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21. 发明申请

WO2002092780A2 NOVEL ANTIGEN BINDING MOLECULES FOR THERAPEUTIC, DIAGNOSTIC, PROPHYLACTIC, ENZYMATIC, INDUSTRIAL, AND AGRICULTURAL APPLICATIONS, AND METHODS FOR GENERATING AND SCREENING THEREOF 审中-公开
标题翻译：用于治疗，诊断，预防，食用，工业和农业应用的新型抗原结合分子及其产生和筛选的方法
公开(公告)号：WO2002092780A2
公开(公告)日：2002-11-21
申请号：PCT/US2002/015767
申请日：2002-05-17
申请人： DIVERSA CORPORATION , SHORT, Jay, M.
发明人： SHORT, Jay, M.
IPC分类号： C12N
CPC分类号： C12N15/1093 , C12N15/102 , C12N15/1027 , C12N15/66
摘要： The invention is directed to methods for generating sets, or libraries, of nucleic acids encoding antigen-binding sites, such as antibodies, antibody domains or other fragments, including single and double stranded antibodies, major histocompatibility complex (MHC) molecules, T cell receptors (TCRs), and the like. This invention provides methods for generating variant antigen binding sites, e.g., antibodies and specific domains or fragments of antibodies (e.g., Fab or Fc domains), by altering template nucleic acids including by saturation mutagenesis, synthetic ligation reassembly, or a combination thereof. In one aspect, the invention provides methods for generating all human or humanized antibodies and evolving them to achieve optimized properties related to stability, duration, expression, production, enzymatic activity, affinity, avidity, localization, and other immunological properties. Polypeptides generated by these methods can be analyzed using a novel capillary array platform, which provides unprecedented ultra-high throughput screening.
摘要翻译：本发明涉及用于产生编码抗原结合位点的核酸（例如抗体，抗体结构域或其它片段，包括单链和双链抗体，主要组织相容性复合体（MHC）分子，T细胞受体（TCR）等。本发明提供了通过改变模板核酸，包括饱和诱变，合成连接重组或其组合来产生变体抗原结合位点，例如抗体和抗体的特异结构域或片段（例如，Fab或Fc结构域）的方法。一方面，本发明提供了产生所有人源化或人源化抗体并进化出来以实现与稳定性，持续时间，表达，产生，酶活性，亲和力，亲合力，定位和其他免疫学性质相关的优化性质的方法。通过这些方法产生的多肽可以使用新颖的毛细管阵列平台进行分析，提供前所未有的超高通量筛选。

22. 发明申请

WO0229032A2 WHOLE CELL ENGINEERING BY MUTAGENIZING A SUBSTANTIAL PORTION OF A STARTING GENOME, COMBINING MUTATIONS, AND OPTIONALLY REPEATING 审中-公开
标题翻译：通过将起始基因组的重要部分，组合突变和可选择重复的整体细胞工程整合
公开(公告)号：WO0229032A2
公开(公告)日：2002-04-11
申请号：PCT/US0131004
申请日：2001-10-01
申请人： DIVERSA CORP , SHORT JAY M , FU PENGCHENG , LATTERICH MARTIN , WEI JING , LEVIN MICHAEL
发明人： SHORT JAY M , FU PENGCHENG , LATTERICH MARTIN , WEI JING , LEVIN MICHAEL
IPC分类号： C12N15/10 , C12N15/82 , G01N33/534 , G01N33/68 , C12N15/00
CPC分类号： C12N15/1089 , C12N15/102 , C12N15/1027 , C12N15/1058 , C12N15/8241 , G01N33/534 , G01N33/6848 , G01N2800/52
摘要： An invention comprising cellular transformation, directed evolution, and screening methods for creating novel transgenic organisms having desirable properties. In one embodiment, this invention provides a method of generating a transgenic organism, such as a microbe or a plant, having a plurality of traits that are differentially activatable. This invention also provides a method of retooling genes and gene pathways by the introduction of regulatory sequences, such as promoters, that are operable in an intended host, this conferring operability to a novel gene pathway when it is introduced into an intended host. For example a novel man-made gene pathway, generated based on microbially-derived progenitor templates, that is operable in a plant cell. This invention also provides a method of generating novel host organisms having increased expression of desirable traits, recombinant genes, and gene products. This invention provides novel methods for determining polypeptide profiles, and protein expression variations, which methods are applicable to all sample types disclosed herein. The present invention provides methods of simultaneously identifying and quantifying individual proteins in complex protein mixtures. Additionally this invention provides methods for cellular and metabolic engineering of new and modified phenotypes by using "on-line" or "real-time" metabolic flux analysis.
摘要翻译：一种包含细胞转化，定向进化和用于产生具有所需性质的新型转基因生物的筛选方法的发明。在一个实施方案中，本发明提供了产生具有差异可激活的多种性状的转基因生物体如微生物或植物的方法。本发明还提供了通过引入可在预期宿主中操作的调节序列（例如启动子）来重新组合基因和基因途径的方法，当将其导入预期的宿主时，这赋予了新基因途径的可操作性。例如，基于微生物来源的祖细胞模板产生的新型人造基因途径，其可在植物细胞中操作。本发明还提供了产生具有所需性状，重组基因和基因产物表达增加的新型宿主生物的方法。本发明提供了用于确定多肽谱和蛋白质表达变化的新方法，该方法适用于本文公开的所有样品类型。本发明提供同时鉴定和定量复合蛋白质混合物中的各种蛋白质的方法。此外，本发明通过使用“在线”或“实时”代谢通量分析提供新的和修饰的表型的细胞和代谢工程的方法。

