Entries |
Document | Title | Date |
20080207459 | ANTIBODY DIVERSITY GENERATION - Methods for improving antibodies by a variety of DNA diversification and selection procedures are provided. Improvements include increases in affinity, alterations in specificity and effector function, as well as reduced antigenicity, e.g. humanization. Libraries of recombinant antibody sequences are provided, as are cells expressing members of such libraries. Novel phage display vectors are provided. Methods for the coevolution of an antibody and its cognate antigen are provided. Coevolution is used to evolve HIV envelope proteins with increased antigenicity and broadly neutralizing antibodies that interact therewith. Methods of improving antibodies for use in the detection of biological warfare agents are provided. | 08-28-2008 |
20080227649 | Methods and compositions for cellular and metabolic engineering - The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering. | 09-18-2008 |
20080227650 | Incrementally Truncated Nucleic Acids and Methods of Making Same - A series of methods that utilize the incremental truncation of nucleic acids are described to create a plurality of modified nucleic acids and hybrid polypeptides. A plurality of substantially all possible single base-pair deletions of a given nucleic acid sequence is created. A method of making shuffled incremental truncated nucleic acids, which is independent of nucleic acid sequence homology, is also described. These methods can be used in protein engineering, protein folding, protein evolution, and the chemical synthesis of novel hybrid proteins and polypeptides. | 09-18-2008 |
20080274904 | Method of target enrichment - The present invention is directed to a method for reducing the complexity of a nucleic acid sample in a reproducible manner by enriching for specific nucleic acid target sequences in the population of nucleic acids. More specifically, the invention relates to a method for enriching specific target sequences in a population using libraries of oligonucleotides. | 11-06-2008 |
20080287304 | Mixture of at Least Two Fusion Proteins as Well as Their Production and Use - The present invention concerns a protein mixture comprising at least a first fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence, which effects that the fusion protein upon expression in a bacterium is translocated through the cytoplasmic membrane in an essentially unfolded state and at least a second fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence which effects that the fusion protein is translocated through the cytoplasmic membrane upon expression in a bacterium in an essentially folded state, wherein the interaction domain of the first protein can bind to those of the second protein. | 11-20-2008 |
20080318795 | Methods for making character strings, polynucleotides and polypeptides having desired characteristics - In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided. | 12-25-2008 |
20090036315 | Device and methods for detecting and quantifying one or more target agents - The present invention provides a device and methods for the detection and quantification of one or more target agents in a sample by rapid and specific electrochemical detection. The present invention includes kits, devices and compositions capable of performing rapid, specific and accurate detection of one or more target agents in a sample. | 02-05-2009 |
20090105081 | METHODS AND SYSTEMS FOR SOLUTION BASED SEQUENCE ENRICHMENT - The present invention provides methods and systems for the capture and enrichment of target nucleic acids and analysis of the enriched target nucleic acids. In particular, the present invention provides for the enrichment of targeted sequences in a solution based format. | 04-23-2009 |
20090143232 | METHOD FOR SYNTHESISING TEMPLATED MOLECULES - The invention relates to a method for synthesizing templated molecules attached to the templated which directed the synthesis thereof. The method involves a template, a scaffold functional entity and a functional entity attached to a building block, which, in turn, is attached the template. The scaffold functional entity and the functional entity of the building block are both provided with complementary dimerization domains allowing the functional entities to come into close proximity when the complementary domains interact with to each other. The method may be used for generating libraries of templated molecules which may be selected for biological activity. | 06-04-2009 |
20090149331 | Methods and compositions for polypeptide engineering - Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed. | 06-11-2009 |
20090170711 | Selection Method for Cell Internalizing Nucleic Acids - The present invention includes compositions and methods for contacting one or more cells with a random RNA-containing library, treating the contacted cells and with a denaturing agent or digestion with one or more nucleases, and extracting from the cells one or more internalized nucleic acids resistant to the nucleases or denaturants. | 07-02-2009 |
20090170712 | Using Oligonucleotide Microarrays to Analyze Genomic Differences for the Prediction of Heterosis - A novel method for prediction of the degree of heterotic phenotypes in plants is disclosed. Structural variation analyses of the genome are used to predict the degree of a heterotic phenotype in plants. In some examples, copy number variation is used to predict the degree of heterotic phenotype. In some methods copy number variation is detected using competitive genomic hybridization arrays. Further, methods for optimizing the arrays are disclosed, together with kits for producing such arrays, as well as hybrid plants selected for development based on the predicted results. | 07-02-2009 |
20090203530 | Polymer evolution via templated synthesis - The invention provides a method for producing polymers having a desirable property, for example, catalytic activity or binding activity, via evolutionary nucleic acid-mediated chemistry. | 08-13-2009 |
20090264298 | Methods for enriching subpopulations - Methods of enriching a subpopulation of beads are described. In one embodiment, first beads comprise immobilized first amplified product, said first amplified product encoding a truncated version of a first protein, and second beads comprise immobilized second amplified product, said second amplified product encoding an untruncated version of said first protein. Both first and second beads are exposed to a translation system under conditions such that said truncated and untruncated versions of said first protein are generated from at least a portion of said first and second immobilized amplified products, and these protein products are captured on the first and second beads, respectively. Using a ligand (e.g. with affinity for the untruncated version of said first protein), a portion of the second beads is separated from the mixture, thereby enriching a subpopulation of beads comprising truncated protein. | 10-22-2009 |
20090318297 | Antibody Ultrahumanization by Predicted Mature CDR Blasting and Cohort Library Generation and Screening - Methods and compositions directed to improved universal antibody libraries that rationally exploit human diversity information contained within reference antibody libraries, such as universal antibody libraries, are disclosed. The disclosed processes involve use of a query CDR sequence to guide incorporation of human antibody diversity present within the reference library into cohort libraries of the invention. Methods for making and screening such cohort libraries for isolating therapeutics suitable for treating disease are also disclosed. | 12-24-2009 |
20100048407 | METHOD FOR DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS - The present invention provides bioengineered high affinity polypeptides for use in a method for the detection of the presence of human immunodeficiency virus, HIV, in a biological sample. The present invention also provides a method for producing bioengineered high affinity polypeptides. | 02-25-2010 |
20100081575 | Methods for creating diversity in libraries and libraries, display vectors and methods, and displayed molecules - Provided herein are methods for generating diverse polypeptide and nucleic acid molecule libraries and collections, and the collections and libraries; methods for selecting variant polypeptides and nucleic acid molecules from the libraries; and molecules selected from the libraries. Exemplary of the polypeptides and nucleic acid molecules are antibodies and nucleic acids encoding the antibodies (including antibody fragments and domain exchanged antibodies). Also provided herein are methods of displaying polypeptides such as antibodies, for example on the surface of genetic packages, such as phage; and libraries and collections of the displayed polypeptides and vectors for producing the displayed polypeptides, libraries and collections. Exemplary of the displayed antibodies are domain exchanged antibodies. | 04-01-2010 |
