CA2441820C - Evolving new molecular function - Google Patents
Evolving new molecular function Download PDFInfo
- Publication number
- CA2441820C CA2441820C CA2441820A CA2441820A CA2441820C CA 2441820 C CA2441820 C CA 2441820C CA 2441820 A CA2441820 A CA 2441820A CA 2441820 A CA2441820 A CA 2441820A CA 2441820 C CA2441820 C CA 2441820C
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- reaction product
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- oligonucleotide
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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
- C12N15/1068—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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
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Families Citing this family (118)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7666588B2 (en) | 2001-03-02 | 2010-02-23 | Ibis Biosciences, Inc. | Methods for rapid forensic analysis of mitochondrial DNA and characterization of mitochondrial DNA heteroplasmy |
| US20040121335A1 (en) | 2002-12-06 | 2004-06-24 | Ecker David J. | Methods for rapid detection and identification of bioagents associated with host versus graft and graft versus host rejections |
| US20030027135A1 (en) | 2001-03-02 | 2003-02-06 | Ecker David J. | Method for rapid detection and identification of bioagents |
| US7226739B2 (en) | 2001-03-02 | 2007-06-05 | Isis Pharmaceuticals, Inc | Methods for rapid detection and identification of bioagents in epidemiological and forensic investigations |
| EP2332896A3 (en) * | 2001-03-19 | 2012-09-26 | President and Fellows of Harvard College | Evolving new molecular function |
| 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 |
| US8073627B2 (en) * | 2001-06-26 | 2011-12-06 | Ibis Biosciences, Inc. | System for indentification of pathogens |
| US7217510B2 (en) | 2001-06-26 | 2007-05-15 | Isis Pharmaceuticals, Inc. | Methods for providing bacterial bioagent characterizing information |
| DE10147074A1 (de) * | 2001-09-25 | 2003-05-08 | Beru Ag | Verfahren zum Betreiben einer aus mehreren Heizelementen bestehenden mehrstufigen elektrischen Heizung |
| DE20200926U1 (de) * | 2002-01-23 | 2002-04-18 | Hegenscheidt Mfd Gmbh & Co Kg | Festwalzgerät einer Festwalzmaschine für Kurbelwellen |
| US20060154246A1 (en) | 2002-03-08 | 2006-07-13 | Dario Neri | Encoded self-assembling chemical libraries (esachel) |
| WO2003078050A2 (en) * | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c-c bond upon reaction |
| CN101006177B (zh) | 2002-03-15 | 2011-10-12 | 纽韦卢森公司 | 改善的用于合成模制分子的方法 |
| EP1487850A2 (en) * | 2002-03-15 | 2004-12-22 | Nuevolution A/S | A building block forming a c-c or a c-hetero atom bond upon reaction |
| AU2003218630A1 (en) * | 2002-03-15 | 2003-09-29 | Nuevolution A/S | A building block capable of functional entity transfer to nucleophil |
| AU2003247266A1 (en) * | 2002-08-01 | 2004-02-23 | Nuevolution A/S | Multi-step synthesis of templated molecules |
| JP4657919B2 (ja) * | 2002-08-19 | 2011-03-23 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 進化する新しい分子機能 |
| WO2004024929A2 (en) * | 2002-09-12 | 2004-03-25 | Nuevolution A/S | Proximity-aided synthesis of templated molecules |
| EP1545762A2 (en) | 2002-09-27 | 2005-06-29 | Carlsberg A/S | Spatially encoded polymer matrix |
| AU2011226815B2 (en) * | 2002-10-30 | 2014-09-25 | Nuevolution A/S | Enzymatic encoding |
| DK3299463T3 (da) | 2002-10-30 | 2020-12-07 | Nuevolution As | Enzymatisk kodning |
| EP1578399A4 (en) * | 2002-12-06 | 2007-11-28 | Isis Pharmaceuticals Inc | METHODS FOR RAPID IDENTIFICATION OF PATHOGENS IN HUMANS AND BEETS |
| EP2175019A3 (en) | 2002-12-19 | 2011-04-06 | Nuevolution A/S | Quasirandom structure and function guided synthesis methods |
