EA032438B1 - Способы мечения днк-кодированных библиотек - Google Patents
Способы мечения днк-кодированных библиотек Download PDFInfo
- Publication number
- EA032438B1 EA032438B1 EA201490534A EA201490534A EA032438B1 EA 032438 B1 EA032438 B1 EA 032438B1 EA 201490534 A EA201490534 A EA 201490534A EA 201490534 A EA201490534 A EA 201490534A EA 032438 B1 EA032438 B1 EA 032438B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- oligonucleotide
- label
- crosslinking
- structural element
- library
- Prior art date
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1065—Preparation or screening of tagged libraries, e.g. tagged microorganisms by STM-mutagenesis, tagged polynucleotides, gene tags
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1068—Template (nucleic acid) mediated chemical library synthesis, e.g. chemical and enzymatical DNA-templated organic molecule synthesis, libraries prepared by non ribosomal polypeptide synthesis [NRPS], DNA/RNA-polymerase mediated polypeptide synthesis
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
- C40B50/16—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support involving encoding steps
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
Landscapes
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- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Structural Engineering (AREA)
- Medicinal Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
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| US201161531820P | 2011-09-07 | 2011-09-07 | |
| US201161536929P | 2011-09-20 | 2011-09-20 | |
| PCT/US2012/054228 WO2013036810A1 (en) | 2011-09-07 | 2012-09-07 | Methods for tagging dna-encoded libraries |
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| EA201490534A1 EA201490534A1 (ru) | 2014-06-30 |
| EA032438B1 true EA032438B1 (ru) | 2019-05-31 |
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| EA201490534A EA032438B1 (ru) | 2011-09-07 | 2012-09-07 | Способы мечения днк-кодированных библиотек |
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| IL163822A0 (en) * | 2002-03-15 | 2005-12-18 | Nuevolution As | An improved method for synthesising templated molecules |
| GB2467691A (en) | 2008-09-05 | 2010-08-11 | Aueon Inc | Methods for stratifying and annotating cancer drug treatment options |
| EP3653763A1 (en) | 2009-02-13 | 2020-05-20 | X-Chem, Inc. | Methods of creating and screening dna-encoded libraries |
| IN2013MN00522A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2010-09-24 | 2015-05-29 | Univ Leland Stanford Junior | |
| EP2748357B1 (en) * | 2011-09-07 | 2018-04-04 | X-Chem, Inc. | Methods for tagging dna-encoded libraries |
| EP2872680B1 (en) * | 2012-07-13 | 2018-04-04 | X-Chem, Inc. | Dna-encoded libraries having encoding oligonucleotide linkages not readable by polymerases |
| WO2014093406A1 (en) * | 2012-12-10 | 2014-06-19 | Fred Hutchinson Cancer Research Center | Methods for screening |
| CN103882532B (zh) * | 2012-12-20 | 2015-10-21 | 成都先导药物开发有限公司 | 一种先导化合物的合成及筛选方法与试剂盒 |
| EP2934551B1 (en) * | 2012-12-20 | 2017-11-29 | Sirna Therapeutics, Inc. | Post-synthetic orthogonal amidation plus metal catalyzed azide-alkyne cycloaddition click chemistry on si-rna |
| GB201322692D0 (en) * | 2013-12-20 | 2014-02-05 | Philochem Ag | Production of encoded chemical libraries |
| GB201404552D0 (en) * | 2014-03-14 | 2014-04-30 | Philochem Ag | Purification of dna-conjugate products |
