WO2000014098A1 - Methods for the preparation of conjugated oligomers - Google Patents

Methods for the preparation of conjugated oligomers Download PDF

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Publication number
WO2000014098A1
WO2000014098A1 PCT/US1999/019828 US9919828W WO0014098A1 WO 2000014098 A1 WO2000014098 A1 WO 2000014098A1 US 9919828 W US9919828 W US 9919828W WO 0014098 A1 WO0014098 A1 WO 0014098A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
alkyl
oligonucleotide
group
Prior art date
Application number
PCT/US1999/019828
Other languages
English (en)
French (fr)
Inventor
Muthiah Manoharan
Original Assignee
Isis Pharmaceuticals, Inc.
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 Isis Pharmaceuticals, Inc. filed Critical Isis Pharmaceuticals, Inc.
Priority to EP99942546A priority Critical patent/EP1112279A4/en
Priority to AU55899/99A priority patent/AU5589999A/en
Publication of WO2000014098A1 publication Critical patent/WO2000014098A1/en

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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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US1999/019828 1998-09-07 1999-08-27 Methods for the preparation of conjugated oligomers WO2000014098A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP99942546A EP1112279A4 (en) 1998-09-07 1999-08-27 METHOD FOR THE PRODUCTION OF CONJUGATED OLIGOMERS
AU55899/99A AU5589999A (en) 1998-09-07 1999-08-27 Methods for the preparation of conjugated oligomers

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/149,156 1998-09-07
US09/149,156 US6335437B1 (en) 1998-09-07 1998-09-07 Methods for the preparation of conjugated oligomers

Publications (1)

Publication Number Publication Date
WO2000014098A1 true WO2000014098A1 (en) 2000-03-16

Family

ID=22529021

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/019828 WO2000014098A1 (en) 1998-09-07 1999-08-27 Methods for the preparation of conjugated oligomers

Country Status (4)

Country Link
US (1) US6335437B1 (US06335437-20020101-C00041.png)
EP (1) EP1112279A4 (US06335437-20020101-C00041.png)
AU (1) AU5589999A (US06335437-20020101-C00041.png)
WO (1) WO2000014098A1 (US06335437-20020101-C00041.png)

