CA2325351C - Non-stochastic generation of genetic vaccines and enzymes - Google Patents
Non-stochastic generation of genetic vaccines and enzymes Download PDFInfo
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Priority Applications (1)
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| CA2492661A CA2492661C (en) | 1999-02-04 | 2000-02-04 | Non-stochastic generation of genetic vaccines and enzymes |
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| US09/246,178 | 1999-02-04 | ||
| US09/246,178 US6171820B1 (en) | 1995-12-07 | 1999-02-04 | Saturation mutagenesis in directed evolution |
| PCT/US2000/003086 WO2000046344A2 (en) | 1999-02-04 | 2000-02-04 | Non-stochastic generation of genetic vaccines and enzymes |
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| CA2492661A Division CA2492661C (en) | 1999-02-04 | 2000-02-04 | Non-stochastic generation of genetic vaccines and enzymes |
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| US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US6406855B1 (en) | 1994-02-17 | 2002-06-18 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6335160B1 (en) | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6995017B1 (en) | 1994-02-17 | 2006-02-07 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US6165793A (en) | 1996-03-25 | 2000-12-26 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US6395547B1 (en) | 1994-02-17 | 2002-05-28 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US6764835B2 (en) * | 1995-12-07 | 2004-07-20 | Diversa Corporation | Saturation mutageneis in directed evolution |
| US5830696A (en) | 1996-12-05 | 1998-11-03 | Diversa Corporation | Directed evolution of thermophilic enzymes |
| US6713279B1 (en) | 1995-12-07 | 2004-03-30 | Diversa Corporation | Non-stochastic generation of genetic vaccines and enzymes |
| US6939689B2 (en) | 1995-12-07 | 2005-09-06 | Diversa Corporation | Exonuclease-mediated nucleic acid reassembly in directed evolution |
| US6740506B2 (en) * | 1995-12-07 | 2004-05-25 | Diversa Corporation | End selection in directed evolution |
| US20030219752A1 (en) * | 1995-12-07 | 2003-11-27 | Diversa Corporation | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof |
| US6096548A (en) | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
| US6506602B1 (en) | 1996-03-25 | 2003-01-14 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US20070009930A1 (en) * | 1996-12-18 | 2007-01-11 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| AU743305C (en) | 1997-01-17 | 2006-03-30 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
| US7148054B2 (en) * | 1997-01-17 | 2006-12-12 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
| US6326204B1 (en) | 1997-01-17 | 2001-12-04 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
| US6159688A (en) | 1997-03-18 | 2000-12-12 | Novo Nordisk A/S | Methods of producing polynucleotide variants |
| EP1025217B1 (en) * | 1997-10-24 | 2006-10-04 | Invitrogen Corporation | Recombinational cloning using nucleic acids having recombination sites |
| IL136574A0 (en) | 1997-12-08 | 2001-06-14 | California Inst Of Techn | A method for forming a polynucleotide of desired properties |
| US7390619B1 (en) * | 1998-02-11 | 2008-06-24 | Maxygen, Inc. | Optimization of immunomodulatory properties of genetic vaccines |
