CA2266978A1 - Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery - Google Patents

Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery

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Publication number
CA2266978A1
CA2266978A1 CA002266978A CA2266978A CA2266978A1 CA 2266978 A1 CA2266978 A1 CA 2266978A1 CA 002266978 A CA002266978 A CA 002266978A CA 2266978 A CA2266978 A CA 2266978A CA 2266978 A1 CA2266978 A1 CA 2266978A1
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CA
Canada
Prior art keywords
methods
compositions
sensitive
rapid
drug discovery
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.)
Granted
Application number
CA002266978A
Other languages
French (fr)
Other versions
CA2266978C (en
Inventor
Michael A. Whitney
Paul A. Negulescu
Frank Craig
Lora Mere
Gordon J. Foulkes
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.)
Vertex Pharmaceuticals San Diego LLC
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Individual
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 Individual filed Critical Individual
Publication of CA2266978A1 publication Critical patent/CA2266978A1/en
Application granted granted Critical
Publication of CA2266978C publication Critical patent/CA2266978C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1082—Preparation or screening gene libraries by chromosomal integration of polynucleotide sequences, HR-, site-specific-recombination, transposons, viral vectors
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1051—Gene trapping, e.g. exon-, intron-, IRES-, signal sequence-trap cloning, trap vectors
    • 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
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • 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
    • C12Q1/6897—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5073—Stem cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/978—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • G01N2333/986—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides (3.5.2), e.g. beta-lactamase (penicillinase, 3.5.2.6), creatinine amidohydrolase (creatininase, EC 3.5.2.10), N-methylhydantoinase (3.5.2.6)
    • 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
    • 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

Abstract

The invention provides for methods and compositions for identifying proteins or chemicals that directly or indirectly modulate a genomic polynucleotide and methods for identifying active genomic polynucleotides. Generally, the method comprises inserting a BL
(beta-lactamase) expression construct into an eukaryotic genome, usually non-yeast, contained in at least one living cell, contacting the cell with a predetermined concentration of a modulator, and detecting BL.
activity in the cell.
CA002266978A 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery Expired - Fee Related CA2266978C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/719,697 US5928888A (en) 1996-09-26 1996-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and secondary screening capabilities
US08/719,697 1996-09-26
PCT/US1997/017395 WO1998013353A1 (en) 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA002409901A Division CA2409901A1 (en) 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery

Publications (2)

Publication Number Publication Date
CA2266978A1 true CA2266978A1 (en) 1998-04-02
CA2266978C CA2266978C (en) 2005-06-07

Family

ID=24891025

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002266978A Expired - Fee Related CA2266978C (en) 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery
CA002409901A Abandoned CA2409901A1 (en) 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA002409901A Abandoned CA2409901A1 (en) 1996-09-26 1997-09-26 Methods and compositions for sensitive and rapid, functional identification of genomic polynucleotides and use for cellular assays in drug discovery

Country Status (10)

Country Link
US (1) US5928888A (en)
EP (2) EP0952976B1 (en)
AT (2) ATE414165T1 (en)
AU (1) AU4505797A (en)
CA (2) CA2266978C (en)
DE (2) DE69717856T2 (en)
DK (2) DK0952976T3 (en)
ES (2) ES2315327T4 (en)
PT (1) PT1262478E (en)
WO (1) WO1998013353A1 (en)