| EP1597395A2 (en) | 2003-02-21 | 2005-11-23 | 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 |
| DE602004019764D1 (de) * | 2003-03-20 | 2009-04-16 | Nuevolution As | Ligationsvermittelnde codierung von kleinen molekülen |
| US8017323B2 (en) | 2003-03-26 | 2011-09-13 | President And Fellows Of Harvard College | Free reactant use in nucleic acid-templated synthesis |
| US8046171B2 (en) | 2003-04-18 | 2011-10-25 | Ibis Biosciences, Inc. | Methods and apparatus for genetic evaluation |
| US8057993B2 (en) | 2003-04-26 | 2011-11-15 | Ibis Biosciences, Inc. | Methods for identification of coronaviruses |
| US20050010029A1 (en) * | 2003-05-08 | 2005-01-13 | Brown Dennis M. | Recombined molecules and preparation thereof |
| US7964343B2 (en) | 2003-05-13 | 2011-06-21 | Ibis Biosciences, Inc. | Method for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture |
| US8158354B2 (en) | 2003-05-13 | 2012-04-17 | Ibis Biosciences, Inc. | Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture |
| WO2004110964A2 (en) * | 2003-06-16 | 2004-12-23 | Nuevolution A/S | Encoded molecules by translation (emt) |
| WO2005003778A2 (en) * | 2003-07-02 | 2005-01-13 | Nuevolution A/S | A method for identifying a synthetic molecule having affinity towards a target |
| US8546082B2 (en) | 2003-09-11 | 2013-10-01 | Ibis Biosciences, Inc. | Methods for identification of sepsis-causing bacteria |
| US8242254B2 (en) | 2003-09-11 | 2012-08-14 | Ibis Biosciences, Inc. | Compositions for use in identification of bacteria |
| US8097416B2 (en) | 2003-09-11 | 2012-01-17 | Ibis Biosciences, Inc. | Methods for identification of sepsis-causing bacteria |
| EP1670939B1 (en) * | 2003-09-18 | 2009-11-04 | Nuevolution A/S | A method for obtaining structural information concerning an encoded molecule and method for selecting compounds |
| US8163895B2 (en) | 2003-12-05 | 2012-04-24 | Ibis Biosciences, Inc. | Compositions for use in identification of orthopoxviruses |
| US7972994B2 (en) | 2003-12-17 | 2011-07-05 | Glaxosmithkline Llc | Methods for synthesis of encoded libraries |
| RU2470077C2 (ru) | 2003-12-17 | 2012-12-20 | ГЛЭКСОСМИТКЛАЙН ЭлЭлСи | Биологически активное соединение, содержащее кодирующий олигонуклеотид (варианты), способ его синтеза, библиотека соединений (варианты), способ ее синтеза и способ поиска соединения, связывающегося с биологической мишенью (варианты) |
| EP1723255B1 (en) | 2004-02-17 | 2010-12-29 | Nuevolution A/S | Method for enrichment involving elimination by mismatch hybridisation |
| US7666592B2 (en) | 2004-02-18 | 2010-02-23 | Ibis Biosciences, Inc. | Methods for concurrent identification and quantification of an unknown bioagent |
| US8119336B2 (en) | 2004-03-03 | 2012-02-21 | Ibis Biosciences, Inc. | Compositions for use in identification of alphaviruses |
| ATE447020T1 (de) * | 2004-03-22 | 2009-11-15 | Nuevolution As | Ligationscodierung unter verwendung von oligonukleotidbausteinen |
| WO2005117270A2 (en) | 2004-05-24 | 2005-12-08 | Isis Pharmaceuticals, Inc. | Mass spectrometry with selective ion filtration by digital thresholding |
| US20050266411A1 (en) | 2004-05-25 | 2005-12-01 | Hofstadler Steven A | Methods for rapid forensic analysis of mitochondrial DNA |
| CA2565967A1 (en) * | 2004-06-10 | 2005-12-29 | Perkinelmer Las, Inc. | Multiplexing assays for analyte detection |
| US7811753B2 (en) | 2004-07-14 | 2010-10-12 | Ibis Biosciences, Inc. | Methods for repairing degraded DNA |
| KR101411361B1 (ko) | 2004-11-08 | 2014-06-25 | 비퍼겐 에이피에스 | 구조적 핵산에 의해 가이드되는 화학적 합성 |
| ATE420170T1 (de) | 2004-11-22 | 2009-01-15 | Peter Birk Rasmussen | Matrizengerichtete split-and-mix-synthese von bibliotheken kleiner moleküle |
