CA2785038A1 - Bmp-7 variants with reduced immunogenicity - Google Patents
Bmp-7 variants with reduced immunogenicity Download PDFInfo
- Publication number
- CA2785038A1 CA2785038A1 CA2785038A CA2785038A CA2785038A1 CA 2785038 A1 CA2785038 A1 CA 2785038A1 CA 2785038 A CA2785038 A CA 2785038A CA 2785038 A CA2785038 A CA 2785038A CA 2785038 A1 CA2785038 A1 CA 2785038A1
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- bmp
- variant
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- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28922009P | 2009-12-22 | 2009-12-22 | |
| US61/289,220 | 2009-12-22 | ||
| PCT/US2010/061437 WO2011087768A1 (en) | 2009-12-22 | 2010-12-21 | Bmp-7 variants with reduced immunogenicity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2785038A1 true CA2785038A1 (en) | 2011-07-21 |
Family
ID=43735952
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2785038A Abandoned CA2785038A1 (en) | 2009-12-22 | 2010-12-21 | Bmp-7 variants with reduced immunogenicity |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20130190236A1 (enExample) |
| EP (1) | EP2516456A1 (enExample) |
| JP (1) | JP2013514811A (enExample) |
| CN (1) | CN102822197A (enExample) |
| AU (1) | AU2010341565A1 (enExample) |
| CA (1) | CA2785038A1 (enExample) |
| WO (1) | WO2011087768A1 (enExample) |
Families Citing this family (3)
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|---|---|---|---|---|
| JP6851965B2 (ja) * | 2014-09-26 | 2021-03-31 | サハイ バートナガール ラジェンドラ | 疾患及び障害の治療のためのｎｆカッパｂ活性の阻害剤 |
| EP3240563B1 (en) | 2014-12-29 | 2020-12-09 | Bioventus LLC | Systems and methods for improved delivery of osteoinductive molecules in bone repair |
| WO2019148140A2 (en) * | 2018-01-26 | 2019-08-01 | Wu Joseph C | Implantable biomaterials that enhance stem cell survival and function |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL83003A (en) | 1986-07-01 | 1995-07-31 | Genetics Inst | Osteoinductive factors |
| US6919308B2 (en) | 1988-04-08 | 2005-07-19 | Stryker Corporation | Osteogenic devices |
| US5266683A (en) | 1988-04-08 | 1993-11-30 | Stryker Corporation | Osteogenic proteins |
| US5011691A (en) | 1988-08-15 | 1991-04-30 | Stryker Corporation | Osteogenic devices |
| ATE184052T1 (de) | 1990-06-15 | 1999-09-15 | Carnegie Inst Of Washington | Gdf-1 und uog1 proteine |
| US5674844A (en) | 1991-03-11 | 1997-10-07 | Creative Biomolecules, Inc. | Treatment to prevent loss of and/or increase bone mass in metabolic bone diseases |
| US5656593A (en) | 1991-03-11 | 1997-08-12 | Creative Biomolecules, Inc. | Morphogen induced periodontal tissue regeneration |
| US6800603B2 (en) | 1991-03-11 | 2004-10-05 | Curis, Inc. | Morphogen-induced neural cell adhesion |
| US5849686A (en) | 1991-03-11 | 1998-12-15 | Creative Biomolecules, Inc. | Morphogen-induced liver regeneration |
| US6949505B1 (en) | 1991-03-11 | 2005-09-27 | Curis, Inc. | Morphogen-induced dendritic growth |
| US6506729B1 (en) | 1991-03-11 | 2003-01-14 | Curis, Inc. | Methods and compositions for the treatment and prevention of Parkinson's disease |
| US6287816B1 (en) | 1991-06-25 | 2001-09-11 | Genetics Institute, Inc. | BMP-9 compositions |
| DE69233022T2 (de) | 1991-11-04 | 2004-02-12 | Genetics Institute, LLC, Cambridge | Rekombinante knochenmorphogenetische protein heterodimere, zusammensetzungen und verfahren zur verwendung |
