WO1996032496A3 - Covalently linked oligonucleotide minor groove binder conjugates - Google Patents

Covalently linked oligonucleotide minor groove binder conjugates Download PDF

Info

Publication number
WO1996032496A3
WO1996032496A3 PCT/US1996/004559 US9604559W WO9632496A3 WO 1996032496 A3 WO1996032496 A3 WO 1996032496A3 US 9604559 W US9604559 W US 9604559W WO 9632496 A3 WO9632496 A3 WO 9632496A3
Authority
WO
WIPO (PCT)
Prior art keywords
minor groove
groove binder
covalently linked
linked oligonucleotide
binder conjugates
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.)
Ceased
Application number
PCT/US1996/004559
Other languages
French (fr)
Other versions
WO1996032496A2 (en
Inventor
Igor V Kutyavin
Eugeny A Lukhtanov
Howard B Gamper
Rich B Meyer Jr
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.)
Epoch Biosciences Inc
Original Assignee
MicroProbe Corp
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 MicroProbe Corp filed Critical MicroProbe Corp
Priority to EP96910723A priority Critical patent/EP0819133B1/en
Priority to AU53842/96A priority patent/AU716108B2/en
Priority to JP53105196A priority patent/JP4948690B2/en
Priority to DK96910723T priority patent/DK0819133T3/en
Priority to CA002223678A priority patent/CA2223678C/en
Priority to DE69637389T priority patent/DE69637389T2/en
Publication of WO1996032496A2 publication Critical patent/WO1996032496A2/en
Publication of WO1996032496A3 publication Critical patent/WO1996032496A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • C07H19/073Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • C07H19/173Purine radicals with 2-deoxyribosyl as the saccharide radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/23Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Minor groove binding molecules are covalently bound to oligonucleotides which in their base sequence are complementary to a target sequence of single stranded or double stranded DNA, RNA or hybrids thereof. The covalently bound oligonucleotide minor groove binder conjugates strongly bind to the target sequence of the complementary strand.
PCT/US1996/004559 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder conjugates Ceased WO1996032496A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP96910723A EP0819133B1 (en) 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder conjugates
AU53842/96A AU716108B2 (en) 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder conjugates
JP53105196A JP4948690B2 (en) 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder complex
DK96910723T DK0819133T3 (en) 1995-04-03 1996-04-03 Covalently coupled oligonucleotide (minor groove binding) conjugates
CA002223678A CA2223678C (en) 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder conjugates
DE69637389T DE69637389T2 (en) 1995-04-03 1996-04-03 COVALENT-COUPLED OLIGONUCLEOTIDE (MINOR-GROOVE-BINDER) CONJUGATE

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/415,370 1995-04-03
US08/415,370 US5801155A (en) 1995-04-03 1995-04-03 Covalently linked oligonucleotide minor grove binder conjugates

Publications (2)

Publication Number Publication Date
WO1996032496A2 WO1996032496A2 (en) 1996-10-17
WO1996032496A3 true WO1996032496A3 (en) 1996-11-28

Family

ID=23645421

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/004559 Ceased WO1996032496A2 (en) 1995-04-03 1996-04-03 Covalently linked oligonucleotide minor groove binder conjugates

Country Status (12)

Country Link
US (6) US5801155A (en)
EP (1) EP0819133B1 (en)
JP (1) JP4948690B2 (en)
CN (3) CN1187363C (en)
AT (1) ATE382627T1 (en)
AU (1) AU716108B2 (en)
CA (1) CA2223678C (en)
DE (1) DE69637389T2 (en)
DK (1) DK0819133T3 (en)
ES (1) ES2300106T3 (en)
PT (1) PT819133E (en)
WO (1) WO1996032496A2 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6972328B2 (en) 1999-11-23 2005-12-06 Epoch Biosciences, Inc. Non-aggregating non-quenching oligomer comprising nucelotide analogs, method of synthesis and use thereof
US7759126B2 (en) 2003-10-28 2010-07-20 Elitech Holding B.V. Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for amplification (or PCR) analysis
US8691785B2 (en) 1997-07-01 2014-04-08 Isis Pharmaceuticals, Inc. Compositions and methods for non-parenteral delivery of oligonucleotides

