ATE308336T1 - Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten - Google Patents

Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten

Info

Publication number
ATE308336T1
ATE308336T1 AT93900497T AT93900497T ATE308336T1 AT E308336 T1 ATE308336 T1 AT E308336T1 AT 93900497 T AT93900497 T AT 93900497T AT 93900497 T AT93900497 T AT 93900497T AT E308336 T1 ATE308336 T1 AT E308336T1
Authority
AT
Austria
Prior art keywords
treatment
bone diseases
metabolic bone
osteogenic proteins
bone
Prior art date
Application number
AT93900497T
Other languages
English (en)
Inventor
Thangavel Kuberasampath
Charles M Cohen
Hermann Oppermann
Engin Ozkaynak
David C Rueger
Roy H L Pang
John E Smart
Original Assignee
Curis Inc
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 Curis Inc filed Critical Curis Inc
Application granted granted Critical
Publication of ATE308336T1 publication Critical patent/ATE308336T1/de

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/23—Calcitonins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • 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
    • 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
    • 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
    • C07K14/575—Hormones
    • C07K14/62—Insulins
    • C07K14/625—Extraction from natural sources
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6881—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005—The prosthesis being constructed from a particular material
    • A61F2310/00365—Proteins; Polypeptides; Degradation products thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Analytical Chemistry (AREA)
  • Rheumatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Obesity (AREA)
  • Transplantation (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Wood Science & Technology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
AT93900497T 1991-08-30 1992-08-28 Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten ATE308336T1 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US75286191A 1991-08-30 1991-08-30
US75285791A 1991-08-30 1991-08-30
US75276491A 1991-08-30 1991-08-30
US92378092A 1992-07-31 1992-07-31
PCT/US1992/007432 WO1993005751A2 (en) 1991-08-30 1992-08-28 Osteogenic proteins in the treatment of bone deseases

Publications (1)

Publication Number Publication Date
ATE308336T1 true ATE308336T1 (de) 2005-11-15

Family

ID=27505659

Family Applications (1)

Application Number Title Priority Date Filing Date
AT93900497T ATE308336T1 (de) 1991-08-30 1992-08-28 Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten

Country Status (7)

Country Link
EP (2) EP0601135B1 (de)
JP (2) JP4235689B2 (de)
AT (1) ATE308336T1 (de)
CA (1) CA2116559C (de)
DE (1) DE69233559T2 (de)
ES (1) ES2253736T3 (de)
WO (1) WO1993005751A2 (de)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7378392B1 (en) 1990-05-16 2008-05-27 Genetics Institute, Llc Bone and cartilage inductive proteins
US5688678A (en) * 1990-05-16 1997-11-18 Genetics Institute, Inc. DNA encoding and methods for producing BMP-8 proteins
US6395883B1 (en) 1991-03-11 2002-05-28 Curis, Inc. Soluble morphogenic protein complex compositions of matter
ATE175441T1 (de) * 1991-06-25 1999-01-15 Genetics Inst Bmp-9 zusammensetzungen
US6287816B1 (en) * 1991-06-25 2001-09-11 Genetics Institute, Inc. BMP-9 compositions
EP0601135B1 (de) * 1991-08-30 2005-11-02 Curis, Inc. Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten
KR950702627A (ko) * 1992-07-31 1995-07-29 찰스 엠. 코헨 모르포겐 단백질의 가용성 복합체 및 그의 조성물(Morphogenic Protein Soluble Complex and Composition Thereof)
AU5129293A (en) * 1992-09-15 1994-04-12 Creative Biomolecules, Inc. 60a protein-induced morphogenesis
EP0672064A1 (de) * 1992-11-03 1995-09-20 Creative Biomolecules, Inc. Op 3 - induzierte morphogenese
US5942496A (en) * 1994-02-18 1999-08-24 The Regent Of The University Of Michigan Methods and compositions for multiple gene transfer into bone cells
DE4427221A1 (de) * 1994-08-01 1996-02-08 Gsf Forschungszentrum Umwelt Retrovirus-induzierte Osteoklasten-Modulation für die Osteoporose-Therapie
US6040431A (en) 1995-06-07 2000-03-21 Stryker Corporation Single chain analogs of the TGF-β superfamily (morphons)
US5869041A (en) * 1996-01-12 1999-02-09 The Miriam Hospital Delivery of bioactive compounds to an organism
ATE244574T1 (de) 1996-03-22 2003-07-15 Curis Inc Verfahren zur verbesserten funktionelle erholung der motorische koordiination, der sprache oder der sinneswahrnehmung nach trauma oder ischämie des zns
AU7142000A (en) * 1996-05-06 2001-01-25 Curis, Inc. Morphogen treatment for chronic renal failure
AU757969B2 (en) * 1996-05-06 2003-03-13 Stryker Corporation Therapies for chronic renal failure
US6498142B1 (en) 1996-05-06 2002-12-24 Curis, Inc. Morphogen treatment for chronic renal failure
ATE239514T1 (de) † 1997-02-07 2003-05-15 Stryker Corp Matrixlose osteogene vorrichtungen und implantate und verfahren zu deren verwendung
US6034062A (en) * 1997-03-13 2000-03-07 Genetics Institute, Inc. Bone morphogenetic protein (BMP)-9 compositions and their uses
JP5033276B2 (ja) * 1997-05-05 2012-09-26 ストライカー コーポレイション 急性腎不全の治療
EP2309261A1 (de) * 1997-05-30 2011-04-13 Stryker Corporation Verfahren zur Beurteilung von Gewebemorphogenese und- aktivität
US7147839B2 (en) 1998-05-29 2006-12-12 Curis, Inc. Methods for evaluating tissue morphogenesis and activity
WO2000066620A2 (en) * 1999-04-30 2000-11-09 Curis, Inc. Morphogen-induced enhancement of fertility
GB9921121D0 (en) * 1999-09-07 1999-11-10 Novartis Ag Organic compounds
DE10059336A1 (de) * 2000-11-29 2002-06-13 Scil Proteins Gmbh Herstellung von rekombinantem BMP-2
DK1448246T4 (en) 2001-11-19 2015-12-21 Scil Technology Gmbh Homogeneously coated device with osteoinductive and osteoconductive properties
JP4654029B2 (ja) 2002-06-17 2011-03-16 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
DK1539261T3 (da) 2002-09-10 2006-08-07 Scil Technology Gmbh Metalimplantat belagt under nedsat oxygenkoncentration med osteoinduktiv protein
PL1737734T3 (pl) 2004-03-10 2011-02-28 Scil Tech Gmbh Powlekane implanty, ich wytwarzanie i zastosowanie
US7625867B2 (en) * 2004-03-26 2009-12-01 Acceleron Pharma Inc. BMP-3 propeptides and related methods
CA2571218C (en) 2004-06-17 2015-11-03 William D. Carlson Tdf-related compounds and analogs thereof
HUE026634T2 (en) 2005-09-20 2016-07-28 Thrasos Innovation Inc TDF-related compounds and analogues thereof
US20080020014A1 (en) * 2006-07-19 2008-01-24 Paul Consigny Implantable devices containing nuclear receptor ligands for the treatment of vascular and related disorders
WO2009102966A2 (en) 2008-02-13 2009-08-20 Keith Hruska Method of treating vascular sclerosis

