DE69737809T2 - Methoden zur herstellung von op-1 morphogen analoge - Google Patents
Methoden zur herstellung von op-1 morphogen analoge Download PDFInfo
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- DE69737809T2 DE69737809T2 DE69737809T DE69737809T DE69737809T2 DE 69737809 T2 DE69737809 T2 DE 69737809T2 DE 69737809 T DE69737809 T DE 69737809T DE 69737809 T DE69737809 T DE 69737809T DE 69737809 T2 DE69737809 T2 DE 69737809T2
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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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (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 |
|---|---|---|---|
| US589552 | 1990-09-28 | ||
| US58955296A | 1996-01-22 | 1996-01-22 | |
| PCT/US1997/001071 WO1997026277A2 (en) | 1996-01-22 | 1997-01-22 | Morphogen analogs and methods for producing them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69737809D1 DE69737809D1 (de) | 2007-07-26 |
| DE69737809T2 true DE69737809T2 (de) | 2008-02-21 |
Family
ID=24358486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69737809T Expired - Lifetime DE69737809T2 (de) | 1996-01-22 | 1997-01-22 | Methoden zur herstellung von op-1 morphogen analoge |
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) |
Families Citing this family (32)
| 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 |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| IL158623A0 (en) | 2001-04-30 | 2004-05-12 | Symbiontics Inc | Subcellular targeting of therapeutic proteins |
| US20040005309A1 (en) * | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
| US20030072761A1 (en) * | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| MXPA04006728A (es) * | 2002-01-10 | 2005-08-19 | Osteotrophin Llc | Tratamiento de desordenes oseos con medicamentos anabolicos esqueleticos. |
| DK1572950T3 (da) * | 2002-06-17 | 2013-02-04 | Thrasos Inc | Enkeltdomæne TDF-relaterede forbindelser og analoger deraf |
| 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 |
| CA2517848A1 (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 |
| US20050009877A1 (en) * | 2003-05-15 | 2005-01-13 | Henry Lu | Methods of identifying HCV NS5B polymerase inhibitors and their uses |
| US20050244400A1 (en) * | 2004-02-10 | 2005-11-03 | Zystor Therapeutics, Inc. | Acid alpha-glucosidase and fragments thereof |
| JP2008500816A (ja) * | 2004-03-31 | 2008-01-17 | ゼンコー・インコーポレイテッド | 改善された性質を有するｂｍｐ−７変異体 |
| EP1773871B1 (en) | 2004-06-17 | 2014-10-15 | 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 |
| PL2497780T3 (pl) * | 2005-09-20 | 2015-09-30 | Thrasos Innovation Inc | Związki pokrewne TDF oraz ich analogi |
| ATE543833T1 (de) * | 2005-12-22 | 2012-02-15 | Janssen Biotech Inc | Bmp-7-varianten-zusammensetzungen, verfahren und verwendungen |
| US7659250B2 (en) * | 2005-12-22 | 2010-02-09 | Centocor, Inc. | BMP-7 variant compositions, methods and uses |
| AU2007322123A1 (en) * | 2006-11-13 | 2008-05-29 | Biomarin Pharmaceutical Inc. | Methods for treating Pompe disease |
| CA2718592A1 (en) * | 2008-02-13 | 2009-08-20 | Keith Hruska | Method of treating vascular sclerosis |
| US20090291967A1 (en) * | 2008-03-05 | 2009-11-26 | Adherex Technologies, Inc. | Small molecule modulators of cell adhesion |
| HUE034850T2 (en) | 2008-05-07 | 2018-03-28 | Biomarin Pharm Inc | Lysosomal targeting peptides and their use |
| EP3679942A1 (en) | 2009-06-17 | 2020-07-15 | 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 |
| EP3341397B1 (en) * | 2015-08-25 | 2024-12-18 | Histide AG | Compounds for inducing tissue formation and uses thereof |
Family Cites Families (39)
| 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 |
| ATE142644T1 (de) * | 1988-04-08 | 1996-09-15 | Stryker Corp | Biosynthetische osteogene proteine und sie enthaltende osteogene vorrichtungen |
| US5284756A (en) * | 1988-10-11 | 1994-02-08 | Lynn Grinna | Heterodimeric osteogenic factor |
| US5118791A (en) | 1989-05-25 | 1992-06-02 | Genentech, Inc. | Biologically active polypeptides based on transforming growth factor-β |
| US5061786A (en) | 1989-05-25 | 1991-10-29 | 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 |
| EP0551440B1 (en) | 1990-09-14 | 2002-12-18 | The Trustees Of The University Of Pennsylvania | Design of bioactive peptides based on immunoglobulin structure |
| 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 |
| US5824647A (en) * | 1990-12-12 | 1998-10-20 | Postlethwaite; Arnold E. | Chemotactic wound healing peptides |
| US5331573A (en) | 1990-12-14 | 1994-07-19 | Balaji Vitukudi N | Method of design of compounds that mimic conformational features of selected 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 |
| JP3645258B2 (ja) * | 1993-01-12 | 2005-05-11 | ジョーンズ ホプキンス ユニバーシティー スクール オブ メディシン | 増殖分化因子−５ |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| EP0746569A4 (en) | 1993-02-03 | 1999-03-24 | Amrad Corp Ltd | DETERMINANT FOR FIXING THE RECEPTOR FROM THE LEUKEMIA INHIBITION 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 |
| JPH09500625A (ja) | 1993-07-09 | 1997-01-21 | スミスクライン・ビーチャム・コーポレイション | 環状セミランダムペプチドライブラリー |
| 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 |
| ATE272719T1 (de) | 1993-11-26 | 2004-08-15 | Lawrence B Hendry | Der entwurf von medikamenten, die in die rezeptor-ligand-dna wechselwirkungen eingreifen |
| 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 |
| ATE354802T1 (de) * | 2000-11-06 | 2007-03-15 | Thrasos Inc | Methoden zum screening knochenmorphogenetishemimetika |
-
1997
- 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 CA CA002244228A patent/CA2244228A1/en not_active Abandoned
- 1997-01-22 US US08/786,284 patent/US6273598B1/en not_active Expired - Lifetime
- 1997-01-22 EP EP97905604A patent/EP0876401B1/en not_active Expired - Lifetime
- 1997-01-22 AT AT97905604T patent/ATE364629T1/de not_active IP Right Cessation
- 1997-01-22 DE DE69737809T patent/DE69737809T2/de not_active Expired - Lifetime
-
2001
- 2001-02-22 US US09/791,946 patent/US20020028453A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2000501744A (ja) | 2000-02-15 |
| EP0876401A2 (en) | 1998-11-11 |
| US6273598B1 (en) | 2001-08-14 |
| AU2244997A (en) | 1997-08-11 |
| EP0876401B1 (en) | 2007-06-13 |
| DE69737809D1 (de) | 2007-07-26 |
| WO1997026277A2 (en) | 1997-07-24 |
| US20020028453A1 (en) | 2002-03-07 |
| CA2244228A1 (en) | 1997-07-24 |
| AU725295B2 (en) | 2000-10-12 |
| WO1997026277A3 (en) | 1997-09-25 |
| ATE364629T1 (de) | 2007-07-15 |
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| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: BRANDEIS UNIVERSITY, WALTHAM, MASS., US Owner name: STRYKER CORP., KALAMAZOO, MICH., US |
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| 8328 | Change in the person/name/address of the agent |
Representative=s name: LICHTI PATENTANWAELTE, 76227 KARLSRUHE |