| US8084207B2 (en) | 2005-03-03 | 2011-12-27 | Ibis Bioscience, Inc. | Compositions for use in identification of papillomavirus |
| US20060205040A1 (en) | 2005-03-03 | 2006-09-14 | Rangarajan Sampath | Compositions for use in identification of adventitious viruses |
| EP1891244B1 (en) * | 2005-04-13 | 2010-10-06 | Ibis Biosciences, Inc. | Compositions for use in identification of adenoviruses |
| EP1885892A2 (en) * | 2005-05-03 | 2008-02-13 | Ensemble Discovery Corporation | Turnover probes and use thereof for nucleic acid detection |
| US20070154899A1 (en) * | 2005-05-26 | 2007-07-05 | Coull James M | Biodetection by nucleic acid-templated chemistry |
| WO2006135654A2 (en) * | 2005-06-07 | 2006-12-21 | President And Fellows Of Harvard College | Polymer evolution via templated synthesis related applications |
| DE602006021580D1 (de) | 2005-06-09 | 2011-06-09 | Praecis Pharm Inc | Verfahren zur synthese codierter bibliotheken |
| WO2006138666A2 (en) * | 2005-06-17 | 2006-12-28 | President And Fellows Of Harvard College | Iterated branching reaction pathways via nucleic acid-mediated chemistry |
| US20090035824A1 (en) * | 2005-06-17 | 2009-02-05 | Liu David R | Nucleic acid-templated chemistry in organic solvents |
| WO2007011722A2 (en) | 2005-07-15 | 2007-01-25 | President And Fellows Of Harvard College | Reaction discovery system |
| CA2616281C (en) | 2005-07-21 | 2014-04-22 | Isis Pharmaceuticals, Inc. | Methods for rapid identification and quantitation of mitochondrial dna variants |
| DE602005003374T2 (de) * | 2005-10-17 | 2008-09-11 | Pls-Design Gmbh | Verfahren zur Bestimmung einer unbekannten PNS Seqenz und seine Verwendungen |
| CA2626325A1 (en) | 2005-10-28 | 2007-05-10 | Praecis Pharmaceuticals Incorporated | Methods for identifying compounds of interest using encoded libraries |
| DK2341140T3 (da) | 2005-12-01 | 2017-11-06 | Nuevolution As | Fremgangsmåde til enzymatisk kodning ved effektiv syntese af store biblioteker |
| EP2021470A1 (en) | 2006-05-03 | 2009-02-11 | Vipergen APS | A method for preparing compounds by nucleic acid directed synthesis |
| US9149473B2 (en) | 2006-09-14 | 2015-10-06 | Ibis Biosciences, Inc. | Targeted whole genome amplification method for identification of pathogens |
| AU2007297671A1 (en) * | 2006-09-18 | 2008-03-27 | Ensemble Discovery Corporation | Receptor family profiling |
| WO2008054600A2 (en) * | 2006-09-28 | 2008-05-08 | Ensemble Discovery Corporation | Compositions and methods for biodetection by nucleic acid-templated chemistry |
| US8871471B2 (en) | 2007-02-23 | 2014-10-28 | Ibis Biosciences, Inc. | Methods for rapid forensic DNA analysis |
| WO2008151023A2 (en) | 2007-06-01 | 2008-12-11 | Ibis Biosciences, Inc. | Methods and compositions for multiple displacement amplification of nucleic acids |
| WO2009018003A2 (en) * | 2007-07-27 | 2009-02-05 | Ensemble Discovery Corporation | Detection assays and use thereof |
| WO2009134470A2 (en) * | 2008-01-18 | 2009-11-05 | The Johns Hopkins University | Methods for identifying eubacteria |
| WO2010022249A2 (en) * | 2008-08-20 | 2010-02-25 | Ensemble Discovery Corporation | Macrocyclic compounds for inhibition of tumor necrosis factor alpha |
| WO2010031002A1 (en) * | 2008-09-14 | 2010-03-18 | Incitor, Llc | Nanoscale molecule synthesis |
| WO2010033625A1 (en) | 2008-09-16 | 2010-03-25 | Ibis Biosciences, Inc. | Microplate handling systems and related computer program products and methods |
| WO2010033599A2 (en) | 2008-09-16 | 2010-03-25 | Ibis Biosciences, Inc. | Mixing cartridges, mixing stations, and related kits, systems, and methods |
| US8148163B2 (en) | 2008-09-16 | 2012-04-03 | Ibis Biosciences, Inc. | Sample processing units, systems, and related methods |
