ATE265529T1 - Bmp-10 zusammensetzungen - Google Patents

Bmp-10 zusammensetzungen

Info

Publication number
ATE265529T1
ATE265529T1 AT94917363T AT94917363T ATE265529T1 AT E265529 T1 ATE265529 T1 AT E265529T1 AT 94917363 T AT94917363 T AT 94917363T AT 94917363 T AT94917363 T AT 94917363T AT E265529 T1 ATE265529 T1 AT E265529T1
Authority
AT
Austria
Prior art keywords
bmp
proteins
compositions
disclosed
bone
Prior art date
Application number
AT94917363T
Other languages
English (en)
Inventor
Anthony J Celeste
John M Wozney
Original Assignee
Inst Genetics Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Inst Genetics Llc filed Critical Inst Genetics Llc
Application granted granted Critical
Publication of ATE265529T1 publication Critical patent/ATE265529T1/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Epoxy Resins (AREA)
  • Dental Preparations (AREA)
  • Lubricants (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
AT94917363T 1993-05-12 1994-05-12 Bmp-10 zusammensetzungen ATE265529T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6169593A 1993-05-12 1993-05-12
PCT/US1994/005290 WO1994026893A1 (en) 1993-05-12 1994-05-12 Bmp-10 compositions

Publications (1)

Publication Number Publication Date
ATE265529T1 true ATE265529T1 (de) 2004-05-15

Family

ID=22037505

Family Applications (1)

Application Number Title Priority Date Filing Date
AT94917363T ATE265529T1 (de) 1993-05-12 1994-05-12 Bmp-10 zusammensetzungen

Country Status (12)

Country Link
EP (1) EP0698095B1 (de)
JP (1) JPH09501305A (de)
KR (1) KR100231640B1 (de)
AT (1) ATE265529T1 (de)
AU (1) AU677849B2 (de)
BR (1) BR9406716A (de)
CA (1) CA2161807A1 (de)
DE (1) DE69433742T2 (de)
FI (1) FI955420A7 (de)
NO (1) NO954525D0 (de)
OA (1) OA10192A (de)
WO (1) WO1994026893A1 (de)