20100292083 | PROVIDING IMPROVED IMMUNOGLOBULIN SEQUENCES BY MUTATING CDR AND/OR FR POSITIONS - The present invention relates to methods and techniques for providing improved amino acid sequences that can be used as single antigen-binding domains. In particular, the invention relates to methods and techniques for providing improved amino acid sequences that can be used as single antigen-binding domains that comprise or essentially consist of at least one immunoglobulin sequence. More in particular, the amino acid sequences provided herein may comprise or essentially consist of at least one variable domain sequence or a suitable fragment thereof, such as at least one light chain variable domain sequence (e.g. a V | 11-18-2010 |
20100331192 | SURFACE DISPLAY OF RECOMBINANT PROTEINS IN LOWER EUKARYOTES - Methods for display of recombinant proteins or protein libraries on the surface of lower eukaryotes such as yeast and filamentous fungi are described. The methods are useful for screening libraries of recombinant proteins in lower eukaryotes to identify particular proteins with desired properties from the array of proteins in the libraries. The methods are particularly useful for constructing and screening antibody libraries in lower eukaryotes. | 12-30-2010 |
20110045989 | SELECTIVE ENRICHMENT OF N-TERMINALLY MODIFIED PEPTIDES FROM COMPLEX SAMPLES - The present invention relates to methods allowing the selective enrichment of N-terminal fragments of polypeptides and/or peptides from complex samples by combining a particular polypeptide/peptide labeling and fractionation strategy with specific chemical and/or enzymatic reactions targeting the N-terminal fragments to be analyzed. | 02-24-2011 |
20110053781 | METHODS AND COMPOSITIONS FOR POLYPEPTIDE ENGINEERING - Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed. | 03-03-2011 |
20110065587 | EPITOPE TESTING USING SOLUBLE HLA - The present invention relates generally to a methodology for assaying the binding of a peptide to an individual, specific, soluble HLA molecule. | 03-17-2011 |
20110092372 | Methods of Affinity Maturing Antibodies - The invention relates to methods of affinity maturing antibodies. | 04-21-2011 |
20110098184 | Competitve differntial screeing - The invention is drawn to a novel method useful for screening. In particular, the present invention provides methods for competitive differential screening. In some preferred embodiments, the present invention provides methods for competitive differential screening that facilitate the identification of tight binders. In some preferred embodiments, the agents used in the methods of the present invention comprise tight and weak binders. In other embodiments, the present invention provides methods that utilize competitive binders that recognize and bind targets, but with binding that is less strong than that of binders of interest. | 04-28-2011 |
20110118124 | METHOD FOR IMPROVING THE PROPERTIES OF A DRUG LEAD COMPOUND - The present patent application introduces methods for generating mixture compound libraries from a drug lead. The mixture compound libraries are then screened for the discovery of modified drug lead compounds which possess desired improved drug properties. The process utilizes a non-selective reaction to modify the drug lead compound structure. Compared to existing methods of modifying a drug lead compound, this new method can modify more structural positions of a drug lead compound. As a consequence, there will be greater probability of finding a product with improved drug properties. | 05-19-2011 |
20110183855 | SOMATIC HYPERMUTATION SYSTEMS - The present application relates to somatic hypermutation (SHM) systems and synthetic genes. Synthetic genes can be designed using computer-based approaches to increase or decrease susceptibility of a polynucleotide to somatic hypermutation. Genes of interest are inserted into the vectors and subjected to activation-induced cytidine deaminase to induce somatic hypermutation. Proteins or portions thereof encoded by the modified genes can be introduced into a SHM system for somatic hypermutation and proteins or portions thereof exhibiting a desired phenotype or function can be isolated for in vitro or in vivo diagnostic or therapeutic uses. | 07-28-2011 |
20110190140 | EVOLUTION OF WHOLE CELLS AND ORGANISMS BY RECURSIVE SEQUENCE RECOMBINATION - The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites. | 08-04-2011 |
20110190141 | Evolving New Molecular Function - Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The power of Nature and the flexibility of organic synthesis are combined in nucleic acid-templated synthesis. The present invention provides a variety of template architectures for performing nucleic acid-templated synthesis, methods for increasing the selectivity of nucleic acid-templated reactions, methods for performing stereoselective nucleic acid-templated reactions, methods of selecting for reaction products resulting from nucleic acid-templated synthesis, and methods of identifying new chemical reactions based on nucleic acid-templated synthesis. | 08-04-2011 |
20110201506 | Methods of Primer Extension Using Porous Particle Supports - The invention provides particle compositions having applications in nucleic acid analysis. Nucleic acid polymer particles of the invention allow polynucleotides to be attached throughout their volumes for higher loading capacities than those achievable solely with surface attachment. In one aspect, nucleic acid polymer particles of the invention comprise polyacrylamide particles with uniform size distributions having low coefficients of variations, which result in reduced particle-to-particle variation in analytical assays. Such particle compositions are used in various amplification reactions to make amplicon libraries from nucleic acid fragment libraries. | 08-18-2011 |
20110212842 | METHOD FOR SCREENING LIGAND - The present invention provides a method for screening for a ligand having an affinity for a target substance and having readiness for conformational change forming a desired conformation upon binding to a target substance. The method includes the steps of (a) contacting a first mixture of candidate ligands with a carrier, followed by separating and collecting, as a second mixture of candidate ligands, a mixture of free candidate ligands not bound to the carrier, (b) contacting the second mixture of candidate ligands with the target substance, and (c) contacting the carrier with a solution containing the target substance and the mixture of candidate ligands obtained in step (b), and then separating and enriching a ligand, at least a part of which forms the particular conformation. | 09-01-2011 |
20110263434 | SELECTIVE ENRICHMENT OF CPG ISLANDS - The present invention provides compositions and methods for selectively enriching genomic CpG island (CGI)- and other epigenetically informative CG-rich polynucleotide targets. The method involves co-incubation of denatured or partially denatured polynucleotide fragments containing the CGI- or CG-targeted region(s) of interest with an oligonucleotide capture pool collectively designed to selectively target CGIs. The oligonucleotide capture pool includes a plurality of different oligonucleotides, each oligonucleotide coupled to a capture tag, whereby the oligonucleotide includes a CpG target sequence restricted to 4 to 10 bases. Upon binding, capture oligonucleotides bound to the target fragments are enriched by separating the bound fragments from the unbound fragments. The enriched fragments may be subjected to further analyses, including bisulfite sequencing to generate a methylation profile at the single nucleotide level. | 10-27-2011 |
20110306503 | TEMPLATE-DEPENDENT NUCLEIC ACID POLYMERIZATION USING OLIGONUCLEOTIDE TRIPHOSPHATES BUILDING BLOCKS - A novel use of a template-dependent polymerase. The novel use is effected by employing the template-dependent polymerase for incorporating at least one oligonucleotide triphosphate onto a nascent oligonucleotide-3′-OH in a template-dependent manner. | 12-15-2011 |
20120015819 | MIXTURE OF AT LEAST TWO FUSION PROTEINS, THE PRODUCTION THEREOF AND THE USE OF THE SAME - The present invention concerns a protein mixture comprising at least a first fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence, which effects that the fusion protein upon expression in a bacterium is translocated through the cytoplasmic membrane in an essentially unfolded state and at least a second fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence which effects that the fusion protein is translocated through the cytoplasmic membrane upon expression in a bacterium in an essentially folded state, wherein the interaction domain of the first protein can bind to those of the second protein. | 01-19-2012 |