| DK0625989T3 (da) | 1992-02-12 | 2000-06-26 | Bioph Biotech Entw Pharm Gmbh | DNA-sekvenser kodende for hidtil ukendte vækst-/differentieringsfaktorer |
| JPH08503198A (ja) | 1992-11-03 | 1996-04-09 | クリエイティブ バイオモレキュルズ，インコーポレイテッド | Ｏｐ−３誘導形態形成 |
| EP1439190A1 (en) | 1993-01-12 | 2004-07-21 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-5 |
| WO1994015966A1 (en) | 1993-01-12 | 1994-07-21 | Johns Hopkins University School Of Medicine | Growth differentiation factor-9 |
| EP0690873B1 (en) | 1993-03-19 | 2003-06-11 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-8 |
| EP0698094B1 (en) | 1993-05-12 | 2004-02-04 | Genetics Institute, LLC | Bmp-11 compositions |
| JPH09501305A (ja) | 1993-05-12 | 1997-02-10 | ジェネティックス・インスティテュート・インコーポレイテッド | Ｂｍｐ−１０組成物 |
| AU697625B2 (en) | 1993-07-09 | 1998-10-15 | Johns Hopkins University School Of Medicine, The | Growth differentiation factor-6 |
| US6204047B1 (en) | 1993-10-08 | 2001-03-20 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-10 |
| JP3300500B2 (ja) | 1993-10-12 | 2002-07-08 | 新日本製鐵株式会社 | 疲労強度、降伏強度および被削性に優れる熱間鍛造用鋼の製造方法 |
| DE4334646C1 (de) | 1993-10-12 | 1994-09-29 | Quinting Friedhelm | Durchsichtige Analog-Zeituhr |
| US5399677A (en) | 1993-12-07 | 1995-03-21 | Genetics Institute, Inc. | Mutants of bone morphogenetic proteins |
| JP3717930B2 (ja) | 1993-12-07 | 2005-11-16 | ジェネティックス・インスチチュート・リミテッド・ライアビリティ・カンパニー | Ｂｍｐ−１２、ｂｍｐ−１３およびそれらの腱誘導組成物 |
| IL114397A0 (en) | 1994-07-01 | 1995-10-31 | Bioph Biotech Entw Pharm Gmbh | Growth/differentiation factor of the TGF-beta-family |
| US5914234A (en) | 1994-07-08 | 1999-06-22 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-11 |
| AU1120295A (en) | 1994-11-07 | 1996-05-31 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Cartilage-derived morphogenetic proteins |
| US5635372A (en) | 1995-05-18 | 1997-06-03 | Genetics Institute, Inc. | BMP-15 compositions |
| US6214796B1 (en) | 1996-03-22 | 2001-04-10 | The General Hospital Corporation | Administration of polypeptide growth factors following central nervous system ischemia or trauma |
| US6498142B1 (en) | 1996-05-06 | 2002-12-24 | Curis, Inc. | Morphogen treatment for chronic renal failure |
| US7041641B2 (en) | 1997-03-20 | 2006-05-09 | Stryker Corporation | Osteogenic devices and methods of use thereof for repair of endochondral bone and osteochondral defects |
| US6958149B2 (en) | 1998-10-06 | 2005-10-25 | Stryker Corporation | Repair of larynx, trachea, and other fibrocartilaginous tissues |
| US6846906B1 (en) | 1998-10-07 | 2005-01-25 | Stryker Corporation | Modified proteins of the TGF-β superfamily, including morphogenic proteins |
| US6677432B1 (en) | 1998-10-07 | 2004-01-13 | Stryker Corporation | Mutations of the C-terminal portion of TGF-β superfamily proteins |
| EP2128260A3 (en) | 1998-10-07 | 2010-06-16 | STRYKER CORPORATION (a Michigan corporation) | Modified TGF-beta superfamily proteins |
| US6949251B2 (en) | 2001-03-02 | 2005-09-27 | Stryker Corporation | Porous β-tricalcium phosphate granules for regeneration of bone tissue |
| US8154581B2 (en) | 2002-10-15 | 2012-04-10 | Revolutionary Concepts, Inc. | Audio-video communication system for receiving person at entrance |
| EP1692505B1 (en) * | 2003-11-03 | 2012-09-05 | Danisco US Inc. | Cd4+ epitopes of bone morphogenetic proteins |
| EP1730186A2 (en) | 2004-03-31 | 2006-12-13 | Xencor, Inc. | Bmp-7 variants with improved properties |