| US10900065B2 (en) | 2014-11-14 | 2021-01-26 | University Of Washington | Methods and kits for labeling cellular molecules |
| MA41298A (fr) * | 2014-12-30 | 2017-11-07 | X Chem Inc | Procédés de marquage de banques codées par de l'adn |
| CN104894651B (zh) * | 2015-06-29 | 2017-04-12 | 天津诺禾医学检验所有限公司 | 微量起始dna的高通量测序文库构建方法及其所构建的高通量测序文库 |
| CN115820806A (zh) * | 2016-06-16 | 2023-03-21 | 哈斯达克科学公司 | 寡核苷酸指导和记录的编码探针分子的组合合成 |
| CN107130300A (zh) * | 2016-10-08 | 2017-09-05 | 深圳劲宇生物科技有限公司 | 一种dna编码分子库的合成方法及dna模板 |
| WO2018107093A1 (en) * | 2016-12-09 | 2018-06-14 | University Of Southern California | Genome-wide mapping of dna-dna proximities in the nucleus |
| EP3360962A1 (en) * | 2017-02-14 | 2018-08-15 | Technische Universität Dortmund | Synthesis of dna-encoded libraries by micellar catalysis |
| EP3515880B1 (en) | 2017-03-17 | 2023-05-10 | Hitgen Inc. | Methods and compositions for synthesis of encoded libraries |
| EP3619340A4 (en) * | 2017-05-02 | 2021-01-20 | Haystack Sciences Corporation | OLIGONUCLEOTID-DRIVEN COMBINATORY SYNTHESIS VERIFICATION MOLECULES AND ASSOCIATED MANUFACTURING AND USE PROCESSES |
| WO2019006269A1 (en) * | 2017-06-30 | 2019-01-03 | The Regents Of The University Of California | METHODS AND SYSTEMS FOR ASSESSING METHYLATION OF DNA IN ACELLULAR DNA |
| US20200263163A1 (en) * | 2017-09-25 | 2020-08-20 | Haystack Sciences Corporation | Multinomial encoding for oligonucleotide-directed combinatorial chemistry |
| CN108070009B (zh) * | 2017-12-12 | 2021-04-13 | 上海药明康德新药开发有限公司 | 一种制备dna编码化合物文库的方法及起始头片段化合物和制得的dna编码化合物 |
| US11667941B2 (en) | 2018-01-12 | 2023-06-06 | Camena Bioscience Limited | Compositions and methods for template-free geometric enzymatic nucleic acid synthesis |
| WO2019149198A1 (zh) * | 2018-01-31 | 2019-08-08 | 成都先导药物开发股份有限公司 | 一种dna编码化合物库及化合物筛选方法 |
| WO2019157692A1 (zh) * | 2018-02-14 | 2019-08-22 | 深圳劲宇生物科技有限公司 | Dna 编码分子库及无靶点限制的化合物筛选方法 |
| WO2019157693A1 (zh) * | 2018-02-14 | 2019-08-22 | 深圳劲宇生物科技有限公司 | Dna编码分子库及应用广的化合物筛选方法 |
| CN112166199B (zh) | 2018-04-02 | 2025-04-29 | 埃努梅拉分子股份有限公司 | 用于对核酸分子进行计数的方法、系统和组合物 |
| WO2020001560A1 (zh) * | 2018-06-29 | 2020-01-02 | 成都先导药物开发股份有限公司 | 一种合成dna编码化合物中的反应监测方法 |
| CN109468310B (zh) * | 2018-10-25 | 2020-12-01 | 深圳劲宇生物科技有限公司 | Dna编码碎片分子库的合成方法和连接基团的筛选方法 |
| CA3120895A1 (en) | 2018-12-20 | 2020-06-25 | Sergey N. Krylov | Binder selection using capillary electrophoresis |
| EP3929205A4 (en) * | 2019-02-18 | 2022-11-16 | Ajinomoto Co., Inc. | PROCESS FOR PREPARING MODIFIED OLIGONUCLEOTIDE WITH COMPLEMENTARY SEQUENCE |
| WO2020206170A1 (en) | 2019-04-02 | 2020-10-08 | Progenity, Inc. | Methods, systems, and compositions for counting nucleic acid molecules |
| KR20210148304A (ko) * | 2019-04-05 | 2021-12-07 | 클라렛 바이오사이언스, 엘엘씨 | 핵산을 분석하기 위한 방법 및 조성물 |
| CA3132835A1 (en) * | 2019-05-09 | 2020-11-12 | Pacific Biosciences Of California, Inc. | Compositions and methods for improved cdna synthesis |
| CA3144759A1 (en) * | 2019-07-25 | 2021-01-28 | X-Chem, Inc. | Methods for tagging and encoding of pre-existing compound libraries |
| WO2023077001A1 (en) * | 2021-10-27 | 2023-05-04 | Juan Pablo Maianti | Dna-encoded and affinity-tagged masked-warhead compounds and use thereof in assembling libraries of small molecules enabled for late-stage purification and multiplexed screening of covalent ligands |
