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WO1997019180A3 - Vector consisting of a transcriptional regulatory DNA sequence linked to a DNA sequence encoding beta-lactamase for enzyme prodrug therapy - Google Patents

Vector consisting of a transcriptional regulatory DNA sequence linked to a DNA sequence encoding beta-lactamase for enzyme prodrug therapy Download PDF

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Publication number
WO1997019180A3
WO1997019180A3 PCT/GB1996/002845 GB9602845W WO9719180A3 WO 1997019180 A3 WO1997019180 A3 WO 1997019180A3 GB 9602845 W GB9602845 W GB 9602845W WO 9719180 A3 WO9719180 A3 WO 9719180A3
Authority
WO
WIPO (PCT)
Prior art keywords
dna sequence
lactamase
enzyme
transcriptional regulatory
vector consisting
Prior art date
Application number
PCT/GB1996/002845
Other languages
French (fr)
Other versions
WO1997019180A2 (en
Inventor
Inderjit Dev
John Tomlin Moore
Carol-Ann Dinsmore Ohmstede
Original Assignee
Glaxo Group Ltd
Inderjit Dev
John Tomlin Moore
Ohmstede Carol Ann Dinsmore
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 Glaxo Group Ltd, Inderjit Dev, John Tomlin Moore, Ohmstede Carol Ann Dinsmore filed Critical Glaxo Group Ltd
Priority to AU75839/96A priority Critical patent/AU7583996A/en
Publication of WO1997019180A2 publication Critical patent/WO1997019180A2/en
Publication of WO1997019180A3 publication Critical patent/WO1997019180A3/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 organic compound
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 organic compound
    • A61K47/542Carboxylic acids, e.g. a fatty acid or an amino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 organic compound
    • A61K47/55Medicinal 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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/552Medicinal 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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being an antibiotic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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
    • A61K47/66Medicinal 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
    • A61K47/67Enzyme prodrug therapy, e.g. gene directed enzyme drug therapy [GDEPT] or VDEPT
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4721Lipocortins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/57572Gastrin releasing peptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/665Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/785Alveolar surfactant peptides; Pulmonary surfactant peptides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86Viral vectors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/78Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/86Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides, e.g. penicillinase (3.5.2)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/13011Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041Use of virus, viral particle or viral elements as a vector
    • C12N2740/13043Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/13011Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041Use of virus, viral particle or viral elements as a vector
    • C12N2740/13045Special targeting system for viral vectors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00Vector systems having a special element relevant for transcription
    • C12N2830/008Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
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  • Biochemistry (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
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  • Nanotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
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  • Crystallography & Structural Chemistry (AREA)
  • Cell Biology (AREA)
  • Virology (AREA)
  • Medical Informatics (AREA)
  • Pulmonology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a molecular chimaera for use in therapy with a prodrug, the chimaera comprising a transcriptional regulatory DNA sequence capable of being activated in a targetted mammalian call and a DNA coding sequence operatively linked to the tanscriptional regulatory DNA sequence and encoding a β-lactamase enzyme such that on expression of said coding sequence in the targetted cell, the β-lactamase enzyme is capable of catalysing conversion of the prodrug into an agent toxic to the targetted call. The enzyme β-lactamase has particular advantages when used in GDEPT or VDEPT in terms of the range of prodrugs that can be produced which are capable of being converted to the active species by the enzyme.
PCT/GB1996/002845 1995-11-20 1996-11-19 Vector consisting of a transcriptional regulatory dna sequence linked to a dna sequence encoding beta-lactamase for enzyme prodrug therapy WO1997019180A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU75839/96A AU7583996A (en) 1995-11-20 1996-11-19 Vector consisting of a transcriptional regulatory dna sequence linked to a dna sequence encoding beta-lactamase for enzyme prodrug therapy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9523703.8A GB9523703D0 (en) 1995-11-20 1995-11-20 Enzyme prodrug thearapy
GB9523703.8 1995-11-20

Publications (2)

Publication Number Publication Date
WO1997019180A2 WO1997019180A2 (en) 1997-05-29
WO1997019180A3 true WO1997019180A3 (en) 1997-08-28

Family

ID=10784158

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/GB1996/002846 WO1997019183A2 (en) 1995-11-20 1996-11-19 Tissue-specific transcription of dna sequence encoding a heterologous enzyme for use in prodrug therapy to lung cancer
PCT/GB1996/002845 WO1997019180A2 (en) 1995-11-20 1996-11-19 Vector consisting of a transcriptional regulatory dna sequence linked to a dna sequence encoding beta-lactamase for enzyme prodrug therapy

