| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 201 | Graphic design of combinatorial material libraries | US09420334 | 1999-10-18 | US07199809B1 | 2007-04-03 | Steven D. Lacy; Eric W. McFarland; Adam L. Safir; Stephen J. Turner; Lynn Van Erden; Pei Wang |
| Computer-implemented methods, programs and apparatus for generating a library design for a combinatorial library of materials. A library design includes a set of sources representing components to be used in preparing the combinatorial library, destinations replying arrangements of cells and mappings, defining one or more distribution patterns for assigning components to cells in the destination arrangement or arrangements. Mappings include gradients and sets of user-defined equations, and are used to calculate the amount of on components to be assigned to a cell or cells in an arrangement. A library design can also include one or more process parameters defined to vary over time or across a plurality of destination cells. The invention outputs a data file defining the library design, including electronic data representing the sources, the destinations and the mapping, in a format suitable for implementing manually or using automated material handling apparatus. | ||||||
| 202 | Method for selecting an optimally diverse library of small molecules based on validated molecular structural descriptors | US09776708 | 2001-02-05 | US07184893B2 | 2007-02-27 | Richard D. Cramer; Robert D. Clark |
| The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets. By the appropriate application of validated metrics, the method of this invention selects a subset of a combinatorial accessible chemical universe such that the molecules of the subset are representative of all the diversity present in the universe and yet do not contain multiple members which represent the same diversity (oversample). The use of the neighborhood definition of a validated metric may also be used to combine (without oversampling the same diversity) any number of combinatorial screening libraries. | ||||||
| 203 | Virtual library searchable for possible combinatorially derived product molecules having desired properties without the necessity of generating product structures | US09866543 | 2001-05-25 | US07136758B2 | 2006-11-14 | David E. Patterson; Richard D. Cramer |
| The problem of how to select out of a large chemically accessible universe molecules representative of the diversity of that universe is resolved by the discovery of a method to validate molecular structural descriptors. Using the validated descriptors, optimally diverse subsets can be selected. In addition, from the universe, molecules with characteristics similar to a selected molecule can be identified. The validated descriptors also enable the generation of a huge virtual library of potential product molecules which could be formed by combinatorial arrangement of structural variations and cores. In this virtual library it is possible to search billions of possible product compounds in relatively short time frames. | ||||||
| 204 | Structure-based selection and affinity maturation of antibody library | US10153159 | 2002-05-20 | US07117096B2 | 2006-10-03 | Peizhi Luo; Mark Hsieh; Pingyu Zhong; Caili Wang |
| The present invention provides a structure-based methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as antibodies with high binding affinity and low immunogenicity in humans. 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 an amino acid sequence of the variable region of the heavy chain (VH) or light chain (VL) of a lead antibody, the lead antibody having a known three dimensional structure which is defined as a lead structural template; identifying the amino acid sequences in the CDRs of the lead antibody; selecting one of the CDRs in the VH or VL region of the lead antibody; providing an amino acid sequence that comprises at least 3 consecutive amino acid residues in the selected CDR, the selected amino acid sequence being a lead sequence; comparing the lead sequence profile with a plurality of tester protein sequences; selecting from the plurality of tester protein sequences at least two peptide segments that have at least 10% sequence identity with lead sequence, the selected peptide segments forming a hit library; determining if a member of the hit library is structurally compatible with the lead structural template using a scoring function; and selecting the members of the hit library that score equal to or better than or equal to the lead sequence. The selected members of the hit library can be expressed in vitro or in vivo to produce a library of recombinant antibodies that can be screened for novel or improved function(s) over the lead antibody. | ||||||
