ES2089014T3 - Metodo de sintesis de oligonucleotidos adaptable a la sintesis en gran escala. - Google Patents
Metodo de sintesis de oligonucleotidos adaptable a la sintesis en gran escala.Info
- Publication number
- ES2089014T3 ES2089014T3 ES90905919T ES90905919T ES2089014T3 ES 2089014 T3 ES2089014 T3 ES 2089014T3 ES 90905919 T ES90905919 T ES 90905919T ES 90905919 T ES90905919 T ES 90905919T ES 2089014 T3 ES2089014 T3 ES 2089014T3
- Authority
- ES
- Spain
- Prior art keywords
- phosphonate
- oligonucleotides
- sealing
- synthesis
- activating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title abstract 4
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000002515 oligonucleotide synthesis Methods 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 108091034117 Oligonucleotide Proteins 0.000 abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract 3
- 238000007789 sealing Methods 0.000 abstract 3
- 230000003213 activating effect Effects 0.000 abstract 2
- 238000005859 coupling reaction Methods 0.000 abstract 2
- 239000000178 monomer Substances 0.000 abstract 2
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00281—Individual reactor vessels
- B01J2219/00286—Reactor vessels with top and bottom openings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00389—Feeding through valves
- B01J2219/00391—Rotary valves
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/005—Beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/0059—Sequential processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/0068—Means for controlling the apparatus of the process
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
SE PRESENTA UN METODO PARA PRODUCIR OLIGONUCLEOTIDOS A PEQUEÑA O GRAN ESCALA UTILIZANDO MONOMEROS DE NUCLEOXIDO H-FOSFONATO. EL METODO PUEDE UTILIZARSE PARA SINTETIZAR OLIGONUCLEOTIDOS DE CUALQUIER LONGITUD, INCLUYENDO OLIGODESOXIRIBONUCLEOTIDOS Y OLIGORIBONUCLEOTIDOS. EL METODO DA COMO RESULTADO UNA EFICIENCIA DE ACOPLAMIENTO MAYOR DEL 97% Y CONSUME SOLAMENTE DE DOS A TRES EQUIVALENTES DE MONOMERO ACTIVADOR POR REACCION DE ACOPLAMIENTO. ADEMAS, EL METODO NO PRECISA UN PASO DE OBTURACION APARTE NI UN REACTIVO DE OBTURACION PORQUE EL REACTIVO ACTIVADOR PROPORCIONA UNA FUNCION DE OBTURACION PROPIA PREVINIENDO DE ESE MODO EL ALARGAMIENTO DE SECUENCIAS FALLIDAS. LAS UNIONES DE H-FOSFONATO DEL OLIGONUCLEOTIDO SINTETIZADO COMPLETAMENTE PUEDEN SER OXIDADAS CON UNA VARIEDAD DE REACTIVOS PARA OBTENER O DIESTER DE FOSFONATO U OTROS TIPOS DE OLIGONUCLEOTIDOS MODIFICADOS.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/334,679 US5149798A (en) | 1989-04-06 | 1989-04-06 | Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2089014T3 true ES2089014T3 (es) | 1996-10-01 |
Family
ID=23308303
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES90905919T Expired - Lifetime ES2089014T3 (es) | 1989-04-06 | 1990-04-05 | Metodo de sintesis de oligonucleotidos adaptable a la sintesis en gran escala. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5149798A (es) |
| EP (1) | EP0593422B1 (es) |
| JP (1) | JPH04504420A (es) |
| AT (1) | ATE137760T1 (es) |
| BR (1) | BR9007268A (es) |
| CA (1) | CA2051692A1 (es) |
| DE (1) | DE69026963T2 (es) |
| DK (1) | DK0593422T3 (es) |
| ES (1) | ES2089014T3 (es) |
| WO (1) | WO1990012024A1 (es) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5149797A (en) * | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| EP0588881A1 (en) * | 1991-05-10 | 1994-03-30 | HYBRIDON, Inc. | 3'-end blocked oligonucleotides |
| US5977343A (en) * | 1992-05-14 | 1999-11-02 | Ribozyme Pharmaceuticals, Inc. | Synthesis, deprotection, analysis and purification of RNA and ribozymes |
| TW244371B (es) * | 1992-07-23 | 1995-04-01 | Tri Clover Inc | |
| US6346614B1 (en) * | 1992-07-23 | 2002-02-12 | Hybridon, Inc. | Hybrid oligonucleotide phosphorothioates |
| US6087491A (en) * | 1993-01-08 | 2000-07-11 | Hybridon, Inc. | Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks |
| AU678821B2 (en) * | 1993-01-08 | 1997-06-12 | Hybridon, Inc. | Detection of synthetic oligonucleotides extracted from body fluids or tissues |
