ES2139002T3 - Terapia medicamentosa citotoxica. - Google Patents

Terapia medicamentosa citotoxica.

Info

Publication number
ES2139002T3
ES2139002T3 ES93901820T ES93901820T ES2139002T3 ES 2139002 T3 ES2139002 T3 ES 2139002T3 ES 93901820 T ES93901820 T ES 93901820T ES 93901820 T ES93901820 T ES 93901820T ES 2139002 T3 ES2139002 T3 ES 2139002T3
Authority
ES
Spain
Prior art keywords
cytotoxic agent
drug therapy
cytotoxic drug
tumorous
inactivation
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
ES93901820T
Other languages
English (en)
Inventor
Kenneth Dawson Bagshawe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Enzacta R&D Ltd
Original Assignee
Enzacta R&D Ltd
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 Enzacta R&D Ltd filed Critical Enzacta R&D Ltd
Application granted granted Critical
Publication of ES2139002T3 publication Critical patent/ES2139002T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/66—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
    • A61K47/665—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/66—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
    • A61K47/67—Enzyme prodrug therapy, e.g. gene directed enzyme drug therapy [GDEPT] or VDEPT
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6895—Rescue therapy; Agonist-antagonist; Antidotes; Targeted rescue or protection, e.g. by folic acid-folinic acid or conjugated to antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6899—Antibody-Directed Enzyme Prodrug Therapy [ADEPT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3007—Carcino-embryonic Antigens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/54—F(ab')2
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/809—Drug, bio-affecting and body treating compositions involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/819—Multifunctional antigen or antibody

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Nanotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Oncology (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

UN COMPONENTE COMPRENDE UNA PARTE DE OBJETIVO ESPECIFICO DE CELULAS, TALES COMO UN ANTICUERPO ESPECIFICO PARA ANTIGENOS DE CELULAS TUMOROSAS, Y UNA PARTE DE INACTIVACION, TAL COMO UNA ENZIMA, CAPAZ DE CONVERTIR UNA SUSTANCIA QUE EN SU ESTADO NATIVO ES CAPAZ DE INHIBIR LOS EFECTOS DE UN AGENTE CITOTOXICO EN UNA SUSTANCIA QUE TENGA MENOS EFECTO CONTRA DICHO AGENTE CITOTOXICO. LA ACCION PROLONGADA DE UN AGENTE CITOTOXICO EN LUGARES TUMOROSOS ES POR TANTO POSIBLE A LA VEZ QUE SE PROTEGEN LOS TEJIDOS NORMALES DE LOS EFECTOS DEL AGENTE CITOTOXICO.
ES93901820T 1992-01-09 1993-01-11 Terapia medicamentosa citotoxica. Expired - Lifetime ES2139002T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB929200417A GB9200417D0 (en) 1992-01-09 1992-01-09 Cytotoxic drug therapy

Publications (1)

Publication Number Publication Date
ES2139002T3 true ES2139002T3 (es) 2000-02-01

Family

ID=10708338

Family Applications (1)

Application Number Title Priority Date Filing Date
ES93901820T Expired - Lifetime ES2139002T3 (es) 1992-01-09 1993-01-11 Terapia medicamentosa citotoxica.

Country Status (8)

