Therapeutic Antibody for RSV IIB

RSV IIB 治疗性抗体

基本信息

批准号：
10063931
负责人：
Lawrence Michael Kauvar
金额：
$ 99.77万
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 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063931
关键词：
Address Affinity Anti-Inflammatory Agents Antibiotic Resistance Antibodies Antiviral Agents B-Lymphocytes Bacterial Proteins Binding Biological Assay Biological Markers Biological Sciences Birth Weight Cessation of life Characteristics Child Chinese Hamster Ovary Cell Clinical Clinical Trials Clinical assessments Communicable Diseases Communities Complement Consult Cytomegalovirus Data Development Disease Dose Drug Industry Epitopes Formulation Foundations Funding G-substrate GTP-Binding Proteins Generations Goals Grant Hospitalization Human Immunocompromised Host Infant Infection Inflammatory Influenza Innate Immune System Interferons Investigation Legal patent Lower respiratory tract structure Malignant Neoplasms Measures MicroRNAs Molecular Monoclonal Antibodies Morbidity - disease rate Mus Natural Immunity Palivizumab Palliative Care Pathology Pharmaceutical Preparations Pharmacologic Substance Phase Phase I/II Trial Population Premature Birth Production Property Prophylactic treatment Proteins Published Comment Publishing Rattus Reagent Recovery Research Research Personnel Respiratory Syncytial Virus Infections Respiratory Tract Diseases Respiratory syncytial virus Respiratory syncytial virus RSV F proteins Respiratory syncytial virus RSV proteins Sentinel Severity of illness Small Business Innovation Research Grant Standardization Surveys Technology Therapeutic Therapeutic Agents Therapeutic antibodies Toxic effect Toxicokinetics Transfection Uncertainty Vaccines Very Low Birth Weight Infant Viral Viral Envelope Proteins Viral Proteins Virus Diseases Work base cell bank clinical candidate clinical development clinical investigation clinical lot commercialization cost estimate early phase clinical trial efficacy evaluation expectation experience human tissue immune function improved innovation insight interest manufacturing process meetings mouse model neutralizing antibody novel older patient pre-clinical preclinical development prevent programs prophylactic pulmonary function research clinical testing response safety assessment sex therapeutically effective trend

项目摘要

Abstract Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract disease in infants, leading annually to ~200,000 deaths and 3-4 million hospitalizations worldwide. Close to $1 billion has been invested by the RSV community over the past two decades in clinical trials seeking to improve upon the marketed monoclonal antibody Synagis®, which is only approved for prophylaxis of very low birth weight premature birth infants. None of these efforts, which have attacked the same viral protein as Synagis (the F protein), has yielded a new approved drug or vaccine. Based on insights into the pathology of RSV infection gained over the past ten years by numerous investigators, Trellis has chosen to target the only other major viral envelope protein (the G protein). Preclinical data support the expectation of substantially improved activity of Trellis’ monoclonal antibody TRL3D3 as a post-infection therapeutic, thereby addressing major populations not served by Synagis, including full-term infants, the elderly and immunocompromised patients. With funding from an SBIR Phase II grant, Trellis has established a commercially-attractive manufacturing process for TRL3D3. In this Phase IIB proposal, we seek funding to complete the IND-enabling work and initiate production of the first clinical lot. We also propose to explore the impact in mice of TRL3D3 on biomarkers that may have utility for establishing efficacy trends in early clinical trials.

抽象的呼吸道合胞病毒 (RSV) 是婴儿严重下呼吸道疾病的主要原因，导致全球每年约有 20 万人死亡和 3-40 万人住院。 RSV 社区在过去二十年中进行了临床试验，寻求改进市售单克隆抗体抗体 Synagis®，仅被批准用于预防极低出生体重的早产儿。这些努力攻击了与 Synagis（F 蛋白）相同的病毒蛋白，并产生了一种新的基于过去十年对 RSV 感染病理学的深入了解。经过众多研究人员的研究，Trellis 选择针对唯一的其他主要病毒蛋白（G 蛋白）。临床前数据支持 Trellis 单克隆抗体 TRL3D3 活性显着提高的预期作为感染后治疗，从而解决 Synagis 未服务的主要人群，包括足月儿在 SBIR 二期拨款的资助下，Trellis 已针对婴儿、老年人和免疫功能低下的患者进行了研究。在此 IIB 阶段提案中，我们寻求为 TRL3D3 建立具有商业吸引力的制造工艺。我们还建议提供资金来完成 IND 启动工作并启动第一个临床批次的生产。探索 TRL3D3 对小鼠的生物标志物的影响，这些生物标志物可能有助于建立早期疗效趋势临床试验。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structure-Based Design and Antigenic Validation of Respiratory Syncytial Virus G Immunogens.

DOI：
10.1128/jvi.02201-21
发表时间：
2022-04-13
期刊：
JOURNAL OF VIROLOGY
影响因子：
5.4
作者：
Castrejon, Ana M. Nunez;O'Rourke, Sara M.;Kauvar, Lawrence M.;DuBois, Rebecca M.
通讯作者：
DuBois, Rebecca M.