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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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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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 US6171820B1 (en) | 1995-12-07 | 1999-02-04 | Saturation mutagenesis in directed evolution |
| US09/246,178 | 1999-02-04 | ||
| 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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| CA2325351A1 CA2325351A1 (en) | 2000-08-10 |
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| 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 |
| US6406855B1 (en) | 1994-02-17 | 2002-06-18 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6117679A (en) | 1994-02-17 | 2000-09-12 | 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 |
| US6939689B2 (en) | 1995-12-07 | 2005-09-06 | Diversa Corporation | Exonuclease-mediated nucleic acid reassembly in directed evolution |
| US6713279B1 (en) | 1995-12-07 | 2004-03-30 | Diversa Corporation | Non-stochastic generation of genetic vaccines and enzymes |
| US6740506B2 (en) * | 1995-12-07 | 2004-05-25 | Diversa Corporation | End selection in directed evolution |
| US5830696A (en) | 1996-12-05 | 1998-11-03 | Diversa Corporation | Directed evolution of thermophilic enzymes |
| US6764835B2 (en) * | 1995-12-07 | 2004-07-20 | Diversa Corporation | Saturation mutageneis 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 |
| EP2261373A3 (en) | 1997-01-17 | 2011-12-14 | Codexis Mayflower Holdings, LLC | 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 |
| WO1999021977A1 (en) * | 1997-10-24 | 1999-05-06 | Life Technologies, Inc. | Recombinational cloning using nucleic acids having recombination sites |
| WO1999029902A1 (en) | 1997-12-08 | 1999-06-17 | California Institute Of Technology | Method for creating polynucleotide and polypeptide sequences |
| US6541011B2 (en) | 1998-02-11 | 2003-04-01 | Maxygen, Inc. | Antigen library immunization |
| US7390619B1 (en) | 1998-02-11 | 2008-06-24 | Maxygen, Inc. | Optimization of immunomodulatory properties of genetic vaccines |
| CA2325567A1 (en) | 1998-05-01 | 1999-11-11 | 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 |
| US20030104417A1 (en) * | 1998-08-12 | 2003-06-05 | Proteus S.A. | Template-mediated, ligation-oriented method of nonrandomly shuffling polynucleotides |
| US6991922B2 (en) * | 1998-08-12 | 2006-01-31 | Proteus S.A. | Process for in vitro creation of recombinant polynucleotide sequences by oriented ligation |
| US20030092023A1 (en) * | 1998-08-12 | 2003-05-15 | Daniel Dupret | Method of shuffling polynucleotides using templates |
| ATE439437T1 (de) * | 1999-01-05 | 2009-08-15 | Univ Boston | Verbessertes klonierungsverfahren |
| US20040005673A1 (en) * | 2001-06-29 | 2004-01-08 | Kevin Jarrell | System for manipulating nucleic acids |
| US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
| EP1151409A1 (en) * | 1999-01-18 | 2001-11-07 | Maxygen, Inc. | Methods of populating data stuctures 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 |
| US6365377B1 (en) | 1999-03-05 | 2002-04-02 | Maxygen, Inc. | Recombination of insertion modified nucleic acids |
