Next-Generation Antibody Discovery and Development Technology

下一代抗体发现和开发技术

• 批准号: 9174883
• 负责人: David Scott Johnson
• 金额: $ 87.98万
• 依托单位: GIGAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9174883
• 关键词: Accounting; Address; Affinity; Antibodies; Antigens; B cell repertoire; B-Lymphocytes; Biological Products; Biotechnology; Blood; CLIA certified; Cancer Patient; Capital; Cells; Cessation of life; DNA; DNA Library; DNA Sequence; Development; Diagnosis; Diagnostic; Diagnostic tests; Directed Molecular Evolution; Disease; Doctor of Philosophy; Engineering; Flavoring; Flow Cytometry; Genomics; Human; Hybridomas; Immune; Immunization; In Vitro; Innovation Corps; Interview; Investments; Lead; Libraries; Link; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Methods; Microfluidics; Molecular; Monoclonal Antibodies; Mus; Phage Display; Pharmaceutical Preparations; Pharmacotherapy; Phase; Proteins; Scientist; Screening for cancer; Sensitivity and Specificity; Sequoia; Services; Small Business Innovation Research Grant; Specialist; Technology; Therapeutic; Therapeutic antibodies; Time; Trastuzumab; Treatment Cost; United States National Institutes of Health; antibody libraries; base; bevacizumab; cancer therapy; commercialization; inhibitor/antagonist; interest; killings; new technology; next generation; novel; novel therapeutics; oncology; oncology program; product development; programs; research and development; rituximab; screening; technology development; tumor immunology

PROJECT SUMMARY Project Title: Next-Generation Antibody Discovery and Development Technology Organization: GigaGen Inc. PI: David S. Johnson, Ph.D. Despite an enormous investment in novel therapies, cancer still accounts for 25% of US deaths, killing >1500 people every day. For example, only 25% of pancreatic cancer patients and 17% of lung cancer patients survive one year after diagnosis. Additionally, oncology treatments cost $127 billion per year in the US, and are expected to grow at 27% per year through 2020. Monoclonal antibodies (mAbs) are now the biological agents of choice for cancer therapy. Three of the top six grossing therapeutics worldwide (bevacizumab, rituximab, and trastuzumab) are oncology mAbs. Today, most mAb discovery programs use either some flavor of single chain variable fragment (scFv) display or mouse immunization followed by hybridoma isolation. Display technologies like phage display have tremendous ease of use, which enables R&D programs to screen through billions of antibodies in parallel. Unlike conventional phage display technologies, mouse immunizations produce fully natural antibodies, which are often easier to develop than antibodies discovered through display. Though display and mouse immunizations have produced breakthrough therapeutic antibodies, R&D programs are always looking for faster, deeper, and more efficient antibody technologies. The Specific Aim of this IMAT Phase II SBIR project is to develop GigaLink™, a next-generation high-throughput molecular technology for discovery and development of oncology drugs from mammalian B cell repertoires. GigaLink™ is the only technology that uses primary B cells to make millions- to billions-diverse DNA libraries of antibodies, and then expresses the DNA libraries as protein for affinity screening and antigen discovery. As a DNA-based technology, GigaLink™ uniquely enables massively parallel antibody screening, engineering, and development. A successful IMAT Phase II SBIR project will show that the GigaLink™ antibody R&D platform can help our customers understand basic tumor immunology and discover and develop therapeutic antibody candidates. We will use the profits from GigaLink™ service revenues plus venture capital to build our own internal programs for oncology therapeutic antibody discovery.

项目总结 项目名称：新一代抗体发现与开发技术 组织：GigaGen Inc. 派：大卫·S·约翰逊，博士。 尽管在新疗法上投入了大量资金，但癌症仍占美国死亡人数的25%，导致1500人死亡 每天都有人。例如，只有25%的胰腺癌患者和17%的肺癌患者 确诊后存活一年。此外，在美国，肿瘤治疗每年花费1270亿美元，而且 预计到2020年将以每年27%的速度增长。 目前，单抗是治疗癌症的首选生物制剂。前六名中的三名 全世界最畅销的治疗药物(贝伐单抗、利妥昔单抗和曲妥珠单抗)都是肿瘤学单抗。今天，大多数 MAb发现程序使用某种风格的单链可变片段(ScFv)显示或鼠标 免疫后进行杂交瘤分离。像噬菌体展示这样的展示技术非常容易 这使得研发程序能够并行地通过数十亿种抗体进行筛选。与传统不同 噬菌体展示技术，小鼠免疫产生完全自然的抗体，通常更容易 发展出比通过展示发现的抗体更好的抗体。 尽管展示和老鼠免疫已经产生了突破性的治疗性抗体，但研发计划 一直在寻找更快、更深、更有效的抗体技术。这次IMAT的具体目的是 第二阶段SBIR项目是开发GigaLink™，这是一种新一代高通量分子技术，用于 哺乳动物B细胞库中肿瘤药物的发现和发展。GigaLink™是唯一 使用原代B细胞制造数百万到数十亿种不同的DNA抗体库的技术，然后 将DNA文库表达为蛋白质，用于亲和筛选和抗原发现。作为一种基于DNA的 技术，GigaLink™独一无二地实现了大规模并行抗体筛选、工程和 发展。 一个成功的IMAT第二期SBIR项目将表明GigaLink™抗体研发平台可以帮助我们的 客户了解基本的肿瘤免疫学，并发现和开发治疗性抗体候选。 我们将使用GigaLink™服务收入的利润加上风险资本来建立我们自己的内部 肿瘤学治疗性抗体发现计划。