Therapeutic antibody for RSV

RSV 治疗性抗体

基本信息

批准号：
9046676
负责人：
Lawrence Michael Kauvar
金额：
$ 126.88万
依托单位：
TRELLIS BIOSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9046676
关键词：
Advanced Development Advanced Manufacturing Technology Affinity Age Animals Anti-Inflammatory Agents Anti-inflammatory Antibodies Antiviral Agents B-Lymphocytes Binding Biological Models Biological Sciences Bioreactors Biotechnology Cell Line Cells Cessation of life Child Chinese Hamster Ovary Cell Clinical Clinical Pathology Clinical Trials Collaborations Complement Cost Savings Cost-Benefit Analysis Costs and Benefits Cytomegalovirus Data Development Drug Industry Epitopes Funding GTP-Binding Proteins Glycoproteins Goals Hospitalization Human Immune Immune response Immune system Infant Infection Influenza Investigation Laboratories Legal patent Licensing Link Lower respiratory tract structure Lung Inflammation Medical Monoclonal Antibodies National Institute of Allergy and Infectious Disease Nature Palivizumab Pathology Pharmaceutical Preparations Phase Population Premature Birth Preparation Probability Process Production Productivity Property Prophylactic treatment Proteins Publishing Research Respiratory Syncytial Virus Infections Respiratory Tract Diseases Respiratory physiology Respiratory syncytial virus Rivers Services Small Business Innovation Research Grant Staging System Technology Testing Therapeutic Monoclonal Antibodies Therapeutic antibodies Tissues Toxicology Vaccines Viral Virus Diseases Work analytical method cell bank commercialization cost experience flasks human monoclonal antibodies human tissue in vitro activity innovation mouse model novel novel strategies prevent process optimization programs public health relevance response screening shear stress small molecule

项目摘要

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, leading annually to 200,000 deaths and 3 million hospitalizations of young children worldwide. Immune prophylaxis with a monoclonal antibody (mAb), Synagis(tm) (Medimmune, Inc.), was shown to be effective 15 years ago to reduce complications of infection in premature birth infants, but it has not shown efficacy as a post-infection treatment in the much larger population of full term infants. No safe and effective antiviral drugs are available and no effective vaccine has been produced to date. Accordingly, there remains a large unmet medical need. Using a proprietary technology for screening single human B cells, Trellis has cloned a native human mAb, 3D3 that overcomes the limitations of Synagis, providing unprecedented curative responses in animals post exposure. The new mAb targets a different envelope glycoprotein, one that has been implicated in sabotage of the host immune response. This antibody has an affinity of 1 pM for a highly conserved epitope. It has direct antiviral activity in vitro in the presence of complement, with potency 100-fold better than Synagis. In mouse models, 3D3 has shown potent activity as both a direct antiviral agent and as an agent to block the lung inflammation linked to clinical pathology. This dual activity is qualitatively different from Synagis, or from any of the small molecule antiviral drugs under investigation for treating RSV. As expected for a native human antibody, 3D3 showed no binding to a panel of human tissues. It has been expressed in stably transformed CHO cells at 0.3 g/L prior to selection, indicating feasibility of generating a high expressing cell line. Thus,all of the goals normally associated with Phase I SBIR research have been achieved. The goals of this Direct Phase II proposal are to develop a Master Cell Bank of expressing cells with the capacity of producing 3D3 at commercially useful levels (>2 g/L), and to develop the analytical and toxicological data needed for initiation of human testing (IND data package).

描述（由应用提供）：呼吸道合胞病毒（RSV）是下呼吸道疾病的主要原因，每年导致全球幼儿的200,000次死亡和300万个住院治疗。用单克隆抗体（MAB），下al（TM）（Medimmune，Inc。）进行免疫预防，显示出15年前有效的，可减少早产儿的感染并发症，但尚未显示出在更大的全年婴儿中的感染后治疗中有效作为一种后期的感染治疗。迄今为止，没有安全有效的抗病毒药物，也没有生产有效的疫苗。彼此之间，仍然有很大的未满足医疗需求。 Trellis使用专有技术来筛选单个人类B细胞，克隆了一个本地人物mAB，3D3克服了下沿的局限性，从而在暴露后在动物中提供了前所未有的治疗反应。新的mAb靶向一种不同的包膜糖蛋白，该糖蛋白已暗示宿主免疫反应。该抗体的亲和力为高度保守的表位。它在完成的情况下在体外具有直接的抗病毒活性，效力比下沿。在小鼠模型中，3D3既表现为直接抗病毒剂，又是阻断与临床病理相关的肺部感染的药物。这种双重活性在质量上与犹太会议或与正在研究的RSV治疗的任何小分子抗病毒药物不同。正如原生人类抗体所预期的那样，3D3没有与人类组织的结合。在选择之前，它在稳定转化的CHO细胞中以0.3 g/L的形式表达，表明产生高表达细胞系的可行性。这是实现了通常与I期SBIR研究相关的所有目标。该直接II期建议的目标是开发具有在商业上有用的水平（> 2 g/L）产生3D3的能力的表达细胞的大细胞库，并开发启动人类测试所需的分析和毒理学数据（IND数据包）。