PT1423400E - Evolução de nova função molecular - Google Patents
Evolução de nova função molecular Download PDFInfo
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- PT1423400E PT1423400E PT02753671T PT02753671T PT1423400E PT 1423400 E PT1423400 E PT 1423400E PT 02753671 T PT02753671 T PT 02753671T PT 02753671 T PT02753671 T PT 02753671T PT 1423400 E PT1423400 E PT 1423400E
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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
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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
- 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
-
- 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 |
---|---|---|---|---|
US20030027135A1 (en) | 2001-03-02 | 2003-02-06 | Ecker David J. | Method for rapid detection and identification of bioagents |
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 |
US7226739B2 (en) | 2001-03-02 | 2007-06-05 | Isis Pharmaceuticals, Inc | Methods for rapid detection and identification of bioagents in epidemiological and forensic investigations |
WO2004060278A2 (en) | 2002-12-06 | 2004-07-22 | Isis Pharmaceuticals, Inc. | Methods for rapid identification of pathogens in humans and animals |
US20040121309A1 (en) | 2002-12-06 | 2004-06-24 | Ecker David J. | Methods for rapid detection and identification of bioagents in blood, bodily fluids, and bodily tissues |
US7070928B2 (en) * | 2001-03-19 | 2006-07-04 | President And Fellows Of Harvard College | Evolving new molecular function |
EP1402024B1 (en) * | 2001-06-20 | 2007-08-22 | Nuevolution A/S | Templated molecules and methods for using such molecules |
WO2002102820A1 (en) | 2001-06-20 | 2002-12-27 | Nuevolution A/S | Nucleoside derivatives for library preparation |
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 |
DK1483585T3 (da) | 2002-03-08 | 2009-06-22 | Eidgenoess Tech Hochschule | Kodede, selvsamlende kemiske biblioteker (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 |
IL163822A0 (en) * | 2002-03-15 | 2005-12-18 | Nuevolution As | An improved method for synthesising templated molecules |
WO2003078050A2 (en) * | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c-c bond upon reaction |
AU2003218630A1 (en) * | 2002-03-15 | 2003-09-29 | Nuevolution A/S | A building block capable of functional entity transfer to nucleophil |
WO2004013070A2 (en) * | 2002-08-01 | 2004-02-12 | Nuevolution A/S | Multi-step synthesis of templated molecules |
AU2003263937B2 (en) * | 2002-08-19 | 2010-04-01 | The 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 |
WO2004028682A2 (en) | 2002-09-27 | 2004-04-08 | Carlsberg A/S | Spatially encoded polymer matrix |
AU2011226815B2 (en) * | 2002-10-30 | 2014-09-25 | Nuevolution A/S | Enzymatic encoding |
PT1558744E (pt) | 2002-10-30 | 2011-09-22 | Nuevolution As | Codificação enzimática |
ATE450609T1 (de) | 2002-12-19 | 2009-12-15 | Nuevolution As | Durch quasizufallsstrukturen und funktionen geführte synthesemethode |
EP1597395A2 (en) * | 2003-02-21 | 2005-11-23 | Nuevolution A/S | Method for producing second-generation library |
WO2004074501A2 (en) * | 2003-02-21 | 2004-09-02 | Nuevolution A/S | A method for obtaining structural information about an encoded molecule |
ATE424455T1 (de) * | 2003-03-20 | 2009-03-15 | 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 |
WO2005016851A1 (en) * | 2003-05-08 | 2005-02-24 | Valent Technologies, Llc | Recombined molecules and preparation thereof |
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 |
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 |
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 |
US20120122099A1 (en) | 2003-09-11 | 2012-05-17 | Rangarajan Sampath | 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 |
WO2005058479A2 (en) | 2003-12-17 | 2005-06-30 | Praecis Pharmaceuticals, Inc. | Methods for synthesis of encoded libraries |
US7972994B2 (en) | 2003-12-17 | 2011-07-05 | Glaxosmithkline Llc | Methods for synthesis of encoded libraries |
WO2005078122A2 (en) | 2004-02-17 | 2005-08-25 | 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 |
EP2458619B1 (en) | 2004-05-24 | 2017-08-02 | Ibis Biosciences, 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 |
