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1. 发明申请

WO2003070190A3 SURROGATE ANTIBODIES AND METHODS OF PREPARATION AND USE THEREOF 审中-公开
公开(公告)号：WO2003070190A3
公开(公告)日：2003-08-28
申请号：PCT/US2003/004946
申请日：2003-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, B.
发明人： FRIEDMAN, Stephen, B.
IPC分类号： A61K48/00
摘要： A process is described for producing surrogate antibody molecules that mimic the structure, stability, and binding characteristics of a natural antibody. Surrogate antibody structure, composition of surrogate antibody libraries, methods of surrogate antibody preparation, and surrogate antibody applications are disclosed. Also disclosed are methods of surrogate antibody structural stabilization and resistance to nucleases. The surrogate antibodies comprise a specificity strand and a stabilization strand. The specificity strand comprises a nucleic acid sequence having a specificity region flanked by a first constant region and a second constant region. The stabilization strand comprises a first stabilization region and a second stabilization region that interacts with the second constant region. They can be used as an effective replacement for natural antibody molecules for testing therapeutic agents and research purposes.

2. 发明申请

US20040018508A1 Surrogate antibodies and methods of preparation and use thereof 审中-公开
公开(公告)号：US20040018508A1
公开(公告)日：2004-01-29
申请号：US10370052
申请日：2003-02-19
申请人： Syntherica Corporation
发明人： Stephen B. Friedman
IPC分类号： C12Q001/68 , C07K009/00 , C07H021/02 , C07H021/04
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： A process is described for producing surrogate antibody molecules that mimic the structure, stability, and binding characteristics of a natural antibody. Surrogate antibody structure, composition of surrogate antibody libraries, methods of surrogate antibody preparation, and surrogate antibody applications are disclosed. Also disclosed are methods of surrogate antibody structural stabilization and resistance to nucleases. The surrogate antibodies comprise a specificity strand and a stabilization strand. The specificity strand comprises a nucleic acid sequence having a specificity region flanked by a first constant region and a second constant region. The stabilization strand comprises a first stabilization region that interacts with the first constant region and a second stabilization region that interacts with the second constant region. In further embodiments, the stabilization strand and the specificity strand comprise distinct molecules. In other embodiments, the surrogate antibody molecules may comprise polyoligonucleotides that have at least one nucleotide sequence that forms a loop with specific ligand-binding properties. Surrogate antibody libraries containing a large population of random binding molecules are pre-assembled and used in a process that captures and amplifies those molecules having prerequisite binding characteristics. The amplified surrogate antibody molecule produced by the process has identical structure and binding characteristics to the parent molecule captured from the initially assembled library. Surrogate antibody molecules contain binding loop(s) that are formed and stabilized by the hybridization of at least two adjacent and juxtaposed strands, one strand having a greater number of nucleotides than the other. The preparation of a polyclonal surrogate antibody reagent proceeds through phases of capture/enrichment and amplification, specificity enhancement, and affinity enhancement. Depending upon the intended application, polyclonal surrogate antibody reagents can be processed to monoclonality. These molecules expand upon the binding characteristics of natural immunoglobulins, and do not require animals, animal facilities, cell culture or the stimulation of an immune response, in their development. They can be used as an effective replacement for natural antibody molecules, and therefore can be used in testing methods like immunoassay, as therapeutic agents, for specific labeling, and for research purposes. Targets ligands compatible with the development of surrogate antibodies include compounds, organisms, and cells that when complexed to a surrogate antibody in solution attain characteristics that can be physically or chemically differentiated from uncomplexed surrogate antibody.