| US20040002474A1 (en) * | 1999-10-07 | 2004-01-01 | Maxygen Inc. | IFN-alpha homologues |
| EP1230269A2 (en) | 1999-11-03 | 2002-08-14 | Maxygen, Inc. | Antibody diversity generation |
| US7115712B1 (en) * | 1999-12-02 | 2006-10-03 | Maxygen, Inc. | Cytokine polypeptides |
| IL150291A0 (en) * | 2000-01-11 | 2002-12-01 | Maxygen Inc | Integrated systems and methods for diversity generation and screening |
| AU2001241939A1 (en) * | 2000-02-28 | 2001-09-12 | Maxygen, Inc. | Single-stranded nucleic acid template-mediated recombination and nucleic acid fragment isolation |
| US20010049104A1 (en) * | 2000-03-24 | 2001-12-06 | Stemmer Willem P.C. | 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 |
| AU2001272978A1 (en) * | 2000-06-23 | 2002-01-08 | Maxygen, Inc. | Novel co-stimulatory molecules |
| WO2002004629A2 (en) * | 2000-07-07 | 2002-01-17 | Maxygen, Inc. | Molecular breeding of transposable elements |
| US6858422B2 (en) * | 2000-07-13 | 2005-02-22 | Codexis, Inc. | Lipase genes |
| AU2001277014A1 (en) * | 2000-07-21 | 2002-02-05 | Trustees Of Boston University | 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 |
| CN1468313A (zh) * | 2000-08-24 | 2004-01-14 | �����ɷ� | 新颖的构建物及其在代谢途径工程中的用途 |
| 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 |
| US20040006778A1 (en) * | 2002-02-15 | 2004-01-08 | Diversa Corporation | Chimeric cannulae proteins, nucleic acids encoding them and methods for making and using them |
| 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 |
| CA2436214C (en) * | 2001-02-02 | 2012-12-04 | Large Scale Biology Corporation | A method of increasing complementarity in a heteroduplex polynucleotide |
| 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 |
| CA2462930C (en) | 2001-10-10 | 2012-07-10 | Shawn De Frees | Remodeling and glycoconjugation of peptides |
| JP2005511045A (ja) * | 2001-12-03 | 2005-04-28 | ディヴァーサ コーポレイション | 染色体飽和変異誘発 |
| 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 |
| WO2003068948A1 (en) | 2002-02-13 | 2003-08-21 | Dow Global Technologies Inc. | Over-expression of extremozyme genes in pseudomonads and closely related bacteria |
| US20030224404A1 (en) * | 2002-02-25 | 2003-12-04 | Manuel Vega | High throughput directed evolution of nucleic acids by rational mutagenesis |
| AU2003217716A1 (en) * | 2002-02-25 | 2003-09-09 | Cabot Corporation | Custom ligand design for biomolecular filtration and purification for bioseperation |
| AU2003216507A1 (en) | 2002-03-01 | 2003-09-16 | Maxygen, Inc. | Methods, systems, and software for identifying functional bio-molecules |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US20030199068A1 (en) * | 2002-03-05 | 2003-10-23 | Bott Richard R. | High throughput mutagenesis screening method |
| US20030171543A1 (en) * | 2002-03-05 | 2003-09-11 | Bott Richard R. | High throughput mutagenesis screening method |
| AU2003213846A1 (en) | 2002-03-09 | 2003-09-29 | Maxygen, Inc. | Optimization of crossover points for directed evolution |
| EA010903B1 (ru) | 2002-04-19 | 2008-12-30 | Дайверса Корпорейшн | Фосфолипазы, нуклеиновые кислоты, кодирующие их, и способы их получения и применения |
| US7226771B2 (en) | 2002-04-19 | 2007-06-05 | Diversa Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
