WO2003023032A3 - High throughput directed evolution by rational mutagenesis - Google Patents

High throughput directed evolution by rational mutagenesis Download PDF

Info

Publication number
WO2003023032A3
WO2003023032A3 PCT/IB2002/003921 IB0203921W WO03023032A3 WO 2003023032 A3 WO2003023032 A3 WO 2003023032A3 IB 0203921 W IB0203921 W IB 0203921W WO 03023032 A3 WO03023032 A3 WO 03023032A3
Authority
WO
WIPO (PCT)
Prior art keywords
proteins
high throughput
directed evolution
rational mutagenesis
throughput directed
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2002/003921
Other languages
French (fr)
Other versions
WO2003023032A2 (en
Inventor
Manuel Vega
Lila Drittanti
Marjorie Flaux
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nautilus Biotech SA
Original Assignee
Nautilus Biotech SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nautilus Biotech SA filed Critical Nautilus Biotech SA
Priority to EP02798018A priority Critical patent/EP1427823A2/en
Publication of WO2003023032A2 publication Critical patent/WO2003023032A2/en
Publication of WO2003023032A3 publication Critical patent/WO2003023032A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C12N15/1086—Preparation or screening of expression libraries, e.g. reporter assays
    • 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
    • C12N15/1058—Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms
    • 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
    • C12N15/1075—Isolating an individual clone by screening libraries by coupling phenotype to genotype, not provided for in other groups of this subclass
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Ecology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Processes and systems for the high throughput directed evolution of peptides and proteins, particularly those that act in complex biological settings, are provided. The proteins and peptides include, but are not limited to, intracellular proteins, messenger/signaling/hormone proteins and viral proteins. Also provided is a rational method for generating protein variants and also a method for titering viruses.
PCT/IB2002/003921 2001-08-27 2002-08-16 High throughput directed evolution by rational mutagenesis Ceased WO2003023032A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02798018A EP1427823A2 (en) 2001-08-27 2002-08-16 High throughput directed evolution by rational mutagenesis

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US31538201P 2001-08-27 2001-08-27
US60/315,382 2001-08-27
US10/022,249 US7647184B2 (en) 2001-08-27 2001-12-17 High throughput directed evolution by rational mutagenesis
US10/022,249 2001-12-17

Publications (2)

Publication Number Publication Date
WO2003023032A2 WO2003023032A2 (en) 2003-03-20
WO2003023032A3 true WO2003023032A3 (en) 2003-10-23

Family

ID=26695719

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2002/003921 Ceased WO2003023032A2 (en) 2001-08-27 2002-08-16 High throughput directed evolution by rational mutagenesis

Country Status (3)

