HUE028615T2 - Treatment of osteoarthritis - Google Patents
Treatment of osteoarthritis Download PDFInfo
- Publication number
- HUE028615T2 HUE028615T2 HUE09833924A HUE09833924A HUE028615T2 HU E028615 T2 HUE028615 T2 HU E028615T2 HU E09833924 A HUE09833924 A HU E09833924A HU E09833924 A HUE09833924 A HU E09833924A HU E028615 T2 HUE028615 T2 HU E028615T2
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- Prior art keywords
- antibody
- csf
- ser
- seq
- leu
- Prior art date
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Classifications
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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Landscapes
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| WO2010071923A1 (en) | 2008-12-22 | 2010-07-01 | The University Of Melbourne | Pain treatment |
| AU2009329814B2 (en) | 2008-12-22 | 2015-06-18 | The University Of Melbourne | Osteoarthritis treatment |
| CN109999195A (zh) | 2012-09-20 | 2019-07-12 | 莫弗系统股份公司 | 类风湿关节炎的治疗 |
| DE102013222200A1 (de) * | 2013-10-31 | 2015-08-27 | Osram Opto Semiconductors Gmbh | Elektronisches Bauelement und Verfahren zum Herstellen eines elektronischen Bauelements |
| WO2019034985A1 (en) * | 2017-08-14 | 2019-02-21 | Zynerba Pharmaceuticals, Inc. | METHODS OF TREATING ARTHROSIS USING CANNABIDIOL TRANSDERMAL GEL |
| WO2020104833A1 (en) * | 2018-11-19 | 2020-05-28 | 4P-Pharma | Composition and methods for regulating chondrocyte proliferation and increasing of cartilage matrix production |
| CN110075304B (zh) * | 2019-05-29 | 2020-02-11 | 四川大学华西医院 | 一种治疗骨关节炎的药物组合物及其用途 |
Family Cites Families (36)
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|---|---|---|---|---|
| US5225539A (en) * | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| PH27534A (en) | 1989-07-14 | 1993-08-18 | Schering Corp | Antoganists of gm-csf derived from the carboxyl terminus |
| JP3267966B2 (ja) | 1989-08-11 | 2002-03-25 | アムラド・コーポレイション・リミテッド | 顆粒球―マクロファージコロニー刺激因子受容体およびその誘導体における改良 |
| US5747032A (en) | 1990-08-10 | 1998-05-05 | Amrad Corporation Limited | Monoclonal antibody to human granulocyte macrophage colony stimulating factor |
| EP0673389A1 (en) | 1992-11-19 | 1995-09-27 | Dana Farber Cancer Institute | Antibodies for gm-csf receptor and uses thereof |
| ES2176484T3 (es) | 1995-08-18 | 2002-12-01 | Morphosys Ag | Bancos de proteinas/(poli)peptidos. |
| AUPP525198A0 (en) | 1998-08-13 | 1998-09-03 | Medvet Science Pty. Ltd. | Monoclonal antibody inhibitor of GM-CSF, IL-3 and IL-5 and other cytokines and uses thereof |
| US7108852B2 (en) | 2000-03-20 | 2006-09-19 | Warner-Lambert Company Llc | Methods of treating inflammation using antibodies to M-CSF |
| US7455836B2 (en) * | 2000-05-08 | 2008-11-25 | The University Of Melbourne | Method of treatment and agents useful for same |
| JP2005507915A (ja) * | 2001-10-26 | 2005-03-24 | ノバルティス アクチエンゲゼルシャフト | 変形性関節症の処置方法およびその組成物 |
| US7381801B2 (en) | 2002-02-13 | 2008-06-03 | Ludwig Institute For Cancer Research | Chimerized GM-CSF antibodies |
| US20040241755A1 (en) * | 2003-06-02 | 2004-12-02 | Pfizer Inc. | Human cell assay to determine effect of sample compounds on Col2 enhancer expression |
| DE602005020743D1 (de) | 2004-02-11 | 2010-06-02 | Warner Lambert Co | Verfahren zur behandlung von osteoarthritis mit anti-il-6 antikörpern |