20120015820 | METHODS AND COMPOSITIONS FOR POLYPEPTIDE ENGINEERING - Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed. | 01-19-2012 |
20120028811 | DEVICE FOR RAPID IDENTIFICATION OF NUCLEIC ACIDS FOR BINDING TO SPECIFIC CHEMICAL TARGETS - The present invention relates to microfluidic chips and their use in SELEX. The microfluidic chip preferably includes a reaction chamber that contains a high surface area material that contains target. One preferred high surface area material is a sol-gel derived material. Methods of making the microfluidic chips are described herein, as are uses of these devices to select aptamers against the target. | 02-02-2012 |
20120028812 | METHOD FOR PRODUCING SECOND-GENERATION LIBRARY - The present invention relates to a method for generating a second-generation library. In a first step, a library of encoded molecules associated with an identifier nucleic acid comprising codons identifying chemical entities that have participated in the formation of the encoded molecule is provided. In a second step, the library is partitioned and encoded molecules having a certain property are selected. Codons of identifiers of selected encoded molecules are subsequently identified, and a second-generation library is prepared using at least some of the chemical entities coded for by the identified codons. The new focussed library may be used for another partition step to select encoded molecules with a certain property. | 02-02-2012 |
20120046175 | METHODS AND SYSTEMS FOR SOLUTION BASED SEQUENCE ENRICHMENT - The present invention provides methods and systems for the capture and enrichment of target nucleic acids and analysis of the enriched target nucleic acids. In particular, the present invention provides for the enrichment of targeted sequences in a solution based format. | 02-23-2012 |
20120115734 | IN SILICO PREDICTION OF HIGH EXPRESSION GENE COMBINATIONS AND OTHER COMBINATIONS OF BIOLOGICAL COMPONENTS - Various systems and methods for selecting candidate biological components and/or combinations of biological components that affect a biological process are described. For example, a computing device may use a computer model to simulate the biological process and predict a phenotypic outcome. In this manner, the impact of candidate components and combinations may be determined using the computer model. The computing device may determine optimal characteristics such as expression levels of biological components that result in a desirable phenotypic outcome of the biological process as predicted by the computer model. The computing device may perform sensitivity analysis around the optimal characteristics. The sensitivity analysis may be used to determine whether the candidate combinations are robust across a range of the optimal characteristics. The computing device may select various candidate components and combinations based on the sensitivity analysis and the predicted phenotypic outcome. | 05-10-2012 |
20120129702 | Structure-Based Selection and Affinity Maturation of Antibody Library - The present invention provides a structure-based methodology for efficiently generating and screening a library of recombinant antibodies for optimized antibodies with desirable functions, such as higher binding affinity or low immunogenicity. In one embodiment, a method is provided for constructing a library of antibody sequences based on a three dimensional structure of a lead antibody. The method comprises: providing a lead structural template comprising the amino acid sequence of the variable region of the heavy chain (V | 05-24-2012 |
20120165201 | SIMULTANEOUS, INTEGRATED SELECTION AND EVOLUTION OF ANTIBODY/PROTEIN PERFORMANCE AND EXPRESSION IN PRODUCTION HOSTS - The present disclosure provides methods of integrating therapeutic protein and antibody generation and/or selection, evolution and expression in a eukaryotic host for manufacturing in a single system. Therapeutic proteins, including antibodies, are generated, optimized and manufactured in the same eukaryotic host system. The disclosed system of Comprehensive Integrated Antibody Optimization (CIAO!™) allows for simultaneous evolution of protein performance and expression optimization. | 06-28-2012 |
20120172235 | PEPTIDE LIBRARIES - The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c). | 07-05-2012 |
20120172236 | Selection and Enrichment of Proteins Using In Vitro Compartmentalization - Compositions and methods are provided for selection and enrichment of a target gene from a library of polynucleotide sequences such as might be formed from a genome or by random mutagenesis of a genetic sequence. The selection and enrichment occurs in aqueous droplets formed in an emulsion that compartmentalize individual polynucleotides from the library or a plurality of polynucleotides that may include polynucleotides not derived from the library, transcription and translation reagents and optionally additional chemical and enzyme reagents. The selection and enrichment method utilizes a polynucleotide adaptor which when ligated to the polynucleotide fragment enables amplification to occur in the presence of an adaptor specific primer. | 07-05-2012 |
20120208704 | UNIVERSAL FIBRONECTIN TYPE III BOTTOM-SIDE BINDING DOMAIN LIBRARIES - The invention pertains to a natural-variant combinatorial library of fibronectin Type 3 domain (Fn3) polypeptides useful in screening for the presence of one or more polypeptides having a selected binding or enzymatic activity. The library polypeptides include (a) regions A, AB, B, C, CD, D, E, EF, F, and G having wildtype amino acid sequences of a selected native fibronectin Type 3 polypeptide or polypeptides, and (b) loop regions AB, CD, and EF having selected lengths (Bottom Loops). The Fn3 may also have loop regions BC, DE, and FG having wildtype amino acid sequences, having selected lengths, or mutagenized amino acid sequences (Top Loops). | 08-16-2012 |
20120245036 | SIMULTANEOUS, INTEGRATED SELECTION AND EVOLUTION OF ANTIBODY/PROTEIN PERFORMANCE AND EXPRESSION IN PRODUCTION HOSTS - The present disclosure provides methods of integrating therapeutic protein and antibody generation and/or selection, evolution and expression in a eukaryotic host for manufacturing in a single system. Therapeutic proteins, including antibodies, are generated, optimized and manufactured in the same eukaryotic host system. The disclosed system of Comprehensive Integrated Antibody Optimization (CIAO!™) allows for simultaneous evolution of protein performance and expression optimization. | 09-27-2012 |
20120252681 | EVOLUTION OF WHOLE CELLS AND ORGANISMS BY RECURSIVE SEQUENCE RECOMBINATION - The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites. | 10-04-2012 |
20120258865 | MIRAC PROTEINS - This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures. | 10-11-2012 |
20120264616 | LENTIVIRAL-BASED VECTOR AND ITS USE IN DIRECTED EVOLUTION OF GENOMIC REGIONS, GENES AND POLYNUCLEOTIDES - The present invention concerns a method of directing evolution of a target polynucleotide of interest for obtaining variants of this target polynucleotide, as well as a method to generate genetic variability by preparing a cell library. This invention also relates to a method to isolate or to screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells, and to identify theses polynucleotide variants or protein variants responsible for this phenotype. | 10-18-2012 |
20120295793 | METHODS OF GENERATING MODIFIED POLYNUCLEOTIDE LIBRARIES AND METHODS OF USING THE SAME FOR DIRECTED PROTEIN EVOLUTION - The invention provides for methods of generating modified polynucleotide libraries by inserting and/or deleting at least three nucleotide residues in polynucleotide sequences. Theses methods may be used with other methods of gene modification such as gene shuffling. The invention further provides methods of directed molecular evolution using the modified polynucleotide libraries produced by these methods. | 11-22-2012 |
20120316071 | METHODS FOR AFFINITY MATURATION-BASED ANTIBODY OPTIMIZATION - Provided herein is a rational method of affinity maturation to evolve the activity of an antibody or portion thereof based on the structure/affinity or activity relationship of an antibody. The resulting affinity matured antibodies exhibit improved or optimized binding affinity for a target antigen. | 12-13-2012 |
