Serum Hepcidin Immunoassay: Laboratory to Marketplace

血清铁调素免疫测定：从实验室到市场

• 批准号: 7748580
• 负责人: Mark Edward Westerman
• 金额: $ 35.64万
• 依托单位: INTRINSIC LIFESCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-14 至 2010-09-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748580
• 关键词: Address; Adult; Affect; Amino Acids; Anemia; Anemia due to Chronic Disorder; Antibodies; Antibody Affinity; Antibody Formation; Antigens; Area; Behavior; Biological; Biological Assay; Biological Markers; Biomedical Research; Biotechnology; Blood; Blood Cells; Cells; Clinical; Clinical Medicine; Collaborations; Communities; Contracts; Development; Diagnostic; Diet; Dietary Iron; Disease; Enzyme-Linked Immunosorbent Assay; FDA approved; Failure; Fishes; Funding; Genetic; Goals; Heart; Hematology; Hemoglobin; Hereditary Disease; Hereditary hemochromatosis; Homeostasis; Hormones; Human; Hybrid Cells; Hybridomas; Immune response; Immunoassay; Infection; Inflammatory; Inflammatory Bowel Diseases; Inherited; Intervention; Iron; Iron Metabolism Disorders; Iron Overload; Iron deficiency anemia; Laboratories; Legal patent; Liquid substance; Liver; Maintenance; Malaria; Malignant Neoplasms; Mammals; Mass Spectrum Analysis; Measures; Mediating; Medical; Medical Research; Medicine; Methods; Molecular; Monoclonal Antibodies; Mus; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Normal Range; Organ failure; Oryctolagus cuniculus; Patients; Peptides; Pharmacologic Substance; Phase; Plasma; Plasma Cells; Production; Recycling; Refractory; Research; Research Personnel; Resistance; Rheumatoid Arthritis; Role; Sales; Serum; Small Business Innovation Research Grant; Structure; Technology; Testing; Thalassemia; Tissues; Translations; United States National Institutes of Health; Urine; absorption; analog; antibody engineering; assay development; base; commercialization; design; hepcidin; human disease; immunogenic; immunogenicity; instrumentation; iron metabolism; metal transporting protein 1; monoclonal antibody production; new technology; next generation; novel; peptide hormone; polyclonal antibody; prototype; public health relevance; receptor; small molecule; success; tool

DESCRIPTION (Provided by Applicant): Disorders of iron metabolism are among the most common human diseases. During the last decade, rapid progress has been made in the understanding of the molecular basis or iron homeostasis and its disorders. The peptide hormone hepcidin has emerged as the master regulator of iron metabolism. Dysregulation of hepcidin is the principal or contributing factor in most systemic iron disorders. There is a well recognized unmet need for a robust and widely available clinical assay for serum hepcidin but progress towards this goal has been slowed by the poor immunogenicity of hepcidin. Intrinsic LifeSciences (ILS) has assembled a team of top experts in this area and has developed and validated the world's first serum hepcidin immunoassay. SBIR funding is requested in this revised application to produce monoclonal antibodies necessary to develop the next generation assay for rapid dissemination to the medical and pharmaceutical communities. Under Phase I of this proposal we will: 1) Produce murine monoclonal antibodies suitable for use in high-capacity automated C-ELISA 2) Produce rabbit monoclonal antibodies in collaboration with a strategic alliance partner, BioAtla, using novel antibody engineering methods The overlapping approaches that we propose are designed to overcome the critical bottleneck in the development of monoclonal antibodies necessary for a standardized clinical hepcidin immunoassay. Successful completion of Phase I will enable ILS to develop a serum hepcidin immunoassay that can quench the global unmet need for a serum hepcidin immunoassay by clinicians and pharmaceutical researchers. PUBLIC HEALTH RELEVANCE: Hepcidin is a small hormone essential for the maintenance of healthy blood iron levels. Hepcidin regulates iron absorption from the diet and its release from body stores. Abnormally high serum hepcidin levels cause a debilitating anemia by limiting iron available to make hemoglobin for blood cells. At the other extreme, low serum hepcidin levels cause toxic accumulation of iron in tissues with consequent organ failure including the liver and heart. Despite hepcidin's key role in disorders affecting millions of patients worldwide, and despite great demand for a serum hepcidin test, no FDA-approved serum hepcidin immunoassay is currently available for use in research and clinical medicine. A serum hepcidin test will fill an important unmet medical need. Intrinsic LifeSciences (ILS) has developed and validated the world's first immunoassay for serum hepcidin using ILS technologies matched with antibodies produced in a UCLA medical research laboratory. Pent-up demand has led to contract sales of this novel immunoassay to clinical and pharmaceutical investigators worldwide. However, the antibody supply is not sufficient for commercialization of the hepcidin assay and its routine use in medicine. ILS requests NIH SBIR Phase I funding to implement novel technologies to produce immortalized, hybrid cell clones (hybridomas) that secrete unlimited amounts of antibodies specific to hepcidin. Development of monoclonal antibodies specific to hepcidin will enable commercial scale antibody production and accurate hepcidin immunoassay's suitable for FDA-approval. With a standardized and unlimited monoclonal antibody supply, hepcidin tests will achieve worldwide use in pharmaceutical development, biomedical research, and clinical medicine.