23. 发明申请

WO1997004077A1 SCREENING METHODS FOR ENZYMES AND ENZYME KITS 审中-公开
标题翻译：酶和酶合成酶的筛选方法
公开(公告)号：WO1997004077A1
公开(公告)日：1997-02-06
申请号：PCT/US1996011854
申请日：1996-07-17
申请人： RECOMBINANT BIOCATALYSIS, INC. , SHORT, Jay, M. , MARRS, Barry , STEIN, Jeffrey, L.
发明人： RECOMBINANT BIOCATALYSIS, INC.
IPC分类号： C12N09/00
CPC分类号： C12N15/1086 , C12N15/1034 , C12N15/1079 , C12N15/1093 , C12N15/52 , C12Q1/00
摘要： Recombinant enzyme libraries and kits where a plurality of enzymes are each characterized by different physical and/or chemical characteristics and classified by common characteristics. The characteristics are determined by screening of recombinant enzymes expressed by a DNA library produced from various microorganisms. Also disclosed is a process for identifying clones of a recombinant library which express a protein with a desired activity by screening a library of expression clones randomly produced from DNA of at least one microorganism, said screening being effected on expression products of said clones to thereby identify clones which express a protein with a desired activity. Also disclosed is a process of screening clones having DNA from an uncultivated microorganism for a specified protein activity by screening for a specified protein activity in a library of clones prepared by (i) recovering DNA from a DNA population derived from at least one uncultivated microorganism; and (ii) transforming a host with recovered DNA to produce a library of clones which is screened for the specified protein activity.
摘要翻译：重组酶文库和试剂盒，其中多个酶各自以不同的物理和/或化学特征为特征，并通过共同特征分类。通过筛选由各种微生物产生的DNA文库表达的重组酶来确定特征。还公开了通过筛选由至少一种微生物的DNA随机产生的表达克隆文库来鉴定表达具有所需活性的蛋白质的重组文库的克隆的方法，所述筛选是对所述克隆的表达产物进行鉴定，从而鉴定表达具有所需活性的蛋白质的克隆。还公开了通过筛选通过（i）从源自至少一个未培养微生物的DNA群体中回收DNA的克隆文库中筛选特定蛋白质活性来筛选具有来自未培养的微生物的具有DNA的克隆的克隆的方法，以获得特定的蛋白质活性; 和（ii）用回收的DNA转化宿主以产生筛选特定蛋白质活性的克隆文库。

24. 发明申请

WO2018129007A1 PROTEIN THERAPEUTICS FOR TREATMENT OF SENESCENT CELLS 审中-公开
公开(公告)号：WO2018129007A1
公开(公告)日：2018-07-12
申请号：PCT/US2018/012136
申请日：2018-01-03
申请人： BIOATLA LLC , SHORT, Jay M.
发明人： SHORT, Jay M.
IPC分类号： C07K16/28 , C07K14/00 , G01N33/50 , A61K47/68
摘要： Methods of generating conditionally active proteins that target senescent cells and which are conditionally active in an extracellular environment of a senescent cell. The methods include discovery methods using libraries of evolved proteins and assays employing physiological concentrations of components of bodily fluids. Also disclosed are conditionally active proteins for killing or removing senescent cells, pharmaceutical compositions employing these conditionally active proteins and methods for treatment of age-related diseases, conditions or disorders using same. The conditionally active proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety.