20130005581 | STRUCTURAL NUCLEIC ACID GUIDED CHEMICAL SYNTHESIS - Disclosed is a composition comprising the nucleic acid and a chemical compound, said composition forming a star structure defining 3 or more stems extending from a reaction center. The stems are formed by a nucleic acid duplex and the chemical compound has been formed in the reaction center as the reaction product of 3 or more chemical groups. The advantage of the composition is that a close proximity is provided between the chemical groups in the reaction center, thereby promoting a reaction. The invention also relates to a method for preparation of the composition. The advantage of the method is that it does not require the pre-synthesis of a large number of templates and that it is not dependent upon codon/anti-codon recognition for an encoded molecule to be formed. | 01-03-2013 |
20130005582 | PREPARATION OF RESTRICTION ENDONUCLEASES IN IVCS USING FRET AND FACS SELECTION - Method of preparation of restriction endonucleases, particularly those exhibiting the desired sequential specificity consists in that a fluorescence-marked DNA probe is used for screening a library of mutants, preferably in IVC format, and/or using other high-performance screening (HTS) technique, which is attained through expression of proteins included in the library of mutants in a cell-free system in the presence and by means of the DNA probe, and proteins thus obtained, resulting from expression of clones from the library, degrade the DNA probe, if their substrate specificity matches the searched one, the degradation of the DNA probe being detected as a disappearance of the FRET phenomenon between fluorescence markers included in the probe, and then microcompartments in which the FRET phenomenon ceases to occur, are separated from the remaining ones using Fluorescence Activated Cell Sorter (FACS) and/or other equipment for HTS analysis, and then DNA coding clones capable of degrading the probe are amplified using polymerase chain reaction (PCR) technique and are used as a basis for construction of the subsequent library of mutants, which is searched during the subsequent round of screening, according to the scheme mentioned above, and the subsequent rounds of screening are carried out until the enzyme having the desired properties is obtained. | 01-03-2013 |
20130029850 | Competitive Differential Screening - The invention is drawn to a novel method useful for screening. In particular, the present invention provides methods for competitive differential screening. In some preferred embodiments, the present invention provides methods for competitive differential screening that facilitate the identification of tight binders. In some preferred embodiments, the agents used in the methods of the present invention comprise tight and weak binders. In other embodiments, the present invention provides methods that utilize competitive binders that recognize and bind targets, but with binding that is less strong than that of binders of interest. | 01-31-2013 |
20130040823 | METHOD FOR THE SYNTHESIS OF A BIFUNCTIONAL COMPLEX - Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part, wherein a nascent bifuntional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site is using one or more enzymes. | 02-14-2013 |
20130045871 | ENGINEERING CORRECTLY FOLDED ANTIBODIES USING INNER MEMBRANE DISPLAY OF TWIN-ARGININE TRANSLOCATION INTERMEDIATES - The present invention provides systems, vectors and methods for isolation of enhanced ligand-binding proteins from combinatorial libraries displayed on the inner membrane of a host cell. | 02-21-2013 |
20130059732 | AAV CAPSID PROTEINS FOR NUCLEIC ACID TRANSFER - Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided. | 03-07-2013 |
20130085072 | RECOMBINANT RENEWABLE POLYCLONAL ANTIBODIES - Described herein are methods that combine phage and yeast display to create polyclonal antibodies that are renewable, and when amplified over 100 million fold, maintain diversity without loss of representation of any of the antibodies present. The antibody representation remains essentially constant, as confirmed by deep sequencing. The provided methods allow generation, use and propagation of polyclonal antibodies, without concern that representation is lost. Furthermore, because the derivation of the polyclonal pool is carried out in vitro using phage and yeast display, it is possible in various embodiments to eliminate reactivities that are considered undesirable. Additionally, the polyclonal pool can be enriched for higher affinity antibodies. | 04-04-2013 |
20130090246 | METHOD OF GENERATING GENE MOSAICS - The invention relates to a method for generating a gene mosaic by somatic in vivo recombination, comprising: e) in a single step procedure (vii) transforming a cell with at least one gene A having a sequence homology of less than 99.5% to another gene to be recombined that is an integral part of the cell genome or presented in the framework of a genetic construct, (viii) recombining said genes, (ix) generating a gene mosaic of the genes at an integration site of a target genome, wherein said at least one gene A has a single flanking target sequence either at the 5′ end or 3′ end anchoring to the 5′ or 3′ end of said integration site, and f) selecting clones comprising the gene mosaic, as well as a method of producing a diversity of gene mosaics and gene assembly. | 04-11-2013 |
20130116125 | NOVEL METHODS OF PROTEIN EVOLUTION - The present invention is relevant to proteins and novel methods of protein evolution. The present invention further relates to methods of identifying and mapping mutant polypeptides formed from, or based upon, a template polypeptide. | 05-09-2013 |
20130137582 | QUANTITATIVE PCR-BASED METHOD TO PREDICT THE EFFICIENCY OF TARGET ENRICHMENT FOR NEXT-GENERATION SEQUENCING USING REPETITIVE DNA ELEMENTS (LINES/SINES) AS NEGATIVE CONTROLS - A method for determining an efficiency of target enrichment from a DNA library, includes: adding a negative control sequence and a positive control sequence to the DNA library, or picking a negative control sequence and/or a positive control sequence from the library; determining a pre-capture amount of the negative control sequence and a pre-capture amount of the positive control sequence; performing enrichment of a target sequence from the DNA library using a bait sequence to produce a post-capture library; determining a post-capture amount of the negative control sequence and a post-capture amount of the positive control sequence in the post-capture library; and determining the efficiency of the target enrichment, based on the post-capture amount of the positive control sequence, the post-capture amount of the negative control sequence, the pre-capture amount of the positive control sequence, and the pre-capture amount of the negative control sequence. | 05-30-2013 |
20130178368 | IN VITRO EVOLUTION IN MICROFLUIDIC SYSTEMS - The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention. | 07-11-2013 |
20130184160 | NUCLEOTIDES AND APTAMERS CONTAINING BORONIC ACID GROUPS HAVING BIASED BINDING TO GLYCOSYLATED PROTEINS, AND USES THEREOF - The present disclosure encompasses oligonucleotide aptamers selectively binding a target glycosylated polypeptide or protein, and having biased affinity for the glycan through a boronic acid linked to a nucleosidic base of a nucleotide(s). The disclosure further encompasses methods for isolating an aptamer(s) selectively binding a target glycosylated polypeptide, where, from a population of randomized oligonucleotides that have at least one nucleotide having a boronic acid label linked to a base, is selected a first subpopulation of aptamers binding to the target glycosylated polypeptide or protein. This subpopulation is then amplified without using boronic acid-modified TTP, and amplification products not binding to a target glycosylated polypeptide or protein are selected. The second subpopulation of aptamers is then amplified using boronic acid-modified TTP to provide a population of boronic acid-modified aptamers capable of selectively binding to a glycosylation site of a target polypeptide or protein. Other aspects of the disclosure encompass methods for the use of the modified aptamers to detect glycosylated species of a polypeptide or protein. | 07-18-2013 |
20130190189 | IN VITRO SORTING METHOD - The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising of the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having a desired activity. The invention enables the in vitro evolution of nucleic acids by repeated mutagenesis and iterative applications of the method of the invention. | 07-25-2013 |
