JP2008501309A - 骨形成タンパク質の変異タンパク質及びその使用 - Google Patents
骨形成タンパク質の変異タンパク質及びその使用 Download PDFInfo
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| EP04005192A EP1571159A1 (en) | 2004-03-04 | 2004-03-04 | Mutein of a bone morphogenetic protein and use thereof |
| PCT/EP2005/002328 WO2005085281A1 (en) | 2004-03-04 | 2005-03-04 | Mutein of a bone morphogenetic protein and use thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012152866A Division JP2012235784A (ja) | 2004-03-04 | 2012-07-06 | 骨形成タンパク質の変異タンパク質及びその使用 |
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| JP2008501309A true JP2008501309A (ja) | 2008-01-24 |
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| JP2012152866A Withdrawn JP2012235784A (ja) | 2004-03-04 | 2012-07-06 | 骨形成タンパク質の変異タンパク質及びその使用 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2012152866A Withdrawn JP2012235784A (ja) | 2004-03-04 | 2012-07-06 | 骨形成タンパク質の変異タンパク質及びその使用 |
Country Status (6)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008509087A (ja) * | 2004-05-27 | 2008-03-27 | アクセルロン ファーマ インコーポレーテッド | Ｔｇｆ抑制解除因子およびそれに関連する使用方法 |
| JP2021513960A (ja) * | 2018-02-15 | 2021-06-03 | ユーシービー バイオファルマ エスアールエル | 骨折又は骨欠損の処置のためのグレムリン−１阻害剤 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1571159A1 (en) | 2004-03-04 | 2005-09-07 | Bayerische Julius-Maximilians-Universität Würzburg | Mutein of a bone morphogenetic protein and use thereof |
| US20090042780A1 (en) * | 2004-05-20 | 2009-02-12 | Acceleron Pharma Inc | Modified TGF-Beta Superfamily Polypeptides and Related Methods |
| US7771995B2 (en) | 2005-11-14 | 2010-08-10 | Merial Limited | Plasmid encoding human BMP-7 |
| EP3147296A1 (en) | 2005-11-14 | 2017-03-29 | Merial, Inc. | Gene therapy for renal failure |
| CN101301467B (zh) * | 2008-04-22 | 2012-01-25 | 同济大学 | Bmp-7在制备预防和/或治疗肝纤维化药物中的应用 |
| US11078248B2 (en) | 2010-03-19 | 2021-08-03 | Lifenet Health | BMP peptides and methods of use |
| US9688735B2 (en) | 2010-08-20 | 2017-06-27 | Wyeth Llc | Designer osteogenic proteins |
| US9856305B2 (en) | 2010-08-20 | 2018-01-02 | Wyeth Llc | Designer osteogenic proteins |
| AU2015202418B2 (en) * | 2010-08-20 | 2017-02-02 | Wyeth Llc | Designer osteogenic proteins |
| SG187589A1 (en) * | 2010-08-20 | 2013-03-28 | Wyeth Llc | Designer osteogenic proteins |
| US20150064163A1 (en) | 2011-09-02 | 2015-03-05 | Lifenet Health | BMP Peptides & Methods of Use |
| EP2602264A1 (en) | 2011-12-05 | 2013-06-12 | Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka mbH | GDF-5 mutant for inducing cartilage formation |
| GB201412290D0 (en) | 2014-07-10 | 2014-08-27 | Cambridge Entpr Ltd | Novel use |
| KR20180014714A (ko) | 2015-06-05 | 2018-02-09 | 노파르티스 아게 | 골 형태형성 단백질 9 (bmp9)를 표적화하는 항체 및 그에 대한 방법 |
| GB201621635D0 (en) | 2016-12-19 | 2017-02-01 | Ucb Biopharma Sprl | Crystal structure |
| US20200121760A1 (en) * | 2017-01-04 | 2020-04-23 | The Trustees Of The University Ofpennsylvania | Methods for scar reduction by converting scar fibroblasts into adipocytes with hair follicle-derived signals |