| WO1995009236A1 (en) * | 1993-09-28 | 1995-04-06 | The General Hospital Corporation | USING ANTISENSE OLIGONUCLEOTIDES TO MODULATE NERVE GROWTH AND TO REVERSE β/A4 AMYLOID-INDUCED MORPHOLOGY |
| US5550047A (en) * | 1994-02-18 | 1996-08-27 | University Of Massachusetts | Oligonucleotides with anti-Epstein-Barr virus activity |
| US5801235A (en) * | 1994-05-25 | 1998-09-01 | Hybridon, Inc. | Oligonucleotides with anti-cytomegalovirus activity |
| US5866699A (en) * | 1994-07-18 | 1999-02-02 | Hybridon, Inc. | Oligonucleotides with anti-MDR-1 gene activity |
| WO1996003417A1 (en) * | 1994-07-25 | 1996-02-08 | Hybridon, Inc. | Improved methods of detritylation for oligonucleotide synthesis |
| US5554744A (en) * | 1994-09-23 | 1996-09-10 | Hybridon, Inc. | Method for loading solid supports for nucleic acid synthesis |
| US5833944A (en) * | 1994-11-07 | 1998-11-10 | Hybridon, Inc. | Procedure for the solid phase synthesis of 35 S-labeled oligonucleotides with 3H-1,2-benzodithiol-3-one-1,1-dioxide |
| US6117993A (en) * | 1995-05-23 | 2000-09-12 | Hybridon, Inc. | Synthons for oligonucleotide synthesis |
| US5750674A (en) * | 1995-05-23 | 1998-05-12 | Hybridon, Inc. | Methods and compounds for the stereoselective enrichment of oligonucleotide diastereomers and oligonucleotides thereby produced |
| US6509459B1 (en) | 1995-06-01 | 2003-01-21 | Hybridon, Inc. | Base protecting groups and rapid process for oligonucleotide synthesis |
| US6140482A (en) * | 1995-06-01 | 2000-10-31 | Hybridon, Inc. | Primary phosphoramidate internucleoside linkages and oligonucleotides containing the same |
| US5955599A (en) * | 1995-06-01 | 1999-09-21 | Hybridon, Inc. | Process for making oligonucleotides containing o- and s- methylphosphotriester internucleoside linkages |
| US5614622A (en) * | 1995-06-01 | 1997-03-25 | Hybridon, Inc. | 5-pentenoyl moiety as a nucleoside-amino protecting group, 4-pentenoyl-protected nucleotide synthons, and related oligonucleotide syntheses |
| US6667293B1 (en) | 1995-09-12 | 2003-12-23 | Hybridon, Inc. | Use of cyclodextrins to modulate gene expression with reduced immunostimulatory response |
| KR19990064332A (ko) | 1995-10-19 | 1999-07-26 | 래리 더블유. 스미스, 코크란 아담 | 올리고뉴클레오티드의 액상 합성법 |
| WO1998041531A2 (en) | 1997-03-20 | 1998-09-24 | University Of Washington | Solvent for biopolymer synthesis, solvent microdroplets and methods of use |
| US6419883B1 (en) | 1998-01-16 | 2002-07-16 | University Of Washington | Chemical synthesis using solvent microdroplets |
| US6028189A (en) * | 1997-03-20 | 2000-02-22 | University Of Washington | Solvent for oligonucleotide synthesis and methods of use |
| GB9717158D0 (en) * | 1997-08-13 | 1997-10-22 | King S College London | Solution synthesis of oligonucleotides and their phosphorothioate analogues |
| US6538128B1 (en) * | 1997-09-08 | 2003-03-25 | Avecia Biotechnology, Inc. | Detritylation solvents for nucleic acid synthesis |
| US6184347B1 (en) | 1998-11-19 | 2001-02-06 | Agilent Technologies Inc. | Minimization of blooming in high-density arrays by using reactive wash reagents |
| US6207819B1 (en) | 1999-02-12 | 2001-03-27 | Isis Pharmaceuticals, Inc. | Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds |
| US20040082774A1 (en) * | 1999-03-16 | 2004-04-29 | Guzaev Andrei P. | Novel phosphate and thiophosphate protecting groups |
| US6121437A (en) | 1999-03-16 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Phosphate and thiophosphate protecting groups |
| EP2314693A3 (en) | 1999-08-13 | 2012-11-28 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| US20010011126A1 (en) * | 1999-09-10 | 2001-08-02 | Bock Elisabeth Marianne | Neurogenic compositions and methods |
| US6620796B1 (en) * | 1999-11-08 | 2003-09-16 | Micrologix Biotech Inc. | Combinatorial library synthesis and pharmaceutically active compounds produced thereby |