| US6541011B2 (en) | 1998-02-11 | 2003-04-01 | Maxygen, Inc. | Antigen library immunization |
| EP1073670A1 (en) | 1998-05-01 | 2001-02-07 | Maxygen, Inc. | Optimization of pest resistance genes using dna shuffling |
| US7153655B2 (en) * | 1998-06-16 | 2006-12-26 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function involving the use of exonuclease enzyme and two populations of parent polynucleotide sequence |
| US6365408B1 (en) | 1998-06-19 | 2002-04-02 | Maxygen, Inc. | Methods of evolving a polynucleotides by mutagenesis and recombination |
| US6951719B1 (en) | 1999-08-11 | 2005-10-04 | Proteus S.A. | Process for obtaining recombined nucleotide sequences in vitro, libraries of sequences and sequences thus obtained |
| US6991922B2 (en) * | 1998-08-12 | 2006-01-31 | Proteus S.A. | Process for in vitro creation of recombinant polynucleotide sequences by oriented ligation |
| US20030104417A1 (en) * | 1998-08-12 | 2003-06-05 | Proteus S.A. | Template-mediated, ligation-oriented method of nonrandomly shuffling polynucleotides |
| US20030092023A1 (en) * | 1998-08-12 | 2003-05-15 | Daniel Dupret | Method of shuffling polynucleotides using templates |
| US20040005673A1 (en) * | 2001-06-29 | 2004-01-08 | Kevin Jarrell | System for manipulating nucleic acids |
| WO2000040715A2 (en) * | 1999-01-05 | 2000-07-13 | Trustees Of Boston University | Improved nucleic acid cloning |
| US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
| AU2415200A (en) * | 1999-01-18 | 2000-08-01 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
| US20070065838A1 (en) * | 1999-01-19 | 2007-03-22 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US20090130718A1 (en) * | 1999-02-04 | 2009-05-21 | Diversa Corporation | Gene site saturation mutagenesis |
| JP3399518B2 (ja) * | 1999-03-03 | 2003-04-21 | インターナショナル・ビジネス・マシーンズ・コーポレーション | 半導体構造およびその製造方法 |
| AU3719500A (en) | 1999-03-05 | 2000-09-21 | Maxygen, Inc. | Recombination of insertion modified nucleic acids |
| US20040002474A1 (en) * | 1999-10-07 | 2004-01-01 | Maxygen Inc. | IFN-alpha homologues |
| AU1456101A (en) | 1999-11-03 | 2001-05-14 | Maxygen, Inc. | Antibody diversity generation |
| US7115712B1 (en) * | 1999-12-02 | 2006-10-03 | Maxygen, Inc. | Cytokine polypeptides |
| SG121902A1 (en) * | 2000-01-11 | 2006-05-26 | Maxygen Inc | Integrated systems for diversity generation and screening |
| WO2001064864A2 (en) * | 2000-02-28 | 2001-09-07 | Maxygen, Inc. | Single-stranded nucleic acid template-mediated recombination and nucleic acid fragment isolation |
| EP1276861A2 (en) * | 2000-03-24 | 2003-01-22 | Maxygen, Inc. | Methods for modulating cellular and organismal phenotypes |
| US6479262B1 (en) | 2000-05-16 | 2002-11-12 | Hercules, Incorporated | Solid phase enzymatic assembly of polynucleotides |
| AU2001268716A1 (en) * | 2000-06-23 | 2002-01-08 | Maxygen, Inc. | Novel chimeric promoters |
| EP1360290A2 (en) | 2000-06-23 | 2003-11-12 | Maxygen, Inc. | Co-stimulatory molecules |
| US20020072097A1 (en) * | 2000-07-07 | 2002-06-13 | Delcardayre Stephen | Molecular breeding of transposable elements |
| US6858422B2 (en) * | 2000-07-13 | 2005-02-22 | Codexis, Inc. | Lipase genes |