Families Citing this family (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040171031A1 (en) * 1996-06-06 2004-09-02 Baker Brenda F. Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric 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
US20040203024A1 (en) * 1996-06-06 2004-10-14 Baker Brenda F. Modified oligonucleotides for use in RNA interference
US20040147022A1 (en) * 1996-06-06 2004-07-29 Baker Brenda F. 2'-methoxy substituted oligomeric compounds and compositions for use in gene modulations
US5898031A (en) * 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20050053976A1 (en) * 1996-06-06 2005-03-10 Baker Brenda F. Chimeric oligomeric compounds and their use in gene modulation
US20040266706A1 (en) * 2002-11-05 2004-12-30 Muthiah Manoharan Cross-linked oligomeric compounds and their use in gene modulation
US20050119470A1 (en) * 1996-06-06 2005-06-02 Muthiah Manoharan Conjugated oligomeric compounds and their use in gene modulation
AU2003290598A1 (en) * 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Modified oligonucleotides for use in rna interference
US20040198640A1 (en) * 2003-04-02 2004-10-07 Dharmacon, Inc. Stabilized polynucleotides for use in RNA interference
WO2005044976A2 (en) * 2003-06-20 2005-05-19 Isis Pharmaceuticals, Inc. Oligomeric compounds for use in gene modulation
DE602005017362D1 (de) * 2004-02-06 2009-12-10 Dharmacon Inc Stabilisierte rnas als transfektionskontrollen und silencing-reagentien
US20090280567A1 (en) * 2004-02-06 2009-11-12 Dharmacon, Inc. Stabilized sirnas as transfection controls and silencing reagents
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
KR101147147B1 (ko) * 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Rna 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드
JP2008501694A (ja) * 2004-06-03 2008-01-24 アイシス ファーマシューティカルズ、インク. 遺伝子調節の使用のために個別に修飾された鎖を有する二本鎖組成物
US8394947B2 (en) * 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US7884086B2 (en) * 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
US7923206B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Method of determining a cellular response to a biological agent
US7935811B2 (en) * 2004-11-22 2011-05-03 Dharmacon, Inc. Apparatus and system having dry gene silencing compositions
US7923207B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Apparatus and system having dry gene silencing pools
US20060223777A1 (en) * 2005-03-29 2006-10-05 Dharmacon, Inc. Highly functional short hairpin RNA
US7368550B2 (en) * 2005-10-31 2008-05-06 Agilent Technologies, Inc. Phosphorus protecting groups
JP5352462B2 (ja) * 2006-09-22 2013-11-27 ダーマコン, インコーポレイテッド 二本鎖オリゴヌクレオチド複合体、rna干渉による遺伝子サイレンシング方法、および医薬品組成物
WO2009045536A2 (en) * 2007-10-05 2009-04-09 The University Of North Carolina At Chapel Hill Receptor targeted oligonucleotides
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation
WO2009126933A2 (en) 2008-04-11 2009-10-15 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
AU2009293658A1 (en) 2008-09-22 2010-03-25 James Cardia Reduced size self-delivering RNAi compounds
WO2010039548A2 (en) 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
EP3238738B1 (en) 2008-11-10 2020-09-23 Arbutus Biopharma Corporation Novel lipids and compositions for the delivery of therapeutics
US9745574B2 (en) 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
EP2669290A1 (en) 2009-03-02 2013-12-04 Alnylam Pharmaceuticals Inc. Nucleic Acid Chemical Modifications
SI3431076T1 (sl) 2009-06-10 2022-04-29 Arbutus Biopharma Corporation Izboljšana lipidna formulacija
EP3296398A1 (en) 2009-12-07 2018-03-21 Arbutus Biopharma Corporation Compositions for nucleic acid delivery
AU2010330814B2 (en) 2009-12-18 2017-01-12 Acuitas Therapeutics Inc. Methods and compositions for delivery of nucleic acids
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)
WO2011119852A1 (en) 2010-03-24 2011-09-29 Rxi Pharmaceuticals Corporation Reduced size self-delivering rnai compounds
EP2552947A4 (en) 2010-03-26 2013-11-13 Dartmouth College VISTA REGULATORY T CELL MEDIATOR PROTEIN, VISTA BINDING ACTIVE SUBSTANCES 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
US20150231215A1 (en) 2012-06-22 2015-08-20 Randolph J. Noelle VISTA Antagonist and Methods of Use
WO2011123621A2 (en) 2010-04-01 2011-10-06 Alnylam Pharmaceuticals Inc. 2' and 5' modified monomers and oligonucleotides
US9725479B2 (en) 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
WO2011133868A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Conformationally restricted dinucleotide monomers and oligonucleotides
WO2011163121A1 (en) 2010-06-21 2011-12-29 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
US20130189268A1 (en) 2010-06-22 2013-07-25 Precision Biologics, Inc. Colon and pancreas cancer specific antigens and antibodies
US20130202652A1 (en) 2010-07-30 2013-08-08 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
CA2812556C (en) 2010-09-23 2023-02-14 Xue-Ping Wang Colon and pancreas cancer peptidomimetics
WO2012044992A2 (en) 2010-09-30 2012-04-05 Agency For Science, Technology And Research (A*Star) Methods and reagents for detection and treatment of esophageal metaplasia
ES2847891T3 (es) 2010-11-23 2021-08-04 Vitaeris Inc Anticuerpos anti-IL-6 para el tratamiento de la mucositis oral
CA2824526C (en) 2011-01-11 2020-07-07 Alnylam Pharmaceuticals, Inc. Pegylated lipids and their use for drug delivery
AU2012260601B2 (en) 2011-05-25 2018-02-01 Innate Pharma, S.A. Anti-KIR antibodies for the treatment of inflammatory disorders
US9701623B2 (en) 2011-09-27 2017-07-11 Alnylam Pharmaceuticals, Inc. Di-aliphatic substituted pegylated lipids
AU2013277051B2 (en) 2012-06-22 2018-06-07 King's College London Novel VISTA-Ig constructs and the use of VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders
US9890215B2 (en) 2012-06-22 2018-02-13 King's College London Vista modulators for diagnosis and treatment of cancer
AU2013312211B2 (en) 2012-09-07 2018-03-29 King's College London VISTA modulators for diagnosis and treatment of cancer
MY173826A (en) 2012-11-15 2020-02-24 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
CA2896723C (en) 2012-12-28 2024-02-13 Precision Biologics, Inc. Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer
BR112015018161A2 (pt) 2013-01-30 2017-08-22 Hoffmann La Roche Conjugado de oligômeros antisense de lna, composição farmacêutica e uso de um conjugado de oligômeros antisense de lna
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
CA2918194C (en) 2013-03-27 2022-12-06 The General Hospital Corporation Methods and agents for treating alzheimer's disease
CN112263682A (zh) 2013-06-27 2021-01-26 罗氏创新中心哥本哈根有限公司 靶向pcsk9的反义寡聚体和缀合物
WO2015097536A2 (en) 2013-12-24 2015-07-02 Janssen Pharmaceutical Nv Anti-vista antibodies and fragments
US11014987B2 (en) 2013-12-24 2021-05-25 Janssen Pharmaceutics Nv Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
AU2015274504B2 (en) 2014-06-11 2021-02-04 Kathy A. Green Use of VISTA agonists and antagonists to suppress or enhance humoral immunity
AU2015357463B2 (en) 2014-12-05 2021-10-07 Immunext, Inc. Identification of VSIG8 as the putative vista receptor and its use thereof to produce vista/VSIG8 modulators
AU2015364508A1 (en) 2014-12-18 2017-07-06 Alnylam Pharmaceuticals, Inc. ReversirTM compounds
BR112017027870A2 (pt) 2015-06-24 2018-08-28 Janssen Pharmaceutica Nv anticorpos e fragmentos anti-vista
WO2017015109A1 (en) 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
US10899836B2 (en) 2016-02-12 2021-01-26 Janssen Pharmaceutica Nv Method of identifying anti-VISTA antibodies
AU2017235278C1 (en) 2016-03-14 2022-03-10 F. Hoffmann-La Roche Ag Oligonucleotides for reduction of PD-L1 expression
CA3020848A1 (en) 2016-04-15 2017-10-19 Janssen Pharmaceuticals, Inc. Anti-human vista antibodies and use thereof
CA3098623A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
EP3856907A1 (en) 2018-09-28 2021-08-04 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
US20220211743A1 (en) 2019-05-17 2022-07-07 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
CN114945669A (zh) 2019-11-06 2022-08-26 阿尔尼拉姆医药品有限公司 肝外递送
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
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
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
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
WO2023003922A1 (en) 2021-07-21 2023-01-26 Alnylam Pharmaceuticals, Inc. Metabolic disorder-associated target gene irna compositions and methods of use thereof
WO2023064530A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
WO2023220744A2 (en) 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
WO2024081849A1 (en) * 2022-10-13 2024-04-18 Carnegie Mellon University Post-synthetic modification of polynucleotides via acylation reagents