| DK1504098T4 (da) * | 2002-05-17 | 2011-05-23 | Alligator Bioscience Ab | Fremgangsmåde til molekyulær udvikling in vitro af proteinfunktion |
| AU2003253992A1 (en) * | 2002-07-18 | 2004-02-09 | Robert P. Bennett | Viral vectors containing recombination sites |
| EP1546349A1 (en) * | 2002-08-02 | 2005-06-29 | 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. |
| ATE466085T1 (de) * | 2002-09-09 | 2010-05-15 | Hanall Pharmaceutical Co Ltd | Protease-resistente modifizierte interferon alpha polypeptide |
| 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 |
| EP3321282A1 (en) | 2002-09-27 | 2018-05-16 | Xencor, Inc. | Optimized fc variants and methods for their generation |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| MX295545B (es) | 2003-03-07 | 2012-02-03 | Diversa Corp | Hidrolasas, acidos nucleicos que las codifican, y metodos para hacerlas y usarlas. |
| US20070026485A1 (en) | 2003-04-09 | 2007-02-01 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| JP2007500514A (ja) | 2003-04-29 | 2007-01-18 | パイオニア ハイ−ブレッド インターナショナル, インコーポレイテッド | 新規なグリホセートn−アセチルトランスフェラーゼ(gat)遺伝子 |
| US20050095615A1 (en) * | 2003-06-26 | 2005-05-05 | Welch Peter J. | 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 |
| ATE469984T1 (de) | 2003-12-01 | 2010-06-15 | Life Technologies Corp | Rekombinationsstellen enthaltende nukleinsäuremoleküle und verfahren zur verwendung davon |
| US7204950B2 (en) * | 2003-12-19 | 2007-04-17 | Pepsico, Inc. | Dispensing package |
| AR048744A1 (es) | 2004-02-25 | 2006-05-24 | Pionner Hi Bred Internat Inc | Polipeptidos cristalinos y polinucleotidos de bacillus thuringiensis y composiciones con los mismos |
| CN101023181A (zh) | 2004-05-21 | 2007-08-22 | 加利福尼亚大学董事会 | 提高类异戊二烯化合物的产生的方法 |
| CA2735315A1 (en) | 2004-06-09 | 2005-12-29 | Pioneer Hi-Bred International, Inc. | Plastid transit peptides |
| US8216804B2 (en) | 2004-10-27 | 2012-07-10 | 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 |
| CA2614769A1 (en) | 2005-03-10 | 2006-09-21 | Verenium Corporation | Lyase enzymes, nucleic acids encoding them and methods for making and using them |
| CN102943085A (zh) | 2005-03-15 | 2013-02-27 | 维莱尼姆公司 | 纤维素酶、编码它们的核酸及其制备和应用的方法 |
| 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 |
| RU2518295C2 (ru) | 2005-06-21 | 2014-06-10 | Ксома Текнолоджи Лтд. | IL-1бета-СВЯЗЫВАЮЩИЕ АНТИТЕЛА И ИХ ФРАГМЕНТЫ |
| GB2432366B (en) * | 2005-11-19 | 2007-11-21 | Alligator Bioscience Ab | A method for in vitro molecular evolution of protein function |
| EP2216403A3 (en) | 2006-02-02 | 2010-11-24 | Verenium Corporation | Esterases and related nucleic acids and methods |
| NZ595497A (en) | 2006-02-10 | 2013-09-27 | Verenium Corp | 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 |
| EP1999256B1 (en) | 2006-03-07 | 2012-03-07 | Verenium Corporation | Aldolases, nucleic acids encoding them and methods for making and using them |
| AU2007223913B2 (en) | 2006-03-07 | 2013-06-13 | Cargill, Incorporated | Aldolases, nucleic acids encoding them and methods for making and using them |
| US20080014205A1 (en) | 2006-05-15 | 2008-01-17 | Lawrence Horowitz | Neutralizing Antibodies to Influenza Viruses |
| US20070294785A1 (en) * | 2006-06-13 | 2007-12-20 | Athenix Corporation | Methods for generating genetic diversity by permutational mutagenesis |