Family Cites Families (11)

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Publication number Priority date Publication date Assignee Title
AU645244B2 (en) * 1988-04-08 1994-01-13 Genetics Institute, Llc Bone and cartilage inductive compositions
EP0723013B1 (de) * 1988-04-08 2003-06-18 Stryker Corporation Biosynthetische knochenbildende Proteine, und sie enthaltende knochenbildende Vorrichtungen
US5011691A (en) * 1988-08-15 1991-04-30 Stryker Corporation Osteogenic devices
JP3045398B2 (ja) * 1989-09-06 2000-05-29 武田薬品工業株式会社 蛋白質、ｄｎａおよびその用途
DK0448704T3 (da) * 1989-10-17 1999-04-06 Stryker Corp Osteogene anordninger
ES2137931T3 (es) * 1990-06-15 2000-01-01 Carnegie Inst Of Washington Proteinas gdf-1 y uog-1.
WO1992015323A1 (en) * 1991-03-11 1992-09-17 Creative Biomolecules, Inc. Protein-induced morphogenesis
US5118667A (en) * 1991-05-03 1992-06-02 Celtrix Pharmaceuticals, Inc. Bone growth factors and inhibitors of bone resorption for promoting bone formation
AU662155B2 (en) * 1991-05-10 1995-08-24 Celtrix Pharmaceuticals, Inc. Targeted delivery of bone growth factors
SK136693A3 (en) * 1991-06-05 1994-10-05 Procter & Gamble Therapeutic compositions for osteoinduction
EP0601135B1 (de) * 1991-08-30 2005-11-02 Curis, Inc. Osteogenische proteine in der behandlung von metabolischen knochenkrankheiten

Also Published As

Publication number Publication date
JP4235689B2 (ja) 2009-03-11
JP2007197455A (ja) 2007-08-09
EP1637156A1 (de) 2006-03-22
DE69233559T2 (de) 2006-08-31
EP0601135B1 (de) 2005-11-02
DE69233559D1 (de) 2005-12-08
AU3176293A (en) 1993-04-27
CA2116559A1 (en) 1993-04-01
JPH07502021A (ja) 1995-03-02
WO1993005751A2 (en) 1993-04-01
WO1993005751A3 (en) 1993-05-13
EP0601135A1 (de) 1994-06-15
CA2116559C (en) 2005-05-10
ES2253736T3 (es) 2006-06-01
AU670558B2 (en) 1996-07-25

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