Country Link
US (3) US5658568A (es)
EP (1) EP0620741B1 (es)
JP (2) JP3592711B2 (es)
CA (1) CA2124218C (es)
DE (1) DE69326539T2 (es)
ES (1) ES2139002T3 (es)
GB (2) GB9200417D0 (es)
WO (1) WO1993013805A1 (es)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776093A (en) 1985-07-05 1998-07-07 Immunomedics, Inc. Method for imaging and treating organs and tissues
FR2686899B1 (fr) 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
DE4233152A1 (de) 1992-10-02 1994-04-07 Behringwerke Ag Antikörper-Enzym-Konjugate zur Prodrug-Aktivierung
GB9524942D0 (en) * 1995-12-06 1996-02-07 Aepact Ltd Drug therapy
GB9526733D0 (en) * 1995-12-30 1996-02-28 Delta Biotechnology Ltd Fusion proteins
JP3266276B2 (ja) * 1996-07-25 2002-03-18 ゲーエスエフ―フォルシュングスツェントゥルム・フューア・ウムヴェルト・ウント・ゲズントハイト・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 二重特異性抗体断片の簡易化した製造
GB9712370D0 (en) 1997-06-14 1997-08-13 Aepact Ltd Therapeutic systems
WO1999018792A1 (en) * 1997-10-10 1999-04-22 Johns Hopkins University Gene delivery compositions and methods
US6043367A (en) * 1998-09-30 2000-03-28 Roffler; Steve Proactive antitumor compounds
EP2267026A1 (en) * 2000-04-12 2010-12-29 Human Genome Sciences, Inc. Albumin fusion proteins
US20030147874A1 (en) * 2000-12-14 2003-08-07 Volker Schellenberger Targeted enzyme prodrug therapy
US20030049689A1 (en) * 2000-12-14 2003-03-13 Cynthia Edwards Multifunctional polypeptides
US20080248544A1 (en) * 2000-12-14 2008-10-09 Murray Christopher J Methods And Compositions For Grafting Functional Loops Into A Protein
US7445802B2 (en) * 2000-12-26 2008-11-04 Yeda Research And Development Co. Ltd Site-specific in situ generation of allicin using a targeted alliinase delivery system for the treatment of cancers, tumors, infectious diseases and other allicin-sensitive diseases
CA2446739A1 (en) * 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Chemokine beta-1 fusion proteins
EP2009019A1 (en) * 2001-06-05 2008-12-31 Altor BioScience Corporation P53 binding T cell receptor molecules and uses thereof
PT1463751E (pt) 2001-12-21 2013-08-26 Human Genome Sciences Inc Proteínas de fusão de albumina
WO2005003296A2 (en) 2003-01-22 2005-01-13 Human Genome Sciences, Inc. Albumin fusion proteins
DE10205520A1 (de) * 2002-02-08 2003-08-14 Aventis Behring Gmbh Inhibitorischer, monoklonaler Antikörper gegen die den Blutgerinnungsfaktor VII aktivierende Protease
ES2358730T3 (es) 2002-07-15 2011-05-13 Board Of Regents, The University Of Texas System Anticuerpos seleccionados y péptidos de duramicina que se enlazan a fosfolípidos aniónicos y aminofosfolípidos y sus usos en el tratamiento de infecciones virales y del cáncer.
DE10256042B4 (de) * 2002-11-30 2006-06-08 Universität Potsdam Verfahren zur Selektion von Zellen, die spezifisch bindende Moleküle produzieren
WO2004078215A2 (en) 2003-02-28 2004-09-16 The Board Of Trustees Of The University Of Illinois Use of antibody conjugated deoxycytidine kinase for adept
CA2553261C (en) * 2004-01-16 2014-03-18 Stefan Barth Immunokinases
US20080044400A1 (en) * 2004-12-09 2008-02-21 Volker Schellenberger Targeted enzyme prodrug therapy
EP1800695A1 (en) * 2005-12-21 2007-06-27 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Immuno-RNA-constructs
CA2693155A1 (en) * 2007-07-25 2009-01-29 Fraunhofer Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Self coupling recombinant antibody fusion proteins
ES2572356T3 (es) 2007-11-09 2016-05-31 Peregrine Pharmaceuticals Inc Composiciones de anticuerpos dirigidos contra VEGF y procedimientos
WO2009143048A2 (en) 2008-05-19 2009-11-26 The Board Of Trustees Of The University Of Illinois Use of specifically engineered enzymes to enhance the efficacy of prodrugs
GB201308363D0 (en) * 2013-05-09 2013-06-19 Bagshawe Kenneth D Tumour therapy

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Publication number Priority date Publication date Assignee Title
US4624846A (en) * 1983-07-29 1986-11-25 Immunomedics, Inc. Method for enhancing target specificity of antibody localization and clearance of non-target diagnostic and therapeutic principles
ATE81467T1 (de) * 1987-02-24 1992-10-15 Xoma Corp Immunosuppression bei der auf immunotoxin basierten behandlung von menschen.
GB8705477D0 (en) * 1987-03-09 1987-04-15 Carlton Med Prod Drug delivery systems
NZ225599A (en) * 1987-08-04 1991-09-25 Bristol Myers Co Antibody-enzyme conjugates and combinations with prodrugs for the treatment of tumour cells
US4859449A (en) * 1987-09-14 1989-08-22 Center For Molecular Medicine And Immunology Modified antibodies for enhanced hepatocyte clearance
GB8809616D0 (en) * 1988-04-22 1988-05-25 Cancer Res Campaign Tech Further improvements relating to drug delivery systems
CA2055497A1 (en) * 1989-03-13 1990-09-14 Kenneth N. Matsumura Method for reducing side effects of a drug
WO1991009134A1 (en) * 1989-12-15 1991-06-27 Takeda Chemical Industries, Ltd. Biospecific antibody to cancer cell and enzyme with prodrug-activating characteristics
CA2062582C (en) * 1991-03-27 1996-03-26 Tse-Wen Chang Methods and substances for recruiting therapeutic agents to solid tissues

Also Published As

Publication number Publication date
DE69326539D1 (de) 1999-10-28
GB2276623B (en) 1995-10-18
GB9200417D0 (en) 1992-02-26
US6299876B1 (en) 2001-10-09
EP0620741A1 (en) 1994-10-26
WO1993013805A1 (en) 1993-07-22
US5658568A (en) 1997-08-19
CA2124218A1 (en) 1993-07-22
GB9410236D0 (en) 1994-07-27
DE69326539T2 (de) 2000-05-04
US6015556A (en) 2000-01-18
JP3592711B2 (ja) 2004-11-24
GB2276623A (en) 1994-10-05
EP0620741B1 (en) 1999-09-22
JP2003292458A (ja) 2003-10-15
JPH07506338A (ja) 1995-07-13
CA2124218C (en) 2002-06-11

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