20130274112 | LIGAND SCREENING AND DISCOVERY - Disclosed is a method that includes: (i) providing a plurality of initial nucleic acid cassettes that include: a) a first coding region encoding a first immunoglobulin variable domain, b) a second coding region encoding a second immunoglobulin variable domain, and c) a ribosomal binding site disposed between the first and second coding regions for translation of the second polypeptide in a first expression system, wherein the first and second coding regions are in the same translational orientation; (ii) modifying each nucleic acid cassette of the plurality in a single reaction mixture so that it is functional in a second expression system, wherein the first and second region remain physically attached during the modifying; (iii) introducing each modified nucleic acid cassette into a mammalian cell to produce a mixture of transfected cells; and (iv) expressing each modified nucleic acid cassette in the transfected cells. | 10-17-2013 |
20130274113 | MULTIPLEX MICROFLUIDIC DEVICE FOR SELECTING NUCLEIC ACID APTAMERS, AND HIGH THROUGHPUT SELECTION METHOD FOR NUCLEIC ACID APTAMERS USING SAME - The present invention relates to a multiplex microfluidic device for selection of nucleic acid aptamers and a method for high-throughput selection of nucleic acid aptamers using the same, and more particularly to a multiplex microfluidic device (SELEX lap-on-a-chip) that uses an improved multiplex platform in place of the development of an aptamer for a single target and to a method for high throughput selection of aptamers using the same together with high-throughput sequencing. A multiplex microfluidic device according to the present invention can simultaneously detect aptamers for a plurality of targets, and it can greatly increase the screening throughput and greatly shorten the process time compared to conventional multiplex techniques. Particularly, when a process for selecting aptamers is performed using the device of the invention together with a high-throughput sequencing method, the number of target binding/elution/amplification rounds can be greatly reduced, and the process can be performed in an automated manner. Thus, the device of the invention is highly useful. | 10-17-2013 |
20130281303 | COMPREHENSIVE MONOCLONAL ANTIBODY GENERATION - The present invention relates to methods for efficiently generating recombinant monoclonal antibodies derived from B cells of a non-human host which has been immunochallenged with one or more target antigens. The methods comprise the steps of identifying and isolating B cell that bind to the antigen by FACS, and recombining and enriching for thousands of cells to create a B cell library. Related products and methods, such as methods of producing expression libraries, are also disclosed. | 10-24-2013 |
20130316910 | Peptide with Safer Secondary Structure, Peptide Library, and Production Methods for Same - An object of the invention is to provide a peptide having a stabilized secondary structure. | 11-28-2013 |
20130345064 | CONTINUOUS DIRECTED EVOLUTION - The invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided. | 12-26-2013 |
20140094373 | HIGHLY MULTIPLEX PCR METHODS AND COMPOSITIONS - The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons. | 04-03-2014 |
20140100120 | METHODS OF X-APTAMER GENERATION AND COMPOSITIONS THEREOF - Provided herein are methods for a novel bead-based next-generation “X-aptamer” selection scheme that extends aptamer technology to include X-modified bases, thus resulting in X-aptamers, at any position along the sequence because the aptamers are chemically synthesized via a split-pool scheme on individual beads. Also provides are application to a wide range of commonly used DNA modifications, including, but not limited to, monothioate and dithioate backbone substitutions. This new class of aptamer allows chemical modifications introduced to any of the bases in the aptamer sequence as well as the phosphate backbones and can be extended to other carbohydrate-based systems. | 04-10-2014 |
20140121115 | CUSTOM-MADE MEGANUCLEASE AND USE THEREOF - New rare-cutting endonucleases, also called custom-made meganucleases, which recognize and cleave a specific nucleotide sequence, derived polynucleotide sequences, recombinant vector cell, animal, or plant comprising said polynucleotide sequences, process for producing said rare-cutting endonucleases and any use thereof, more particularly, for genetic engineering, antiviral therapy and gene therapy. | 05-01-2014 |
20140200145 | METHOD OF METABOLIC EVOLUTION - The invention relates to a method for metabolic evolution of a variant of a natural small aromatic molecule product of a metabolic pathway, by somatic in vivo assembly and recombination of said metabolic pathway employing a gene mosaic of at least one gene A, which comprises a) in a single step procedure (i) transforming a cell with at least one gene A having a sequence homology of less than 99.5% to another gene to be recombined that is an integral part of the cell genome or presented in the framework of a genetic construct, (ii) recombining said genes, (iii) generating a gene mosaic of the genes at an integration site of a target genome, wherein said at least one gene A has a single flanking target sequence either at the 5′ end or 3′ end anchoring to the 5′ or 3′ end of said integration site, (iv) recombining eventual further genes of said metabolic pathway, and b) selecting clones comprising said gene mosaic and said eventual further genes capable of expressing said variant, methods of preparing a library of cells producing variants of natural small aromatic molecule products of a metabolic pathway, the libraries so produced and used to prepare said variants. | 07-17-2014 |
20140213459 | ANTIBODIES WITH IMPROVED FOLDING STABILITY - The present invention relates to methods for improving the folding stability of antibodies, to antibodies with improved folding stability, nucleic acid and vectors encoding such antibodies, and to uses of such antibodies, nucleic acid and vectors. | 07-31-2014 |
20140213460 | RNA-YY1 Interactions - Methods relating to obtaining libraries of YY1-binding long non-coding RNAs, libraries obtained thereby, and methods of use thereof. | 07-31-2014 |
20140221216 | METHODS, SYSTEMS, AND SOFTWARE FOR IDENTIFYING BIO-MOLECULES USING MODELS OF MULTIPLICATIVE FORM - The present invention provides methods for identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. More specifically, some embodiments of the present invention provide methods for building sequence-activity models comprising multiplicative terms and using the models to guide directed evolution. In some embodiments, the sequence-activity models include one or more interaction terms, each of which including an interaction coefficient representing the contribution to activity of two or more defined residues. In some embodiments, the models describe relation between protein or nucleic acid sequences and protein activities. In some embodiments, the present invention also provides methods for preparing sequence-activity models, including but not limited to stepwise addition or subtraction techniques, Bayesian regression, ensemble regression and other methods. The present invention further provides digital systems and software for performing the methods provided herein. | 08-07-2014 |
20140243208 | COMPOSITIONS AND METHODS FOR SELECTING APTAMERS - The invention encompasses compositions and methods for selecting aptamers. | 08-28-2014 |
20140243209 | METHOD FOR DETECTING PROTEIN THAT INTERACTS WITH TARGET SUBSTANCE - The present invention provides a method for detecting an interaction, which method can solve not only the problem of false negatives but also the problem of false positives. This method is a method for detecting a protein(s) that interact(s) with a target substance(s), the method comprising repeating a (1) transcription step, (2) assignment step, (3) selection step, and (4) amplification step, wherein: (a) in each of a plurality of times of preparation of a cDNA library among the initial preparation of a cDNA library and the round(s) of preparation of a cDNA library in the later amplification step(s), the cDNA library is prepared using a primer(s) having a sequence(s) specific to the time of preparation; (b) the cDNA libraries prepared using the primers having sequences specific to the times of preparation are mixed, and sequences in the cDNA library mixture are determined; (c) the determined sequences are subjected to measurement of the number(s) of molecules encoding the same candidate protein(s) for each time of preparation based on the sequence(s) specific to the time of preparation; and (d) a candidate protein(s) encoded by a molecule(s) that significantly increase(s) as the preparation rounds proceed is/are detected as the protein(s) that interact(s) with the target substance(s). | 08-28-2014 |
