| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 161 | Molecular interaction sites of interleukin-2 RNA and methods of modulating the same | US09310844 | 1999-05-12 | US06969763B1 | 2005-11-29 | David J. Ecker; Richard Griffey; Stanley T. Crooke; Ranga Sampath; Eric Swayze; Venkatraman Mohan; Steven Hofstadler; John McNeil |
| Methods for the identification of compounds which modulate, either inhibit or stimulate, biomolecules are provided. Nucleic acids, especially RNAs are preferred substrates for such modulation. The present methods are particularly powerful in that they provide novel combinations of techniques which give rise to compounds, usually “small” organic compounds, which are highly potent modulators of RNA and other biomolecular activity. In accordance with preferred aspects of the invention, very large numbers of compounds may be tested essentially simultaneously to determine whether they are likely to interact with a molecular interaction site and modulate the activity of the biomolecule. Pharmaceuticals, veterinary drugs, agricultural chemicals, industrial chemicals, research chemicals and many other beneficial compounds may be identified in accordance with embodiments of this invention. | ||||||
| 162 | Method and computer program product for designing combinatorial arrays | US09794106 | 2001-02-28 | US06671627B2 | 2003-12-30 | Dimitris K. Agrafiotis; Victor S. Lobanov; Francis Raymond Salemme |
| A greedy method for designing combinatorial arrays. An array of reagents are initially selected from a list of candidate reagents in a combinatorial library. The reagents in the array that maximize a design objective are determined in an iterative manner, by examining each variation site in the combinatorial library in a strictly alternating sequence. During each step, each candidate reagent at a given variation site is evaluated by constructing and evaluating the sub-array resulting from the systematic combination of that reagent with the selected reagents at all the other variation sites in the library. The candidate reagents at that variation site are ranked according to the fitness of their respective sub-arrays, and the reagents with the highest fitness are selected. The process is repeated for each variation site in the combinatorial library, until the fitness of the full combinatorial array can no longer be improved. | ||||||
| 163 | Method for selecting an optimally diverse library of small molecules based on validated molecular structural descriptors | US09776708 | 2001-02-05 | US20030167128A1 | 2003-09-04 | 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. | ||||||
| 164 | Pharmacokinetic-based drug design tool and method | US09320545 | 1999-05-26 | US06542858B1 | 2003-04-01 | 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. | ||||||
| 165 | Structure-based selection and affinity maturation of antibody library | US10153159 | 2002-05-20 | US20020177170A1 | 2002-11-28 | 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. | ||||||
| 166 | Method of generating chemical compounds having desired properties | US09213156 | 1998-12-17 | US06434490B1 | 2002-08-13 | 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. | ||||||
| 167 | Knowledge-based process for the development of materials | US09921929 | 2001-08-06 | US20020086791A1 | 2002-07-04 | Enrique Iglesia; Laurent Kieken; Matthew Neurock |
| A catalyst development engine for providing a rapid approach to the rational development of scalable heterogeneous catalysts and of high-performance solid materials. The catalyst development engine includes three main components: the high-throughput data generation cycle, the knowledge generation cycle, and the knowledge repository or database. The high-throughput data generation cycle rapidly generates high quality data in a high-throughput mode for the virtual and experimental evaluation of new catalytic materials and also generates data on well-characterized systems for use in the knowledge generation cycle. The knowledge generation cycle generates working hypotheses, relating performance to key catalyst properties, which guide the search for better catalysts, and generates fundamental structure-property relationships required in order to select catalysts for further experimental evaluation in the high-throughput cycle. Both cycles run concurrently with the theoretical and experimental modules highly integrated. Catalyst synthesis modules use methods such as impregnation, precipitation, and others. Catalyst evaluation is done free of transport limitations to generate kinetic data which can be used in the knowledge cycle. Such an approach accelerates development and scale-up of new materials without the impediments introduced by conventional combinatorial approaches based on randomly selected materials prepared under unrealistic and difficult to scale up conditions. | ||||||
| 168 | Method for screening and producing compound libraries | US09989533 | 2001-11-21 | US20020061540A1 | 2002-05-23 | 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. | ||||||