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5955275A (en) 1997-02-14 1999-09-21 Arcaris, Inc. Methods for identifying nucleic acid sequences encoding agents that affect cellular phenotypes
US6207371B1 (en) * 1996-10-04 2001-03-27 Lexicon Genetics Incorporated Indexed library of cells containing genomic modifications and methods of making and utilizing the same
US6060240A (en) * 1996-12-13 2000-05-09 Arcaris, Inc. Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom
US6623922B1 (en) 1997-02-14 2003-09-23 Deltagen Proteomics Methods for identifying, characterizing, and evolving cell-type specific CIS regulatory elements
US6759206B1 (en) 1997-02-27 2004-07-06 Cellomics, Inc. System for cell-based screening
US7853411B2 (en) 1997-02-27 2010-12-14 Cellomics, Inc. System for cell-based screening
JP2002511741A (en) * 1997-03-11 2002-04-16 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ DNA-based transposon system for introducing nucleic acid into cell DNA
US6200762B1 (en) * 1997-08-01 2001-03-13 Aurora Biosciences Corporation Photon reducing agents and compositions for fluorescence assays
US6221612B1 (en) * 1997-08-01 2001-04-24 Aurora Biosciences Corporation Photon reducing agents for use in fluorescence assays
US6214563B1 (en) * 1997-08-01 2001-04-10 Aurora Biosciences Corporation Photon reducing agents for reducing undesired light emission in assays
US6828099B2 (en) * 1998-02-02 2004-12-07 Odyssey Thera Inc. Protein fragment complementation assay (PCA) for the detection of protein-protein, protein-small molecule and protein nucleic acid interactions based on the E. coli TEM-1 β-Lactamase
US6284461B1 (en) * 1998-04-28 2001-09-04 Aurora Biosciences Corporation Use of inhibitors in reporter assays
US6280934B1 (en) * 1998-05-13 2001-08-28 Millennium Pharmaceuticals, Inc. Assay for agents which alter G-protein coupled receptor activity
US6031094A (en) * 1998-07-23 2000-02-29 The Regents Of The University Of California Beta-lactam substrates and uses thereof
CN1326361A (en) 1998-09-08 2001-12-12 亨利福特保健系统公司 Methods for detecting, preventing, and treating renal disorders by modulating, regulating and inhibiting connective tissue growth factor
US6063578A (en) * 1998-10-22 2000-05-16 Signal Pharmaceuticals, Inc. Dual reporter system and methods of use therefor
US7160682B2 (en) * 1998-11-13 2007-01-09 Regents Of The University Of Minnesota Nucleic acid transfer vector for the introduction of nucleic acid into the DNA of a cell
US6835540B2 (en) * 2001-03-16 2004-12-28 Mendel Biotechnology, Inc. Biosynthetic pathway transcription factors
EP1169481A1 (en) * 1999-04-15 2002-01-09 Curagen Corporation Method of identifying toxic agents using differential gene expression
JP2003518365A (en) * 1999-07-02 2003-06-10 キュラジェン コーポレイション Methods for identifying virulence factors using differential gene expression
WO2001053481A1 (en) * 2000-01-20 2001-07-26 Cell Therapeutics, Inc. Methods and compositions for identification of genomic polynucleotides which are transcriptionally regulated
EP1254179A4 (en) 2000-01-24 2005-06-01 Univ Columbia An in vivo screen using chemical inducers of dimerization
US6897020B2 (en) * 2000-03-20 2005-05-24 Newlink Genetics Inc. Methods and compositions for elucidating relative protein expression levels in cells
US20060134629A1 (en) * 2000-03-20 2006-06-22 Link Charles J Methods and compositions for elucidating protein expression profiles in cells
US7029842B2 (en) 2000-04-07 2006-04-18 Novozymes A/S Signal sequence trapping
JP2003530106A (en) * 2000-04-07 2003-10-14 ノボザイムス アクティーゼルスカブ Signal sequence trapping
US20020150912A1 (en) * 2000-09-07 2002-10-17 Owman Christer S. O. Reporter system for cell surface receptor-ligand binding