| EP4594520A2 (en) | 2022-09-30 | 2025-08-06 | Sixfold Bioscience Ltd. | Compositions containing oligonucleotides with theranostic applications |
| WO2025042899A2 (en) * | 2023-08-24 | 2025-02-27 | X-Chem, Inc. | Methods for identifying compounds binding to a target molecule using mirror-imaging of the target molecule |
| KR102774172B1 (ko) * | 2023-10-25 | 2025-02-28 | 서울대학교산학협력단 | Rna 변형의 모든 주변 서열을 포함하는 광범위한 rna 변형 라이브러리 설계법 및 그 이용 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6867290B2 (en) * | 1999-04-30 | 2005-03-15 | Cyclops Genome Sciences, Ltd. | Modified polynucleotides and uses thereof |
| WO2010094036A1 (en) * | 2009-02-13 | 2010-08-19 | X-Chem, Inc. | Methods of creating and screening dna-encoded libraries |
| US20110104785A1 (en) * | 2009-11-05 | 2011-05-05 | Ramesh Vaidyanathan | Methods and kits for 3'-end-tagging of rna |
Family Cites Families (158)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3788914T2 (de) | 1986-09-08 | 1994-08-25 | Ajinomoto Kk | Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere. |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5025388A (en) | 1988-08-26 | 1991-06-18 | Cramer Richard D Iii | Comparative molecular field analysis (CoMFA) |
| US5670633A (en) * | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US6005087A (en) * | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5723289A (en) | 1990-06-11 | 1998-03-03 | Nexstar Pharmaceuticals, Inc. | Parallel selex |
| US5660985A (en) | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
| JP2780572B2 (ja) | 1991-09-13 | 1998-07-30 | 株式会社島津製作所 | オリゴヌクレオチドの酵素的合成法及びオリゴヌクレオチドのプライマーとしての使用 |
| JP2001524926A (ja) | 1991-09-18 | 2001-12-04 | アフィマックス テクノロジーズ ナームロゼ フェンノートシャップ | オリゴマーの雑多ライブラリーの集合体を合成する方法 |
| US5639603A (en) | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| US6503759B1 (en) | 1992-10-01 | 2003-01-07 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| EP0665897B1 (en) | 1992-10-01 | 2003-07-09 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| US5807683A (en) | 1992-11-19 | 1998-09-15 | Combichem, Inc. | Combinatorial libraries and methods for their use |
| US5681943A (en) | 1993-04-12 | 1997-10-28 | Northwestern University | Method for covalently linking adjacent oligonucleotides |
| ATE246702T1 (de) | 1993-04-12 | 2003-08-15 | Univ Northwestern | Verfahren zur darstellung von oligonukleotiden |
| US5840485A (en) | 1993-05-27 | 1998-11-24 | Selectide Corporation | Topologically segregated, encoded solid phase libraries |
| ATE366741T1 (de) | 1993-05-27 | 2007-08-15 | Aventis Pharma Inc | Topologisch getrennte, kodierende festphasen- bibliotheken |
| JPH09500378A (ja) | 1993-07-02 | 1997-01-14 | リンクス セラピューティクス，インコーポレイティド | 枝分れされそして複雑に結合された高分子構造体の集中的合成 |
| US5571903A (en) | 1993-07-09 | 1996-11-05 | Lynx Therapeutics, Inc. | Auto-ligating oligonucleotide compounds |
| US6087186A (en) | 1993-07-16 | 2000-07-11 | Irori | Methods and apparatus for synthesizing labeled combinatorial chemistry libraries |
| GB9315847D0 (en) | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
| AU7390994A (en) | 1993-08-25 | 1995-03-21 | Symbicom Aktiebolag | Molecular modelling and drug design |
| US5658782A (en) | 1993-10-20 | 1997-08-19 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University A Non-Profit Organization | Amino acid transporters and uses |
| WO1995012608A1 (en) | 1993-11-02 | 1995-05-11 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