WO2006135400A2 (en) | 2004-08-24 | 2006-12-21 | Isis Pharmaceuticals, Inc. | Methods for rapid identification of recombinant organisms |
CA2587010C (en) | 2004-11-08 | 2017-08-15 | Vipergen Aps | Structural nucleic acid guided chemical synthesis |
DK1828381T3 (da) | 2004-11-22 | 2009-02-23 | Peter Birk Rasmussen | Templatedirigeret split-and-mix-syntese af småmolekylebiblioteker |
US20060205040A1 (en) | 2005-03-03 | 2006-09-14 | Rangarajan Sampath | Compositions for use in identification of adventitious viruses |
US8084207B2 (en) | 2005-03-03 | 2011-12-27 | Ibis Bioscience, Inc. | Compositions for use in identification of papillomavirus |
CA2605021A1 (en) * | 2005-04-13 | 2007-08-02 | Isis Pharmaceuticals, 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 |
US20090203530A1 (en) * | 2005-06-07 | 2009-08-13 | Liu David R | Polymer evolution via templated synthesis |
CA2611512C (en) | 2005-06-09 | 2018-05-22 | Praecis Pharmaceuticals, Inc. | Methods for synthesis of encoded libraries |
US20090035824A1 (en) * | 2005-06-17 | 2009-02-05 | Liu David R | Nucleic acid-templated chemistry in organic solvents |
DE602006013134D1 (de) * | 2005-06-17 | 2010-05-06 | Harvard College | Iterierte verzweigende reaktionswege über nukleinsäure-vermittelte chemie |
WO2007011722A2 (en) | 2005-07-15 | 2007-01-25 | President And Fellows Of Harvard College | Reaction discovery system |
AU2006272776B2 (en) | 2005-07-21 | 2012-01-19 | Ibis Biosciences, Inc. | Methods for rapid identification and quantitation of nucleic acid variants |
EP1785490B1 (en) * | 2005-10-17 | 2007-11-14 | RiNA Netzwerk RNA-Technologien GmbH | Method for determining an unknown PNA sequence and uses thereof |
EP1940755A2 (en) | 2005-10-28 | 2008-07-09 | Praecis Pharmaceuticals Inc. | Methods for identifying compounds of interest using encoded libraries |
DE602006018648D1 (de) | 2005-12-01 | 2011-01-13 | Nuevolution As | Enzymvermittelnde kodierungsmethoden für eine effiziente synthese von grossen bibliotheken |
US7928211B2 (en) | 2006-05-03 | 2011-04-19 | Vipergen Pharmaceuticals Aps | Method for preparing compounds by nucleic acid directed synthesis |
AU2007353877B2 (en) | 2006-09-14 | 2012-07-19 | Ibis Biosciences, Inc. | Targeted whole genome amplification method for identification of pathogens |
WO2008036273A2 (en) * | 2006-09-18 | 2008-03-27 | Ensemble Discovery Corporation | Receptor family profiling |
CA2664649A1 (en) | 2006-09-28 | 2008-05-08 | Ensemble Discovery Corporation | Compositions and methods for biodetection by nucleic acid-templated chemistry |
JP5680304B2 (ja) | 2007-02-23 | 2015-03-04 | アイビス バイオサイエンシズ インコーポレイティッド | 迅速な法医学的dna分析法 |
WO2008151023A2 (en) | 2007-06-01 | 2008-12-11 | Ibis Biosciences, Inc. | Methods and compositions for multiple displacement amplification of nucleic acids |
CN101952719A (zh) * | 2007-07-27 | 2011-01-19 | 通信改革公司 | 检测测定法及其用途 |
US20130217588A1 (en) * | 2008-01-18 | 2013-08-22 | The Johns Hopkins University | Methods for Identifying Eubacteria |
US8338565B2 (en) * | 2008-08-20 | 2012-12-25 | Ensemble Therapeutics Corporation | Macrocyclic compounds for inhibition of tumor necrosis factor alpha |
WO2010031002A1 (en) * | 2008-09-14 | 2010-03-18 | Incitor, Llc | Nanoscale molecule synthesis |
EP2344893B1 (en) | 2008-09-16 | 2014-10-15 | Ibis Biosciences, Inc. | Microplate handling systems and methods |
US8148163B2 (en) | 2008-09-16 | 2012-04-03 | Ibis Biosciences, Inc. | Sample processing units, systems, and related methods |
EP2349549B1 (en) | 2008-09-16 | 2012-07-18 | Ibis Biosciences, Inc. | Mixing cartridges, mixing stations, and related kits, and system |
EP2396803A4 (en) | 2009-02-12 | 2016-10-26 | Ibis Biosciences Inc | IONIZATION PROBE ASSEMBLIES |
SG2014011381A (en) | 2009-02-13 | 2014-06-27 | Chem Inc X | Methods of creating and screening dna-encoded libraries |
WO2010150103A2 (en) | 2009-06-22 | 2010-12-29 | Universite De Strasbourg | Method of preparing an adduct |
WO2011008972A1 (en) | 2009-07-17 | 2011-01-20 | Ibis Biosciences, Inc. | Systems for bioagent identification |
US8950604B2 (en) | 2009-07-17 | 2015-02-10 | Ibis Biosciences, Inc. | Lift and mount apparatus |