Families Citing this family (105)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE20004692U1 (de) 2000-03-14 2001-07-26 Sofamor Danek GmbH, 94469 Deggendorf Wirbelimplantat zum Einschrauben in einen Wirbelzwischenraum
US6150328A (en) 1986-07-01 2000-11-21 Genetics Institute, Inc. BMP products
KR100227406B1 (ko) * 1993-05-12 1999-12-01 브루스 엠. 에이센 Bmp-11 조성물
US6291206B1 (en) 1993-09-17 2001-09-18 Genetics Institute, Inc. BMP receptor proteins
AU689184B2 (en) 1993-12-07 1998-03-26 Genetics Institute, Llc BMP-12, BMP-13 and tendon-inducing compositions thereof
US5906827A (en) * 1994-06-03 1999-05-25 Creative Biomolecules, Inc. Matrix for the manufacture of autogenous replacement body parts
US5846770A (en) * 1994-11-22 1998-12-08 Genetics Institute, Inc. DNA molecules encoding human chordin
US5782919A (en) 1995-03-27 1998-07-21 Sdgi Holdings, Inc. Interbody fusion device and method for restoration of normal spinal anatomy
US5645084A (en) * 1995-06-07 1997-07-08 Danek Medical, Inc. Method for spinal fusion without decortication
US6206922B1 (en) 1995-03-27 2001-03-27 Sdgi Holdings, Inc. Methods and instruments for interbody fusion
US5635372A (en) * 1995-05-18 1997-06-03 Genetics Institute, Inc. BMP-15 compositions
HU222664B1 (hu) 1995-06-05 2003-09-29 Genetics Institute, Llc Csont morfogenetikus protein (BMP) alkalmazása csont és ín vagy szalag funkcionális összeköttetésének regenerálására
US5902785A (en) * 1995-06-06 1999-05-11 Genetics Institute, Inc. Cartilage induction by bone morphogenetic proteins
US6423095B1 (en) 1995-10-16 2002-07-23 Sdgi Holdings, Inc. Intervertebral spacers
US5989289A (en) 1995-10-16 1999-11-23 Sdgi Holdings, Inc. Bone grafts
US5700774A (en) * 1996-03-26 1997-12-23 Genetics Institute, Inc. Compositions comprising bone morphogenic proteins and truncated parathyroid hormone related peptide, and methods of inducing cartilage by administration of same
US5965403A (en) * 1996-09-18 1999-10-12 Genetics Institute, Inc. Nucleic acids encoding bone morphogenic protein-16 (BMP-16)
KR20000052740A (ko) 1996-10-23 2000-08-25 에스디지아이 홀딩스 인코포레이티드 척수간극기
US6037519A (en) * 1997-10-20 2000-03-14 Sdgi Holdings, Inc. Ceramic fusion implants and compositions
JP4388602B2 (ja) 1997-02-07 2009-12-24 ストライカー コーポレイション マトリクスを含まない骨形成デバイス、移植片、およびその使用方法
US20010016646A1 (en) 1998-03-20 2001-08-23 David C. Rueger Osteogenic devices and methods of use thereof for repair of endochondral bone, osteochondral and chondral defects
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
TW562807B (en) * 1997-04-01 2003-11-21 Chugai Pharmaceutical Co Ltd Novel secretory membrane protein
EP2309261A1 (de) 1997-05-30 2011-04-13 Stryker Corporation Verfahren zur Beurteilung von Gewebemorphogenese und- aktivität
US5972368A (en) * 1997-06-11 1999-10-26 Sdgi Holdings, Inc. Bone graft composites and spacers
US20020052026A1 (en) 1997-10-08 2002-05-02 Steven M. Vicik Methods of refolding proteins
US6511509B1 (en) 1997-10-20 2003-01-28 Lifenet Textured bone allograft, method of making and using same
AU1906599A (en) * 1997-12-09 1999-06-28 Ontogeny, Inc. Pancreatic-derived factors, and uses related thereto
US6027917A (en) 1997-12-10 2000-02-22 Genetics Institute, Inc. Bone morphogenetic protein (BMP)-17 and BMP-18 compositions
US7147839B2 (en) 1998-05-29 2006-12-12 Curis, Inc. Methods for evaluating tissue morphogenesis and activity
US6270528B1 (en) 1998-08-06 2001-08-07 Sdgi Holdings, Inc. Composited intervertebral bone spacers
US6727224B1 (en) 1999-02-01 2004-04-27 Genetics Institute, Llc. Methods and compositions for healing and repair of articular cartilage
EP2286847A1 (de) 1999-10-15 2011-02-23 Genetics Institute, LLC Hyaluronsäure enthaltende Zusammensetzungen zur Abgabe osteogener Proteine
US6752831B2 (en) 2000-12-08 2004-06-22 Osteotech, Inc. Biocompatible osteogenic band for repair of spinal disorders
AU2002245092A1 (en) 2000-12-08 2002-07-30 Todd M. Boyce Implant for orthopedic applications
US7226587B2 (en) 2001-06-01 2007-06-05 Wyeth Compositions and methods for systemic administration of sequences encoding bone morphogenetic proteins
TWI267378B (en) 2001-06-08 2006-12-01 Wyeth Corp Calcium phosphate delivery vehicles for osteoinductive proteins
AU2002365538A1 (en) * 2001-11-27 2003-06-10 Nexyte Ab Production of eukaryotic proteins and nucleic acid molecules in c. elegans