| US6117976A (en) | 1993-11-04 | 2000-09-12 | Medical Research Council | Manufacture and use of polypeptides tagged using binding molecules |
| AU692212B2 (en) | 1993-12-17 | 1998-06-04 | Roger S. Cubicciotti | Nucleotide-directed assembly of bimolecular and multimolecular drugs and devices |
| US6936477B2 (en) | 1994-04-13 | 2005-08-30 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| JPH08268A (ja) | 1994-06-16 | 1996-01-09 | Koichi Nishigaki | 連結した２本鎖ｄｎａの製造方法 |
| US5525734A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies N.V. | Methods for synthesizing diverse collections of pyrrolidine compounds |
| US5525735A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies Nv | Methods for synthesizing diverse collections of pyrrolidine compounds |
| NZ291554A (en) | 1994-07-26 | 1999-02-25 | Scripps Research Inst | Production of soluble polymer-linked peptide/nucleic acid libraries |
| US6654505B2 (en) | 1994-10-13 | 2003-11-25 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
| US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
| USRE43097E1 (en) | 1994-10-13 | 2012-01-10 | Illumina, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
| US6013445A (en) | 1996-06-06 | 2000-01-11 | Lynx Therapeutics, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
| US5695934A (en) | 1994-10-13 | 1997-12-09 | Lynx Therapeutics, Inc. | Massively parallel sequencing of sorted polynucleotides |
| US5846719A (en) | 1994-10-13 | 1998-12-08 | Lynx Therapeutics, Inc. | Oligonucleotide tags for sorting and identification |
| WO1996038726A1 (en) | 1995-05-30 | 1996-12-05 | Ecole Polytechnique Federale De Lausanne (Epfl) | Covalently immobilized phospholipid bilayers on solid surfaces |
| US5780613A (en) | 1995-08-01 | 1998-07-14 | Northwestern University | Covalent lock for self-assembled oligonucleotide constructs |
| DE19646372C1 (de) | 1995-11-11 | 1997-06-19 | Evotec Biosystems Gmbh | Genotyp und Phänotyp koppelnde Verbindung |
| US5780231A (en) | 1995-11-17 | 1998-07-14 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
| US5962228A (en) | 1995-11-17 | 1999-10-05 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
| US5763175A (en) | 1995-11-17 | 1998-06-09 | Lynx Therapeutics, Inc. | Simultaneous sequencing of tagged polynucleotides |
| US6537776B1 (en) | 1999-06-14 | 2003-03-25 | Diversa Corporation | Synthetic ligation reassembly in directed evolution |
| US5846839A (en) | 1995-12-22 | 1998-12-08 | Glaxo Group Limited | Methods for hard-tagging an encoded synthetic library |
| US6027890A (en) | 1996-01-23 | 2000-02-22 | Rapigene, Inc. | Methods and compositions for enhancing sensitivity in the analysis of biological-based assays |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| DE19642751A1 (de) | 1996-10-16 | 1998-04-23 | Deutsches Krebsforsch | Saccharid-Bibliothek |
| CA2278786C (en) | 1997-01-21 | 2010-07-20 | The General Hospital Corporation | Selection of proteins using rna-protein fusions |
| WO2002034935A2 (en) | 2000-10-27 | 2002-05-02 | Research Development Foundation | In vitro selection of signaling aptamers |
| US5888737A (en) | 1997-04-15 | 1999-03-30 | Lynx Therapeutics, Inc. | Adaptor-based sequence analysis |
| US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
| JP4294740B2 (ja) | 1997-05-23 | 2009-07-15 | ソレクサ・インコーポレイテッド | 分析物の系列的プロセシングのためのシステムおよび装置 |
