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Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 276.19K | Year: 2014

DESCRIPTION (provided by applicant): Hepcidin is the peptide hormone responsible for regulating circulating iron concentrations. Overexpression of hepcidin results in severe iron deficiency and anemia, whereas hepcidin deficiency leads to iron overload. Not surprisingly, abnormalities in hepcidin production and circulating concentrations are highly correlated with various disease states such as renal disease, cancer, hereditary hemochromatosis (HH), hypoxia, anemia of inflammation, infection, inflammatory diseases, and heart disease. Accurate methods for detecting hepcidin in serum will lead to improvements in our understanding, diagnosis, and clinical management of iron metabolism disorders. Unfortunately, there is no FDA approved assay for measuring hepcidin levels in serum. The development of a clinically relevant hepcidin assay has been hindered by hepcidin's very low immunogenicity, making it extremely challenging to produce antibodies against the hormone. The few immunoassays that do exist are poor

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 280.77K | Year: 2014

DESCRIPTION (provided by applicant): Inflammatory Bowel Disease (IBD), comprised primarily of ulcerative colitis (UC) and Crohn's disease (CD), is characterized by a chronic, uncontrolled inflammation of the intestinal mucosa. As many as 1.4 Million peoplein the United States and 2.2 Million people in Europe currently suffer from IBD, with 30,000 new cases reported each year in the US. Unfortunately, there is no cure for IBD, which necessitates a lifetime of care. There are limited treatment options for CDand UC in the United States, and patients typically receive corticosteroids and immunosuppressive drugs to alleviate symptoms. However, given the toxicity and side effects of these drugs, there is an urgent need for new treatment options for patients withUC and CD. Inflammation of the gastrointestinal tract in IBD is mediated by granulocytes and monocytes. An exciting new therapy for IBD is based on selectively removing these cells from peripheral blood using a strategy known as granulocyte/monocyte

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 280.55K | Year: 2014

DESCRIPTION (provided by applicant): In order to reduce the cost of bringing a new drug to market, drug candidates with a high probability for failure must be identified early in their development. The pharmaceutical industry employs in vitro liver modelsto screen new drugs for undesirable toxic metabolites and harmful drug-drug interactions. Primary human hepatocytes are the preferred model for assessing drug metabolism, hepatoxicity, drug-drug interactions, and CYP450 enzyme induction. However, the availability of fresh human hepatocytes is unpredictable, leading researchers to develop cryopreservation methods that enable long-term hepatocyte storage. Despite the advantages of this technique, 50% of hepatocytes lose their ability to attach to culture plates following cryopreservation. Unlike plated hepatocytes that remain viable for days to weeks, hepatocytes in suspension are only viable for a few hours; thus, non-plateable hepatocytes are limited in use to only short-term metabolic assays. Ultimate

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 256.98K | Year: 2015

DESCRIPTION provided by applicant Severe Gram positive infections are difficult to treat and associated with high mortality in hospital settings Daptomycin is a broad spectrum antibiotic that has been successfully used to treat persisting Gram positive infections including skin and soft tissue infections right sided endocarditis and bacteremia Daptomycin is also highly effective against drug resistant strains such as methicillin resistant S aureus MRSA and vancomycin resistant enterococci VRE Current daptomycin dosing guidelines are derived from limited studies in healthy individuals where pharmacokinetics is highly predictable Unfortunately daptomycin pharmacokinetics are highly variable in the critically ill patients that typically receive the drug This leads to sub therapeutic dosing increased rates of treatment failure and recently the emergence of daptomycin resistant strains Therapeutic monitoring of daptomycin concentrations would thus enable clinicians to adjust doses in order to maintain an effective circulating concentration ultimately improving outcomes and preventing adverse effects Unfortunately there is no FDA approved test to measure daptomycin concentrations in a clinical setting Multiple clinical studies have concluded that current daptomycin dosing guidelines for critically ill and septic patients need to be reevaluated and adjusted and regular measurement of daptomycin levels in these patients are needed to ensure effective treatment To address this critical need Affinergy has begun development of an assay to measure circulating daptomycin concentrations We have identified a series of phage that bind with high affinity and specificity to daptomycin and we are developing an ELISA type assay using phage as a highly sensitive detection reagent At the conclusion of Phase we expect to have a technology that can be scaled up in Phase for use by clinicians and researchers to measure daptomycin concentrations in biological fluids PUBLIC HEALTH RELEVANCE Daptomycin is successfully used to treat severe Gram positive infections including methicillin resistant S aureus MRSA and vancomycin resistant enterococci VRE Current daptomycin dosing guidelines are derived from healthy patients However daptomycin pharmacokinetics is highly variable in critically ill patients and there are no FDA approved assays that can be used to therapeutically monitor daptomycin concentrations in the clinic In this application we propose to develop a novel phage based assay to facilitate measurement of daptomycin concentration in biological fluids

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 293.82K | Year: 2015

DESCRIPTION provided by applicant Approximately Americans undergo regular dialysis treatment because of complete kidney failure otherwise known as end stage renal disease ESRD The number of patients afflicted with this condition increased six fold between and In ESRD patients serum concentrations of microglobulin m readily accumulate times higher than normal levels leading to the formation of m fibrils that deposit in the bone and joint space in a painful debilitating condition termed dialysis related amyloidosis DRA Current data indicates that depleting m from the circulation of ESRD patients reduces the severity of DRA symptoms Furthermore the amount of m removed is proportional to the extent of symptom improvement This suggests that removal of m from circulation is an effective strategy for treating DRA and that treatment efficacy would be maximized by removing as much m as possible To this end we will develop plasmapheresis columns that use small peptides to selectively deplete m from human plasma In the apheresis product we envision an automated and continuous in line circuit will be used to remove an ESRD patientsandapos blood which will then be separated into cell and plasma fractions The plasma fraction will flow through our m depletion column recombine with the patientandapos s blood cells and then be safely reintroduced into the body Current apheresis columns for treating DRA e g Lixelle approved in Japan but not available in the U S deplete m from blood This device depletes only of m from ESRD patients even when using the maximum safely allowable column size mL Moreover the column is non specific Lixelle depletes other proteins such as cytokines and also binds blood cells through non specific interactions with the column substrate This lack of specificity coupled with the columnandapos s large volume leads to significant adverse events such as hypotension and anemia that require many patients to halt treatment To remedy specificity concerns researchers have developed antibody based columns that can deplete m from plasma but these columns deplete even less m lower than Lixelle due to the large mass of antibodies We expect that depletion columns made with small peptides will be specific for m and bind up to fold more m than all existing techniques The specificity of peptide mediated m depletion from perfused plasma will drastically reduce side effects maximizing the benefits of this treatment for the largest number of patients Moreover mass scale production of peptides will be significantly less expensive than antibodies enhancing the commercialization potential of our device In this Phase application we will use phage display biopanning to identify small kD peptides that bind with high affinity and specificity to m These peptides will be grafted onto agarose substrates and used to capture m from human plasma Ultimately this technology will improve the quality of life for ESRD patients on long term dialysis PUBLIC HEALTH RELEVANCE Dialysis related amyloidosis DRA is a painful debilitating condition caused by excess microglobulin concentrations DRA affects a large portion of end stage renal disease patients undergoing dialysis Presently no treatments for this condition are available in the United States In Japan sorbent columns that deplete the microglobulin protein are available but current technologies bind low quantities of the protein or are non specific In this application we propose the development of peptide based sorbent columns that bind large quantities of microglobulin with high specificity

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