| 169 | PHARMACOKINETIC-BASED DRUG DESIGN TOOL AND METHOD | US09320371 | 1999-05-26 | US20020013662A1 | 2002-01-31 | 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. | ||||||
| 170 | Method and computer program product for designing combinatorial arrays | US09794106 | 2001-02-28 | US20010029026A1 | 2001-10-11 | Dimitris K. Agrafiotis; Victor S. Lobanov; Francis R. Salemme |
| A greedy method for designing combinatorial arrays. An array of reagents are initially selected from a list of candidate reagents in a combinatorial library. The reagents in the array that maximize a design objective are determined in an iterative manner, by examining each variation site in the combinatorial library in a strictly alternating sequence. During each step, each candidate reagent at a given variation site is evaluated by constructing and evaluating the sub-array resulting from the systematic combination of that reagent with the selected reagents at all the other variation sites in the library. The candidate reagents at that variation site are ranked according to the fitness of their respective sub-arrays, and the reagents with the highest fitness are selected. The process is repeated for each variation site in the combinatorial library, until the fitness of the full combinatorial array can no longer be improved. | ||||||
| 171 | Method to clone mRNAs | US09068860 | 1998-05-19 | US06261770B1 | 2001-07-17 | Peter Rolf Warthoe |
| Disclosed and claimed is a method for preparing a normalized sub-divided library of amplified cDNA fragments from the coding region of mRNAs contained in a sample. The method includes the steps of: a) subjecting the mRNA population to reverse transcription using at least one cDNA primer, thereby obtaining first strand cDNA fragments, b) synthesizing second strand cDNA complementary to the first strand cDNA fragments by use of the first strand DNA fragments as templates, thereby obtaining double stranded cDNA fragments, c) digesting the double stranded cDNA fragments with at least one restriction endonuclease, the endonuclease leaving protruding sticky ends of similar size at the termini of the DNA after digestion, thereby obtaining cleaved cDNA fragments, d) adding at least two adapter fragments containing known sequences to the cleaved cDNA fragments obtained in step c), the at least two adapter fragments being able to bind specifically to the sticky ends of the double stranded cDNA produced in step c), the one adapter fragment being able to anneal to the primer having formula I in step f), the second adapter fragment being a termination fragment introducing a block against DNA polymerization in the 5′→3′ direction setting out from said termination fragment and the termination fragment being unable to anneal to any primer of the at least two primer sets in step f) during the molecular amplification procedure, the at least two adapter fragments being ligated to the cleaved cDNA fragments obtained in step c) so as to obtain ligated cDNA fragments, e) sub-dividing the ligated cDNA fragments obtained in step d) into 4n1 pools where 1≦n1≦4, and f) subjecting each pool of ligated cDNA fragments obtained in step e) to a molecular amplification procedure so as to obtain amplified cDNA fragments, wherein is used, for an adapter fragment used in step d), a set of amplification primers having the general formula I 5′-Com-Nn1-3′ I wherein Com is a sequence complementary to at least the 5′-end of an adapter fragment which is ligated to the 3′-end of a cleaved cDNA fragment, N is A, G, T, or C, the one primer having the general formula I where n1=0, and the second primer having the general formula I where 1≦n1≦4, the second primer being capable of priming amplification of any nucleotide sequence ligated in its 3′-end to the adapter fragment complementary in its 5′-end to Com. | ||||||
| 172 | Technique for representing combinatorial chemistry libraries resulting from selective combination of synthons | US812417 | 1997-03-06 | US6061636A | 2000-05-09 | Eric Horlbeck |
| A computer-implemented method and apparatus are provided for the generation and representation of combinatorial chemical libraries produced by a series of chemical reaction stages, each stage involving a multiplicity of simultaneous chemical reactions utilizing a set of potential synthons. The disclosed method and apparatus are implemented when one or more of the potential synthons are omitted from certain reactions during one or more of the reaction stages. | ||||||
| 173 | Method and apparatus for generating and representing combinatorial chemistry libraries | US605464 | 1996-02-26 | US5880972A | 1999-03-09 | Eric G. Horlbeck |
| A method and apparatus is provided for the generation and representation of chemical libraries. More particularly, a computer-implemented method and apparatus is provided for the generation and representation of combinatorial chemistry libraries. | ||||||
