DE69813243D1 - Synthese von oligonukleotiden in lösung - Google Patents

Synthese von oligonukleotiden in lösung

Info

Publication number: DE69813243D1
Authority: DE; Germany
Prior art keywords: phosphonate; synthesis; solution; oligonucleotids; alcohol
Prior art date: 1997-08-13
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 - Fee Related

Application number

DE69813243T

Other languages

English (en)

Other versions

DE69813243T2 (de

Inventor

Colin Bernard Reese

Quanlai Song

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.)

Nitto Denko Avecia Inc

Original Assignee

Avecia Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-08-13

Filing date

1998-08-10

Publication date

2003-05-15

1998-08-10 Application filed by Avecia Ltd filed Critical Avecia Ltd

2003-05-15 Publication of DE69813243D1 publication Critical patent/DE69813243D1/de

2004-01-29 Application granted granted Critical

2004-01-29 Publication of DE69813243T2 publication Critical patent/DE69813243T2/de

2018-08-11 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000015572 biosynthetic process Effects 0.000 title abstract 3
238000003786 synthesis reaction Methods 0.000 title abstract 2
-1 phosphorothioate triester Chemical class 0.000 abstract 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 2
108091034117 Oligonucleotide Proteins 0.000 abstract 2
238000000034 method Methods 0.000 abstract 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
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 1
239000003795 chemical substances by application Substances 0.000 abstract 1
230000008878 coupling Effects 0.000 abstract 1
239000007822 coupling agent Substances 0.000 abstract 1
238000010168 coupling process Methods 0.000 abstract 1
238000005859 coupling reaction Methods 0.000 abstract 1
238000011065 in-situ storage Methods 0.000 abstract 1
239000002777 nucleoside Substances 0.000 abstract 1
125000003835 nucleoside group Chemical group 0.000 abstract 1
229910052717 sulfur Inorganic materials 0.000 abstract 1
239000011593 sulfur Substances 0.000 abstract 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
- C07D265/33—Two oxygen atoms, in positions 3 and 5
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
- C07F9/18—Esters of thiophosphoric acids with hydroxyaryl compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
- C07H11/04—Phosphates; Phosphites; Polyphosphates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- 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
- 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
- C07H21/04—Compounds 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Biochemistry (AREA)
Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

DE69813243T 1997-08-13 1998-08-10 Synthese von oligonukleotiden in lösung Expired - Fee Related DE69813243T2 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9717158.1A GB9717158D0 (en)	1997-08-13	1997-08-13	Solution synthesis of oligonucleotides and their phosphorothioate analogues
PCT/GB1998/002407 WO1999009041A2 (en)	1997-08-13	1998-08-10	Solution phase synthesis of oligonucleotides

Publications (2)

Publication Number	Publication Date
DE69813243D1 true DE69813243D1 (de)	2003-05-15
DE69813243T2 DE69813243T2 (de)	2004-01-29

Family

ID=10817430

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DE69813243T Expired - Fee Related DE69813243T2 (de)	1997-08-13	1998-08-10	Synthese von oligonukleotiden in lösung

Country Status (21)