| 205 | COMPUTER-AIDED METHOD FOR THE PROVISION, IDENTIFICATION AND DESCRIPTION OF MOLECULES CAPABLE OF EXHIBITING A DESIRED BEHAVIOR, MORE PARTICULARLY IN THE PHARMACEUTICAL SECTOR, AND MOLECULES OBTAINED BY SAID METHOD | US09359181 | 1999-07-22 | US07024311B1 | 2006-04-04 | Gérard Grassy; Michel Kaczorek; Roger Lahana; Abdelaziz Yasri |
| The present invention is concerned with a computer-aided method for the provision, identification and description of molecules exhibiting a desired behaviour, more particularly in the pharmaceutical sector, employing a molecular modelling step, a combinatorial library building step and a step of selecting potentially useful molecules, said method including a step whereby the candidate molecules are filtered using a dynamic filter representing constraints of conformational variations which the molecules must satisfy in order to exhibit said activity. | ||||||
| 206 | Method for screening and producing compound libraries | US09989533 | 2001-11-21 | US06996473B2 | 2006-02-07 | George M. Grass; Glen D. Leesman; Daniel A. Norris; Patrick J. Sinko; John E. Wehrli |
| A secondary compound library produced by a method of screening a compound library or portion thereof by absorption is provided. The method includes a step (i) that screens a primary compound library or portion thereof having a plurality of test samples containing isolated compounds or isolated mixtures of compounds per test sample by generating an in vivo absorption profile for each of the test samples from initial dose data and from in vitro bioavailability data comprising permeability and solubility data for each of the test samples, wherein the absorption profile includes at least one of rate of absorption, extent of absorption, and concentration of a test sample. Step (ii) produces a secondary compound library that includes at least one compound from the primary compound library having a desired absorption profile. | ||||||
| 207 | Method of superposing molecular structures of compounds | US10297598 | 2001-06-13 | US06937940B2 | 2005-08-30 | Shuichi Hirono; Kazuhiko Iwase |
| With compounds for drugs, agricultural chemicals, etc., the invention provides a novel method for superposing molecular structures of those compounds. A method for superposing molecular structures of compounds characterized in that, upon superposing the molecular structures of a plurality of compounds, (1) the characteristic groups (atoms) of compounds are roughly divided into four types of hydrophobicity (aliphatic chain/ring, aromatic ring and halogen), hydrogen-bonding donor, hydrogen-bonding acceptor and hydrogen-bonding donor/acceptor, (2) a molecule of compound with large radius of inertia calculated from constituting characteristic groups (atoms) is fixed, superposition is performed among a set of characteristic groups (atoms) with the same nature between two molecules of compounds, and operations of translation and rotation are performed in its neighborhood, (3) when causing the superposition of characteristic groups (atoms) between molecules of compounds by the operations of translation and rotation in (2), a score is given depending on the combination between respective characteristic groups (atoms), (4) scores of superposition are summed up, and (5) said operations of (2) through (4) are repeated to find out an orientation that acquires the highest score value. | ||||||
| 208 | Method for selecting an optimally diverse library of small molecules based on validated molecular structural descriptors | US09776711 | 2001-02-05 | US20040215397A1 | 2004-10-28 | Richard D. Cramer; David E. Patterson |
| The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets. By the appropriate application of validated metrics, the method of this invention selects a subset of a combinatorial accessible chemical universe such that the molecules of the subset are representative of all the diversity present in the universe and yet do not contain multiple members which represent the same diversity (oversample). The use of the neighborhood definition of a validated metric may also be used to combine (without oversampling the same diversity) any number of combinatorial screening libraries. | ||||||
| 209 | SINGLE-TUBE, READY-TO-USE ASSAY KITS, AND METHODS USING SAME | US10335690 | 2003-01-02 | US20040063109A2 | 2004-04-01 | Michael W. Hunkapiller; Dennis A. Gilbert; Kenneth J. Livak; Junko Stevens; Susan K. Eddins; Michael Lucero |
| Abstract of the Disclosure An assay kit is provided that includes assay reagents stored in a single-tube container, and a data storage medium containing information about the contents of the container. Methods are provided for using the data provided with the kit to direct instruments and/or processes, for example, to control an instrument to perform amplification and/or sequencing reactions. | ||||||