| WO2010093943A1 (en) | 2009-02-12 | 2010-08-19 | Ibis Biosciences, Inc. | Ionization probe assemblies |
| NZ594420A (en) * | 2009-02-13 | 2013-06-28 | Chem Inc X | Methods of creating and screening dna-encoded libraries |
| DK2446033T3 (da) | 2009-06-22 | 2014-01-27 | Univ Strasbourg | Fremgangsmåde til fremstilling af et addukt |
| WO2011008971A1 (en) | 2009-07-17 | 2011-01-20 | Ibis Biosciences, Inc. | Lift and mount apparatus |
| EP2454000A4 (en) | 2009-07-17 | 2016-08-10 | Ibis Biosciences Inc | SYSTEMS FOR IDENTIFYING BIOLOGICAL SUBSTANCES |
| EP2488656B1 (en) | 2009-10-15 | 2015-06-03 | Ibis Biosciences, Inc. | Multiple displacement amplification |
| US11225655B2 (en) | 2010-04-16 | 2022-01-18 | Nuevolution A/S | Bi-functional complexes and methods for making and using such complexes |
| JP6193761B2 (ja) | 2010-09-27 | 2017-09-06 | ビペルゲン | 富化ライブラリーを作製する方法 |
| CA2835942C (en) * | 2011-05-19 | 2019-01-22 | Sequenom, Inc. | Products and processes for multiplex nucleic acid identification |
| BR112014005205A2 (pt) | 2011-09-07 | 2017-03-21 | X-Chem Inc | métodos para etiquetar bibliotecas codificadas com dna |
| CN110257493A (zh) | 2012-07-13 | 2019-09-20 | X-化学有限公司 | 具有聚合酶不可读的编码性寡核苷酸连接的dna编码文库 |
| EP4036579A1 (en) * | 2013-03-15 | 2022-08-03 | Arizona Board of Regents on behalf of Arizona State University | Biosensor microarray compositions and methods |
| US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| GB201322692D0 (en) | 2013-12-20 | 2014-02-05 | Philochem Ag | Production of encoded chemical libraries |
| WO2016022363A2 (en) | 2014-07-30 | 2016-02-11 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| US10040048B1 (en) | 2014-09-25 | 2018-08-07 | Synthego Corporation | Automated modular system and method for production of biopolymers |
| WO2016074683A1 (en) | 2014-11-11 | 2016-05-19 | Lundorf Pedersen Materials Aps | Method for identification of molecules with desired characteristics |
| CN107532162A (zh) * | 2014-12-12 | 2018-01-02 | 托德·M·伍尔夫 | 用于利用寡核苷酸编辑细胞中核酸的组合物和方法 |
| CA2983224A1 (en) | 2015-04-24 | 2016-10-27 | Agena Bioscience, Inc. | Multiplexed method for the identification and quantitation of minor alleles and polymorphisms |
| WO2017218293A1 (en) | 2016-06-16 | 2017-12-21 | Richard Edward Watts | Oligonucleotide directed and recorded combinatorial synthesis of encoded probe molecules |
| CN109804066A (zh) | 2016-08-09 | 2019-05-24 | 哈佛大学的校长及成员们 | 可编程cas9-重组酶融合蛋白及其用途 |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| WO2018081534A1 (en) | 2016-10-28 | 2018-05-03 | President And Fellows Of Harvard College | Assay for exo-site binding molecules |
| WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
| US11898179B2 (en) | 2017-03-09 | 2024-02-13 | President And Fellows Of Harvard College | Suppression of pain by gene editing |
| US11542496B2 (en) | 2017-03-10 | 2023-01-03 | President And Fellows Of Harvard College | Cytosine to guanine base editor |
| WO2018204420A1 (en) | 2017-05-02 | 2018-11-08 | Haystack Sciences Corporation | Molecules for verifying oligonucleotide directed combinatorial synthesis and methods of making and using the same |
| US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
| EP3658573A1 (en) | 2017-07-28 | 2020-06-03 | President and Fellows of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (pace) |
| US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
| WO2019051430A1 (en) * | 2017-09-11 | 2019-03-14 | Synthego Corporation | METHOD AND SYSTEM FOR BIOPOLYMER SYNTHESIS |
| EP3697906A1 (en) | 2017-10-16 | 2020-08-26 | The Broad Institute, Inc. | Uses of adenosine base editors |
| US11674136B2 (en) | 2018-02-09 | 2023-06-13 | President And Fellows Of Harvard College | DNA-templated macrocycle library |