| US20020034732A1 (en) | 1997-07-30 | 2002-03-21 | Daniel J. Capon | Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening |
| CA2302292A1 (en) | 1997-08-29 | 1999-03-04 | Selective Genetics, Inc. | Methods using phage display for selecting internalizing ligands for gene delivery |
| US6607878B2 (en) | 1997-10-06 | 2003-08-19 | Stratagene | Collections of uniquely tagged molecules |
| EP1090137B1 (de) * | 1998-06-22 | 2002-04-03 | Larova Biochemie GmbH | Herstellung von polymeren aus nukleotidischen und/oder nicht-nukleotidischen bausteinen auf enzymatischem weg |
| US6846655B1 (en) | 1998-06-29 | 2005-01-25 | Phylos, Inc. | Methods for generating highly diverse libraries |
| AU6502599A (en) | 1998-10-05 | 2000-04-26 | Lynx Therapeutics, Inc. | Enzymatic synthesis of oligonucleotide tags |
| WO2000023458A1 (en) | 1998-10-19 | 2000-04-27 | The Board Of Trustees Of The Leland Stanford Junior University | Dna-templated combinatorial library chemistry |
| US5942609A (en) | 1998-11-12 | 1999-08-24 | The Porkin-Elmer Corporation | Ligation assembly and detection of polynucleotides on solid-support |
| DK1137812T3 (da) | 1998-12-02 | 2007-05-21 | Adnexus Therapeutics Inc | DNA-proteinfusioner og anvendelser deraf |
| US6087112A (en) * | 1998-12-30 | 2000-07-11 | Oligos Etc. Inc. | Arrays with modified oligonucleotide and polynucleotide compositions |
| US7033753B1 (en) | 1999-01-15 | 2006-04-25 | University Of Rochester | Compositions and methods for nonenzymatic ligation of oligonucleotides and detection of genetic polymorphisms |
| EP1208219A1 (en) | 1999-04-08 | 2002-05-29 | Pavel Sergeev | Synthesis of biologically active compounds in cells |
| US7270969B2 (en) | 1999-05-05 | 2007-09-18 | Phylogica Limited | Methods of constructing and screening diverse expression libraries |
| US6436665B1 (en) | 1999-08-27 | 2002-08-20 | Phylos, Inc | Methods for encoding and sorting in vitro translated proteins |
| ATE363074T1 (de) | 1999-09-14 | 2007-06-15 | Xenoport Inc | Substrate und screeningverfahren für transportproteine |
| AU7856600A (en) | 1999-10-04 | 2001-05-10 | University Of Medicine And Dentistry Of New Jersey | Novel carbamates and ureas |
| US6844324B1 (en) | 1999-11-12 | 2005-01-18 | Massachusetts Institute Of Technology | Modular peptide mediated intracellular delivery system and uses therefore |
| AU2001241668A1 (en) | 2000-02-23 | 2001-09-03 | Xenoport, Inc. | Self-encoded combinatorial synthesis of compound multiplets |
| US6936467B2 (en) | 2000-03-27 | 2005-08-30 | University Of Delaware | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides |
| US7998673B2 (en) | 2000-03-29 | 2011-08-16 | Lgc Limited | Hybridisation beacon and method of rapid sequence detection and discrimination |
| US6479262B1 (en) * | 2000-05-16 | 2002-11-12 | Hercules, Incorporated | Solid phase enzymatic assembly of polynucleotides |
| US6994963B1 (en) | 2000-07-10 | 2006-02-07 | Ambion, Inc. | Methods for recombinatorial nucleic acid synthesis |
| US20020072887A1 (en) | 2000-08-18 | 2002-06-13 | Sandor Szalma | Interaction fingerprint annotations from protein structure models |
| US6627748B1 (en) | 2000-09-11 | 2003-09-30 | The Trustees Of Columbia University In The City Of New York | Combinatorial fluorescence energy transfer tags and their applications for multiplex genetic analyses |
| US7493385B2 (en) | 2000-09-20 | 2009-02-17 | Arkray, Inc. | Client support system |