Families Citing this family (273)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6339066B1 (en) 1990-01-11 2002-01-15 Isis Pharmaceuticals, Inc. Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate βI, βII, γ, δ, Ε, ζ and η isoforms of human protein kinase C
US6537973B1 (en) 1992-03-16 2003-03-25 Isis Pharmaceuticals, Inc. Oligonucleotide inhibition of protein kinase C
US5985558A (en) * 1997-04-14 1999-11-16 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos
US6312894B1 (en) * 1995-04-03 2001-11-06 Epoch Pharmaceuticals, Inc. Hybridization and mismatch discrimination using oligonucleotides conjugated to minor groove binders
US5801155A (en) * 1995-04-03 1998-09-01 Epoch Pharmaceuticals, Inc. Covalently linked oligonucleotide minor grove binder conjugates
AU6757698A (en) 1996-02-26 1998-10-30 California Institute Of Technology Stereochemical control of the dna binding affinity, sequence specificity, and orientation-preference of chiral hairpin polyamides in the minor groove
US6555692B1 (en) 1996-02-26 2003-04-29 California Institute Of Technology Preparation and use of bifunctional molecules having DNA sequence binding specificity
US6143901A (en) * 1996-07-31 2000-11-07 Genesoft, Inc. Complex formation between dsDNA and pyrrole imidazole polyamides
US6506906B1 (en) 1996-02-26 2003-01-14 California Institute Of Technology Preparation and use of bifunctional molecules having DNA sequence binding specificity
US6635417B1 (en) 1996-07-31 2003-10-21 California Institute Of Technology Complex formation between DSDNA and oligomer of cyclic heterocycles
US6090947A (en) * 1996-02-26 2000-07-18 California Institute Of Technology Method for the synthesis of pyrrole and imidazole carboxamides on a solid support
WO1998037066A1 (en) 1996-02-26 1998-08-27 California Institute Of Technology Improved polyamides for binding in the minor groove of double stranded dna
CN1260006A (en) 1996-02-26 2000-07-12 加利福尼亚州技术学院 Complex formation between double-stranded DNA and heterocyclic oligomers
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20040266706A1 (en) * 2002-11-05 2004-12-30 Muthiah Manoharan Cross-linked oligomeric compounds and their use in gene modulation
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
AU749953B2 (en) * 1996-08-01 2002-07-04 California Institute Of Technology Inhibition of gene transcription by polyamide DNA-binding ligands
US6143877A (en) * 1997-04-30 2000-11-07 Epoch Pharmaceuticals, Inc. Oligonucleotides including pyrazolo[3,4-D]pyrimidine bases, bound in double stranded nucleic acids
US6312925B1 (en) * 1997-05-08 2001-11-06 Epoch Pharmaceuticals, Inc. Methods and compositions to facilitate D-loop formation by oligonucleotides
US6262252B1 (en) * 1997-05-19 2001-07-17 Mirus, Inc. Single-step method for labeling nucleic acids with mustard or aziridine labeling reagents
US6133246A (en) * 1997-08-13 2000-10-17 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the modulation of JNK proteins
US5877309A (en) * 1997-08-13 1999-03-02 Isis Pharmaceuticals, Inc. Antisense oligonucleotides against JNK
US6809193B2 (en) 1997-08-13 2004-10-26 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions and methods for the modulation of JNK proteins
US6518017B1 (en) * 1997-10-02 2003-02-11 Oasis Biosciences Incorporated Combinatorial antisense library
US20030165888A1 (en) * 2001-07-18 2003-09-04 Brown Bob D. Oligonucleotide probes and primers comprising universal bases for diagnostic purposes
US20060167239A1 (en) * 1997-12-02 2006-07-27 Slattum Paul M Compounds and processes for single-pot attachment of a label to siRNA
US6683173B2 (en) * 1998-04-03 2004-01-27 Epoch Biosciences, Inc. Tm leveling methods
US6127121A (en) * 1998-04-03 2000-10-03 Epoch Pharmaceuticals, Inc. Oligonucleotides containing pyrazolo[3,4-D]pyrimidines for hybridization and mismatch discrimination
US6949367B1 (en) 1998-04-03 2005-09-27 Epoch Pharmaceuticals, Inc. Modified oligonucleotides for mismatch discrimination
US7715989B2 (en) * 1998-04-03 2010-05-11 Elitech Holding B.V. Systems and methods for predicting oligonucleotide melting temperature (TmS)
US7045610B2 (en) * 1998-04-03 2006-05-16 Epoch Biosciences, Inc. Modified oligonucleotides for mismatch discrimination
US6072046A (en) * 1998-08-26 2000-06-06 Epoch Pharmaceuticals, Inc. Diaziridinyl-aryl and bis-[di(chloroethyl)amino]-aryl oligonucleotide conjugates and reagents for making the same
US6432642B1 (en) * 1999-01-15 2002-08-13 Pe Corporation (Ny) Binary probe and clamp composition and methods for a target hybridization detection
US6410231B1 (en) * 1999-02-26 2002-06-25 Incyte Genomics, Inc. SNP detection
WO2000061810A1 (en) * 1999-04-08 2000-10-19 Oasis Biosciences, Inc. Antisense oligonucleotides comprising universal and/or degenerate bases
US6339147B1 (en) 1999-07-29 2002-01-15 Epoch Biosciences, Inc. Attachment of oligonucleotides to solid supports through Schiff base type linkages for capture and detection of nucleic acids
US20040081959A9 (en) * 1999-12-08 2004-04-29 Epoch Biosciences, Inc. Fluorescent quenching detection reagents and methods
US6727356B1 (en) 1999-12-08 2004-04-27 Epoch Pharmaceuticals, Inc. Fluorescent quenching detection reagents and methods
US7205105B2 (en) * 1999-12-08 2007-04-17 Epoch Biosciences, Inc. Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for PCR analysis
EP1261616B1 (en) * 2000-03-01 2010-08-18 Epoch Biosciences, Inc. Modified oligonucleotides for mismatch discrimination
EP1944310A3 (en) 2000-03-01 2008-08-06 Epoch Biosciences, Inc. Modified oligonucleotides for mismatch discrimination
US7078536B2 (en) * 2001-03-14 2006-07-18 Genesoft Pharmaceuticals, Inc. Charged compounds comprising a nucleic acid binding moiety and uses therefor
KR20030043785A (en) 2000-03-16 2003-06-02 젠소프트, 인크. Charged compounds comprising a nucleic acid binding moiety and uses therefor
EP1313880A2 (en) * 2000-05-30 2003-05-28 PE Corporation (NY) Methods for detecting target nucleic acids using coupled ligation and amplification
US6887664B2 (en) 2000-06-06 2005-05-03 Applera Corporation Asynchronous primed PCR
EP1307469B1 (en) * 2000-08-03 2008-01-23 Boehringer Mannheim Gmbh Nucleic acid binding compounds containing pyrazolo¬3,4-d pyrimidine analogues of purin-2,6-diamine and their uses
US6358679B1 (en) * 2000-08-24 2002-03-19 Pe Corporation (Ny) Methods for external controls for nucleic acid amplification
WO2002072864A2 (en) 2001-03-08 2002-09-19 Applera Corporation Reagents for oligonucleotide cleavage and deprotection
US6774082B2 (en) * 2001-05-11 2004-08-10 Ibc Advanced Technologies, Inc. Compositions for separating heterocyclic aromatic amine bases, nucleosides, nucleotides, and nucleotide sequences
AU2002339853A1 (en) * 2001-05-24 2002-12-03 Genospectra, Inc. Pairs of nucleic acid probes with interactive signaling moieties and nucleic acid probes with enhanced hybridization efficiency and specificity
US6825228B2 (en) 2001-06-13 2004-11-30 Genesoft Pharmaceuticals, Inc. Benzothiophene compounds having antiinfective activity
US6972339B2 (en) * 2001-09-07 2005-12-06 Epoch Biosciences, Inc. Compounds and methods for fluorescent labeling
US8569516B2 (en) 2001-09-07 2013-10-29 Elitech Holding B.V. Compounds and methods for fluorescent labeling
US6744502B2 (en) * 2001-09-28 2004-06-01 Pe Corporation (Ny) Shaped illumination geometry and intensity using a diffractive optical element
US6818420B2 (en) 2002-02-27 2004-11-16 Biosource International, Inc. Methods of using FET labeled oligonucleotides that include a 3′-5′ exonuclease resistant quencher domain and compositions for practicing the same
US7582739B2 (en) * 2002-03-11 2009-09-01 Epoch Biosciences, Inc. Negatively charged minor groove binders
AU2003258022A1 (en) 2002-08-02 2004-02-23 Genesoft Pharmaceuticals, Inc. Biaryl compounds having anti-infective activity
AU2003275138A1 (en) * 2002-09-19 2004-04-08 Applied Biosystems, Llc. Methods and compositions for detecting targets
CA2498320A1 (en) * 2002-09-20 2004-04-01 Integrated Dna Technologies, Inc. Anthraquinone quencher dyes, their methods of preparation and use
US20040235005A1 (en) * 2002-10-23 2004-11-25 Ernest Friedlander Methods and composition for detecting targets
WO2004039318A2 (en) * 2002-10-25 2004-05-13 Genesoft Pharmaceuticals, Inc. Anti-infective biaryl compounds
WO2004043979A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004043350A2 (en) * 2002-11-14 2004-05-27 The Scripps Research Institute PURIFIED COMPOUNDS THAT INHIBIT INTRACELLULAR α4/PAXILLIN BINDING
EP1579005A4 (en) * 2002-11-15 2007-07-25 Sangamo Biosciences Inc Methods and compositions for analysis of regulatory sequences
CA2508769A1 (en) 2002-12-10 2004-06-24 Oscient Pharmaceuticals Corporation Antibacterial compounds having a (pyrrole carboxamide)-(benzamide)-(imidazole carboxamide) motif