US20020127557A1 (en) * 2001-03-09 2002-09-12 Ruoying Tan Method for identification of cDNAs encoding signal peptides
JP2004527746A (en) * 2001-03-16 2004-09-09 キューティエル・バイオシステムズ・リミテッド・ライアビリティ・カンパニー Bioassay based on fluorescent polymer superquenching
AU2002305391A1 (en) * 2001-05-04 2002-11-18 Health Research, Inc. A high throughput assay for identification of gene expression modifiers
MXPA04001725A (en) * 2001-08-24 2005-04-11 Advanced Cell Tech Inc Screening assays for identifying differentiation-inducing agents and production of differentiated cells for cell therapy.
AU2002330151A1 (en) * 2001-09-27 2003-04-07 Functional Genetics, Inc. Methods and compositions for generating homozygous mutations
US20030170611A1 (en) * 2002-03-09 2003-09-11 Cardone Michael H. Cell-based screening methods
US20030170850A1 (en) * 2002-03-09 2003-09-11 Cardone Michael H. Cell-based screening methods
US6730492B2 (en) * 2002-03-09 2004-05-04 Merrimack Pharmaceuticals, Inc. Cell-based screening methods
US20050181464A1 (en) * 2002-04-04 2005-08-18 Affinium Pharmaceuticals, Inc. Novel purified polypeptides from bacteria
WO2003089618A2 (en) * 2002-04-22 2003-10-30 Regents Of The University Of Minnesota Transposon system and methods of use
US7083918B2 (en) 2002-04-24 2006-08-01 The Trustees Of Columbia University In The City Of New York Bacterial small-molecule three-hybrid system
WO2004035748A2 (en) * 2002-10-16 2004-04-29 Advanced Cell Technology, Inc. Methods using gene trapped stem cells for marking pathways of stem cell differentiation and making and isolating differentiated cells
EP1587914A4 (en) * 2003-01-16 2007-06-27 Health Research Inc Method for comprehensive identification of cell lineage specific genes
US8426194B2 (en) 2003-01-21 2013-04-23 Ptc Therapeutics, Inc. Methods and agents for screening for compounds capable of modulating VEGF expression
US8460864B2 (en) 2003-01-21 2013-06-11 Ptc Therapeutics, Inc. Methods for identifying compounds that modulate untranslated region-dependent gene expression and methods of using same
US9068234B2 (en) * 2003-01-21 2015-06-30 Ptc Therapeutics, Inc. Methods and agents for screening for compounds capable of modulating gene expression
US20040191873A1 (en) * 2003-03-27 2004-09-30 Won-Bin Young Method for high throughput elucidation of transcriptional profiles and genome annotation
SE0302840D0 (en) * 2003-10-29 2003-10-29 Affibody Ab Detection method
US20070072186A1 (en) * 2003-11-17 2007-03-29 Anuradha Mehta Methods and agents for screening for compounds capable of modulating her2 expression
GB0410105D0 (en) * 2004-05-06 2004-06-09 Amersham Biosciences Uk Ltd Method for characterising compounds
WO2005113791A2 (en) * 2004-05-07 2005-12-01 Johnson & Johnson Product Research And Development Methods of identifying modulators of bacterial type iii protein secretion system
US20060026699A1 (en) * 2004-06-04 2006-02-02 Largaespada David A Methods and compositions for identification of genomic sequences
US20070044343A1 (en) * 2005-08-30 2007-03-01 Harris Rodger M Disposable footwear cover
US8283115B1 (en) 2007-06-20 2012-10-09 Ptc Therapeutics, Inc. Methods of screening for compounds for treating muscular dystrophy using UTRN mRNA translation regulation
US8283116B1 (en) 2007-06-22 2012-10-09 Ptc Therapeutics, Inc. Methods of screening for compounds for treating spinal muscular atrophy using SMN mRNA translation regulation
AU2013359166B2 (en) * 2012-12-12 2019-09-19 Promega Corporation Recognition of cellular target binding by a bioactive agent using intracellular bioluminescence resonance energy transfer
US20230384290A1 (en) * 2020-10-16 2023-11-30 Biomems Analytics Llc Cellular Response Analysis Method
EP4281034A1 (en) 2021-01-24 2023-11-29 Forrest, Michael, David Inhibitors of atp synthase - cosmetic and therapeutic uses