| JP2002315577A (ja) | 2000-11-14 | 2002-10-29 | Gencom Co | 核酸ライブラリーの作製方法 |
| US20030049616A1 (en) | 2001-01-08 | 2003-03-13 | Sydney Brenner | Enzymatic synthesis of oligonucleotide tags |
| DE60213826T3 (de) | 2001-03-19 | 2013-10-17 | President And Fellows Of Harvard College | Entwicklung neuer molekularer funktionen |
| US20030143561A1 (en) | 2001-06-20 | 2003-07-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| EP1401850A1 (en) | 2001-06-20 | 2004-03-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| ES2571945T3 (es) | 2001-06-20 | 2016-05-27 | Nuevolution As | Moléculas y métodos con plantilla para el uso de tales moléculas |
| WO2004001042A2 (en) | 2002-06-20 | 2003-12-31 | Nuevolution A/S | Microarrays displaying encoded molecules |
| US20060234231A1 (en) | 2001-06-20 | 2006-10-19 | Nuevolution A/S | Microarrays displaying encoded molecules |
| US20070213519A1 (en) | 2002-03-01 | 2007-09-13 | Nuevolution A/S | Building Block Forming A C=C Double Bond Upon Reaction |
| CA2478203C (en) | 2002-03-08 | 2011-06-14 | Eidgenossische Technische Hochschule Zurich | Encoded self-assembling chemical libraries (esachel) |
| AU2003218629A1 (en) | 2002-03-15 | 2003-09-29 | Nuevolution A/S | A building block forming a c-c or a c-hetero atom bond uponreaction |
| WO2003078626A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block capable of transferring a functional entity |
| IL163822A0 (en) | 2002-03-15 | 2005-12-18 | Nuevolution As | An improved method for synthesising templated molecules |
| US20050221318A1 (en) | 2002-03-15 | 2005-10-06 | Gouliaev Alex H | Building block forming a c-c bond upon reaction |
| CA2492048A1 (en) | 2002-07-18 | 2004-01-29 | The Board Of Trustees Of The Leland Stanford Junior University | Detection of chemical ligation using fluorescence quenching leaving groups |
| EP1527173A1 (en) | 2002-07-23 | 2005-05-04 | Nuevolution A/S | Gene shuffing by template switching |
| AU2003247266A1 (en) | 2002-08-01 | 2004-02-23 | Nuevolution A/S | Multi-step synthesis of templated molecules |
| US7491494B2 (en) | 2002-08-19 | 2009-02-17 | President And Fellows Of Harvard College | Evolving new molecular function |
| WO2004024929A2 (en) | 2002-09-12 | 2004-03-25 | Nuevolution A/S | Proximity-aided synthesis of templated molecules |
| DK1558744T3 (da) * | 2002-10-30 | 2011-10-10 | Nuevolution As | Enzymatisk kodning |
| WO2004056994A2 (en) | 2002-12-19 | 2004-07-08 | Nuevolution A/S | Quasirandom structure and function guided synthesis methods |
| US20070026397A1 (en) | 2003-02-21 | 2007-02-01 | Nuevolution A/S | Method for producing second-generation library |
| US20060269920A1 (en) | 2003-02-21 | 2006-11-30 | Nuevolution A/S | Method for obtaining structural information about an encoded molecule |
| ATE424455T1 (de) | 2003-03-20 | 2009-03-15 | Nuevolution As | Ligationsvermittelnde codierung von kleinen molekülen |
| US20070134662A1 (en) | 2003-07-03 | 2007-06-14 | Juswinder Singh | Structural interaction fingerprint |
| EP1668157A4 (en) | 2003-07-07 | 2007-10-24 | One Cell Systems Inc | HAIRPIN MARKED PROBES AND METHOD OF USE |
| EP1533385A1 (en) | 2003-09-05 | 2005-05-25 | Nuevolution A/S | Templated compounds for generation of encoded molecules and directional methods using such compounds |
| US7365179B2 (en) | 2003-09-09 | 2008-04-29 | Compass Genetics, Llc | Multiplexed analytical platform |