| JP4825667B2 (ja) * | 2004-03-31 | 2011-11-30 | 一和 中尾 | 関節炎症治療剤又は予防剤 |
| DE602004021773D1 (de) | 2004-05-05 | 2009-08-13 | Micromet Ag | Herstellung eines einkettigen fv Antikörperfragments |
| JP2008510168A (ja) * | 2004-08-18 | 2008-04-03 | アメリカ合衆国 | 骨関節炎のバイオマーカー |
| US20060040258A1 (en) | 2004-08-23 | 2006-02-23 | Huiyan Guo | Water-soluble conjugates and methods of preparation |
| UA94403C2 (ru) | 2005-04-18 | 2011-05-10 | Микромет Аг | Человеческое моноклональное антитело, которое нейтрализует gm-csf |
| SI3620171T1 (sl) * | 2005-05-18 | 2022-09-30 | Morphosys Ag | Protitelesa proti GM-CSF in uporabe zanje |
| JP4736037B2 (ja) | 2005-10-26 | 2011-07-27 | 株式会社イーベック | ヒトｇｍ−ｃｓｆに結合するヒトのモノクローナル抗体並びにその抗原結合部分 |
| EA200801166A1 (ru) * | 2005-12-01 | 2008-12-30 | Домантис Лимитед | Форматы конкурентного доменного антитела, которые связываются с рецептором интерлейкина 1 первого типа |
| WO2007092939A2 (en) * | 2006-02-08 | 2007-08-16 | Morphotek, Inc. | Antigenic gm-csf peptides and antibodies to gm-csf |
| CA2647449C (en) * | 2006-03-27 | 2017-05-16 | Medimmune Limited | Binding member for gm-csf receptor |
| US7741273B2 (en) | 2006-04-13 | 2010-06-22 | Warsaw Orthopedic, Inc. | Drug depot implant designs |
| EP2402013A1 (en) | 2006-11-21 | 2012-01-04 | Kalobios Pharmaceuticals, Inc. | Methods of Treating Chronic Inflammatory Diseases using a GM-CSF Antagonist |
| WO2008080134A2 (en) * | 2006-12-22 | 2008-07-03 | Rigel Pharmaceuticals, Inc. | 4-amin0-2- (hetero) arylamino-5- (hetero) arylthiazoles useful as axl inhibitors |
| WO2008141391A1 (en) * | 2007-05-23 | 2008-11-27 | Crc For Asthma And Airways Ltd | Neutralizing antibodies |
| TW200918553A (en) * | 2007-09-18 | 2009-05-01 | Amgen Inc | Human GM-CSF antigen binding proteins |
| WO2009042854A1 (en) * | 2007-09-26 | 2009-04-02 | Musculoskeletal Research Llc | Ion-channel regulator compositions and methods of using same |
| WO2009062238A1 (en) | 2007-11-12 | 2009-05-22 | Crc For Asthma And Airways Ltd | Epitope for neutralizing antibodies |
| CN104072613A (zh) | 2007-11-13 | 2014-10-01 | Evec股份有限公司 | 与hGM-CSF结合的单克隆抗体及包含它的药物组合物 |
| JP2011517672A (ja) | 2008-03-24 | 2011-06-16 | アボツト・バイオテクノロジー・リミテツド | 骨損失を治療するための方法及び組成物 |
| EA201001691A1 (ru) * | 2008-04-28 | 2011-10-31 | Калобайос Фармасьютикалз, Инк. | Антитела к гранулоцитарно-макрофагальному колониестимулирующему фактору |
| WO2010071923A1 (en) | 2008-12-22 | 2010-07-01 | The University Of Melbourne | Pain treatment |
| AU2009329814B2 (en) * | 2008-12-22 | 2015-06-18 | The University Of Melbourne | Osteoarthritis treatment |
| SG175305A1 (en) | 2009-04-23 | 2011-11-28 | Theraclone Sciences Inc | Granulocyte-macrophage colony-stimulating factor (gm-csf) neutralizing antibodies |
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2009
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- 2009-12-21 BR BRPI0918356-6A patent/BRPI0918356B1/pt active IP Right Grant
- 2009-12-21 CA CA2746827A patent/CA2746827C/en active Active
- 2009-12-21 HR HRP20160577TT patent/HRP20160577T4/hr unknown
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2015
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2016
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2017
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