| US20030017552A1 (en) * | 2000-07-21 | 2003-01-23 | Jarrell Kevin A. | Modular vector systems |
| US7435562B2 (en) * | 2000-07-21 | 2008-10-14 | Modular Genetics, Inc. | Modular vector systems |
| US7198924B2 (en) * | 2000-12-11 | 2007-04-03 | Invitrogen Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
| US20020132308A1 (en) * | 2000-08-24 | 2002-09-19 | Mpep @ Page 300-M | Novel constructs and their use in metabolic pathway engineering |
| JP2002083691A (ja) * | 2000-09-06 | 2002-03-22 | Sharp Corp | アクティブマトリックス駆動型有機ｌｅｄ表示装置及びその製造方法 |
| US6958213B2 (en) | 2000-12-12 | 2005-10-25 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function |
| US20020086292A1 (en) | 2000-12-22 | 2002-07-04 | Shigeaki Harayama | Synthesis of hybrid polynucleotide molecules using single-stranded polynucleotide molecules |
| ATE447019T1 (de) * | 2001-02-02 | 2009-11-15 | Large Scale Biology Corp | Methode zur erhöhung der komplementarität in einem heteroduplex-polynucleotid |
| US20030036854A1 (en) * | 2001-02-06 | 2003-02-20 | The Penn State Research Foundation | Apparatus and method for designing proteins and protein libraries |
| EP1277835A1 (en) * | 2001-07-19 | 2003-01-22 | Libragen | Methods of creating genetic diversity |
| US7647184B2 (en) * | 2001-08-27 | 2010-01-12 | Hanall Pharmaceuticals, Co. Ltd | High throughput directed evolution by rational mutagenesis |
| US20030129203A1 (en) * | 2001-08-27 | 2003-07-10 | Nautilus Biotech S.A. | Mutant recombinant adeno-associated viruses |
| ES2411007T3 (es) | 2001-10-10 | 2013-07-04 | Novo Nordisk A/S | Remodelación y glicoconjugación de péptidos |
| CA2468710A1 (en) * | 2001-12-03 | 2003-06-12 | Diversa Corporation | Chromosomal saturation mutagenesis |
| TWI262083B (en) * | 2001-12-28 | 2006-09-21 | Syngenta Participations Ag | Microbially-expressed thermotolerant phytase for animal feed |
| US20040009498A1 (en) * | 2002-01-14 | 2004-01-15 | Diversa Corporation | Chimeric antigen binding molecules and methods for making and using them |
| MXPA04007886A (es) | 2002-02-13 | 2004-10-15 | Dow Global Technologies Inc | Sobre-expresion de genes de extremozimo en pseudomonadas y bacterias estrechamente relacionadas. |
| AU2003213108A1 (en) * | 2002-02-15 | 2003-09-09 | Verenium Corporation | Chimeric cannulae proteins, nucleic acids encoding them and methods for making and using them |
| US20030166010A1 (en) * | 2002-02-25 | 2003-09-04 | Affholter Joseph A. | Custom ligand design for biomolecular filtration and purification for bioseperation |
| US20030224404A1 (en) * | 2002-02-25 | 2003-12-04 | Manuel Vega | High throughput directed evolution of nucleic acids by rational mutagenesis |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| ES2564570T3 (es) | 2002-03-01 | 2016-03-23 | Codexis Mayflower Holdings, Llc | Métodos, sistemas y software para la identificación de biomoléculas funcionales |
| US20030171543A1 (en) * | 2002-03-05 | 2003-09-11 | Bott Richard R. | High throughput mutagenesis screening method |
| US20030199068A1 (en) * | 2002-03-05 | 2003-10-23 | Bott Richard R. | High throughput mutagenesis screening method |
| EP1488335A4 (en) | 2002-03-09 | 2006-11-15 | Maxygen Inc | OPTIMIZING CROSSOVER POINTS FOR THE ADJUSTED EVOLUTION |