| 174 | METHOD AND SYSTEM FOR DRUG VIRTUAL SCREENING AND CONSTRUCTION OF FOCUSED SCREENING LIBRARY | US15531213 | 2015-11-26 | US20180218129A1 | 2018-08-02 | Wan Kyu Kim; Yea Jee Kwon; Hae Seung Lee |
| The present invention relates to a virtual drug screening method with high prediction accuracy based on various biological activities extracted from multiple drug screening data, without using structures or structural attribute information of target proteins or compounds; an intensive screening library constructing method; and a system therefor. | ||||||
| 175 | COMPUTER-IMPLEMENTED METHOD FOR DESIGNING SYNTHETIC DNA, AND TERMINAL, SYSTEM AND COMPUTER-READABLE MEDIUM FOR THE SAME | US15849731 | 2017-12-21 | US20180173849A1 | 2018-06-21 | Eli LYONS |
| A method, comprising displaying indicia, broadcasting data, or transmitting instructions, to solicit collection of or to access data uniquely representative of, or uniquely indicating, one or more digitally-input synthetic DNA design parameters; establishing direct or indirect communication access and linkage between the terminal and either (a) a store at the terminal, or (b) the at least one remote computer(s), on which are stored, or by which access is available to receive: data representative of an entire synthetic DNA sequence of a DNA library, the synthetic DNA sequence being (remotely or at the terminal) calculated based on the one or more DNA design parameters; and data representative of an entire synthetic DNA barcode sequence that is calculated based on the calculated synthetic DNA sequence. A terminal, system and computer-readable medium are also provided. | ||||||
| 176 | Method for constructing a novel affinity peptide library for binding immunoglobulin G based on a protein affinity model of protein A | US14654731 | 2013-08-19 | US10001489B2 | 2018-06-19 | Yan Sun; Weiwei Zhao; Fufeng Liu; Qinghong Shi |
| An affinity ligand peptide library of IgG constructed on the basis of Protein A affinity model and the application of a design method thereof. According to the Molecular Mechanics—Poisson-Boltzmann surface area (MM/PBSA) method and on the basis of the known human IgG-Protein A complex structure, the hot spots of Protein A that have high affinity for human IgG are obtained analytically, and a Protein A simplified affinity model is built thereof. An affinity peptide library of IgG is constructed including heptapeptide and octapeptide structural modes. On the basis of the peptide structural modes, the types of inserted amino acids that ‘X’ residues represent are further identified using amino acid location method. Then, molecular docking and molecular dynamics simulation methods are used to screen the candidate peptides successively. Finally, the affinity peptide ligands that can effectively purify IgG are identified using affinity chromatography. | ||||||
| 177 | CANCER NEOEPITOPES | US15568487 | 2016-04-25 | US20180141998A1 | 2018-05-24 | Andrew Nguyen; Kayvan Niazi; Patrick Soon-Shiong; Shahrooz Rabizadeh; Stephen Charles Benz |
| Contemplated compositions and methods are directed to cancer neoepitopes and uses of such neoepitopes, especially to generate synthetic antibodies against neoepitopes that may then be employed in the manufacture of a therapeutic agent. Preferred therapeutic agents will comprise a synthetic antibody against a neoepitope, and most preferably in combination with a cellular or non-cellular component for use as a diagnostic or therapeutic agent. | ||||||
| 178 | COMPUTATIONAL METHODS FOR DESIGNING POLYPEPTIDE LIBRARIES | US15685611 | 2017-08-24 | US20180057961A1 | 2018-03-01 | Lior ZIMMERMAN |
| The invention relates to systems and methods for generating a polypeptide library. Specifically, the invention relates to computer-implemented systems and methods for generating a library of polypeptides, for example, antibodies. | ||||||
| 179 | Epitope focusing by variable effective antigen surface concentration | US14398084 | 2013-05-21 | US09884893B2 | 2018-02-06 | Jacob E. Glanville |
| The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition. | ||||||
| 180 | METHOD FOR RAPID DESIGN OF VALID HIGH-QUALITY PRIMERS AND PROBES FOR MULTIPLE TARGET GENES IN QPCR EXPERIMENTS | US15497244 | 2017-04-26 | US20170369934A1 | 2017-12-28 | Min Soo Kim; HYERIN KIM; JAEHYUNG KOO; Na Na Kang; KyuHyeon An |
| Disclosed is a method of designing a valid primer pair satisfying a specificity condition. The method includes searching for an identifier of a base sequence from a genetic information index based on a query language associated with a gene, searching for a candidate primer from a provided candidate primer set index to satisfy the specificity condition based on the identifier of the base sequence, filtering the candidate primer based on primer-related filtering conditions, and providing information about a primer pair satisfying the query language and the filtering conditions based on a result of the filtering. | ||||||
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