Country	Link
US (3)	US6506894B1 (de)
EP (2)	EP1325927A3 (de)
JP (1)	JP2001515086A (de)
KR (1)	KR20010022840A (de)
CN (1)	CN1231492C (de)
AT (1)	ATE236916T1 (de)
BR (1)	BR9811166A (de)
CA (1)	CA2300874A1 (de)
DE (1)	DE69813243T2 (de)
DK (1)	DK1003758T3 (de)
EA (1)	EA003091B1 (de)
ES (1)	ES2197491T3 (de)
GB (1)	GB9717158D0 (de)
HU (1)	HUP0002684A3 (de)
IL (1)	IL134517A (de)
IN (1)	IN190784B (de)
NO (1)	NO20000690L (de)
NZ (1)	NZ502684A (de)
PL (1)	PL338888A1 (de)
TR (1)	TR200000384T2 (de)
WO (1)	WO1999009041A2 (de)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9924285D0 (en) *	1999-10-14	1999-12-15	Avecia Ltd	Process
GB0004889D0 (en) *	2000-03-01	2000-04-19	Avecia Ltd	Synthesis of oligonucleotides
AU2002339175A1 (en) *	2001-11-21	2003-06-10	Avecia Biotechnology Inc.	Coupling reagent for h-phosphonate chemistry
CA2477039A1 (en) *	2002-02-22	2003-09-04	Honeywell International Inc.	Methods of producing phosphitylated compounds
GB0209539D0 (en)	2002-04-26	2002-06-05	Avecia Ltd	Monomer Polymer and process
WO2005077966A1 (en) *	2004-02-10	2005-08-25	Isis Pharmaceuticals, Inc.	Substituted pixyl protecting groups for oligonucleotide synthesis
AU2009323766B2 (en)	2008-12-02	2016-10-06	Wave Life Sciences Ltd.	Method for the synthesis of phosphorus atom modified nucleic acids
US8272150B2 (en) *	2008-12-12	2012-09-25	Speedplay, Inc.	Shoe sole mounting standard for bicycle cleat
WO2010072831A1 (en)	2008-12-23	2010-07-01	Girindus America, Inc	Sulfurizing reagents and their use for oligonucleotides synthesis
BR112012000828A8 (pt)	2009-07-06	2017-10-10	Ontorii Inc	Novas pró-drogas de ácido nucleico e métodos de uso das mesmas
JP2013531665A (ja) *	2010-06-30	2013-08-08	ギリンダス・アメリカ・インコーポレイテッド	オリゴヌクレオチド合成のためにｎ−チオ化合物を用いる新規な方法
WO2012039448A1 (ja)	2010-09-24	2012-03-29	株式会社キラルジェン	不斉補助基
WO2013012758A1 (en)	2011-07-19	2013-01-24	Ontorii, Inc.	Methods for the synthesis of functionalized nucleic acids
US20140179875A1 (en)	2011-07-29	2014-06-26	Girindus America, Inc.	Sulfurization reagents on solid supports
WO2014010250A1 (en)	2012-07-13	2014-01-16	Chiralgen, Ltd.	Asymmetric auxiliary group
AU2013289880B2 (en)	2012-07-13	2018-08-02	Wave Life Sciences Ltd.	Chiral control
CA2879066C (en)	2012-07-13	2019-08-13	Shin Nippon Biomedical Laboratories, Ltd.	Chiral nucleic acid adjuvant
WO2014085471A1 (en) *	2012-11-28	2014-06-05	Prognosdx Health, Inc.	Acid-activated compositions for the treatment of cancers, methods of their use and methods of their preparation
US10149905B2 (en)	2014-01-15	2018-12-11	Shin Nippon Biomedical Laboratories, Ltd.	Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
WO2015108047A1 (ja)	2014-01-15	2015-07-23	株式会社新日本科学	免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
US10322173B2 (en)	2014-01-15	2019-06-18	Shin Nippon Biomedical Laboratories, Ltd.	Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
SG11201605782UA (en)	2014-01-16	2016-08-30	Wave Life Sciences Ltd	Chiral design
WO2018215049A1 (en) *	2017-05-23	2018-11-29	F. Hoffmann-La Roche Ag	Process for galnac oligonucleotide conjugates

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3444300A (en) *	1964-05-05	1969-05-13	Chevron Res	N-polyhaloalkylthio compounds as fungicidal agents
FR1519704A (fr) *	1967-02-14	1968-04-05	Roussel Uclaf	Nouveaux composés dithiocarbamiques hétérocycliques et procédé de préparation
US3546185A (en)	1968-03-20	1970-12-08	Monsanto Co	Inhibiting premature vulcanization of diene rubbers
US5149798A (en) *	1989-04-06	1992-09-22	Worcester Foundation For Experimental Biology	Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses
KR960700262A (ko) *	1993-01-08	1996-01-19	다알렌 반스톤	이합체 블록의 합성 및 그것의 올리고누클레오티드 어셈블리에의 사용 방법(synthesis of dimmer blocks and their use in assembling oligonucleotides)
GB9501465D0 (en)	1995-01-25	1995-03-15	King S College London	Nucleoside phosphorothioate derivatives,synthesis and use thereof
GB0004889D0 (en) *	2000-03-01	2000-04-19	Avecia Ltd	Synthesis of oligonucleotides

