序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
101 METHOD FOR MODULATING THE EVOLUTION OF A POLYPEPTIDE ENCODED BY A NUCLEIC ACID SEQUENCE EP05850658.5 2005-09-19 EP1799823A2 2007-06-27 MAZEL, Didier; CAMBRAY, Guillaume
A method for modulating the ability of a gene to mutate by analyzing codon usage within the gene and selecting a synonymous nucleotide sequence with a higher, lower or different capacity to mutate. The method permits widening and optimization of the evolutionary landscape of a protein. A computer-implemented method for analyzing and selecting nucleotide sequences with an altered ability to mutate.
102 METHOD FOR OBTAINING CELLS WITH NEW PROPERTIES EP02767746.7 2002-07-08 EP1404846A1 2004-04-07 MUTZEL, Ruppert; MARLIERE, Philippe; MAZEL, Didier
The present invention relates to a method for generating a novel form of life comprising the steps consisting of: a) irreversible alteration of the genome of a microbial clone; b) cultivation of a vast population of microbial cells originating from the altered clone obtained in step a) during numerous generations under conditions allowing selection for a higher and stable proliferation rate; c) isolation of descendant clones within the cultivated population of step b) still bearing the alteration of step a).
103 DESIGN OF MOLECULES PCT/GB2010051940 2010-11-22 WO2011061548A3 2011-08-11 HOPKINS ANDREW LEE; BESNARD JEREMY
A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA 1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1-In) from the population (PG=0); and evaluating members (I1-In) of the initial population (Pparent) against at least one of the n achievement objectives (OA 1-x), where x is from 1 to n.
104 GENETIC SELECTION FOR PROTEIN FOLDING AND SOLUBILITY IN THE BACTERIAL PERIPLASM PCT/US2008050991 2008-01-14 WO2008089132A3 2008-11-13 DELISA MATTHEW P; MANSELL THOMAS J; FISHER ADAM C
The present invention relates to the fields of microbiology, molecular biology and protein biochemistry. More particularly, it relates to compositions and methods for analyzing and altering (e.g., enhancing or inhibiting) protein folding and solubility (e.g., within periplasm). The present invention provides an engineered assay for protein folding and solubility in the E. coli periplasm based on co-translational translocation of a chimera comprising a protein of interest fused to TEM-I ß-lactamase that is targeted for export via the signal recognition particle (SRP)-dependent pathway. Using an array of native and heterologous proteins, it is demonstrated that periplasmic folding behavior of proteins is intimately coupled to in vivo ß-lactamase activity. As a result of this coupling, the reporter is useful for (1) facile discovery of extrinsic periplasmic factors that affect protein folding and solubility; and (2) genetic selection of solubility-enhanced proteins.
105 METHOD FOR OBTAINING CELLS WITH NEW PROPERTIES PCT/IB0203398 2002-07-08 WO03004656A8 2004-02-12 MUTZEL RUPPERT; MARLIERE PHILIPPE; MAZEL DIDIER
The present invention relates to a method for generating a novel form of life comprising the steps consisting of: a) irreversible alteration of the genome of a microbial clone; b) cultivation of a vast population of microbial cells originating from the altered clone obtained in step a) during numerous generations under conditions allowing selection for a higher and stable proliferation rate; c) isolation of descendant clones within the cultivated population of step b) still bearing the alteration of step a).
106 STRUCTURE-ACTIVITY RELATIONSHIPS PCT/US2008001907 2008-02-12 WO2009008908A3 2009-02-26 MUNDORFF EMILY; DAVIS SIMON CHRISTOPHER; HUISMAN W GJALT; KREBBER ANKE; GRATE H JOHN
The present disclosure relates to compositions and methods for screening a plurality of polypeptide variants.
107 GENERATION OF LIBRARY OF SOLUBLE RANDOM POLYPEPTIDES LINKED TO mRNA PCT/US2008053757 2008-02-12 WO2008100961A3 2008-12-11 WILLIAMS RICHARD B
Methods and compositions are provided for producing libraries of soluble random polypeptides. In the methods, the fraction of hydrophilic residues in the polypeptide is controlled so as to maintain the solubility of the polypeptide constructs.
108 EVOLVED ORTHOGONAL RIBOSOMES PCT/GB2007004562 2007-11-28 WO2008065398A3 2008-07-17 CHIN JASON; WANG KAIHANG; NEUMANN HEINZ
There is provided a method for evolving an orthogonal rRNA molecule, comprising the steps of: providing one or more libraries of mutant orthogonal rRNA molecules and introducing the libraries into cells such that the orthogonal rRNA is incorporated into ribosomes to provide orthogonal ribosomes; providing one or more orthogonal mRNA molecules which (i) are not translated by natural ribosomes, and (ii) comprise one or more orthogonal mRNA codons; assaying the translation of the of the orthogonal mRNA and selecting the orthogonal rRNA molecules which translate the orthogonal mRNA, wherein the assay in step (c) requires translation of one or more orthogonal mRNA codons in the orthogonal mRNA; and orthogonal ribosomes incorporating such rRNA molecules.