20140249035 | METHODS, SYSTEMS, AND SOFTWARE FOR IDENTIFYING FUNCTIONAL BIO-MOLECULES - The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods. | 09-04-2014 |
20140256557 | METHOD OF GENERATING AN OPTIMIZED, DIVERSE POPULATION OF VARIANTS - The disclosure relates to a method of generating a diverse set of variants to screen improved and novel properties within the variant population, a system for creating the diverse set of variants, and the variant peptides. | 09-11-2014 |
20140302998 | AKT-SPECIFIC CAPTURE AGENTS, COMPOSITIONS, AND METHODS OF USING AND MAKING - The present application provides stable peptide-based Akt capture agents and the use thereof as detection, diagnosis, and treatment agents. The application further provides novel methods of developing stable peptide-based capture agents, including Akt capture agents, using iterative on-bead in situ click chemistry. | 10-09-2014 |
20140302999 | METHOD FOR DETERMINATION OF PHARMACOLOGICAL PROPERTIES OF RECOMBINANT PROTEINS - The present invention is directed to a method for obtaining an in vitro pharmacological model of a recombinant protein drug in a given host. A plurality of biomolecules are selected which are known or suspected to influence pharmacology of the recombinant protein in the host via a binding interaction with the recombinant protein. The recombinant protein is contacted with each selected biomolecule and the binding kinetics parameters for each interaction are determined using a binding assay. These steps are then repeated with all selected biomolecules to produce a plurality of binding kinetics parameters for the selected biomolecules. The combined results provide an in vitro pharmacological model of the recombinant protein in the host. The in vitro pharmacological model may then be used in several applications, such as optimizing new batches of recombinant protein drugs, developing biosimilar or bio-better drug candidates. | 10-09-2014 |
20140323315 | POLYSPECIFICITY REAGENTS, METHODS FOR THEIR PREPARATION AND USE - The present invention relates, inter alia, to polyspecificity reagents, methods of making the same, and methods of using the same in, inter alia, the selection, screening, enrichment, and identification of non-polyspecific, and thus developable, polypeptides. | 10-30-2014 |
20140342918 | Method For Affinity Purification - The disclosure relates to a switchable aptamer having a high affinity for a selected target such as a virus, cell or antibody when in the presence of a binding ion and a low affinity for said target in the absence of said binding ion. The switchable aptamer may be isolated from a pool comprising a mixture of aptamers by incubating the pool with the target ligand and a binding ion to form target-aptamer complexes; separating unbound aptamer molecules from the target-aptamer complexes; contacting the target-aptamer complexes with a chelating agent having affinity for the binding ion wherein a switchable aptamer specific to said target is released from the target-aptamer complexes; and isolating the switchable aptamer released in the preceding step. | 11-20-2014 |
20140349855 | T CELL RECEPTOR DISPLAY - A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identification of high affinity TCRs. Several high affinities are disclosed. | 11-27-2014 |
20140357497 | DESIGNING PADLOCK PROBES FOR TARGETED GENOMIC SEQUENCING - Methods, systems, and computer programs for designing probes or primers for nucleic acid sequencing, generating libraries of nucleic acid sequences, and mapping genomic sequences are provided herein, | 12-04-2014 |
20150024944 | SIMULTANEOUS, INTEGRATED SELECTION AND EVOLUTION OF ANTIBODY/PROTEIN PERFORMANCE AND EXPRESSION IN PRODUCTION HOSTS - The present disclosure provides methods of integrating therapeutic protein and antibody generation and/or selection, evolution and expression in a eukaryotic host for manufacturing in a single system. Therapeutic proteins, including antibodies, are generated, optimized and manufactured in the same eukaryotic host system. The disclosed system of Comprehensive Integrated Antibody Optimization (CIAO!™) allows for simultaneous evolution of protein performance and expression optimization. | 01-22-2015 |
20150031549 | Cellular High Throughput Encapsulation for Screening or Selection - The invention relates to a method for selecting a sequence set from a library of expressed nucleic acid sequences, wherein cells are provided, each cell comprises an expressed nucleic acid sequence expressed as a target protein. The cells are encapsulated by treating them with a cationic polysaccharide and subsequently treating them with an anionic polysaccharide, yielding encapsulated cells, perforating the membrane of the encapsulated cells, yielding solubilized compartments, contacting them with a ligand to said target protein, the ligand bearing a detectable label, and selecting a subset of solubilized compartments as a function of detectable label and isolating the expressed nucleic acid sequences from the selection as a selected sequence set. | 01-29-2015 |
20150119254 | NUCLEIC ACID FRAGMENT BINDING TO TARGET PROTEIN - An object of the present invention is to develop and provide a method for efficiently producing a nucleic acid aptamer, particularly, a DNA aptamer, having higher specificity and binding activity against a target substance than those of nucleic acid aptamers obtained by conventional methods. The present invention provides a transcribable or replicable nucleic acid aptamer comprising a natural nucleotide and a non-natural nucleotide having an artificial base-pairable artificial base. The present invention also provides a method for sequencing a non-natural nucleotide-containing single-stranded nucleic acid molecule selected from a single-stranded nucleic acid library. | 04-30-2015 |
20150133305 | METHODS FOR ISOLATING A PEPTIDE METHODS FOR IDENTIFYING A PEPTIDE - The present invention is directed to methods, for example phage display assays, for bioengineering peptides that bind to individual distinct nucleotides. Also provided are peptides engineered by such methods. Specifically, cyclic peptides that bind individual distinct nucleotides are provided herein. | 05-14-2015 |
20150133306 | METHODS OF EVOLUTIONARY SYNTHESIS INCLUDING EMBODIED CHEMICAL SYNTHESES - The invention provides a method for preparing a compound or a product having one or more characteristics that meet or exceed a user specification, the process comprising the step of selecting a first combination of chemical inputs, optionally together with physical inputs, and supplying those inputs to a reaction space, thereby to generate a first product; analysing one or more characteristics of the product generated; comparing the one or more characteristics against a user specification; using a genetic algorithm selecting a second combination of chemical inputs, optionally together with physical inputs, wherein the second combination differs from the first combination, and supplying those inputs to the reaction space, thereby to generate a second product; analysing one or more characteristics of the second product generated; comparing the one or more characteristics generated against the user specification; repeating the selecting and analysing steps for further individual combinations of chemical and/or physical inputs, to provide an array of products wherein the flow chemistry system operates continuously to provide the first, second and further products, thereby to identify one or more products meeting or exceeding the user specification. | 05-14-2015 |
20150133307 | AUTOMATED SCREENING OF ENZYME VARIANTS - Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided. | 05-14-2015 |
20150133308 | METHOD FOR IMPROVING REPEBODY CONTAINING REPEAT MODULES - The present invention relates to a method for improving a repebody protein comprising repeat modules and a nucleotide library encoding a repebody protein library for improving the repebody protein. More particularly, the present invention relates to a method for improving a repebody protein using a module evolution method of sequentially mutating repeat modules constituting the repebody protein, and a nucleotide library encoding a repebody protein library used to improve the protein. According to the module evolution method of the present invention, an improved repebody protein can be screened which has a high binding affinity and accordingly increased specificity and activity, and thus it is easy to express a repebody used as an inhibitor, a therapeutic agent, and an analysis means against a target substance. | 05-14-2015 |
20150148237 | Method for Generating Aptamers with Improved Off-Rates - The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods. | 05-28-2015 |