| BRPI0309391B1 (pt) | 2002-04-19 | 2018-10-30 | Dsm Food Specialties B V | vetor compreendendo ácido nucléico que codifica polipeptídeo com atividade de fosfolipase, célula transformada, preparado de proteína, método de preparação e métodos relacionados |
| US7226771B2 (en) | 2002-04-19 | 2007-06-05 | Diversa Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
| CA2485506C (en) * | 2002-05-17 | 2012-02-28 | Alligator Bioscience Ab | A method for in vitro molecular evolution of protein function |
| JP2005532829A (ja) * | 2002-07-18 | 2005-11-04 | インヴィトロジェン コーポレーション | 組換え部位を含むウイルスベクター |
| AU2003256731A1 (en) * | 2002-08-02 | 2004-02-23 | Aromagen Corporation | Methods for making (-) -menthol and oxygenated menthane compounds |
| MXPA05001287A (es) | 2002-08-06 | 2005-08-03 | Verdia Llc | Variantes de amino oxidasa ap1. |
| WO2004022593A2 (en) * | 2002-09-09 | 2004-03-18 | Nautilus Biotech | Rational evolution of cytokines for higher stability, the cytokines and encoding nucleic acid molecules |
| US20060020396A1 (en) * | 2002-09-09 | 2006-01-26 | Rene Gantier | Rational directed protein evolution using two-dimensional rational mutagenesis scanning |
| US20050202438A1 (en) * | 2002-09-09 | 2005-09-15 | Rene Gantier | Rational directed protein evolution using two-dimensional rational mutagenesis scanning |
| KR100980065B1 (ko) | 2002-09-27 | 2010-09-03 | 젠코어 인코포레이티드 | 최적화된 Ｆｃ 변이체 및 그의 제조 방법 |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| AU2004277368B2 (en) | 2003-03-07 | 2011-01-20 | Dsm Ip Assets B.V. | Hydrolases, nucleic acids encoding them and mehods for making and using them |
| PL1615945T3 (pl) | 2003-04-09 | 2012-03-30 | Ratiopharm Gmbh | Sposoby glikopegylacji i białka/peptydy wytwarzane tymi sposobami |
| CA2521284C (en) | 2003-04-29 | 2014-07-08 | Pioneer Hi-Bred International, Inc. | Novel glyphosate-n-acetyltransferase (gat) genes |
| WO2005028615A2 (en) * | 2003-06-26 | 2005-03-31 | Invitrogen Corporation | Methods and compositions for detecting promoter activity and expressing fusion proteins |
| AU2003283943A1 (en) * | 2003-11-20 | 2005-06-08 | Agency For Science Technology And Research | Method |
| JP2007512838A (ja) | 2003-12-01 | 2007-05-24 | インヴィトロジェン コーポレーション | 組換え部位を含む核酸分子およびその使用方法 |
| US7204950B2 (en) * | 2003-12-19 | 2007-04-17 | Pepsico, Inc. | Dispensing package |
| CN101671680B (zh) | 2004-02-25 | 2012-11-28 | 先锋高级育种国际公司 | 新的苏云金芽孢杆菌晶体多肽、多核苷酸及其组合物 |
| AU2005327292B2 (en) | 2004-05-21 | 2010-11-04 | The Regents Of The University Of California | Method for enhancing production of isoprenoid compounds |
| CA2735315A1 (en) | 2004-06-09 | 2005-12-29 | Pioneer Hi-Bred International, Inc. | Plastid transit peptides |
| WO2006110182A2 (en) | 2004-10-27 | 2006-10-19 | The Scripps Research Institute | Orthogonal translation components for the in vivo incorporation of unnatural amino acids |
| US7998930B2 (en) * | 2004-11-04 | 2011-08-16 | Hanall Biopharma Co., Ltd. | Modified growth hormones |
| JP2008519602A (ja) * | 2004-11-11 | 2008-06-12 | モジュラー ジェネティクス， インコーポレイテッド | 多様性を生じるためのラダーアセンブリおよびシステム |
| US20090038023A1 (en) | 2005-03-10 | 2009-02-05 | Verenium Corporation | Lyase Enzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them |
| KR101393679B1 (ko) | 2005-03-15 | 2014-05-21 | 비피 코포레이션 노쓰 아메리카 인코포레이티드 | 셀룰라제, 이것을 암호화하는 핵산 및 이들을 제조 및사용하는 방법 |