| EP3899521A4 (en) | 2018-12-20 | 2022-08-24 | Sergey N. Krylov | BINDER SELECTION USING CAPILLARY ELECTROPHORESIS |
| JP2022518242A (ja) | 2019-01-22 | 2022-03-14 | ビペルゲン エーピーエス | 細胞内のインビトロディスプレイライブラリのスクリーニング方法 |
| DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
| JP2023525304A (ja) | 2020-05-08 | 2023-06-15 | ザ ブロード インスティテュート，インコーポレーテッド | 標的二本鎖ヌクレオチド配列の両鎖同時編集のための方法および組成物 |
| WO2023164224A1 (en) * | 2022-02-28 | 2023-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Functionalized nanoclusters and their use in treating bacterial infections |
Family Cites Families (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US277081A (en) | 1883-05-08 | Scalding napped hats and sizing or felting hat and other fabrics | ||
| US4194550A (en) * | 1976-01-26 | 1980-03-25 | Insulating Shade (Limited Partnership) | Apparatus for insulating against conductive, convective and radiant heat transmission |
| US4863857A (en) | 1985-03-01 | 1989-09-05 | Board Of Regents, The University Of Texas System | Polypeptide complementary to peptides or proteins having an amino acid sequence or nucleotide coding sequence at least partially known |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4703034A (en) * | 1986-04-28 | 1987-10-27 | Merck & Co., Inc. | Novel cyclic tetrapeptide |
| US5449602A (en) * | 1988-01-13 | 1995-09-12 | Amoco Corporation | Template-directed photoligation |
| US5162218A (en) | 1988-11-18 | 1992-11-10 | The Regents Of The University Of California | Conjugated polypeptides and methods for their preparation |
| US6291161B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertiore |
| US6291160B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for producing polymers having a preselected activity |
| US6680192B1 (en) | 1989-05-16 | 2004-01-20 | Scripps Research Institute | Method for producing polymers having a preselected activity |
| AU638762B2 (en) | 1989-10-05 | 1993-07-08 | Optein Inc | Cell-free synthesis and isolation of novel genes and polypeptides |
| US5660985A (en) | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
| US5637682A (en) * | 1990-06-11 | 1997-06-10 | Nexstar Pharmaceuticals, Inc. | High-affinity oligonucleotide ligands to the tachykinin substance P |
| US5723289A (en) | 1990-06-11 | 1998-03-03 | Nexstar Pharmaceuticals, Inc. | Parallel selex |
| US20020038000A1 (en) | 1990-08-02 | 2002-03-28 | Larry Gold | Systematic polypeptide evolution by reverse translation |
| US5843701A (en) | 1990-08-02 | 1998-12-01 | Nexstar Pharmaceticals, Inc. | Systematic polypeptide evolution by reverse translation |
| WO1992002536A1 (en) | 1990-08-02 | 1992-02-20 | The Regents Of The University Of Colorado | Systematic polypeptide evolution by reverse translation |
| US6140496A (en) | 1990-10-09 | 2000-10-31 | Benner; Steven Albert | Precursors for deoxyribonucleotides containing non-standard nucleosides |
| US6037120A (en) | 1995-10-12 | 2000-03-14 | Benner; Steven Albert | Recognition of oligonucleotides containing non-standard base pairs |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5641625A (en) | 1992-05-22 | 1997-06-24 | Isis Pharmaceuticals, Inc. | Cleaving double-stranded DNA with peptide nucleic acids |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| WO1993005060A1 (de) | 1991-08-28 | 1993-03-18 | Boehringer Mannheim Gmbh | Funktionalisierte trägermaterialien für gleichzeitige synthese und direktmarkierung von oligonukleotiden als primer für matrizenabhängige enzymatische nukleinsäuresynthesen |
| US5639603A (en) | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
| US5770358A (en) | 1991-09-18 | 1998-06-23 | Affymax Technologies N.V. | Tagged synthetic oligomer libraries |