| US11596712B2 (en) | 2017-10-19 | 2023-03-07 | Genera Istrazivanja D.O.O. | Autologous bone graft substitute composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH02500241A (ja) * | 1986-07-01 | 1990-02-01 | ジェネテイックス・インスティテュート・インコーポレイテッド | 新規骨誘導組成物 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631142A (en) * | 1986-07-01 | 1997-05-20 | Genetics Institute, Inc. | Compositions comprising bone morphogenetic protein-2 (BMP-2) |
| US5304541A (en) | 1988-12-15 | 1994-04-19 | Bristol-Myers Squibb Company | Methods using novel chimeric transforming growth factor-β1/β2 |
| DE69528128T2 (de) | 1994-06-10 | 2003-03-13 | United States Surgical Corp | Rekombinante Chimäre Proteine und Verfahren zur deren Verwendung |
| US5965403A (en) | 1996-09-18 | 1999-10-12 | Genetics Institute, Inc. | Nucleic acids encoding bone morphogenic protein-16 (BMP-16) |
| US6743613B2 (en) | 1999-04-23 | 2004-06-01 | Human Genome Sciences, Inc. | Lysyl-oxidase HOHEC84 polynucleotides |
| DE10026713A1 (de) | 2000-05-30 | 2001-12-06 | Walter Sebald | Mutein einer Kette eines Proteins aus der Superfamilie des Wachstumsfaktors TGF-beta |
| EP1571159A1 (en) | 2004-03-04 | 2005-09-07 | Bayerische Julius-Maximilians-Universität Würzburg | Mutein of a bone morphogenetic protein and use thereof |
| US20090042780A1 (en) | 2004-05-20 | 2009-02-12 | Acceleron Pharma Inc | Modified TGF-Beta Superfamily Polypeptides and Related Methods |
| JP2008509087A (ja) | 2004-05-27 | 2008-03-27 | アクセルロン ファーマ インコーポレーテッド | Ｔｇｆ抑制解除因子およびそれに関連する使用方法 |
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2004
- 2004-03-04 EP EP04005192A patent/EP1571159A1/en not_active Withdrawn
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2005
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- 2005-03-04 US US10/591,482 patent/US7786080B2/en not_active Expired - Fee Related
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- 2005-03-04 EP EP05715753A patent/EP1720902A1/en not_active Withdrawn
- 2005-03-04 CA CA002557788A patent/CA2557788A1/en not_active Abandoned
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02500241A (ja) * | 1986-07-01 | 1990-02-01 | ジェネテイックス・インスティテュート・インコーポレイテッド | 新規骨誘導組成物 |
Non-Patent Citations (5)
| Title |
|---|
| JPN5007002778; Ｊ． Ｂｏｎｅ Ｊｏｉｎｔ Ｓｕｒｇ． ８３-Ａ（ｓｕｐｐｌ．１， ｐａｒｔ１）（２００１）, ｐ．Ｓ１-７-Ｓ１-１４ * |
| JPN5007002779; Ｎａｔ． Ｓｔｒｕｃｔ． Ｂｉｏｌ． ７（６）（２０００）, ｐ．４９２-４９６ * |
| JPN6011000621; 'Ｃｈａｉｎ Ａ， Ｓｔｒｕｃｔｕｒｅ Ｏｆ Ｔｈｅ Ｂｏｎｅ Ｍｏｒｐｈｏｇｅｎｅｔｉｃ Ｐｒｏｔｅｉｎ ２ Ｍｕｔａｎｔ Ｌ５１ｐ．' Ｄａｔａｂａｓｅ ＰＤＢ［ｏｎｌｉｎｅ］， Ａｃｃｅｓｓｉｏｎ Ｎｏ．１ＲＥＵ＿Ａ * |
| JPN6011000623; ＥＭＢＯ Ｊ． １９（１３）（２０００）, ｐ．３３１４-３３２４ * |
| JPN6011000625; Ｄｅｖ． Ｂｉｏｌ． ２５０（２００２）, ｐ．２３１-２５０ * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008509087A (ja) * | 2004-05-27 | 2008-03-27 | アクセルロン ファーマ インコーポレーテッド | Ｔｇｆ抑制解除因子およびそれに関連する使用方法 |
| JP2021513960A (ja) * | 2018-02-15 | 2021-06-03 | ユーシービー バイオファルマ エスアールエル | 骨折又は骨欠損の処置のためのグレムリン−１阻害剤 |
| JP7395485B2 (ja) | 2018-02-15 | 2023-12-11 | ユーシービー バイオファルマ エスアールエル | 骨折又は骨欠損の処置のためのグレムリン－１阻害剤 |
Also Published As
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| AU2005219556B2 (en) | 2012-03-01 |
| AU2005219556A1 (en) | 2005-09-15 |
| JP2012235784A (ja) | 2012-12-06 |
| EP1720902A1 (en) | 2006-11-15 |
| US20070293425A1 (en) | 2007-12-20 |
| US7786080B2 (en) | 2010-08-31 |
| CA2557788A1 (en) | 2005-09-15 |
| EP1571159A1 (en) | 2005-09-07 |
| WO2005085281A1 (en) | 2005-09-15 |
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