CH695985A5 (de) * 2002-01-21 2006-11-15 Straumann Holding Ag Oberflächenmodifizierte Implantate.
US7491691B2 (en) 2002-05-03 2009-02-17 Sindrey Dennis R Connective tissue stimulating peptides
ES2282904T3 (es) 2003-09-12 2007-10-16 Wyeth Barras solidas de fosfato calcico inyectables para el suministro de proteinas osteogenicas.
PL1737734T3 (pl) 2004-03-10 2011-02-28 Scil Tech Gmbh Powlekane implanty, ich wytwarzanie i zastosowanie
EP1732589A2 (de) 2004-03-26 2006-12-20 Acceleron Pharma Inc. Bmp-3-propeptide und relevante verfahren
EP1740609A2 (de) 2004-04-27 2007-01-10 Research Development Foundation Antagonismus des tgf-beta superfamily signal rezeptors
US7741284B2 (en) 2004-05-12 2010-06-22 Acceleron Pharma Inc. BMP10 propeptides and related methods
CA2567405A1 (en) 2004-05-25 2005-12-08 Stryker Corporation Use of morphogenic proteins for treating cartilage defects
US7749268B2 (en) 2004-05-26 2010-07-06 Warsaw Orthopedic, Inc. Methods for treating the spine
AU2005258286A1 (en) 2004-06-24 2006-01-05 Acceleron Pharma Inc. GDF3 propeptides and related methods
ES2561048T3 (es) 2004-07-23 2016-02-24 Acceleron Pharma Inc. Polipéptidos del receptor ActRII
US7473678B2 (en) 2004-10-14 2009-01-06 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods of use thereof
ME00380B (me) 2005-11-23 2011-10-10 Acceleron Pharma Inc Amtagonisti aktivin-actriia i primjene za stimulaciju rasta kosti
US8128933B2 (en) 2005-11-23 2012-03-06 Acceleron Pharma, Inc. Method of promoting bone growth by an anti-activin B antibody
US8147860B2 (en) 2005-12-06 2012-04-03 Etex Corporation Porous calcium phosphate bone material
ES2427993T3 (es) 2006-02-09 2013-11-05 Biomimetic Therapeutics, Llc Composiciones y métodos para el tratamiento de hueso
US20090298761A1 (en) 2006-05-17 2009-12-03 Donald Engelman Methods of treating cartilage defects using a soluble morphogenic protein complex
US9642891B2 (en) 2006-06-30 2017-05-09 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
AU2007234612B2 (en) 2006-12-14 2013-06-27 Johnson & Johnson Regenerative Therapeutics, Llc Protein stabilization formulations
US8895016B2 (en) 2006-12-18 2014-11-25 Acceleron Pharma, Inc. Antagonists of activin-actriia and uses for increasing red blood cell levels
ES2447516T3 (es) 2006-12-21 2014-03-12 Stryker Corporation Formulaciones de liberación sostenida que comprenden cristales BMP-7
US9526759B2 (en) 2007-02-01 2016-12-27 Acceleron Pharma Inc. Activin-actriia antagonists and uses for treating or preventing breast cancer
TW201940502A (zh) 2007-02-02 2019-10-16 美商艾瑟勒朗法瑪公司 衍生自ＡｃｔＲＩＩＢ的變體與其用途
KR101672156B1 (ko) 2007-02-09 2016-11-02 악셀레론 파마 인코포레이티드 액티빈-ＡｃｔＲⅡＡ 길항제 및 암 환자에서 골 생장을 촉진시키기 위한 이의 용도
US7678764B2 (en) 2007-06-29 2010-03-16 Johnson & Johnson Regenerative Therapeutics, Llc Protein formulations for use at elevated temperatures
US8058237B2 (en) 2007-08-07 2011-11-15 Advanced Technologies & Regenerative Medicine, LLC Stable composition of GDF-5 and method of storage
CN107412734A (zh) 2007-09-18 2017-12-01 阿塞勒隆制药公司 活化素‑actriia拮抗剂和减少或抑制fsh分泌的用途
CA2718592A1 (en) 2008-02-13 2009-08-20 Keith Hruska Method of treating vascular sclerosis
WO2009129101A1 (en) 2008-04-14 2009-10-22 Advanced Technologies And Regenerative Medicine, Llc Liquid buffered gdf-5 formulations
LT3750552T (lt) 2008-08-14 2023-06-26 Acceleron Pharma Inc. Gdf gaudyklės
US8216997B2 (en) 2008-08-14 2012-07-10 Acceleron Pharma, Inc. Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators
MX2011002555A (es) 2008-09-09 2011-08-03 Biomimetic Therapeutics Inc Composiciones de factor de crecimiento derivadas de plaquetas y metodo para el tratamiento de lesiones de tendon y ligamentos.
CA2749544A1 (en) 2009-01-13 2010-07-22 Acceleron Pharma Inc. Methods for increasing adiponectin
CA2752157A1 (en) 2009-02-12 2010-08-19 Stryker Corporation Peripheral administration of proteins including tgf-.beta. superfamily members for systemic treatment of disorders and disease
JP5819734B2 (ja) 2009-02-12 2015-11-24 ストライカー コーポレイションＳｔｒｙｋｅｒ Ｃｏｒｐｏｒａｔｉｏｎ ＴＧＦ−βスーパーファミリーメンバー含有タンパク質の最小に侵襲性の全身送達のための組成物および方法
US20120148539A1 (en) 2009-03-24 2012-06-14 Moulay Hicham Alaoui-Ismaili Methods and Compositions for Tissue Engineering
MX385318B (es) 2009-06-08 2025-03-18 Acceleron Pharma Inc Metodos para aumentar adipocitos termogenicos.
WO2010144696A1 (en) 2009-06-11 2010-12-16 Burnham Institute For Medical Research Directed differentiation of stem cells
