JP2000501744A - モルホゲン類似体およびその製法 - Google Patents
モルホゲン類似体およびその製法Info
- Publication number
- JP2000501744A JP2000501744A JP9526303A JP52630397A JP2000501744A JP 2000501744 A JP2000501744 A JP 2000501744A JP 9526303 A JP9526303 A JP 9526303A JP 52630397 A JP52630397 A JP 52630397A JP 2000501744 A JP2000501744 A JP 2000501744A
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- human
- morphogen
- cells
- hop
- analog
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US58955296A | 1996-01-22 | 1996-01-22 | |
| US08/589,552 | 1996-01-22 | ||
| PCT/US1997/001071 WO1997026277A2 (en) | 1996-01-22 | 1997-01-22 | Morphogen analogs and methods for producing them |
Publications (2)
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|---|---|
| JP2000501744A true JP2000501744A (ja) | 2000-02-15 |
| JP2000501744A5 JP2000501744A5 (enExample) | 2004-11-11 |
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| JP9526303A Ceased JP2000501744A (ja) | 1996-01-22 | 1997-01-22 | モルホゲン類似体およびその製法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US6273598B1 (enExample) |
| EP (1) | EP0876401B1 (enExample) |
| JP (1) | JP2000501744A (enExample) |
| AT (1) | ATE364629T1 (enExample) |
| AU (1) | AU725295B2 (enExample) |
| CA (1) | CA2244228A1 (enExample) |
| DE (1) | DE69737809T2 (enExample) |
| WO (1) | WO1997026277A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006507804A (ja) * | 2002-06-17 | 2006-03-09 | トラソス インコーポレイテッド | 単一ドメインtdf関連化合物およびその類似体 |
| JP2019502674A (ja) * | 2015-08-25 | 2019-01-31 | ヒスタイド アクツィエンゲゼルシャフト | 組織形成誘導用化合物及びその使用 |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030185792A1 (en) * | 1996-01-22 | 2003-10-02 | Curis, Inc. | Morphogen analogs of bone morphogenic proteins |
| US7122623B2 (en) | 1996-07-12 | 2006-10-17 | Adherex Technologies, Inc. | Compounds and methods for modulating cell adhesion |
| US20040006011A1 (en) * | 1996-07-12 | 2004-01-08 | Gour Barbara J. | Peptidomimetic modulators of cell adhesion |
| US5922558A (en) * | 1997-09-12 | 1999-07-13 | Lumigen, Inc. | Methods and compositions for generating chemiluminescence with a peroxidase |
| DE19831758A1 (de) * | 1998-07-15 | 2000-02-03 | Jerini Bio Tools Gmbh | Ligandenbestimmung für Proteine |
| WO2001053331A2 (en) * | 2000-01-24 | 2001-07-26 | Adherex Technologies, Inc. | Peptidomimetic modulators of cell adhesion |
| US7629309B2 (en) * | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20040005309A1 (en) * | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
| US7560424B2 (en) * | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| EP1974752B1 (en) | 2001-04-30 | 2012-09-26 | BioMarin Pharmaceutical Inc. | Subcellular targeting of therapeutic proteins |
| US20030072761A1 (en) * | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| US7015195B2 (en) * | 2002-01-10 | 2006-03-21 | Osteotrophin, Llc | Treatment of bone disorders with skeletal anabolic drugs |
| AU2002950183A0 (en) * | 2002-07-12 | 2002-09-12 | The Council Of The Queensland Institute Of Medical Research | Expression of hydrophobic proteins |
| US20040093164A1 (en) * | 2002-11-08 | 2004-05-13 | Carlson William D. | Computer system and methods for producing morphogen analogs of human TDF-1 |
| AU2004205643A1 (en) * | 2003-01-21 | 2004-08-05 | The Trustees Of The University Of Pennsylvania | Computational design of a water-soluble analog of a protein, such as phospholamban and potassium channel KcsA |
| US20040204862A1 (en) * | 2003-04-11 | 2004-10-14 | Wainer Irving W. | Computer-based model for identification and characterization for non-competitive inhibitors of nicotinic acetylcholine receptors and related ligand-gated ion channel receptors |
| WO2005000308A2 (en) * | 2003-05-15 | 2005-01-06 | Rigel Pharmaceuticals, Inc. | Methods of identifying hcv ns5b polymerase inhibitors and use against hepatitis c |
| EP1716232B9 (en) * | 2004-02-10 | 2010-10-13 | ZyStor Therapeutics , Inc. | Acid alpha-glucosidase and fragments thereof |
| EP1730186A2 (en) * | 2004-03-31 | 2006-12-13 | Xencor, Inc. | Bmp-7 variants with improved properties |
| CA2897218A1 (en) * | 2004-06-17 | 2006-01-26 | Thrasos Innovation, Inc. | Tdf-related compounds and analogs thereof |