Country Link
US (1) US7647184B2 (en)
EP (1) EP1427823A2 (en)
WO (1) WO2003023032A2 (en)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2808804B1 (en) * 2000-05-09 2002-08-02 Nautilus Biotech METHOD FOR DETERMINING THE TITLE OF BIOLOGICAL AGENTS IN REAL TIME IN LIVING TARGET CELLS AND ITS APPLICATIONS
FR2823219B1 (en) * 2001-04-10 2003-07-04 Pasteur Institut MUTANTS OF DESOXYCYTIDINE KINASE WITH ENLARGED ENZYMATIC ACTIVITY
US20030129203A1 (en) * 2001-08-27 2003-07-10 Nautilus Biotech S.A. Mutant recombinant adeno-associated viruses
US7647184B2 (en) 2001-08-27 2010-01-12 Hanall Pharmaceuticals, Co. Ltd High throughput directed evolution by rational mutagenesis
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
DE60332358D1 (en) * 2002-09-09 2010-06-10 Hanall Pharmaceutical Co Ltd PROTEASE-RESISTANT MODIFIED INTERFERON ALPHA POLYPEPTIDE
AU2003267700A1 (en) * 2002-09-09 2004-03-29 Nautilus Biotech Rational directed protein evolution using two-dimensional rational mutagenesis scanning
US9233131B2 (en) 2003-06-30 2016-01-12 The Regents Of The University Of California Mutant adeno-associated virus virions and methods of use thereof
US9441244B2 (en) 2003-06-30 2016-09-13 The Regents Of The University Of California Mutant adeno-associated virus virions and methods of use thereof
CA2572917C (en) * 2004-07-06 2012-04-03 Bioren Inc. Look-through mutagenesis for developing altered polypeptides with enhanced properties
US7998930B2 (en) * 2004-11-04 2011-08-16 Hanall Biopharma Co., Ltd. Modified growth hormones
ES2525067T3 (en) 2005-04-07 2014-12-17 The Trustees Of The University Of Pennsylvania Method of increasing the function of an AAV vector
WO2006120580A2 (en) * 2005-05-04 2006-11-16 Nautilus Biotech Modified interferon-gamma polypeptides and methods for using modified interferon-gamma polypeptides
US20080038224A1 (en) * 2006-03-28 2008-02-14 Thierry Guyon Modified interferon-beta (IFN-beta) polypeptides
EP2423307A1 (en) 2006-06-19 2012-02-29 Catalyst Biosciences, Inc. Modified coagulation factor IV polypeptides and use thereof for treatment
WO2008065372A2 (en) * 2006-11-28 2008-06-05 Nautilus Biotech, S.A. Modified erythropoietin polypeptides and uses thereof for treatment
SG10201700096VA (en) 2009-07-17 2017-02-27 Bioatla Llc Simultaneous, Integrated Selection And Evolution Of Antibody/Protein Performance And Expression In Production Hosts
WO2011109726A2 (en) * 2010-03-05 2011-09-09 Bioatla Llc Homologous multi-specific antibodies
ES2741175T3 (en) 2010-07-16 2020-02-10 Bioatla Llc New methods of protein evolution
CA2807702C (en) 2010-08-20 2018-07-24 Codexis, Inc. Use of glycoside hydrolase 61 family proteins in processing of cellulose
MX360946B (en) 2010-09-22 2018-10-29 Amgen Inc Star CARRYING IMMUNOGLOBULINS AND USES OF THE SAME.
US8663624B2 (en) 2010-10-06 2014-03-04 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
CN105755044A (en) 2011-04-22 2016-07-13 加利福尼亚大学董事会 Adeno-associated Virus Virions With Variant Capsid And Methods Of Use Thereof
WO2012166392A1 (en) 2011-05-20 2012-12-06 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Paenibacillus alvei strain ts-15 and its use in controlling pathogenic organisms
EP2748317B1 (en) 2011-08-22 2017-04-19 Codexis, Inc. Gh61 glycoside hydrolase protein variants and cofactors that enhance gh61 activity
EP2946006B1 (en) 2013-01-18 2019-04-10 Codexis, Inc. Engineered biocatalysts useful for carbapenem synthesis
EP3003391B1 (en) 2013-05-31 2021-09-22 The Regents of The University of California Adeno-associated virus variants and methods of use thereof
EP3800191B1 (en) 2014-03-17 2025-08-20 Adverum Biotechnologies, Inc. Compositions and methods for enhanced gene expression in cone cells
US11021519B2 (en) 2015-03-02 2021-06-01 Adverum Biotechnologies, Inc. Compositions and methods for intravitreal delivery of polynucleotides to retinal cones
JP6836999B2 (en) 2015-03-24 2021-03-03 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアＴｈｅ Ｒｅｇｅｎｔｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃａｌｉｆｏｒｎｉａ Adeno-associated virus mutants and how to use them
AU2017302013B2 (en) 2016-07-29 2022-05-26 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
CA3040179A1 (en) 2016-10-19 2018-04-26 Adverum Biotechnologies, Inc. Modified aav capsids and uses thereof
CA3053154A1 (en) 2017-06-30 2019-01-03 The Regents Of The University Of California Adeno-associated virus virions with variant capsids and methods of use thereof
JP2020534788A (en) 2017-08-28 2020-12-03 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Adeno-associated virus capsid mutant and how to use it
JP2022504802A (en) 2018-10-11 2022-01-13 インヒブルクス インコーポレイテッド 5T4 single domain antibody and therapeutic composition thereof
CN120623346A (en) 2018-10-11 2025-09-12 因荷布瑞克斯生物科学公司 PD-1 single domain antibody and therapeutic composition thereof
JP7611820B2 (en) 2018-10-11 2025-01-10 インヒブルクス バイオサイエンシズ インコーポレイテッド DLL3 single domain antibodies and therapeutic compositions thereof
CN113166261A (en) 2018-10-11 2021-07-23 印希比股份有限公司 B7H3 single domain antibodies and therapeutic compositions thereof
EP4127135A1 (en) 2020-04-02 2023-02-08 uniQure biopharma B.V. Dual bifunctional vectors for aav production
EP4127146A1 (en) 2020-04-02 2023-02-08 uniQure biopharma B.V. Novel cell line
WO2022207899A1 (en) 2021-04-02 2022-10-06 Uniqure Biopharma B.V. Methods for producing single insect cell clones