| CA2398432C (en) * | 2000-01-26 | 2012-06-19 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| WO2001074346A2 (en) * | 2000-04-03 | 2001-10-11 | Hybridon, Inc. | Sensitization of cells to cytotoxic agents using oligonucleotides directed to nucleotide excision repair or transcritpion coupled repair genes |
| AU5736601A (en) | 2000-05-01 | 2001-11-12 | Hybridon Inc | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| US6809195B1 (en) * | 2000-08-16 | 2004-10-26 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotides |
| AU2001294750C1 (en) * | 2000-09-26 | 2008-09-18 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| US20030072689A1 (en) * | 2001-08-15 | 2003-04-17 | Third Wave Technologies, Inc. | Polymer synthesizer |
| US6932943B1 (en) | 2001-01-26 | 2005-08-23 | Third Wave Technologies | Nucleic acid synthesizers |
| US7435390B2 (en) * | 2001-01-26 | 2008-10-14 | Third Wave Technologies, Inc. | Nucleic acid synthesizers |
| US20080261220A1 (en) * | 2000-11-30 | 2008-10-23 | Third Wave Technologies, Inc. | Nucleic Acid Detection Assays |
| US6825338B2 (en) | 2001-03-30 | 2004-11-30 | Isis Pharmaceuticals, Inc. | Labeled oligonucleotides, methods for making same, and compounds useful therefor |
| US7105495B2 (en) * | 2001-04-30 | 2006-09-12 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| WO2002092006A2 (en) | 2001-05-16 | 2002-11-21 | Micrologix Biotech, Inc. | Nucleic acid-based compounds and methods of use thereof |
| US6921812B1 (en) | 2001-07-03 | 2005-07-26 | Isis Pharmaceuticals, Inc. | Methods of modulating pharmacokinetics of oligonucleotides |
| US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
| US20040009483A1 (en) * | 2002-07-12 | 2004-01-15 | Ilsley Diane D. | Method of linear mRNA amplification using total RNA |
| CA2512484A1 (en) * | 2003-01-16 | 2004-05-08 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides |
| CA2549173A1 (en) | 2003-12-08 | 2005-07-07 | Hybridon, Inc. | Modulation of immunostimulatory properties by small oligonucleotide-based compounds |
| US7776834B2 (en) * | 2005-11-07 | 2010-08-17 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| EP2371956A3 (en) | 2005-11-07 | 2012-01-04 | Idera Pharmaceuticals | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US7470674B2 (en) * | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US20070255054A1 (en) * | 2005-12-30 | 2007-11-01 | Affymetrix, Inc. | Oligonucleotide synthesis with intermittent and post synthetic oxidation |
| WO2009117327A2 (en) * | 2008-03-15 | 2009-09-24 | Hologic, Inc. | Compositions and methods for analysis of nucleic acid molecules during amplification reactions |
| WO2014158628A1 (en) | 2013-03-14 | 2014-10-02 | Hologic, Inc. | Compositions and methods for analysis of nucleic acid molecules |
| CN120442758A (zh) | 2021-09-30 | 2025-08-08 | 简·探针公司 | 可温度选择的fret盒信号传导 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4959463A (en) * | 1985-10-15 | 1990-09-25 | Genentech, Inc. | Intermediates |
-
1989
- 1989-04-06 US US07/334,679 patent/US5149798A/en not_active Expired - Fee Related
-
1990
- 1990-04-05 JP JP2505889A patent/JPH04504420A/ja active Pending
- 1990-04-05 DK DK90905919.8T patent/DK0593422T3/da active
- 1990-04-05 CA CA002051692A patent/CA2051692A1/en not_active Abandoned
- 1990-04-05 AT AT90905919T patent/ATE137760T1/de not_active IP Right Cessation
- 1990-04-05 WO PCT/US1990/001865 patent/WO1990012024A1/en not_active Ceased
- 1990-04-05 EP EP90905919A patent/EP0593422B1/en not_active Expired - Lifetime
- 1990-04-05 DE DE69026963T patent/DE69026963T2/de not_active Expired - Fee Related
- 1990-04-05 ES ES90905919T patent/ES2089014T3/es not_active Expired - Lifetime
- 1990-04-05 BR BR909007268A patent/BR9007268A/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990012024A1 (en) | 1990-10-18 |
| EP0593422A1 (en) | 1994-04-27 |
| ATE137760T1 (de) | 1996-05-15 |
| DK0593422T3 (da) | 1996-07-29 |
| CA2051692A1 (en) | 1990-10-07 |
| BR9007268A (pt) | 1992-03-17 |
| DE69026963D1 (de) | 1996-06-13 |
| DE69026963T2 (de) | 1996-11-07 |
| EP0593422B1 (en) | 1996-05-08 |
| JPH04504420A (ja) | 1992-08-06 |
| US5149798A (en) | 1992-09-22 |
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