25. 发明申请

WO2015175375A1 CONDITIONALLY ACTIVE BIOLOGICAL PROTEINS 审中-公开
标题翻译：有条件的活性生物蛋白
公开(公告)号：WO2015175375A1
公开(公告)日：2015-11-19
申请号：PCT/US2015/030086
申请日：2015-05-11
申请人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
发明人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C12N15/09 , C12Q1/68 , C07K16/00 , C07K16/46 , C07K19/00
CPC分类号： C12N15/1058 , C07K14/475 , C07K14/52 , C07K14/54 , C07K14/575 , C07K16/00 , C07K16/28 , C07K16/46 , C07K2317/31 , C07K2317/52 , C07K2319/00 , C07K2319/30 , C12N9/00 , C12N15/09 , C12Q1/68 , G01N33/6854 , G01N2333/705
摘要： 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 some physiological conditions. For example, conditionally active biologic proteins are active in tumors, but virtually inactive at other body parts, or conditionally active antibodies capable of crossing blood-brain-barrier.
摘要翻译：本公开涉及从野生型蛋白质，特别是在某些生理条件下可逆地或不可逆地灭活的治疗性蛋白质产生条件活性生物蛋白质的方法。例如，有条件活跃的生物蛋白在肿瘤中是活性的，但在其他身体部位实际上是无活性的，或者能够穿过血脑屏障的条件活性抗体。

26. 发明申请

WO2004035729A3 ESTERASES, NUCLEIC ACIDS ENCODING THEM AND METHODS OF MAKING AND USING THEM 审中-公开
标题翻译： ESTERASES，NUCLEIC ACID ENCODING THEM AND METHODS OF MAKING AND USING THEM
公开(公告)号：WO2004035729A3
公开(公告)日：2005-08-18
申请号：PCT/US0222336
申请日：2002-07-10
申请人： DIVERSA CORP , ROBERTSON DAN , MURPHY DENNIS , REID JOHN , MAFFIA ANTHONY III , LINK STEVEN , SWANSON RONALD V , WARREN PATRICK V , LENOX ANNA , SHORT JAY M , MATHUR ERIC J
发明人： ROBERTSON DAN , MURPHY DENNIS , REID JOHN , MAFFIA ANTHONY III , LINK STEVEN , SWANSON RONALD V , WARREN PATRICK V , LENOX ANNA , SHORT JAY M , MATHUR ERIC J
IPC分类号： A61K38/00 , C12N9/16 , C12N9/18 , C12P13/04 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/55 , C12N15/63
CPC分类号： C12N9/18 , A01K2217/05 , A61K38/00 , C12N9/16 , C12P13/04
摘要： The invention is directed to enzymes having an esterase activity, including thermostable and thermotolerant esterase activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The esterase activities of the enzymes of the invention include lipase activity (in the hydrolysis of lipids), acidolysis reactions (to replace an esterified fatty acid with a free fatty acid), transesterification reactions (exchange of fatty acids between triglycerides), in ester synthesis, and ester interchange reactions. The enzymes of the invention are used in organic synthesis reactions in the manufacture of medicaments, pesticides or intermediates thereof.
摘要翻译：本发明涉及具有酯酶活性的酶，包括耐热和耐热酯酶活性，以及编码这些酶的多核苷酸，以及制备和使用这些多核苷酸和多肽。本发明的酶的酯酶活性包括脂肪酶活性（脂质水解），酸解反应（用游离脂肪酸代替酯化的脂肪酸），酯交换反应（甘油三酯之间的脂肪酸交换），酯合成和酯交换反应。本发明的酶用于制备药物，农药或其中间体的有机合成反应中。