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/GB1996/002846 WO1997019183A2 (en) 1995-11-20 1996-11-19 Tissue-specific transcription of dna sequence encoding a heterologous enzyme for use in prodrug therapy to lung cancer

Country Status (3)

Country Link
AU (2) AU7700496A (en)
GB (1) GB9523703D0 (en)
WO (2) WO1997019183A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7227013B1 (en) 1999-03-31 2007-06-05 Metamorphix, Inc. Growth differentiation factor-9 regulatory sequences and uses therefor

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741657A (en) 1995-03-20 1998-04-21 The Regents Of The University Of California Fluorogenic substrates for β-lactamase and methods of use
US5928888A (en) * 1996-09-26 1999-07-27 Aurora Biosciences Corporation Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and secondary screening capabilities
US5955604A (en) * 1996-10-15 1999-09-21 The Regents Of The University Of California Substrates for β-lactamase and uses thereof
GB9709421D0 (en) 1997-05-10 1997-07-02 Zeneca Ltd Chemical compounds
EP1053023B2 (en) 1998-02-03 2011-03-30 Protiva Biotherapeutics Inc. Systemic delivery of serum stable plasmid lipid particles for cancer therapy
US6410328B1 (en) 1998-02-03 2002-06-25 Protiva Biotherapeutics Inc. Sensitizing cells to compounds using lipid-mediated gene and compound delivery
AU3462699A (en) * 1998-04-01 1999-10-18 Metamorphix International, Inc. Growth differentiation factor-9 regulatory sequences and uses therefor
WO2000020608A1 (en) * 1998-10-02 2000-04-13 Genotherapeutics, Inc. Method of treating prostate cancer with an adenovirus expression vector encoding a prodrug enzyme
US7148035B1 (en) 1998-11-18 2006-12-12 Oxford Biomedica (Uk) Limited Polypeptide
GB0400443D0 (en) 2004-01-09 2004-02-11 Oxford Biomedica Ltd Cascade
GB9910077D0 (en) * 1999-05-01 1999-06-30 Univ Manchester Chemical compounds
GB0203420D0 (en) 2002-02-13 2002-04-03 Oxford Biomedica Ltd Peptide
GB0203419D0 (en) 2002-02-13 2002-04-03 Oxford Biomedica Ltd Peptide
US20100291543A1 (en) * 2007-02-05 2010-11-18 Rachel De Las Heras Homogeneous in vitro fec assays and components

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Publication number Priority date Publication date Assignee Title
EP0415731A2 (en) * 1989-08-30 1991-03-06 The Wellcome Foundation Limited Novel entities for cancer therapy
WO1996016179A1 (en) * 1994-11-18 1996-05-30 The Wellcome Foundation Limited Enzyme gene therapy catalysing prodrug extracellular conversion

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0415731A2 (en) * 1989-08-30 1991-03-06 The Wellcome Foundation Limited Novel entities for cancer therapy
WO1996016179A1 (en) * 1994-11-18 1996-05-30 The Wellcome Foundation Limited Enzyme gene therapy catalysing prodrug extracellular conversion

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DE SUTTER, K. AND FIERST WALTER: "A bifunctional murine::human chimeric antibody with one antigen-binding arm replaced by bacterial beta-lactamase", MOLECULAR IMMUNOLOGY, vol. 31, no. 4, March 1994 (1994-03-01), pages 261 - 267, XP000654846 *
HARRIS, J.D. ET AL.: "Gene therapy for cancer using tumour-specific prodrug activation", GENE THERAPY, vol. 1, no. 3, May 1994 (1994-05-01), pages 170 - 175, XP000654731 *
HUBER, B.E. ET AL.: "Virus-directed enzyme/prodrug therapy (VDEPT)", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 716, May 1994 (1994-05-01), pages 104 - 114, XP000654773 *
MEYER, D.L. ET AL.: "Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models", CANCER RESEARCH, vol. 53, no. 17, 1 September 1993 (1993-09-01), pages 3956 - 3963, XP000561816 *
WALLACE, P.M. ET AL.: "Intratumoral generation of 5-fluorouracil mediated by an antibody cytosine deaminase conjugate in combination with 5-fluorocytosine", CANCER RESEARCH, vol. 54, no. 10, 15 May 1994 (1994-05-15), pages 2719 - 2723, XP000655095 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7227013B1 (en) 1999-03-31 2007-06-05 Metamorphix, Inc. Growth differentiation factor-9 regulatory sequences and uses therefor

Also Published As

Publication number Publication date
WO1997019180A2 (en) 1997-05-29
AU7700496A (en) 1997-06-11
WO1997019183A2 (en) 1997-05-29
GB9523703D0 (en) 1996-01-24
AU7583996A (en) 1997-06-11

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