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995023813A1 (en) * 1994-03-04 1995-09-08 Merck & Co., Inc. In vitro antibody affinity maturation using alanine scanning mutagenesis
US6013478A (en) * 1988-10-28 2000-01-11 Genentech, Inc. Method for identifying active domains and amino acid residues in polypeptides and hormone variants
WO2001032844A1 (en) * 1999-11-05 2001-05-10 Novozymes A/S Microtiter plate (mtp) based high throughput screening (hts) assays
WO2001044809A2 (en) * 1999-12-16 2001-06-21 Nautilus Biotech Evaluation of biological agents in living target cells
WO2001086291A1 (en) * 2000-05-09 2001-11-15 Nautilus Biotech Method for determining biological agents in living target cells

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3171820A (en) 1964-02-17 1965-03-02 Scott Paper Co Reticulated polyurethane foams and process for their production
US4797368A (en) 1985-03-15 1989-01-10 The United States Of America As Represented By The Department Of Health And Human Services Adeno-associated virus as eukaryotic expression vector
DE229046T1 (en) 1985-03-30 1987-12-17 Marc Genf/Geneve Ballivet METHOD FOR OBTAINING DNA, RNS, PEPTIDES, POLYPEPTIDES OR PROTEINS BY DNA RECOMBINANT METHOD.
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
EP0240224A3 (en) 1986-03-31 1989-02-01 Interferon Sciences, Inc. An alpha interferon analogue
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5096815A (en) 1989-01-06 1992-03-17 Protein Engineering Corporation Generation and selection of novel dna-binding proteins and polypeptides
US5436146A (en) 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
US5262568A (en) 1990-03-02 1993-11-16 State Of Oregon Tri- and tetra-substituted guanidines and their use as excitatory amino acid antagonists
CA2079802C (en) 1990-04-05 2001-09-18 Roberto Crea Walk-through mutagenesis
US5871974A (en) 1990-09-28 1999-02-16 Ixsys Inc. Surface expression libraries of heteromeric receptors
US5770434A (en) 1990-09-28 1998-06-23 Ixsys Incorporated Soluble peptides having constrained, secondary conformation in solution and method of making same
US6258530B1 (en) 1990-09-28 2001-07-10 Ixsys, Inc. Surface expression libraries of randomized peptides
US6165793A (en) 1996-03-25 2000-12-26 Maxygen, Inc. Methods for generating polynucleotides having desired characteristics by iterative selection and recombination
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
FR2722208B1 (en) * 1994-07-05 1996-10-04 Inst Nat Sante Rech Med NEW INTERNAL RIBOSOME ENTRY SITE, VECTOR CONTAINING SAME AND THERAPEUTIC USE
IL116816A (en) 1995-01-20 2003-05-29 Rhone Poulenc Rorer Sa Cell for the production of a defective recombinant adenovirus or an adeno-associated virus and the various uses thereof
US6057103A (en) 1995-07-18 2000-05-02 Diversa Corporation Screening for novel bioactivities
US20030215798A1 (en) 1997-06-16 2003-11-20 Diversa Corporation High throughput fluorescence-based screening for novel enzymes
US6171820B1 (en) 1995-12-07 2001-01-09 Diversa Corporation Saturation mutagenesis in directed evolution
US6238884B1 (en) 1995-12-07 2001-05-29 Diversa Corporation End selection in directed evolution