20150291952 | RNA APTAMER ISOLATION VIA DUAL-CYCLE (RAPID) SELECTION - The present invention relates to a method for selecting an aptamer for a target molecule. The method involves providing a random oligonucleotide library comprising a plurality of unique random sequence oligonucleotides; providing a target mixture comprising at least one target molecule; and subjecting the random oligonucleotide library and the target mixture to at least one round of an aptamer isolation protocol to yield at least one aptamer for the target molecule, wherein a round of the aptamer isolation protocol comprises at least one selection cycle followed by an amplification cycle. The present invention also relates to systems and devices for implementing or performing the method of the present invention. The present invention further relates to using the method to isolate aptamers for high-throughput sequencing analysis and other aptamer analysis protocols. | 10-15-2015 |
20150315566 | METHOD FOR GENERATING HIGH AFFINITY, BIVALENT BINDING AGENTS - A combined Kunkel mutagenesis and phage-display method for producing bivalent binding agents is provided. | 11-05-2015 |
20150337293 | METHOD FOR SCREENING FOR HIGH L-TRYPTOPHAN PRODUCING MICROORGANISMS USING RIBOSWITCH - A method of screening a high L-tryptophan-producing microorganism using a riboswitch is provided. More particularly, a riboswitch for screening a high L-tryptophan-producing microorganism including a tryptophan aptamer, a DNA sequence consisting of 1 to 20 nucleotides and a selectable marker gene, and a method of screening a high L-tryptophan-producing microorganism using the same are provided. The riboswitch and the method of screening a high L-tryptophan-producing microorganism using the same can be useful in selecting a strain producing a high concentration of L-tryptophan in a relatively quick and easy manner, and thus enhancing price competitiveness of tryptophan production using microorganisms. | 11-26-2015 |
20150353923 | Method for Identifying RNA Segments Bound by RNA-Binding Proteins or Ribonucleoprotein Complexes - The present invention relates to a method for identifying a binding site on an RNA transcript, wherein the binding site binds to one or more binding moieties. The method includes, among other things, introducing a photoreactive nucleoside into living cells wherein the living cells incorporate the photoreactive nucleoside into RNA transcripts during transcription thereby producing modified RNA transcripts; reverse transcribing the RNA of isolated cross-linked segments thereby generating cDNA transcripts with one mutation wherein the photoreactive nucleoside is transcribed to a mismatched deoxynucleoside; amplifying the cDNA transcripts thereby generating amplicons; and analyzing the sequences of the amplicons aligned against the reference sequence so as to identify the binding site, wherein the sequences of each amplicon having a mutation resulting from the introduction of the photoreactive nucleoside is considered to be a valid amplicon comprising at least a portion of a binding site on the RNA transcript. | 12-10-2015 |
20150368637 | ACCELERATED DIRECTED EVOLUTION OF MICROBIAL CONSORTIA FOR THE DEVELOPMENT OF DESIRABLE PLANT PHENOTYPIC TRAITS - The disclosure relates to methods for the screening, identification, and/or application of one or more microorganisms of use in imparting one or more beneficial properties to one or more plants. | 12-24-2015 |
20150368703 | PRIMER TECHNOLOGY - The present invention provides a method of nucleic acid manipulation comprising: (i) hybridizing a double stranded primer to the 3′ end of a single stranded nucleic acid template, wherein said primer comprises a double stranded region and a single stranded region, wherein the single stranded region is a 3′ overhang region and wherein the 3′ overhang region enables the double stranded primer to target and hybridize to the 3′ end of the nucleic acid template, wherein said single stranded 3′ overhang region comprises a degenerate sequence or a sequence comprising universal bases, and wherein the double stranded primer is made up of two separate strands; (ii) at least one round of polymerization using a polypeptide with 5′ to 3′ DNA polymerization activity, wherein at least the first round of polymerization comprises using a polypeptide with 5′ to 3′ DNA polymerization activity to carry out a primer extension reaction to synthesise nucleotides in a template dependent manner from the 3′ end of the single stranded region of said hybridized double stranded primer; wherein the hybridizing step (i) and at least the first primer extension reaction from the 3′ end of the single stranded region of said hybridized double stranded primer in step (ii) takes place without the formation of a phosphodiester bond between the 3′ end of the nucleic acid template and the double stranded primer of step (i). Products, kits and compositions suitable for use in such methods are also provided. | 12-24-2015 |
20150376605 | Methods and Compositions for Sample Analysis - The present disclosure relates to methods and systems for sample processing and analyzing when the total quantity of input sample is low or when a target of interest is present as a relatively minor or rare population within the overall sample. The disclosure particularly relates to analyzing nucleic acid samples, including samples where a target nucleic acid of interest is present as a relatively low proportion of the overall nucleic acids. | 12-31-2015 |
20150376606 | PROCESSES FOR DETECTING OR QUANTIFYING NUCLEIC ACIDS USING AN ARRAY OF FIXED OR IMMOBILIZED NUCLEIC ACIDS - This invention provides novel compositions and processes for analyte detection, quantification and amplification. Nucleic acid arrays and libraries of analytes are usefully incorporated into such compositions and processes. Universal detection elements, signaling entities and the like are employed to detect and if necessary or desirable, to quantify analytes. Amplification of target analytes are also provided by the compositions and processes of this invention. | 12-31-2015 |
20150376607 | AAV CAPSID PROTEINS FOR NUCLEIC ACID TRANSFER - Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided. | 12-31-2015 |
20160017317 | Methods For Selecting Microbes From A Diverse Genetically Modified Library to Detect and Optimize the Production of Metabolites - The present invention relates to genetically modified bacteria and methods of optimizing genetically modified bacteria for the production of a metabolite. | 01-21-2016 |
20160017318 | GENE SIGNATURES TO IDENTIFY MOLECULAR SUBGROUPS IN MEDULLOBLASTOMA TUMORS - Described herein are methods for determining the subgroup of medulloblastoma in a subject in need thereof. The subgroups of medulloblastoma include Group 3, Group 4, WNT and SHH. The subjects are children diagnosed with medulloblastoma or children suspected of having medulloblastoma. | 01-21-2016 |
20160017319 | Method of screening cell clones - A method of screening cell clones expressing a high yield of a polypeptide of interest is provided. The method employs the consecutive use of fluorescence activated cell sorting followed by colony picking based selection of cell clones with high expression rates and high proliferation rates. Furthermore, the invention pertains to a method of producing a polypeptide of interest using cells obtained by the described screening method. | 01-21-2016 |
20160033504 | PROTOCOL FOR IDENTIFYING AND ISOLATING ANTIGEN-SPECIFIC B CELLS AND PRODUCING ANTIBODIES TO DESIRED ANTIGENS - Methods of identifying antigen-specific antibody-secreting and antibody-forming cells, such as antigen-specific B cells, and methods for cloning the antigen-specific antibody sequences of the antibody produced by these cells are provided. In particular, the methods include enriching B cells for antigen-specific B cells, culturing the antigen-specific B cells to generate clonal B cell populations, detecting clonal B cells that produce a single antigen-specific antibody, optionally screening the clonal B cell populations for functional activity, staining and sorting the cells to isolate the antigen-specific B cells, sequencing the nucleic acids encoding the antigen-specific antibody sequences, expressing the sequences to produce an antibody, isolating the antibody and screening the antibody for antigen recognition. The methods provide improved enrichment and selection of antigen-specific antibody-secreting and antibody-forming cells, which enhances recovery of antigen-specific antibodies. | 02-04-2016 |
20160040157 | MULTI-CHAIN EUKARYOTIC DISPLAY VECTORS AND USES THEREOF - A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets. | 02-11-2016 |