| US20070184472A1 (en) * | 2005-06-08 | 2007-08-09 | Toagosei Co., Ltd | Method of purifying environmental dna and method of efficiently screening for protein-encoding gene from environmental dna |
| ES2335232T3 (es) | 2005-06-21 | 2010-03-23 | Xoma Technology Ltd. | Anticuerpos y fragmentos de los mismos que se unen a la il-1 beta. |
| GB2432366B (en) * | 2005-11-19 | 2007-11-21 | Alligator Bioscience Ab | A method for in vitro molecular evolution of protein function |
| US20090324574A1 (en) | 2006-02-02 | 2009-12-31 | Verenium Corporation | Esterases and Related Nucleic Acids and Methods |
| AU2006338208B2 (en) | 2006-02-10 | 2013-10-24 | Bp Corporation North America Inc. | Cellulolytic enzymes, nucleic acids encoding them and methods for making and using them |
| EP2548954A1 (en) | 2006-02-14 | 2013-01-23 | Verenium Corporation | Xylanases, nucleic acids encoding them and methods for making and using them |
| KR101744157B1 (ko) | 2006-03-07 | 2017-06-08 | 바스프 엔자임스 엘엘씨 | 알돌라제, 이것을 코딩하는 핵산과 그 제조 방법 및 사용 방법 |
| CN101437954B (zh) | 2006-03-07 | 2015-09-09 | 嘉吉公司 | 醛缩酶和编码醛缩酶的核酸以及它们的制备和使用方法 |
| EP2024393A2 (en) | 2006-05-15 | 2009-02-18 | Sea Lane Biotechnologies,llc. | Neutralizing antibodies to influenza viruses |
| AR061365A1 (es) * | 2006-06-13 | 2008-08-20 | Athenix Corp | Metodos para generar diversidad genetica mediante mutagenesis con permutaciones |
| DK2069389T3 (en) | 2006-08-04 | 2015-01-12 | Bp Corp North America Inc | Glucanases, nucleic acids encoding them, and processes for their preparation and use |
| ES2451266T3 (es) | 2006-09-21 | 2014-03-26 | Dsm Ip Assets B.V. | Fosfolipasas, ácidos nucleicos que las codifican, y métodos para obtenerlas y usarlas |
| EP2617815B1 (en) | 2006-09-21 | 2015-11-18 | BASF Enzymes LLC | Phytases, nucleic acids encoding them and methods for making and using them |
| CN101675074B (zh) | 2006-12-20 | 2016-02-24 | Mmr全球公司 | 抗体及其制备和使用方法 |
| ES2531167T5 (es) | 2006-12-21 | 2018-05-21 | Basf Enzymes Llc | Amilasas y glucoamilasas, ácidos nucleicos que las codifican y métodos para formarlas y utilizarlas |
| EP2074136A4 (en) | 2007-01-30 | 2012-11-07 | Verenium Corp | ENZYMES FOR TREATING LIGNOCELLULOSE, FOR SUCH CODING NUCLEIC ACIDS, AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| EP2139515B2 (en) | 2007-03-30 | 2023-12-20 | The Research Foundation of the State University of New York | Attenuated viruses useful for vaccines |
| WO2009018449A1 (en) | 2007-07-31 | 2009-02-05 | Verenium Corporation | Tailored multi-site combinatorial assembly |
| MX2010003600A (es) | 2007-10-03 | 2010-12-14 | Verenium Corp | Xilanasas, acidos nucleicos que las codifican, y metodos para hacerlas y usarlas. |
| EP2219469B1 (en) | 2007-12-03 | 2017-08-30 | Syngenta Participations AG | Engineering enzymatically susceptible proteins |
| WO2009088924A2 (en) * | 2007-12-31 | 2009-07-16 | Xoma Technology Ltd. | Methods and materials for targeted affinity enhancement |
| DK2238242T5 (en) | 2008-01-03 | 2015-08-03 | Basf Enzymes Llc | -Transferases and oxidoreductases, nucleic acids encoding FOR THEM, AND PROCESSES FOR THE STILL LING AND USE THEREOF |
| DK2238261T3 (da) | 2008-01-03 | 2014-02-10 | Verenium Corp | Isomeraser, nukleinsyrer der koder for dem og fremgangsmåder til fremstilling og anvendelse deraf |
