Engineered proteins from transgenic animals

来自转基因动物的工程蛋白

• 批准号: 8311351
• 负责人: Philip Leighton
• 金额: $ 103万
• 依托单位: CRYSTAL BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311351
• 关键词: Animals; Antibodies; Antibody Affinity; Antibody Formation; Antigens; Autoimmunity; B-Lymphocytes; Biotechnology; Birds; Breeding; Cell Line; Cells; Chickens; Complementarity Determining Regions; Data; Development; Engineering; Epitopes; Evaluation; Framework Regions; Gene Conversion; Genome; Genomics; Homologous Gene; Human; Human Engineering; IGH@ gene cluster; Immunization; Immunoglobulin Genes; In Vitro; Industry; Integrase; Knock-in Mouse; Knock-out; Light; Lymphoid Cell; Malignant Neoplasms; Methods; Modification; Monoclonal Antibodies; Mus; Oryctolagus cuniculus; Outcome; Phase; Phylogenetic Analysis; Positioning Attribute; Process; Property; Protein Engineering; Proteins; Pseudogenes; Randomized; Research; Route; Serine; Site; Source; Specificity; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Therapeutic antibodies; Time; Tissues; Transgenic Animals; Transgenic Organisms; Tryptophan; Tyrosine; Work; antibody engineering; base; cost effective; human disease; human monoclonal antibodies; improved; large scale production; meetings; novel; protein protein interaction; research study; transmission process; vector

DESCRIPTION (provided by applicant): Approximately 25% of the products being developed by the biotechnology industry are antibodies and many of these antibodies are directed to epitopes on human cells and tissues. We are proposing a novel concept for the production of antibodies with therapeutic potential that is based on recent advances in protein-protein interactions and recent developments in transgenic technology. Execution of this concept will obviate many of the expensive and time consuming modifications that are frequently required after potentially therapeutic monoclonal antibodies are identified in order to optimize their pharmacological properties and to make them amenable to large scale production. By combining recent data derived from in vitro studies with the nascent understanding of genomics, we will extend the range of epitopes that can be accessed and, therefore, extend the range of potentially therapeutic antibodies. PUBLIC HEALTH RELEVANCE: During the past 15 years, more than 20 therapeutic antibodies have been developed to treat human disease, particularly in the fields of autoimmunity and cancer. We have proposed a novel method to obtain potentially therapeutic antibodies that will recognize targets that cannot be obtained from conventional sources. In addition, the technology will engineer antibodies that have improved pharmacological attributes and better manufacturing properties. This technology will provide a cost-effective route to increasing the range of therapeutic candidates for the treatment of human disease.

描述（由申请人提供）：生物技术行业正在开发的产品中大约 25% 是抗体，其中许多抗体针对人体细胞和组织上的表位。我们基于蛋白质-蛋白质相互作用的最新进展和转基因技术的最新发展，提出了一种生产具有治疗潜力的抗体的新概念。这一概念的实施将避免许多昂贵且耗时的修改，这些修改在确定潜在的治疗性单克隆抗体后经常需要，以优化其药理学特性并使其适合大规模生产。通过将来自体外研究的最新数据与对基因组学的初步了解相结合，我们将扩大可访问的表位范围，从而扩大潜在治疗性抗体的范围。 公共卫生相关性：在过去 15 年中，已经开发了 20 多种治疗性抗体来治疗人类疾病，特别是在自身免疫和癌症领域。我们提出了一种新方法来获得潜在的治疗性抗体，该抗体将识别无法从常规来源获得的靶标。此外，该技术将设计具有改进的药理属性和更好的制造特性的抗体。该技术将为增加人类疾病治疗候选药物的范围提供一种经济有效的途径。