EP0876512A1 (en) * 1996-01-23 1998-11-11 Viropharma Incorporated Methods for identifying inhibitors of rna viruses
US6096548A (en) 1996-03-25 2000-08-01 Maxygen, Inc. Method for directing evolution of a virus
EP0927044A4 (en) 1996-04-16 1999-09-08 Immusol Inc Targeted viral vectors
US5763239A (en) 1996-06-18 1998-06-09 Diversa Corporation Production and use of normalized DNA libraries
JP2001504325A (en) 1996-09-27 2001-04-03 マキシジェン，インコーポレイテッド A method for optimization of gene therapy by recursive sequence shuffling and selection
US5862514A (en) 1996-12-06 1999-01-19 Ixsys, Inc. Method and means for synthesis-based simulation of chemicals having biological functions
US6605429B1 (en) 1997-01-23 2003-08-12 Immusol, Incorporated Gene functional analysis and discovery using randomized or target-specific ribozyme gene vector libraries
US5779434A (en) 1997-02-06 1998-07-14 Baker Hughes Incorporated Pump mounted thrust bearing
US6037177A (en) 1997-08-08 2000-03-14 Cell Genesys, Inc. Method for increasing the efficiency of recombinant AAV production
DK1009808T3 (en) 1997-09-05 2013-01-21 Genzyme Corp METHODS FOR GENERATION OF HELP-FREE PREPARATIONS OF HIGH TITER RECOMBINANT AAV VECTORS
US6156509A (en) 1997-11-12 2000-12-05 Genencor International, Inc. Method of increasing efficiency of directed evolution of a gene using phagemid
US6413776B1 (en) 1998-06-12 2002-07-02 Galapagos Geonomics N.V. High throughput screening of gene function using adenoviral libraries for functional genomics applications
AU7739000A (en) 1999-10-01 2001-05-10 University Of Florida Temperature-sensitive regulation of viral vector production
WO2001025438A2 (en) 1999-10-07 2001-04-12 Maxygen, Inc. Ifn-alpha homologues
WO2001032711A2 (en) 1999-10-21 2001-05-10 Board Of Trustees Of The University Of Arkansas Adeno-associated virus aav rep78 major regulatory protein, mutants thereof and uses thereof
WO2001061344A1 (en) 2000-02-17 2001-08-23 California Institute Of Technology Computationally targeted evolutionary design
FR2813314B1 (en) 2000-08-25 2004-05-07 Biomethodes MASSIVE DIRECTED MUTAGENESIS PROCESS
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
US20030224404A1 (en) 2002-02-25 2003-12-04 Manuel Vega High throughput directed evolution of nucleic acids by rational mutagenesis
DE60332358D1 (en) 2002-09-09 2010-06-10 Hanall Pharmaceutical Co Ltd PROTEASE-RESISTANT MODIFIED INTERFERON ALPHA POLYPEPTIDE
US20050202438A1 (en) 2002-09-09 2005-09-15 Rene Gantier Rational directed protein evolution using two-dimensional rational mutagenesis scanning
AU2003267700A1 (en) 2002-09-09 2004-03-29 Nautilus Biotech Rational directed protein evolution using two-dimensional rational mutagenesis scanning
US20060020396A1 (en) 2002-09-09 2006-01-26 Rene Gantier Rational directed protein evolution using two-dimensional rational mutagenesis scanning
JP5622351B2 (en) 2004-09-03 2014-11-12 クレアビリス・セラピューティクス・エスピーエー Protease resistant human and non-human HMGB1Box-A variants and their use in therapy / diagnosis
US7998930B2 (en) 2004-11-04 2011-08-16 Hanall Biopharma Co., Ltd. Modified growth hormones
WO2006120580A2 (en) 2005-05-04 2006-11-16 Nautilus Biotech Modified interferon-gamma polypeptides and methods for using modified interferon-gamma polypeptides

