Human Proteolytic Beta-Amyloid Specific Antibodies for Treatment of Alzheimers Di

用于治疗阿尔茨海默病的人蛋白水解 β-淀粉样蛋白特异性抗体 Di

基本信息

批准号：
8121071
负责人：
Hiep T Tran
金额：
$ 28.25万
依托单位：
ABZYME THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-15 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8121071
关键词：
Affinity Alzheimer&apos s Disease Amino Acids Amyloid Amyloid beta-Protein Animal Model Antibodies Antibody Formation Binding Binding Proteins Biotechnology Cells Characteristics Chimeric Proteins Chromosomes Cleaved cell Clinical Trials Deaminase Development Dimerization Diploidy Disease Estrogens FOS gene Gene Conversion Genes Genetic Crossing Over Genetic Transcription Goals Human Hydrolysis Immunoglobulin G JUN gene Leucine Zippers Libraries Light Mating Types Mediating Membrane Modality Monoclonal Antibodies Oryctolagus cuniculus Partner in relationship Peptide Hydrolases Phase Phenotype Plasmids Property Reporter Reporter Genes Research Screening procedure Site Specificity System Technology Testing Therapeutic Monoclonal Antibodies Toxic effect VP 16 Validation Western Blotting Yeasts activation-induced cytidine deaminase amyloid peptide base beta-Galactosidase combinatorial cost dosage endodeoxyribonuclease SceI expression vector human monoclonal antibodies improved mouse model mutant neurotoxic neurotoxicity novel novel strategies novel therapeutics peptide A pre-clinical preclinical study research clinical testing response success transcription factor uracil-DNA glycosylase

Affinity Alzheimer&apos s Disease Amino Acids Amyloid Amyloid beta-Protein Animal Model Antibodies Antibody Formation Binding Binding Proteins Biotechnology Cells Characteristics Chimeric Proteins Chromosomes Cleaved cell Clinical Trials Deaminase Development Dimerization Diploidy Disease Estrogens FOS gene Gene Conversion Genes Genetic Crossing Over Genetic Transcription Goals Human Hydrolysis Immunoglobulin G JUN gene Leucine Zippers Libraries Light Mating Types Mediating Membrane Modality Monoclonal Antibodies Oryctolagus cuniculus Partner in relationship Peptide Hydrolases Phase Phenotype Plasmids Property Reporter Reporter Genes Research Screening procedure Site Specificity System Technology Testing Therapeutic Monoclonal Antibodies Toxic effect VP 16 Validation Western Blotting Yeasts activation-induced cytidine deaminase amyloid peptide base beta-Galactosidase combinatorial cost dosage endodeoxyribonuclease SceI expression vector human monoclonal antibodies improved mouse model mutant neurotoxic neurotoxicity novel novel strategies novel therapeutics peptide A pre-clinical preclinical study research clinical testing response success transcription factor uracil-DNA glycosylase

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项目摘要

DESCRIPTION (provided by applicant): Proteolytic antibodies are a novel therapeutic modality potentially impacting current antibody- based therapy. The ultimate goal of this project is to develop potent proteolytic human monoclonal antibodies (mAb) against beta Amyloids (Ab) for treatment of Alzheimer's disease. To achieve the objective, a novel approach was developed to produce a yeast intracellular human monoclonal antibody library (iHuMab) that can create 1016 possible unique antibodies. A (beta amyloid) specific monoclonal antibodies with protease activity will be screened using iHuMAbeta library and highly specific and tightly regulated multi-reporter system. At the end of phase I, we expect up to 10 unique A specific proteolytic antibodies will be expressed, purified and characterized. Their A40 specific hydrolysis, binding affinity and neutralization capacity will be validated. In phase II A specific antibodies having the highest affinity and protease activity will be produced in large scale quantities for further testing of A40 neutralization effects in mouse models of Alzhemer's disease. Also in Phase II, the most promising molecules would be subjected to pre-clinical evaluation in animal models, pursuant to submission of an IND application for clinical trials. PUBLIC HEALTH RELEVANCE: Therapeutic monoclonal antibodies are one of the fastest growing biotechnology sectors showing marked success for the treatment of various diseases. Proteolytic antibodies are a potential novel therapeutic that could provide a comparable or better benefit but requiring reduced dosages, therefore reducing the cost while increase efficacy. In this project, iHuMAbeta technology platform is developed to identify human proteolytic antibodies against beta-amyloid peptide, a promising target for the treatment of Alzheimer's Disease.

描述（由申请人提供）：蛋白水解抗体是一种新型的治疗方式，可能会影响基于抗体的治疗。该项目的最终目标是开发针对β-淀粉样蛋白（AB）治疗阿尔茨海默氏病的有效的蛋白水解人单克隆抗体（MAB）。为了实现目标，开发了一种新的方法来产生酵母细胞内人类单克隆抗体库（IHUMAB），该抗体可以产生1016个可能的独特抗体。（β-淀粉样蛋白）具有蛋白酶活性的（β-淀粉样蛋白）的单克隆抗体将使用iHumabeta库和高度特异性且受到严格调节的多重孢子系统进行筛选。在第一阶段结束时，我们期望多达10个独特的特定蛋白水解抗体将被表达，纯化和表征。他们的A40特异性水解，结合亲和力和中和能力将得到验证。在II期中，将大量生产具有最高亲和力和蛋白酶活性的特异性抗体，以进一步测试阿尔茨海默氏病小鼠模型中A40中和效应。同样在第二阶段，最有希望的分子将在动物模型中接受临床前评估，根据提交IND临床试验的申请。公共卫生相关性：治疗性单克隆抗体是增长最快的生物技术部门之一，显示出各种疾病的成功成功。蛋白水解抗体是一种潜在的新型治疗性，可以提供可比或更好的益处，但需要减少剂量，从而降低成本同时提高疗效。在该项目中，Ihumabeta技术平台旨在鉴定针对β-淀粉样蛋白肽的人类蛋白水解抗体，这是治疗阿尔茨海默氏病的有希望的靶标。