描述（由申请人提供）：铁代谢障碍是最常见的人类疾病之一。在过去的十年中，在理解铁稳态及其紊乱的分子基础方面取得了快速进展。肽激素铁调素已经成为铁代谢的主要调节剂。铁调素的失调是大多数系统性铁障碍的主要或促成因素。对于用于血清铁调素的稳健且广泛可用的临床测定存在公认的未满足的需求，但由于铁调素的免疫原性差，该目标的进展已经放缓。Intrinsic LifeSciences（ILS）组建了一个由该领域顶级专家组成的团队，并开发和验证了世界上第一个血清铁调素免疫测定法。SBIR在此修订申请中要求提供资金，以生产开发下一代快速传播到医学和制药界的检测所需的单克隆抗体。在本提案的第一阶段，我们将：1）生产适用于高容量自动化C-ELISA的鼠单克隆抗体2）与战略联盟伙伴BioAtla合作生产兔单克隆抗体，我们提出的重叠方法旨在克服标准化临床hepcidin所必需的单克隆抗体开发中的关键瓶颈。免疫测定法第一阶段的成功完成将使ILS能够开发血清hepcidin免疫测定法，可以满足临床医生和制药研究人员对血清hepcidin免疫测定法的全球未满足的需求。公共卫生相关性：铁调素是一种维持健康血液铁水平所必需的小激素。铁调素调节铁从饮食中的吸收及其从身体储存中的释放。异常高的血清铁调素水平通过限制可用于为血细胞制造血红蛋白的铁而引起衰弱性贫血。在另一个极端，低血清铁调素水平导致组织中铁的毒性积累，随后器官衰竭，包括肝脏和心脏。尽管铁调素在影响全世界数百万患者的病症中起关键作用，并且尽管对血清铁调素测试的需求很大，但目前没有FDA批准的血清铁调素免疫测定可用于研究和临床医学。血清hepcidin测试将填补一个重要的未满足的医疗需求。Intrinsic LifeSciences（ILS）开发并验证了世界上第一个使用ILS技术与UCLA医学研究实验室生产的抗体相匹配的血清铁调素免疫测定法。被压抑的需求导致了这种新型免疫测定的合同销售给世界各地的临床和制药研究人员。然而，抗体供应不足以用于铁调素测定的商业化及其在医学中的常规用途。ILS要求NIH SBIR第一阶段资金用于实施新技术，以产生分泌无限量铁调素特异性抗体的永生化杂交细胞克隆（杂交瘤）。铁调素特异性单克隆抗体的开发将使商业规模的抗体生产和适用于FDA批准的准确的铁调素免疫测定成为可能。随着标准化和无限制的单克隆抗体供应，铁调素测试将在全球范围内用于药物开发，生物医学研究和临床医学。