109 A METHOD FOR IN VITRO MOLECULAR EVOLUTION OF ANTIBODY FUNCTION PCT/EP0104065 2001-04-04 WO0175091A3 2002-04-18 OHLIN MATS; SODERLIND ESKIL; CARLSSON ROLAND
The present invention provides a method for producing a polynucleotide sequence encoding an antibody variable domain, the variable domain comprising complementarity-determining regions (CDRs) located within a selected framework (the 'master framework'), the method comprising the steps of (a) providing at least one nucleic acid molecule encoding one or more CDRs and associated framework regions (the 'original framework'), (b) amplifying at least one CDR-encoding portion of the nucleic acid molecule(s) of step (a) using one or more pairs of oligonucleotides as amplification primers and (c) assembling a polynucleotide sequence encoding an antibody variable domain by combining the amplified CDR-encoding nucleotide sequences produced in step (b) with nucleotide sequences encoding said master framework, wherein the oligonucleotide primers of step (b) comprise nucleotide sequences which differ from the corresponding nucleotide sequences encoding said master framework. The invention further provides an antibody library, such as a phage display library, and methods of making the same.
110 AUTONOMOUS IN VITRO EVOLUTION PCT/US2009036065 2009-03-04 WO2009111586A2 2009-09-11 REIF JOHN H; SCHULTES ERIK A; LABEAN THOMAS H
Compositions and methods for the autonomous in vitro evolution of molecules having specific properties, employing one-pot continuous evolution are disclosed.
111 CELL SURFACE DISPLAY, SCREENING AND PRODUCTION OF PROTEINS OF INTEREST PCT/US2008003978 2008-03-26 WO2008118476A3 2008-11-13 RAKESTRAW JAMES A; LIPOVSEK DASA
Aspects of the invention provide compositions and methods for displaying engineered polypeptides on a cell surface. According to aspects of the invention, immobilized polypeptides can be screened to identify one or more variants having one or more functional or structural properties of interest. Aspects of the invention provide composition and methods for producing engineered protein or protein variants having a functional or a structural property of interest.
112 METHOD FOR CARRYING OUT THE SELECTIVE EVOLUTION OF PROTEINS IN VITRO PCT/EP2006007798 2006-08-07 WO2007017229A3 2007-05-18 LISS MICHAEL
The invention relates to the production of variants of a protein in an in vitro evolution method, comprising the steps: (A) preparing an in vitro expression system, comprising: (i) a nucleic acid sequence S, which codes for a protein Y to be varied; (ii) a target molecule X1 capable of binding to protein Y and/or at least one variant Y thereof; (iii) an RNA polymerase (Pol) capable of transcribing the nucleic acid sequence S; (iv) a reverse transcriptase (RT) capable of reverse transcribing transcripts of nucleic acid sequence S, the target molecule X being coupled to Pol and protein Y to RT, or target molecule X being coupled to RT and protein Y being coupled to Pol; (B) incubating the in vitro expression system from (A) under conditions that enable a transcription, a reverse transcription and a translation while forming variants Y' of protein Y and nucleic acid sequences S' coding therefor, and which promote the formation of variants Y' with improved binding properties for target molecule X; (C) isolating and optionally characterizing those variants Y' that have improved binding properties for binding to X and/or isolation nucleic acid sequence variants S' that code for Y'.
113 METHOD FOR MODULATING THE EVOLUTION OF A POLYPEPTIDE ENCODED BY A NUCLEIC ACID SEQUENCE PCT/IB2005003317 2005-09-19 WO2006046132A3 2006-08-17 MAZEL DIDIER; CAMBRAY GUILLAUME
A method for modulating the ability of a gene to mutate by analyzing codon usage within the gene and selecting a synonymous nucleotide sequence with a higher, lower or different capacity to mutate. The method permits widening and optimization of the evolutionary landscape of a protein. A computer-implemented method for analyzing and selecting nucleotide sequences with an altered ability to mutate.
114 METHOD FOR OBTAINING CELLS WITH NEW PROPERTIES PCT/IB0203398 2002-07-08 WO03004656A9 2003-06-05 MUTZEL RUPPERT; MARLIERE PHILIPPE; MAZEL DIDIER
The present invention relates to a method for generating a novel form of life comprising the steps consisting of: a) irreversible alteration of the genome of a microbial clone; b) cultivation of a vast population of microbial cells originating from the altered clone obtained in step a) during numerous generations under conditions allowing selection for a higher and stable proliferation rate; c) isolation of descendant clones within the cultivated population of step b) still bearing the alteration of step a).
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