peptido beta amiloide y composiciones de los mismos. |
| DE10303974A1 (de) * | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| BRPI0619605B8 (pt) * | 2005-12-12 | 2021-05-25 | Hoffmann La Roche | composições compreendendo moléculas de anticorpos contra amilóide beta4 com glicosilação na região variável, usos das mesmas, método de preparação de uma molécula de anticorpo, e kit |
| CN101553504A (zh) * | 2006-12-11 | 2009-10-07 | 豪夫迈·罗氏有限公司 | Aβ抗体胃肠外制剂 |
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