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6013478A (en) * 1988-10-28 2000-01-11 Genentech, Inc. Method for identifying active domains and amino acid residues in polypeptides and hormone variants
WO1995023813A1 (en) * 1994-03-04 1995-09-08 Merck & Co., Inc. In vitro antibody affinity maturation using alanine scanning mutagenesis
WO2001032844A1 (en) * 1999-11-05 2001-05-10 Novozymes A/S Microtiter plate (mtp) based high throughput screening (hts) assays
WO2001044809A2 (en) * 1999-12-16 2001-06-21 Nautilus Biotech Evaluation of biological agents in living target cells
WO2001086291A1 (en) * 2000-05-09 2001-11-15 Nautilus Biotech Method for determining biological agents in living target cells

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DRITTANTI L ET AL: "High throughput production, screening and analysis of adeno-associated viral vectors.", GENE THERAPY, vol. 7, no. 11, June 2000 (2000-06-01), pages 924 - 929, XP002242834, ISSN: 0969-7128 *

Also Published As

Publication number Publication date
EP1427823A2 (en) 2004-06-16
WO2003023032A2 (en) 2003-03-20
US7647184B2 (en) 2010-01-12
US20030134351A1 (en) 2003-07-17

Similar Documents

Publication Publication Date Title
WO2003023032A3 (en) High throughput directed evolution by rational mutagenesis
WO2004022593A3 (en) Rational evolution of cytokines for higher stability, the cytokines and encoding nucleic acid molecules
Hrabal et al. The hairpin stack fold, a novel protein architecture for a new family of protein growth factors
WO2001060974A3 (en) Method for an extraction of proteins from a single cell
WO2002002783A3 (en) Expression vectors
AU7473500A (en) Identification of peptides that facilitate uptake and cytoplasmic and/or nucleartransport of proteins, dna and viruses
WO2002099035A3 (en) Chimeric alphavirus replicon particles
AU2002335788A1 (en) Flexible processing apparatus for isolating and purifying viruses, soluble proteins and peptides from plant sources
PT1012295E (en) ALFAVIRUS RNA REPLICATION SYSTEMS
WO2005056807A3 (en) Bovine adeno-associated viral (baav) vector and uses thereof
DK0688227T3 (en) Preparation of human papillomavirus capsid protein and virus-like particles
GB0100513D0 (en) Process
WO2003048348A3 (en) Production of viruses, viral isolates and vaccines
WO2005047459A3 (en) Sars nucleic acids, proteins, antibodies, and uses thereof
WO2004101598A3 (en) Insertion of furin protease cleavage sites in membrane proteins and uses thereof
IL165988A0 (en) Process for the preparation of fibrinogen
WO2007053188A3 (en) Production of multivalent virus like particles
DE60044087D1 (en) METHOD AND MEANS FOR MANIPULATING THE EXPRESSION OF THE UNCOUPLING PROTEIN
EP1272669A4 (en) HIGH THROUGHPUT SCREENING OF DNA LIBRARIES EXPRESSED IN FILAMENTOUS FUNGI
WO1996038474A3 (en) Diagnosis of, and vaccination against, a positive stranded RNA virus using an isolated, unprocessed polypeptide
WO2002077012A3 (en) Human papilloma virus immunoreative peptides
ATE374814T1 (en) PROTEIN SYNTHESIS METHOD USING CELL-FREE PROTEIN SYNTHESIS SYSTEM
WO2001072769A3 (en) Methods for purifying highly anionic proteins
MXPA02012593A (en) Bvdv virus-like particles.
WO2004024904A3 (en) Infectious hepacivirus pseudo-particles containing functional e1, e2 envelope proteins

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BY BZ CA CH CN CO CR CU CZ DE DM DZ EC EE ES FI GB GD GE GH HR HU ID IL IN IS JP KE KG KP KR LC LK LR LS LT LU LV MA MD MG MN MW MX MZ NO NZ OM PH PL PT RU SD SE SG SI SK SL TJ TM TN TR TZ UA UG US UZ VC VN YU ZA ZM

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2002798018

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002798018

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP