Therapeutic Antibody for RSV IIB

RSV IIB 治疗性抗体

• 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
• 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

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 呼吸综合病毒（RSV）是婴儿严重下呼吸道疾病的主要原因，领先 全球范围内的独一无二的死亡和3-400万个住院治疗。已投资了近10亿美元 在过去的二十年中，RSV社区在临床试验中寻求改善市场的单克隆 抗体Synagis®，仅批准用于预防非常低出生体重的早产儿。没有任何 在这些努力中，它们已经攻击了与下颌骨（F蛋白）相同的病毒蛋白 批准的药物或疫苗。基于对过去十年中RSV感染的病理的见解 由众多研究者，Trellis选择靶向唯一的其他主要病毒包膜蛋白（G蛋白）。 临床前数据支持对格子单克隆抗体TRL3D3的活性的预期 作为感染后的疗法，因此解决了下颌骨未服务的主要人群，包括完整期 婴儿，古老的和免疫功能低下的患者。在SBIR第二阶段赠款的资金中，Trellis拥有 为TRL3D3建立了商业吸引人的制造过程。在此阶段IIB提案中，我们寻求 资金以完成成就工作并启动第一个临床地段的生产。我们还建议 探索TRL3D3小鼠对生物标志物的影响，这些标志物可能具有建立早期效率趋势的实用性 临床试验。

项目成果

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.