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5371241A (en) * 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5476930A (en) * 1993-04-12 1995-12-19 Northwestern University Non-enzymatic ligation of oligonucleotides

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
USRE34069E (en) 1983-08-18 1992-09-15 Biosyntech Gmbh Process for the preparation of oligonucleotides
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US4816571A (en) 1987-06-04 1989-03-28 Applied Biosystems, Inc. Chemical capping by phosphitylation during oligonucleotide synthesis
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US5512668A (en) 1991-03-06 1996-04-30 Polish Academy Of Sciences Solid phase oligonucleotide synthesis using phospholane intermediates
US5210264A (en) 1992-01-10 1993-05-11 Isis Pharmaceuticals, Inc. S-(2,4-dichlorobenzyl)-β-cyanoethyl phosphorothioate diester
IL114237A (en) * 1994-07-14 2000-08-31 Schering Ag Oligonucleotide conjugates and diagnostic processes utilizing the same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5371241A (en) * 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5476930A (en) * 1993-04-12 1995-12-19 Northwestern University Non-enzymatic ligation of oligonucleotides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1112279A4 *

Also Published As

Publication number Publication date
AU5589999A (en) 2000-03-27
US6335437B1 (en) 2002-01-01
EP1112279A1 (en) 2001-07-04
EP1112279A4 (en) 2002-06-19

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