| US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| DE69233331T3 (de) | 1991-11-22 | 2007-08-30 | Affymetrix, Inc., Santa Clara | Kombinatorische Strategien zur Polymersynthese |
| US5573905A (en) * | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5565324A (en) | 1992-10-01 | 1996-10-15 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| US5721099A (en) | 1992-10-01 | 1998-02-24 | Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| US6436635B1 (en) | 1992-11-06 | 2002-08-20 | Boston University | Solid phase sequencing of double-stranded nucleic acids |
| US5605798A (en) | 1993-01-07 | 1997-02-25 | Sequenom, Inc. | DNA diagnostic based on mass spectrometry |
| WO1994016101A2 (en) | 1993-01-07 | 1994-07-21 | Koester Hubert | Dna sequencing by mass spectrometry |
| US6194144B1 (en) | 1993-01-07 | 2001-02-27 | Sequenom, Inc. | DNA sequencing by mass spectrometry |
| AU687801B2 (en) | 1993-03-19 | 1998-03-05 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
| US6074823A (en) | 1993-03-19 | 2000-06-13 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
| US5840485A (en) | 1993-05-27 | 1998-11-24 | Selectide Corporation | Topologically segregated, encoded solid phase libraries |
| GB9315847D0 (en) * | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
| US5922545A (en) | 1993-10-29 | 1999-07-13 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
| US5925517A (en) * | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| AU8102694A (en) * | 1993-11-17 | 1995-06-06 | Id Biomedical Corporation | Cycling probe cleavage detection of nucleic acid sequences |
| US6127154A (en) | 1994-02-10 | 2000-10-03 | Mosbach; Klaus | Methods for direct synthesis of compounds having complementary structure to a desired molecular entity and use thereof |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US6048698A (en) | 1994-09-20 | 2000-04-11 | Nexstar Pharmaceuticals, Inc. | Parallel SELEX™ |
| US20030099945A1 (en) | 1994-09-20 | 2003-05-29 | Invenux, Inc. | Parallel selex |
| US5597697A (en) | 1994-09-30 | 1997-01-28 | Diamond; Paul | Screening assay for inhibitors and activators of RNA and DNA-dependent nucleic acid polymerases |
| GB9524630D0 (en) * | 1994-12-24 | 1996-01-31 | Zeneca Ltd | Chemical compounds |
| US5559000A (en) | 1995-01-18 | 1996-09-24 | The Scripps Research Institute | Encoded reaction cassette |
| DE19646372C1 (de) | 1995-11-11 | 1997-06-19 | Evotec Biosystems Gmbh | Genotyp und Phänotyp koppelnde Verbindung |
| US5846839A (en) | 1995-12-22 | 1998-12-08 | Glaxo Group Limited | Methods for hard-tagging an encoded synthetic library |
| US5888971A (en) * | 1996-02-20 | 1999-03-30 | Ortho Pharmaceutical Corporation, Inc. | Macrocyclic peptides useful in the treatment of thrombin related disorders |
| DE69738687D1 (de) * | 1996-04-12 | 2008-06-26 | Phri Properties Inc | Sonden, kits und assays |
| US5998140A (en) | 1996-07-31 | 1999-12-07 | The Scripps Research Institute | Complex formation between dsDNA and oligomer of cyclic heterocycles |
| US6140053A (en) | 1996-11-06 | 2000-10-31 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
| US5958703A (en) | 1996-12-03 | 1999-09-28 | Glaxo Group Limited | Use of modified tethers in screening compound libraries |
| US6080826A (en) | 1997-01-06 | 2000-06-27 | California Institute Of Technology | Template-directed ring-closing metathesis and ring-opening metathesis polymerization of functionalized dienes |
| EP0968223B1 (en) * | 1997-01-08 | 2016-12-21 | Sigma-Aldrich Co. LLC | Bioconjugation of macromolecules |
| KR100566859B1 (ko) | 1997-01-21 | 2006-04-03 | 제너럴 하스피톨 코포레이션 | Ｒｎａ-단백질 융합물을 이용한 단백질의 선별 |
| US6261804B1 (en) | 1997-01-21 | 2001-07-17 | The General Hospital Corporation | Selection of proteins using RNA-protein fusions |