| MX369001B (es) | 2006-08-04 | 2019-10-24 | Basf Enzymes Llc | Glucanasas, acidos nucleicos que las codifican, y metodos para hacerlas y usarlas. |
| PL2057274T3 (pl) | 2006-09-21 | 2014-05-30 | Dsm Ip Assets Bv | Fosfolipazy, kodujące je kwasy nukleinowe i sposoby ich wytwarzania i stosowania |
| EP2617823B1 (en) | 2006-09-21 | 2015-07-01 | BASF Enzymes LLC | Phytases, nucleic acids encoding them and methods for making and using them |
| KR101378302B1 (ko) | 2006-12-20 | 2014-03-28 | 엠엠알글로벌, 인코포레이티드 | 항체 및 이들의 제조 및 사용 방법 |
| ES2575912T3 (es) | 2006-12-21 | 2016-07-04 | Basf Enzymes Llc | Amilasas y glucoamilasas, ácidos nucleicos que las codifican y métodos para formarlas y utilizarlas |
| WO2008095033A2 (en) | 2007-01-30 | 2008-08-07 | Verenium Corporation | Enzymes for the treatment of lignocellulosics, nucleic acids encoding them and methods for making and using them |
| CN103476425B (zh) | 2007-03-30 | 2015-07-15 | 纽约州州立大学研究基金会 | 用于疫苗的减毒病毒 |
| BRPI0815046A2 (pt) | 2007-07-31 | 2014-10-14 | Verenium Corp | Personalização de montagem combinatória de múltiplos locais |
| NZ584967A (en) | 2007-10-03 | 2012-08-31 | Verenium Corp | Xylanases, nucleic acids encoding them and methods for making and using them |
| EP2219469B1 (en) | 2007-12-03 | 2017-08-30 | Syngenta Participations AG | Engineering enzymatically susceptible proteins |
| US9102711B2 (en) * | 2007-12-31 | 2015-08-11 | Xoma Technology Ltd. | Methods and materials for targeted mutagenesis |
| PL2238242T3 (pl) | 2008-01-03 | 2015-06-30 | Basf Enzymes Llc | Transferazy i oksydoreduktazy, kwasy nukleinowe kodujące je oraz sposoby ich wytwarzania i zastosowania |
| US8541220B2 (en) | 2008-01-03 | 2013-09-24 | Verenium Corporation | Isomerases, nucleic acids encoding them and methods for making and using them |
| JP2011518115A (ja) * | 2008-01-28 | 2011-06-23 | タップイミューン インコーポレイテッド | 免疫応答を増強するためのタパシン増加 |
| EP2698380A1 (en) | 2008-03-28 | 2014-02-19 | Sea Lane Biotechnologies, LLC | Neutralizing molecules to viral antigens |
| JP5718221B2 (ja) * | 2008-05-30 | 2015-05-13 | マサチューセッツ インスティテュート オブ テクノロジー | 細胞の空間的分離およびスクリーニングのための組成物および方法 |
| 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 |
| US8153391B2 (en) | 2008-08-29 | 2012-04-10 | 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 |
| US8357503B2 (en) | 2008-08-29 | 2013-01-22 | Bunge Oils, Inc. | Hydrolases, nucleic acids encoding them and methods for making and using them |
| PE20110942A1 (es) * | 2008-12-02 | 2011-12-30 | Consejo Nac Invest Cient Tec | Protozoo modificado que expresa multiples proteinas variables de superficie (vsp), composicion inmunogenica que lo comprende y procedimientos |
| AU2010247086A1 (en) | 2009-05-12 | 2011-12-01 | Council Of Scientific & Industrial Research | LipA and its variant useful for biofuel production |
| BRPI1011160A8 (pt) | 2009-05-21 | 2018-01-02 | Verenium Corp | Fitases, preparação de proteína que as compreende, e seus usos |
| BR122015012748A2 (pt) | 2009-07-17 | 2020-01-07 | Bioatla, Llc | Métodos de evolução, identificação e produção de uma proteína |
| 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 |
| ES2966088T3 (es) | 2010-07-16 | 2024-04-18 | Bioatla Inc | Nuevos métodos de evolución de proteínas |