ES2628739T3 (es) | 2009-10-15 | 2017-08-03 | Ibis Biosciences, Inc. | Amplificación por desplazamiento múltiple |
ES2713873T3 (es) | 2010-04-16 | 2019-05-24 | Nuevolution As | Complejos bifuncionales y métodos para hacer y utilizar tales complejos |
EP2622073B1 (en) | 2010-09-27 | 2018-04-18 | Vipergen | A method for making an enriched library |
CN103717751A (zh) * | 2011-05-19 | 2014-04-09 | 塞昆纳姆股份有限公司 | 用于多重核酸鉴定的产品和方法 |
EP3828271A1 (en) | 2011-09-07 | 2021-06-02 | X-Chem, Inc. | Methods for tagging dna-encoded libraries |
EA034141B1 (ru) | 2012-07-13 | 2020-01-09 | Икс-Чем, Инк. | Днк-кодированные библиотеки, содержащие связи кодирующих олигонуклеотидов, не доступные для считывания полимеразами |
EP2971280B1 (en) | 2013-03-15 | 2018-08-29 | Arizona Board of Regents on behalf of Arizona State University | Biosensor microarray compositions and methods |
US9163284B2 (en) | 2013-08-09 | 2015-10-20 | 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 |
US10077453B2 (en) | 2014-07-30 | 2018-09-18 | 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 |
US20180340174A1 (en) | 2014-11-11 | 2018-11-29 | Nanocore Aps | Method for identification of molecules with desired characteristics |
WO2016094845A2 (en) * | 2014-12-12 | 2016-06-16 | Woolf Tod M | Compositions and methods for editing nucleic acids in cells utilizing oligonucleotides |
WO2016172571A1 (en) | 2015-04-24 | 2016-10-27 | Agena Bioscience, Inc. | Multiplexed method for the identification and quantitation of minor alleles and polymorphisms |
JP7283727B2 (ja) | 2016-06-16 | 2023-05-30 | ヘイスタック サイエンシィズ コーポレーション | コードプローブ分子のコンビナトリアル合成が指令されかつ記録されたオリゴヌクレオチド |
AU2017308889B2 (en) | 2016-08-09 | 2023-11-09 | President And Fellows Of Harvard College | Programmable Cas9-recombinase fusion proteins and uses thereof |
US11542509B2 (en) | 2016-08-24 | 2023-01-03 | 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 |
WO2018165504A1 (en) | 2017-03-09 | 2018-09-13 | 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 |
EP3619340A4 (en) | 2017-05-02 | 2021-01-20 | Haystack Sciences Corporation | MOLECULES FOR THE VERIFICATION OF OLIGONUCLEOTIDE DIRECTED COMBINATIONAL SYNTHESIS AND METHOD OF MANUFACTURING AND USING THEREOF |
WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
JP2020534795A (ja) | 2017-07-28 | 2020-12-03 | 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 | ファージによって支援される連続的進化(pace)を用いて塩基編集因子を進化させるための方法および組成物 |
WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
GB2582865B (en) * | 2017-09-11 | 2022-05-04 | Synthego Corp | Biopolymer synthesis system and method |
US11795443B2 (en) | 2017-10-16 | 2023-10-24 | The Broad Institute, Inc. | Uses of adenosine base editors |
WO2019168654A2 (en) | 2018-02-09 | 2019-09-06 | President And Fellows Of Harvard College | Dna-templated macrocycle library |
WO2020124213A1 (en) | 2018-12-20 | 2020-06-25 | Krylov Sergey N | Binder selection using capillary electrophoresis |
WO2020152028A1 (en) | 2019-01-22 | 2020-07-30 | Vipergen Aps | A method for screening of an in vitro display library within a cell |
JP2022526908A (ja) | 2019-03-19 | 2022-05-27 | ザ ブロード インスティテュート,インコーポレーテッド | 編集ヌクレオチド配列を編集するための方法および組成物 |
AU2021267940A1 (en) | 2020-05-08 | 2022-12-08 | President And Fellows Of Harvard College | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
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 |
US6680192B1 (en) * | 1989-05-16 | 2004-01-20 | Scripps Research Institute | Method for producing polymers having a preselected activity |
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 |
CA2067194C (en) | 1989-10-05 | 2003-03-18 | Glenn Kawasaki | Cell-free synthesis and isolation of novel genes and polypeptides |
US5637682A (en) | 1990-06-11 | 1997-06-10 | Nexstar Pharmaceuticals, Inc. | High-affinity oligonucleotide ligands to the tachykinin substance P |
US5660985A (en) * | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
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 |
US6037120A (en) | 1995-10-12 | 2000-03-14 | Benner; Steven Albert | Recognition of oligonucleotides containing non-standard base pairs |
US6140496A (en) * | 1990-10-09 | 2000-10-31 | Benner; Steven Albert | Precursors for deoxyribonucleotides containing non-standard nucleosides |