| KR20110011595A (ko) * | 2008-01-28 | 2011-02-08 | 탭이뮨, 인크. | 면역 반응 증진을 위한 타파신 증대 |
| AU2009228058A1 (en) | 2008-03-28 | 2009-10-01 | Sea Lane Biotechnologies, Llc | Neutralizing molecules to viral antigens |
| US20110124520A1 (en) * | 2008-05-30 | 2011-05-26 | Massachuesetts Institute Of Technology | Compositions and Methods for Spatial Separation and Screening of Cells |
| US20090312196A1 (en) * | 2008-06-13 | 2009-12-17 | Codexis, Inc. | Method of synthesizing polynucleotide variants |
| US8383346B2 (en) * | 2008-06-13 | 2013-02-26 | Codexis, Inc. | Combined automated parallel synthesis of polynucleotide variants |
| US8357503B2 (en) | 2008-08-29 | 2013-01-22 | Bunge Oils, Inc. | Hydrolases, nucleic acids encoding them and methods for making and using them |
| US8198062B2 (en) | 2008-08-29 | 2012-06-12 | Dsm Ip Assets B.V. | Hydrolases, nucleic acids encoding them and methods for making and using them |
| US8153391B2 (en) | 2008-08-29 | 2012-04-10 | Bunge Oils, Inc. | Hydrolases, nucleic acids encoding them and methods for making and using them |
| PT2364156T (pt) * | 2008-12-02 | 2018-04-24 | Consejo Nacional De Investigaciones Cientificas Y Tecn Conicet | Protozoário modificado que expressa pelo menos duas proteínas de superfície variável (vsp), uma vacina que compreende o mesmo e procedimentos, utilizações e métodos dos mesmos |
| EP2430042A1 (en) | 2009-05-12 | 2012-03-21 | Council of Scientific & Industrial Research | Lipa and its variant useful for biofuel production |
| WO2010135588A2 (en) | 2009-05-21 | 2010-11-25 | Verenium Corporation | Phytases, nucleic acids encoding them and methods for making and using them |
| ES2581318T3 (es) | 2009-07-17 | 2016-09-05 | Bioatla Llc | Selección y evolución simultáneas e integradas de rendimiento y expresión de anticuerpos/proteínas en huéspedes de producción |
| UA109884C2 (uk) | 2009-10-16 | 2015-10-26 | Поліпептид, що має активність ферменту фосфатидилінозитол-специфічної фосфоліпази с, нуклеїнова кислота, що його кодує, та спосіб його виробництва і застосування | |
| UA111708C2 (uk) | 2009-10-16 | 2016-06-10 | Бандж Ойлз, Інк. | Спосіб рафінування олії |
| WO2011109726A2 (en) * | 2010-03-05 | 2011-09-09 | Bioatla Llc | Homologous multi-specific antibodies |
| SG187033A1 (en) | 2010-07-16 | 2013-02-28 | Bioatla Llc | Novel methods of protein evolution |
| BR112013003224A2 (pt) | 2010-08-13 | 2016-06-07 | Pioneer Hi Bred Int | "construto de promotor quimérico, cassete de expressão, vetor de expressão, método de obtenção de uma planta, método para regular a expressão de um polinucleotídeo de interesse, polinucleotídeo, método para expressar um polinucleotídeo de interesse" |
| BR112013008347A2 (pt) | 2010-10-06 | 2016-06-14 | Bp Corp North America Inc | polipeptídeos de variantes cbh i |
| US20140199682A1 (en) | 2010-11-17 | 2014-07-17 | Sea Lane Biotechnologies, Llc | Influenza neutralizing agents |
| US20140182011A1 (en) | 2011-11-03 | 2014-06-26 | The University Of Hong Kong | Methods Using Acyl-Coenzyme A-Binding Proteins to Enchance Drought Tolerance in Genetically Modified Plants |
| WO2013138768A1 (en) | 2012-03-16 | 2013-09-19 | Bp Corporation North America Inc. | Polypeptides having endoglucanase activity |
