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1. 发明授权

US07488600B2 Compositions and methods for the identification and selection of nucleic acids and polypeptides 有权
标题翻译：用于鉴定和选择核酸和多肽的组合物和方法
公开(公告)号：US07488600B2
公开(公告)日：2009-02-10
申请号：US10960453
申请日：2004-10-07
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C12N15/01 , C12N15/09 , C12N15/11 , C12P19/34
CPC分类号： C12N15/1034 , C12N15/1062 , G01N33/58 , G01N33/6845 , G01N2458/10
摘要： This invention relates generally to systems and methods for identifying and selecting, desired proteins or nucleic acid molecules by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties. Modified mRNAs operable to crosslink to tRNAs are also provided. Methods of producing a psoralen monoadduct or a crosslink are also provided.
摘要翻译：本发明一般涉及通过将mRNA与已知或未知序列连接到其翻译的蛋白质以形成同源对来鉴定和选择所需蛋白质或核酸分子的系统和方法。基于蛋白质或核酸的所需性质选择同源对。该方法还包括通过扩增所选择的同源对的核酸部分，引入核酸的变异，翻译核酸，将核酸连接到其蛋白质以形成第二个同源物，从而演化期望的蛋白质或核酸分子并且基于所需的属性重新选择该同源对。还提供了可操作以交联至tRNA的修饰的mRNA。还提供了补骨脂素单加成物或交联剂的制备方法。

2. 发明公开

US20240016927A1 MODULAR TARGETED THERAPEUTIC AGENTS AND METHODS OF MAKING SAME 审中-公开
公开(公告)号：US20240016927A1
公开(公告)日：2024-01-18
申请号：US18306189
申请日：2023-04-24
申请人： PROTEONOVA, INC.
发明人： Richard B. Williams , Robert Guerrero
IPC分类号： A61K39/395 , C12N15/10 , G01N33/68 , G01N33/531 , C07K16/30 , C12N15/62
CPC分类号： A61K39/395 , C12N15/1062 , G01N33/6845 , G01N33/531 , C07K16/30 , C12N15/62 , C12N15/1068 , C12P19/34
摘要： Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

3. 发明授权

US07410761B2 System for rapid identification and selection of nucleic acids and polypeptides, and method thereof 有权
标题翻译：用于快速鉴定和选择核酸和多肽的系统及其方法
公开(公告)号：US07410761B2
公开(公告)日：2008-08-12
申请号：US10847087
申请日：2004-05-17
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12N15/1034 , C12N15/1062
摘要： This invention relates generally to systems and methods for identifying and selecting, desired proteins or nucleic acid molecules by linking mRNA, with known or unknown sequences, to its translated protein to form a cognate pair. The cognate pair is selected based upon desired properties of the protein or the nucleic acid. This method also includes the evolution of a desired protein or nucleic acid molecule by amplifying the nucleic acid portion of the selected cognate pair, introducing variation into the nucleic acid, translating the nucleic acid, attaching the nucleic acid to its protein to form a second cognate pair, and re-selecting this cognate pair based upon desired properties. Modified MRNAs operable to crosslink to tRNAs are also provided. Methods of producing a psoralen monoadduct or a crosslink are also provided.
摘要翻译：本发明一般涉及通过将mRNA与已知或未知序列连接到其翻译的蛋白质以形成同源对来鉴定和选择所需蛋白质或核酸分子的系统和方法。基于蛋白质或核酸的所需性质选择同源对。该方法还包括通过扩增所选择的同源对的核酸部分，引入核酸的变异，翻译核酸，将核酸连接到其蛋白质以形成第二个同源物，从而演化期望的蛋白质或核酸分子并且基于所需的属性重新选择该同源对。还提供了可操作地与tRNA交联的修饰MRNA。还提供了补骨脂素单加成物或交联剂的制备方法。