| AU2012201060B2 (en) * | 2005-09-20 | 2015-01-22 | Thrasos Innovation, Inc. | TDF-related compounds and analogs thereof |
| HUE026634T2 (en) * | 2005-09-20 | 2016-07-28 | Thrasos Innovation Inc | TDF-related compounds and analogues thereof |
| 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 |
| WO2008063511A2 (en) * | 2006-11-13 | 2008-05-29 | Zystor Therapeutics, Inc. | Methods for treating pompe disease |
| EP2268302B1 (en) * | 2008-02-13 | 2014-04-09 | Keith Hruska | Bmp-7 for use in treating neointimal hyperplasia |
| US20090291967A1 (en) * | 2008-03-05 | 2009-11-26 | Adherex Technologies, Inc. | Small molecule modulators of cell adhesion |
| EP3187508A1 (en) | 2008-05-07 | 2017-07-05 | BioMarin Pharmaceutical Inc. | Lysosomal targeting peptides and uses thereof |
| EP2475376B1 (en) | 2009-06-17 | 2016-03-30 | BioMarin Pharmaceutical Inc. | Formulations for lysosomal enzymes |
| US9721070B2 (en) | 2013-12-19 | 2017-08-01 | Chevron Phillips Chemical Company Lp | Selective oligomerization catalysts and methods of identifying same |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03500655A (ja) * | 1988-04-08 | 1991-02-14 | ストライカー・コーポレーション | 骨形成デバイス |
| US5331573A (en) * | 1990-12-14 | 1994-07-19 | Balaji Vitukudi N | Method of design of compounds that mimic conformational features of selected peptides |
| JPH07500487A (ja) * | 1990-10-18 | 1995-01-19 | ストライカー コーポレイション | 骨形成ペプチド |
| JPH08506018A (ja) * | 1993-01-28 | 1996-07-02 | アムジエン・インコーポレーテツド | G−csf類似体組成物及び方法 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4908773A (en) | 1987-04-06 | 1990-03-13 | Genex Corporation | Computer designed stabilized proteins and method for producing same |
| US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
| US5266683A (en) * | 1988-04-08 | 1993-11-30 | Stryker Corporation | Osteogenic proteins |
| US5284756A (en) * | 1988-10-11 | 1994-02-08 | Lynn Grinna | Heterodimeric osteogenic factor |
| US5061786A (en) | 1989-05-25 | 1991-10-29 | Genentech, Inc. | Biologically active polypeptides based on transforming growth factor-β |
| US5118791A (en) | 1989-05-25 | 1992-06-02 | Genentech, Inc. | Biologically active polypeptides based on transforming growth factor-β |
| GB8914122D0 (en) * | 1989-06-20 | 1989-08-09 | Wellcome Found | Polypeptide expression |
| US5194596A (en) * | 1989-07-27 | 1993-03-16 | California Biotechnology Inc. | Production of vascular endothelial cell growth factor |
| US5350836A (en) * | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
| GB8927546D0 (en) * | 1989-12-06 | 1990-02-07 | Ciba Geigy | Process for the production of biologically active tgf-beta |
| US5688678A (en) * | 1990-05-16 | 1997-11-18 | Genetics Institute, Inc. | DNA encoding and methods for producing BMP-8 proteins |
| WO1992001933A1 (en) | 1990-07-20 | 1992-02-06 | E.I. Du Pont De Nemours And Company | Generation of a complete set of structural coordinates of a molecule from a set of partial coordinates |
| JPH06504271A (ja) | 1990-09-14 | 1994-05-19 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | 免疫グロブリンの構造に基づく生物活性なペプチドのデザイン |
| US5824647A (en) * | 1990-12-12 | 1998-10-20 | Postlethwaite; Arnold E. | Chemotactic wound healing peptides |
| EP0590055B1 (en) * | 1991-06-19 | 1997-12-03 | New York Medical College | M-protein peptides of influenza virus as antiviral agents |
| AU3320193A (en) | 1991-07-22 | 1993-02-23 | Regents Of The University Of California, The | Methods of designing specific affectors using three-dimensional conformation of enzyme/affector complex |
| JPH05262788A (ja) | 1991-09-03 | 1993-10-12 | Hitachi Chem Co Ltd | ペプチド類、その設計方法及び製造方法並びに受容体上の生理活性ペプチドの結合部位の決定方法 |
| US5353236A (en) | 1992-04-23 | 1994-10-04 | The Board Of Trustees Of The Leland Stanford University | High-resolution crystallographic modelling of a macromolecule |
| US5322933A (en) | 1992-05-07 | 1994-06-21 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Crystal structure of TGF-β-2 |
| AU4801393A (en) * | 1992-08-03 | 1994-03-03 | New York University | Cloning, expression and uses for neurocan as a chondroitin sulfate proteoglycan |