27. 发明申请

WO03060084A9 METHODS FOR MAKING POLYNUCLEOTIDES AND PURIFYING DOUBLE-STRANDED POLYNUCLEOTIDES 审中-公开
标题翻译：制备多核苷酸并纯化双链多核苷酸的方法
公开(公告)号：WO03060084A9
公开(公告)日：2004-04-22
申请号：PCT/US0301189
申请日：2003-01-14
申请人： DIVERSA CORP , FREY GERHARD , SHORT JAY M , PARRA-GESSERT LILIAN
发明人： FREY GERHARD , SHORT JAY M , PARRA-GESSERT LILIAN
IPC分类号： A01K67/027 , B01J20/281 , C07H21/04 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/10 , C12P21/08 , C12Q1/68 , G01N30/88 , C12N
CPC分类号： C12Q1/6806 , C12Q2521/514 , C12Q2563/131
摘要： The invention provides methods for identifying and purifying double-stranded polynucleotides lacking base pair mismatches, insertion/deletion loops and/or nucleotide gaps. The invention provides libraries of nucleic acid building blocks and methods for generating any nucleic acid sequence, including synthetic genes, antisense constructs and polypeptide coding sequences. The invention provides chimeric antigen binding molecules and the nucleic acids that encode them.
摘要翻译：本发明提供了用于鉴定和纯化缺乏碱基对错配，插入/缺失环和/或核苷酸缺口的双链多核苷酸的方法。本发明提供了用于产生任何核酸序列的核酸构建体和方法的文库，所述核酸序列包括合成基因，反义构建体和多肽编码序列。本发明提供了嵌合抗原结合分子和编码它们的核酸。

28. 发明申请

WO03083054A8 AMYLASES, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR MAKING AND USING THEM 审中-公开
标题翻译：氨基酸，编码它们的核酸及其制备和使用它们的方法
公开(公告)号：WO03083054A8
公开(公告)日：2004-02-12
申请号：PCT/US0308906
申请日：2003-03-24
申请人： DIVERSA CORP , CALLEN WALTER , RICHARDSON TOBY , FREY GERHARD , MILLER CARL A , KAZAOKA MARTIN , MATHUR ERIC , SHORT JAY M
发明人： CALLEN WALTER , RICHARDSON TOBY , FREY GERHARD , MILLER CARL A , KAZAOKA MARTIN , MATHUR ERIC , SHORT JAY M
IPC分类号： C12N1/21 , C12N9/28 , C12P19/14 , C12N
CPC分类号： C12N9/2417 , C12P19/14
摘要： In one aspect, the invention is directed to polypeptides having an amylase activity, polynucleotides encoding the polypeptides, and methods for making and using these polynucleotides and polypeptides. In one aspect, the polypeptides of the invention can be used as amylases, for example, alpha amylases, to catalyze the hydrolysis of starch into 10 sugars.
摘要翻译：一方面，本发明涉及具有淀粉酶活性的多肽，编码多肽的多核苷酸，以及制备和使用这些多核苷酸和多肽的方法。一方面，本发明的多肽可用作淀粉酶，例如α-淀粉酶，以催化淀粉水解成10个糖。

29. 发明申请

WO03097810A2 NITRILASES, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR MAKING AND USING THEM 审中-公开
标题翻译： NITRILASES，NUCLEIC ACID ENCODING THEM AND METHODS FOR MAKING AND USING THEM
公开(公告)号：WO03097810A2
公开(公告)日：2003-11-27
申请号：PCT/US0315712
申请日：2003-05-15
申请人： DIVERSA CORP , DESANTIS GRACE , SHORT JAY M , BURK MARK , WONG KEVIN , FARWELL ROBERT , CHATMAN KELLY
发明人： DESANTIS GRACE , SHORT JAY M , BURK MARK , WONG KEVIN , FARWELL ROBERT , CHATMAN KELLY
IPC分类号： C12N1/21 , C12N9/78 , C12P7/42 , C12P13/00 , C12P13/04 , C12P41/00 , C12N
CPC分类号： C12P7/42 , C12N9/78 , C12P13/004 , C12P13/04 , C12P41/006
摘要： The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
摘要翻译：本发明涉及腈水解酶和编码腈水解酶的核酸。另外还提供了设计新腈水解酶的方法及其使用方法。在增加的pH和温度下，腈水解酶具有增加的活性和稳定性。

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