| 210 | Method, system, and computer program product for encoding and building products of a virtual combinatorial library | US09956252 | 2001-09-20 | US06678619B2 | 2004-01-13 | Victor S. Lobanov; Dimitris K. Agrafiotis; Francis R. Salemme |
| The present invention provides a method, system, and computer program product for encoding and building products of a virtual combinatorial library. A chemical reaction and reagent data for forming products of the virtual combinatorial library are encoded in a computer readable form. A compiler then operates on the encoded information and generates reagent mapping data. The compiler compiles the encoded chemical reaction to genenerate computer instructions that control the operation of a processor. A compact data structure containing data is generated and stored in a memory. This data structure is then used to gain immediate access to any of the products of the virtual combinatorial library. | ||||||
| 211 | Pharmacokinetic-based drug design tool and method | US09320371 | 1999-05-26 | US06647358B2 | 2003-11-11 | George M. Grass; Glen D. Leesman; Daniel A. Norris; Patrick J. Sinko; John E. Wehrli |
| The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data. The PK tool of the invention may be provided as a computer system, as an article of manufacture in the form of a computer-readable medium, or a computer program product and the like. Subsystems and individual components of the PK tool also can be utilized and adapted in a variety of disparate applications for predicting the fate of an administered compound. The PK tool and methods of the invention can be used to screen and design compound libraries, select and design drugs, as well as predict drug efficacy in mammals from in vitro and/or in vivo data of one or more compounds of interest. The PK tool and methods of the invention also finds use in selecting, designing, and preparing drug compounds, and multi-compound drugs and drug formulations (i.e., drug delivery system) for preparation of medicaments for use in treating mammalian disorders. | ||||||
| 212 | Knowledge-based process for the development of materials | US09921929 | 2001-08-06 | US06647342B2 | 2003-11-11 | Enrique Iglesia; Laurent Kieken; Matthew Neurock |
| A method and system for the development of materials includes a high-throughput data-generation cycle, a knowledge-generation cycle, and a knowledge repository or database. The data-generation cycle generates high-quality data for the virtual and experimental evaluation of new catalytic materials. The knowledge-generation cycle generates working hypotheses, relating performance to catalyst properties, from analysis and modeling of experimental and virtual data and data from literature, from correlations generated from experimental, theoretical, and/or modeling findings, and optionally from computational chemistry modeling investigations, in order to identify better materials. | ||||||
| 213 | Optimization of crossover points for directed evolution | US10386903 | 2003-03-10 | US20030198988A1 | 2003-10-23 | Emily C. Mundorff; Sridhar Govindarajan; Claes Gustafsson; Jeremy S. Minshull |
| Methods and devices for more efficiently engineering diversity into recombinant polypeptides and/or nucleic acids are provided herein. For example, a variety of methods of selecting and/or assessing potential crossover sites in an amino acid sequence or a nucleotide sequence are provided, as well as the resulting chimeric product sequences. These methods include, e.g., consideration of structural, functional and/or statistical data in the selection and assessment of sequences and crossover sites for use in recombination. | ||||||
| 214 | Methods and apparatus for designing high-dimensional combinatorial experiments | US10024649 | 2001-12-17 | US20020152057A1 | 2002-10-17 | Youqi Wang; Marco Falcioni; Stephen J. Turner; C. Eric Ramberg |
| Computer-implemented methods, systems and apparatus, including computer program apparatus, provide techniques for designing a set of experiments to be performed with a set of resources. A plurality of experimental configurations are generated based on a set of parameters describing factors to be varied in the experiments and a set of constraints representing limitations on operations that can be performed with the set of resources. A set of experiments is defined based on a selected configuration. The constraints can be represented as patterns defining an application of a parameter to a set of one or more points of an experimental lattice. | ||||||
| 215 | Further method of creating and rapidly searching a virtual library of potential molecules using validated molecular structural descriptors | US09866543 | 2001-05-25 | US20020099526A1 | 2002-07-25 | David E. Patterson; Richard D. Cramer |