| BR112014027468A2 (pt) | 2012-05-04 | 2017-06-27 | Du Pont | polinucleotídeo isolado ou recombinante, construção de dna recombinante, célula, planta, explante vegetal, semente transgênica, polipeptídeo isolado, composição, métodos de produção de meganuclease, de introdução de rompimento e de integração de um polinucleotídeo. |
| KR102089526B1 (ko) | 2012-05-10 | 2020-03-17 | 바이오아트라, 엘엘씨 | 다중-특이적 모노클로날 항체 |
| CN104870640A (zh) | 2012-08-16 | 2015-08-26 | 孟加拉朱特研究所 | 来自菜豆壳球孢菌的纤维素和/或半纤维素降解酶及其用途 |
| AU2013302535B2 (en) | 2012-08-16 | 2018-12-06 | Bangladesh Jute Research Institute | Pectin degrading enzymes from Macrophomina phaseolina and uses thereof |
| US10253325B2 (en) | 2012-12-19 | 2019-04-09 | Boston Medical Center Corporation | Methods for elevating fat/oil content in plants |
| CN105074463B (zh) * | 2013-01-31 | 2018-09-25 | 科德克希思公司 | 使用相乘形式的模型鉴定生物分子的方法、系统和软件 |
| GB201308828D0 (en) | 2013-03-12 | 2013-07-03 | Verenium Corp | Phytase |
| AU2014236154A1 (en) | 2013-03-14 | 2015-09-17 | Pioneer Hi-Bred International, Inc. | Compositions having dicamba decarboxylase activity and methods of use |
| AU2014236162A1 (en) | 2013-03-14 | 2015-09-17 | Arzeda Corp. | Compositions having dicamba decarboxylase activity and methods of use |
| GB201308843D0 (en) | 2013-03-14 | 2013-07-03 | Verenium Corp | Phytase formulation |
| JP2016525354A (ja) | 2013-07-25 | 2016-08-25 | ビーエーエスエフ エンザイムズ エルエルシー | フィターゼ |
| US11293929B2 (en) | 2014-01-07 | 2022-04-05 | Bioatla, Inc. | Proteins targeting orthologs |
| EP3359669B1 (en) | 2015-10-06 | 2020-05-13 | Pierce Biotechnology, Inc. | Devices and methods for producing proteins |
| AU2016343738B2 (en) | 2015-10-30 | 2021-05-13 | Beth Israel Deaconess Medical Center, Inc. | Methods for determination of bioactivity, quantity, removal, or inactivation of cereal amylase trypsin inhibitors in cereals, flours, plants, and complex foods |
| CN111148528A (zh) | 2016-12-28 | 2020-05-12 | 英福瓦克思公司 | 流感疫苗 |
| CN111278970B (zh) | 2017-10-25 | 2024-09-27 | 巴斯夫欧洲公司 | β-淀粉酶 |
| US12110489B2 (en) * | 2017-12-20 | 2024-10-08 | Basf Se | Gene site saturation mutagenesis (GSSM) method |
| CN112368375A (zh) | 2018-04-26 | 2021-02-12 | 巴斯夫欧洲公司 | 脂肪酶 |
| WO2019211143A1 (en) | 2018-05-03 | 2019-11-07 | Basf Se | Amylase enzymes |
| WO2019229101A1 (en) | 2018-05-29 | 2019-12-05 | Basf Se | Amylase enzymes |
| AU2019286396A1 (en) | 2018-06-14 | 2020-12-17 | Bioatla, Inc. | Multi-specific antibody constructs |
| EP3847264A1 (en) | 2018-09-07 | 2021-07-14 | Basf Plant Science Company GmbH | Improved method for the production of high levels of pufa in plants |
| US12460221B2 (en) | 2018-09-07 | 2025-11-04 | Basf Plant Science Company Gmbh | Method for the production of high levels of PUFA in plants |
| CN112996915A (zh) | 2018-09-07 | 2021-06-18 | 巴斯夫植物科学有限公司 | 用于在植物中产生高水平pufa的改进方法 |
| EP3938504A1 (en) | 2019-03-11 | 2022-01-19 | Basf Se | Amylases and methods for making and using them |
| US20220220463A1 (en) | 2019-04-23 | 2022-07-14 | Basf Se | Beta-amylase variants |
| MX2022007714A (es) | 2019-12-20 | 2022-07-19 | Basf Se | Disminucion de la toxicidad de terpenos y aumento de la posible produccion en microorganismos. |