20160046928 | STRUCTURED PEPTIDE PROCESSING - The invention relates to a method for modifying one or more peptide ligands, comprising polypeptides covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of providing one or more peptide ligands, wherein the polypeptide comprises two or more reactive groups which form a covalent linkage to the molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; exposing the peptide ligands to one or more proteases; and sorting the ligands according to the extent of proteolytic cleavage. | 02-18-2016 |
20160046929 | METHODS AND COMPOSITIONS FOR IDENTIFYING A PEPTIDE HAVING AN INTERMOLECULAR INTERACTION WITH A TARGET OF INTEREST - This invention provides, in one embodiment, a recombinant virus or a recombinant virus library wherein each virus comprises a protein involved in viral attachment or infection, a polypeptide which differs by at least a single amino acid from another peptide or polypeptide in the library, and a modified cleavage site that is proximal to the peptide and the protein, wherein the cleavage site is modified such that a compound mediating cleavage has a reduced binding affinity for it as compared to a non-modified cleavage site. The invention further provides a target of interest complex comprising a protease, a target of interest involved in an intermolecular interaction, and a flexible linker that attaches the protease and target of interest. The invention further provides uses thereof, including a method for identifying a peptide which has an intermolecular interaction with a target of interest or identifying the agonistic or antagonistic feature of a peptide that has an intermolecular reaction with a target of interest. | 02-18-2016 |
20160068835 | FLEXIBLE DISPLAY METHOD - An improved method used in selecting a useful protein, peptide, peptide analog by an evolution molecule engineering is provided. A transcription-linker association-translation coupling reaction system characterized by incorporation of a template DNA library to enable a step of forming translation product/linker/mRNA complexes through transcription of a template DNA library to mRNAs, association of mRNAs with linkers, translation of mRNAs, and binding with translation products to be automatically performed in a reaction system, comprising factors necessary for transcription, factors necessary for translation, and linkers. | 03-10-2016 |
20160069894 | METHODS FOR AFFINITY MATURATION-BASED ANTIBODY OPTIMIZATION - Provided herein is a rational method of affinity maturation to evolve the activity of an antibody or portion thereof based on the structure/affinity or activity relationship of an antibody. The resulting affinity matured antibodies exhibit improved or optimized binding affinity for a target antigen. | 03-10-2016 |
20160083720 | METHOD FOR THE SYNTHESIS OF A BIFUNCTIONAL COMPLEX - Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site is using one or more enzymes. | 03-24-2016 |
20160097050 | DEVICES AND METHODS FOR DISPLAY OF ENCODED PEPTIDES, POLYPEPTIDES, AND PROTEINS ON DNA - A novel method for displaying proteins and peptides is disclosed in which individual proteins or peptides remain associated with the DNA encoding them. Proteins or peptides can be generated by in vitro translation of DNA templates, either free in solution or arrayed on a solid support, such that the proteins or peptides remain immobilized on their DNA templates. In particular, high throughput sequencing can be combined with high throughput functional characterization of encoded proteins and peptides, wherein the identity of each protein or peptide is determined by DNA sequencing, and functional studies are carried out directly on each protein or peptide while immobilized on the DNA template encoding it. The methods of the invention should find numerous applications, for example, in high throughput genetic or pharmacological screening, epitope mapping, and protein engineering and directed evolution. | 04-07-2016 |
20160102306 | High Fidelity Restriction Endonucleases - Compositions and methods are provided for enzymes with altered properties that involve a systematic approach to mutagenesis and a screening assay that permits selection of the desired proteins. Embodiments of the method are particularly suited for modifying specific properties of restriction endonucleases such as star activity. The compositions includes restriction endonucleases with reduced star activity as defined by an overall fidelity index improvement factor. | 04-14-2016 |
20160122748 | SCALABLE METHOD FOR ISOLATION AND SEQUENCE-VERIFICATION OF OLIGONUCLEOTIDES FROM COMPLEX LIBRARIES - A novel method for preparing sequence-verified oligonucleotides is disclosed. In particular, the invention relates to a simple, affordable, and scalable method that combines high-throughput mating of yeast clones, a unique selectable system for combining DNA sequences in yeast, and next-generation sequencing. This method allows sequence-verified oligonucleotides to be readily isolated from complex libraries. | 05-05-2016 |
20160122750 | ACCELERATED DIRECTED EVOLUTION OF MICROBIAL CONSORTIA FOR THE DEVELOPMENT OF DESIRABLE PLANT PHENOTYPIC TRAITS - The disclosure relates to methods for the screening, identification, and/or application of one or more microorganisms of use in imparting one or more beneficial properties to one or more plants. | 05-05-2016 |
20160130575 | SCREENING OF NUCLEIC ACID AGENTS VIA PARTICLE DISPLAY - The present disclosure provides a method for identifying one or more nucleic acid agents, e.g., aptamers, having a desired property from a mixture of candidate nucleic acid agents. The method generally includes immobilizing the mixture of candidate nucleic acid agents onto particles, wherein only a subset of the candidate nucleic acid agents are immobilized on any one of the particles, and wherein the subset is present in multiple copies. The particles are exposed to a target, and particles including candidate nucleic acid agents having the desired property are isolated. In this way, one or more nucleic acid agents having the desired property may be identified. Related compositions and nucleic acid agents identified as having one or more desired properties are also provided. | 05-12-2016 |
20160132639 | DESIGN AND CONSTRUCTION OF DIVERSE SYNTHETIC PEPTIDE AND POLYPEPTIDE LIBRARIES - The present invention concerns the design and construction of diverse peptide and polypeptide libraries. In particular, the invention concerns methods of analytical database design for creating datasets using multiple relevant parameters as filters, and methods for generating sequence diversity by directed multisyntheses oligonucleotide synthesis. The present methods enable the reduction of large complex annotated databases to simpler datasets of related sequences, based upon relevant single or multiple key parameters that can be individually directly defined. The methods further enable the creation of diverse libraries based on this approach, using multisynthetic collections of discrete and degenerate oligonucleotides to capture the diverse collection of sequences, or portions thereof. | 05-12-2016 |
20160138063 | METHDS AND COMPOSITIONS FOR REPLICATION OF THREOSE NUCLEIC ACIDS - Methods and compositions for replication of threose nucleic acids (TNAs) are described. The described methods include a method for transcribing a DNA template into a TNA, and a method for reverse transcribing a threose nucleic acid into a cDNA. | 05-19-2016 |
20160145604 | An Integrated System for Library Construction, Affinity Binder Screening and Expression Thereof - A recombinant polynucleotide suitable for use in a display vector is provided. The recombinant polynucleotide includes from 5′ to 3′: a first nucleic acid sequence (or insert) encoding an amino acid sequence to be displayed on a surface; a first pre-selected restriction site; a second nucleic acid sequence encoding a surface peptide capable of being displayed on the surface; and a second pre-selected restriction site. Corresponding display vectors that can be converted into expression vectors in a high-throughput fashion, as well as methods of use thereof, are also provided. | 05-26-2016 |
20160162632 | METHOD OF SCREENING REACTIONS OR BIOLOGICAL PATHWAYS INDUCED BY COMPOUND - Provided is a method of screening biochemical reactions induced by a compound or biological pathways induced by a compound. | 06-09-2016 |
20160177386 | CALIBRATION PANELS AND METHODS FOR DESIGNING THE SAME | 06-23-2016 |
20160196412 | DESIGN OF MOLECULES | 07-07-2016 |
20160201053 | Inducible mutagenesis of target genes | 07-14-2016 |
20160251703 | ALLERGEN DETECTION | 09-01-2016 |
20170233723 | Method For Affinity Purification | 08-17-2017 |
20190144920 | COMPOSITIONS AND METHODS FOR TARGETED DEPLETION, ENRICHMENT, AND PARTITIONING OF NUCLEIC ACIDS USING CRISPR/CAS SYSTEM PROTEINS | 05-16-2019 |