| US20090042780A1 (en) | 2004-05-20 | 2009-02-12 | Acceleron Pharma Inc | Modified TGF-Beta Superfamily Polypeptides and Related Methods |
| CA2567405A1 (en) | 2004-05-25 | 2005-12-08 | Stryker Corporation | Use of morphogenic proteins for treating cartilage defects |
| US7659250B2 (en) * | 2005-12-22 | 2010-02-09 | Centocor, Inc. | BMP-7 variant compositions, methods and uses |
| EP1978994B1 (en) | 2005-12-22 | 2012-02-01 | Janssen Biotech, Inc. | Bmp-7 variant compositions, methods and uses |
| WO2008051526A2 (en) * | 2006-10-23 | 2008-05-02 | Stryker Corporation | Bone morphogenetic proteins |
| EP2222696A1 (en) * | 2007-12-21 | 2010-09-01 | Stryker Corporation | Bmp mutants with decreased susceptibility to noggin |
| JPWO2010117047A1 (ja) | 2009-04-10 | 2012-10-18 | 株式会社ニコン | 光学材料、光学素子、及びその製造方法 |
| JP2011211450A (ja) | 2010-03-30 | 2011-10-20 | Victor Co Of Japan Ltd | 立体映像表示装置、立体映像撮像装置および立体映像表示方法 |
| US9507084B2 (en) | 2010-12-03 | 2016-11-29 | Ofs Fitel, Llc | Single-mode, bend-compensated, large-mode-area optical fibers designed to accomodate simplified fabrication and tighter bends |
| US8886307B2 (en) | 2012-01-30 | 2014-11-11 | Medtronic, Inc. | Adaptive cardiac resynchronization therapy |
| CN104081272B (zh) | 2012-06-07 | 2017-10-17 | 旭化成微电子株式会社 | 位置检测装置 |
| US9298469B2 (en) | 2012-06-15 | 2016-03-29 | International Business Machines Corporation | Management of multiple nested transactions |
| US9405290B1 (en) | 2013-01-17 | 2016-08-02 | Kla-Tencor Corporation | Model for optical dispersion of high-K dielectrics including defects |
| JP6154215B2 (ja) | 2013-06-28 | 2017-06-28 | 株式会社日立国際電気 | 半導体装置の製造方法、基板処理装置およびプログラム |
| US9170581B2 (en) | 2013-09-30 | 2015-10-27 | Crown Equipment Limited | Industrial vehicles with overhead light based localization |
| JP6541301B2 (ja) | 2014-03-28 | 2019-07-10 | キヤノン株式会社 | ロボット装置、ロボット装置の制御方法、ロボット制御プログラム、及び記録媒体 |
| US9411440B2 (en) | 2014-08-22 | 2016-08-09 | Qualcomm Incorporated | Digital ultrasonic emitting base station |
| US9407762B2 (en) | 2014-10-10 | 2016-08-02 | Bank Of America Corporation | Providing enhanced user authentication functionalities |
| US9412814B2 (en) | 2014-12-24 | 2016-08-09 | Taiwan Semiconductor Manufacturing Co., Ltd. | Structure and formation method of FinFET device |
| US9400685B1 (en) | 2015-01-30 | 2016-07-26 | Huawei Technologies Co., Ltd. | Dividing, scheduling, and parallel processing compiled sub-tasks on an asynchronous multi-core processor |
-
2010
- 2010-12-21 CA CA2785038A patent/CA2785038A1/en not_active Abandoned
- 2010-12-21 JP JP2012546131A patent/JP2013514811A/ja active Pending
- 2010-12-21 EP EP10801334A patent/EP2516456A1/en not_active Withdrawn
- 2010-12-21 CN CN2010800643966A patent/CN102822197A/zh active Pending
- 2010-12-21 AU AU2010341565A patent/AU2010341565A1/en not_active Abandoned
- 2010-12-21 WO PCT/US2010/061437 patent/WO2011087768A1/en not_active Ceased
-
2013
- 2013-02-13 US US13/766,014 patent/US20130190236A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2516456A1 (en) | 2012-10-31 |
| US20130190236A1 (en) | 2013-07-25 |
| JP2013514811A (ja) | 2013-05-02 |
| AU2010341565A1 (en) | 2012-07-12 |
| CN102822197A (zh) | 2012-12-12 |
| WO2011087768A1 (en) | 2011-07-21 |
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| FZDE | Discontinued |
Effective date: 20161221 |