| EP0690871A4 (en) * | 1993-01-12 | 1999-10-20 | Univ Johns Hopkins Med | GROWTH DIFFERENTIATION FACTOR-5 |
| WO1994018236A1 (en) | 1993-02-03 | 1994-08-18 | Amrad Corporation Limited | Receptor-binding determinant from leukaemia inhibitory factor |
| US5453937A (en) | 1993-04-28 | 1995-09-26 | Immunex Corporation | Method and system for protein modeling |
| US5637480A (en) * | 1993-05-12 | 1997-06-10 | Genetics Institute, Inc. | DNA molecules encoding bone morphogenetic protein-10 |
| US6194544B1 (en) | 1993-07-09 | 2001-02-27 | Smithkline Beecham Corporation | Cyclic semi-random peptide libraries |
| GB9317120D0 (en) | 1993-08-17 | 1993-09-29 | Royal Postgrad Med School | Human serum amyloid p component |
| US5856122A (en) | 1993-08-24 | 1999-01-05 | University Of Alberta | Modification of pertussis toxin |
| US5652334A (en) | 1993-09-08 | 1997-07-29 | City Of Hope | Method for design of substances that enhance memory and improve the quality of life |
| US5565352A (en) * | 1993-11-24 | 1996-10-15 | Arch Development Corporation | Deubiquitinating enzyme: compositions and methods |
| EP0740708B1 (en) | 1993-11-26 | 2004-08-04 | Lawrence B. Hendry | Design of drugs involving receptor-ligand-dna interactions |
| US6040431A (en) * | 1995-06-07 | 2000-03-21 | Stryker Corporation | Single chain analogs of the TGF-β superfamily (morphons) |
| US5932716A (en) * | 1995-07-26 | 1999-08-03 | Creative Biomolecules, Inc. | Morphogen-responsive regulatory elements |
| US6677432B1 (en) * | 1998-10-07 | 2004-01-13 | Stryker Corporation | Mutations of the C-terminal portion of TGF-β superfamily proteins |
| JP3786533B2 (ja) * | 1998-11-12 | 2006-06-14 | 善彦 西村 | ペプチド及び骨形成促進剤 |
| CA2431552A1 (en) * | 2000-11-06 | 2002-05-16 | Thrasos, Inc. | Screening methods for bone morphogenetic mimetics |
-
1997
- 1997-01-22 CA CA002244228A patent/CA2244228A1/en not_active Abandoned
- 1997-01-22 EP EP97905604A patent/EP0876401B1/en not_active Expired - Lifetime
- 1997-01-22 DE DE69737809T patent/DE69737809T2/de not_active Expired - Lifetime
- 1997-01-22 WO PCT/US1997/001071 patent/WO1997026277A2/en not_active Ceased
- 1997-01-22 AU AU22449/97A patent/AU725295B2/en not_active Ceased
- 1997-01-22 JP JP9526303A patent/JP2000501744A/ja not_active Ceased
- 1997-01-22 AT AT97905604T patent/ATE364629T1/de not_active IP Right Cessation
- 1997-01-22 US US08/786,284 patent/US6273598B1/en not_active Expired - Lifetime
-
2001
- 2001-02-22 US US09/791,946 patent/US20020028453A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03500655A (ja) * | 1988-04-08 | 1991-02-14 | ストライカー・コーポレーション | 骨形成デバイス |
| JPH07500487A (ja) * | 1990-10-18 | 1995-01-19 | ストライカー コーポレイション | 骨形成ペプチド |
| US5331573A (en) * | 1990-12-14 | 1994-07-19 | Balaji Vitukudi N | Method of design of compounds that mimic conformational features of selected peptides |
| JPH08506018A (ja) * | 1993-01-28 | 1996-07-02 | アムジエン・インコーポレーテツド | G−csf類似体組成物及び方法 |
Non-Patent Citations (5)
| Title |
|---|
| JPN4007000050, J Mol Biol 244 p.657−658 (1994) * |
| JPN6010052329, J Mol Biol 244 p.657−658 (1994) * |
| JPN6010052330, Proc Natl Acad Sci USA 93 p.878−883 (1996 Jan) * |
| JPNX007000092, Proc Natl Acad Sci USA 93 p.878−883 (1996 Jan) * |
| JPNX007000093, Nature 420 p.636 (2002) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006507804A (ja) * | 2002-06-17 | 2006-03-09 | トラソス インコーポレイテッド | 単一ドメインtdf関連化合物およびその類似体 |
| JP2019502674A (ja) * | 2015-08-25 | 2019-01-31 | ヒスタイド アクツィエンゲゼルシャフト | 組織形成誘導用化合物及びその使用 |
| JP2022043261A (ja) * | 2015-08-25 | 2022-03-15 | ヒスタイド アクツィエンゲゼルシャフト | 組織形成誘導用化合物及びその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US6273598B1 (en) | 2001-08-14 |
| DE69737809D1 (de) | 2007-07-26 |
| CA2244228A1 (en) | 1997-07-24 |
| EP0876401B1 (en) | 2007-06-13 |
| WO1997026277A3 (en) | 1997-09-25 |
| EP0876401A2 (en) | 1998-11-11 |
| ATE364629T1 (de) | 2007-07-15 |
| US20020028453A1 (en) | 2002-03-07 |
| WO1997026277A2 (en) | 1997-07-24 |
| AU2244997A (en) | 1997-08-11 |
| AU725295B2 (en) | 2000-10-12 |
| DE69737809T2 (de) | 2008-02-21 |
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