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.

摘要 呼吸道合胞病毒（RSV）是婴儿严重下呼吸道疾病的主要原因， 每年约有20万人死亡，3-4百万人住院治疗。近10亿美元的投资， RSV社区在过去二十年的临床试验中寻求改善上市的单克隆抗体， 抗体Synagis®，其仅被批准用于预防极低出生体重早产儿。没有一 这些努力中，攻击了与Synagis相同的病毒蛋白（F蛋白），已经产生了一种新的 批准的药物或疫苗。基于过去十年对RSV感染病理学的了解， 经过众多研究人员的研究，Trellis选择针对唯一的另一种主要病毒包膜蛋白（G蛋白）。 临床前数据支持Trellis单克隆抗体TRL 3D 3活性大幅提高的预期 作为感染后治疗，从而解决Synagis未服务的主要人群，包括足月妊娠 婴儿、老年人和免疫功能低下的患者。在SBIR第二阶段赠款的资助下，Trellis 为TRL 3D 3建立了具有商业吸引力的制造工艺。在第二阶段的建议中，我们寻求 完成IND启动工作并启动第一批临床批次的生产。我们亦建议 探索TRL 3D 3在小鼠中对生物标志物的影响，这些生物标志物可用于建立早期 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.