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.

Serum Hepcidin Immunoassay for Medicine: Lab To Marketplace Narrative 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.