US20050239089A1 (en) * 2003-06-06 2005-10-27 Johnson Martin D Mobility cassettes
US7348146B2 (en) * 2003-10-02 2008-03-25 Epoch Biosciences, Inc. Single nucleotide polymorphism analysis of highly polymorphic target sequences
WO2005049849A2 (en) 2003-11-14 2005-06-02 Integrated Dna Technologies, Inc. Fluorescence quenching azo dyes, their methods of preparation and use
WO2005051967A2 (en) * 2003-11-19 2005-06-09 Allelogic Biosciences Corp. Oligonucleotides labeled with a plurality of fluorophores
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
GB0406015D0 (en) * 2004-03-17 2004-04-21 Dynal Biotech Asa Improvements in magnetic polymer particles
US7445898B2 (en) * 2004-04-01 2008-11-04 Bio-Rad Laboratories, Inc. Quantitative amplification with a labeled probe and 3′ to 5′ exonuclease activity
US8044184B2 (en) * 2004-04-26 2011-10-25 Wako Pure Chemical Industries, Ltd. Probe and primer for tubercle bacillus detection, and method of detecting human tubercle bacillus therewith
EP2290073A3 (en) * 2004-05-28 2011-08-31 Asuragen, Inc. Methods and compositions involving microRNA
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US20070054276A1 (en) * 2004-08-12 2007-03-08 Sampson Jeffrey R Polynucleotide analysis and methods of using nanopores
EP1789587B1 (en) 2004-08-13 2011-05-04 Epoch Biosciences, Inc. Amplification methods
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
EP1791982B1 (en) 2004-09-21 2011-01-05 Life Technologies Corporation TWO-COLOR REAL-TIME/END-POINT QUANTITATION OF MICRORNAS (MIRNAs)
US20060078894A1 (en) * 2004-10-12 2006-04-13 Winkler Matthew M Methods and compositions for analyzing nucleic acids
CA2857878A1 (en) 2004-11-12 2006-12-28 Asuragen, Inc. Methods and compositions involving mirna and mirna inhibitor molecules
JP2008527979A (en) * 2005-01-12 2008-07-31 アプレラ コーポレイション Compositions, methods and kits for selective amplification of nucleic acids
JP2008535518A (en) 2005-04-14 2008-09-04 アプレラ コーポレイション 3 'modified oligonucleotides containing pseudoisocytosine nucleobase derivatives and their application as primers or probes
US8242249B2 (en) 2005-05-13 2012-08-14 Wako Pure Chemical Industries, Ltd. Primer and probe for use in detection of Mycobacterium kansasii and method for detection of Mycobacterium kansasii using the same
CA2601554A1 (en) * 2005-05-20 2006-11-30 Integrated Dna Technologies, Inc. Compounds and methods for labeling oligonucleotides
CA2611507A1 (en) * 2005-06-09 2006-12-21 Epoch Biosciences, Inc. Improved primer-based amplification methods
US20070087360A1 (en) * 2005-06-20 2007-04-19 Boyd Victoria L Methods and compositions for detecting nucleotides
WO2007041201A2 (en) 2005-10-03 2007-04-12 Applera Corporation Compositions, methods, and kits for amplifying nucleic acids
CN101400806A (en) 2006-03-13 2009-04-01 和光纯药工业株式会社 Method for detection of mutant gene
US20080166712A1 (en) * 2006-04-10 2008-07-10 Ryusuke Murayama Gene detection method
US8188256B2 (en) 2006-05-02 2012-05-29 Wako Pure Chemical Industries, Ltd. Primer and probe for detection of Mycobacterium intracellulare
US20100003679A1 (en) * 2006-06-09 2010-01-07 University Of Miami Assessment of cellular composition and fractional viability and uses thereof
WO2008002920A2 (en) * 2006-06-26 2008-01-03 Epoch Biosciences, Inc. Methods for generating target nucleic acid sequences
EP2484781B1 (en) 2006-08-01 2017-08-23 Applied Biosystems, LLC Detection of analytes and nucleic acids
JP2010500290A (en) 2006-08-04 2010-01-07 アイシス ファーマシューティカルズ, インコーポレーテッド Compositions and methods for modulating JNK protein
GB0619325D0 (en) * 2006-09-30 2006-11-08 Univ Strathclyde New compounds
US7902345B2 (en) * 2006-12-05 2011-03-08 Sequenom, Inc. Detection and quantification of biomolecules using mass spectrometry
US20080131878A1 (en) * 2006-12-05 2008-06-05 Asuragen, Inc. Compositions and Methods for the Detection of Small RNA
US8133701B2 (en) * 2006-12-05 2012-03-13 Sequenom, Inc. Detection and quantification of biomolecules using mass spectrometry
WO2008073919A2 (en) * 2006-12-08 2008-06-19 Asuragen, Inc. Mir-20 regulated genes and pathways as targets for therapeutic intervention
EP2479273A3 (en) 2006-12-18 2012-10-10 Wako Pure Chemical Industries, Ltd. Primer and probe for detection of mycobacterium avium and method for detection of mycobacterium avium using the same
US9938641B2 (en) * 2006-12-18 2018-04-10 Fluidigm Corporation Selection of aptamers based on geometry
US20110091377A1 (en) 2007-05-11 2011-04-21 The Johns Hopkins University Biomarkers for melanoma
US8143006B2 (en) * 2007-08-03 2012-03-27 Igor Kutyavin Accelerated cascade amplification (ACA) of nucleic acids comprising strand and sequence specific DNA nicking
US8071338B2 (en) * 2007-08-08 2011-12-06 Roche Molecular Systems, Inc. Suppression of amplification using an oligonucleotide and a polymerase significantly lacking 5′-3′ nuclease activity
US9404150B2 (en) 2007-08-29 2016-08-02 Sequenom, Inc. Methods and compositions for universal size-specific PCR
EP2198050A1 (en) 2007-09-14 2010-06-23 Asuragen, INC. Micrornas differentially expressed in cervical cancer and uses thereof
WO2009045536A2 (en) * 2007-10-05 2009-04-09 The University Of North Carolina At Chapel Hill Receptor targeted oligonucleotides
WO2009052386A1 (en) * 2007-10-18 2009-04-23 Asuragen, Inc. Micrornas differentially expressed in lung diseases and uses thereof
WO2009070805A2 (en) 2007-12-01 2009-06-04 Asuragen, Inc. Mir-124 regulated genes and pathways as targets for therapeutic intervention
JPWO2009099037A1 (en) 2008-02-08 2011-05-26 和光純薬工業株式会社 Primer and probe for detection of Chlamydophila caviae, and detection method of Chlamydophila caviae using the same
MX2010010881A (en) 2008-04-01 2011-03-04 Biosearch Tech Inc Stabilized nucleic acid dark quencher-fluorophore probes.
WO2009126726A1 (en) * 2008-04-08 2009-10-15 Asuragen, Inc Methods and compositions for diagnosing and modulating human papillomavirus (hpv)
EP3604533A1 (en) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
US8258111B2 (en) 2008-05-08 2012-09-04 The Johns Hopkins University Compositions and methods related to miRNA modulation of neovascularization or angiogenesis
WO2009145181A1 (en) 2008-05-28 2009-12-03 和光純薬工業株式会社 Primer and probe for detection of mycobacterium intracellulare, and method for detection of mycobacterium intracellulare using the primer or the probe
US8097412B2 (en) * 2008-07-12 2012-01-17 Biodiagnostics, Inc. DNA-based test for detection of annual and intermediate ryegrass
US20110171649A1 (en) * 2008-09-10 2011-07-14 Igor Kutyavin Detection of nucleic acids by oligonucleotide probes cleaved in presence of endonuclease v
US20100076185A1 (en) * 2008-09-22 2010-03-25 Nils Adey Selective Processing of Biological Material on a Microarray Substrate
EP2342616A2 (en) 2008-09-23 2011-07-13 Alnylam Pharmaceuticals Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
EP4241767B1 (en) 2008-11-10 2024-10-23 Arbutus Biopharma Corporation Novel lipids and compositions for the delivery of therapeutics
EP2376659B1 (en) * 2008-12-17 2015-12-02 Life Technologies Corporation Methods, compositions, and kits for detecting allelic variants
EP3424939A1 (en) 2009-03-02 2019-01-09 Alnylam Pharmaceuticals Inc. Nucleic acid chemical modifications
US20100279295A1 (en) * 2009-03-18 2010-11-04 Sequenom, Inc. Use of thermostable endonucleases for generating reporter molecules
EP3249053A1 (en) 2009-03-27 2017-11-29 Life Technologies Corporation Methods, compositions, and kits for detecting allelic variants
TR201811076T4 (en) 2009-06-10 2018-08-27 Arbutus Biopharma Corp Improved lipid formulation.
EP2483425B1 (en) 2009-09-28 2016-08-24 Igor Kutyavin Methods and compositions for detection of nucleic acids based on stabilized oligonucleotide probe complexes
WO2011046972A2 (en) * 2009-10-12 2011-04-21 Life Technologies Corporation Compositions and methods for suppressing primer interactions
EP2547769B1 (en) * 2009-11-25 2016-04-06 ELITechGroup B.V. Minor groove binder (mgb)-oligonucleotide mirna antagonists
WO2011071860A2 (en) 2009-12-07 2011-06-16 Alnylam Pharmaceuticals, Inc. Compositions for nucleic acid delivery
EP3494963A1 (en) 2009-12-18 2019-06-12 The University of British Columbia Methods and compositions for delivery of nucleic acids
WO2011087707A1 (en) 2009-12-22 2011-07-21 Elitech Holding B.V. Hypertheromostable endonuclease iv substrate probe
WO2011094580A2 (en) 2010-01-28 2011-08-04 Alnylam Pharmaceuticals, Inc. Chelated copper for use in the preparation of conjugated oligonucleotides
WO2011100131A2 (en) 2010-01-28 2011-08-18 Alnylam Pharmacuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
CN102918155B (en) 2010-03-23 2015-12-16 和光纯药工业株式会社 Chlamydia trachomatis detection primer and probe and use the detection method of chlamydia trachomatis of this primer and probe