4. 发明授权

US11633474B2 Modular targeted therapeutic agents and methods of making same 有权
公开(公告)号：US11633474B2
公开(公告)日：2023-04-25
申请号：US16231099
申请日：2018-12-21
申请人： PROTEONOVA, INC.
发明人： Richard B. Williams , Robert Guerrero
IPC分类号： C12N15/10 , G01N33/531 , C12N15/62 , C12P19/34 , C07K14/00 , A61K39/395 , G01N33/68 , C07K16/30 , C40B30/04
摘要： Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

5. 发明授权

US09193795B2 Method for making targeted therapeutic agents 有权
标题翻译：靶向治疗剂的制备方法
公开(公告)号：US09193795B2
公开(公告)日：2015-11-24
申请号：US13016576
申请日：2011-01-28
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： C07K14/00 , C07K16/30 , G01N33/531 , G01N33/68
CPC分类号： C07K16/30 , C07K14/00 , C07K2319/30 , G01N33/531 , G01N33/6845
摘要： Provided herein are methods and kits for making a targeted therapeutic for treating a disease or condition. The therapeutic agents can be targeted to patient-specific disease markers. In one of these methods, the method includes obtaining a biological sample from a patient having the disease or condition, or who is at risk for developing the disease or condition. In this particular method, the sample includes a population of diseased cells, screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent. Some of the methods further include preparing a library with proteins linked to their cognate mRNAs. In certain of these methods, the preparation of the library includes providing at least two candidate mRNA molecules in which each of the mRNA molecules includes a cross-linker, translating at least two of the candidate mRNA molecules to generate at least one translated protein, and linking at least one of the candidate mRNA molecules to its corresponding translated protein via the cross-linker to form at least one cognate pair.
摘要翻译：本文提供了用于制备用于治疗疾病或病症的靶向治疗剂的方法和试剂盒。治疗剂可以靶向患者特异性疾病标记物。在这些方法之一中，该方法包括从具有疾病或病症的患者或患有发展疾病或病症风险的患者获得生物样品。在该特定方法中，样品包括患病细胞群，筛选包含与其同源mRNA相连的蛋白质的文库，以鉴定结合病变细胞的mRNA-蛋白质对，从鉴定的mRNA-蛋白质对分离一种或多种蛋白质，并将分离的蛋白质与治疗剂缀合。一些方法还包括用与其同源mRNA相连的蛋白质制备文库。在这些方法的某些中，文库的制备包括提供至少两个候选mRNA分子，其中每个mRNA分子包括交联剂，翻译候选mRNA分子中的至少两个以产生至少一个翻译的蛋白质，以及通过交联剂将候选mRNA分子中的至少一种与其相应的翻译蛋白连接以形成至少一个同源对。

6. 发明授权

US09080256B2 Generation of library of soluble random polypeptides linked to mRNA 有权
标题翻译：生成与mRNA连接的可溶性随机多肽的文库
公开(公告)号：US09080256B2
公开(公告)日：2015-07-14
申请号：US12525437
申请日：2008-02-12
申请人： Richard B Williams
发明人： Richard B Williams
IPC分类号： C40B50/06 , C40B40/02 , C07K14/00 , C12N15/10 , C40B10/00 , C40B40/08
CPC分类号： C40B40/02 , C07K14/003 , C12N15/1037 , C12N15/1062 , C12N15/1075 , C40B10/00 , C40B40/08 , C40B50/06
摘要： Methods and compositions are provided for producing libraries of soluble random polypeptides. In the methods, the fraction of hydrophilic residues in the polypeptide is controlled so as to maintain the solubility of the polypeptide constructs.
摘要翻译：提供了用于生产可溶性随机多肽文库的方法和组合物。在该方法中，控制多肽中亲水残基的分数，以维持多肽构建体的溶解度。

7. 发明授权

US10206998B2 Modular targeted therapeutic agents and methods of making same 有权
公开(公告)号：US10206998B2
公开(公告)日：2019-02-19
申请号：US13791615
申请日：2013-03-08
申请人： Proteonova, Inc.
发明人： Richard B Williams , Robert Guerrero
IPC分类号： C12N15/10 , A61K39/395 , G01N33/531 , G01N33/68 , C40B30/04 , C12P19/34
摘要： Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