| US6969584B2 (en) | 1997-06-12 | 2005-11-29 | Rigel Pharmaceuticals, Inc. | Combinatorial enzymatic complexes |
| US6607878B2 (en) | 1997-10-06 | 2003-08-19 | Stratagene | Collections of uniquely tagged molecules |
| EP1051515A2 (en) * | 1998-01-27 | 2000-11-15 | Cytocell Limited | Modified nucleic acid probes and uses thereof |
| US5945325A (en) * | 1998-04-20 | 1999-08-31 | California Institute Of Technology | Thermally stable para-nitrobenzyl esterases |
| US6287765B1 (en) | 1998-05-20 | 2001-09-11 | Molecular Machines, Inc. | Methods for detecting and identifying single molecules |
| US6175001B1 (en) | 1998-10-16 | 2001-01-16 | The Scripps Research Institute | Functionalized pyrimidine nucleosides and nucleotides and DNA's incorporating same |
| US7479472B1 (en) * | 1998-10-19 | 2009-01-20 | The Board Of Trustees Of The Leland Stanford Junior University | DNA-templated combinatorial library chemistry |
| WO2000061775A1 (en) * | 1999-04-08 | 2000-10-19 | Pavel Sergeev | Synthesis of biologically active compounds in cells |
| KR20020022808A (ko) * | 1999-08-12 | 2002-03-27 | 리우, 루 | 조합 화학 및 의약 화학용 효소의 진화 및 용도 |
| AU779653B2 (en) * | 1999-08-27 | 2005-02-03 | Bristol-Myers Squibb Company | Methods for encoding and sorting in vitro translated proteins |
| US7306904B2 (en) * | 2000-02-18 | 2007-12-11 | Olink Ab | Methods and kits for proximity probing |
| US6511809B2 (en) * | 2000-06-13 | 2003-01-28 | E. I. Du Pont De Nemours And Company | Method for the detection of an analyte by means of a nucleic acid reporter |
| EP2332896A3 (en) | 2001-03-19 | 2012-09-26 | President and Fellows of Harvard College | Evolving new molecular function |
| ES2571945T3 (es) * | 2001-06-20 | 2016-05-27 | Nuevolution As | Moléculas y métodos con plantilla para el uso de tales moléculas |
| EP1401850A1 (en) | 2001-06-20 | 2004-03-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| WO2004001042A2 (en) | 2002-06-20 | 2003-12-31 | Nuevolution A/S | Microarrays displaying encoded molecules |
| US20030143561A1 (en) | 2001-06-20 | 2003-07-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| WO2003078445A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c=c double bond upon reaction |
| US20060154246A1 (en) | 2002-03-08 | 2006-07-13 | Dario Neri | Encoded self-assembling chemical libraries (esachel) |
| CN101006177B (zh) | 2002-03-15 | 2011-10-12 | 纽韦卢森公司 | 改善的用于合成模制分子的方法 |
| AU2003218630A1 (en) | 2002-03-15 | 2003-09-29 | Nuevolution A/S | A building block capable of functional entity transfer to nucleophil |
| WO2003078050A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c-c bond upon reaction |
| EP1487850A2 (en) | 2002-03-15 | 2004-12-22 | Nuevolution A/S | A building block forming a c-c or a c-hetero atom bond upon reaction |
| US7255991B2 (en) | 2002-03-22 | 2007-08-14 | Emory University | Template-drive processes for synthesizing polymers and components related to such processes |
| JP4657919B2 (ja) | 2002-08-19 | 2011-03-23 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 進化する新しい分子機能 |
| US8017323B2 (en) * | 2003-03-26 | 2011-09-13 | President And Fellows Of Harvard College | Free reactant use in nucleic acid-templated synthesis |
| WO2006133312A2 (en) | 2005-06-07 | 2006-12-14 | President And Fellows Of Harvard College | Ordered multi-step synthesis by nucleic acid-mediated chemistry |
| US20090035824A1 (en) | 2005-06-17 | 2009-02-05 | Liu David R | Nucleic acid-templated chemistry in organic solvents |
| WO2006138666A2 (en) | 2005-06-17 | 2006-12-28 | President And Fellows Of Harvard College | Iterated branching reaction pathways via nucleic acid-mediated chemistry |
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