US20150231215A1 (en) 2012-06-22 2015-08-20 Randolph J. Noelle VISTA Antagonist and Methods of Use
US9506057B2 (en) 2010-03-26 2016-11-29 Integrated Dna Technologies, Inc. Modifications for antisense compounds
MX342017B (en) 2010-03-26 2016-09-09 Dartmouth College Vista regulatory t cell mediator protein, vista binding agents and use thereof.
US10745467B2 (en) 2010-03-26 2020-08-18 The Trustees Of Dartmouth College VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders
EP2553123B1 (en) 2010-03-26 2016-08-24 Integrated DNA Technologies, Inc. Methods for enhancing nucleic acid hybridization
WO2011123621A2 (en) 2010-04-01 2011-10-06 Alnylam Pharmaceuticals Inc. 2' and 5' modified monomers and oligonucleotides
WO2011133433A2 (en) 2010-04-16 2011-10-27 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention Real time pcr assay for detection of bacterial respiratory pathogens
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
US20130260460A1 (en) 2010-04-22 2013-10-03 Isis Pharmaceuticals Inc Conformationally restricted dinucleotide monomers and oligonucleotides
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
GB201007868D0 (en) 2010-05-11 2010-06-23 Enigma Diagnostics Ltd Sequence detection assay
US9309565B2 (en) 2010-05-14 2016-04-12 Life Technologies Corporation Karyotyping assay
WO2011150277A2 (en) 2010-05-28 2011-12-01 Life Technologies Corporation Synthesis of 2', 3'-dideoxynucleosides for automated dna synthesis and pyrophosphorolysis activated polymerization
BR112012030682B1 (en) 2010-06-02 2021-09-21 Merck Patent Gmbh GENETICALLY MODIFIED BACTERIA OF THE SPECIES LISTERIA MONOCYTOGENES, METHOD OF MANUFACTURING THE SAME, AS WELL AS KIT AND METHODS FOR DETECTING AND DETERMINING THE PRESENCE OR AMOUNT OF WILD-TYPE LISTERIA MONOCYTOGENES IN A SAMPLE
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
CA2803391C (en) 2010-06-22 2021-11-09 Neogenix Oncology, Inc. Npc1 antibodies that bind a muc5ac epitope
WO2012016188A2 (en) 2010-07-30 2012-02-02 Alnylam Pharmaceuticals, Inc. Methods and compositions for delivery of active agents
US20130323269A1 (en) 2010-07-30 2013-12-05 Muthiah Manoharan Methods and compositions for delivery of active agents
EP2614149B1 (en) 2010-09-07 2015-04-08 Integrated Dna Technologies, Inc. Modifications for antisense compounds
WO2012040617A2 (en) 2010-09-23 2012-03-29 Neogenix Oncology, Inc. Colon and pancreas cancer peptidomimetics
CA2818814A1 (en) 2010-11-23 2012-05-31 Alder Biopharmaceuticals, Inc. Anti-il-6 antibodies for the treatment of anemia
JP5902197B2 (en) 2011-01-11 2016-04-13 アルニラム・ファーマシューティカルズ・インコーポレーテッド PEGylated lipids and their use for drug delivery
US20120208189A1 (en) 2011-01-14 2012-08-16 Life Technologies Corporation Methods for isolation, identification, and quantification of mirnas
ES2632768T3 (en) 2011-01-17 2017-09-15 Life Technologies Corporation Workflow for the detection of ligands using nucleic acids
EP2689031B1 (en) 2011-03-23 2016-10-19 ELITechGroup B.V. Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use
US8969003B2 (en) 2011-03-23 2015-03-03 Elitech Holding B.V. Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use
WO2012142003A2 (en) 2011-04-15 2012-10-18 Life Technologies Corporation Chemical ligation
DK2714939T3 (en) 2011-05-24 2015-06-29 Elitech Holding Bv DETECTION OF METHICILLIN-RESISTENT STAPHYLOCOCCUS AUREUS
ES2765874T3 (en) 2011-05-25 2020-06-11 Innate Pharma Sa Anti-KIR antibodies for the treatment of inflammatory disorders
WO2012170907A2 (en) 2011-06-08 2012-12-13 Life Technologies Corporation Polymerization of nucleic acids using proteins having low isoelectric points
DK2718260T3 (en) 2011-06-08 2018-11-19 Life Technologies Corp DESIGN AND DEVELOPMENT OF NEW DETERGENTS FOR USE IN PCR SYSTEMS
WO2012178187A1 (en) 2011-06-23 2012-12-27 Paul Yager Reagent patterning in capillarity-based analyzers and associated systems and methods
JP6182529B2 (en) 2011-07-26 2017-08-16 エリテックグループ・ベスローテン・フェンノートシャップElitechgroup B.V. Minor groove binder phosphoramidites and methods of use
WO2013040251A2 (en) 2011-09-13 2013-03-21 Asurgen, Inc. Methods and compositions involving mir-135b for distinguishing pancreatic cancer from benign pancreatic disease
EP2760477B1 (en) 2011-09-27 2018-08-08 Alnylam Pharmaceuticals, Inc. Di-aliphatic substituted pegylated lipids
GB201119903D0 (en) * 2011-11-17 2011-12-28 Univ Vilnius Nucleic acid production and sequence analysis
US8981318B1 (en) 2011-12-30 2015-03-17 Gene Capture, Inc. Multi-dimensional scanner for nano-second time scale signal detection
CN104640856B (en) 2012-05-11 2017-09-15 复位治疗公司 Carbazole-containing sulfonamides as cryptochrome modulators
US9394574B2 (en) 2012-06-12 2016-07-19 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Methods for detecting Legionella nucleic acids in a sample
KR20210072137A (en) 2012-06-14 2021-06-16 라이프 테크놀로지스 코포레이션 Novel compositions, methods and kits for polymerase chain reaction (pcr)
CN104619722B (en) 2012-06-22 2022-10-04 达特茅斯大学理事会 Novel VISTA-IG constructs and use of VISTA-IG for treatment of autoimmune, allergic and inflammatory diseases
US9890215B2 (en) 2012-06-22 2018-02-13 King's College London Vista modulators for diagnosis and treatment of cancer
CA2884704C (en) 2012-09-07 2023-04-04 Randolph J. Noelle Vista modulators for diagnosis and treatment of cancer
MY167603A (en) 2012-10-04 2018-09-20 The Board Of Trustees Of Leland Stanford Junior Univ Method and reagents for detection, quantitation, and serotyping of dengue viruses
PL3260558T3 (en) 2012-11-02 2020-08-10 Life Technologies Corporation NEW COMPOSITIONS AND WAYS TO IMPROVE PCR SPECIFICATIONS
AU2013370171B2 (en) 2012-12-28 2018-09-13 Precision Biologics, Inc. Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer
CN105050720A (en) 2013-01-22 2015-11-11 华盛顿大学商业化中心 Sequential delivery of fluid volumes and associated devices, systems and methods
US11254977B2 (en) 2013-03-12 2022-02-22 Life Technologies Corporation Universal reporter-based genotyping methods and materials
WO2014164874A2 (en) 2013-03-13 2014-10-09 Becton, Dickinson And Company Methods and compositions for modulation of amplification efficiency
WO2014159063A1 (en) 2013-03-14 2014-10-02 Elitech Holding B.V. Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use
AU2014227883B9 (en) 2013-03-15 2020-09-10 Life Technologies Corporation Classification and actionability indices for lung cancer
US9937231B2 (en) 2013-03-27 2018-04-10 The General Hospital Corporation Methods and agents for treating Alzheimer's disease
EP2981621B1 (en) 2013-04-05 2019-05-22 Life Technologies Corporation Gene fusions
US9328384B2 (en) 2013-05-13 2016-05-03 Elitechgroup B.V. Droplet digital PCR with short minor groove probes
CN105722996A (en) 2013-09-13 2016-06-29 生命科技公司 Classification and actionability indices for cancer
EP3060686B1 (en) 2013-10-22 2018-08-01 The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services Compositions and methods for detection of influenza viruses
CN106458885B (en) 2013-10-25 2019-12-10 生命技术公司 Novel compounds for use in polymerase chain reaction systems and uses thereof
WO2015062699A1 (en) 2013-10-30 2015-05-07 Merck Patent Gmbh Method for isolating microorganisms from a complex sample
US11014987B2 (en) 2013-12-24 2021-05-25 Janssen Pharmaceutics Nv Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
EP4043493A1 (en) 2013-12-24 2022-08-17 Janssen Pharmaceutica NV Anti-vista antibodies and fragments
US20170058366A1 (en) 2014-02-21 2017-03-02 The United States of America, as represented by th e Secretary, Dept. of Health and Human Services Hiv-2 nucleic acids and methods of detection
EP3122901B1 (en) 2014-03-27 2018-08-15 Life Technologies Corporation Gene fusions and gene variants associated with cancer
TWI690521B (en) 2014-04-07 2020-04-11 美商同步製藥公司 Carbazole-containing amides, carbamates, and ureas as cryptochrome modulators
US20170044631A1 (en) 2014-04-14 2017-02-16 The Unite States of America, as represented by the Secretary, Dept. of Health and Human Services Methods for rapid detection and identification of viral nucleic acids
EP3154585B1 (en) 2014-06-11 2022-02-23 Kathy A. Green Use of vista agonists and antagonists to suppress or enhance humoral immunity
KR20170016915A (en) 2014-06-11 2017-02-14 마이크로닉스 인코포레이티드. Microfluidic cartridges and apparatus with integrated assay controls for analysis of nucleic acids
US9212388B1 (en) 2014-06-30 2015-12-15 Life Technologies Corporation Direct quantitative PCR absent minor groove binders
EP3207156A1 (en) 2014-10-13 2017-08-23 Life Technologies Corporation Methods, kits & compositions for determining gene copy numbers
JP2018505911A (en) 2014-12-05 2018-03-01 イミュネクスト,インコーポレーテッド Identification of VSIG8 as a putative VISTA receptor and its use to produce a VISTA / VSIG8 modulator