| DK1670939T3 (da) | 2003-09-18 | 2010-03-01 | Nuevolution As | Fremgangsmåde til opnåelse af strukturel information om et kodet molekyle og fremgangsmåde til udvælgelse af forbindelser |
| WO2005050224A2 (en) | 2003-11-13 | 2005-06-02 | Epitome Biosystems Inc. | Small molecule and peptide arrays and uses thereof |
| US7972994B2 (en) | 2003-12-17 | 2011-07-05 | Glaxosmithkline Llc | Methods for synthesis of encoded libraries |
| EP2366705A1 (en) | 2003-12-17 | 2011-09-21 | Praecis Pharmaceuticals Incorporated | Methods for synthesis of encoded libraries |
| US20050153321A1 (en) | 2003-12-30 | 2005-07-14 | Saba James A. | Libraries of multiple-ligand-conjugated nucleic acids |
| JP2007521833A (ja) | 2004-02-12 | 2007-08-09 | コンパス ジェネティクス エルエルシー | 配列特異的分類による遺伝的分析 |
| EP1723255B1 (en) | 2004-02-17 | 2010-12-29 | Nuevolution A/S | Method for enrichment involving elimination by mismatch hybridisation |
| DE602005017370D1 (de) | 2004-03-22 | 2009-12-10 | Nuevolution As | Ligationscodierung unter verwendung von oligonukleotidbausteinen |
| US7405287B2 (en) | 2004-08-03 | 2008-07-29 | Board Of Regents, The University Of Texas System | Method of treating a cancer |
| US7745614B2 (en) | 2004-09-03 | 2010-06-29 | The Board Of Trustees Of The Leland Stanford Junior University | Universal linker compositions for the release or transfer of chemical agents from a polynucleotide |
| WO2006047791A2 (en) | 2004-10-27 | 2006-05-04 | The Board Of Trustees Of The Leland Stanford Junior University | Dna-templated combinatorial library device and method for use |
| EP1809743B1 (en) | 2004-11-08 | 2008-12-31 | Vipergen APS | Structural nucleid acid guided chemical synthesis |
| US8168381B2 (en) | 2004-11-22 | 2012-05-01 | Peter Birk Rasmussen | Template directed split and mix systhesis of small molecule libraries |
| JP2008524237A (ja) | 2004-12-17 | 2008-07-10 | ダイナバックス テクノロジーズ コーポレイション | 免疫寛容の誘導又は促進のための方法及び組成物 |
| CN101090979A (zh) * | 2004-12-22 | 2007-12-19 | 埃克斯魁恩公司 | 用于分析核酸混合物的探针、文库和试剂盒及其构建方法 |
| DE602006007819D1 (de) * | 2005-01-21 | 2009-08-27 | Harvard College | Verwendung freier reaktanten bei der nukleinsäuretemplatgesteuerten synthese |
| US7407757B2 (en) | 2005-02-10 | 2008-08-05 | Population Genetics Technologies | Genetic analysis by sequence-specific sorting |
| US7393665B2 (en) | 2005-02-10 | 2008-07-01 | Population Genetics Technologies Ltd | Methods and compositions for tagging and identifying polynucleotides |
| WO2006099604A2 (en) | 2005-03-16 | 2006-09-21 | Compass Genetics, Llc | Methods and compositions for assay readouts on multiple analytical platforms |
| EP2258870B1 (en) | 2005-06-09 | 2013-01-02 | GlaxoSmithKline LLC | Method for identifying compounds which bind to biological target molecule |
| US20090035824A1 (en) | 2005-06-17 | 2009-02-05 | Liu David R | Nucleic acid-templated chemistry in organic solvents |
| US20080220982A1 (en) | 2005-07-26 | 2008-09-11 | Vu Tania Q | Nanoparticle Probes for Capture, Sorting and Placement of Targets |
| US20090005256A1 (en) | 2005-07-29 | 2009-01-01 | Bittker Joshua A | Analysis of Encoded Chemical Libraries |
| CN101321877B (zh) | 2005-10-03 | 2013-04-10 | 应用生物系统有限责任公司 | 用于扩增核酸的组合物、方法和试剂盒 |
| JP2009513135A (ja) | 2005-10-28 | 2009-04-02 | プリーシス・ファーマシューティカルズ・インコーポレイテッド | エンコードされたライブラリーを用いて興味のある化合物を同定する方法 |
| DK2341140T3 (da) | 2005-12-01 | 2017-11-06 | Nuevolution As | Fremgangsmåde til enzymatisk kodning ved effektiv syntese af store biblioteker |