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5071773A (en) * 1986-10-24 1991-12-10 The Salk Institute For Biological Studies Hormone receptor-related bioassays
US4935363A (en) * 1987-03-30 1990-06-19 Board Of Regents, The University Of Texas System Sterol regulatory elements
US5378603A (en) * 1987-03-30 1995-01-03 Board Of Regents, The University Of Texas System Method and composition for identifying substances which activate transcription of the LDL receptor gene
EP0291893A1 (en) * 1987-05-19 1988-11-23 The Du Pont Merck Pharmaceutical Company Stable human cell lines expressing an indicator gene product under virus-specific genetic controls
US4980281A (en) * 1988-02-10 1990-12-25 Housey Gerard M Method of screening for protein inhibitors and activators
US5266464A (en) * 1988-02-10 1993-11-30 Ict Pharmaceuticals, Inc. Method of screening for protein inhibitors and activators
US5264354A (en) * 1988-09-30 1993-11-23 Eli Lilly And Company Method for isolating transposable elements from streptomyces
CA2045129A1 (en) * 1989-02-01 1990-08-02 Alfred I. Geller Herpes simplex virus type i expression vector
US5665543A (en) * 1989-07-18 1997-09-09 Oncogene Science, Inc. Method of discovering chemicals capable of functioning as gene expression modulators
AU660405B2 (en) * 1989-07-18 1995-06-29 Osi Pharmaceuticals, Inc. Method of transcriptionally modulating gene expression and of discovering chemicals capable of functioning as gene expression modulators
US5580722A (en) * 1989-07-18 1996-12-03 Oncogene Science, Inc. Methods of determining chemicals that modulate transcriptionally expression of genes associated with cardiovascular disease
US5464764A (en) * 1989-08-22 1995-11-07 University Of Utah Research Foundation Positive-negative selection methods and vectors
US5364783A (en) * 1990-05-14 1994-11-15 Massachusetts Institute Of Technology Retrovirus promoter-trap vectors
US5614396A (en) * 1990-06-14 1997-03-25 Baylor College Of Medicine Methods for the genetic modification of endogenous genes in animal cells by homologous recombination
US5401629A (en) * 1990-08-07 1995-03-28 The Salk Institute Biotechnology/Industrial Associates, Inc. Assay methods and compositions useful for measuring the transduction of an intracellular signal
CA2092000A1 (en) * 1990-09-24 1992-03-25 Roger Brent Screening assays
DE69129897T2 (en) * 1990-10-25 1998-12-17 Clague Pitman Hodgson METHOD OF GENTRANSFER BY MEANS OF RETROTRANSPOSONS
WO1993004179A1 (en) * 1991-08-16 1993-03-04 GSF-Forschungszentrum für Umwelt und Gesundheit Dna construct and in vitro test for detecting tumor promoters by means of said dna construct
US5326691A (en) * 1991-11-21 1994-07-05 John Hozier Micro-libraries and methods of making and manipulating them methods for generating and analyzing micro-libraries
DE4138621A1 (en) * 1991-11-25 1993-06-17 Boehringer Ingelheim Int METHOD FOR SCREENING SUBSTANCES WITH MODULATING EFFECT ON A RECEPTACLE-RELATED CELLULAR SIGNAL TRANSMISSION PATH
US5338843A (en) * 1992-01-30 1994-08-16 Becton, Dickinson And Company Fluorogenic and chromogenic β-lactamase substrates
WO1993025712A1 (en) * 1992-06-15 1993-12-23 The Regents Of The University Of California Screening assay for the identification of immunosuppressive drugs
AU4663493A (en) * 1992-07-06 1994-01-31 Hybritech Incorporated Method for delivery of cytotoxic agents and components thereof
US5652128A (en) * 1993-01-05 1997-07-29 Jarvik; Jonathan Wallace Method for producing tagged genes, transcripts, and proteins
ES2111289T5 (en) * 1993-01-21 2005-07-16 President And Fellows Of Harvard College METHODS AND DIAGNOSIS KITS THAT USE STRESS PROMOTERS IN MAMMALS TO DETERMINE THE TOXICITY OF A COMPOUND.
US5958721A (en) * 1993-04-07 1999-09-28 Cancer Research Campaign Technology, Ltd. Methods for screening of substances for therapeutic activity and yeast for use therein
AU678234B2 (en) * 1993-04-21 1997-05-22 University Of Edinburgh, The Expression of heterologous genes according to a targeted expression profile
US5704555A (en) * 1993-08-02 1998-01-06 Illinois Institute Of Technology Single-screw extruder for solid state shear extrusion pulverization and method
GB9317193D0 (en) * 1993-08-18 1993-10-06 Zeneca Ltd Method
US5604090A (en) * 1994-06-06 1997-02-18 Fred Hutchinson Cancer Research Center Method for increasing transduction of cells by adeno-associated virus vectors
US6010861A (en) * 1994-08-03 2000-01-04 Dgi Biotechnologies, Llc Target specific screens and their use for discovering small organic molecular pharmacophores
AU1916595A (en) * 1994-08-12 1996-03-07 Enzymed, Inc. Biocatalytic methods for synthesizing and identifying biologically active compounds
GB9423367D0 (en) * 1994-11-18 1995-01-11 Wellcome Found Enzyme prodrug therapy
US5789653A (en) * 1995-01-10 1998-08-04 University Of Edinburgh Secretory gene trap
US5741657A (en) * 1995-03-20 1998-04-21 The Regents Of The University Of California Fluorogenic substrates for β-lactamase and methods of use
US5777888A (en) * 1995-08-09 1998-07-07 Regents Of The University Of California Systems for generating and analyzing stimulus-response output signal matrices
US5569588A (en) * 1995-08-09 1996-10-29 The Regents Of The University Of California Methods for drug screening
GB9523703D0 (en) * 1995-11-20 1996-01-24 Wellcome Found Enzyme prodrug thearapy

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EP1262478B1 (en) 2008-11-12
WO1998013353A1 (en) 1998-04-02
ATE229508T1 (en) 2002-12-15
AU4505797A (en) 1998-04-17
DK0952976T3 (en) 2003-04-07
EP1262478A2 (en) 2002-12-04
US5928888A (en) 1999-07-27
DK1262478T3 (en) 2009-02-09
EP0952976A4 (en) 1999-12-01
DE69717856T2 (en) 2004-02-19
EP1262478B9 (en) 2009-04-15
ES2190802T3 (en) 2003-08-16
EP1262478A3 (en) 2003-03-26
CA2409901A1 (en) 1998-04-02
CA2266978C (en) 2005-06-07
EP0952976A1 (en) 1999-11-03
ES2315327T3 (en) 2009-04-01
DE69739110D1 (en) 2008-12-24
EP0952976B1 (en) 2002-12-11
ATE414165T1 (en) 2008-11-15
ES2315327T4 (en) 2009-10-21
PT1262478E (en) 2009-01-20
DE69717856D1 (en) 2003-01-23

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