EP3230467A1 (en) 2014-12-12 2017-10-18 ELITechGroup B.V. Methods and compositions for detecting antibiotic resistant bacteria
EP3230468B1 (en) 2014-12-12 2020-09-16 ELITechGroup, Inc. Methods and kits for detecting antibiotic resistant bacteria
EP3234141A4 (en) 2014-12-18 2018-06-20 Alnylam Pharmaceuticals, Inc. Reversir tm compounds
EP3722314A1 (en) 2015-06-24 2020-10-14 Janssen Pharmaceutica NV Anti-vista antibodies and fragments
DK3324980T3 (en) 2015-07-17 2022-02-14 Alnylam Pharmaceuticals Inc MULTI-TARGETED SIMPLICITY CONJUGATES
TW202216201A (en) 2016-02-12 2022-05-01 比利時商楊森製藥公司 Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
JP7184751B2 (en) 2016-04-15 2022-12-06 イミュネクスト インコーポレイテッド ANTI-HUMAN VISTA ANTIBODY AND USES THEREOF
US11155885B2 (en) 2016-05-20 2021-10-26 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Real-time reverse transcriptase-polymerase chain reaction assay with modified probe for the diagnosis of rabies viruses and other lyssaviruses
US20170362640A1 (en) 2016-06-16 2017-12-21 Life Technologies Corporation Novel compositions, methods and kits for microorganism detection
WO2018005284A1 (en) 2016-06-27 2018-01-04 The United State Of America, As Represented By The Secretary, Department Of Health And Human Services Methods and compositions for influenza a virus subtyping
CN118207299A (en) 2016-08-26 2024-06-18 生命技术公司 Nucleic acid extraction and amplification controls and methods of use thereof
WO2018047148A1 (en) 2016-09-12 2018-03-15 Novartis Ag Compounds for the inhibition of mirna
WO2018162516A1 (en) 2017-03-08 2018-09-13 Etablissement Francais Du Sang Rhd gene allele associated with a weak d phenotype and its uses
US10738346B2 (en) 2017-03-09 2020-08-11 Elitechgroup, Inc. Nitrodiarylethenes as fluorescence quenchers for nucleic acid probes
EP3668884B1 (en) 2017-08-17 2022-03-09 ELITechGroup Inc. Duplex stabilizing fluorescence quenchers for nucleic acid probes
JP2021502825A (en) 2017-11-13 2021-02-04 ライフ テクノロジーズ コーポレイション Compositions, methods, and kits for detecting urethral microbes
US10724017B1 (en) 2017-12-06 2020-07-28 Cepheid Inhibition of DNA polymerases by uracil-DNA glycosylase-cleavable oligonucleotide ligands
US10724083B1 (en) 2017-12-06 2020-07-28 Cepheid Inhibition of nucleic acid polymerases by endonuclease V-cleavable oligonucleotide ligands
US10689629B1 (en) 2017-12-06 2020-06-23 Cepheid Inhibition of nucleic acid polymerases by endonuclease V-cleavable circular oligonucleotide ligands
EP3790970A1 (en) 2018-05-07 2021-03-17 Alnylam Pharmaceuticals Inc. Extrahepatic delivery
EP3802526A1 (en) 2018-05-29 2021-04-14 ELITechGroup, Inc. Carborhodamine compounds and methods of preparation thereof
WO2020037290A1 (en) 2018-08-16 2020-02-20 Life Technologies Corporation Reagents, mixtures, kits and methods for amplification of nucleic acids
JP7470107B2 (en) 2018-09-28 2024-04-17 アルナイラム ファーマシューティカルズ, インコーポレイテッド Transthyretin (TTR) iRNA Compositions and Methods of Use Thereof for Treating or Preventing TTR-Related Eye Diseases - Patent application
WO2020072409A1 (en) 2018-10-01 2020-04-09 Gen-Probe Incorporated Compositions and methods for amplifying or detecting varicella-zoster virus
US20220211743A1 (en) 2019-05-17 2022-07-07 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
KR102861357B1 (en) * 2019-10-28 2025-09-18 제론 코포레이션 Amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane salts and methods of making the same
AU2020375734B2 (en) 2019-10-28 2026-04-09 Geron Corporation Crystalline solids of 3-palmitoyl-amido-1,2-propanediol and 3-palmitoyl-amido-2-hydroxy-1-dimethoxytriphenylmethylether-propane and methods of making and using the same
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
AU2020378414A1 (en) 2019-11-06 2022-05-26 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
CN116113714A (en) 2020-02-18 2023-05-12 生命技术公司 Compositions, kits and methods for detecting viral sequences
GB2627644B (en) 2020-03-04 2024-11-20 Verve Therapeutics Inc Method for the preparation of GalNAc-lipid nanoparticle
DE202021100985U1 (en) 2020-06-26 2021-06-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein A diagnostic assay kit and means to detect coronavirus nucleic acid
EP3929310A1 (en) 2020-06-26 2021-12-29 FRAUNHOFER-GESELLSCHAFT zur Förderung der angewandten Forschung e.V. Methods and means for corona virus nucleic acid detection
WO2022011214A1 (en) 2020-07-10 2022-01-13 Alnylam Pharmaceuticals, Inc. Circular sirnas
CA3186955A1 (en) 2020-07-23 2022-01-27 Scott Benson Energy transfer dye conjugates for use in biological assays
US20230304932A1 (en) 2020-07-23 2023-09-28 Life Technologies Corporation Compositions, systems and methods for biological analysis involving energy transfer dye conjugates and analytes comprising the same
EP4208549A4 (en) 2020-09-04 2025-04-16 Verve Therapeutics, Inc. Compositions and methods for capping rnas
WO2022147214A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
EP4271695A2 (en) 2020-12-31 2023-11-08 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
US20250270619A1 (en) 2021-01-18 2025-08-28 Life Technologies Corporation Compositions, kits and methods for direct amplification from crude biological samples
WO2022159874A1 (en) 2021-01-25 2022-07-28 Life Technologies Corporation Compositions, kits and methods for detection of viral variant sequences
US20250333806A1 (en) 2021-03-23 2025-10-30 Life Technologies Corporation Compositions, kits, and methods for variant-resistant detection of target viral sequences
EP4074839A1 (en) 2021-04-16 2022-10-19 Biotype GmbH Optimized oligonucleotide tx probe for a multiplexing analysis of nucleic acids and a multiplexing method
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
KR20240036041A (en) 2021-07-21 2024-03-19 알닐람 파마슈티칼스 인코포레이티드 Metabolic Disorder-Associated Target Gene iRNA Composition and Methods of Using Same
WO2023004400A1 (en) 2021-07-21 2023-01-26 Life Technologies Corporation Dibenzoxanthene quenchers, uses, and methods of preparation
WO2023014729A1 (en) 2021-08-02 2023-02-09 Life Technologies Corporation Compositions, kits, and methods for detection of nucleic acid sequence loads
EP4380576A4 (en) 2021-08-03 2026-04-29 Verve Therapeutics Inc COMPOSITIONS AND METHODS FOR TARGETED RNA DELIVERIES
IL311864A (en) 2021-10-15 2024-06-01 Alnylam Pharmaceuticals Inc Extra-hepatic delivery irna compositions and methods of use thereof
EP4419712A1 (en) 2021-10-20 2024-08-28 Life Technologies Corporation Compositions, kits, and methods for quantification of nucleic acid sequences using an internal quantitative standard
JP2025516680A (en) 2022-05-13 2025-05-30 アルナイラム ファーマシューティカルズ, インコーポレイテッド Single-stranded loop oligonucleotide
CN114672482B (en) * 2022-05-31 2022-08-30 上海百力格生物技术有限公司 Method for preparing nucleic acid probe
CN119768474A (en) 2022-06-29 2025-04-04 生命科技股份有限公司 Multiple dye compounds
WO2024006924A1 (en) 2022-06-29 2024-01-04 Life Technologies Corporation Systems and methods for analyte detection from multiplexed assays
EP4547683A2 (en) 2022-06-30 2025-05-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024054925A1 (en) 2022-09-09 2024-03-14 Life Technologies Corporation Compositions, kits and methods for detection of viral variant sequences
JP2025532985A (en) 2022-09-30 2025-10-03 アルナイラム ファーマシューティカルズ, インコーポレイテッド Modified double-stranded RNA agents
EP4350002A1 (en) 2022-10-07 2024-04-10 Biotype GmbH Nachweis von molekularen analyten auf der grundlage massgeschneiderter sondenkonkurrenz
WO2024102839A1 (en) 2022-11-10 2024-05-16 Life Technologies Corporation Compositions, kits, and methods for detection of viral sequences
WO2024148013A1 (en) 2023-01-02 2024-07-11 Life Technologies Corporation Compositions, kits and methods for detection of viral sequences
US20240254568A1 (en) 2023-01-27 2024-08-01 Life Technologies Corporation Compositions, kits, and methods for detecting sti pathogen sequences
AU2024217843A1 (en) 2023-02-09 2025-07-31 Alnylam Pharmaceuticals, Inc. Reversir molecules and methods of use thereof
CN121816199A (en) 2023-04-12 2026-04-07 阿尔尼拉姆制药公司 Extrahepatic delivery of double stranded RNA agents
CN121335987A (en) 2023-05-12 2026-01-13 生命科技股份有限公司 Systems and methods for multiplex polymerase chain reaction processes and data analysis.
CN121729491A (en) 2023-05-12 2026-03-24 阿尔尼拉姆制药公司 Single-stranded loop oligonucleotides
DE102023124346A1 (en) 2023-09-09 2025-03-13 Biotype Gmbh Method for the detection of endometrial carcinoma subtype CN high
IL326940A (en) 2023-09-21 2026-05-01 Alnylam Pharmaceuticals Inc Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof
EP4613876A1 (en) 2024-03-08 2025-09-10 Pxlence BV Nucleic acid quantification using universal detection probes