| US7537897B2 (en) | 2006-01-23 | 2009-05-26 | Population Genetics Technologies, Ltd. | Molecular counting |
| WO2007124758A1 (en) | 2006-05-03 | 2007-11-08 | Vipergen Aps | A method for preparing compounds by nucleic acid directed synthesis |
| CN101528673B (zh) | 2006-10-26 | 2012-08-01 | 住友化学株式会社 | 不对称铜络合物结晶的制造方法 |
| CN101219219B (zh) | 2007-01-10 | 2013-02-13 | 北京普罗吉生物科技发展有限公司 | 包含血管抑素或其片段的复合物、其制备方法及应用 |
| JP5604302B2 (ja) | 2007-10-22 | 2014-10-08 | エルジーシー・リミテッド | オリゴヌクレオチドおよびその使用 |
| CA2706222C (en) | 2007-11-19 | 2013-08-27 | Japan Advanced Institute Of Science And Technology | Light-responsive artificial nucleotide having photo-crosslinking ability |
| WO2009077173A2 (en) * | 2007-12-19 | 2009-06-25 | Philochem Ag | Dna-encoded chemical libraries |
| US20120107840A1 (en) | 2008-04-09 | 2012-05-03 | Sru Biosystems, Inc | Methods for Label Free Testing of Cells |
| JP4814904B2 (ja) | 2008-04-16 | 2011-11-16 | 国立大学法人北陸先端科学技術大学院大学 | 核酸類の配列選択的な精製方法 |
| JP5774474B2 (ja) * | 2008-05-02 | 2015-09-09 | エピセンター テクノロジーズ コーポレーションＥｐｉｃｅｎｔｒｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｒｎａへの選択的な５’ライゲーションによるタグの付加 |
| TW201011006A (en) | 2008-06-16 | 2010-03-16 | Nuevolution As | IAP binding compounds |
| CN102177438A (zh) | 2008-07-25 | 2011-09-07 | 理查德·W·瓦格纳 | 蛋白筛选方法 |
| AU2010209508C1 (en) | 2009-01-30 | 2017-10-19 | Oxford Nanopore Technologies Limited | Hybridization linkers |
| AU2010213497A1 (en) | 2009-02-13 | 2011-08-25 | X-Body, Inc. | Identification of nucleic acid delivery vehicles using DNA display |
| DK2396430T3 (da) | 2009-02-16 | 2013-07-15 | Epict Technologies Corp | Template-uafhængig ligering af enkelt-strenget dna |
| AU2010270715C1 (en) | 2009-07-06 | 2016-03-17 | Trilink Biotechnologies | Chemically modified ligase cofactors, donors and acceptors |
| DE102009058769A1 (de) | 2009-12-16 | 2011-06-22 | MagForce Nanotechnologies AG, 10589 | Temperaturabhängige Aktivierung von katalytischen Nukleinsäuren zur kontrollierten Wirkstofffreisetzung |
| JP2013523095A (ja) | 2010-03-26 | 2013-06-17 | エックス−ボディ インコーポレイテッド | 化合物ライブラリーをスクリーニングするための人工多能性細胞および他の細胞の使用法 |
| ES2713873T3 (es) | 2010-04-16 | 2019-05-24 | Nuevolution As | Complejos bifuncionales y métodos para hacer y utilizar tales complejos |
| ES2926988T3 (es) | 2011-03-15 | 2022-10-31 | X Body Inc | Métodos de cribado de anticuerpos |
| US8846883B2 (en) | 2011-08-16 | 2014-09-30 | University Of Southhampton | Oligonucleotide ligation |
| EP2748357B1 (en) | 2011-09-07 | 2018-04-04 | X-Chem, Inc. | Methods for tagging dna-encoded libraries |
| EP2872680B1 (en) | 2012-07-13 | 2018-04-04 | X-Chem, Inc. | Dna-encoded libraries having encoding oligonucleotide linkages not readable by polymerases |
| GB201322692D0 (en) | 2013-12-20 | 2014-02-05 | Philochem Ag | Production of encoded chemical libraries |
-
2012
- 2012-09-07 EP EP12830083.7A patent/EP2748357B1/en not_active Revoked
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6867290B2 (en) * | 1999-04-30 | 2005-03-15 | Cyclops Genome Sciences, Ltd. | Modified polynucleotides and uses thereof |
| WO2010094036A1 (en) * | 2009-02-13 | 2010-08-19 | X-Chem, Inc. | Methods of creating and screening dna-encoded libraries |
| US20110104785A1 (en) * | 2009-11-05 | 2011-05-05 | Ramesh Vaidyanathan | Methods and kits for 3'-end-tagging of rna |
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