| CA2805937A1 (en) | 2010-08-13 | 2012-02-16 | Pioneer Hi-Bred International, Inc. | Chimeric promoters and methods of use |
| US9234216B2 (en) | 2010-10-06 | 2016-01-12 | Bp Corporation North America Inc. | Variant CBH I polypeptides |
| 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 |
| CN104540939A (zh) | 2012-03-16 | 2015-04-22 | Bp北美公司 | 具有内切葡聚糖酶活性的多肽 |
| CA2872096A1 (en) | 2012-05-04 | 2013-11-07 | E. I. Du Pont De Nemours And Company | Compositions and methods comprising sequences having meganuclease activity |
| US9969813B2 (en) | 2012-05-10 | 2018-05-15 | Bioatla, Llc | Multi-specific monoclonal antibodies |
| PT2885406T (pt) | 2012-08-16 | 2018-11-16 | Bangladesh Jute Res Institute | Enzimas degradantes de celulose e/ou hemiceluloses de macrophomina phaseolina e utilizações das mesmas |
| ES2674922T3 (es) | 2012-08-16 | 2018-07-05 | Bangladesh Jute Research Institute | Enzimas degradantes de pectina a partir de macrophomina phaseolina y usos de las mismas |
| US10253325B2 (en) | 2012-12-19 | 2019-04-09 | Boston Medical Center Corporation | Methods for elevating fat/oil content in plants |
| AU2014212430B2 (en) * | 2013-01-31 | 2019-06-20 | Codexis, Inc. | Methods, systems, and software for identifying bio-molecules with interacting components |
| GB201308828D0 (en) | 2013-03-12 | 2013-07-03 | Verenium Corp | Phytase |
| EP2970935A1 (en) | 2013-03-14 | 2016-01-20 | Pioneer Hi-Bred International, Inc. | Compositions having dicamba decarboxylase activity and methods of use |
| GB201308843D0 (en) | 2013-03-14 | 2013-07-03 | Verenium Corp | Phytase formulation |
| US20140287419A1 (en) | 2013-03-14 | 2014-09-25 | Arzeda Corp. | Compositions Having Dicamba Decarboxylase Activity and Methods of Use |
| AR095173A1 (es) | 2013-07-25 | 2015-09-30 | Basf Enzymes Llc | Fitasa |
| CA2935577C (en) | 2014-01-07 | 2023-04-04 | Bioatla, Llc | Proteins targeting orthologs |
| WO2017062343A1 (en) | 2015-10-06 | 2017-04-13 | Pierce Biotechnology, Inc. | Devices and methods for producing nucleic acids and proteins |
| US11291221B2 (en) | 2015-10-30 | 2022-04-05 | 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 |
| AU2017386682A1 (en) | 2016-12-28 | 2019-07-25 | Invvax, Inc. | Influenza vaccines |
| US11542487B2 (en) | 2017-10-25 | 2023-01-03 | Basf Se | Beta-amylase enzymes |
| WO2019126211A1 (en) * | 2017-12-20 | 2019-06-27 | 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 |
| EP3788145A1 (en) | 2018-05-03 | 2021-03-10 | Basf Se | Amylase enzymes |
| US12351841B2 (en) | 2018-05-29 | 2025-07-08 | Basf Se | Amylase enzymes |
| CN112513081A (zh) | 2018-06-14 | 2021-03-16 | 生物蛋白有限公司 | 多重特异性抗体构建体 |
| WO2020049159A1 (en) | 2018-09-07 | 2020-03-12 | Basf Plant Science Company Gmbh | Improved method for the production of high levels of pufa in plants |
| AU2019334671A1 (en) | 2018-09-07 | 2021-03-25 | Basf Plant Science Company Gmbh | Improved method for the production of high levels of PUFA in plants |
| WO2020049155A1 (en) | 2018-09-07 | 2020-03-12 | Basf Plant Science Company Gmbh | Improved method for the production of high levels of pufa in plants |
| EP3938504A1 (en) | 2019-03-11 | 2022-01-19 | Basf Se | Amylases and methods for making and using them |