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4665184A (en) * 1983-10-12 1987-05-12 California Institute Of Technology Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid
US4942227A (en) * 1982-01-11 1990-07-17 California Institute Of Technology Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid, their preparation and use to cleave DNA
US5395849A (en) * 1993-10-05 1995-03-07 Bristol-Myers Squibb Company Hybrid antitumor compounds containing a cyclic enediyne and a DNA-binder
WO1995029184A1 (en) * 1994-04-25 1995-11-02 Universite Louis Pasteur Polycationic nucleic bases and oligonucleotides containing same
WO1996006831A1 (en) * 1994-08-26 1996-03-07 Auckland Division Cancer Society Of New Zealand Inc. Novel dna-targeted alkylating agents

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4169888A (en) 1977-10-17 1979-10-02 The Upjohn Company Composition of matter and process
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4358535A (en) * 1980-12-08 1982-11-09 Board Of Regents Of The University Of Washington Specific DNA probes in diagnostic microbiology
US4711955A (en) * 1981-04-17 1987-12-08 Yale University Modified nucleotides and methods of preparing and using same
CA1190838A (en) 1981-07-17 1985-07-23 Cavit Akin Homogeneous nucleic acid hybridization diagnostics by non-radiative energy transfer
FR2540122B1 (en) * 1983-01-27 1985-11-29 Centre Nat Rech Scient NOVEL COMPOUNDS COMPRISING A SEQUENCE OF OLIGONUCLEOTIDE LINKED TO AN INTERCALATION AGENT, THEIR SYNTHESIS PROCESS AND THEIR APPLICATION
US4883750A (en) * 1984-12-13 1989-11-28 Applied Biosystems, Inc. Detection of specific sequences in nucleic acids
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) * 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4868105A (en) * 1985-12-11 1989-09-19 Chiron Corporation Solution phase nucleic acid sandwich assay
US4800159A (en) * 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US4868103A (en) * 1986-02-19 1989-09-19 Enzo Biochem, Inc. Analyte detection by means of energy transfer
US6270961B1 (en) 1987-04-01 2001-08-07 Hyseq, Inc. Methods and apparatus for DNA sequencing and DNA identification
US5202231A (en) * 1987-04-01 1993-04-13 Drmanac Radoje T Method of sequencing of genomes by hybridization of oligonucleotide probes
US5525464A (en) * 1987-04-01 1996-06-11 Hyseq, Inc. Method of sequencing by hybridization of oligonucleotide probes
US5124246A (en) * 1987-10-15 1992-06-23 Chiron Corporation Nucleic acid multimers and amplified nucleic acid hybridization assays using same
AU622426B2 (en) 1987-12-11 1992-04-09 Abbott Laboratories Assay using template-dependent nucleic acid probe reorganization
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
CA1341584C (en) 1988-04-06 2008-11-18 Bruce Wallace Method of amplifying and detecting nucleic acid sequences
US4921788A (en) 1988-04-12 1990-05-01 The Research Foundation Of State University Of New York Competitive nucleic acid immunoassay for the detection of analytes
WO1990003370A1 (en) 1988-09-28 1990-04-05 Microprobe Corporation DERIVATIVES OF PYRAZOLO[3,4-d]PYRIMIDINE
US5849482A (en) 1988-09-28 1998-12-15 Epoch Pharmaceuticals, Inc. Crosslinking oligonucleotides
WO1990014353A1 (en) 1989-05-18 1990-11-29 Microprobe Corporation Crosslinking oligonucleotides
CA2024548C (en) * 1989-09-05 2002-05-28 David Issachar Analyte specific chemical sensor
DK0942000T3 (en) 1989-10-24 2004-11-01 Isis Pharmaceuticals Inc 2'-modified oligonucleotides
US5237101A (en) * 1990-01-26 1993-08-17 The Trustees Of The Univ. Of Penna. Propargylic and allenic sulfones
US5210015A (en) * 1990-08-06 1993-05-11 Hoffman-La Roche Inc. Homogeneous assay system using the nuclease activity of a nucleic acid polymerase
US5512667A (en) * 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5296350A (en) 1990-10-31 1994-03-22 The Research Foundation Of State University Of New York Ion triggered alkylation of biological targets by silyloxy aromatic agents
WO1992010588A1 (en) 1990-12-06 1992-06-25 Affymax Technologies N.V. Sequencing by hybridization of a target nucleic acid to a matrix of defined oligonucleotides
WO1992020698A1 (en) * 1991-05-17 1992-11-26 Uab Research Foundation Sequence specific dna binding drugs
US5340716A (en) 1991-06-20 1994-08-23 Snytex (U.S.A.) Inc. Assay method utilizing photoactivated chemiluminescent label
US5419966A (en) * 1991-06-10 1995-05-30 Microprobe Corporation Solid support for synthesis of 3'-tailed oligonucleotides
WO1993003736A1 (en) 1991-08-21 1993-03-04 Microprobe Corporation Cross-linking oligonucleotides for enzyme-mediated triple strand formation
US5574142A (en) * 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
AU6296294A (en) 1993-01-26 1994-08-15 Microprobe Corporation Bifunctional crosslinking oligonucleotides adapted for linking to a desired gene sequence of invading organism or cell
US5786138A (en) 1993-01-29 1998-07-28 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Hyperstabilizing antisense nucleic acid binding agents
US5925517A (en) * 1993-11-12 1999-07-20 The Public Health Research Institute Of The City Of New York, Inc. Detectably labeled dual conformation oligonucleotide probes, assays and kits
US5538848A (en) * 1994-11-16 1996-07-23 Applied Biosystems Division, Perkin-Elmer Corp. Method for detecting nucleic acid amplification using self-quenching fluorescence probe
US5446137B1 (en) * 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5646126A (en) * 1994-02-28 1997-07-08 Epoch Pharmaceuticals Sterol modified oligonucleotide duplexes having anticancer activity
US5556752A (en) * 1994-10-24 1996-09-17 Affymetrix, Inc. Surface-bound, unimolecular, double-stranded DNA
US5801155A (en) * 1995-04-03 1998-09-01 Epoch Pharmaceuticals, Inc. Covalently linked oligonucleotide minor grove binder conjugates
US6312894B1 (en) * 1995-04-03 2001-11-06 Epoch Pharmaceuticals, Inc. Hybridization and mismatch discrimination using oligonucleotides conjugated to minor groove binders
EP0826066B1 (en) * 1995-05-05 2000-09-13 The Perkin-Elmer Corporation Methods and reagents for combined pcr amplification and hybridization probing assay
US5912340A (en) 1995-10-04 1999-06-15 Epoch Pharmaceuticals, Inc. Selective binding complementary oligonucleotides
US5659022A (en) * 1996-01-05 1997-08-19 Epoch Pharmaceuticals, Inc. Oligonucleotide-cyclopropapyrroloindole conjugates as sequence specific hybridization and crosslinking agents for nucleic acids
US5776907A (en) * 1996-05-20 1998-07-07 Texas Biotechnology Corporation Mitomycin oligonucleotide conjugates
US5955590A (en) 1996-07-15 1999-09-21 Worcester Foundation For Biomedical Research Conjugates of minor groove DNA binders with antisense oligonucleotides
CA2286232A1 (en) 1997-04-06 1998-11-05 California Institute Of Technology Dna-binding pyrrole and imidazole polyamide derivatives
US6080868A (en) * 1998-01-23 2000-06-27 The Perkin-Elmer Corporation Nitro-substituted non-fluorescent asymmetric cyanine dye compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4942227A (en) * 1982-01-11 1990-07-17 California Institute Of Technology Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid, their preparation and use to cleave DNA
US4665184A (en) * 1983-10-12 1987-05-12 California Institute Of Technology Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid
US5395849A (en) * 1993-10-05 1995-03-07 Bristol-Myers Squibb Company Hybrid antitumor compounds containing a cyclic enediyne and a DNA-binder
WO1995029184A1 (en) * 1994-04-25 1995-11-02 Universite Louis Pasteur Polycationic nucleic bases and oligonucleotides containing same
WO1996006831A1 (en) * 1994-08-26 1996-03-07 Auckland Division Cancer Society Of New Zealand Inc. Novel dna-targeted alkylating agents