3. 发明申请

WO2003070192A2 COMPOSITIONS AND METHODS FOR SURROGATE ANTIBODY MODULATION OF AN IMMUNE RESPONSE AND TRANSPORT 审中-公开
标题翻译：免疫反应和运输的现状抗体调节的组合物和方法
公开(公告)号：WO2003070192A2
公开(公告)日：2003-08-28
申请号：PCT/US2003/005000
申请日：2003-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, B.
发明人： FRIEDMAN, Stephen, B.
IPC分类号： A61K
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： Methods and compositions for the modulation of an immune response are provided. Compositions comprise a bi-functional surrogate antibody molecule that interacts with a ligand of interest, wherein the bi-functional surrogate antibody further has attached thereto an immunomodulatory agent and/or a transporting agent. The compositions of the invention find use in a method for delivering an immunomodulatory agent to a ligand of interest. Further provided are methods for modulating an immune response in a subject against a ligand of interest. The method comprises administering a therapeutically effective amount of a bi-functional surrogate antibody of the invention. The methods of the invention also find use in improving the clinical outcome of a subject in need of a modulation in the immune response. Methods are further provided for the treatment or prevention of a variety of conditions and/or disorders including cancer, autoimmune diseases, allergies, prions, and various diseases or conditions of bacterial, parasitic, yeast or viral etiology.
摘要翻译：提供了用于调节免疫应答的方法和组合物。组合物包含与目的配体相互作用的双功能替代抗体分子，其中双功能替代抗体还附有免疫调节剂和/或转运剂。本发明的组合物用于将免疫调节剂递送至感兴趣的配体的方法。进一步提供的是调节受试者相对于目的配体的免疫应答的方法。该方法包括施用治疗有效量的本发明的双功能替代抗体。本发明的方法还用于改善需要在免疫应答中调节的受试者的临床结果。还提供了用于治疗或预防各种病症和/或病症的方法，包括癌症，自身免疫性疾病，过敏症，朊病毒以及细菌，寄生虫，酵母或病毒病因的各种疾病或病症。

4. 发明申请

WO2005022153A2 COMOSITIONS AND METHODS FOR SCREENING USING POPULATIONS OF SURROGATE ANTIBODIES 审中-公开
标题翻译：使用现场抗体人群进行筛选的方法和方法
公开(公告)号：WO2005022153A2
公开(公告)日：2005-03-10
申请号：PCT/US2004/004903
申请日：2004-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, Barry
发明人： FRIEDMAN, Stephen, Barry
IPC分类号： G01N33/53
CPC分类号： C12Q1/6825 , C12N15/1048 , C12Q1/6804 , G01N33/6845 , C12Q2565/519 , C12Q2563/185 , C12Q2541/101
摘要： Methods and compositions for the detection, identification, and quantification of compounds of interest in a sample are provided. The compositions and methods include arrays and kits comprising a population of surrogate antibodies that bind compounds of interest. The surrogate antibodies can be immobilized on to a solid support by means of an interaction between a recognition nucleotide sequence comprised in the surrogate antibody and a capture nucleotide sequence comprised in a capture probe attached to the solid support. Also provided are methods of using the arrays for research and clinical diagnostics, drug discovery, environmental testing, food testing, and testing for the use of agents of biological and chemical warfare.
摘要翻译：提供了用于检测，鉴定和定量样品中感兴趣的化合物的方法和组合物。组合物和方法包括阵列和试剂盒，其包含结合感兴趣化合物的替代抗体群。替代抗体可以通过包含在替代抗体中的识别核苷酸序列与附在固体支持物上的捕获探针中的捕获核苷酸序列之间的相互作用固定在固体支持物上。还提供了使用阵列进行研究和临床诊断，药物发现，环境测试，食品测试和使用生物和化学战剂的测试的方法。

5. 发明申请

WO2003070192A3 COMPOSITIONS AND METHODS FOR SURROGATE ANTIBODY MODULATION OF AN IMMUNE RESPONSE AND TRANSPORT 审中-公开
公开(公告)号：WO2003070192A3
公开(公告)日：2003-08-28
申请号：PCT/US2003/005000
申请日：2003-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, B. , DRUTZ, David, J.
发明人： FRIEDMAN, Stephen, B. , DRUTZ, David, J.
IPC分类号： C07H21/00
摘要： Methods and compositions for the modulation of an immune response are provided. Compositions comprise a bi-functional surrogate antibody molecule that interacts with a ligand of interest, wherein the bi-functional surrogate antibody further has attached thereto an immunomodulatory agent and/or a transporting agent. The compositions of the invention find use in a method for delivering an immunomodulatory agent to a ligand of interest. Further provided are methods for modulating an immune response in a subject against a ligand of interest. The method comprises administering a therapeutically effective amount of a bi-functional surrogate antibody of the invention. The methods of the invention also find use in improving the clinical outcome of a subject in need of a modulation in the immune response. Methods are further provided for the treatment or prevention of a variety of conditions and/or disorders including cancer, autoimmune diseases, allergies, prions, and various diseases or conditions of bacterial, parasitic, yeast or viral etiology.