8. 发明申请

US20130129769A1 METHOD FOR MAKING TARGETED THERAPEUTIC AGENTS DIRECTED TO SOLUBLE TARGETS 审中-公开
标题翻译：制造针对可溶性目标的针对性治疗药物的方法
公开(公告)号：US20130129769A1
公开(公告)日：2013-05-23
申请号：US13738861
申请日：2013-01-10
申请人： PROTEONOVA, INC.
发明人： Richard B. Williams , Robert Guerrero
IPC分类号： A61K39/00 , C12N15/10
CPC分类号： C12P19/34 , C12N15/1068 , C12N15/1075
摘要： Provided herein are methods for making targeted therapeutics that target soluble agents such as toxins, venoms, and factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments the targeted therapeutics comprise a portion that interacts with a soluble agent of interest and a second portion that interacts with a subject's immune system, which enables treatment of a patient for exposure to the soluble agent.
摘要翻译：本文提供了制备靶向治疗剂的方法，其靶向可溶性试剂，例如毒素，毒液和改变生理生物学途径的因子，以及使用这些治疗剂治疗患者或患者群体以减少，消除或灭活有害可溶性物质的方法，已经暴露了这样的患者或患者群体。在几个实施方案中，靶向治疗剂包含与感兴趣的可溶性药物相互作用的部分和与受试者的免疫系统相互作用的第二部分，其能够治疗患者暴露于可溶性试剂。

9. 发明申请

US20110212119A1 METHODS FOR MAKING HIV VACCINES AND RELATED COMPOSITIONS 审中-公开
标题翻译：制备HIV疫苗的方法及相关成分
公开(公告)号：US20110212119A1
公开(公告)日：2011-09-01
申请号：US13126935
申请日：2009-10-22
申请人： Richard B. Williams
发明人： Richard B. Williams
IPC分类号： A61K39/385 , C40B30/04 , A61P31/18
CPC分类号： C12N15/1062 , A61K39/0005 , A61K39/12 , A61K39/21 , A61K2039/54 , A61K2039/55555 , C12N2740/16034 , G01N33/56988 , G01N33/6854 , G01N2333/162 , G01N2333/70514 , G01N2500/04
摘要： Provided herein are methods and kits for making a targeted therapeutic for prevent and treating HIV infection. In one of these methods, the method includes preparing a library of soluble peptides, and screening the library for proteins that bind to the region of CD4 that binds gp120. In this particular method, these proteins are used as the antigen to make the HIV vaccine.
摘要翻译：本文提供了用于制备预防和治疗HIV感染的靶向治疗剂的方法和试剂盒。在这些方法之一中，该方法包括制备可溶性肽文库，并筛选文库以结合结合gp120的CD4区域的蛋白质。在这种特定的方法中，使用这些蛋白质作为抗原来制备HIV疫苗。

10. 发明申请

US20100113302A1 GENERATION OF LIBRARY OF SOLUBLE RANDOM POLYPEPTIDES LINKED TO mRNA 有权
标题翻译：可溶性随机多肽连接到mRNA的库的生成
公开(公告)号：US20100113302A1
公开(公告)日：2010-05-06
申请号：US12525437
申请日：2008-02-12
申请人： Richard B Williams
发明人： Richard B Williams
IPC分类号： C40B40/02 , C40B40/06 , C40B50/10
CPC分类号： C40B40/02 , C07K14/003 , C12N15/1037 , C12N15/1062 , C12N15/1075 , C40B10/00 , C40B40/08 , C40B50/06
摘要： Methods and compositions are provided for producing libraries of soluble random polypeptides. In the methods, the fraction of hydrophilic residues in the polypeptide is controlled so as to maintain the solubility of the polypeptide constructs.
摘要翻译：提供了用于生产可溶性随机多肽文库的方法和组合物。在该方法中，控制多肽中亲水残基的分数，以维持多肽构建体的溶解度。

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