1997
- 1997-08-13 GB GBGB9717158.1A patent/GB9717158D0/en active Pending
1998
- 1998-08-10 ES ES98938782T patent/ES2197491T3/es not_active Expired - Lifetime
- 1998-08-10 CN CNB988099314A patent/CN1231492C/zh not_active Expired - Fee Related
- 1998-08-10 AT AT98938782T patent/ATE236916T1/de not_active IP Right Cessation
- 1998-08-10 TR TR2000/00384T patent/TR200000384T2/xx unknown
- 1998-08-10 JP JP2000509720A patent/JP2001515086A/ja active Pending
- 1998-08-10 PL PL98338888A patent/PL338888A1/xx unknown
- 1998-08-10 DK DK98938782T patent/DK1003758T3/da active
- 1998-08-10 NZ NZ502684A patent/NZ502684A/xx unknown
- 1998-08-10 DE DE69813243T patent/DE69813243T2/de not_active Expired - Fee Related
- 1998-08-10 CA CA002300874A patent/CA2300874A1/en not_active Abandoned
- 1998-08-10 HU HU0002684A patent/HUP0002684A3/hu unknown
- 1998-08-10 US US09/485,606 patent/US6506894B1/en not_active Expired - Lifetime
- 1998-08-10 EA EA200000211A patent/EA003091B1/ru not_active IP Right Cessation
- 1998-08-10 WO PCT/GB1998/002407 patent/WO1999009041A2/en not_active Application Discontinuation
- 1998-08-10 BR BR9811166-3A patent/BR9811166A/pt not_active IP Right Cessation
- 1998-08-10 EP EP03007651A patent/EP1325927A3/de not_active Withdrawn
- 1998-08-10 EP EP98938782A patent/EP1003758B1/de not_active Expired - Lifetime
- 1998-08-10 KR KR1020007001442A patent/KR20010022840A/ko active IP Right Grant
- 1998-08-10 IL IL13451798A patent/IL134517A/en active IP Right Grant
- 1998-08-12 IN IN2353DE1998 patent/IN190784B/en unknown
2000
- 2000-02-11 NO NO20000690A patent/NO20000690L/no not_active Application Discontinuation
2002
- 2002-11-15 US US10/294,794 patent/US7019127B2/en not_active Expired - Lifetime
2005
- 2005-06-28 US US11/167,145 patent/US20050240015A1/en not_active Abandoned

Also Published As

Publication number	Publication date
EP1325927A2 (de)	2003-07-09
HUP0002684A2 (hu)	2000-12-28
WO1999009041A2 (en)	1999-02-25
EP1003758B1 (de)	2003-04-09
GB9717158D0 (en)	1997-10-22
ES2197491T3 (es)	2004-01-01
CA2300874A1 (en)	1999-02-25
AU8738698A (en)	1999-03-08
EA003091B1 (ru)	2002-12-26
PL338888A1 (en)	2000-11-20
DK1003758T3 (da)	2003-07-21
IL134517A0 (en)	2001-04-30
CN1274361A (zh)	2000-11-22
ATE236916T1 (de)	2003-04-15
US7019127B2 (en)	2006-03-28
NZ502684A (en)	2002-12-20
EP1003758A2 (de)	2000-05-31
US20030083490A1 (en)	2003-05-01
BR9811166A (pt)	2000-07-25
WO1999009041A3 (en)	1999-05-06
TR200000384T2 (tr)	2000-11-21
KR20010022840A (ko)	2001-03-26
IN190784B (de)	2003-08-23
EA200000211A1 (ru)	2000-08-28
US20050240015A1 (en)	2005-10-27
NO20000690L (no)	2000-04-11
US6506894B1 (en)	2003-01-14
AU749343B2 (en)	2002-06-27
JP2001515086A (ja)	2001-09-18
IL134517A (en)	2004-02-19
NO20000690D0 (no)	2000-02-11
HUP0002684A3 (en)	2001-11-28
CN1231492C (zh)	2005-12-14
EP1325927A3 (de)	2008-07-02
DE69813243T2 (de)	2004-01-29

Publication	Publication Date	Title
ATE236916T1 (de)	2003-04-15	Synthese von oligonukleotiden in lösung
IT7923980A0 (it)	1979-06-29	Pinza per l'applicazione di graffe all'ovidotto.
TR199800046A3 (tr)	1998-10-21	Aktif maddeler yaratilmasi için nükleik asit olusumu.
PT748382E (pt)	2003-03-31	Acidos nucleicos enzimaticos contendo nao-nucleotidos
DE69521517D1 (de)	2001-08-02	Prodrug-oligonukleotide
IT8021794A0 (it)	1980-05-05	Pinza per l'applicazione di graffe all'ovidotto.
BR9302680A (pt)	1994-02-08	Processo para hidroformilacao para produzir 1,6-hexanodiais
DE59910853D1 (de)	2004-11-18	Kieselsäureester
NO20024155L (no)	2002-10-24	Fremgangsmåte for fremstilling av fosforotioattriestere
DE69319972D1 (de)	1998-09-03	Hyperthermophilische alpha-amylase Gene
NO884833L (no)	1989-05-02	Maalrettede former av metyltritio-anti-tumormidler.
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FR2760024B1 (fr)	1999-05-14	Procede de caracterisation de duplex d'acide nucleique
BR9004059A (pt)	1991-09-03	Processo para a preparacao de formulacoes liquidas aquosas de enzimas efetivas proteoliticamente
ID20373A (id)	1998-12-03	Proses untuk menetralisasi asam petroleum
IT7848785A0 (it)	1978-04-06	Processo per il microincapsulamento di prodotti chimici agrari contenenti derivati dell'acido fosforico
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KR960033179U (ko)	1996-11-19	양액 재배용 배수골판
AU2782989A (en)	1989-07-05	Dna and rna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
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