6. 发明申请

WO2003070190A2 SURROGATE ANTIBODIES AND METHODS OF PREPARATION AND USE THEREOF 审中-公开
标题翻译：抗生素及其制备方法及其用途
公开(公告)号：WO2003070190A2
公开(公告)日：2003-08-28
申请号：PCT/US2003/004946
申请日：2003-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, B.
发明人： FRIEDMAN, Stephen, B.
IPC分类号： A61K
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： A process is described for producing surrogate antibody molecules that mimic the structure, stability, and binding characteristics of a natural antibody. Surrogate antibody structure, composition of surrogate antibody libraries, methods of surrogate antibody preparation, and surrogate antibody applications are disclosed. Also disclosed are methods of surrogate antibody structural stabilization and resistance to nucleases. The surrogate antibodies comprise a specificity strand and a stabilization strand. The specificity strand comprises a nucleic acid sequence having a specificity region flanked by a first constant region and a second constant region. The stabilization strand comprises a first stabilization region that interacts with the first constant region and a second stabilization region that interacts with the second constant region. In further embodiments, the stabilization strand and the specificity strand comprise distinct molecules. In other embodiments, the surrogate antibody molecules may comprise polyoligonucleotides that have at least one nucleotide sequence that forms a loop with specific ligand-binding properties. Surrogate antibody libraries containing a large population of random binding molecules are preassembled and used in a process that captures and amplifies those molecules having prerequisite binding characteristics. The amplified surrogate antibody molecule produced by the process has identical structure and binding characteristics to the parent molecule captured from the initially assembled library. Surrogate antibody molecules contain binding loop(s) that are formed and stabilized by the hybridization of at least two adjacent and juxtaposed strands, one strand having a greater number of nucleotides than the other. The preparation of a polyclonal surrogate antibody reagent proceeds through phases of capture/enrichment and amplification, specificity enhancement, and affinity enhancement. Depending upon the intended application, polyclonal surrogate antibody reagents can be processed to monoclonality. These molecules expand upon the binding characteristics of natural immunoglobulins, and do not require animals, animal facilities, cell culture or the stimulation of an immune response, in their development. They can be used as an effective replacement for natural antibody molecules, and therefore can be used in testing methods like immunoassay, as therapeutic agents, for specific labeling, and for research purposes targets ligands compatible with the development of surrogate antibodies include compounds, organisms, and cells that when complexed to a surrogate antibody in solution attain characteristics that can be physically or chemically differentiated from uncomplexed surrogate antibody.
摘要翻译：描述了用于产生模拟天然抗体的结构，稳定性和结合特征的替代抗体分子的方法。公开了替代抗体结构，替代抗体文库的组成，替代抗体制备方法和替代抗体应用。还公开了替代抗体结构稳定化和对核酸酶的抗性的方法。替代抗体包含特异性链和稳定链。特异性链包含具有侧翼为第一恒定区和第二恒定区的特异性区的核酸序列。稳定链包括与第一恒定区相互作用的第一稳定区和与第二恒定区相互作用的第二稳定区。在另外的实施方案中，稳定链和特异性链包括不同的分子。在其它实施方案中，替代抗体分子可以包含具有形成具有特定配体结合性质的环的至少一个核苷酸序列的多元双胍。包含大量随机结合分子的替代抗体文库被预组装并用于捕获并扩增具有先决条件结合特征的那些分子的过程。通过该方法产生的扩增的替代抗体分子与从初始组装的文库捕获的母体分子具有相同的结构和结合特征。替代抗体分子含有通过至少两个相邻和并置的链的杂交而形成和稳定的结合环，一条链具有比另一个更多的核苷酸数量。多克隆替代抗体试剂的制备通过捕获/富集和扩增，特异性增强和亲和力增强的阶段进行。根据预期的应用，可将多克隆替代抗体试剂加工成单克隆抗体。这些分子在天然免疫球蛋白的结合特征上扩展，并且在其发育中不需要动物，动物设备，细胞培养物或免疫应答的刺激。它们可以用作天然抗体分子的有效替代物，因此可以用于测试方法，如免疫测定，作为治疗剂，用于特异性标记，并用于研究目的，与替代抗体发展相容的配体包括化合物，生物体，并且当与溶液中的替代抗体复合时获得可以与未复合的替代抗体物理或化学分化的特征的细胞。

