CN106397591A - 骨关节炎治疗 - Google Patents
骨关节炎治疗 Download PDFInfo
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- CN106397591A CN106397591A CN201610822096.9A CN201610822096A CN106397591A CN 106397591 A CN106397591 A CN 106397591A CN 201610822096 A CN201610822096 A CN 201610822096A CN 106397591 A CN106397591 A CN 106397591A
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13967908P | 2008-12-22 | 2008-12-22 | |
| US61/139,679 | 2008-12-22 | ||
| US16448609P | 2009-03-30 | 2009-03-30 | |
| US61/164,486 | 2009-03-30 | ||
| CN2009801516359A CN102271705A (zh) | 2008-12-22 | 2009-12-21 | 骨关节炎治疗 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113038966A (zh) * | 2018-11-19 | 2021-06-25 | 4移动生物技术 | 调节软骨细胞增殖和增加软骨基质生成的组合物和方法 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2978209T3 (es) | 2008-12-22 | 2024-09-09 | Univ Melbourne | Tratamiento del dolor |
| US9243061B2 (en) * | 2008-12-22 | 2016-01-26 | 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 |
| IL301622A (en) * | 2017-08-14 | 2023-05-01 | Zynerba Pharmaceuticals Inc | Methods for treating degenerative joint disease with cannabidiol gel through the skin |
| 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 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101218255A (zh) * | 2005-05-18 | 2008-07-09 | 莫菲西斯公司 | 抗gm-csf抗体和其用途 |
| CN101501070A (zh) * | 2006-02-08 | 2009-08-05 | 诺福泰克公司 | 抗原性gm-csf肽和针对gm-csf的抗体 |
| CN101687926A (zh) * | 2007-05-23 | 2010-03-31 | 哮喘和气道Crc有限公司 | 中和抗体 |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225539A (en) * | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| CA2062975A1 (en) | 1989-07-14 | 1991-01-15 | Gail F. Seelig | Antagonists of gm-csf derived from the carboxyl terminus |
| DE69031914T2 (de) | 1989-08-11 | 1998-07-30 | Amrad Corp. Ltd., Kew, Victoria | Rezeptor für granulozyten-macrophagen-koloniestimulierungsfaktor und seine derivate |
| WO1994009149A1 (en) | 1990-08-10 | 1994-04-28 | Amrad Corporation Limited | Monoclonal antibody |
| CA2149881A1 (en) | 1992-11-19 | 1994-05-26 | Paul T. Jubinsky | Antibodies for gm-csf receptor and uses thereof |
| CA2229043C (en) | 1995-08-18 | 2016-06-07 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Protein/(poly)peptide libraries |
| 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 |
| US20060067938A1 (en) * | 2001-10-26 | 2006-03-30 | Sherif Daouti | Methods for the treatment of osteoarthritis and compositions thereof |
| ATE444308T1 (de) | 2002-02-13 | 2009-10-15 | Ludwig Inst Cancer Res | Fusionsproteine humanisierter g250-spezifischer antikörper sowie verwendungen davon |
| US20040241755A1 (en) * | 2003-06-02 | 2004-12-02 | Pfizer Inc. | Human cell assay to determine effect of sample compounds on Col2 enhancer expression |
| JP2008505054A (ja) | 2004-02-11 | 2008-02-21 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | Ｉｌ−６アンタゴニストで骨関節炎を治療する方法 |
| JP4825667B2 (ja) * | 2004-03-31 | 2011-11-30 | 一和 中尾 | 関節炎症治療剤又は予防剤 |
| EP1593690B1 (en) | 2004-05-05 | 2009-07-01 | Micromet AG | Preparation of ScFv antibody fragments |
| US7662573B2 (en) * | 2004-08-18 | 2010-02-16 | The United States Of America As Represented By The Department Of Health And Human Services | Methods for evaluating osteoarthritis risk |
| US20060040258A1 (en) | 2004-08-23 | 2006-02-23 | Huiyan Guo | Water-soluble conjugates and methods of preparation |
| EA013162B1 (ru) | 2005-04-18 | 2010-02-26 | Микромет Аг | Антитела-нейтрализаторы гранулоцитарно-макрофагального колониестимулирующего фактора человека |
| 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 |
| CA2629850A1 (en) * | 2005-12-01 | 2007-06-07 | Domantis Limited | Competitive domain antibody formats that bind interleukin 1 receptor type 1 |
| CN103641916A (zh) | 2006-03-27 | 2014-03-19 | 医学免疫有限公司 | Gm-csf受体结合元件 |
| US7741273B2 (en) * | 2006-04-13 | 2010-06-22 | Warsaw Orthopedic, Inc. | Drug depot implant designs |
| NZ598345A (en) * | 2006-11-21 | 2013-09-27 | 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 |
| TW200918553A (en) | 2007-09-18 | 2009-05-01 | Amgen Inc | Human GM-CSF antigen binding proteins |
| US20090163440A1 (en) * | 2007-09-26 | 2009-06-25 | Waddell David D | Ion-Channel Regulator Compositions and Methods of Using Same |
| EP2217626A4 (en) | 2007-11-12 | 2011-06-22 | Crc For Asthma And Airways Ltd | EPITOP FOR NEUTRALIZING ANTIBODIES |
| TWI434854B (zh) | 2007-11-13 | 2014-04-21 | Evec Inc | 結合ｈＧＭ－ＣＳＦ的單株抗體以及包含其之醫學組成物 |
| WO2009118662A2 (en) | 2008-03-24 | 2009-10-01 | Abbott Biotechnology Ltd. | Methods and compositions for treating bone loss |
| JP5688363B2 (ja) * | 2008-04-28 | 2015-03-25 | カロバイオス ファーマシューティカルズ インコーポレイティッド | 顆粒球−マクロファージコロニー刺激因子に対する抗体 |
| US9243061B2 (en) | 2008-12-22 | 2016-01-26 | University Of Melbourne | Osteoarthritis treatment |
| ES2978209T3 (es) | 2008-12-22 | 2024-09-09 | Univ Melbourne | Tratamiento del dolor |
| SG175305A1 (en) | 2009-04-23 | 2011-11-28 | Theraclone Sciences Inc | Granulocyte-macrophage colony-stimulating factor (gm-csf) neutralizing antibodies |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101218255A (zh) * | 2005-05-18 | 2008-07-09 | 莫菲西斯公司 | 抗gm-csf抗体和其用途 |
| CN101501070A (zh) * | 2006-02-08 | 2009-08-05 | 诺福泰克公司 | 抗原性gm-csf肽和针对gm-csf的抗体 |
| CN101687926A (zh) * | 2007-05-23 | 2010-03-31 | 哮喘和气道Crc有限公司 | 中和抗体 |
Non-Patent Citations (2)
| Title |
|---|
| C PLATER-ZYBERK: "GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice", 《EXTENDED REPORT》 * |
| J. L. HUEBNER: "Assessment of the utility of biomarkers of osteoarthritis in the guinea pig", 《OSTEOARTHRITIS AND CARTILAGE》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113038966A (zh) * | 2018-11-19 | 2021-06-25 | 4移动生物技术 | 调节软骨细胞增殖和增加软骨基质生成的组合物和方法 |
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