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
B.H.GEIERSTANGER ET AL.: "Structural and Dynamic Charaterization of the Heterodimeric and Homodimeric Complexes of Distamycin and 1-Methylimidazole-2-carboxamide-Netropsin Bound to the Minor Groove of DNA.", BIOCHEMISTRY, vol. 33, no. 10, 15 March 1994 (1994-03-15), EASTON, PA US, pages 3055 - 3062, XP002014646 *
F.L.BOYD ET AL.: "Characterization of the Structure of the Anthramycin-d(ATGCAT)2 Adduct by NMR and Molecular Modeling Studies. Determination of the Stereochemistry of the Covalent Linkage Site, Orientation in the Minor Groove of DNA, and Effect on Local DNA Structure.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 112, no. 9, 25 April 1990 (1990-04-25), DC US, pages 3279 - 3289, XP002014648 *
H.GOULAOUIC ET AL.: "Selective Binding to Polynucleotides of the Hybrid Intercalating Groove Binder Bis(pyrrolecarboxamide)-Oxazolopyridocarbazole: A Molecular Modeling Study.", BIOCHEMISTRY, vol. 33, no. 6, 15 February 1994 (1994-02-15), EASTON, PA US, pages 1412 - 1418, XP002014643 *
J.A.PARKINSON ET AL.: "NMR Probing of Binding Interactions used by Minor Groove Binding, DNA-Directed Ligands : Assignment of the Binding Site of Hoechst 33258 on the Self-Complmentary Oligonucleotide, d(CGCGAATTCGCG).", JOURNAL OF THE CHEMICAL SOCIETY, CHEMICAL COMMUNICATIONS, no. 15, 1 August 1989 (1989-08-01), LETCHWORTH GB, pages 1023 - 1025, XP002014647 *
M.MANOHARAN ET AL.: "Novel Functionalization of the Sugar Moiety of Nucleic Acids for Multiple Labeling in the Minor Groove.", TETRAHEDRON LETTERS, vol. 32, no. 49, 2 December 1991 (1991-12-02), OXFORD GB, pages 7171 - 7174, XP002014641 *
M.MRKSICH ET AL.: "Antiparallel Side-by-side Dimeric Motif for Sequence-Specific Recognition in the Minor Groove of DNA by the Designed Peptide 1-methylimidazole-2-carboxamide Netropsin.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 89, no. 16, 15 August 1992 (1992-08-15), WASHINGTON US, pages 7586 - 7590, XP002014645 *
M.SRIRAM ET AL.: "Conformation of B-DNA Containing O6-ethyl-G-C Base Pairs Stabilized by Minor Groove Binding Drugs : Molecular Structure of d(CGC(e6G)AATTCGCG) Complexed with Hoechst 33258 or Hoechst 33342.", EMBO JOURNAL, vol. 11, no. 1, January 1992 (1992-01-01), EYNSHAM, OXFORD GB, pages 225 - 232, XP002014642 *
R.COSSTICK ET AL.: "Molecular Recognition in the Minor Groove of the DNA Helix. Studies on the Synthesis of Oligonucleotides and Polynucleotides Containing 3-Deaza-2'-deoxyadenosine. Interaction of teh Oligonucleotides with the restriction of Endonuclease EcoRV.", NUCLEIC ACIDS RESEARCH, vol. 18, no. 16, 25 August 1990 (1990-08-25), OXFORD GB, pages 4771 - 4778, XP002014644 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691785B2 (en) 1997-07-01 2014-04-08 Isis Pharmaceuticals, Inc. Compositions and methods for non-parenteral delivery of oligonucleotides
US6972328B2 (en) 1999-11-23 2005-12-06 Epoch Biosciences, Inc. Non-aggregating non-quenching oligomer comprising nucelotide analogs, method of synthesis and use thereof
US7759126B2 (en) 2003-10-28 2010-07-20 Elitech Holding B.V. Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for amplification (or PCR) analysis