JP2012529294A (ja) 2009-06-12 2012-11-22 アクセルロン ファーマ， インコーポレイテッド 切断型ＡｃｔＲＩＩＢ−Ｆｃ融合タンパク質
US9399086B2 (en) 2009-07-24 2016-07-26 Warsaw Orthopedic, Inc Implantable medical devices
WO2011031856A1 (en) 2009-09-09 2011-03-17 Stryker Corporation Bmp -7 for use in treating pain induced by injuries and diseases of an articular joint
ES2387379T3 (es) 2009-09-17 2012-09-21 Stryker Corporation Tampones para controlar el pH de las proteínas morfogenéticas óseas
EP2501400B1 (de) 2009-11-17 2017-11-01 Acceleron Pharma, Inc. Actriib-proteine und varianten davon sowie ihre anwendung zur utrophin-induktion für therapien gegen muskuläre dystrophie
AU2010341565A1 (en) 2009-12-22 2012-07-12 Stryker Corporation BMP-7 variants with reduced immunogenicity
WO2011103598A1 (en) 2010-02-22 2011-08-25 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods for the treatment of tendinopathies
WO2011139594A2 (en) 2010-04-27 2011-11-10 Medtronic, Inc. Artificial bursa for intra-articular drug delivery
WO2012064771A1 (en) 2010-11-08 2012-05-18 Acceleron Pharma, Inc. Actriia binding agents and uses thereof
US9809636B2 (en) 2012-04-06 2017-11-07 Acceleron Pharma Inc. Methods for increasing red blood cell levels comprising administering BMP9
WO2014012101A1 (en) 2012-07-13 2014-01-16 Trustees Of Tufts College Silk powder compaction for production of constructs with high mechanical strength and stiffness
RU2018145985A (ru) 2012-11-02 2019-02-18 Селджин Корпорейшн Антагонисты активина-actrii и их применение для лечения нарушений костной ткани и других нарушений
WO2014172692A1 (en) 2013-04-19 2014-10-23 Theracell, Inc. Demineralized bone fibers having controlled geometry and shapes and methods thereof
TN2016000553A1 (en) 2014-06-13 2018-04-04 Acceleron Pharma Inc Methods and compositions for treating ulcers
GB201412290D0 (en) 2014-07-10 2014-08-27 Cambridge Entpr Ltd Novel use
MA41052A (fr) 2014-10-09 2017-08-15 Celgene Corp Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii
DK3227675T3 (da) 2014-12-03 2023-05-30 Celgene Corp Activin-actrii-antagonister og anvendelser til behandling af myelodysplastisk syndrom
US10610366B2 (en) 2015-01-29 2020-04-07 Theracell, Inc. Demineralized bone fiber composition for use in minimally invasive surgery
KR20180019646A (ko) 2015-06-17 2018-02-26 워쏘우 오르쏘페딕 인코포레이티드 옥시스테롤을 포함하는 임플란트 및 사용 방법
EP3821880A1 (de) 2015-10-26 2021-05-19 President and Fellows of Harvard College Oxidierte polysaccharide und verfahren zur verwendung davon
US10688222B2 (en) 2016-11-21 2020-06-23 Warsaw Orthopedic, Inc. Lyophilized moldable implants containing an oxysterol
US10639157B2 (en) 2017-03-14 2020-05-05 Theracell, Inc. Demineralized bone fiber composition for use in minimally invasive surgery
US11464888B2 (en) 2017-06-12 2022-10-11 Warsaw Orthopedic, Inc. Moldable formulations containing an oxysterol in an acellular tissue matrix
US12109326B2 (en) 2017-08-11 2024-10-08 Theracell, Llc Demineralized bone fiber composition for augmentation of fixation
US11103618B2 (en) 2018-02-22 2021-08-31 Warsaw Orthopedic, Inc. Demineralized bone matrix having improved handling characteristics
EP3920852B1 (de) 2019-02-09 2025-04-09 Theracell, LLC Entmineralisierte knochenfaserimplantatzusammensetzungen und ihre herstellungsmethoden
US11498880B2 (en) 2019-07-26 2022-11-15 Warsaw Orthopedic, Inc. Calcium phosphate granules and methods of making them
CN113603792B (zh) * 2021-08-26 2023-06-30 深圳市人民医院 一种重组骨形态发生蛋白-2及其制备方法和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06500991A (ja) * 1990-05-16 1994-01-27 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 骨および軟骨誘導蛋白質
DK0592562T3 (da) * 1991-06-25 1999-08-30 Genetics Inst BMP-9-præparater

Also Published As

Publication number Publication date
FI955420A0 (fi) 1995-11-10
NO954525L (no) 1995-11-09
KR960701997A (ko) 1996-03-28
EP0698095B1 (de) 2004-04-28
KR100231640B1 (ko) 1999-12-01
NO954525D0 (no) 1995-11-09
OA10192A (en) 1996-12-18
JPH09501305A (ja) 1997-02-10
BR9406716A (pt) 1996-02-06
EP0698095A1 (de) 1996-02-28
CA2161807A1 (en) 1994-11-24
FI955420L (fi) 1996-01-08
DE69433742T2 (de) 2005-07-07
DE69433742D1 (de) 2004-06-03
AU677849B2 (en) 1997-05-08
WO1994026893A1 (en) 1994-11-24
FI955420A7 (fi) 1996-01-08
AU6910794A (en) 1994-12-12

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