| DK3958890T3 (da) | 2019-04-23 | 2025-02-17 | Basf Se | Beta-amylasevarianter |
| KR20220119408A (ko) | 2019-12-20 | 2022-08-29 | 바스프 에스이 | 터펜의 독성 감소 및 미생물에서 생산 잠재성 증가 |
| EP4162061A1 (en) | 2020-06-04 | 2023-04-12 | Isobionics B.V. | Synthetic santalene synthases |
| EP4015626A1 (en) | 2020-12-18 | 2022-06-22 | Isobionics B.V. | Enzymes and methods for fermentative production of monoterpene esters |
| JP2024528957A (ja) | 2021-08-02 | 2024-08-01 | ビーエーエスエフ ソシエタス・ヨーロピア | イオニリデンエタンシンターゼによる新規な芳香化合物の生成 |
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 |
| EP0436597B1 (en) | 1988-09-02 | 1997-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5198346A (en) | 1989-01-06 | 1993-03-30 | Protein Engineering Corp. | Generation and selection of novel DNA-binding proteins and polypeptides |
| US5096815A (en) | 1989-01-06 | 1992-03-17 | Protein Engineering Corporation | Generation and selection of novel dna-binding proteins and polypeptides |
| DE69332908T2 (de) | 1992-11-24 | 2003-12-24 | G.D. Searle & Co., Chicago | Interleukin-3 (il-3)-polypeptide mith mehreren mutationen |
| WO1995010603A1 (en) * | 1993-10-08 | 1995-04-20 | Novo Nordisk A/S | Amylase variants |
| 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 |
| AU3330895A (en) | 1994-08-18 | 1996-03-14 | Cytogen Corporation | Peptide librairies as a source of syngenes |
| US5885577A (en) | 1994-09-21 | 1999-03-23 | Cytogen Corporation | Antigen binding peptides (abtides) from peptide libraries |
| ATE217344T1 (de) | 1994-09-21 | 2002-05-15 | Cytogen Corp | Antigen bindende peptide (abtides) aus peptidbibliotheken |
| WO1996041865A1 (en) | 1995-06-07 | 1996-12-27 | Ariad Gene Therapeutics, Inc. | Rapamcycin-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 |
| ES2273415T3 (es) | 1997-04-07 | 2007-05-01 | Genentech, Inc. | Anticuerpos anti-vegf. |
| WO1998048024A1 (en) | 1997-04-18 | 1998-10-29 | Biogen, Inc. | Type ii tgf-beta receptor/immunoglobulin constant region fusion proteins |
| AU7171098A (en) | 1997-05-01 | 1998-11-24 | Board Of Regents, The University Of Texas System | Directed evolution of enzymes and antibodies |
| WO1999025845A1 (en) * | 1997-11-17 | 1999-05-27 | Novo Nordisk Biotech, Inc. | Polypeptides having 5-aminolevulinic acid synthase activity and nucleic acids encoding same |
| KR100511655B1 (ko) * | 1997-12-16 | 2005-08-31 | 노보자임스 에이/에스 | 아미노펩티다제 활성을 갖는 폴리펩티드 및 그것을 코드화하는 핵산 |
| WO1999036553A2 (en) | 1998-01-15 | 1999-07-22 | Ariad Gene Therapeutics, Inc. | Regulation of biological events using multimeric chimeric proteins |
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- 2000-02-04 AU AU34839/00A patent/AU3483900A/en not_active Abandoned
- 2000-02-04 JP JP2000597406A patent/JP2003524392A/ja active Pending
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2005
- 2005-03-18 JP JP2005080273A patent/JP2005245453A/ja active Pending
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| WO2000046344A3 (en) | 2000-12-28 |
| JP2003524392A (ja) | 2003-08-19 |
| AU3483900A (en) | 2000-08-25 |
| WO2000046344A2 (en) | 2000-08-10 |
| CA2325351A1 (en) | 2000-08-10 |
| US6171820B1 (en) | 2001-01-09 |
| JP2005245453A (ja) | 2005-09-15 |
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