US5539082A (en) * | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5719262A (en) * | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5641625A (en) * | 1992-05-22 | 1997-06-24 | Isis Pharmaceuticals, Inc. | Cleaving double-stranded DNA with peptide nucleic acids |
ATE163308T1 (de) * | 1991-08-28 | 1998-03-15 | Boehringer Mannheim Gmbh | Primer für matrizenabhängige enzymatische nukleinsäuresynthesen |
CA2118806A1 (en) | 1991-09-18 | 1993-04-01 | William J. Dower | Method of synthesizing diverse collections of oligomers |
US5639603A (en) * | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
US5270170A (en) * | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
WO1993009668A1 (en) | 1991-11-22 | 1993-05-27 | Affymax Technology N.V. | Combinatorial strategies for polymer synthesis |
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 |
US6194144B1 (en) | 1993-01-07 | 2001-02-27 | Sequenom, Inc. | DNA sequencing by mass spectrometry |
DE69433811T2 (de) | 1993-01-07 | 2005-06-23 | Sequenom, Inc., San Diego | Dns - sequenzierung durch massenspektronomie |
US6074823A (en) | 1993-03-19 | 2000-06-13 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
AU687801B2 (en) | 1993-03-19 | 1998-03-05 | 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 |
EP0892808B1 (en) | 1996-04-12 | 2008-05-14 | PHRI Properties, Inc. | Detection probes, kits and 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 |
WO1998030575A1 (en) * | 1997-01-08 | 1998-07-16 | Proligo Llc | Bioconjugation of macromolecules |
ATE332368T1 (de) * | 1997-01-21 | 2006-07-15 | Gen Hospital Corp | Selektion von proteinen mittels rns-protein fusionen |
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 |
AU1318400A (en) * | 1998-10-19 | 2000-05-08 | Board Of Trustees Of The Leland Stanford Junior University | Dna-templated combinatorial library chemistry |
EP1208219A1 (en) * | 1999-04-08 | 2002-05-29 | 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 |
US6436665B1 (en) * | 1999-08-27 | 2002-08-20 | Phylos, Inc | 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 |
US7070928B2 (en) | 2001-03-19 | 2006-07-04 | President And Fellows Of Harvard College | Evolving new molecular function |
WO2002102820A1 (en) | 2001-06-20 | 2002-12-27 | Nuevolution A/S | Nucleoside derivatives for library preparation |
US20030143561A1 (en) * | 2001-06-20 | 2003-07-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
EP1402024B1 (en) | 2001-06-20 | 2007-08-22 | Nuevolution A/S | Templated molecules and methods for using such molecules |
WO2003078445A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c=c double bond upon reaction |
DK1483585T3 (da) | 2002-03-08 | 2009-06-22 | Eidgenoess Tech Hochschule | Kodede, selvsamlende kemiske biblioteker (ESACHEL) |
AU2003218630A1 (en) | 2002-03-15 | 2003-09-29 | Nuevolution A/S | A building block capable of functional entity transfer to nucleophil |
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 |
WO2003078050A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c-c bond upon reaction |
IL163822A0 (en) | 2002-03-15 | 2005-12-18 | Nuevolution As | An improved method for synthesising templated molecules |
US7255991B2 (en) | 2002-03-22 | 2007-08-14 | Emory University | Template-drive processes for synthesizing polymers and components related to such processes |
AU2003240436A1 (en) | 2002-06-20 | 2004-01-06 | Nuevolution A/S | Microarrays displaying encoded molecules |
AU2003263937B2 (en) * | 2002-08-19 | 2010-04-01 | The President And Fellows Of Harvard College | Evolving new molecular function |
US8017323B2 (en) | 2003-03-26 | 2011-09-13 | President And Fellows Of Harvard College | Free reactant use in nucleic acid-templated synthesis |
ATE461279T1 (de) * | 2005-06-07 | 2010-04-15 | Harvard College | Geordnete mehrschrittsynthese mittels nukleinsäurevermittelter chemie |
DE602006013134D1 (de) | 2005-06-17 | 2010-05-06 | Harvard College | Iterierte verzweigende reaktionswege über nukleinsäure-vermittelte chemie |
US20090035824A1 (en) * | 2005-06-17 | 2009-02-05 | Liu David R | Nucleic acid-templated chemistry in organic solvents |
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