| MX2022015338A (es) | 2020-06-04 | 2023-01-16 | Isobionics B V | Santaleno sintasas sinteticas. |
| EP4015626A1 (en) | 2020-12-18 | 2022-06-22 | Isobionics B.V. | Enzymes and methods for fermentative production of monoterpene esters |
| MX2024001532A (es) | 2021-08-02 | 2024-02-13 | Basf Se | Produccion novedosa de compuestos aromaticos con ionilidenoetano sintasas. |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4959312A (en) | 1985-05-31 | 1990-09-25 | The University Of Tennessee Research Corporation | Full spectrum mutagenesis |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| AU4308689A (en) | 1988-09-02 | 1990-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5096815A (en) | 1989-01-06 | 1992-03-17 | Protein Engineering Corporation | Generation and selection of novel dna-binding proteins and polypeptides |
| US5198346A (en) | 1989-01-06 | 1993-03-30 | Protein Engineering Corp. | Generation and selection of novel DNA-binding proteins and polypeptides |
| EP1361273A3 (en) | 1992-11-24 | 2004-02-11 | G.D. Searle & Co. | Interleukin-3 (IL-3) multiple mutation polypeptides |
| CN1189558C (zh) * | 1993-10-08 | 2005-02-16 | 诺沃奇梅兹有限公司 | 淀粉酶变体 |
| US6187579B1 (en) | 1993-10-28 | 2001-02-13 | Carlsberg A/S | Customized proteases |
| US6140466A (en) | 1994-01-18 | 2000-10-31 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| US5389537A (en) | 1994-01-21 | 1995-02-14 | Wisconsin Alumni Research Foundation | Nuclease having altered specificity |
| EP0777748A1 (en) | 1994-08-18 | 1997-06-11 | Cytogen Corporation | Peptide librairies as a source of syngenes |
| JPH10506463A (ja) | 1994-09-21 | 1998-06-23 | サイトーゲン コーポレーション | ペプチドライブラリー由来の抗原結合性ペプチド（アブチド） |
| US5885577A (en) | 1994-09-21 | 1999-03-23 | Cytogen Corporation | Antigen binding peptides (abtides) from peptide libraries |
| CA2219080A1 (en) | 1995-06-07 | 1996-12-27 | Ariad Gene Therapeutics, Inc. | Rapamycin-based regulation of biological events |
| US5789166A (en) | 1995-12-08 | 1998-08-04 | Stratagene | Circular site-directed mutagenesis |
| US5885827A (en) | 1996-01-23 | 1999-03-23 | The Regents Of The Universtiy Of California | Eukaryotic high rate mutagenesis system |
| DK1325932T5 (da) | 1997-04-07 | 2005-10-03 | Genentech Inc | Anti-VEGF antistoffer |
| KR20010006534A (ko) | 1997-04-18 | 2001-01-26 | 아스트루 마이클 제이 | Ⅱ형 ｔｇｆ-베타 수용체／면역글로불린 불변 영역 융합 단백질 |
| AU7171098A (en) | 1997-05-01 | 1998-11-24 | Board Of Regents, The University Of Texas System | Directed evolution of enzymes and antibodies |
| AU1526099A (en) * | 1997-11-17 | 1999-06-07 | Novo Nordisk Biotech, Inc. | Polypeptides having 5-aminolevulinic acid synthase activity and nucleic acids encoding same |
| EP1042457B1 (en) * | 1997-12-16 | 2006-03-08 | Novozymes A/S | Polypeptides having aminopeptidase activity and nucleic acids encoding same |
| CA2318402A1 (en) | 1998-01-15 | 1999-07-22 | Ariad Gene Therapeutics, Inc. | Regulation of biological events using multimeric chimeric proteins |
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| JP2003524392A (ja) | 2003-08-19 |
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| JP2005245453A (ja) | 2005-09-15 |
| WO2000046344A3 (en) | 2000-12-28 |
| AU3483900A (en) | 2000-08-25 |
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