Also Published As

Publication number Publication date
CN1186496A (en) 1998-07-01
WO1996032496A2 (en) 1996-10-17
US20110275070A1 (en) 2011-11-10
DK0819133T3 (en) 2008-05-13
DE69637389D1 (en) 2008-02-14
US6486308B2 (en) 2002-11-26
US7794945B2 (en) 2010-09-14
US20020052482A1 (en) 2002-05-02
CN1187363C (en) 2005-02-02
EP0819133A2 (en) 1998-01-21
PT819133E (en) 2008-04-07
US5801155A (en) 1998-09-01
AU716108B2 (en) 2000-02-17
CA2223678A1 (en) 1996-10-17
US20090048427A1 (en) 2009-02-19
CA2223678C (en) 2009-09-08
JPH11504626A (en) 1999-04-27
US6426408B1 (en) 2002-07-30
US6084102A (en) 2000-07-04
US8465921B2 (en) 2013-06-18
DE69637389T2 (en) 2008-12-18
CN1644585A (en) 2005-07-27
ATE382627T1 (en) 2008-01-15
CN101914099A (en) 2010-12-15
AU5384296A (en) 1996-10-30
EP0819133B1 (en) 2008-01-02
ES2300106T3 (en) 2008-06-01
JP4948690B2 (en) 2012-06-06

Similar Documents

Publication Publication Date Title
CA2223678A1 (en) Covalently linked oligonucleotide minor groove binder conjugates
EP1310507A3 (en) Novel peptide nucleic acids
CA2382521A1 (en) Oligonucleotide n3'.fwdarw.p5' thiophosphoramidates: their synthesis and use
EP0786469A3 (en) Nucleic acid ligands
CA2153898A1 (en) Method for generating single-stranded dna molecules
CA2265477A1 (en) System for in vitro transposition using modified tn5 transposase
AU1884392A (en) Peptide nucleic acids
AU3883297A (en) Conjugates of minor groove dna binders with antisense oligonucleotides
WO2005003291A3 (en) Bead bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries
CA2006008A1 (en) Method for making synthetic oligonucleotides which bind specifically to target sites on duplex dna molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use
AU8588498A (en) Surface-bound, bimolecular, double-stranded dna arrays
ATE283353T1 (en) COVALENT BINDING OF DNA TO RNA STRANDS CATALYSED BY VACCINIA TOPOISOMERASE
AU5752696A (en) Dna binding antibodies
EP1743901A3 (en) Oligonucleotides having A-DNA or B-DNA form
AU3418000A (en) Covalently closed immunostimulating nucleic acid molecule
AU7542498A (en) Nucleic acid binding proteins
AU3719700A (en) Enzymatic dna molecules that contain modified nucleotides
WO2003078450A3 (en) Negatively charged minor groove binders
CA2217780A1 (en) Polyether nucleic acids
WO2002010432A3 (en) Triphosphate oligonucleotide modification reagents and uses thereof
WO2003087115A3 (en) Oligomeric compounds having modified phosphate groups
AU4854999A (en) Methods, compositions and apparatus for making nucleic acid molecules having a selected affinity to a target molecule
WO2002010431A3 (en) Functional biopolymer modification reagents and uses thereof
WO2002061110A8 (en) Nucleic acid derivatives
AU6915198A (en) Energetically favorable binding site determination between two molecules

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 96194421.8

Country of ref document: CN

AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AU AZ BB BG BR BY CA CN CZ EE FI GE HU IS JP KE KG KP KR KZ LK LR LS LT LV MD MG MK MN MW MX NO NZ PL RO RU SD SG SI SK TJ TM TR TT UA UG UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AU AZ BB BG BR BY CA CN CZ EE FI GE HU IS JP KE KG KP KR KZ LK LR LS LT LV MD MG MK MN MW MX NO NZ PL RO RU SD SG SI SK TJ TM TR TT UA UG UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1996910723

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2223678

Country of ref document: CA

Ref document number: 2223678

Country of ref document: CA

Kind code of ref document: A

Ref document number: 1996 531051

Country of ref document: JP

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 1996910723

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1996910723

Country of ref document: EP