Development of Fludase as an Anti-Influenza Agent

Fludase 作为抗流感药物的开发

• 批准号: 7269392
• 负责人: MANG YU
• 金额: $ 101.57万
• 依托单位: NEXBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269392
• 关键词: Acute; Address; Animal Model; Animals; Anti-influenza Agent; Antiviral Agents; Applications Grants; Benchmarking; Biological Assay; Canis familiaris; Class; Clinical; Deposition; Development; Development Plans; Disease Outbreaks; Dose; Drug Kinetics; Engineering; Epidemic; Excision; Ferrets; Guanosine Monophosphate; Human; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Inhalant dose form; Inhalation Toxicology; Macaca; Medical; Modeling; Molecular; Mus; Neuraminidase inhibitor; Pharmaceutical Preparations; Phase II Clinical Trials; Production; Prophylactic treatment; Range; Rattus; Recombinant Fusion Proteins; Recurrence; Resistance; Respiratory Tract Infections; Safety; Sialic Acids; Surface; Therapeutic; Therapeutic Index; Toxicology; United States Food and Drug Administration; Update; Vaccines; Virus; Virus Diseases; Work; airway hyperresponsiveness; base; day; in vivo; influenza epidemic; influenza virus strain; influenzavirus; interest; manufacturing process; novel; pandemic disease; pandemic influenza; pathogenic bacteria; pre-clinical; preclinical study; receptor; respiratory; scale up; tissue culture

DESCRIPTION (provided by applicant): Influenza is a highly infectious acute respiratory viral disease that is characterized by recurrent annual epidemics and periodic major worldwide pandemics. Outbreaks are caused by infection of the highly diverse and mutable influenza viruses A and B (IFV A & IFV B). Novel broad-spectrum prophylaxis and therapeutics are critically needed to address the annual influenza epidemics and the escalating threat of pandemic influenza. NexBio has created a novel recombinant fusion protein-based anti-IFV agent, referred to as Fludase(r). Distinct from conventional vaccines and antivirals, Fludase(r) works by eliminating influenza virus receptors on the airway surface. It potentially confers broad-spectrum protection against all subtypes and strains of influenza viruses without the need for annual updates. Fludase(r) also has several built-in features to enable long drug retention on the airway surface and was engineered to be nonimmunogenic in humans. In the last 2 years, NexBio has finalized the molecular sequence of Fludase(r) and demonstrated its broad and potent anti-IFV efficacy in tissue culture and in two animal models. These accomplishments have provided strong justification for further developmental studies of Fludase(r). During the recent pre-IND meeting, the FDA raised several preclinical questions and indicated that as a first-in-class drug candidate, a thorough understanding of the Fludase(r) safety issues and mechanism of action is necessary. The main focus of this Challenge Grant proposal is to address the FDA's specific requests. Additionally, this grant proposal addresses new and important issues arising from Fludase(r) analytical and manufacture development.

描述（申请人提供）：流感是一种传染性极强的急性呼吸道病毒性疾病，其特点是每年反复流行，并在世界范围内周期性发生大流行。暴发是由高度多样化和变异的甲型和乙型流感病毒（IFV A 和 IFV B）感染引起的。迫切需要新型广谱预防和治疗方法来应对每年的流感流行和大流行性流感不断升级的威胁。 NexBio 创造了一种新型的基于重组融合蛋白的抗 IFV 药物，称为 Fludase(r)。与传统疫苗和抗病毒药物不同，Fludase(r) 通过消除气道表面的流感病毒受体发挥作用。它可能提供针对流感病毒所有亚型和毒株的广谱保护，而无需每年更新。 Fludase(r) 还具有多种内置功能，可以使药物在气道表面长时间保留，并且经过精心设计，对人体无免疫原性。在过去的两年里，NexBio 已经确定了 Fludase(r) 的分子序列，并在组织培养和两种动物模型中证明了其广泛而有效的抗 IFV 功效。这些成就为 Fludase(r) 的进一步开发研究提供了强有力的理由。在最近的 IND 前会议上，FDA 提出了几个临床前问题，并表示作为一流候选药物，有必要彻底了解 Fludase(r) 的安全问题和作用机制。该挑战拨款提案的主要重点是满足 FDA 的具体要求。此外，该拨款提案还解决了 Fludase(r) 分析和制造开发中出现的新的重要问题。