| The problem of how to select out of a large chemically accessible universe molecules representative of the diversity of that universe is resolved by the discovery of a method to validate molecular structural descriptors. Using the validated descriptors, optimally diverse subsets can be selected. In addition, from the universe, molecules with characteristics similar to a selected molecule can be identified. The validated descriptors also enable the generation of a huge virtual library of potential product molecules which could be formed by combinatorial arrangement of structural variations and cores. In this virtual library it is possible to search billions of possible product compounds in relatively short time frames. | ||||||
| 216 | Method, system, and computer program product for encoding and building products of a virtual combinatorial library | US09956252 | 2001-09-20 | US20020045991A1 | 2002-04-18 | Victor S. Lobanov; Dimitris K. Agrafiotis; Francis R. Salemme |
| The present invention provides a method, system, and computer program product for encoding and building products of a virtual combinatorial library. A chemical reaction and reagent data for forming products of the virtual combinatorial library are encoded in a computer readable form. A compiler then operates on the encoded information and generates reagent mapping data. The compiler compiles the encoded chemical reaction to genenerate computer instructions that control the operation of a processor. A compact data structure containing data is generated and stored in a memory. This data structure is then used to gain immediate access to any of the products of the virtual combinatorial library. | ||||||
| 217 | IDENTIFICATION OF GENETIC TARGETS FOR MODULATION BY OLIGONUCLEOTIDES AND GENERATION OF OLIGONUCLEOTIDES FOR GENE MODULATION | US09067638 | 1998-04-28 | US20020028923A1 | 2002-03-07 | LEX M. COWSERT; BRENDA F. BAKER; JOHN MCNEIL; SUSAN M. FREIER; HENRI M. SASMOR |
| Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A nullvirtualnull oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified. | ||||||
| 218 | Method for selecting an optimally diverse library of small molecules based on validated molecular structural descriptors | US08592132 | 1996-01-26 | US06185506B2 | 2001-02-06 | Richard D. Cramer; David E. Patterson; Robert D. Clark; Allan M. Ferguson |
| The use of biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets. By the appropriate application of validated metrics, the method of this invention selects a subset of a combinatorial accessible chemical universe such that the molecules of the subset are representative of all the diversity present in the universe and yet do not contain multiple members which represent the same diversity (oversample). The use of the neighborhood definition of a validated metric may also be used to combine (without oversampling the same diversity) any number of combinatorial screening libraries. | ||||||
| 219 | System, method, and computer program product for at least partially automatically generating chemical compounds with desired properties from a list of potential chemical compounds to synthesize | US904737 | 1997-08-01 | US5901069A | 1999-05-04 | Dimitris K. Agrafiotis; Roger F. Bone; Francis R. Salemme; Richard M. Soll |
| A computer based, iterative process for generating chemical entities with defined physical chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration. | ||||||
| 220 | Three dimensional measurement of molecular diversity | US357580 | 1994-12-13 | US5703792A | 1997-12-30 | David Chapman |
| A method and system for selecting molecules or molecular parts for screening. A base set of molecules on which chemical tests are to be performed is defined, and once defined, the base set may be extended by selecting molecules which are determined to maximize the diversity of the extended set. Diversity of a set of molecules is measured by reference to steric, electrostatic, and hydrogen bonding features of the set of 3D conformational shapes which each molecule in the set may take on. Each molecule is assigned a measure of incremental (added) diversity with respect to the base set of molecules on which chemical tests are to be performed. To do this, for each new molecule, a set of conformations is defined, and for each conformation, a measure of dissimilarity from each conformation of those molecules in the base set is defined. The molecule's measure of added diversity is responsive to a closest match between the any conformation of that molecule and any conformation of any molecule already in the base set. This measure of dissimilarity is determined by means of a continuous function minimization technique, such as gradient descent or simulated annealing. The base set may then be extended with the molecule whose measure of added diversity is greatest. | ||||||
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