7. 发明公开

EP1476456A2 COMPOSITIONS AND METHODS FOR SURROGATE ANTIBODY MODULATION OF AN IMMUNE RESPONSE AND TRANSPORT 审中-公开
标题翻译：组合物和方法免疫反应和运输更换抗体调制
公开(公告)号：EP1476456A2
公开(公告)日：2004-11-17
申请号：EP03716085.0
申请日：2003-02-19
申请人： Syntherica Corporation
发明人： FRIEDMAN, Stephen, B. , DRUTZ, David, J.
IPC分类号： C07H21/00 , C12Q1/00
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： Methods and compositions for the modulation of an immune response are provided. Compositions comprise a bi-functional surrogate antibody molecule that interacts with a ligand of interest, wherein the bi-functional surrogate antibody further has attached thereto an immunomodulatory agent and/or a transporting agent. The compositions of the invention find use in a method for delivering an immunomodulatory agent to a ligand of interest. Further provided are methods for modulating an immune response in a subject against a ligand of interest. The method comprises administering a therapeutically effective amount of a bi-functional surrogate antibody of the invention. The methods of the invention also find use in improving the clinical outcome of a subject in need of a modulation in the immune response. Methods are further provided for the treatment or prevention of a variety of conditions and/or disorders including cancer, autoimmune diseases, allergies, prions, and various diseases or conditions of bacterial, parasitic, yeast or viral etiology.

8. 发明公开

EP1482984A2 SURROGATE ANTIBODIES AND METHODS OF PREPARATION AND USE THEREOF 审中-公开
标题翻译： SPARE抗体及其制备方法和用途
公开(公告)号：EP1482984A2
公开(公告)日：2004-12-08
申请号：EP03713533.2
申请日：2003-02-19
申请人： Syntherica Corporation
发明人： FRIEDMAN, Stephen, B.
IPC分类号： A61K48/00 , C07H21/04
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： A process is described for producing surrogate antibody molecules that mimic the structure, stability, and binding characteristics of a natural antibody. Surrogate antibody structure, composition of surrogate antibody libraries, methods of surrogate antibody preparation, and surrogate antibody applications are disclosed. Also disclosed are methods of surrogate antibody structural stabilization and resistance to nucleases. The surrogate antibodies comprise a specificity strand and a stabilization strand. The specificity strand comprises a nucleic acid sequence having a specificity region flanked by a first constant region and a second constant region. The stabilization strand comprises a first stabilization region and a second stabilization region that interacts with the second constant region. They can be used as an effective replacement for natural antibody molecules for testing therapeutic agents and research purposes.

9. 发明公开

EP1594992A2 COMOSITIONS AND METHODS FOR SCREENING USING POPULATIONS OF SURROGATE ANTIBODIES 审中-公开
标题翻译：成分和方法，人口替代抗体筛查
公开(公告)号：EP1594992A2
公开(公告)日：2005-11-16
申请号：EP04785838.6
申请日：2004-02-19
申请人： Syntherica Corporation
发明人： FRIEDMAN, Stephen, Barry
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6825 , C12N15/1048 , C12Q1/6804 , G01N33/6845 , C12Q2565/519 , C12Q2563/185 , C12Q2541/101
摘要： Methods and compositions for the detection, identification, and quantification of compounds of interest in a sample are provided. The compositions and methods include arrays and kits comprising a population of surrogate antibodies that bind compounds of interest. The surrogate antibodies can be immobilized on to a solid support by means of an interaction between a recognition nucleotide sequence comprised in the surrogate antibody and a capture nucleotide sequence comprised in a capture probe attached to the solid support. Also provided are methods of using the arrays for research and clinical diagnostics, drug discovery, environmental testing, food testing, and testing for the use of agents of biological and chemical warfare.

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